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Abstract Background Polycystic Ovary Syndrome (PCOS) affects a significant proportion of human females worldwide and is characterized by hormonal, metabolic, and reproductive dysfunctions, including infertility, irregular menstrual cycles, acanthosis nigricans, and hirsutism. Mutations in the estrogen receptor genes ESR1 and ESR2, involved in normal follicular development and ovulation, can contribute to development of the PCOS. The present study focuses on investigating the potential correlation between single nucleotide polymorphisms (SNPs) of ESR1 and ESR2 genes and the incidence of this syndrome. Methods For this study, SNPs in ESR1 and ESR2 genes were retrieved from the ENSEMBL database and analyzed for their effect on mutated proteins using different bioinformatics tools including SIFT, PolyPhen, CADD, REVEL, MetaLR, I-Mutant, CELLO2GO, ProtParam, SOPMA, SWISS-MODEL and HDDOCK. Results All the SNPs documented in the present study were deleterious. All the SNPs except rs1583384537, rs1450198518, and rs78255744 decreased protein stability. Two variants rs1463893698 and rs766843910 in the ESR2 gene altered the localization of mutated proteins i.e. in addition to the nucleus, proteins were also found in mitochondria and extracellular, respectively. SNPs rs104893956 in ESR1 and rs140630557, rs140630557, rs1596423459, rs766843910, rs1596405923, rs762454979 and rs1384121511 in ESR2 gene significantly changed the secondary structure of proteins (2D). SNPs that markedly changed 3D configuration included rs1554259481, rs188957694 and rs755667747 in ESR1 gene and rs1463893698, rs140630557, rs1596423459, rs766843910, rs1596405923, rs762454979 and rs1384121511 in ESR2 gene. Variants rs1467954450 (ESR1) and rs140630557 (ESR2) were identified to reduce the binding tendency of ESRα and β receptors with estradiol as reflected by the docking scores i.e. -164.97 and -173.23, respectively. Conclusion Due to the significant impact on the encoded proteins, these variants might be proposed as biomarkers to predict the likelihood of developing PCOS in the future and for diagnostic purposes.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder caused by the accumulation of amyloid-beta (Aβ) proteins and neurofibrillary tangles in the brain. There have been recent advancements in antiamyloid therapy for AD. This narrative review explores the recent advancements and challenges in antiamyloid therapy. In addition, a summary of evidence from antiamyloid therapy trials is presented with a focus on lecanemab. Lecanemab is the most recently approved monoclonal antibody that targets Aβ protofibrils for the treatment of patients with early AD and mild cognitive impairment (MCI). Lecanemab was the first drug shown to slow cognitive decline in patients with MCI or early onset AD dementia when administered as an infusion once every two weeks. In the Clarity AD trial, lecanemab was associated with infusion-site reactions (26.4%) and amyloid-related imaging abnormalities (12.6%). The clinical relevance and long-term side effects of lecanemab require further longitudinal observation. However, several challenges must be addressed before the drug can be routinely used in clinical practice. The drug’s route of administration, need for imaging and genetic testing, affordability, accessibility, infrastructure, and potential for serious side effects are some of these challenges. Lecanemab’s approval has fueled interest in the potential of other antiamyloid therapies, such as donanemab. Future research must focus on developing strategies to prevent AD; identify easy-to-use validated plasma-based assays; and discover newer user-friendly, and cost-effective drugs that target multiple pathways in AD pathology.

Abstract Vitis vinifera L., commonly known as grape is a major fruit crop in the world. Grapes seem to confer health benefits due to their chemical components, biological and antioxidant activities. The present study is conducted to evaluate the biochemical constituents, antioxidant, and antimicrobial potential of ethanolic grape peduncles (EGP) extract. The result of phytochemical analysis revealed the presence of various phytochemicals such as flavonoid, tannin, carbohydrates, alkaloids, cardiac glycoside, phenol, steroid, terpenoids, quinones and anthraquinones. Furthermore, total phenolic content (TPC) and total flavonoid contents (TFC) were 7.35 ± 0.25 mg GAE/g (Gallic Acid Equivalent per gram) and 29.67 ± 0.13 mg QE/g (Quercetin Equivalent per gram) respectively. DPPH (2, 2-diphenyl-1-picrylhydrazyl) free radical scavenging assay revealed IC50 = 159.3 μg/mL. The antibacterial and antifungal study disclosed that the extract was highly potent against Salmonella typhi with maximum zone of inhibition of 27.2 ± 1.60 mm and Epidermophyton floccosum with 74 ± 1.81% inhibition. The extract was analyzed for its cytotoxicity and antileishmanial activity and showed no activity against HeLa cell line and promastigotes of Leishmania major. Elements Fe, Mn, Ni, Pb and Cd were determined by atomic absorption spectroscopy and approximately 50 compounds were identified by Gas Chromatography-Mass Spectrometry (GC–MS). Current work suggest that grape peduncles can be a promising source of bioactive medicinal component.

