COVID-19 in the Arab countries: Three-year study.

Background: Twenty-two Arab countries share a common language, history, and culture. Nevertheless, governmental policies, healthcare systems, and resources differ from one Arab country to another. We have been following Coronavirus (COVID-19) from the beginning in each Arab country. In the present study, we aimed to assess the prevalence of COVID-19 in the Arab world and to compare these findings with other significantly affected countries. Methods: Websites of the World Health Organization, World COVID-vaccinations tracker, Worldometer, and Ministries of Health were used to extract COVID-19 data in all Arab countries between the period January 2020 to December 2022. Results: All Arab countries had 14,218,042 total confirmed COVID-19 cases, 13,384,924 total recovered cases and 173,544 total related deaths. The trend demonstrated that the third quarter of 2021 recorded the highest death toll and the first quarter of 2022 recorded the highest number of confirmed and recovered cases. Compared to the top 15 affected countries, the Arab world ranked last as it had the lowest overall incidence per million population (PMP) of 31,609. The data on total deaths PMP showed that India had the lowest number of deaths with only 377 cases followed by the Arab world with 386 cases. Conclusions: Although the number of confirmed, death, and recovered cases of COVID-19 have greatly reduced in the last quarter of 2022 in most Arab countries, many Arab countries still need to re-campaign about COVID-19 vaccines and raise awareness programs about boosters. COVID-19 has had a relatively smaller impact on Arab countries than on other countries that have been significantly affected.

Addition of Gallic Acid Overcomes Resistance to Cisplatin in Ovarian Cancer Cell Lines.

OBJECTIVE: Ovarian cancer is one of the leading causes of cancer-related mortality in women, and is often associated with drug resistance. Therefore, finding effective drugs, including naturally derived compounds, is urgently needed. Herein, we aimed to test the anti-cancer potential of gallic acid monohydrate (GA) and its congeners on cisplatin-sensitive (A2780S), and resistant (A2780CP) ovarian cancer and normal ovarian (HOSE6-3) cell lines. METHODS: Cytotoxicity was assessed by AlamarBlue and CCK08 assays by exposing cells to different concentrations of cisplatin (0-21µg/mL), GA and its congeners (0-100µg/mL), and a combination of GA and cisplatin. Apoptosis was estimated by Hoechst stain and monitoring the relative RNA expression of the apoptotic effector caspase-3 using qRT-PCR. RESULTS: GA decreased cell viability in a concentration-dependent manner in all cell lines, with an IC50 of 19.39µg/mL (A2780S), 35.59 µg/mL (A2780CP), and 49.32µg/mL (HOSE6-3). GA displayed higher cytotoxicity than its congeners. An apoptotic rate estimation of approximately 20% and 30% was obtained in A2780S and A2780CP. While the cytotoxicity observed with cisplatin and GA was comparable, combining the two enhanced the cytotoxicity significantly, especially in the A2780CP cell line (p<0.05). CONCLUSION: These data suggest that GA may help overcome the resistance. Hence, the cytotoxic effects of GA, especially on chemo-resistant ovarian cancer cells merit further investigation.
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Hymenialdisine is Cytotoxic Against Cisplatin-Sensitive but Not Against Cisplatin-Resistant Cell Lines.

OBJECTIVES: New compounds are needed to overcome the resistance to commonly used cytotoxic chemotherapy for epithelial ovarian cancer. Marine sponges are a rich source of diverse chemical compounds and hymenialdisine has been found to have antiproliferative effects. This study aimed to investigate the cytotoxic effect of hymenialdisine in cisplatin-sensitive and cisplatin resistant ovarian cancer cell lines. METHODS: This study took place at Sultan Qaboos University, Muscat, Oman between August and November, 2019. The anti-cancer effects of hymenialdisine or cisplatin were assessed using treating cells with different concentrations of hymenialdisine and cisplatin. Cell viability was determined using the AlamarBlue® Assay. RESULTS: The half-maximal inhibitory concentration (IC50) of cisplatin was estimated at 31.4 µM for A2780S and 76.9 µM for A2780CP, whereas the IC50 of hymenialdisine was evaluated at 146.8 µM for A2780S cells. Despite the higher concentrations of hymenialdisine (up to 300 µM), IC50 could not be determined for the A2780CP cell line. CONCLUSION: When compared to cisplatin, hymenialdisine was less toxic against both A2780S and A2780CP ovarian cancer cell lines.

