Evaluation of biogenically synthesized MgO NPs anticancer activity against breast cancer cells.

Background: Magnesium is recognized to have pharmacological potential, and its nanoformulation is anticipated to offer significant therapeutic effects, particularly against cancer. In this study, we analyzed the anticancer effect of biogenically synthesized magnesium oxide nanoparticles (MgO NPs) against breast cancer cells (MDA-MB-231). Methods: Different biological evaluations, such as cytotoxicity, cellular morphology, induction of apoptosis, generation of ROS, cell adhesion and cellular migration were estimated using well established methodology. Results: The biogenic MgO NPs exhibited increased cytotoxicity, induced apoptosis, enhanced formation of ROS, promoted cell adhesion and inhibited cellular migration in a dose-dependent manner, showing its therapeutic potential against MDA-MB-231 cells. Conclusion: The current study observed strong anticancer activity of MgO NPs against studied cancer cell lines. However, our study must be validated in an appropriate animal/xenograft model to authenticate the effectiveness of MgO NPs against breast cancer.

Non-enzymatic glycation and aggregation of camel immunoglobulins induce breast cancer cell proliferation.

Glycation of biomolecules results in the formation of advanced glycation end products (AGEs). Immunoglobulin G (IgG) has been implicated in the progression of various diseases, including diabetes and cancer. This study purified three IgG subclasses (IgG1, IgG2, and IgG3) from Camelus dromedarius colostrum using ammonium sulfate fractionation and chromatographic procedures. SDS-PAGE was performed to confirm the purity and molecular weight of the IgG subclasses. Several biochemical and biophysical techniques were employed to study the effect of glycation on camel IgG using methylglyoxal (MGO), a dicarbonyl sugar. Early glycation measurement showed an increase in the fructosamine content by ~four-fold in IgG2, ~two-fold in IgG3, and a slight rise in IgG1. AGEs were observed in all classes of IgGs with maximum hyperchromicity (96.6%) in IgG2. Furthermore, glycation-induced oxidation of IgGs led to an increase in carbonyl content and loss of -SH groups. Among subclass, IgG2 showed the highest (39.7%) increase in carbonyl content accompanied by 82.5% decrease in -SH groups. Far UV-CD analysis illustrated perturbation of ß-sheet structure during glycation reaction with MGO. Moreover, glycation of IgG proceeds to various conformational states like aggregation and increased hydrophobicity. In addition, the cytotoxicity assay (MTT) illustrated the proliferation of breast cancer cells (MCF-7) with IgG2 treatment.

Gramine Exerts Cytoprotective Effects and Antioxidant Properties Against H2O2-Induced Oxidative Stress in HEK 293 Cells.

Oxidative stress caused due to the perturbations in the oxidant-antioxidant system can damage molecules and cause cellular alteration leading to the pathogenesis of multiple diseases. This study was designed and performed to investigate the antioxidant and anti-inflammatory effects of an alkaloid, gramine on H2O2-induced oxidative stress on HEK 293 cells. Cell viability and morphometric analysis of cells treated with H2O2 and gramine were studied. Oxidative stress and inflammatory and antioxidant enzymes such as ROS, LPO, NO, SOD, GSH, and CAT were analyzed. Furthermore, mRNA expression of SOD, CAT, and COX-2 was also evaluated. H2O2 at concentration > 0.3 mM and gramine at concentration > 80 µg/mL affect the proliferation. Viability and morphometric analysis showed that gramine has protective effects. Treating cells with gramine suppressed oxidative stress and inflammatory enzymes, whereas antioxidant enzymes were enhanced. SOD and CAT mRNA levels were overexpressed and COX-2 mRNA levels were decreased in the treated groups. Gramine possesses effective antioxidant potential and can regulate oxidative stress and damages associated with it.

Assessment of Risk Perception of COVID-19 Post Vaccination amongst the General Population of Riyadh Region.

