Varicella-zoster virus-related neurological complications: From infection to immunomodulatory therapies.

The Varicella-zoster virus (VZV), classified as a neurotropic member of the Herpesviridae family, exhibits a characteristic pathogenicity, predominantly inducing varicella, commonly known as chickenpox, during the initial infectious phase, and triggering the reactivation of herpes zoster, more commonly recognized as shingles, following its emergence from a latent state. The pathogenesis of VZV-associated neuroinflammation involves a complex interplay between viral replication within sensory ganglia and immune-mediated responses that contribute to tissue damage and dysfunction. Upon primary infection, VZV gains access to sensory ganglia, establishing latent infection within neurons. During reactivation, the virus can spread along sensory nerves, triggering a cascade of inflammatory mediators, chemokines, and immune cell infiltration in the affected neural tissues. The role of both adaptive and innate immune reactions, including the contributions of T and B cells, macrophages, and dendritic cells, in orchestrating the immune-mediated damage in the central nervous system is elucidated. Furthermore, the aberrant activation of the natural defence mechanism, characterised by the dysregulated production of immunomodulatory proteins and chemokines, has been implicated in the pathogenesis of VZV-induced neurological disorders, such as encephalitis, myelitis, and vasculopathy. The intricate balance between protective and detrimental immune responses in the context of VZV infection emphasises the necessity for an exhaustive comprehension of the immunopathogenic mechanisms propelling neuroinflammatory processes. Despite the availability of vaccines and antiviral therapies, VZV-related neurological complications remain a significant concern, particularly in immunocompromised individuals and the elderly. Elucidating these mechanisms might facilitate the emergence of innovative immunomodulatory strategies and targeted therapies aimed at mitigating VZV-induced neuroinflammatory damage and improving clinical outcomes. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of VZV infections.

Delineated 3-1-BenCarMethInYlPro-Phosphonic Acid's Adroit Activity against Lung Cancer through Multitargeted Docking, MM\GBSA, QM-DFT and Multiscale Simulations.

Lung cancer is a pervasive and challenging disease with limited treatment options, with global health challenges often present with complex molecular profiles necessitating the exploration of innovative therapeutic strategies. Single-target drugs have shown limited success due to the heterogeneity of this disease. Multitargeted drug designing is imperative to combat this complexity by simultaneously targeting multiple target proteins and pathways, which can enhance treatment efficacy and overcome resistance by addressing the dynamic nature of the disease and stopping tumour growth and spread. In this study, we performed the molecular docking studies of Drug Bank compounds with a multitargeted approach against crucial proteins of lung cancer such as heat shock protein 5 (BIP/GRP78) ATPase, myosin 9B RhoGAP, EYA2 phosphatase inhibitor, RSK4 N-terminal kinase, and collapsin response mediator protein-1 (CRMP-1) using HTVS, SP with XP algorithms, and poses were filtered using MM\GBSA which identified [3-(1-Benzyl-3-Carbamoylmethyl-2-Methyl-1h-Indol-5-Yloxy)-Propyl-]-Phosphonic Acid (3-1-BenCarMethIn YlPro-Phosphonic Acid) (DB02504) as multitargeted drug candidate with docking and MM\GBSA score ranges from -5.83 to -10.66 and -7.56 to -50.14 Kcal/mol, respectively. Further, the pharmacokinetic and QM-based DFT studies have shown complete acceptance results, and interaction fingerprinting reveals that ILE, GLY, VAL, TYR, LEU, and GLN were among the most interacting residues. The 100 ns MD simulation in the SPC water model with NPT ensemble showed stable performance with deviation and fluctuations <2 Å with huge interactions, making it a promising multitargeted drug candidate; however, experimental studies are needed before use.

In Silico Screening and Molecular Dynamics Simulation Studies in the Identification of Natural Compound Inhibitors Targeting the Human Norovirus RdRp Protein to Fight Gastroenteritis.

