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BMC Complementary Medicine and Therapies
Effects of Green cardamom (Elettaria cardamomum Maton) and its combination with cyclophosphamide on Ehrlich solid tumors
Rafa S. Almeer1,
Meshael Alnasser1,
Nada Aljarba2 &
Gadah I. AlBasher1
BMC Complementary Medicine and Therapies volume 21, Article number: 133 (2021) Cite this article
Cardamom (Elettaria cardamomum) is a spice and exhibits potent antioxidant and biological activities through distinct molecular mechanisms. However, the anticancer effect of cardamom was not explored yet in Ehrlich solid tumor (EST)-bearing mice.
This investigation was aimed to evaluate the anti-cancer effects of green cardamom (GCar) alone or combined with the anti-cancer drug cyclophosphamide in an in vivo model to explore its mechanistic role in tumor cell death in EST-bearing mice.
Ehrlich ascites tumor cells were injected in the mice and 5 days later the animals treated with GCar and/or cyclophosphamide for 10 days. Twenty-four hours from the last treatment, animals were sacrificed for the different measurements.
Data recorded for tumor size, percentage of tumor growth inhibition, tumor growth delay and mean survival time of EST-bearing mice demonstrated the effective role of GCar alone or combined with CPO as a promising anti-cancer agent because it reduced tumor size. GCar elevated the mean survival time of EST-bearing mice compared to that of untreated EST and EST + CPO groups. Analysis of qPCR mRNA gene and protein expression revealed that GCar alone or combined with CPO were promising anticancer agents. After the treatment of EST with GCar, the apoptotic-related genes and proteins were significantly modulated. GCar induced markedly significant decreases in oxidative stress biomarkers and a significant increment in glutathione levels and that of antioxidant enzymes. With a marked diminish in liver and kidney function biomarkers.
The results revealed that GCar could serve as an apoptotic stimulator agent, presenting a novel and potentially curative approach for cancer treatment, inducing fewer side effects than those of the commercially used anti-cancer drugs, such as CPO.
Chemotherapy is one of the cancer treatment approaches, which may be undertaken alone or together with other therapies, such as surgery and/or radiotherapies. It utilizes a wide range of remedies that have cytotoxic activities to one or more cancerous tissues. Cyclophosphamide (CPO) is an alkylating cytotoxic agent that has been effectively used in patients for the last century for the curing of neoplastic maladies, such as solid tumors and lymphomas, as well as non-neoplastic maladies, such as rheumatoid arthritis and systemic lupus erythrematosus [1]. However, the medical use of CPO has been inadequate because of its capability to harm normal tissues, which usually results in toxicity in several organs (heart, testes and urinary bladder) [2] Hepatotoxicity is the foremost side effect of CPO because it is metabolized primarily within the hepatocytes by hepatic microsomal cytochrome p450 varied function oxidase system to construct its two-active metabolites phosphoramide mustard (PM) and acrolein. Phosphoramide is linked to the immunosuppressive and antineoplastic outcomes of CPO, while acrolein is associated with the toxic effects of CPO. Studies have indicated that oxidative damage is linked with its hepatotoxic effects [3]. CPO toxicity resulting from acrolein binding to the nucleophilic cellular antioxidants, such as glutathione (GSH), results in the exhaustion of the antioxidant defiance molecules and also initiates lipid peroxidation (LPO) [2, 4].
In recent years, many herbal byproducts and phytomedicines have drawn the attention of researchers mainly because of convincing anticancer activities with insignificant side effects [5]. Cardamom (Elettaria cardamomum) is a spice found in the form of tiny pods with dark seeds. The seeds have strongly sweet and aromatic tastes. Both the seed and the pod have a wealthy smell and are often used in desserts, hot and spicy plates, as well as aromatic beverages, coffees and teas. It is considered as the king of spices and is one of the most luxurious spices, ranking third, with the first and second being saffron (derived from the flower of Crocus sativus) and vanilla (derived from orchids of the genus Vanilla), respectively [6]. Cardamom is a multi-use spice. It was utilized by ancient Egyptians for its medicinal properties and even for breast-cancer anticipation [7]. The pleasant odor profile is an fundamental constituent of cardamom essential oil, the major ingredients of cardamom essential oil are pinene, myrcene, methyl eugenol, 1,8-cineole, a-terpinyl acetate, sabinene, phellandrene, terpinene, limonene, p-cymene, terpinolene, linalool, linalyl acetate, terpinen-4-ol, nerol, citronellol, geraniol, and trans-nerolidal [8]. Cardamom has also been used for teeth, gum and throat infection, as well as against lung congestion, pulmonary tuberculosis and digestive disorders [9]. Cardamom was found to reduce weight gain and associated metabolic damage to the body [10]. Cardamom suppressed edema to a lesser extent, whereas a higher dose of cardamom reveals a more potent anti-inflammatory effect on the skin in the presence of the reference drug, indomethacin [11]. The chemopreventive effect of cardamom has also been demonstrated earlier to control colorectal cancer [12] and to prevent papillomagenesis on the skin [9]. Furthermore, cardamom extract was found to lessen PTSD-like anxiety symptoms in test animals [13]. One study found that when cardamom was consumed during pregnancy, offspring showed enhanced learning, memory, and behavior [14].
The Ehrlich tumor is a transplantable neoplasm, which corresponds to mammary adenocarcinoma in female. When implanted intraperitoneally, it grows in the ascitic form and when implanted subcutaneously, it grows into a solid tumor. This tumor has been used to grow a tumor model [15]. Ehrlich ascites carcinoma (EAC) or Ehrlich solid tumor (EST) model has basically been used for study of tumor pathogenesis and development of anti-tumorigenic agents. In this context, El-Garawani et al. [5] and Salah et al. [16] were used EAC to study the anticancer effect of Candelariella vitellina, and B12 and sitagliptin, respectively.
The aim of this investigation is to examine the possible anticancer efficacies of green cardamom (GCar) alone or in combination with CPO on Ehrlich solid tumor-bearing mice. In addition, the study will extend to examine the protective effects of GCar against CPO-induced hepatotoxicity and nephrotoxicity and determine whether this effect will be modulated through an antioxidant mechanism in the liver and kidney.
The seeds of GCar were collected from a local market in Riyadh, Saudi Arabia, in 2019, and were identified and authenticated by a taxonomist from Department of Botany, College of Science, King Saud University. The seeds were powdered with an electrical grinder and then extracted three times by maceration with 70% methanol. The solvent was evaporated using a vacuum evaporator and then lyophilized to remove water [17]. The GCar extract was stored at − 20 °C until used. The obtained extract was evaluated with HPLC to determine the phenolics and flavonoids constituents of GCar. The HPLC condition was previously reported by Dkhil et al. [18]. The HPLC fingerprint of the GCar revealed the presence of many phenolics and flavonoids compounds, possibly ferulic acid and its derivatives, luteolin, rutin, catechin, caffeic acid, gallic acid and its derivatives, quercetin, and cinnamic acid (Supplementary data; Table S1).
Ehrlich ascites tumor (EAT) cells
The EAT cell line was sourced from the American Type Tissue Culture Collection (Manassas, VA, USA). EAT cells were counted using a Neubauer hemocytometer with the trypan blue dye exclusion procedure. EAT cells (25 × 105/mouse) were diluted with 0.2 mL of physiological sterile saline solution (0.9% NaCl) and injected intramuscularly (i.m.) in the right thigh of male BALB/c mice.
Doses of cardamom and CPO
The dose of cardamom given in this study was 100 mg kg− 1 body weight according to a previous study on the toxicity of this plant by Goyal et al. [19]. However, the selected dose of CPO was 50 mg kg− 1 body weight on the basis of a previous study by Twelves et al. [20].
Experimental animals
