Biophysical, Biochemical, and Molecular Docking Investigations of Anti-Glycating, Antioxidant, and Protein Structural Stability Potential of Garlic.

Garlic has been reported to inhibit protein glycation, a process that underlies several disease processes, including chronic complications of diabetes mellitus. Biophysical, biochemical, and molecular docking investigations were conducted to assess anti-glycating, antioxidant, and protein structural protection activities of garlic. Results from spectral (UV and fluorescence) and circular dichroism (CD) analysis helped ascertain protein conformation and secondary structure protection against glycation to a significant extent. Further, garlic showed heat-induced protein denaturation inhibition activity (52.17%). It also inhibited glycation, advanced glycation end products (AGEs) formation as well as lent human serum albumin (HSA) protein structural stability, as revealed by reduction in browning intensity (65.23%), decrease in protein aggregation index (67.77%), and overall reduction in cross amyloid structure formation (33.26%) compared with positive controls (100%). The significant antioxidant nature of garlic was revealed by FRAP assay (58.23%) and DPPH assay (66.18%). Using molecular docking analysis, some of the important garlic metabolites were investigated for their interactions with the HSA molecule. Molecular docking analysis showed quercetin, a phenolic compound present in garlic, appears to be the most promising inhibitor of glucose interaction with the HSA molecule. Our findings show that garlic can prevent oxidative stress and glycation-induced biomolecular damage and that it can potentially be used in the treatment of several health conditions, including diabetes and other inflammatory diseases

Association of microRNA-34a rs2666433 (A/G) Variant with Systemic Lupus Erythematosus in Female Patients: A Case-Control Study

Several microRNAs (miRNAs) are associated with autoimmune disease susceptibility and phenotype, including systemic lupus erythematosus (SLE). We aimed to explore for the first time the role of the miRNA-34a gene (MIR34A) rs2666433A > G variant in SLE risk and severity. A total of 163 adult patients with SLE and matched controls were recruited. Real-Time allelic discrimination PCR was applied for genotyping. Correlation with disease activity and clinic-laboratory data was done. The rs2666433 variant conferred protection against SLE development under heterozygous [A/G vs. G/G; OR = 0.57, 95%CI = 0.34–0.95], homozygous [A/A vs. G/G; OR = 0.52, 95%CI = 0.29–0.94], dominant [A/G + A/A vs. GG; OR = 0.55, 95%CI = 0.35–0.88], and log-additive [OR = 0.71, 95%CI = 0.53–0.95] models. Data stratification by sex revealed a significant association with SLE development in female participants under heterozygous/homozygous models (p-interaction = 0.004). There was no clear demarcation between SLE patients carrying different genotypes regarding the disease activity index or patients stratified according to lupus nephritis. Enrichment analysis confirmed the implication of MIR34A in the SLE pathway by targeting several genes related to SLE etiopathology. In conclusion, although the MIR34A rs2666433 variant conferred protection against developing SLE disease in the study population, it showed no association with disease activity. Replication studies in other populations are warranted

Antioxidants-Related Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPX), Glutathione-S-Transferase (GST), and Nitric Oxide Synthase (NOS) Gene Variants Analysis in an Obese Population: A Preliminary Case-Control Study

Oxidative stress and antioxidants play an important role in obesity etiopathology. Genetic variants, including single nucleotide polymorphisms (SNPs) of the antioxidant-related genes, may impact disease risk in several populations. This preliminary study aimed to explore the association of 12 SNPs related to superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (GST), and nitric oxide synthase (NOS) genes with obesity susceptibility in a Saudi population. A total of 384 unrelated participants, including 154 (40.1%) obese individuals, were enrolled. TaqMan OpenArray Genotyping assays were used. Six SNPs were significantly more prevalent in obese cohorts: (1) GSTM1 rs1056806*C/T; (2) SOD1 rs2234694*A; (3) SOD2 rs4880*G; (4) SOD3 rs2536512*A; (5) GPX1 rs1800668*A; (6) NOS3 rs1799983*G. Four SNPs were associated with higher obesity risk under heterozygote and dominant models for GSTM1 rs1056806 (C/T), homozygote model for SOD2 rs4880 (A/G), and homozygote and recessive models for GPX1 rs1800668 (A/G). In contrast, SOD3 rs2536512 (A/G) were less likely to be obese under heterozygote and dominant models. The CGAG, CAAA, TGGG, and CGAG combined genotypes showed a higher risk of obesity. In conclusion, the present results suggest that oxidative-stress-related genetic determinants could significantly associate with obesity risk in the study population

Synthesis, Characterization, Antioxidant, and Anticancer Activity against Colon Cancer Cells of Some Cinnamaldehyde-Based Chalcone Derivatives

The purpose of the current investigation was to produce cinammaldehyde-based chalcone derivatives (3a–k) to evaluate their potential effectiveness as antioxidant and inhibitory agents versus human Caco-2 cancer cells. The findings obtained using the DPPH assay showed that compound 3e had the highest effective antioxidant activity with the best IC50 value compared with the other compounds. Moreover, the cytotoxic findings revealed that compound 3e was the best compound for inhibiting Caco-2 development in contrast to all other produced derivatives, with the lowest IC50 concentration (32.19 ± 3.92 µM), and it also had no detrimental effects on healthy human lung cells (wi38 cells). Exposure of Caco-2 cells with this IC50 value of compound 3e resulted in a substantial rise in the number of early and late cells that are apoptotic with a significant comet nucleus when compared with control cells employing the annexin V/PI and comet evaluations, respectively. Furthermore, qRT-PCR and ELISA examinations indicated that compound 3e significantly altered the expression of genes and their relative proteins related to apoptosis in the treated Caco-2 cells, thus significantly inhibiting Caco-2 growth through activating Caspase-3 via an intrinsic apoptotic pathway. As a result, compound 3e could serve as an effective therapy for human colon cancer