Norovirus (HNoV) is a leading cause of gastroenteritis globally, and there are currently no treatment options or vaccines available to combat it. RNA-dependent RNA polymerase (RdRp), one of the viral proteins that direct viral replication, is a feasible target for therapeutic development. Despite the discovery of a small number of HNoV RdRp inhibitors, the majority of them have been found to possess a little effect on viral replication, owing to low cell penetrability and drug-likeness. Therefore, antiviral agents that target RdRp are in high demand. For this purpose, we used in silico screening of a library of 473 natural compounds targeting the RdRp active site. The top two compounds, ZINC66112069 and ZINC69481850, were chosen based on their binding energy (BE), physicochemical and drug-likeness properties, and molecular interactions. ZINC66112069 and ZINC69481850 interacted with key residues of RdRp with BEs of -9.7, and -9.4 kcal/mol, respectively, while the positive control had a BE of -9.0 kcal/mol with RdRp. In addition, hits interacted with key residues of RdRp and shared several residues with the PPNDS, the positive control. Furthermore, the docked complexes showed good stability during the molecular dynamic simulation of 100 ns. ZINC66112069 and ZINC69481850 could be proven as potential inhibitors of the HNoV RdRp in future antiviral medication development investigations.

g-C3N4 Based Photocatalyst for the Efficient Photodegradation of Toxic Methyl Orange Dye: Recent Modifications and Future Perspectives.

Industrial effluents containing dyes are the dominant pollutants, making the drinking water unfit. Among the dyes, methylene orange (MO) dye is mutagenic, carcinogenic and toxic to aquatic organisms. Therefore, its removal from water bodies through effective and economical approach is gaining increased attention in the last decades. Photocatalytic degradation has the ability to convert economically complex dye molecules into non-toxic and smaller species via redox reactions, by using photocatalysts. g-C3N4 is a metal-free n-type semiconductor, typical nonmetallic and non-toxici polymeric photocatalyst. It widely used in photocatalytic materials, due to its easy and simple synthesis, fascinating electronic band structure, high stability and abundant availability. As a photocatalyst, its major drawbacks are its limited efficiency in separating photo-excited electron-hole pairs, high separated charge recombination, low specific surface area, and low absorption coefficient. In this review, we report the recent modification strategies adopted for g-C3N4 for the efficient photodegradation of MO dye. The different modification approaches, such as nanocomposites and heterojunctions, as well as doping and defect introductions, are briefly discussed. The mechanism of the photodegradation of MO dye by g-C3N4 and future perspectives are discussed. This review paper will predict strategies for the fabrication of an efficient g-C3N4-based photocatalyst for the photodegradation of MO dye.

Identification of Small Molecule Inhibitors of Human Cytomegalovirus pUL89 Endonuclease Using Integrated Computational Approaches.

Replication of Human Cytomegalovirus (HCMV) requires the presence of a metal-dependent endonuclease at the C-terminus of pUL89, in order to properly pack and cleave the viral genome. Therefore, pUL89 is an attractive target to design anti-CMV intervention. Herein, we used integrated structure-based and ligand-based virtual screening approaches in combination with MD simulation for the identification of potential metal binding small molecule antagonist of pUL89. In this regard, the essential chemical features needed for the inhibition of pUL89 endonuclease domain were defined and used as a 3D query to search chemical compounds from ZINC and ChEMBL database. Thereafter, the molecular docking and ligand-based shape screening were used to narrow down the compounds based on previously identified pUL89 antagonists. The selected virtual hits were further subjected to MD simulation to determine the intrinsic and ligand-induced flexibility of pUL89. The predicted binding modes showed that the compounds reside well in the binding site of endonuclease domain by chelating with the metal ions and crucial residues. Taken in concert, the in silico investigation led to the identification of potential pUL89 antagonists. This study provided promising starting point for further in vitro and in vivo studies.

Atorvastatin and Fluvastatin Potentiate Blood Pressure Lowering Effect of Amlodipine through Vasorelaxant Phenomenon.