Male Swiss albino mice (6–8 weeks old and weighing 23 ± 4 g) were obtained from Biology Department of Princess Nourah bint Abdulrahman University (PNU; Riyadh, Saudi Arabia). Mice were housed under standard laboratory conditions and provided with water and a normal standard basic diet. Mice were acclimatized to experimental conditions for seven-days prior to the experiments. All experimental protocols were in accordance with the handling and care of animals at Princess Nourah bint Abdulrahman University (Approval number: H-01-R-059/19–0272, Riyadh, Saudi Arabia). All procedures of this study adhere to the ARRIVE Guidelines for reporting animal research. On day zero, all the mice were injected i.m. with EAT cells and then, on the day four, mice were divided at random into six experimental groups (10 mice per group), as follows:
EST untreated control group (Con): Mice were injected intraperitoneally (i.p.) with 0.2 ml of physiological saline solution on the 10th day post tumor inoculation (PTI).
EST + CPO treated group (CPO): Mice were injected i.p. with a single dose of CPO equal to 50 mg kg− 1 body weight on the 10th day PTI for 3 consecutive days.
EST + green cardamom treated group (GCar): Mice were administered orally once daily with GCar at a dose equal to 100 mg kg− 1 body weight for 10 days starting on day 5 PTI.
EST + green cardamom+CPO combined treated group (GCar-CPO): Mice received an oral dose equal to 100 mg kg− 1 body weight of GCar daily for 5 days starting on day 5, on the 10th day PTI they were injected i.p. with a single dose of CPO equal to 50 mg kg− 1 body weight and then they receive a single oral dose equal to 100 mg kg− 1 body weight of GCar daily for another 5 days.
The experimental design was followed our previous study [15]. Twenty-four hours from the last treatment (day 16 PTI), seven animals of each group were sacrificed by intraperitoneal injection of pentobarbital (200 mg kg− 1) and three animals from each group were left to calculate survival time, tumor growth delay time and inhibition of tumor growth.
Body weight (BW) changes
Changes in BW were estimated as follows: initial BW was that on day 12 PTI. Final and net final BWs were estimated on day 20 PTI. Net final BW = final BW – tumor weight. Percentage difference of BW gain was determined as BW gain ([final BW – initial BW]/initial BW) × 100. Tumor mass (mg) was determined via the following equation, as demonstrated by Jaganathan et al. [21]:
$$ \mathrm{Tumor}\ \mathrm{mass}=\frac{\mathrm{Length}\ \left(\mathrm{mm}\right)\times {\left[\mathrm{Width}\ \left(\mathrm{mm}\right)\right]}^2}{2} $$
Tumor volume
Tumor volume was determined using the following equation, as mentioned previously [15]:
$$ \mathrm{Tumor}\kern0.17em \mathrm{volume}\left(\mathrm{V}\right)=4/3\prod {\mathrm{r}}_1^2\times {\mathrm{r}}_2{\left(\mathrm{cm}\right)}^3 $$
Where, r1 and r2 are the radii of tumors in two different planes determined with Vernier calipers.
Evaluation of antitumor activity
The tumor growth inhibition ratio (T/C %) was estimated on day 21 by comparing the average values for the treated and untreated tumor-bearing mice. Tumor growth in untreated EST mice was considered to be 100%.
$$ \mathrm{T}/\mathrm{C}\%=\frac{\left(\mathrm{average}\ \mathrm{tumor}\ \mathrm{mass}\ \mathrm{of}\ \mathrm{EST}\ \mathrm{mice}-\mathrm{average}\ \mathrm{tumor}\ \mathrm{mass}\ \mathrm{of}\ \mathrm{treated}\ \mathrm{mice}\right)\times 100}{\mathrm{Average}\ \mathrm{tumor}\ \mathrm{mass}\ \mathrm{of}\ \mathrm{EST}\ \mathrm{mice}} $$
Percentage increase in life span (ILS)
Mean survival time (MST; n = 3/group) was estimated by monitoring mortality on a daily basis and the % ILS was estimated via the following equation, as reported previously [15]:
$$ \mathrm{MST}=\left(\mathrm{day}\ \mathrm{of}\ \mathrm{first}\ \mathrm{death}+\mathrm{day}\ \mathrm{of}\ \mathrm{last}\ \mathrm{death}\right)/2 $$
$$ \%\mathrm{ILS}=\left(\mathrm{MST}\ \mathrm{of}\ \mathrm{treated}\ \mathrm{group}/\mathrm{MST}\ \mathrm{of}\ \mathrm{EST}-\mathrm{untreated}\ \mathrm{group}\right)\times 100 $$
Gene expression analysis
Apoptosis controlled genes expression such as Bcl2, Bax and caspase-3, − 8 and − 9, was estimated utilizing β-actin as a reference housekeeper gene. RNA was extracted from the EST samples with TRIzol Reagent (Invitrogen, Carlsbad, CA, USA). Reverse Transcription System (Promega, Madison, WI, USA) was used to prepare the cDNA. Real-time PCR was performed using SYBR Green Master Mix (Applied Biosystems) on the Applied Biosystems StepOne™ real-time PCR system (Applied Biosystems, Carlsbad, CA, USA). The PCR was performed as follows: incubation at 95 °C for 10 min followed by 40 cycles for 15 s at 94 °C, 30 s at 58 °C and 30 s at 70 °C. The Pfaffl formula was used for data analysis utilizing the following equation: 2−ΔΔCt [22]. The primer sets were as follows:
β-actin F: 5′-CCA-CCA-TGT-ACC-CAG-GCA-TT-3′.
R: 5′-AGG-GTG-TAA-AAC-GCA-GCT-CA-3′.
Bcl-2 F: 5′-ACA-GGG-TAC-GAT-AAC-CGG-GA-3′.
R: 5′-GCC-CAG-ACT-CAC-ATC-ACC-AA-3′.
Bax F: 5′-GAC-ATT-GGA-CTT-CCT-CCG-GG-3′.
R: 5′-ACA-GGG-ACA-TCA-GTC-GCT-TC-3′.
Caspase-3 F:5′-GCG-GTT-GTA-GAA-GTT-AAT-AAA-GGT-A-3′.
R: 5′-AAC-CAG-GTG-CTG-TGG-AGT-AT-3′.
Caspase-8 F: 5′-GGT-TAG-GGG-ACT-CGG-AGA-CT-3′.
R: 5′-CAG-GCT-CAG-GAA-CTT-GAG-GG-3′.
Caspase-9 F: 5′-TTG-GTG-ATG-TCG-AGC-AGA-AAG-A-3′.
R: 5′-GGG-ACA-CAA-GTC-ACT-AGC-CC-3′.
Liver functions parameters
The serum levels of alanine transferase (ALT) and aspartate transferase (AST) were analyzed with a spectrophotometric method [23]. Total bilirubin (TB) in serum was assayed using the previously described method [24].
Kidney function parameters
The levels of kidney function markers (urea and creatinine) in serum were measured using commercial kits purchased from Cayman Chemical (Ann Arbor, Michigan, USA) and the procedures were performed according to the manufacturer's protocols.
Oxidative stress biomarkers and antioxidant enzyme activities
Malondialdehyde (MDA) amounts, an indicator for LPO, were assayed in EST tissue homogenates by reaction with thiobarbituric acid [25]. Similarly, the homogenates were used to quantify nitric oxide (NO) level [26] using Griess reagent and reduced glutathione (GSH) content [27] by using Ellman's (5,5′-dithiobis-(2-nitrobenzoic acid) or DTNB) reagent. Whereas, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT) were assayed using specific commercial kits obtained from Cayman Chemical and assays procedures were followed the supplier's protocols.
Histopathology and immunohistochemistry analyses
Pieces of tumor samples were fixed in 4% neutral paraformaldehyde for 24 h. Hematoxylin and eosin (H&E) staining for light microscopy was applied. For the recognition of apoptosis controlled proteins, the prepared sections (5 μm thickness) were blocked with 0.1% H2O2 for 15 min. Then, the specimens were incubated with rabbit polyclonal Bcl-2, Bax or caspases-3 antibody at 4 °C during the night. The specimens were rinsed with PBS, incubated with biotinylated goat anti-rabbit immunoglobulins and then with streptavidin–peroxidase complexes at 30 °C for half an hour. The peroxidase activity was developed with diaminobenzidine (DAB)-hydrogen peroxide. Specimens were captured at 400× magnification.
Data were represented as the means ± standard deviations (SD). Statistical significance was determined by one-way analysis of variance (ANOVA), followed by Duncan's post hoc test. A p value < 0.05 was considered statistically significant.
BW and survival of mice
As shown in Fig. 1, EST-inoculated mice treated with GCar, CPO, or GCar-CPO showed a marked (p < 0.05) decline in BW when compared with that of untreated EST mice. The greatest decline in BW was showed in the CPO-treated mice.
Effects of GCar, CPO and GCar-CPO on body weights of the different treatment groups
The results indicated that administration of tumor-bearing EST mice with GCar or CPO alone, or in combination markedly decreased tumor development, as recognized by the reduction in tumor volume and tumor weight, compared with those in the tumor-bearing EST mice (Fig. 2).
Effects of CPO, GCar and GCar-CPO on the tumor weight, length, width of the tumor and tumor volume. Values are expressed as means ± SD. a and b: Significant against control and CPO groups at p < 0.05, respectively
Interestingly, we found that MST for the control EST-bearing mice and CPO-treated mice were 13.7 and 14.6 days, respectively, which increased to 25 and 24.3 days in the GCar and GCar-CPO groups, respectively (Fig. 3). Furthermore, ILS for the GCar and GCar-CPO groups increased significantly in comparsion with that for the CPO-treated mice and untreated EST-bearing mice.
Effects of CPO, GCar and GCar-CPO on the mean survival time (days) and increase of life span ratio (ILS%). Values are expressed as means ± SD. a and b: Significant against control and CPO groups at p < 0.05, respectively
Histopathology of EST in mice