Background: Cigarette smoke (CS) is one of the primary causes of acute lung injury (ALI) via provoking pulmonary inflammation and oxidative stress. Despite substantial studies, no effective treatment for ALI is presently available. Purpose: New prospective treatment options for ALI are required. Thus, this project was designed to investigate the in vivo and in vitro protective effects of 70 % methanolic-aqueous crude extract of whole plant of Cichorium intybus (Ci.Mce) against CS-induced ALI. Study design: /methods: Initially, male Swiss albino mice were subjected to whole-body CS exposure for 10 continuous days to prepare CS-induced ALI models. Normal saline (10 mL/kg), Ci.Mce (100, 200, 300 mg/kg), and Dexamethasone (1 mg/kg) were orally administered to respective animal groups 1 h prior to CS-exposure. 24 hrs after the last CS-exposure, BALF and lungs were harvested to study the key characteristics of ALI. Next, HPLC analysis was done to explore the phytoconstituents. Results: Ci.Mce exhibited significant reductions in lung macrophage and neutrophil infiltration, lung weight coefficient, and albumin exudation. Additionally, it effectively ameliorated lung histopathological alterations and hypoxemia. Notably, Ci.Mce exerted inhibitory effects on the excessive generation of IL-6, IL-1β, and KC in both CS-induced ALI murine models and CSE-stimulated RAW 264.7 macrophages. Noteworthy benefits included the attenuation of oxidative stress induced by CS, evidenced by decreased levels of MDA, TOS, and MPO, alongside enhanced TAC production. Furthermore, Ci.Mce demonstrated a marked reduction in CS-induced NF-κB expression, both in vivo and in vitro. Conclusion: Consequently, Cichorium intybus could be a therapeutic option for CS-induced ALI due to its ability to suppress inflammatory reactions, mitigate oxidative stress, and quell NF-κB p65 activation.

Background: Despite significant advancements in healthcare, the burden of stroke continues to rise in the developed world, especially during the COVID-19 pandemic. Association between COVID-19 infection and stroke is well established. Factors identified for the delay in presentation and management include a lack of awareness regarding stroke. We aimed to assess the general public knowledge and attitudes on stroke and stroke risk factors in the United Arab Emirates during the COVID-19 pandemic. Methods: A cross-sectional study was conducted between September 2021 and January 2022 among adults≥ 18 years old. Participants completed a self-administered questionnaire on sociodemographic characteristics and stroke knowledge and attitudes. Knowledge and attitude scores were calculated based on the number of correct responses. Linear regression analysis was performed to determine the factors related to knowledge and attitude towards stroke. Results: Of the 500 respondents, 69.4% were females, 53.4% were aged between 18 and 25, and nearly half were students (48.4%). The mean knowledge score was 13.66 (range 2-24). Hypertension (69%), smoking (63.2%), stress (56.4%) obesity/overweight (54.4%), and heart disease (53.6%) were identified as risk factors. Overall, the knowledge of signs/symptoms was suboptimal. The mean attitude score was 4.41 (range, 1-6); 70.2% would call an ambulance if someone were having a stroke. A monthly income of 11,000-50,000 AED and being a student were associated with positive knowledge. Being a non-health worker and lacking access to electronic media sources were associated with worse attitudes. Conclusion: Overall, we identified poor knowledge and suboptimal attitudes toward stroke. These findings reflect the need for effective public health approaches to improve stroke awareness, knowledge, and attitudes for effective prevention in the community. Presently, this is of utmost necessity, given the increased occurrence of stroke and its severity among COVID-19 patients.

Background: Recently, many drugs have been approved for halting overweight and obesity—few types of research shifted to using Anti-obesity medications (AOM) solely for well-being and shape-keeping. Objective: This narrative review's objective was to explore the use of AOM in relation to their medical indications, efficacy, and cardiovascular safety. Methods and materials: We have conducted a narrative review of the literature on approved/non-approved AOM used for obesity and overweight. We have shed light on the emerging trials of therapies and evolving remedies. Results: Recently, there has been an enormous change in the use of AOM with high consumption that deserves extensive surveillance for the long-term consequences and impact on social, mental, and physical health. Nearly six AOMs and combined therapy are approved by the Food and Drug Administration. The recent guidelines for obesity management have shifted the focus from weight loss to goals that the patient considers essential and toward targeting the root cause of obesity. Conclusion: The use of AOM increased enormously despite its sometimes-dubious safety and ineffectiveness. The public and medical professionals should be vigilant to the real-world benefits of anti-obesity drugs and their achieved effectiveness with an improved safety profile.