COVID-19 is a highly contagious disease caused by SARS-CoV-2. Vaccination against the virus was first approved in Saudi Arabia in December 2020. Vaccinated individuals are still at risk of getting infected with the virus and can transmit the disease. Therefore, the perception of vaccinated individuals regarding the disease can help limit the spread of the virus. OBJECTIVES: To measure the risk perception of COVID-19 following vaccination and factors that have an effect on risk perception; to identify the health protective behaviours of the vaccinated individuals. METHODOLOGY: This is a quantitative analytical cross-sectional, questionnaire-based study. The target population includes individuals aged 18 and above who live in the Riyadh region and have been vaccinated, during the period of June 2021 to December 2021. RESULTS: The perception of 30.2% of participants did not change after vaccination, with many participants continuing to "always" take precautions even after vaccination. Numerous factors, such as age, gender, marital status, occupational status, employment status, and total household income, have shown significant effects towards risk perception. CONCLUSION: Many vaccinated individuals have continued to take precautionary steps and their risk perception has not changed.

Proinflammatory cytokine profiles in prediabetic Saudi patients.

Prediabetes is an increase-risk state for diabetes that is associated with an increase in blood glucose levels to more than normal, but not increased enough to be termed as type 2 diabetes mellitus (T2DM). A timely intervention and management of prediabetes can stop its further progression to the diabetic state. Many cytokines are involved in diseases including diabetes, however, their role in prediabetes is unknown. In this study, we attempted to analyze numerous proinflammatory cytokines in prediabetic patients. A total of 60 adult Saudi prediabetes patients and healthy control individuals were included in this study. To better understand the role of the proinflammatory cytokines in prediabetes patients and its potential link to the disease outcome, the variations in the levels of these cytokines were investigated using Multi-Analyte ELISA technique. The T helper cells (Th1 and Th2) immune response expression profiling of 84 genes was done using Real Time-quantitative PCR (RT-qPCR) technique. The present finding showed that serum Interleukin IL-2, IL-1ß, and IL-1α levels of all prediabetes patients were increased when compared with healthy control cases (P < 0.05). Inductions of proinflammatory cytokines and upregulation of Th1 and Th2 immune genes might play a potential role during prediabetes status and may be linked to the disease outcome. Further studies are needed to investigate the underlying mechanism of these proinflammatory cytokines in diabetes development. A strong positive correlation was found between IL and 1α with glucose levels than with IL-1ß and IL-2. In conclusion, cytokines, especially IL-1, may play a critical role in the development of diabetes.

Inhibition of carbohydrate hydrolyzing enzymes by a potential probiotic Levilactobacillus brevis RAMULAB49 isolated from fermented Ananas comosus.

The research aimed to explore the potential probiotic characteristics of Levilactobacillus brevis RAMULAB49, a strain of lactic acid bacteria (LAB) isolated from fermented pineapple, specifically focusing on its antidiabetic effects. The importance of probiotics in maintaining a balanced gut microbiota and supporting human physiology and metabolism motivated this research. All collected isolates underwent microscopic and biochemical screenings, and those exhibiting Gram-positive characteristics, negative catalase activity, phenol tolerance, gastrointestinal conditions, and adhesion capabilities were selected. Antibiotic susceptibility was assessed, along with safety evaluations encompassing hemolytic and DNase enzyme activity tests. The isolate's antioxidant activity and its ability to inhibit carbohydrate hydrolyzing enzymes were examined. Additionally, organic acid profiling (LC-MS) and in silico studies were conducted on the tested extracts. Levilactobacillus brevis RAMULAB49 demonstrated desired characteristics such as Gram-positive, negative catalase activity, phenol tolerance, gastrointestinal conditions, hydrophobicity (65.71%), and autoaggregation (77.76%). Coaggregation activity against Micrococcus luteus, Pseudomonas aeruginosa, and Salmonella enterica serovar Typhimurium was observed. Molecular characterization revealed significant antioxidant activity in Levilactobacillus brevis RAMULAB49, with ABTS and DPPH inhibition rates of 74.85% and 60.51%, respectively, at a bacterial cell concentration of 109 CFU/mL. The cell-free supernatant exhibited substantial inhibition of α-amylase (56.19%) and α-glucosidase (55.69%) in vitro. In silico studies supported these findings, highlighting the inhibitory effects of specific organic acids such as citric acid, hydroxycitric acid, and malic acid, which displayed higher Pa values compared to other compounds. These outcomes underscore the promising antidiabetic potential of Levilactobacillus brevis RAMULAB49, isolated from fermented pineapple. Its probiotic properties, including antimicrobial activity, autoaggregation, and gastrointestinal conditions, contribute to its potential therapeutic application. The inhibitory effects on α-amylase and α-glucosidase activities further support its anti-diabetic properties. In silico analysis identified specific organic acids that may contribute to the observed antidiabetic effects. Levilactobacillus brevis RAMULAB49, as a probiotic isolate derived from fermented pineapple, holds promise as an agent for managing diabetes. Further investigations should focus on evaluating its efficacy and safety in vivo to consider its potential therapeutic application in diabetes management.