Healthy mice inoculated with EST cells grew tumor at the site of injection. Figure 4a, indicated that slides from EST-bearing mice demonstrated numerous cellular and nuclear pleomorphisms, as could be seen by the compacted and combined tumor cells extend within the muscles tissue, as well as groups of large, round, and polygonal cells with pleomorphic shapes, binucleation, and hyperchromatic nuclei. However, EST-bearing group cured with CPO showed some necrotic areas and the remnant cancer cells encircled the muscles tissue (Fig. 4b). More demolition of EST tissue was found after the oral administration of GCar alone (Fig. 4c) or in combination with CPO (Fig. 4d). In these groups, the tumor was sporadic and appeared to be developed slowly and fragmented. Our findings demonstrated that GCar had partial anti-cancer activity.
Muscle fibers between destructed tumor cells (red arrow), fat vacuoles in between tumor cells (white arrow) and remnants of dead tumor cells (apoptotic cells: red arrow; necrotic cells: white star) in the treated mice; compaction and aggregation of the large, round and polygonal tumor cells (green arrow). a Control EST, Control EST section shows compaction and aggregation of the large, round and polygonal tumor cells. b CPO, c EST + GCar and d EST + GCar-CPO. All magnifications at × 400
qPCR data and immunohistochemistry results
The data represented in Fig. 5 indicated a significant downregulation in mRNA of Bcl-2 in CPO-treated EST-bearing groups in comparison with that of the control EST-bearing mice. Furthermore, EST-bearing mice treated with GCar mixed with CPO showed a considerable drop in mRNA expression of Bcl-2 at p < 0.05 versus that of CPO treatment alone. Conversely, a highly marked up-regulation was observed in Bax mRNA expression in mice treated with GCar, CPO and GCar-CPO in comparison with that in the control EST-bearing group (Fig. 5). Moreover, highly marked increments were exhibited in mRNA expression for caspase-3, − 8 and − 9 in mice treated with GCar, CPO and GCar-CPO versus that of the control EST-bearing group (Fig. 5).
Effects of CPO, GCar and GCar-CPO on the mRNA expression of Bcl-2, Bax, caspase-3, caspase-8 and caspase-9 in the tumor tissue. Values are expressed as means ± SD of triplicate experiments. a and b: Significant against control and CPO groups at p < 0.05, respectively
Immunohistochemistry analysis was conducted to confirm the effects of GCar on apoptosis-related proteins. The results revealed that GCar administration induced up-regulation of Bax and caspase-3, and down-regulation of Bcl-2 compared to that of the EST-bearing group (Fig. 6). Furthermore, as expected, CPO treatment induced up-regulation of Bax and caspase-3, and down-regulation of Bcl-2 compared to that of the EST-bearing group. The same effects were found in the GCar-CPO treated group.
Figures show apoptotic proteins immunoreactivity in tumor tissues obtained from mice. All magnifications at × 400
Oxidative stress biomarkers
As expected, a marked elevation in MDA level was found in the CPO-treated group, compared to that in the EST-bearing mice (Fig. 7). However, MDA levels markedly declined in the combination treatment group, compared with that in the CPO group, demonstrating the antioxidant effect of cardamom. In addition, a marked elevation in NO levels was shown in the CPO-treated mice compared with that in the EST-bearing mice. Conversely, NO levels declined non-significantly in the GCar group, but significantly increased in the GCar-CPO group compared to that in the EST-bearing mice. GSH levels decreased in the GCar group compared with that in the EST-bearing mice; however, this decrease did not achieve statistical significance. A marked diminishes in GSH levels was observed in the CPO and GCar-CPO-treated mice compared with that in the EST-bearing mice (Fig. 7).
Effects of CPO, GCar and GCar-CPO on the LPO, NO and GSH levels in the tumor tissue. Values are expressed as means ± SD. a and b: Significant against control and CPO groups at p < 0.05, respectively
A significant rise in SOD and GPx activities in EST-treated groups with GCar treatment alone was recorded in comparison to its level in the EST control group. On contrary, there was a marked reduction in antioxidant enzyme activities in the EST–CPO-treated mice in comparison to its levels in the EST-control mice (Fig. 8). Additionally, treatment of EST bearing mice with GCar and GCar-CPO exhibited a marked increase in antioxidant enzyme activities compared to that of CPO treatment alone.
Effects of CPO, GCar and GCar-CPO on the SOD, CAT, GPx and GR activities in the tumor tissue. Values are expressed as means ± SD. a and b: Significant against control and CPO groups at p < 0.05, respectively
Liver and kidney functions results
A non-significant change in liver and kidney function biomarkers were recorded in EST-treated groups with GCar treatment alone. However, there was a marked raise in those biomarkers observed in the CPO-treated mice in comparison to levels in the EST-control mice. On contrary, treatment of EST-bearing mice with GCar combined with CPO exhibited a marked decline in these biomarkers compared to those of the CPO treatment group alone (Fig. 9) suggesting the protective effect of cardamom against CPO.
Effects of CPO, GCar and GCar-CPO on the ALT and AST activities and urea and creatinine levels in the serum. Values are expressed as means ± SD. a and b: Significant against control and CPO groups at p < 0.05, respectively
The findings of the current investigation showed the importance of GCar as an antitumor agent obtained from natural sources whether used alone or combined with an anticancer drug. The anticancer agent suppressed the propagation of tumor cells by enhancing apoptosis and may represent a beneficial mechanistic strategy to both cancer chemoprevention and chemotherapy [28]. The results revealed that GCar displayed antitumor effect against EST tumors in mice, exhibited by the reduction in tumor weight and volume. The decline in body weight gain and diminish in tumor volume are the criteria for judging the efficacy of any anti-tumor drugs [5].
Growing body of evidences indicate that medicinal plants can modulate various molecular pathways involved in tumor initiation and growth. It is expected that researches with natural products will discover a diversity of molecular mechanisms and targets for tumor growth inhibition, apoptosis and especially angiogenesis prevention. To date, clinical trials in chemoprevention using medicinal products conducted for cancer are very limited. Extensive clinical study is warranted to assess further safety and chemo-preventive efficiency of natural products either alone or in combination with chemotherapeutic drugs against tumor [5].
Therapeutic molecules that targeted the cell death signaling, including pro-apoptotic proteins stimulators or suppressors of anti-apoptotic protein, could conquer the dilemma of resistance through directing the cancerous cells to self-destruct [29]. In this context, the examination of novel targeted apoptotic enhancers for cancerous cells could present a new approach in tumor treatment [5]. Accordingly, the goal of the present investigation was to study the apoptotic stimulating effect of GCar on cancer cells relative to their effects on the expression of pro-apoptotic and anti-apoptotic genes, as well as to assess the anticancer potential of GCar against a selected reference anticancer drug, CPO, in an in vivo EST model.
DNA is the principal target in terms of the teratogenic, mutagenic and antineoplastic effects of CPO. Effects of CPO on DNA have been extensively reported in mammalian cells, both of somatic and germ cell origins [30]. CPO is supposed to bring its cytotoxicity via the cross-linking of somatic DNA and researchers have found that following CPO treatment there is an occurrence of inter-strand and DNA-protein cross-links, but no single strand breaks [31]. CPO suppresses embryonic DNA biosynthesis and does so prior to its effect on RNA or protein construction [32]. Although CPO is known to cause DNA cross-links, other DNA damage is produced as well. CPO mediates G0/G1 and S phase arrest [33], accumulation of cells in the G0/G1 phase in comparison to that of the control, whereas higher amounts of CPO causes dose-dependent G0/G1, S and G2/M phase inhibition [34].
The cytotoxic action of CPO is induced mostly because of PM, which causes DNA cross-linking [35]. Alkylation of DNA and proteins by CPO causes the creation of cross-links. Cross-links in transcriptional active regions of the DNA can cause a silence or arrest of the RNA polymerases, negatively affecting transcription elongation and genes expression [36]. PM is a bifunctional alkylating molecule that binds to the N-7 position of guanine [37], to the phosphate backbone of DNA [38]. Exposure of cells to PM results in the generation of a mixture of inter-strand, DNA-protein cross-links and enlargement of cells. PM devastates quickly dividing cells and stimulates the DNA double strand break marker, γH2AX and DNA repair in rat granulosa cells and neonatal ovaries [39]. Acrolein, on the contrary, is found to bind to proteins, form DNA adducts, generate basic sites and to induce DNA single-strand breaks (SSB) [40].