Correlation of expression of Akt1 and E2F1 and their phosphorylated forms in breast cancer patients with clinicopathological parameters.

Breast cancer is the leading cancer worldwide among women. Traditional clinicopathological prognostic and predictive markers need refining to improve clinical outcomes. This study explored the association between traditional clinicopathological factors and the expression of Akt1 and E2F1 transduction proteins and their phosphorylated forms in breast cancer, to determine their value as novel biomarkers and potential therapeutic targets. Tumor tissues from 94 female breast cancer patients were examined for immunophenotypic expression of total Akt1, pAkt1 (Serine 473), pAkt1 (Threonine 308), total E2F1, pE2F1 (Thr433) and pE2F1 (Ser337). The expression of pAkt1 (Ser473) was significantly associated with ER/PR positive status and total E2F1 with older age (> 50), lymph node involvement and HER2 positivity. There was a significant association between triple negative cancers and total and pAkt1 (Thr308). pAkt1 (Ser473) showed an inverse relationship with Luminal B cancers and pE2F1 (Thr433) showed an inverse association with triple negative cancers. Higher expression of pE2F1 (Ser337) was associated with better OS. Both pAkt1 (Ser473 and Thr308) proteins showed significant association with poorer patient outcomes. E2F1 (Ser337) showed a significant positive correlation with response to chemotherapy. The study suggests that a pAkt1-/pE2F1+ phenotype could indicate an opportunity to minimize chemotherapeutic options in older women; conversely a pAkt1+/pE2F1- phenotype could prompt a more aggressive regimen. Further exploration of this phenotype in younger women with breast cancer and triple-negative breast cancers is warranted.

A review of the prevalence of COVID-19 in the Arab world.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a rapidly spreading disease worldwide. It is a real test for all health authorities including Arab countries. In this review, we aimed to assess the prevalence of COVID-19 in the Arab world. In addition, to compare the findings of this study with other top affected countries. METHODOLOGY: We searched for official websites from the Ministries of Health and other official sources in all 22 Arab countries. Medline, Science Direct and Google Scholar websites were also used to search for COVID-19, 2019 novel coronavirus, SARS-CoV-2 and coronavirus. The time period was from 1 January 2020 to 31 May 2020. RESULTS: As of May 31, 2020, COVID-19 has caused 290,428 confirmed cases, 3,696 deaths and 157,886 cured cases in all Arab countries. In terms of confirmed cases, Saudi Arabia followed by Qatar, UAE, Kuwait and Egypt have the highest reported cases. However, the total number of deaths was dominant in Egypt, followed by Algeria, Saudi Arabia, Sudan and UAE. In comparison to other non-Arab countries and confirmed cases, Arab countries come fourth after USA, Brazil and Russia. In terms of death, the Arab world is not listed as the top ten affected countries as only scored eight deaths per million have been recorded. CONCLUSIONS: Most Arab countries took some serious early steps to minimize the outbreak of COVID-19. At the moment, controlling the source of infection, the route of transmission and taking care of infected patients are the main challenges for health authorities in all Arab countries.

Boswellic acid sensitizes gastric cancer cells to Cisplatin-induced apoptosis via p53-mediated pathway.