Background and Objectives: We have recently reported that stains have calcium channel blocking activity in isolated jejunal preparations. In this study, we examined the effects of atorvastatin and fluvastatin on blood vessels for a possible vasorelaxant effect. We also studied the possible additional vasorelaxant effect of atorvastatin and fluvastatin, in the presence of amlodipine, to quantify its effects on the systolic blood pressure of experimental animals. Materials and Methods: Atorvastatin and fluvastatin were tested in isolated rabbits' aortic strip preparations using 80mM Potassium Chloride (KCl) induced contractions and 1 micro molar Norepinephrine (NE) induced contractions. A positive relaxing effect on 80 mM KCl induced contractions were further confirmed in the absence and presence of atorvastatin and fluvastatin by constructing calcium concentration response curves (CCRCs) while using verapamil as a standard calcium channel blocker. In another series of experiments, hypertension was induced in Wistar rats and different test concentrations of atorvastatin and fluvastatin were administered in their respective EC50 values to the test animals. A fall in their systolic blood pressure was noted using amlodipine as a standard vasorelaxant drug. Results: The results show that fluvastatin is more potent than amlodipine as it relaxed NE induced contractions where the amplitude reached 10% of its control in denuded aortae. Atorvastatin relaxed KCL induced contractions with an amplitude reaching 34.4% of control response as compared to the amlodipine response, i.e., 39.1%. A right shift in the EC50 (Log Ca++ M) of Calcium Concentration Response Curves (CCRCs) implies that statins have calcium channel blocking activity. A right shift in the EC50 of fluvastatin with relatively less EC50 value (-2.8 Log Ca++ M) in the presence of test concentration (1.2 × 10-7 M) of fluvastatin implies that fluvastatin is more potent than atorvastatin. The shift in EC50 resembles the shift of Verapamil, a standard calcium channel blocker (-1.41 Log Ca++ M). Conclusions: Atorvastatin and fluvastatin relax the aortic strip preparations predominantly through the inhibition of voltage gated calcium channels in high molar KCL induced contractions. These statins also inhibit the effects of NE induced contractions. The study also confirms that atorvastatin and fluvastatin potentiate blood pressure lowering effects in hypertensive rats.

Evaluation of Renal Function in COVID-19 Patients by Using Urinalysis Following the Administration of Vancomycin.

BACKGROUND: The aim of this study was to evaluate renal function by urinalysis in COVID-19 patients following the administration of vancomycin. METHODS: A retrospective observational study was performed between October 2020 and January 2021, during which time patients were hospitalized in the Prince Mohammed Bin Abdulaziz Hospital in Riyadh, Saudi Arabia. The patients were free of kidney disease. Urinalysis was performed by an automated laboratory system, and the collected results were based upon age, gender, diabetic status, whether the patients had received vancomycin, the mortality rate, and the urinalysis panel including coinfection by bacteria and yeast. RESULTS: A total of 227 patients were included in this study, 147 (64.75%) of whom were male and 80 (35.25%) of whom were female; 54.63% were diabetic, 11.89% were prediabetic, and 33.48% were non-diabetic patients. Proteinuria, hematuria, glycosuria, coinfection, and ketonuria were detected among all participants within the study group, specifically among diabetic patients. The mortality rate was 16.2% among the study group; 6.6% had re-ceived vancomycin, and 9.6% had not received vancomycin. No significant correlation was found between nephrotoxicity and abnormalities in the urine and the mortality rate among members of our study group. CONCLUSIONS: Proteinuria, hematuria, glycosuria, ketonuria, and coinfection were common among members of our study group, especially in the diabetic group. Urinalysis abnormalities were less frequent in the vancomycin group than in the others, except the prediabetic group. No correlation between mortality and vancomycin was identified.

Antidepressant Effect of Crocin in Mice with Chronic Mild Stress.

This study aimed to investigate the antidepressant property of crocin (Crocetin digentiobiose ester) using a chronic mild stress (CMS)-induced depression model in experimental mice. The tail suspension test (TST) and the sucrose preference test were used to evaluate the antidepressant effect on albino mice of either sex after three weeks of CMS. The period of immobility in the TST and percentage preference for sucrose solution were recorded. By monitoring brain malondialdehyde (MDA) level, catalase (CAT) activity, and reduced glutathione (GSH) level, the antioxidant potential was assessed. Three dosages of crocin (4.84, 9.69, and 19.38 mg/kg) were evaluated. When compared to controls, animals that received crocin administration during three periods of CMS had considerably shorter immobility times during the TST. Crocin treatment also raised the percentage preference for sucrose solution in a dose-dependent manner, bringing it to parity with the conventional antidepressant, imipramine. Animals that received a high dose of crocin had a much greater spontaneous locomotor activity. Furthermore, a high dose of crocin remarkably lowered plasma corticosterone and nitrite levels brought on by CMS. Additionally, high doses of crocin given during CMS greatly enhanced reduced glutathione levels while considerably reducing the brain's MDA and catalase activities. In conclusion, high doses of crocin may have an antidepressant effect in an animal model through several mechanisms. However, further studies should be carried out to explore the role of neurotransmitters for their antidepressant property.

Effects of pH and Ionic Salts on the Emulsifying and Rheological Properties of Acorn Protein Isolate.