CPO causes overproduction of ROS, such as the superoxide anions and hydroxyl radicals, which depletes GSH content and suppresses the activities of antioxidant enzyme in renal tissue. ROS may lead to cellular damage and necrosis via several mechanisms, including peroxidation of cellular membrane phospholipids, proteins denaturation and DNA injury [41]. Studies show that CPO induces ROS generation in vivo, which is accountable for the severe unfavorable effects of CPO treatment, including liver and kidney toxicities, which in turn are restrained by supplementation with antioxidants [42].
In the current study, CPO increased levels of LPO and decreased the GSH content in Ehrlich solid tumor-bearing mice. The antitumor activity of CPO was accompanied with the increase of oxidative stress status in tumor tissue. In rats, CPO increased LPO and altered the -SH status of the tissues with simultaneous alterations in enzymatic antioxidant molecules in other studies [43]. GSH content and GR activity are significantly diminished after CPO therapy, whereas GPx and CAT showed a significant improvement in the current study.
CPO-induced production of ROS has also been implicated in its direct cellular toxicity [44]. Acrolein, a reactive aldehyde, is known to be the most toxic metabolite of CPO, through its ability to produce toxic ROS and consequently affect surrounding tissues. ROS have various effects, including suppression of a variety of enzymes, membrane and DNA damage and lipid peroxidation [45]. In this regard, CPO injury can be ameliorated by free radical scavengers [46]. Our study is in agreement with the findings of Kurauchi et al. who found that CPO-induced cardiac apoptosis involves several pathways, including oxidant damage, creation of intrinsic and extrinsic apoptotic cascades and endonucleases [47]. Interestingly, we demonstrated that the treatment with GCar showed a significant reduction in oxidative stress markers and activation of the endogenous antioxidant system that affected by EST, suggesting that counteracting oxidative stress is critical in avoiding the progress of EST. The obtained results are in conformity with previous studies on GCar that showed the antioxidant activity in diethylnitrosamine-induced hepatocellular carcinoma [48]. Also, the attenuation of oxidative stress by GCar was expressed in its ability to restrain lipid peroxidation due to the presence of polyphenols and flavonoids.
Placzek et al. [49] reported that Bcl-2 and Bcl-xL anti-apoptotic proteins were minimally expressed following treatment with CPO. Furthermore, the caspase-3, − 8 and − 9 are over-expressed in the treated tumor cells and this agreed with the results of Schwartz and Waxman [50], suggesting that caspase-9 may mediate apoptosis induced by CPO and its induction could represent a novel approach to the effective treatment of malignant tumors. Moreover, the authors found that Bcl-2 over-expression blocked the cytotoxic actions of activated CPO but did not suppress the drug's cytostatic actions. CPO caused S-phase cell cycle arrest was followed by alteration to an apoptotic pre-G1 state in wild-type 9 L cells. In contrast, Bcl-2-expressing 9 L cells concentrated in G2/M in response to CPO management [50]. In addition, this is in agreement with Yang et al. [51], who showed that CPO treatment induced the activation/cleavage of caspase-3 in A431 cells. As a result, CPO treatment can initiate both the extrinsic and intrinsic pathways of caspases activation. Likewise, CPO-induced caspase-3 in Leukemic T cells [52] and the authors reported that oxidative stress-induced nuclear translocation of apoptosis-inducing factor (AIF) and endonuclease G (EndoG) in 4-hydroperoxy-CPO (4-OOH-CY)-treated T cells might represent an alternative death pathway in the absence of caspase activity. Other antioxidants such as B12 and sitagliptin, have previously been shown to have antitumor activities [16].
CPO induced ROS overproduction in vivo, which is accountable to the severe unwanted side effects of CPO treatment, including liver and kidney toxicities, which in turn are depleted by antioxidants addition. However, understanding the expression of anti- and pro-apoptotic proteins and their relationship to the redox system in the cells, as well as the location of ROS production upon CPO therapy will offer precious insights into new approaches for minimizing CPO unwanted side effects without affecting its effectiveness [53].
GCar has a wide range of biological effects, including anti-diarrheal, anti-hypertensive, anti-arrhythmic, cholesterol lowering, anti-microbial and anti-inflammatory activities [17, 54,55,56,57]. In addition, GCar caused inhibition of tumor cell proliferation and the induction of apoptosis and the mechanism of antitumor action differs among cell lines [54,55,56]. The anticancer effect of GCar may be attributed to the presence many phenolic compounds such as gallic acid and caffeic acid. GCar possesses a strong antioxidant effect with a ability to restrain the formation of tumors in many cancer models. In this context, Elguindy et al. [48] found that GCar treatment markedly diminished the levels of α-feto protein, which revealed the antitumor effect of GCar against hepatocellular carcinoma. Furthermore, Majdalawieh and Carr [2] found that GCar markedly promotes the cytotoxic activity of natural killer cells, suggesting its potential anticancer effect and Shinjini Pal et al. [58] found that zinc oxide nanoparticles green synthesized by GCar induced apoptosis in HepG2 cells. Moreover, Bhattacharjee and Chatterjee [59] observed that eucalyptol, abioactive compound of GCar, bind to Cas-3 and stimulated its activity.
Several cancerous cell lines have been utilized to study the action of GCar and it has been shown to be efficient at relatively low doses on a number of cancers arising from leucocytes, liver, brain, skin, lung, GIT, bone, and breast [9, 54, 56]. GCar extracts significantly improve the cytotoxic effect of natural killer cells, representing its anticancer potential [2]. The mechanism of its antitumor effect is that GCar modulates a variety of transcription signaling, growth factors, protein kinases and inflammatory cytokines [60].
In summary, the combined application of GCar with CPO resulted in a statistically significant diminish in cell survival in comparison with GCar or CPO treatment alone. Therefore, the cytotoxic potential of GCar can be amplified by combination with CPO. Furthermore, our finding indicated that GCar is able to initiate apoptosis in cancer cells and maintained the balance between oxidants and antioxidants molecules.
All relevant data are within the paper.
ALT:
AST:
Aspartate aminotransferase
Bax:
Bcl-2-like protein 4
Bcl-2:
B-cell lymphoma 2
BW:
CPO:
EAC:
Ehrlich Ascites carcinoma
Ehrlich solid tumor
GCar:
GPx:
Glutathione peroxidase
GR:
GSH:
H&E:
Hematoxylin and Eosin
i.m.:
Intramuscular
ILS %:
Increased in life span percent
LPO:
Lipid peroxidation
MDA:
Malonaldehyde
MST:
Mean survival time
ROS:
SOD:
TNF:
tumor necrosis factor
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The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding the work through the Research Group No. RG-1441-306.
This research was funded by the Deanship of Scientific Research at King Saud University for funding the work through the Research Group No. RG-1441-306.
Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
Rafa S. Almeer, Meshael Alnasser & Gadah I. AlBasher
Biology Department, Faculty of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
Nada Aljarba
Rafa S. Almeer
Meshael Alnasser
Gadah I. AlBasher
RA designed the project. RA and MA performed the experiments, analyzed the data, interpreted the data, drafted and edited the manuscript. NA and GA supplied the chemicals and reagents. All authors read and approved the final draft.
Correspondence to Rafa S. Almeer.
All experimental protocols were in accordance with the handling and care of animals at Princess Nourah bint Abdulrahman University (Approval number: H-01-R-059/19–0272, Riyadh, Saudi Arabia).
All authors mentioned no conflicts of interest in this research.
Identification of phytochemical compounds by HPLC in green cardamom (Elettaria cardamomum) seeds.
Almeer, R.S., Alnasser, M., Aljarba, N. et al. Effects of Green cardamom (Elettaria cardamomum Maton) and its combination with cyclophosphamide on Ehrlich solid tumors. BMC Complement Med Ther 21, 133 (2021). https://doi.org/10.1186/s12906-021-03305-2
EST-bearing mice
Submission enquiries: bmccomplementarymedicineandtherapies@biomedcentral.com