Background: Monkeypox virus is an enveloped DNA virus that belongs to Poxviridae family. The virus is transmitted from rodents to primates via infected body fluids, skin lesions, and respiratory droplets. After being infected with virus, the patients experience fever, myalgia, maculopapular rash, and fluid-filled blisters. It is necessary to differentiate monkeypox virus from other poxviruses during diagnosis which can be appropriately envisioned via DNA analysis from swab samples. During small outbreaks, the virus is treated with therapies administered in other orthopoxviruses infections and does not have its own specific therapy and vaccine. Consequently, in this article, two potential peptides have been designed. Methods: For the purpose of designing a vaccine, protein sequences were retrieved followed by the prediction of B- and T-cell epitopes. Afterward, vaccine structures were predicted which were docked with toll-like receptors. The docked complexes were analyzed with iMODS. Moreover, vaccine constructs nucleotide sequences were optimized and expressed in silico. Results: COP-B7R vaccine construct (V1) has antigenicity score of 0.5400, instability index of 29.33, z-score of − 2.11-, and 42.11% GC content whereas COP-A44L vaccine construct (V2) has an antigenicity score of 0.7784, instability index of 23.33, z-score of − 0.61, and 48.63% GC content. It was also observed that COP-A44L can be expressed as a soluble protein in Escherichia coli as compared to COP-B7R which requires a different expression system. Conclusion: The obtained results revealed that both vaccine constructs show satisfactory outcomes after in silico investigation and have significant potential to prevent the monkeypox virus. However, COP-A44L gave better results.

Different research synthetic methods have been developed recently for the synthesis of bis-benzimidazole analogs to investigate various biological significances. In this present study, an attempt was made to synthesize a new series of bis-benzimidazole analogs in a fast and efficient method. A variety of spectroscopic techniques, including 13C NMR, 1H NMR, and HREI-MS, were used to establish the existence of every synthesized scaffold. Molecular docking profiles were also carried out to ascertain the binding interactions of the compounds. All derivatives (1–18) were evaluated for their biological potential to investigate the inhibitory activity of α-amylase and α-glucosidase through SAR study. Almost all derivatives were found to be engaged in a highly promising activity when compared to referenced drug acarbose (IC50 = 8.24 ± 0.08 µM), in this regard among the tested series analog 9 (IC50 = 0.10 ± 0.50 and 0.20 ± 0.50 µM respectively), showed excellent activity. Moreover, ADME predictions were also studied for potent compounds, exhibited drug like properties.

The dark brown and white crystals of manganese and tin (Mn2Se3Cl2O7 and SnSe3O4Cl) have been synthesized by solid-state reaction at 450 C. The morphology and the elemental analysis of newly synthesized compounds were studied by SEM and EDX Analysis. SEM analysis reveals that the particle size for Mn2Se3Cl2O7 was found to be 0.2–2.5 μm and for SnSe3O4Cl 2.0–6.0 μm. The EDX studies showed the presence of Mn, Se, O, Cl, and Sn elements. Powdered XRD confirmed the presence of a new phase present in these compounds. Under UV-vis irradiation, the kinetics of methylene blue (MB) degradation catalyzed by produced nanoparticles were monitored. The dye degradation efficiency was estimated, and results reveals that after 150 min of irradiation, almost 75% of the dye was degraded in the presence of Mn compound while 71% degradation was shown by Sn compound. Both composites display antimicrobial activity against Staphylococcus aureus and Escherichia coli with a maximum value of 34.5 mm. The maximum antimicrobial activity shown by Mn-incorporated nanocomposites estimated at 32.5 mm was against Gram-positive bacteria and 26.4 mm against Gram-negative bacteria. Similarly, the maximum antifungal activity shown by Sn incorporated estimated at 33.9 mm was compared to Gram-positive bacteria and 27.8 mm against Gram-negative bacteria.

A well-known direct-acting antiviral (DAA) drug called daclatasvir may be used to treat chronic hepatitis C virus (HCV) infection. Herein, we reported a selective, precise, and a cost-effective analytical method for the measurement of an active pharmaceutical ingredient (API) of daclatasvir dihydrochloride in drug substances as well as drug products via the reversed-phase RP-HPLC technique. To obtain greater separation, the majority of the chromatographic conditions were improved. Best separation findings were achieved under chromatographic conditions with an HPLC column of USP L1 (150 × 4.6 mm, 5 μm) by utilizing a combination of acetonitrile and buffer solution of KH2PO4 (30 : 70, v/v) as a mobile phase at a stream rate of 1 mL.min−1 with a finding at 300 nm and a column temperature of 40°C. Linearity was examined in the range of 90–210 ppm (R2 = 0.999) for daclatasvir dihydrochloride. The new technique has been verified using industry-recognized criteria, including applicability, system precision, accuracy, robustness, specificity, range, linearity, quantification limit, reagent stability, and detection limit. All the measured metrics were determined to be within acceptable limits using the criteria of the Worldwide Council for Harmonisation (ICH). In pharmaceutical labs, daclatasvir dihydrochloride may be analyzed qualitatively and quantitatively using the well-established RP-HPLC technique. Our study also highlights the need to evaluate the greenness of the method developed using a recognized tool ,i.e., Analytical Greenness Metrics (AGREE).