Prevalence of Chemosensitive Neurological Disorders of Smell and Taste and Association with Blood Groups in SARS-CoV-2 Patients: Cross-Sectional Study.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a highly challenging and threatening situation worldwide. SARS-CoV-2 patients develop various clinical symptoms. The olfactory and taste dysfunctions are potential neurological manifestations among SARS-CoV-2 patients; however, their relationship with blood groups has rarely been investigated. This study aimed to investigate the prevalence of chemosensitive neurological disorders of smell and taste and their association with blood groups in SARS-CoV-2 patients. The present cross-sectional study was performed in the Department of Pathology, and Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. A well-structured, self-administered questionnaire was designed and distributed through social media platforms. A total of 922 Saudi and non-Saudi adults aged 18 years or older participated in the study. Out of 922 participants, the number of people who had anosmia was 309 (33.5%), 211 (22.9%) had hyposmia, and 45 (4.8%) had dysosmia. Moreover, 180 (19.52%) had ageusia, 47 (5.1%) and 293 (31.8%) had hypogeusia and dysgeusia, respectively. Among all the participants, 565 (61.27%) had smell-related disorders and 520 (56.39%) participants had taste-related clinical symptoms. The occurrence of anosmia and ageusia was relatively high among females compared to males (p = 0.024). The prevalence of smell-related disorders was 25.0% (230) and taste-related disorders was 23.21% (214) among the study participants with blood group O compared to all other blood group (A, B, and AB) participants who have smell allied disorders 30.69% (283), and taste allied disorders 27.98% (258). The prevalence of chemosensitive neurological disorders involving impaired smell and taste was higher in SARS-CoV-2 patients. These clinical symptoms were common among the participants with blood group type O compared to all other ABO blood group types. The role of certain demographic characteristics was consistent throughout multiple studies, notably with female gender and young adults.

The effect of novel antihypertensive drug valsartan on lysozyme aggregation: A combined in situ and in silico study.