BACKGROUND: Cisplatin (CDDP) is an effective anticancer drug for Gastric cancer (GC) that induces apoptosis by altering pro- (p53) and anti-apoptotic (Akt and NFkB) proteins; however, chemoresistance remains a big challenge. Additional compounds with promising anticancer effects such as AKBA (Acetyl-keto-beta boswellic acid) may overcome the resistance. However, its role in CDDP-induced apoptosis in GC has not been studied. This study aimed to examine the effectiveness of AKBA on p53-mediated, CDDP-induced apoptosis in GC cells. AGS and NCI-N87 cells were treated with different concentrations (0, 25, 50, 100 µM) of CDDP and/or AKBA. METHODS: P53, Akt and NFkB proteins and apoptosis were assessed by Western blot and flow cytometry. The role of p53 was determined by inhibiting its function via the siRNA approach. RESULTS: The results revealed that CDDP and AKBA significantly increased p53 content in both cells, while Akt and NFkB were significantly decreased. Both compounds significantly induced apoptosis in a dose-dependent manner. AKBA sensitized GC cells to CDDP-induced apoptosis by altering the protein expression. P53 downregulation affected Akt and NFkB proteins with a slight increase in apoptosis induction in the combination treated groups. CONCLUSIONS: Altogether, our findings suggest that AKBA enhances GC cell sensitivity to CDDP-induced apoptosis via the p53 pathway.

Curcumin Ameliorates Kidney Function and Oxidative Stress in Experimental Chronic Kidney Disease.

Chronic kidney disease (CKD) is known to involve inflammation, oxidative stress and apoptosis. Here, we investigated the impact of curcumin (diferuloyl methane, a phenolic turmeric pigment), which has strong antioxidant, anti-inflammatory and anti-apoptotic activities on kidney structure and function in rats with adenine-induced CKD. Rats were treated for 5 weeks with adenine to induce CKD-like renal damage and combined with three doses of curcumin. Markers of kidney function and oxidative stress were quantified in plasma, urine, renal homogenates and on kidney tissue. Curcumin was found to significantly abate adenine-induced toxic effects such as reduced creatinine clearance, elevated neutrophil gelatinase-associated lipocalin levels and raised urinary N-acetyl-ß-D-glucosaminidase activities. Curcumin markedly reduced renal morphological damage and histopathological markers of inflammation, fibrosis and apoptosis. Curcumin further reduced adenine-induced hypertension, urinary albumin, the inflammatory cytokines IL-1ß, IL-6 and TNF-α, cystatin C and adiponectin. It restored plasma sclerostin concentrations and lowered oxidative stress in renal homogenates. In animals treated with the two higher curcumin concentrations, alone or in combination with adenine, an increased expression of the antioxidative transcription factor Nrf2 was found as well as up-regulation of the activity of its direct target glutathione reductase, and of an indirect target, the glutathione level. In conclusion, curcumin exhibits salutary effects against adenine-induced CKD in rats by reducing inflammation and oxidative stress via up-regulation of the transcription factor Nrf2.

Calpain-1 Expression in Triple-Negative Breast Cancer: A Potential Prognostic Factor Independent of the Proliferative/Apoptotic Index.

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer in which calpain system plays an important role in its cellular processes including apoptosis and proliferation. Although such roles have been assessed in tumor pathogenesis, the correlation of its expression to the proliferating/apoptotic index has not been studied yet. Immunohistochemical staining of calpain-1 was performed on paraffin-embedded tissues to correlate its expression with clinicopathological variables and outcome. The proliferation activity was determined by calculating the percentage of cells expressing the Ki-67 antigen. The apoptotic index was assessed morphologically and biochemically using Haematoxylin & Eosin method and Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, respectively. Calpain-1 was significantly expressed in TNBC tissues varying from low to high with a significant correlation to lymph node status but not with the other clinicopathological variables, suggesting its role as a prognostic factor. In addition, a positive correlation was found between both apoptotic counts assays (P < 0.001, r = 0.547) as well as with proliferation (P = 0.045). Calpain-1 expression had no significant correlation with either proliferation (P = 0.29) or apoptotic indices (P = 0.071 and P = 0.100). Determining calpain-1 expression may provide relevant prognostic value for TNBC cancer patients.

Fatty acid synthase regulates the chemosensitivity of breast cancer cells to cisplatin-induced apoptosis.