Heterojunctions have proven to be effective catalysts for removing organic pollutants and heavy metals from wastewater. The following study is also about the formation of 2D heterojunction tellurium-doped zinc oxide composite with sulfur-doped graphitic carbon nitride (Te-ZnO@S-g-C3N4) by adopting a low-cost, simple, and ecofriendly coprecipitation technique. Thiourea was calcined to prepare S-g-C3N4 using the thermal degradation method. The characterization of synthesized photocatalysts was carried out by using SEM-EDX, FTIR, and XRD. The results obtained showed that the incorporation of tellurium caused an alteration in the wurtzite structure of ZnO. SEM-EDX analysis validated the purity of the synthesized samples due to the absence of any additional peaks. The decrease in the bandgap was also noted by the formation of composites. Using methylene blue as a reference dye, the UV-vis spectrophotometer was utilized to calculate the absorbance for photocatalytic degradation behavior. As a result of tellurium doping into the ZnO lattice, photocatalytic oxidation/reduction was improved, according to the results. 3Te-ZnO NPs showed the best degradation rate among dopant series, while an excellent overall degradation rate was noted by fabricated composite 3Te-ZnO@40S-g-C3N4. The best doped ZnO and composites were also used as sorbents for the abstraction of heavy metal (Cr(VI)) from water via adsorption. A definite rise in the removal efficiency percentage of chromium ions was observed by using these sorbents. The overall photo degradation rate and adsorption behavior noted were in ZnO

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Despite the existence of various therapeutic options, NSCLC is still a major health concern due to its aggressive nature and high mutation rate. Consequently, HER3 has been selected as a target protein along with EGFR because of its limited tyrosine kinase activity and ability to activate PI3/AKT pathway responsible for therapy failure. We herein used a BioSolveIT suite to identify potent inhibitors of EGFR and HER3. The schematic process involves screening of databases for constructing compound library comprising of 903 synthetic compounds (602 for EGFR and 301 for HER3) followed by pharmacophore modeling. The best docked poses of compounds with the druggable binding site of respective proteins were selected according to pharmacophore designed by SeeSAR version 12.1.0. Subsequently, preclinical analysis was performed via an online server SwissADME and potent inhibitors were selected. Compound 4k and 4m were the most potent inhibitors of EGFR while 7x effectively inhibited the binding site of HER3. The binding energies of 4k, 4m, and 7x were −7.7, −6.3 and −5.7 kcal/mol, respectively. Collectively, 4k, 4m and 7x showed favorable interactions with the most druggable binding sites of their respective proteins. Finally, in silico pre-clinical testing by SwissADME validated the non-toxic nature of compounds 4k, 4m and 7x providing a promising treatment option for chemoresistant NSCLC.

Background. Aducanumab, a new monoclonal antibody that targets β-amyloid aggregates, has been granted conditional approval by the U.S. FDA for treatment of mild Alzheimer’s disease (AD). The approval of this drug without a confirmed significant clinical impact has resulted in several debates. Objective. In this narrative review, aducanumab approval-related controversy, the drug’s pharmacokinetics and pharmacodynamic characteristics, evidence from the efficacy and safety trials of aducanumab, implications of the drug approval, and the future directions in the management of patients with AD are summarized. Methods. Using relevant keywords, Google Scholar, Web of Science, and MEDLINE databases and manufacturer’s website were searched. Results. Infusion of aducanumab at a higher dose resulted in a modest slowing of cognitive decline among patients with mild cognitive impairment or early-onset AD dementia. The drug however can cause amyloid-related imaging abnormalities. Due to modest impact on cognition, the use of this drug by patients with AD will most likely be limited. The manufacturer is required to run an extended phase IIIb trial to verify the benefit of this drug. Access to therapy requires a careful selection of patients and periodic monitoring to ensure the optimal use of the drug. Conclusion. Despite the limitations, aducanumab is the first disease-modifying therapy approved for the treatment of AD. Aducanumab addresses a part of the pathogenesis of AD; therefore, drugs that can act on multiple targets are needed. In addition, the search for preventive strategies, validated plasma-based assays, and newer drugs for AD, which are effective, safe, convenient, and affordable, is vital.

Alkaptonuria (AKU) is a rare genetic autosomal recessive disorder characterized by elevated serum levels of homogentisic acid (HGA). In this disease, tyrosine metabolism is interrupted because of the alterations in homogentisate dioxygenase (HGD) gene. The patient suffers from ochronosis, fractures, and tendon ruptures. To date, no medicine has been approved for the treatment of AKU. However, physiotherapy and strong painkillers are administered to help mitigate the condition. Recently, nitisinone, an FDA-approved drug for type 1 tyrosinemia, has been given to AKU patients in some countries and has shown encouraging results in reducing the disease progression. However, this drug is not the targeted treatment for AKU, and causes keratopathy. Therefore, the foremost aim of this study is the identification of potent and druggable inhibitors of AKU with no or minimal side effects by targeting 4-hydroxyphenylpyruvate dioxygenase. To achieve our goal, we have performed computational modelling using BioSolveIT suit. The library of ligands for molecular docking was acquired by fragment replacement of reference molecules by ReCore. Subsequently, the hits were screened on the basis of estimated affinities, and their pharmacokinetic properties were evaluated using SwissADME. Afterward, the interactions between target and ligands were investigated using Discovery Studio. Ultimately, compounds c and f were identified as potent inhibitors of 4-hydroxyphenylpyruvate dioxygenase.