text:
La « drôle de guerre » (en , « fausse guerre » ; en , « guerre assise » ; en , « guerre étonnante ») est la période du début de la Seconde Guerre mondiale qui se situe entre la déclaration de guerre par le Royaume-Uni et la France (les Alliés) à l'Allemagne nazie le  et l'offensive allemande du  sur le théâtre européen du conflit. Cette période se caractérise par :
 la campagne de Pologne et ses répercussions sur le front occidental ;
 la guerre russo-finlandaise ou guerre d'Hiver ;
 la campagne de Norvège, dont Narvik est un épisode ;
 la question des Balkans et des pétroles de Roumanie et du Caucase ;
 sur le plan intérieur, l'érosion des gouvernements français et britannique ;
 une politique active d'armement de la part de tous les belligérants.

L'origine de l'expression « drôle de guerre » est revendiquée par le journaliste Roland Dorgelès, mais elle pourrait provenir d'une mauvaise compréhension de l'expression phoney war, confondue avec funny war, utilisée dans un reportage sur les armées franco-britanniques. Elle s'applique au front occidental, où les hostilités se réduisaient à quelques escarmouches après la modeste offensive de la Sarre.

Déroulement

Les premiers mois

Après la signature du pacte germano-soviétique, Hitler lance ses armées contre la Pologne le , sans déclaration de guerre (voir : incident de Gleiwitz). En application de leur alliance, la France et le Royaume-Uni déclarent la guerre à l'Allemagne. En particulier, la France a garanti après 1918 par des traités d'assistance mutuelle l'existence de la plupart des pays nouvellement créés en Europe centrale (avec l'idée de créer un cordon sanitaire autour de l'Allemagne). La Pologne et la France ayant signé en mai 1939 un protocole qui obligeait la France à lancer l'offensive générale dès le quinzième jour de la mobilisation, en septembre 1939, les Polonais attendent, en vain, l'aide française en espérant que la France remplirait ses engagements d'allié. Dès les premiers jours, l'armée française ne fait que lancer l'offensive de la Sarre avant de se replier derrière la ligne Maginot.

Les Allemands appliquent pour la première fois sur le théâtre polonais la tactique de la Blitzkrieg (« guerre-éclair »), qui assure à la Wehrmacht une victoire rapide malgré la contre-offensive polonaise de la Bzura. Ayant attaqué de son côté la Pologne le 17 septembre, l'URSS participe au partage du pays vaincu, puis elle annexe les États baltes. Après l'échec des négociations avec la Finlande pour reculer la frontière soviétique au-delà de Léningrad, l'URSS attaque la Finlande (guerre d'Hiver) et elle annexe la région frontalière de Carélie. L'armistice soviéto-finlandais provoque en France la chute du gouvernement Daladier, le 21 mars 1940, et son remplacement par Paul Reynaud.

Après sa première campagne victorieuse, Hitler se tourne vers l'Ouest, mais il doit reporter plusieurs fois son offensive, et le front reste calme pendant plusieurs mois. Retranchés derrière la ligne Maginot, les Alliés attendent l'assaut des forces allemandes, elles-mêmes retranchées derrière le Westwall ou ligne Siegfried. C'est un conflit sans combats majeurs, seulement quelques escarmouches entre patrouilles de reconnaissance. C'est la « drôle de guerre », selon l'expression attribuée à l'écrivain Roland Dorgelès. L'installation dans la routine plonge l'armée française dans une « dépression d'hiver » : l'obéissance se relâche, l'alcoolisme atteint des sommets historiques, les villages évacués d'Alsace sont pillés par des soldats français.

La « drôle de guerre » avec l'offensive de la Sarre aurait fait dans les trois armées françaises (terre-air-mer) environ . L'historien Michaël Bourlet avance le chiffre de  au combat, durant les huit mois de la drôle de guerre. Les Allemands comptent de leur côté 196 soldats tués et 114 disparus après la contre-offensive de la première armée d'Erwin von Witzleben du 16 au 24 octobre, laquelle ne progressera pas avant le , date du début de la . Cette contre-offensive fut le seul combat d'une certaine envergure sur la frontière durant la « drôle de guerre ».

En mer, un sous-marin allemand coule dès le 3 septembre 1939 le paquebot britannique Athenia, faisant 117 morts. Le 14 octobre suivant, un autre U-Boot réussit à s'introduire dans la rade de Scapa Flow et à couler le cuirassé , causant la mort de 833 marins britanniques.

Le commandement français
En France, la structure de commandement se complexifie avec la création fin 1939 du Grand quartier général français de Doumenc à mi-chemin entre Gamelin et Georges. On se retrouve dès lors pour le secteur clef des opérations avec pas moins de quatre échelons de commandement :
 Gamelin (Général commandant en chef) ;
 Doumenc (Grand Quartier Général intermédiaire) ;
 Georges (Théâtre Nord-Est) ;
 Billotte (premier Groupe d'Armées, c'est-à-dire l'essentiel de l'affaire).
Sans oublier la chaîne « Air » distincte.

Les trois premiers se « partageant » les principaux services d'état-major dont le PC en partie souterrain est installé dans le bois du château de Vincennes, ceux-ci y perdent évidemment en efficacité et plus personne ne dispose dans sa main de tous les outils nécessaires à la conduite de la bataille. « Le haut commandement des années 1930, analyse Jean-Louis Crémieux-Brilhac, n'avait su ni éviter la sclérose intellectuelle et bureaucratique, ni admettre qu'il pût y avoir d'autres formes de guerre que celle de 14-18, ni faire le choix de système d'armes cohérents ». De plus, il faut préciser que les deux premiers gravitent, l'un dans l'ombre de Reynaud, l'autre dans celle de Daladier.

Les opérations en Norvège

Dans le cadre de la stratégie du blocus, les Alliés veulent couper les approvisionnements en minerai de fer de l'Allemagne ; celle-ci reçoit la majeure partie de ses approvisionnements de la Suède. Si le port de Luléa est pris par les glaces une bonne partie de l'hiver, celui de Narvik (Norvège) est en eau libre. Les Alliés décident donc de monter une opération pour prendre le contrôle des mines de Gällivare à partir de Narvik (une voie ferrée relie les deux points). Mais les Allemands devancent les Alliés : ils envahissent le Danemark et la Norvège le 9 avril (les Alliés ont mouillé des mines dans les eaux territoriales norvégiennes le 8 avril, ce qui peut s'apparenter à un acte hostile, la Norvège ayant continuellement affirmé sa volonté de rester neutre). L'intervention allemande est un succès ; les Alliés essuient partout des échecs, sauf à Narvik où Polonais et Français réussissent à prendre pied dans la ville, mais pour très peu de temps. À la suite du début désastreux de la campagne de France, les troupes de Narvik sont rappelées et l'opération s'achève sans être exploitée.