Fatty acid synthase (FASN) is a key enzyme in fat biosynthesis that is over-expressed in advanced breast cancer stages. Cisplatin (CDDP) is a platinum-based drug used in the treatment of certain types of this disease. Although it was shown that FASN inhibition induced apoptosis by enhancing the cytotoxicity of certain drugs in breast cancer, its role in regulating the chemosensitivity of different types of breast cancer cells to CDDP-induced apoptosis is not established yet. Therefore, two different breast cancer cell lines; triple negative breast cancer (TNBC; MDA-MB-231) and triple positive breast cancer (TPBC; BT-474) cells were used to examine such role. We show that TNBC cells had naturally less fat content than TPBC cells. Subsequently, the fat content increased in both cells when treated with Palmitate rather than Oleate, whereas both fatty acids produced apoptotic ultra-structural effects and attenuated FASN expression. However, Oleate increased FASN expression in TPBC cells. CDDP decreased FASN expression and increased apoptosis in TNBC cells. These effects were further enhanced by combining CDDP with fatty acids. We also illustrate that the inhibition of FASN by either siRNA or exogenous inhibitor decreased CDDP-induced apoptosis in TPBC cells suggesting its role as an apoptotic factor, while an opposite finding was observed in TNBC cells when siRNA and fatty acids were used, suggesting its role as a survival factor. To our knowledge, we are the first to demonstrate a dual role of FASN in CDDP-induced apoptosis in breast cancer cells and how it can modulate their chemosensitivity.

Platinum-Based Drugs Differentially Affect the Ultrastructure of Breast Cancer Cell Types.

Breast cancer (BC) is the most common cause of cancer-related death worldwide. Although platinum-based drugs (PBDs) are effective anticancer agents, responsive patients eventually become resistant. While resistance of some cancers to PBDs has been explored, the cellular responses of BC cells are not studied yet. Therefore, we aim to assess the differential effects of PBDs on BC ultrastructure. Three representative cells were treated with different concentrations and timing of Cisplatin, Carboplatin, and Oxaliplatin. Changes on cell surface and ultrastructure were detected by scanning (SEM) and transmission electron microscope (TEM). In SEM, control cells were semiflattened containing microvilli with extending lamellipodia while treated ones were round with irregular surface and several pores, indicating drug entry. Prolonged treatment resembled distinct apoptotic features such as shrinkage, membrane blebs, and narrowing of lamellipodia with blunt microvilli. TEM detected PBDs' deposits that scattered among cellular organelles inducing structural distortion, lumen swelling, chromatin condensation, and nuclear fragmentation. Deposits were attracted to fat droplets, explained by drug hydrophobic properties, while later they were located close to cell membrane, suggesting drug efflux. Phagosomes with destructed organelles and deposits were detected as defending mechanism. Understanding BC cells response to PBDs might provide new insight for an effective treatment.

Cisplatin Induces Apoptosis Through the Endoplasmic Reticulum-mediated, Calpain 1 Pathway in Triple-negative Breast Cancer Cells.

BACKGROUND: Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) is an aggressive type that can be treated using platinum-based chemotherapy such as cisplatin (cis-diamminedichloroplatinum II). Although the calpain protein is essential in many cellular processes, including apoptosis, cell signaling, and proliferation, its role in cisplatin-induced apoptosis in TNBC cells is not fully understood. The present study assessed calpain 1-dependent, cisplatin-induced apoptosis in TNBC cells. MATERIALS AND METHODS: MDA-MB231 cells were treated with different concentrations of cisplatin (0, 20, and 40 µM). The cisplatin deposit and its effect on endoplasmic reticulum and, subsequently, calcium release were detected using transmission electron microscopy and Von Koss staining, respectively. Calpain 1 messenger RNA, protein content, and apoptosis was measured using reverse transcriptase-polymerase chain reaction, Western blotting, and Hoechst stain, respectively. In addition, calpain modulation, by either activation or inhibition, and its effect on cisplatin-induced apoptosis were assessed. RESULTS: Our results showed that cisplatin induced endoplasmic reticulum stress, indicated by an increase in calcium staining and protein expression of glucose-regulated protein 78 and calmodulin, followed by cleavage of α-fodrin and caspase-12 and, eventually, apoptosis. Cyclopiazonic acid showed a similar effect and enhanced the sensitivity of these cells to cisplatin treatment. In contrast, calpain 1 inhibition by both specific small interfering RNA and exogenous inhibitor (calpeptin) attenuated cisplatin-induced apoptosis in these cells. CONCLUSION: Altogether, these findings suggest, for the first time, that calpain 1 activation by endoplasmic reticulum plays an essential role in sensitizing TNBC cells to cisplatin-induced apoptosis. This finding will allow exploration of new insights for the treatment of TNBC by overcoming its resistance to apoptosis.