Alzheimer’s disease (AD) is one of the progressive neurological disorders and the main cause of dementia all over the world. The multifactorial nature of Alzheimer’s disease is a reason for the lack of effective drugs as well as a basis for the development of new structural leads. In addition, the appalling side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with the marketed treatment modalities and many failed clinical trials significantly limit the use of drugs and alarm for a detailed understanding of disease heterogeneity and the development of preventive and multifaceted remedial approach desperately. With this motivation, we herein report a diverse series of piperidinyl-quinoline acylhydrazone therapeutics as selective as well as potent inhibitors of cholinesterase enzymes. Ultrasound-assisted conjugation of 6/8-methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes (4a,b) and (un)substituted aromatic acid hydrazides (7a-m) provided facile access to target compounds (8a-m and 9a-j) in 4–6 min in excellent yields. The structures were fully established using spectroscopic techniques such as FTIR, 1H- and 13C NMR, and purity was estimated using elemental analysis. The synthesized compounds were investigated for their cholinesterase inhibitory potential. In vitro enzymatic studies revealed potent and selective inhibitors of AChE and BuChE. Compound 8c showed remarkable results and emerged as a lead candidate for the inhibition of AChE with an IC50 value of 5.3 ± 0.51 µM. The inhibitory strength of the optimal compound was 3-fold higher compared to neostigmine (IC50 = 16.3 ± 1.12 µM). Compound 8g exhibited the highest potency and inhibited the BuChE selectively with an IC50 value of 1.31 ± 0.05 µM. Several compounds, such as 8a-c, also displayed dual inhibitory strength, and acquired data were superior to the standard drugs. In vitro results were further supported by molecular docking analysis, where potent compounds revealed various important interactions with the key amino acid residues in the active site of both enzymes. Molecular dynamics simulation data, as well as physicochemical properties of the lead compounds, supported the identified class of hybrid compounds as a promising avenue for the discovery and development of new molecules for multifactorial diseases, such as Alzheimer’s disease (AD).

Zika virus (ZIKV) pandemic and its implication in congenital malformations and severe neurological disorders had created serious threats to global health. ZIKV is a mosquito-borne flavivirus which spread rapidly and infect a large number of people in a shorter time-span. Due to the lack of effective therapeutics, this had become paramount urgency to discover effective drug molecules to encounter the viral infection. Various anti-ZIKV drug discovery efforts during the past several years had been unsuccessful to develop an effective cure. The NS2B-NS3 protein was reported as an attractive therapeutic target for inhibiting viral proliferation, due to its central role in viral replication and maturation of non-structural viral proteins. Therefore, the current in silico drug exploration aimed to identify the novel inhibitors of Zika NS2B-NS3 protease by implementing an e-pharmacophore-based high-throughput virtual screening. A 3D e-pharmacophore model was generated based on the five-featured (ADPRR) pharmacophore hypothesis. Subsequently, the predicted model is further subjected to the high-throughput virtual screening to reveal top hit molecules from the various small molecule databases. Initial hits were examined in terms of binding free energies and ADME properties to identify the candidate hit exhibiting a favourable pharmacokinetic profile. Eventually, molecular dynamic (MD) simulations studies were conducted to evaluate the binding stability of the hit molecule inside the receptor cavity. The findings of the in silico analysis manifested affirmative evidence for three hit molecules with −64.28, −55.15 and −50.16 kcal/mol binding free energies, as potent inhibitors of Zika NS2B-NS3 protease. Hence, these molecules holds the promising potential to serve as a prospective candidates to design effective drugs against ZIKV and related viral infections.

Background: Inhaled Corticosteroid therapy is the cornerstone of asthma treatment. Yet, the reported prevalence of steroid phobia among parents of asthmatic children has been concerning. This study aimed to assess the impact of steroid phobia on ICS adherence, and asthma management. Method: A multicenter, cross-sectional study was held among 500 parents of asthmatic children over 12-months. Each participant completed a structured questionnaire that recorded patients' demographic data, and explored participants’ main concerns regarding ICS. Additionally, participants level of asthma control was assessed by the Arabic childhood asthma control test C-ACT. Result: Of 500 interviewed asthmatic children, up to 66.6% reported having ICS fears, yet only 25.8% reported discussing their concerns with their healthcare providers. In addition, over 50% of parents reported requesting ICS sparing. Regarding ICS adherence, a significant difference (