L'offensive allemande à l'Ouest

La drôle de guerre prend définitivement fin le  lorsque les armées allemandes lancent le Fall Gelb, une vaste offensive sur les Pays-Bas, la Belgique, le Luxembourg violant la neutralité de ces États, puis à travers les Ardennes (la percée de Sedan) afin de prendre à revers la ligne Maginot. Le commandant en chef français, le général Gamelin, avait pourtant été prévenu, en janvier 1940, par des contacts militaires secrets avec les Belges, que ceux-ci avaient saisi, dans un avion qui avait fait un atterrissage forcé en Belgique (incident de Mechelen), des instructions militaires montrant que l'Allemagne allait attaquer dans les Ardennes. Le 8 mars, un message de confirmation du roi Léopold III en personne parvint encore au Général Gamelin. Mais l'état-major français n'en tint aucun compte. Et ce fut l'attaque sur Sedan où l'armée française, surprise, ne put s'opposer à la percée allemande menaçant les arrières des armées alliées. Pourtant les troupes d'élite de l'armée belge, les Chasseurs ardennais, avaient contenu les Allemands pendant deux jours, ce qui aurait dû permettre aux Français de mieux se préparer. Un rapport du député français Pierre Taittinger signalait, dès avril, les faiblesses du secteur de Sedan. Mais rien n'y fit. Il en résulta le recul précipité de l'ensemble des armées françaises de l'Est. Pendant ce temps, le gros de l'armée belge était attaqué par le nord de la Belgique et par les Pays-Bas dont l'armée devait se rendre en cinq jours. Les armées franco-anglo-belges, incapables de se reformer pour stopper l'avance allemande, se disloquèrent progressivement après un coup d'arrêt de l'armée belge sur la Dendre et une éphémère et inutile victoire tactique, à Gembloux, des chars français accompagnés par de l'infanterie. La conséquence finale fut l'écrasement de l'armée belge qui capitula le 28 mai, arrivée au bout de ses réserves de munitions. De plus, l'armée anglaise avait sans crier gare abandonné la droite de l'armée belge dès le 25, comme le confirme lord Keyes dans ses mémoires. Les Belges, depuis le 23 jusqu'au 28, continrent seuls l'armée allemande à la bataille de la Lys, alors que l'encerclement du gros des forces alliées empêchait tout approvisionnement. Les Anglais préparaient hâtivement l'opération Dynamo de rembarquement des forces britanniques. Une large partie des troupes françaises put également être recueillie, sous la protection d'un rideau de troupes françaises qui freinèrent l'armée allemande avant d'être finalement capturées, tandis que les équipements lourds étaient perdus. Cette défaite entraîna aussi l'abandon de la Scandinavie par les forces alliées.

Propagande et économie de guerre
La propagande est dirigée en Allemagne par Joseph Goebbels et en France par Jean Giraudoux, nommé commissaire général à l'information le 29 juillet 1939 par le gouvernement Daladier. Les chansons patriotiques de la « der des ders » comme La Madelon sont utilisées en version douce-amère nostalgique.

Les adversaires mettent une économie de guerre au service de leurs armées. Les États-Unis vendent comptant leur matériel militaire uniquement aux Alliés tandis que l'URSS fait commerce de ses ressources avec l'Allemagne. L'accès au minerai de fer suédois déclencha un affrontement en Norvège et son invasion par les nazis. Les Alliés déclenchèrent le blocus et l'Allemagne, quelques attaques par ses sous-marins.

Littérature et culture populaire
L'expression « drôle de guerre », revendiquée par le correspondant de guerre Roland Dorgelès, est utilisée à partir de  par le journal Le Figaro. L'expression pourrait être la traduction de  expression dérisoire attribuée au sénateur américain William Borah et signifiant « fausse guerre, guerre bidon ».

La drôle de guerre sert de contexte à de nombreuses œuvres littéraires comme Un balcon en forêt de Julien Gracq publié en 1958 où l'auteur prend appui sur son expérience de soldat dans les Ardennes au début de la Seconde Guerre mondiale. L'écrivain Lucien Rebatet, lui aussi engagé, déplore pour sa part l'enlisement qu'engendre la Drôle de guerre dans son ouvrage Les Décombres (1942), décrivant une armée mal entrainée, mal dirigée et finalement impropre à se battre, face à la menace allemande.

C'est lors d'une tournée sur la ligne Maginot en 1939 que Pierre Dac introduit le mot « chleuh » pour désigner les soldats allemands.

Une chanson de circonstance, très populaire en Grande-Bretagne comme en France, était On ira pendre notre linge sur la ligne Siegfried.

Une affiche représentant une carte du monde et la disproportion géographique entre les Alliés et les pays de l'Axe reprend la phrase de Paul Reynaud « Nous vaincrons parce que nous sommes les plus forts ».

Notes et références

Bibliographie

Témoignages, récits, essais

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 Léon Noguéro, Soldat en Alsace-Lorraine (1930-1940), Paris, L'Harmattan, coll. « Mémoires du  / Seconde guerre mondiale », 2017, 248 p.
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Études historiques

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Articles

 Olivier Bellec, « Dans le no man's land, la guerre aux avant-postes de la Ligne Maginot », Ligne de Front, , Éditions Caraktère, mars 2010, lire en ligne.
 Vincent Bernard, « La Drôle de Guerre des Français », Histoire(s) de la Dernière Guerre, , Éditions Caraktère, novembre 2009, lire en ligne.
 Christophe Cony et al., « Les combats aériens de la drôle de guerre », revue Batailles Aériennes, , 1997.
 François Delpla, « De Gaulle et Manstein pendant la Drôle de Guerre, drôles de dissertations sur l'arme blindée », Histoire(s) de la Dernière Guerre, , Éditions Caraktère, janvier 2010, lire en ligne.
 .
 Sébastien Laurent, « Sur le front de la guerre secrète, les services de renseignement français pendant la Drôle de Guerre », Histoire(s) de la Dernière Guerre, , Éditions Caraktère, mars 2010, lire en ligne.
 Philippe Lazarus, « Les divertissements du soldat français, 1939 - 1940,  partie », Militaria Magazine, , Histoire & Collections, août 2011, lire en ligne.
 Philippe Lazarus, « Les divertissements du soldat français, 1939 - 1940,  partie », Militaria Magazine, , Histoire & Collections, octobre 2011, lire en ligne.

Annexes

Articles connexes
 Évacuation des civils en France en 1939-1940 | Exode de 1940 en France
 Mobilisation française de 1939
 Chronologie de la Seconde Guerre mondiale

Liens externes

 Dossier .
 www.cheminsdememoire.gouv.fr Chemins de Mémoire (avec Liens additionnels)

Histoire de la France pendant la Seconde Guerre mondiale
Front de l'Ouest de la Seconde Guerre mondiale
1939
1940

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2021 Bentley Bentayga revealed with updated design
Bentley, Car News, SUV, Turbo
Bentley has unveiled the 2021 Bentayga super SUV. It showcases a freshened up design, new interior features, and of course an even high level of pampering luxury.
Perhaps the most interesting thing is Bentley is introducing a major update for the model. This essentially reaffirms the importance of the model line for the company, and proves just how in-demand SUVs are in this day and age. In fact, Bentley has sold over 20,000 Bentaygas since it debuted.
The exterior styling receives various revisions and takes on Bentley's latest design language. At the front are some new circular headlights featuring LED matrix technology, while in between these is a more striking matrix grille. There's also a new front bumper bar with unique sculpting and sportier air intakes.
Around at the back Bentley has applied a new full-width tailgate that wraps around like a big clamshell. Fans will also spot the all-new oval taillights which are similar to those on the latest Continental GT. A freshly-contoured bumper bar supports wide-split exhaust tips. Speaking about the new model's design, Chris Cole, product line director for the Bentayga, said:
"New Bentayga reflects the truly sophisticated qualities and design make-up of other members of the Bentley family, such as the new Continental GT and all-new Flying Spur. It was already the pinnacle of the luxury SUV sector but now we have taken it even higher."
Inside, the dash has been modernised. The old circular 'bullseye' centre climate vents have been swapped for a more elegant wing-like set, while the centre console is tidied up and now offers storage for smaller items such as a mobile phone. A wireless phone charger has also been introduced, and the touch-screen is updated to a higher-resolution 10.9-inch unit that features anti-glare coating.
Buyers will be able to select between three main seating configurations, including traditional five-seat or a more luxurious four-seat layout, or a full three-row seven-seat setting. In five-seat configuration the second row has been modified so that it can recline further, and seat ventilation has been added.
In four-seat form the 2021 Bentayga adds 30mm of rear knee room and up to 100mm in the reclined position. All layouts also welcome new seats that are reshaped to improve comfort, particularly in the shoulder area, with new foam and cover designs. Micro piping is also available for the first time on the SUV.
As for the powertrains, Bentley will be offering a 4.0-litre twin-turbo V8 that produces 405kW and 770Nm. It promises a 0-100km/h sprint time of 4.5 seconds, and a top speed of 290km/h. Alternatively, buyers will be able to option for a plug-in hybrid later down the track, while the upcoming Bentayga Speed will feature the 6.0-litre twin-turbo W12.
Market entry for the new model will take place later this year. Australian pricing and specs are yet to be announced.
New Bentley Bentayga production begins at updated Crewe facility July 22, 2020
2021 Bentley Bentayga Speed previewed, debuts August 12 August 10, 2020
Bentley Bentayga production surpasses 20,000 milestone June 5, 2020
Bentley considers even bigger SUV than Bentayga – report March 20, 2020