This study was designed to evaluate the emulsifying and rheological properties of acorn protein isolate (API) in different pH mediums (pH 3, 7 and 9) and in the presence of ionic salts (1 M NaCl and 1 M CaCl2). API shows higher solubility in distilled water at pH 7, while at the same pH, a decrease in solubility was observed for API in the presence of CaCl2 (61.30%). A lower emulsifying activity index (EAI), lower stability index (ESI), larger droplet sizes and slight flocculation were observed for API in the presence of salts at different pHs. Importantly, CaCl2 treated samples showed relevantly higher EAI (252.67 m2/g) and ESI (152.67 min) values at all pH as compared to NaCl (221.76 m2/g), (111.82 min), respectively. A significant increase in interfacial protein concentration (4.61 mg/m2) was observed for emulsion at pH 9 with CaCl2, while the major fractions of API were observed in an interfacial layer after SDS-PAGE analysis. All of the emulsion shows shear thinning behavior (τc > 0 and n < 1), while the highest viscosity was observed for emulsion prepared with CaCl2 at pH 3 (11.03 ± 1.62). In conclusion, API, in the presence of ionic salts at acidic, neutral and basic pH, can produce natural emulsions, which could be substitutes for synthetic surfactants for such formulations.

Multipotent Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease: Synthesis, Biological Analysis and Molecular Docking Study of Benzimidazole-Based Thiazole Derivatives.

Twenty-four analogues of benzimidazole-based thiazoles (1-24) were synthesized and assessed for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory potential. All analogues were found to exhibit good inhibitory potential against cholinesterase enzymes, having IC50 values in the ranges of 0.10 ± 0.05 to 11.10 ± 0.30 µM (for AChE) and 0.20 ± 0.050 µM to 14.20 ± 0.10 µM (for BuChE) as compared to the standard drug Donepezil (IC50 = 2.16 ± 0.12 and 4.5 ± 0.11 µM, respectively). Among the series, analogues 16 and 21 were found to be the most potent inhibitors of AChE and BuChE enzymes. The number (s), types, electron-donating or -withdrawing effects and position of the substituent(s) on the both phenyl rings B & C were the primary determinants of the structure-activity relationship (SAR). In order to understand how the most active derivatives interact with the amino acids in the active site of the enzyme, molecular docking studies were conducted. The results obtained supported the experimental data. Additionally, the structures of all newly synthesized compounds were elucidated by using several spectroscopic methods like 13C-NMR, 1H-NMR and HR EIMS.

An Evaluation of Antimicrobial, Anticancer, Anti-Inflammatory and Antioxidant Activities of Silver Nanoparticles Synthesized from Leaf Extract of Madhuca longifolia Utilizing Quantitative and Qualitative Methods.

In the current decade, nanoparticles are synthesized using solvents that are environmentally friendly. A number of nanoparticles have been synthesized at room temperature using water as a solvent, such as gold (Au) and silver (Ag) nanoparticles. As part of nanotechnology, nanoparticles are synthesized through biological processes. Biological methods are the preferred method for the synthesis of inorganic nanoparticles (AgNPs) as a result of their simple and non-hazardous nature. Nanoparticles of silver are used in a variety of applications, including catalysts, spectrally selective coatings for solar absorption, optical objectives, pharmaceutical constituents, and chemical and biological sensing. Antimicrobial agents are among the top uses of silver nanoparticles. In the current study, silver nanoparticles were biologically manufactured through Madhuca longifolia, and their antibacterial activity against pathogenic microorganisms, anticancer, anti-inflammatory, and antioxidant activities were assessed. UV-Vis spectroscopy, XRD (X-ray diffraction), transmission electron microscopy, Zeta Potential, and FTIR were used to characterize silver nanoparticles. The current work describes a cheap and environmentally friendly method to synthesize silver nanoparticles from silver nitrate solution by using plant crude extract as a reducing agent.

Studies on antioxidant, anti-diabetic and GC-MS analyses of methanol extract of Aristolochia bracteolata root bark.