Protein misfolding can result in amyloid fiber aggregation, which is associated with various types of diseases. Therefore, preventing or treating abnormally folded proteins may provide therapeutic intervention for these diseases. Valsartan (VAL) is an angiotensin II receptor blocker (ARB) that is used to treat hypertension. In this study, we examine the anti-aggregating effect of VAL against hen egg-white lysozyme (HEWL) amyloid fibrils through spectroscopy, docking, and microscopic analysis. In vitro formation of HEWL amyloid fibrils was indicated by increased turbidity, RLS (Rayleigh light scattering), and ThT fluorescence intensity. 10 µM VAL, amyloid/aggregation was inhibited up to 83% and 72% as measured by ThT and RLS respectively. In contrast, 100 µM VAL significantly increases the fibril aggregation of HEWL. CD spectroscopy results show a stabilization of HEWL α-helical structures in the presence of 10 µM VAL while the increase in ß-sheet was detected at 100 µM concentration of VAL. The hydrophobicity of HEWL was increased at 100 µM VAL, suggesting the promotion of aggregation via its self-association. Steady-state quenching revealed that VAL and HEWL interact spontaneously via hydrogen bonds and van der Waals forces. Transmission electron microscopy (TEM) images illustrate that the needle-like fibers of HEWL amyloid were reduced at 10 µM VAL, while at 100 µM the fibrils of amyloid were increased. Additionally, our computational studies showed that VAL could bind to two binding sites within HEWL. In the BS-1 domain of HEWL, VAL binds to ASN59, ILE98, ILE58, TRP108, VAL109, SER50, ASP52, ASN59, ALA107, and TRP108 residues with a binding energy of -9.72 kcal mol-1. Also, it binds to GLU7, ALA10, ALA11, CYS6, ARG128, and ARG14 in the BS-2 domain with a binding energy of -5.89 kcal mol-1. VAL, therefore, appears to have dual effect against HEWL aggregation. We suggest that VAL stabilizes HEWL's aggregation-prone region (APR) at 10 µM, preventing aggregation. Also, we assume that at 100 µM, VAL occupies BS-2 beside BS-1 and destabilizes the folding structure of HEWL, resulting in aggregation. Further studies are needed to investigate the mechanism of action and determine its potential side effects.

Structure-guided identification of potent inhibitors of ROS1 kinase for therapeutic development against non-small cell lung cancer.

Proto-oncogene tyrosine-protein kinase ROS (ROS1) is a member of the sevenless receptor, which affects epithelial cell differentiation and is highly expressed in a variety of tumor cells. The elevated expression and dysfunction of ROS1 have been involved in various malignancies, such as non-small cell lung cancer (NSCLC), stomach cancer, ovarian, breast cancer, cholangiocarcinoma, colorectal cancer, adenosarcoma, oesophageal cancer, etc. ROS1 has been postulated as a potential drug target in anticancer therapeutics. In this study, we carried out a virtual screening of phytochemicals against ROS1 to identify its potential inhibitors. The virtual screening process was performed on the ROS1 structure, where two phytochemicals, Helioscopinolide C and Taiwanin C, were identified. These compounds resulted from filters like Lipinski rule of five, PAINS filter, binding affinities values, and all-atom molecular dynamics (MD) simulations followed by principal component analysis (PCA) and essential dynamics. The findings of this study highlight the role of ROS1 in multiple physiological candidates and its therapeutic targeting using phytochemicals. This study suggests Helioscopinolide C and Taiwanin C as potential compounds for therapeutic development targeting ROS1-associated non-small cell lung cancer for clinical applications. Further in vitro and in vivo experiments are required to validate these findings.Communicated by Ramaswamy H. Sarma.

Biogenic Synthesis of Cu-Mn Bimetallic Nanoparticles Using Pumpkin Seeds Extract and Their Characterization and Anticancer Efficacy.

BACKGROUND: Cancer is a chronic, heterogeneous illness that progresses through a spectrum of devastating clinical manifestations and remains the 2nd leading contributor to global mortality. Current cancer therapeutics display various drawbacks that result in inefficient management. The present study is intended to evaluate the anticancer potential of Cu-Mn bimetallic NPs (CMBNPs) synthesized from pumpkin seed extract against colon adenocarcinoma cancer cell line (HT-29). METHODS: The CMBNPs were biosynthesized by continuously stirring an aqueous solution of pumpkin seed extract with CuSO4 and manganese (II) acetate tetrahydrate until a dark green solution was obtained. The characteristic features of biogenic CMBNPs were assessed by UV-visible spectrophotometry (UV-vis), X-ray powder diffraction (XRD), energy-dispersive X-ray (EDX), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). A battery of biological assays, viz. neutral red uptake (NRU) assay, in vitro scratch assay, and comet assay, were performed for anticancer efficacy evaluation. RESULTS: The formation of spherical monodispersed bimetallic nanoparticles with an average size of 50 nm was recorded using TEM. We observed dose-dependent cytotoxicity of CMBNPs in the HT-29 cell line with an IC50 dose of 115.2 µg/mL. On the other hand, CMBNPs did not show significant cytotoxicity against normal cell lines (Vero cells). Furthermore, the treatment of CMBNPs inhibited the migration of cancer cells and caused DNA damage with a significant increase in comet tail length. CONCLUSIONS: The results showed substantial anticancer efficacy of CMBNPs against the studied cancer cell line. However, it is advocated that the current work be expanded to different in vitro cancer models so that an in vivo validation could be carried out in the most appropriate cancer model.