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text:
Wheatley's older tenants go green to grow food and help the planet
Green-fingered Wheatley Group tenants are digging deep and growing their own food in communities – to help cut food miles and enjoy a new hobby. Older people living in Wheatley Group's Livingwell communities have been busy in communal gardens across Glasgow, growing fruit and vegetables
Bell Street Stables wins Historic Environment Scotland Conservation and Climate Change Award
A remarkable conversion of a Victorian council depot to create 52 new homes for affordable rent in the centre of Glasgow has been named as the winner of Historic Environment Scotland's Conservation and Climate Change Award, a special category award of the Royal Incorporation of Architects in S
Wheatley Group unveils £100m glazing and insulation investment
Wheatley Group is to invest £100 million in major glazing, insulation and heating initiatives as part of a green agenda drive.
Housing First pilot launches in Dumfries
A new Housing First Pilot Project has been launched in Dumfries. The Housing First concept offers permanent accommodation to the most vulnerable and complexly disadvantaged people as quickly as possible and provides ongoing support to help them recover from any needs they may have, such as mental he
Young people in Paisley get creative about future thanks to Wheatley
Young people in Paisley are re-imagining life post-pandemic as part of a new arts project. 'From The Rubble' brings young people together to build their creative skills and confidence and explore what it's like living in the 'new normal'.
Glasgow women celebrated in new song Glittery Bums
The fourth single from the debut album from award-winning music collective the Ensemble has been released – and celebrates the confidence of the women of Glasgow. Glittery Bums is the latest release from the project, which sees young people team up with professional musicians to write and reco
New home and new lease of life for tenant thanks to GHA
A GHA tenant who lost his leg to diabetes is enjoying a new lease of life thanks to a wheelchair-adapted home in the neighbourhood where he has lived for decades. At the end of May, Allan McNally and his wife Moira moved into their new home in Kennishead Avenue in the south side of Glasgow after spe
£50,000 for artists to help young people in Wheatley communities
Young people across Scotland are being helped to build their skills and confidence thanks to a new arts project.
New move-on service for women experiencing domestic abuse launches in Scotland
Women experiencing domestic abuse will be able to access a new support service to help them find suitable and safe housing in a different area. The 'Revive Scotland' service is a partnership between Wheatley Group and Homefinder UK. The property-management group has teamed up with Homefi
WLHP development in Whitburn shortlisted for prestigious award
A new development by West Lothian Housing Partnership (WLHP) has been shortlisted for a prestigious award.
Last residents of Glasgow's Bellgrove Hotel moved out
The last remaining residents of the Bellgrove Hotel in Glasgow have been moved out. It has been confirmed that the final 50 men who were staying in the city's hostel, which was dedicated to housing homeless people, have been relocated.
Green light for 14 new affordable homes in Linlithgow
Work is now underway to build 14 affordable homes in a prime location within Linlithgow which are being built by CALA Homes (East) on behalf of West Lothian Housing Partnership (WLHP), part of Wheatley Group. The mix of cottage flats and three-bedroom terraced homes will form part of the popular Que
Last chance to apply for Wheatley Group education bursaries
Time is running out for people to apply for 50 further education bursaries from Wheatley Group. The bursaries are worth up to £1500 for full-time students and £750 for part-time studies and help support people on college and university courses.
Glasgow Wheatley tenants treated to iconic photos of the city
Wheatley Group has just opened a new Livingwell complex designed to help older people live independently at Bellrock Street in Cranhill.
Martin Armstrong to step down as Wheatley chief executive next year
Wheatley Group chief executive Martin Armstrong has revealed plans to step down next summer. Mr Armstrong, whose public-sector career across the UK spans a quarter of a century, had intended to step down last year. However, at Wheatley Board's request, he stayed on to lead the group's re


text:
United Nations Human Rights Committee calls on Liberia to Prosecute Perpetrators of Civil War Atrocities
News, Press Releases / By CJA
The United Nations Human Rights Committee (the Committee), a body of independent experts that monitors the implementation of the International Covenant on Civil and Political Rights (ICCPR) by its State parties, has issued strong concluding observations on Liberia's continued impunity for past crimes and human rights violations and calls upon the Liberian government to establish, as a matter of priority, a process of accountability for war crimes.
On 26 July 2018, following the first ever review of the human rights situation by the Committee, which included a dialogue with the Liberian government, the Committee concluded that it "regrets the very few steps taken to implement the bulk of the Truth and Reconciliation Commission (TRC) recommendations of 2009." It also expressed "concern that none of the alleged perpetrators of gross human rights violations and war crimes mentioned in the TRC report, has been brought to justice, and that some of those individuals are or have been holding official executive positions, including in the government."
In advance of this historic meeting, a coalition of 76 organizations—including 56 Liberian NGOs and 20 international organizations—issued a submission to the Committee highlighting the "failure of the Government of Liberia to undertake fair and credible prosecutions of international crimes committed in Liberia during armed conflicts between 1989 and 2003, and to end impunity for civil war-era crimes."
Liberia's back to back civil wars resulted in numerous crimes under international law, including the killing of tens of thousands of civilians, the displacement of half the population, summary executions and numerous large-scale massacres; widespread and systematic rape; mutilation and torture; and large-scale forced conscription and use of child combatants. Despite a Truth and Reconciliation Commission report identifying crimes committed by all sides of the conflict, and recommending reparations for victims as well as justice in the form of a special international-national hybrid court, Liberia has yet to take steps to implement such recommendations. According to the Committee's assessment "such a situation fosters a climate of impunity and fails to achieve transitional justice."
During the review, Liberian government representatives pledged to issue a public statement on plans to implement the TRC report. Since assuming office, President George Weah has yet to publically share his opinion on accountability for grave crimes committed during the country's two civil wars, despite his earlier support while serving as a Goodwill Ambassador to UNICEF. This comes in a context where calls for justice by Liberian civil society and ordinary citizens, in addition to international organizations, continue to grow. Moreover, prosecutions of former rebel commanders and military leaders are taking place in the U.S. and Europe while not a single person has been prosecuted in Liberia for civil war-era crimes.
At a well-attended press conference in Monrovia on August 1, Adama Dempster, Secretary General of the Civil Society Human Rights Advocacy Platform of Liberia noted that the government representatives assured the UN Committee that their position on accountability would be made clear upon their return to Liberia and called on the government to issue a statement without further delay.
Impunity for past crimes in Liberia is now one of three priority issues before the Committee, making accountability for civil war era abuses one of the most pressing matters that Liberia faces under its ICCPR review. Liberia is now tasked with responding to the UN's calls to implement measures to provide justice, truth, and reparations for civil war victims, including: "ensure that all alleged perpetrators of gross human rights violations and war crimes are impartially prosecuted and, if found guilty, convicted and punished in accordance with the gravity of the acts committed"; "remove any persons who have been proven to be involved in gross human rights violations and war crimes from official positions"; take "all measures necessary to implement the TRC recommendations"; and develop and implement reparations for war time victims. Liberia will now need to provide a follow-up report on these matters by 2020 (two years prior to the regularly scheduled periodic report).
Weah's attendance before the UN General Assembly in September may be another opportunity for the government to make clear its intentions to bring to justice, in fair trials, all those suspected of criminal responsibility for war crimes. As the 76 group submission notes, impunity in the name of reconciliation cannot continue in Libera."Justice [for war crimes] must be one of the cardinal points of the President's new agenda," says Hassan Bility, Executive Director of the Global Justice and Research Project, "otherwise there will be no lasting peace in Liberia."
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Just a little story I wrote the other day, I hope it is both amusing and profound and if it aint well...what can I say??
Once upon a time in a not to distant present, lived a man that every one wanted to find and understand. His Name started with the letter "G" and some called him Gravity and some called him God.
For thousands of years people everywhere have been looking for him. The scientist, the physicist have spent millions of hours in the pursuit of "G". The religious people have spent thousands of years defending him and ideologically supporting his existence.
All they knew was that "G" could be felt and not seen and that he was a very attractive proposition for finding him made one like him. If one could feel his attraction one was a part of him. And of course through out reality one could feel his pull. But the attraction was from all directions and we all stumble trying to understand where to start looking for "G" was every where. and no where at the same time.
The scientists called him a weak force and the religious people called him the strongest force. A lot of people couldn't care either way and couldn't decide what he was.
But any way, "G" was pretty smart because he knew that if he stayed out of sight and kept every one chasing the wrong tail he would stay unknown for longer but he also knew that one day some one is going to find him and he will become known.
He knew that the best way to hide was in fact not to, in fact he knew that if he put the answer right in front of the people looking for him that they would never find him.
Then one day people started to realise the truth. That the "G" they were chasing was actually themselves and that when they looked in the mirror they could feel him by simply feeling themselves. For "G" could only be felt and not seen.
For "G" could only be felt and not seen.
Who knows? Higgs may pop up one day allowing us to say, "oh, that's 'g'".
The scientists are not looking for the "G". They are looking for the mirror.
We are part of the universe, and by understanding it we understand ourselves.
would understanding our own nature reveal 'g' to us? i'd say so. I think looking for G and for ourselves amounts to one in the same. I guess that's why i see science and religion so similar. Everyone's looking for the same thing, we just all have out own methods for trying to find it.
"In search of G" You must log in or register to reply here.