Aristolochia bracteolatais utilized in confronting multiple and complicated disease conditions such as cancer, lung inflammation, dysentery, syphilis, gonorrhea, arthritis, skindiseases, snake bite and oxidative stress relating to humans due to their acceptability, affordability and proximity. This investigation seeks to determine the antioxidant and anti-diabetic effects of methanol extract of A. bracteolate root bark in vitro. The phytochemical screening, antioxidant, and enzymes inhibitory (alpha-amylase and alpha-glucosidase) properties of root bark extract were evaluated by standard procedures. The methanol extract indicated the presence of diverse phytochemicals (tannins, saponins, flavonoids, alkaloids, phenols, glycosides and terpenoids) and contained a remarkable amount of saponins (8.20±0.03%), phenols (6.82±0.01%), alkaloids (4.71±0.03%) and flavonoids (3.50±0.12%). The extract showed not only strong antioxidant properties against DPPH, FRAP and TBARS radicals with IC50 value of 57.87, 54.64 and 47.54 mg/ml, respectively but also anti-diabetic activity by inhibiting alpha-amylase (IC50=53.70 mg/ml) and alpha-glucosidase (IC50=49.18 mg/ml). GC-MS chromatogram identified a diverse array of active metabolites in the methanol extract of A. bracteolate root bark. This study suggested that the methanol extract of A. bracteolate root bark possessed anti-oxidative and anti-diabetic activities.

Neuroprotective Potential of Synthetic Mono-Carbonyl Curcumin Analogs Assessed by Molecular Docking Studies.

Cognitive decline in dementia is associated with deficiency of the cholinergic system. In this study, five mono-carbonyl curcumin analogs were synthesized, and on the basis of their promising in vitro anticholinesterase activities, they were further investigated for in vivo neuroprotective and memory enhancing effects in scopolamine-induced amnesia using elevated plus maze (EPM) and novel object recognition (NOR) behavioral mice models. The effects of the synthesized compounds on the cholinergic system involvement in the brain hippocampus and their binding mode in the active site of cholinesterases were also determined. Compound h2 (p < 0.001) and h3 (p < 0.001) significantly inhibited the cholinesterases and reversed the effects of scopolamine by significantly reducing TLT (p < 0.001) in EPM, while (p < 0.001) increased the time exploring the novel object. The % discrimination index (DI) was significantly increased (p < 0.001) in the novel object recognition test. The mechanism of cholinesterase inhibition was further validated through molecular docking study using MOE software. The results obtained from the in vitro, in vivo and ex vivo studies showed that the synthesized curcumin analogs exhibited significantly higher memory-enhancing potential, and h3 could be an effective neuroprotective agent. However, more study is suggested to explore its exact mechanism of action.

PVT1 lncRNA in lung cancer: A key player in tumorigenesis and therapeutic opportunities.

The lncRNA PVT1 has emerged as a pivotal component in the intricate landscape of cancer pathogenesis, particularly in lung cancer. PVT1, situated in the 8q24 chromosomal region, has garnered attention for its aberrant expression patterns in lung cancer, correlating with tumor progression, metastasis, and poor prognosis. Numerous studies have unveiled the diverse mechanisms PVT1 contributes to lung cancer pathogenesis. It modulates critical pathways, such as cell proliferation, apoptosis evasion, angiogenesis, and epithelial-mesenchymal transition. PVT1's interactions with other molecules, including microRNAs and proteins, amplify its oncogenic influence. Recent advancements in genomic and epigenetic analyses have also illuminated the intricate regulatory networks that govern PVT1 expression. Understanding PVT1's complex involvement in lung cancer holds substantial clinical implications. Targeting PVT1 presents a promising avenue for developing novel diagnostic biomarkers and therapeutic interventions. This abstract encapsulates the expanding knowledge regarding the oncogenic role of PVT1 in lung cancer, underscoring the significance of further research to unravel its complete mechanistic landscape and exploit its potential for improved patient outcomes.

HOTAIR: A key regulator of the Wnt/ß-catenin signaling cascade in cancer progression and treatment.

The long non-coding RNA (lncRNA) HOTAIR occupies a central position in the complex domain of cancer biology, particularly concerning its intricate interplay with the Wnt/ß-catenin signaling pathway. This comprehensive review explores the multifaceted interactions between HOTAIR and the Wnt/ß-catenin cascade, elucidating their profound function in cancer growth, progression, and therapeutic strategies. The study commences by underscoring the pivotal role of the Wnt/ß-catenin cascade in governing essential cellular activities, emphasizing its dysregulation as a linchpin in cancer initiation and advancement. It introduces HOTAIR as a crucial regulatory entity, influencing gene expression in both healthy and diseased. The core of this review plunges into the intricacies of HOTAIR's engagement with Wnt/ß-catenin signaling. It unravels how HOTAIR, through epigenetic modifications and transcriptional control, exerts its influence over key pathway constituents, including ß-catenin, Wnt ligands, and target genes. This influence drives unchecked cancer cell growth, invasion, and metastasis. Furthermore, the review underscores the clinical significance of the HOTAIR-Wnt/ß-catenin interplay, elucidating its associations with diverse cancer subtypes, patient prognoses, and prospects as a therapy. It provides insights into ongoing research endeavors to develop HOTAIR-targeted treatments and initiatives to facilitate aberrant Wnt/ß-catenin activation. Concluding on a forward-looking note, the article accentuates the broader implications of HOTAIR's involvement in cancer biology, including its contributions to therapy resistance and metastatic dissemination. It underscores the importance of delving deeper into these intricate molecular relationships to pave the way for groundbreaking cancer treatment.