In Vitro Apoptosis Triggering in the BT-474 Human Breast Cancer Cell Line by Lyophilised Camel's Milk.

Breast cancer is a global health concern and is a major cause of death among women. In Oman, it is the most common cancer in women, with an incidence rate of 15.6 per 100,000 Omani females. Various anticancer remedies have been discovered from natural products in the past and the search is continuing for additional examples. Cytotoxic natural compounds may have a major role in cancer therapy either in potentiating the effect of chemotherapy or reducing its harmful effects. Recently, a few studies have reported advantages of using crude camel milk in treating some forms of cancer. However, no adequate data are available on the lyophilised camel's milk responsibility for triggering apoptosis and oxidative stress associated with human breast cancer. The present study aimed to address the role of the lyophilised camel's milk in inducing proliferation repression of BT-474 and HEp-2 cells compared with the non-cancer HCC1937 BL cell line. Lyophilized camel's milk fundamentally repressed BT-474 cells growth and proliferation through the initiation of either the intrinsic and extrinsic apoptotic pathways as indicated by both caspase-3 mRNA and its action level, and induction of death receptors in BT-474 but not the HEp-2 cell line. In addition, lyophilised camel's milk enhanced the expression of oxidative stress markers, heme-oxygenase-1 and reactive oxygen species production in BT-474 cells. Increase in caspase-3 mRNA levels by the lyophilised camel's milk was completely prevented by the actinomycin D, a transcriptional inhibitor. This suggests that lyophilized camel's milk increased newly synthesized RNA. Interestingly,it significantly (p<0.003) repressed the growth of HEp-2 cells and BT-474 cells after treatment for 72 hours while 24 hours treatment repressed BT-474 cells alone. This finding suggests that the lyophilised camel's milk might instigate apoptosis through initiation of an alternative apoptotic pathway.

Renal and myocardial histopathology and morphometry in rats with adenine - induced chronic renal failure: influence of gum acacia.

BACKGROUND/AIM: Chronic kidney disease (CKD) is associated with increased occurrence of cardiovascular system dysfunction. Previous studies have revealed a number of alterations in the kidneys and heart during CKD. However, unbiased quantitative studies on these structures in this disease have so far not been addressed. MATERIALS AND METHODS: We induced CKD in rats by feeding adenine (0.75% (w/w), four weeks) and using unbiased stereological methods, investigated the effect of the ensuing CKD on the kidneys and left ventricular structure. Since gum acacia (GA) has previously been shown to ameliorate the severity of CKD in humans and rodents, we investigated the effect of giving GA (15% (w/v) in the drinking water concomitantly with adenine) on the kidneys and left ventricular structure using the above model. RESULTS: The CKD was confirmed by standard biochemical indices in plasma and urine and by accumulation of the uremic toxin indoxyl sulfate. Additionally, it increased blood pressure. In rats with CKD absolute volume of left ventricle was significantly increased, and the volume density and absolute volume of myocardial capillaries were decreased, whilst the same parameters of myocardium and interstitial tissue were increased. Renal morphometry demonstrated significant increase in kidney volume and interstitial tissue in adenine- treated rats. Similarly, glomerular Bowman's capsule was significantly thickened. The myocardial and renal changes were significantly mitigated by GA treatment. CONCLUSIONS: These results add to our existing knowledge of the pathophysiology of adenine - CKD and provides plausible histopathological and morphometric evidence for the usefulness of GA in CKD.