text:
WTF? Colin Firth Almost Got Pulled From The Kingsman Church Scene, Here's Why
Feb. 16. 2015 8:49 AM
Super agent Harry Hart (Colin Firth) finds himself behind enemy lines. He has infiltrated a hateful church community in rural Kentucky, where he is supposed to observe a test run of a broadcasting-signal scheme launched by the evil Richmond Valentine (Samuel L. Jackson). Except, the signal affects Harry, leading to one of the most memorable fight sequences we are destined to see on screen this year.
Yet, here's the funny part. Kingsman: The Secret Service director Matthew Vaughn tells me that Firth almost never made it into the scene in the first place. He almost got cut. Why? We'll discuss, but will have to use spoilers from Kingsman. You have been warned!
Vaughn jumped on the phone with me prior to Kingsman opening to an impressive $35.6 million over the weekend. The director was unsure if audiences were going to embrace his comically violent spy-spoof thriller… and we talked about his unusual decision to cast the dapper Colin Firth in a role usually reserved for the likes of Daniel Craig or Matt Damon. But Vaughn said he knew that Firth was physically and mentally prepared to tackle the demanding needs of the film's action – specifically the church sequence – because the director tested his leading man multiple times during the shoot.
The way he explains it, Vaughn says:
I was like… this is a physical role and you're going to have to train for the next six months. And if you're not willing to do it, I'm not willing to give you the role. To be blunt, after three months, I'm going to test you. If I think you're going to pull it off, then you've got the role. But if I think you don't, you're going to thank me for not casting you, because the worst thing [that] can happen is you look like an idiot doing this stuff in a church. Both of our credibility is gone at that point. So there's no point in you blindly doing this movie thinking we're going to pull off the action [and that church fight sequence], because we won't. And to his credit, he said, 'I get it. I'm going to train.' And he trained like you wouldn't believe. And he pulled it off.
Reading the reactions to the church scene has been interesting this weekend. Many audience members who came back to CinemaBlend for post-screen chatter praised the action choreography of the church fight. Some, however, did admit to being turned off to the violence in the sequence, with several members of the church dying violently at the hands of Firth's temporarily brainwashed lethal agent. Listen to Colin Firth and Matthew Vaughn discuss the breakdown of the scene in this MTV interview:
What did you think of the scene? Did Firth convince you that he's a total badass? Or should Matthew Vaughn have gone in a different direction?
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Uplink: Innovation — The Aerospace Company, The space community was in search of a standard to make launching smallsats more flexible.
The Aerospace Corporation (Aerospace) has developed a new and innovative smallsat standard called a Launch Unit (Launch-U).
SSL, a Maxar Technologies company, designs and builds advanced spacecraft systems that enable the firm's customers to connect, inform and protect people around the globe.
Engaging in innovative design, development and the manufacture of mobile, satellite-based antenna systems that are focused on the delivery of broadband internet to any location, C-COM Satellite Systems has developed a proprietary, one-button, auto-acquisition controller technology for rapid antenna point a to GEO satellite with the press of a single button.
At last we know — on July 12, the FCC Commissioners (via a 4 to 0 vote) backed the proposal by Intelsat and SES (with Intel) to see a restructuring of C-band spectrum over the U.S. to help develop 5G — the firms wish this to occur rapidly and might even extend the concept from an initial 100 MHz to 200 or even 300 MHz.
EVERYWHERE Communications LLC launched in June of 2018. To learn more about this enterprise, Patrick Shay, the founder and CEO of the company, discussed this new endeavor.
A new era in mobility and communications is now being entered — an era that is exciting and challenging and one that has the potential to take connectivity to a entirely new level of access and use.
The new space economy presents an opportunity for game-changing innovation through the evolution of satellite capabilities, from communications and transmission platforms to those with cloud service capabilities such as storage and computer resources.
Selling bottled water in space may seem like a giant leap for mankind. However, the news that Surrey Satellite Technology Ltd. (SSTL), Goonhilly Earth Station and Astrobotic have joined forces to design the sophisticated infrastructure required to support a new era of private and public sector lunar endeavors brings this idea into closer orbit.
Being born in the 1960's, I've always felt miniaturization is cool. That feeling hasn't always been shared by my three lovely daughters, taking them round a model village on a nice summer's day looking at the amazing miniature railway junction box. Or, closer to their interest, marveling at how many thousands of milliamps per hour they can now squeeze into a smartphone. They just don't get it and look at me like I'm some boggle eyed alien*.
The market for top tech talent is highly competitive. To meet recruiting goals, employers need to improve the candidate experience and sharpen their social-recruiting practices.
It is hard to read anything about business or technology these days without coming across the Internet of Things (IoT). In 2014, for the first time, the number of mobile phones and other devices equaled the number of human beings on Earth, about 7.2 billion. The analyst firm Gartner says that by 2020, there will be 26 billion connected devices — and most of them will be connecting with other devices rather than people.
The vast amount of plastics produced throughout the world is causing a monumental problem for the governments and organizations that must tackle this growing waste materials crisis.
From mission-critical communications to virtual business meetings, advancements in consumer and government communication technologies over the years have driven a rising demand for reliable connectivity around the world via Low Earth Orbit (LEO) satellites.
NASA is sending two cubesats to observe Mars — the agency is exhibiting some significant changes and adjustments in the electronics and the design of smallsats with this mission.
The current state of the art for interplanetary space travel is essentially unchanged from the techniques that were used to send Mariner 10 to Venus and Mercury in 1973. Once in space, a satellite's chemical rocket engine provides high thrust for a very brief period, starting a long coast phase that takes advantage of as many gravity assist maneuvers as possible. Many months or years are then required to travel anywhere interesting — even maximizing propellant efficiency in this way, there are still significant limitations placed on spacecraft mass and payload.
President of the Mobile Satellite Users Association, Catherine spearheads the group's mission to promote mobility market development and mobility innovation.
There are a number of points to consider in any conversation concerning the broadband issues that the United Kingdom (UK) currently faces. The promise of 10Mbit/s for everyone in the country is an empty one, at least in a world where the government refuses to consider satellite connection for rural areas or considers allowing thousands of satellites to be launched into space by multiple companies.
Uplink: Innovation — AsiaSat, Wet antenna attenuation?
AsiaSat has investigated C-band's exceptionally high rain fade attenuation reported by uplink stations during monsoon seasons in South East Asia — techniques for uplink station operators to mitigate against these issues, to improve their service level availability, are presented in this article.


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Logan @dismydeddybear
To Watch
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Logan Mead @dismydeddybear
Logan Mead
@dismydeddybear


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Q: Extract range from string I have a report that exports to multiple Excel sheets.  The first row on each sheet has a similar statement to the below.

Paste Data in range A1:K44 only.  Data to come from "History" dump in
  Part Inquire.

I need to extract the range from that string.  I've tried to use the split and find functions, but the length of the range changes (i.e. A1:AB53, A15:C20, etc.).
I welcome any input as to how to extract the range.

A: Just use Split() to split your string into an array and then grab the 5th element (index = 4):
Const SOME_TEXT As String = "Paste Data in range A1:K44 only. Data to come from ""History"" dump in Part Inquire."

Dim strRange As String
strRange = Split(SOME_TEXT)(4)

Debug.Print strRange

Output:
A1:K44

If the text that appears isn't quite so consistent, you can use a regex to extract the first range that appears within your string:
Const SOME_TEXT As String = "This string has A1:K44 in it but is inconsistent with the rest."

Dim re
Set re = CreateObject("VBScript.RegExp")
re.Pattern = "\b[A-Z]{1,3}\d+:[A-Z]{1,3}\d+\b"

If re.Test(SOME_TEXT) Then
    Debug.Print re.Execute(SOME_TEXT)(0)
End If

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