HSP70 Expression Signature in Renal Cell Carcinoma: A Clinical and Bioinformatic Analysis Approach

Heat shock proteins (HSPs) are cytoprotective against stressful conditions, as in the case of cancer cell metabolism. Scientists proposed that HSP70 might be implicated in increased cancer cell survival. This study aimed to investigate the HSP70 (HSPA4) gene expression signature in patients with renal cell carcinoma (RCC) in correlation to cancer subtype, stage, grade, and recurrence, combining both clinicopathological and in silico analysis approaches. One hundred and thirty archived formalin-fixed paraffin-embedded samples, including 65 RCC tissue specimens and their paired non-cancerous tissues, were included in the study. Total RNA was extracted from each sample and analyzed using TaqMan quantitative Real-Time Polymerase Chain Reaction. Correlation and validation to the available clinicopathological data and results were executed. Upregulated HSP70 (HSPA4) gene expression was evident in RCC compared to non-cancer tissues in the studied cohort and was validated by in silico analysis. Furthermore, HSP70 expression levels showed significant positive correlations with cancer size, grade, and capsule infiltration, as well as recurrence in RCC patients. The expression levels negatively correlated with the overall survival (r = −0.87, p < 0.001). Kaplan–Meier curves showed lower survival rates in high HSP70 expressor group compared to the low expressors. In conclusion, the HSP70 expression levels are associated with poor RCC prognosis in terms of advanced grade, capsule infiltration, recurrence, and short survival

Curcumin Nanoparticles as Promising Therapeutic Agents for Drug Targets

Curcuma longa is very well-known medicinal plant not only in the Asian hemisphere but also known across the globe for its therapeutic and medicinal benefits. The active moiety of Curcuma longa is curcumin and has gained importance in various treatments of various disorders such as antibacterial, antiprotozoal, cancer, obesity, diabetics and wound healing applications. Several techniques had been exploited as reported by researchers for increasing the therapeutic potential and its pharmacological activity. Here, the dictum is the new room for the development of physicochemical, as well as biological, studies for the efficacy in target specificity. Here, we discussed nanoformulation techniques, which lend support to upgrade the characters to the curcumin such as enhancing bioavailability, increasing solubility, modifying metabolisms, and target specificity, prolonged circulation, enhanced permeation. Our manuscript tried to seek the attention of the researcher by framing some solutions of some existing troubleshoots of this bioactive component for enhanced applications and making the formulations feasible at an industrial production scale. This manuscript focuses on recent inventions as well, which can further be implemented at the community level

Resveratrol biotechnological applications: enlightening its antimicrobial and antioxidant properties

Introduction Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenol obtained from diverse groups of plants, especially in the muscadine grape, red wine, lingonberry, cranberry and redcurrant. Resveratrol's health benefits were first highlighted in the study of the French paradox, which opened up an expansive research endeavor into this compound. Ever since, an array of pharmacological activities, including antioxidant, antiaging, anti-inflammatory, anti-cancer and antidiabetic have been attributed to resveratrol. For many polyphenols, low solubility in biological fluids, as well as by rapid in vivo metabolization, limits their bioavailability. However, improving resveratrol formulation could enhance oral bioavailability and have other beneficial properties. The development of innovative methodological approaches, such as the utilization of innovative formulations has been developed to overcome these limitations and provide a considerable therapeutic amount of resveratrol. Results In this narrative review, a brief outline of historical perspectives of resveratrol is provided, together with an extensive and inclusive overview of various approaches and contemporary developments on the bioavailability, pharmacodynamics and pharmacokinetics of this nutraceutical, along with its biotechnological applications and drug formulations.(undefined)info:eu-repo/semantics/publishedVersio

The Rise of SARS-CoV-2 Variants and the Role of Convalescent Plasma Therapy for Management of Infections

Novel therapies for the treatment of COVID-19 are continuing to emerge as the SARS-Cov-2 pandemic progresses. PCR remains the standard benchmark for initial diagnosis of COVID-19 infection, while advances in immunological profiling are guiding clinical treatment. The SARS-Cov-2 virus has undergone multiple mutations since its emergence in 2019, resulting in changes in virulence that have impacted on disease severity globally. The emergence of more virulent variants of SARS-Cov-2 remains challenging for effective disease control during this pandemic. Major variants identified to date include B.1.1.7, B.1.351; P.1; B.1.617.2; B.1.427; P.2; P.3; B.1.525; and C.37. Globally, large unvaccinated populations increase the risk of more and more variants arising. With successive waves of COVID-19 emerging, strategies that mitigate against community transmission need to be implemented, including increased vaccination coverage. For treatment, convalescent plasma therapy, successfully deployed during recent Ebola outbreaks and for H1N1 influenza, can increase survival rates and improve host responses to viral challenge. Convalescent plasma is rich with cytokines (IL-1β, IL-2, IL-6, IL-17, and IL-8), CCL2, and TNFα, neutralizing antibodies, and clotting factors essential for the management of SARS-CoV-2 infection. Clinical trials can inform and guide treatment policy, leading to mainstream adoption of convalescent therapy. This review examines the limited number of clinical trials published, to date that have deployed this therapy and explores clinical trials in progress for the treatment of COVID-19