Computational insights into overcoming resistance mechanisms in targeted therapies for advanced breast cancer: focus on EGFR and HER2 co-inhibition.

In the present study, the formation of a heterodimer involving both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) has been explored as a potential therapeutic mechanism to inhibit the progression of breast cancer. Virtual screening using molecular docking resulted in the three hit compounds (ZINC08382411, ZINC08382438, and ZINC08382292) with minimum binding scores and commonly binding to both receptors. Further, MD simulation analysis of these complexes illustrated the high stability of these compounds with EGFR and HER2. RMSD showed that ZINC08382411 displayed the most stable RMSD of 2 - 3 Å when bound to both receptors, suggesting to have strong compatibility with the active site of the receptor. Hydrogen bond analysis showed that ZINC08382411 forms the maximum number of H-bonds (2 to 3) in both EGFR and HER2 bound complexes, with the highest occupancy of 62% and 79%, respectively. Binding free energy calculation showed that ZINC08382411 possesses maximum affinity towards both the receptors with ΔGbind = -129.628 and -164.063 kJ/mol, respectively. This approach recognizes the significance of EGFR and HER2 in breast cancer development and aims to disrupt their collaborative signaling, which is known to promote the antagonistic behavior of cancer cells. By focusing on this EGFR/HER2 heterodimer, the study offers a promising avenue for identifying a potential candidate (ZINC08382411) that may inhibit breast cancer cell growth and potentially improve patient outcomes. The study's findings may contribute to the ongoing efforts to advance breast cancer treatment strategies.Communicated by Ramaswamy H. Sarma.

Phenolic phytochemistry, in vitro, in silico, in vivo, and mechanistic anti-inflammatory and antioxidant evaluations of Habenaria digitata.

Excessive and imbalance of free radicals within the body lead to inflammation. The objective of the current research work was to explore the anti-inflammatory and antioxidant potential of the isolated compounds from Habenaria digitata. In this study, the isolated phenolic compounds were investigated for in vitro and in vivo anti-inflammatory potential along with the antioxidant enzyme. The anti-inflammatory and antioxidant potential of the phenolic compounds was assayed via various enzymes like COX-1/2, 5-LOX and ABTS, DPPH, and H2O2 free radical enzyme inhibitory assay. These compounds were also explored for their in vivo antioxidant activity like examining SOD, CAT, GSH-Px, and MDA levels in the brain, heart, and liver. The anti-inflammatory potential was evaluated using the carrageenan-induced pleurisy model in mice. On the basis of initial screening of isolated compounds, the most potent compound was further evaluated for the anti-inflammatory mechanism. Furthermore, the molecular docking study was also performed for the potent compound. The phenolic compounds were isolated and identified by GC-MS/NMR analysis by comparing its spectra to the library spectra. The isolated phenolic compounds from H. digitata were 5-methylpyrimidine-24,4-diol (1), 3,5-dihydroxy-6-methyl-2,3-dihydropyran-4-one (2), 2-isopropyl-5-methylphenol (3), 3-methoxy-4-vinylphenol (4), and 2,6-dimethoxy-4-vinylphenol (5). In in vitro antioxidant assay, the most potent compound was compound 1 having IC50 values of 0.98, 0.90, and 5 µg/mL against ABTS, DPPH, and H2O2, respectively. Similarly, against COX1/2 and 5-LOX ,compound 1 was again the potent compound with IC50 values of 42.76, 10.70, and 7.40 µg/mL. Based on the in vitro results, compound 1 was further evaluated for in vivo antioxidant and anti-inflammatory potential. Findings of the study suggest that H. digitata contains active compounds with potential anti-inflammatory and antioxidant effects. These compounds could be screened as drug candidates for pharmaceutical research, targeting conditions associated with oxidative stress and inflammatory conditions in medicinal chemistry and support their ethnomedicinal use for inflammation and oxidative stress.

