A critical analysis of SARS-CoV-2 (COVID-19) complexities, emerging variants, and therapeutic interventions and vaccination strategies.

Coronavirus is a family of viruses that can cause diseases such as the common cold, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS). The universal outbreak of coronavirus disease 2019 (COVID-19) caused by SARS coronaviruses 2 (SARS-CoV-2) has become a global pandemic. The ß-Coronaviruses, which caused SARS-CoV-2 (COVID-19), have spread in more than 213 countries, infected over 81 million people, and caused more than 1.79 million deaths. COVID-19 symptoms vary from mild fever, flu to severe pneumonia in severely ill patients. Difficult breathing, acute respiratory distress syndrome (ARDS), acute kidney disease, liver damage, and multi-organ failure ultimately lead to death. Researchers are working on different pre-clinical and clinical trials to prevent this deadly pandemic by developing new vaccines. Along with vaccines, therapeutic intervention is an integral part of healthcare response to address the ongoing threat posed by COVID-19. Despite the global efforts to understand and fight against COVID-19, many challenges need to be addressed. This article summarizes the current pandemic, different strains of SARS-CoV-2, etiology, complexities, surviving medications of COVID-19, and so far, vaccination for the treatment of COVID-19.

Resveratrol (RV): A pharmacological review and call for further research.

Resveratrol (RV) is a well-known polyphenolic compound in various plants, including grape, peanut, and berry fruits, which is quite famous for its association with several health benefits such as anti-obesity, cardioprotective neuroprotective, antitumor, antidiabetic, antioxidants, anti-age effects, and glucose metabolism. Significantly, promising therapeutic properties have been reported in various cancer, neurodegeneration, and atherosclerosis and are regulated by several synergistic pathways that control oxidative stress, cell death, and inflammation. Similarly, RV possesses a strong anti-adipogenic effect by inhibiting fat accumulation processes and activating oxidative and lipolytic pathways, exhibiting their cardioprotective effects by inhibiting platelet aggregation. The RV also shows significant antibacterial effects against various food-borne pathogens (Listeria, Campylobacter, Staphylococcus aureus, and E. coli) by inhibiting an electron transport chain (ETC) and F0F1-ATPase, which decreases the production of cellular energy that leads to the spread of pathogens. After collecting and analyzing scientific literature, it may be concluded that RV is well tolerated and favorably affects cardiovascular, neurological, and diabetic disorders. As such, it is possible that RV can be considered the best nutritional additive and a complementary drug, especially a therapeutic candidate. Therefore, this review would increase knowledge about the blend of RV as well as inspire researchers around the world to consider RV as a pharmaceutical drug to combat future health crises against various inhumane diseases. In the future, this article will be aware of discoveries about the potential of this promising natural compound as the best nutraceuticals and therapeutic drugs in medicine.

Sulforaphane Analogues with Heterocyclic Moieties: Syntheses and Inhibitory Activities against Cancer Cell Lines.

Recent studies have shown that sulforaphane (SFN) selectively inhibits the growth of ALDH⁺ breast cancer stem-like cells.Herein, a series of SFN analogues were synthesized and evaluated against breast cancer cell lines MCF-7 and SUM-159, and the leukemia stem cell-like cell line KG-1a. These SFN analogues were characterized by the replacement of the methyl group with heterocyclic moieties, and the replacement of the sulfoxide group with sulfide or sulfone. A growth inhibitory assay indicated that the tetrazole analogs 3d, 8d and 9d were significantly more potent than SFN against the three cancer cell lines. Compound 14c, the water soluble derivative of tetrazole sulfide 3d, demonstrated higher potency against KG-1a cell line than 3d. SFN, 3d and 14c significantly induced the activation of caspase-3, and reduced the ALDH⁺ subpopulation in the SUM159 cell line, while the marketed drug doxrubicin(DOX) increased the ALDH⁺ subpopulation.

p53 suppresses 14-3-3γ by stimulating proteasome-mediated 14-3-3γ protein degradation.

14-3-3 proteins are a family of highly conserved polypeptides that interact with a large number of proteins and play a role in a wide variety of cellular processes. 14-3-3 proteins have been demonstrated overexpressed in several cancers and serving as potential oncogenes. In a previous study we showed one isoform of the 14-3-3 family, 14-3-3γ was negatively regulated by p53 through binding to its promoter and inhibiting its transcription. In the present study we investigated both p53 and 14-3-3γ protein levels in human lung cancerous tissues and normal lung tissues. We found 14-3-3γ expression correlated to p53 overexpression in lung cancer tissues. Ecotopic expression of wild-type p53, but not mutant p53 (R175H) suppressed both endogenous and exogenous 14-3-3γ in colon and lung cancer cell lines. Further examination demonstrated that p53 interacted with C-terminal domain of 14-3-3γ and induced 14-3-3γ ubiquitination. MG132, a specific inhibitor of the 26S proteasome, could block the effect of p53 on 14-3-3γ protein levels, suggesting that p53 suppressed 14-3-3γ by stimulating the process of proteasome-mediated degradation of 14-3-3γ. These results indicate that the inhibitory effect of p53 on 14-3-3γ is mediated also by a post-transcriptional mechanism. Loss of p53 function may result in upregulation of 14-3-3γ in lung cancers.

[Reduced estimated glomerular filtration rate and proteinuria are associated with increased cardiovascular events rate in octogenarian population].

OBJECTIVE: To determine the relationship between estimated glomerular filtration rate (eGFR) and proteinuria with cardiovascular events in subjects aged 80 years or older. METHODS: Data for this retrospective prognostic study were drawn from the patient database for routine checkup in Beijing hospital between January 2001 to December 2001. Baseline eGFR and proteinuria were evaluated in 340 subjects [mean age: (85.6 ± 4.0) years]. eGFR was calculated using the modified abbreviated MDRD equations based on the Chinese chronic kidney disease patients. The subjects were divided into normal renal function group and reduced renal function group (eGFR <60 ml·min(-1)·1.73 m(-2)). The subjects were divided into subjects without proteinuria and subjects with proteinuria group. Cardiovascular events included cardiovascular death, nonfatal myocardial infarction, nonfatal stroke. RESULTS: The proportion of reduced renal function was 36.8% (125/340). The proportion of proteinuria was 10.3% (35/340). The proportion of reduced renal function or proteinuria was 41.8% (142/340). Follow-up time was 79 months (40-114 months). Cardiovascular events rate was significantly higher in reduced renal function group than in normal renal function group [37.6% (47/125) vs. 26.2% (55/210), P < 0.05 ] and in proteinuria group than in without proteinuria group [50.0% (17/34) vs. 28.2% (85/301), P < 0.01 ]. Cox multivariate analysis revealed that both eGFR (HR = 0.978, 95%CI:0.961-0.994, P < 0.05 ) and proteinuria (HR = 2.049, 95%CI:1.132-3.709, P < 0.05) were independent risk factors for cardiovascular events after adjusting for age, gender, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, uric acid, hypertension, coronary heart disease, diabetes mellitus. CONCLUSIONS: Reduced eGFR and presence of proteinuria are independent risk factors for cardiovascular event in subjects aged 80 years or older. eGFR and proteinuria can thus be used for cardiovascular event risk stratification in subjects aged 80 years or older.