Fatal Case of a Child Harboring Enterobius vermicularis.

Enterobius vermicularis is a threadlike parasite also known as "pinworms". It is the most common helminth infection, affecting the gastrointestinal tracts of children worldwide, although it seldom causes any fatalities. Enterobius vermicularis infections are usually asymptomatic and may only cause anal pruritis, with occasional reported cases of ectopic migration into the appendix or the female genital tract by adult pinworms. Here, we report a case of a 15-year-old girl who presented to the emergency department with high-grade fever, vomiting, and vague abdominal pain for three days. She was diagnosed with acute abdominal pain and underwent emergency ileocecectomy, but died the following day. Pathological examination of ileocecal junction showed intraluminal and intramural Enterobius vermicularis, which were attributed as the cause of her death in the absence of any other pathologies. Death due to Enterobius vermicularis is rare; this case calls for clinicians to be vigilant in exploring Enterobius vermicularis infections in patients with undiagnosed acute abdominal pain, since it could be a potential cause of death.

Agitation does not induce fibrillation in reduced hen egg-white lysozyme at physiological temperature and pH.

Several proteins and peptides tend to form an amyloid fibril, causing a range of unrelated diseases, from neurodegenerative to certain types of cancer. In the native state, these proteins are folded and soluble. However, these proteins acquired ß-sheet amyloid fibril due to unfolding and aggregation. The conversion mechanism from well-folded soluble into amorphous or amyloid fibril is not well understood yet. Here, we induced unfolding and aggregation of hen egg-white lysozyme (HEWL) by reducing agent dithiothreitol and applied mechanical sheering force by constant shaking (1000 rpm) on the thermostat for 7 days. Our turbidity results showed that reduced HEWL rapidly formed aggregates, and a plateau was attained in nearly 5 h of incubation in both shaking and non-shaking conditions. The turbidity was lower in the shaking condition than in the non-shaking condition. The thioflavin T binding and transmission electron micrographs showed that reduced HEWL formed amorphous aggregates in both conditions. Far-UV circular dichroism results showed that reduced HEWL lost nearly all alpha-helical structure, and ß-sheet secondary structure was not formed in both conditions. All the spectroscopic and microscopic results showed that reduced HEWL formed amorphous aggregates under both conditions.

Anticancer potential of yohimbine in drug-resistant oral cancer KB-ChR-8-5 cells.

BACKGROUND: The demand for environmentally friendly and cost-effective plant-based products for the development of cancer therapeutics has been increasing. Yohimbine (α2-adrenergic receptor antagonist) is a stimulant and aphrodisiac used to improve erectile dysfunction. In this study, we aimed to evaluate the anticancer potential of yohimbine in drug-resistant oral cancer KB-ChR-8-5 cells using different biomolecular techniques. METHODS: We estimated the anticancer efficacy of yohimbine using different assays, such as MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell cytotoxicity, cell morphology, cell apoptosis, reactive oxygen species (ROS) formation, and modulation in the mitochondrial membrane potential (MMP). RESULTS: Yohimbine showed a dose-dependent increase in cytotoxicity with a 50% inhibitory concentration (IC50) of 44 µM against KB-ChR-8-5 cancer cell lines. Yohimbine treatment at 40 µM and 50 µM resulted in a considerable change in cell morphology, including shrinkage, detachment, membrane blebbing, and deformed shape. Moreover, at the dose of IC50 and above, a significant induction was observed in the generation of ROS and depolarization of MMP. The possible mechanisms of action of yohimbine underlying the dose-dependent increase in cytotoxicity may be due to the induction of apoptosis, ROS generation, and modulation of MMP. CONCLUSION: Overall, yohimbine showed a significant anticancer potential against drug-resistant oral cancer KB-ChR-8-5 cells. Our study suggests that besides being an aphrodisiac, yohimbine can be used as a drug repurposing agent. However, more research is required in different in vitro and in vivo models to confirm the feasibility of yohimbine in clinics.