Modification of 4-(4-chlorothiophen-2-yl)thiazol-2-amine derivatives for the treatment of analgesia and inflammation: synthesis and in vitro, in vivo, and in silico studies.

Inflammation is a protective response to a variety of infectious agents. To develop a new anti-inflammatory drug, we explored a pharmacologically important thiazole scaffold in this study. In a multi-step synthetic approach, we synthesized seven new thiazole derivatives (5a-5g). Initially, we examined the in vitro anti-inflammatory potentials of our compounds using COX-1, COX-2, and 5-LOX enzyme assays. After in vitro confirmation, the potential compounds were subjected to in vivo analgesic and anti-inflammatory studies. The hot plate method was used for analgesia, and carrageenan-induced inflammation was also assayed. Overall, all our compounds proved to be potent inhibitors of COX-2 compared to celecoxib (IC50 0.05 µM), exhibiting IC50 values in the range of 0.76-9.01 µM .Compounds 5b, 5d, and 5e were dominant and selective COX-2 inhibitors with the lowest IC50 values and selectivity index (SI) values of 42, 112, and 124, respectively. Similarly, in the COX-1 assay, our compounds were relatively less potent but still encouraging. Standard aspirin exhibited an IC50 value of 15.32 µM. In the 5-LOX results, once again, compounds 5d and 5e were dominant with IC50 values of 23.08 and 38.46 µM, respectively. Standard zileuton exhibited an IC50 value of 11.00 µM. Based on the COX/LOX and SI potencies, the compounds 5d and 5e were subjected to in vivo analgesic and anti-inflammatory studies. Compounds 5d and 5e at concentrations of 5, 10, and 20 mg/kg body weight were significant in animal models. Furthermore, we explored the potential role of compounds 5d and 5e in various phlogistic agents. Similarly, both compounds 5d and 5e were also significantly potent in the anti-nociceptive assay. The molecular docking interactions of these two compounds with the target proteins of COX and LOX further strengthened their potential for use in COX/LOX pathway inhibitions.

Study of Structurally Diverse Currently Used and Recently Developed Antimycobacterial Drugs.

Despite major antimicrobial therapeutic advancements, widespread use and misuse of antimicrobial drugs have increased antimicrobial drug resistance, posing a severe danger to public health. In particular, the emergence of multidrug-resistant bacteria has provided considerable difficulty in the treatment of pathogenic infections. As a result, the creation of novel drugs to treat resistant bacteria is one of the most significant disciplines of antimicrobial research today. TB therapy has recently gained a lot of attention, in addition to developing novel and efficient antibacterial drugs to battle multidrug-resistant illnesses. The use of a different class of drugs, such as well-known drugs, their derivatives, and various new heterocyclic compounds like nitroimidazoles, imidazole analogues, triazoles, imidazopyridines, quinolines, purines, as well as thioactomycin, mefloquine, deazapteridines, benzothiadiazine and other molecules such as benzoxazines, diterpenoids, tryptanthin and phenazine and toluidine analogues followed by many other classes of compounds and their effects are also discussed. As a result, current and newly found antitubercular drugs and their toxicities and mode of action have been focused.

Assessing the adverse effects of COVID-19 vaccine in different scenarios in Saudi Arabia: A cross-sectional study.

OBJECTIVES: To assess the different side effects of COVID-19 vaccines at different scenarios in Saudi Arabia. METHODS: This cross-sectional study sought to investigate the side effects of COVID-19 vaccines through an online survey of 2,718 participants in Saudi Arabia. RESULTS: People can manage their expectations about vaccine side effects and deal with symptoms better by knowing beforehand that they are likely to experience mild side effects for a short period, symptoms that are manifested regardless of age, and infection before or after vaccination. There are certain uncommon side effects that affect more people who got infected, and not before vaccination; there are side effects that disproportionately impact women, and also the side effects that wane after the second dose. CONCLUSION: These findings can assist in evaluating the concerns regarding vaccine acceptance. The public should be made aware that they are likely to experience at least one side effect, with temporary post-injection inflammation, musculoskeletal pain, fever, and headache as the most commonly reported side effects across the board. However, the common symptoms are mild to moderate, and the side effects last for a short period for most people.