Nanomedicine has emerged as an important approach for targeting RA medication. Rheumatoid arthritis (RA) is a widespread autoimmune disorder marked by multiple inflamed joints. Gold nanoparticles (GNPs) have been demonstrated as efficacious nanocarriers due to their unique characteristics and the relative simplicity of their synthesis in varied sizes; moreover, they have the capability to alleviate several inflammatory markers. The current objective was to combine methotrexate (MTX) with GNPs to overcome MTX restrictions. GNPs were fabricated by a chemical reduction technique, utilizing sodium citrate and tween 20. The MTX-GNPs formulations were characterized in vitro by % entrapment efficiency (%EE), particle size, polydispersity index (PDI) zeta potential, and % release. The MTX-GNPs formulation was administrated as an intra-articular solution, and additionally, incorporated into a Carbopol gel to investigate its anti-arthritic effectiveness and bioavailability in vivo. The results indicated that a %EE of 87.53 ± 1.10%, and a particle size of 60.62 ± 2.41 nm with a PDI of 0.31 ± 0.03, and a zeta potential of −27.80 ± 0.36 mV were optimal. The in vitro release of MTX from the MTX-GNPs formulation demonstrated that the MTX-GNPs formulation’s release was 34.91 ± 1.96% and considerably (p < 0.05) lower than that of free MTX, showing a significant difference in dissolution patterns (p < 0.05). In vivo, MTX-GNPs formulations inhibited IL-6 by 36.52%, ACCP (63.25 %), COMP (28.16%), and RANKL (63.67%), as well as elevated IL-10 by 190.18%. Transdermal MTX-GNPs decreased IL-6 by 22.52%, ACCP (56.63%), COMP (52.64%), and RANKL (79.5%), as well as increased IL-10 by 168.37%. Histological investigation supported these recent findings. Conclusions: Marked improvements in MTX anti-arthritic effects are seen when it is conjugated to GNPs.

Suaeda fruticosa Forssk. Ex J.F.Gmel is traditionally used for inflammatory and digestive disorders, as a carminative, and for diarrhea. This plant is widely distributed in Asia, Africa, and the Mediterranean region. Aqueous methanolic extract of S. fruticosa (Sf.Cr) was prepared and screened for phytoconstituents through qualitative and GC-MS analysis. Quantification of total phenolic and flavonoid contents was performed, while antioxidant capacity was determined by DPPH, CUPRAC, FRAP, and ABTS assays. The gastroprotective activity was assessed in an ethanol-induced ulcer model. Gastric secretory parameters and macroscopic ulcerated lesions were analyzed and scored for ulcer severity. After scoring, histopathology was performed, and gastric mucus contents were determined. Oral pre-treatment of Sf.Cr demonstrated significant gastroprotection. The gastric ulcer severity score and ulcer index were reduced while the %-inhibition of ulcer was increased dose-dependently. The Sf.Cr significantly elevated the pH of gastric juice, while a decrease in total acidity and gastric juice volume was observed. Histopathology demonstrated less oedema and neutrophil infiltration in gastric mucosa of rats pre-treated with the Sf.Cr in comparison to ethanol-intoxicated animals. Furthermore, the gastric mucus contents were increased as determined by alcian blue binding. Sf.Cr showed marked gastroprotective activity, which can be attributed to antioxidant, antisecretory, and cytoprotective effects.

Oxidative stress is the key factor that strengthens free radical generation which stimulates lung inflammation. The aim was to explore antioxidant, bronchodilatory along with anti-asthmatic potential of folkloric plants and the aqueous methanolic crude extract of Ipomoea nil (In.Cr) seeds which may demonstrate as more potent, economically affordable, having an improved antioxidant profile and providing evidence as exclusive therapeutic agents in respiratory pharmacology. In vitro antioxidant temperament was executed by DPPH, TFC, TPC and HPLC in addition to enzyme inhibition (cholinesterase) analysis; a bronchodilator assay on rabbit’s trachea as well as in vivo OVA-induced allergic asthmatic activity was performed on mice. In vitro analysis of 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH) expressed as % inhibition 86.28 ± 0.25 with IC50 17.22 ± 0.56 mol/L, TPC 115.5 ± 1.02 mg GAE/g of dry sample, TFC 50.44 ± 1.06 mg QE/g dry weight of sample, inhibition in cholinesterase levels for acetyl and butyryl with IC50 (0.60 ± 0.67 and 1.5 ± 0.04 mol/L) in comparison with standard 0.06 ± 0.002 and 0.30 ± 0.003, respectively, while HPLC characterization of In.Cr confirmed the existence with identification as well as quantification of various polyphenolics and flavonoids i.e., gallic acid, vanillic acid, chlorogenic acid, quercetin, kaempferol and others. However, oral gavage of In.Cr at different doses in rabbits showed a better brochodilation profile as compared to carbachol and K+-induced bronchospasm. More significant (p < 0.01) reduction in OVA-induced allergic hyper-responses i.e., inflammatory cells grade, antibody IgE as well as altered IFN-α in airways were observed at three different doses of In.Cr. It can be concluded that sound mechanistic basis i.e., the existence of antioxidants: various phenolic and flavonoids, calcium antagonist(s) as well as enzymes’ inhibition profile, validates folkloric consumptions of this traditionally used plant to treat ailments of respiration.