Binding Studies of Caffeic and p-Coumaric Acid with α-Amylase: Multispectroscopic and Computational Approaches Deciphering the Effect on Advanced Glycation End Products (AGEs).

Alpha-amylase (α-amylase) is a key player in the management of diabetes and its related complications. This study was intended to have an insight into the binding of caffeic acid and coumaric acid with α-amylase and analyze the effect of these compounds on the formation of advanced glycation end-products (AGEs). Fluorescence quenching studies suggested that both the compounds showed an appreciable binding affinity towards α-amylase. The evaluation of thermodynamic parameters (ΔH and ΔS) suggested that the α-amylase-caffeic/coumaric acid complex formation is driven by van der Waals force and hydrogen bonding, and thus complexation process is seemingly specific. Moreover, glycation and oxidation studies were also performed to explore the multitarget to manage diabetes complications. Caffeic and coumaric acid both inhibited fructosamine content and AGE fluorescence, suggesting their role in the inhibition of early and advanced glycation end-products (AGEs). However, the glycation inhibitory potential of caffeic acid was more in comparison to p-coumaric acid. This high antiglycative potential can be attributed to its additional -OH group and high antioxidant activity. There was a significant recovery of 84.5% in free thiol groups in the presence of caffeic acid, while coumaric attenuated the slow recovery of 29.4% of thiol groups. In vitro studies were further entrenched by in silico studies. Molecular docking studies revealed that caffeic acid formed six hydrogen bonds (Trp 59, Gln 63, Arg 195, Arg 195, Asp 197 and Asp 197) while coumaric acid formed four H-bonds with Trp 59, Gln 63, Arg 195 and Asp 300. Our studies highlighted the role of hydrogen bonding, and the ligands such as caffeic or coumaric acid could be exploited to design antidiabetic drugs.

Elucidating the binding and inhibitory potential of p-coumaric acid against amyloid fibrillation and their cytotoxicity: Biophysical and docking analysis.

P-Coumaric acid (p-CA) is a plant metabolite with anti-inflammatory and antioxidant effects. Due to its therapeutic potential, p-CA has attracted much attention from the scientific community lately. Oxidative stress, amyloid formation, and impaired proteasomal degradation are hallmarks of neurodegenerative diseases like Alzheimer's (AD) and are targets for developing therapeutics against such conditions. Here, we have investigated the anti-amyloidogenic properties of p-coumaric acid on hen egg white lysozyme (HEWL). Heat, pH, and agitation (55 °C, pH 2.0, 600 rpm) stress were used to induce amyloid formation in lysozyme. The aggregates characterization was done by turbidity, Rayleigh light scattering (RLS), and thioflavin-T (ThT) assays. Moreover, ANS (1-anilino naphthalene sulphate) binding assay and circular dichroism (CD) were employed to unveil protein hydrophobicity and secondary structure perturbation, respectively. Lysozyme demonstrated increased hydrophobicity and transition of α-helix to ß-sheet under aggregating conditions. Moreover, co-incubation of lysozyme with p-coumaric acid attenuates the process of amyloid in a concentration dependent manner. At 50 and 200 µM concentrations of p-coumaric acid, lysozyme retained its native-like folded structure. Cytotoxicity protection on human SK-N-SH neuroblastoma cell line was also observed using MTT assay and phase contrast microscopy. In addition, transmission electron microscopy (TEM) reaffirms the fibrillar nature of lysozyme aggregates and their attenuation by p-coumaric acid. The steady state fluorescence revealed that the mode of fluorescence quenching for the HEWL-p-coumaric acid interaction is static rather than dynamic. Moderate strength of binding in order of 104 M-1 exists between HEWL and p-coumaric acid. Thermodynamic parameters (∆H and ∆S) obtained from van't Hoff plot suggested spontaneous reaction with hydrophobic interaction. A slight micro-environmental change in HEWL around Tyr residue was observed during the binding process with the help of synchronous fluorescence. Molecular docking analysis reported the involvement of amino acid residues (TRP63, LEU75, ASP101, LYS97) to form a complex between HEWL-p-coumaric acid. The observed anti-amyloidogenic and inherent antioxidative properties of p-coumaric acid could be helpful to design a neuroprotective agent.