The development of the embryonic lung demands complex endodermal–mesodermal interactions, which are regulated by a variety of signaling proteins. Hedgehog (Hh) signaling is vital for lung development. It plays a key regulatory role during several morphogenic mechanisms, such as cell growth, differentiation, migration, and persistence of cells. On the other hand, abnormal expression or loss of regulation of Hh signaling leads to airway asthmatic remodeling, which is characterized by cellular matrix modification in the respiratory system, goblet cell hyperplasia, deposition of collagen, epithelial cell apoptosis, proliferation, and activation of fibroblasts. Hh also targets some of the pathogens and seems to have a significant function in tissue repairment and immune-related disorders. Similarly, aberrant Hh signaling expression is critically associated with the etiology of a variety of other airway lung diseases, mainly, bronchial or tissue fibrosis, lung cancer, and pulmonary arterial hypertension, suggesting that controlled regulation of Hh signaling is crucial to retain healthy lung functioning. Moreover, shreds of evidence imply that the Hh signaling pathway links to lung organogenesis and asthmatic airway remodeling. Here, we compiled all up-to-date investigations linked with the role of Hh signaling in the development of lungs as well as the attribution of Hh signaling in impairment of lung expansion, airway remodeling, and immune response. In addition, we included all current investigational and therapeutic approaches to treat airway asthmatic remodeling and immune system pathway diseases.

Rumex vesicarius (L.) is a folklore medicinal herb that has been used for centuries to cure cardiovascular diseases. The present work was carefully designed to ascertain the pharmacological basis for R. vesicarius’s therapeutic efficacy in cardiovascular diseases, as well as the underlying mechanism. In the ex vivo investigation, the aqueous-methanolic leaf extract of R. vesicarius was shown to have endothelium-dependent vasorelaxant effects in rabbit aorta tissue preparations, and its hypotensive responses were quantified by pressure and force transducers coupled to the Power Lab Data Acquisition System. Furthermore, when rabbits were subjected to adrenaline-induced myocardial infarction, R. vesicarius demonstrated cardioprotective characteristics. In contrast to the intoxicated group, the myocardial infarction model showed lower ALP, CK-MB, CRP, LDH, ALT, troponin, and AST levels (p > 0.005–0.000), as well as edema, necrosis, apoptosis, inflammatory cell enrolment, and necrosis. R. vesicarius exhibited significant antioxidant activity and delayed noradrenaline-induced platelet aggregation. Its cardioprotective, anticoagulant, and vasorelaxant properties in both investigations (in vivo and ex vivo) are mediated through partial endothelium-dependent, NO and calcium channel blockade mediated vasorelaxation. The minimizing of adrenaline, oxidative stress, and tissue damage demonstrate its therapeutic efficacy in cardiovascular diseases.

In this paper, green and facile synthesis of sulfur- and nitrogen-codoped carbon nanospheres (CNs) was prepared from the extract of Hibiscus sabdariffa L by a direct hydrothermal method. Finally, sulfur-carbon nanospheres (CNs) were used as the adsorbent to remove Pb+2 ions from aqueous solutions because of the high surface area of S-CNs from CNs and N-CNs. The synthesized nanospheres were examined by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), field emission scanning electron microscopy, transmission electron microscopy (TEM), and nitrogen adsorption-desorption isotherms. The results show spherical shapes have a particle size of up to 65 nm with a high surface area capable of absorbing lead ions efficiently. Additionally, the factors affecting the process of adsorption that include equilibrium time, temperature, pH solution, ionic intensity, and adsorbent dose were studied. The equilibrium removal efficiency was studied employing Langmuir, Freundlich, and Temkin isotherm forms. The kinetic data were analyzed with two different kinetic models, and both apply to the adsorption process depending on the values of correlation coefficients. The thermodynamic parameters including Gibbs free energy (ΔG°), standard enthalpy change (ΔH°), and standard entropy change (ΔS°) were calculated for the adsorption process.

Chronic pain, the most common complication of diabetes, is treated with medication often to no avail. Our study aimed to compare the use of mindfulness meditation and progressive relaxation to reduce chronic pain in older females with diabetes. Methods The 105 study participants were divided randomly into 3 groups: Group MM (mindfulness meditation), Group CM (control meditation), and Group PM (progressive relaxation meditation). Assessment of analgesic effectiveness required changes in average daily pain Brief Pain Inventory (BPI) modified for painful diabetic peripheral neuropathy and Patient Global Impression of Change using descriptive statistics, Student’s t test, and analysis of variance where applicable. Results Both Groups MM and PM experienced significant ( P < .05) reduction in average daily pain in last 24 hours at study end compared to baseline (28.7% and 39.7%, respectively). Group MM had more significant ( P < .01) reduction of pain compared to control, a score of 5.2 ± 1.2 dropped to 3.0 ± 1.1 by week 12 of treatment. Groups MM and PM showed significant improvement in patients’ impression at study end, 75 ± 5.1% (n = 36) and 61 ± 6.5% (n = 32), respectively. In Group MM, patient satisfaction scores increased significantly ( P < .05) to 3.8 ± 1.9 by week 12. Conclusion Integrative therapies such as mindfulness meditation can be part of a comprehensive pain management plan. Benefits include reduction of pain-related medication consumption, better treatment outcomes, improvement in comorbid conditions such as anxiety and depression as well as no risk of addiction or abuse.