Public Perception towards the COVID-19 Vaccine in Riyadh, Saudi Arabia.

The vaccination campaign against COVID-19 is an essential public health strategy to reach herd immunity, eradicate diseases, and prevent a pandemic. This study aimed to investigate the acceptance rate of the COVID-19 vaccine among people in Riyadh, Saudi Arabia. This cross-sectional study was conducted in the Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. Out of the 922 participants involved, 294 (31.9%) were male and 628 (68.1%) were female, with a mean age of 30-49 years. A bilingual, self-administered, computer-based questionnaire was designed and distributed through social media platforms. In total, 900 participants (97.6%) showed a high acceptance rate of the vaccine. The vaccine acceptance rate was higher among people aged 60 years and above than in other age groups (p = 0.008) and single individuals compared to other groups (p = 0.003). The results reveal a relatively high acceptance level of the COVID-19 vaccine among study participants. Importantly, regression analysis results show that female gender and elderly participants are more likely to accept the COVID-19 vaccine than their counterparts. Moreover, the main factor that influenced the participants' perception of the COVID-19 vaccine was the proper timely scientific recommendations.

Expression, purification, and biophysical characterization of recombinant MERS-CoV main (Mpro) protease.

MERS-CoV main protease (Mpro) is essential for the maturation of the coronavirus; therefore, considered a potential drug target. Detailed conformational information is essential to developing antiviral therapeutics. However, the conformation of MERS-CoV Mpro under different conditions is poorly characterized. In this study, MERS-CoV Mpro was recombinantly produced in E.coli and characterized its structural stability with respect to changes in pH and temperatures. The intrinsic and extrinsic fluorescence measurements revealed that MERS-CoV Mpro tertiary structure was exposed to the polar environment due to the unfolding of the tertiary structure. However, the secondary structure of MERS-CoV Mpro was gained at low pH because of charge-charge repulsion. Furthermore, differential scanning fluorometry studies of Mpro showed a single thermal transition at all pHs except at pH 2.0; no transitions were observed. The data from the spectroscopic studies suggest that the MERS-CoV Mpro forms a molten globule-like state at pH 2.0. Insilico studies showed that the covid-19 Mpro shows 96.08% and 50.65% similarity to that of SARS-CoV Mpro and MERS-CoV Mpro, respectively. This study provides a basic understanding of the thermodynamic and structural properties of MERS-CoV Mpro.

Anticancer Potential of Biogenic Silver Nanoparticles: A Mechanistic Study.

The continuous loss of human life due to the paucity of effective drugs against different forms of cancer demands a better/noble therapeutic approach. One possible way could be the use of nanostructures-based treatment methods. In the current piece of work, we have synthesized silver nanoparticles (AgNPs) using plant (Heliotropiumbacciferum) extract using AgNO3 as starting materials. The size, shape, and structure of synthesized AgNPs were confirmed by various spectroscopy and microscopic techniques. The average size of biosynthesized AgNPs was found to be in the range of 15 nm. The anticancer potential of these AgNPs was evaluated by a battery of tests such as MTT, scratch, and comet assays in breast (MCF-7) and colorectal (HCT-116) cancer models. The toxicity of AgNPs towards cancer cells was confirmed by the expression pattern of apoptotic (p53, Bax, caspase-3) and antiapoptotic (BCl-2) genes by RT-PCR. The cell viability assay showed an IC50 value of 5.44 and 9.54 µg/mL for AgNPs in MCF-7 and HCT-116 cell lines respectively. We also observed cell migration inhibiting potential of AgNPs in a concentration-dependent manner in MCF-7 cell lines. A tremendous rise (150-250%) in the production of ROS was observed as a result of AgNPs treatment compared with control. Moreover, the RT-PCR results indicated the difference in expression levels of pro/antiapoptotic proteins in both cancer cells. All these results indicate that cell death observed by us is mediated by ROS production, which might have altered the cellular redox status. Collectively, we report the antimetastasis potential of biogenic synthesized AgNPs against breast and colorectal cancers. The biogenic synthesis of AgNPs seems to be a promising anticancer therapy with greater efficacy against the studied cell lines.

Mechanistic inhibition of non-enzymatic glycation and aldose reductase activity by naringenin: Binding, enzyme kinetics and molecular docking analysis.

The aldose reductase (AR) enzyme is considered a potential target for the management of diabetic complications. In this study, we describe the binding and enzyme kinetics of AR by naringenin, a bioflavonoid present in many dietary sources. Naringenin showed an inhibitory effect on the activity of AR with an IC50 value of 2.6 µM in an uncompetitive manner. Binding studies confirmed that the naringenin-AR complex has high spontaneous affinity (Ka = 1.94-7.88 × 104) with negative ΔG° value (-5.78 kcal mol-1). The interaction was enthalpy driven and the microenvironment of aromatic residues of AR was also altered. Various stages of protein oxidation and glycation were also measured. Naringenin inhibited fructosamine content by approximately 31.6% at 10 µM, and at the same concentration, >93% inhibition of fluorescent advanced glycation end-products (AGEs) was achieved. There was a significant recovery in free thiol groups and carbonyl content of bovine serum albumin (BSA). Furthermore, molecular docking of naringenin with AR revealed that naringenin formed two hydrogen bonds (Asn160 and Ile260), and three Pi-Pi interactions (two with Trp20 and one with His110). This study provides molecular insight of naringenin-AR interaction and mechanism of antiglycation which may be useful in the development of inhibitors for AGEs formation.

Vitamin D Treatment Reverses the Induced Oxidative Stress Damage to DNA.

BACKGROUND AND OBJECTIVE: The aim of the current study was to investigate in detail the effect of the active metabolite of vitamin D3 [1, 25 (OH)2 D3] in ameliorating the induced oxidative damage to DNA. MATERIALS AND METHODS: Primary cortical neuron cultures from one week old Wister rats were set up in sterile conditions. The neuron cultures were maintained for up to 72 h in culture in the presence of varying doses of vitamin D. Cells were exposed to (0.5 mM H2O2) for 2 h prior to collection of condition medium and cell pellet for Biochemical Assays. Control and H2O2 treated cultures were maintained without any treatment with vitamin D. RESULTS: Pre-treatment with 0.25 µg mL-1 for 24 and 48 h significantly reduced the oxidative stress. 8-hydroxydeoxyguanosine a ubiquitous marker of oxidative stress had also shown to be significantly reduced. The DNA damage marker PolyUB of histones was observed in the neuron treated with H2O2 only. CONCLUSION: This study revealed that oxidation of DNA by hydrogen peroxide caused extensive DNA damage, resulting in polyubiquitination of histones. The pre-treatment with vitamin D3 however completely reversed the DNA damage cascade induced by hydrogen peroxide and protected the DNA.