Aim. To evaluate the safety issues and adverse effects of using TCHP regimen (docetaxel, carboplatin, trastuzumab, and pertuzumab) versus TCP regimen (docetaxel, carboplatin, and trastuzumab) in older postmenopausal women with nonmetastatic HER2-positive breast cancer. HER2 overexpressed in 20–25% of breast cancer signals an aggressive form of breast cancer and is treated with trastuzumab and pertuzumab. Methods. The patient record database was accessed to identify all postmenopausal women in the Punjab Care hospital who were above 65 years old, with stages 1–3 HER2-positive breast cancer and treated with neoadjuvant TCHP and neoadjuvant TCP from 2013 till 2016. Results. In TCH-P group and TCH group, mild fatigue (34% versus 36%) and diarrhea (48% versus 49%) were most common toxicities. Fever in TCH-P group and TCH group (12% versus 13%) was common. Anorexia affected 21% and 16% of patients receiving TCH and TCHP regimen, respectively. Febrile neutropenia was higher in TCH-P group 13% (3/23) versus 4.5% (1/22) in TCH group. Also 27.2% (6/22) of TCH-P group was hospitalized for treatment related toxicities versus 21.7% (5/23) of TCH group. Conclusion. Comparing neoadjuvant TCP and neoadjuvant TCH-P showed TCH-P regimen had an acceptable toxicity profile. Severe cardiac dysfunction was not observed. Using TCH-P regimen can be considered as relatively safe therapeutic option for elderly postmenopausal women with nonmetastatic HER2-positive breast cancer.

Background: Depression is recognized as a serious public health concern in developing countries. A person having depression feels very low which hinders his activities of daily living. Present study has found that physical disability is a risk factor for the development of depression. Objectives: The purposes of this study were to describe confidence in people with physical disability and to suggest them occupational therapy, physical therapy with psychotherapy, so they can do activities of daily living independently. Methodology: A cross sectional survey with sample of 35 physically disabled people was conducted. The standard tool Beck Depression Inventory has been used and all required thorough research to ensure the inclusion of as many available assessments as possible, related to depression in physically disabled. Results: Present study indicates that there are symptoms of depression in people with physical disability according the disability symptoms may be mild, moderate or severe. Disabled persons were at substantially elevated risk for depressive symptoms and major depressive disorder. Figure 4.22 shows that out of 35 individuals 2.86% were of mild mood disturbance, 42086% were moderately depressed, 37.14% severely depressed and 14.29% were in extreme depression. Results clearly demonstrate that physical disability can lead to depression. Conclusion: It was concluded that physical disability leads to depression and a standardized self-report scale BDI may well be used effectively to screen those patients with physical disabilities, who may need psychological help. Keywords: Depression, Physical Disability, Beck Depression Inventory

Background: Despite significant advancements in healthcare, the burden of stroke continues to rise in the developed world, especially during the COVID-19 pandemic. Association between COVID-19 infection and stroke is well established. Factors identified for the delay in presentation and management include a lack of awareness regarding stroke. We aimed to assess the general public knowledge and attitudes on stroke and stroke risk factors in the United Arab Emirates during the COVID-19 pandemic. Methods: A cross-sectional study was conducted between September 2021 and January 2022 among adults≥ 18 years old. Participants completed a self-administered questionnaire on sociodemographic characteristics and stroke knowledge and attitudes. Knowledge and attitude scores were calculated based on the number of correct responses. Linear regression analysis was performed to determine the factors related to knowledge and attitude towards stroke. Results: Of the 500 respondents, 69.4% were females, 53.4% were aged between 18 and 25, and nearly half were students (48.4%). The mean knowledge score was 13.66 (range 2-24). Hypertension (69%), smoking (63.2%), stress (56.4%) obesity/overweight (54.4%), and heart disease (53.6%) were identified as risk factors. Overall, the knowledge of signs/symptoms was suboptimal. The mean attitude score was 4.41 (range, 1-6); 70.2% would call an ambulance if someone were having a stroke. A monthly income of 11,000-50,000 AED and being a student were associated with positive knowledge. Being a non-health worker and lacking access to electronic media sources were associated with worse attitudes. Conclusion: Overall, we identified poor knowledge and suboptimal attitudes toward stroke. These findings reflect the need for effective public health approaches to improve stroke awareness, knowledge, and attitudes for effective prevention in the community. Presently, this is of utmost necessity, given the increased occurrence of stroke and its severity among COVID-19 patients.

Background: Despite significant advancements in healthcare, the burden of stroke continues to rise in the developed world, especially during the COVID-19 pandemic. Association between COVID-19 infection and stroke is well established. Factors identified for the delay in presentation and management include a lack of awareness regarding stroke. We aimed to assess the general public knowledge and attitudes on stroke and stroke risk factors in the United Arab Emirates during the COVID-19 pandemic. Methods: A cross-sectional study was conducted between September 2021 and January 2022 among adults ≥18 years old. Participants completed a self-administered questionnaire on sociodemographic characteristics and stroke knowledge and attitudes. Knowledge and attitude scores were calculated based on the number of correct responses. Linear regression analysis was performed to determine the factors related to knowledge and attitude towards stroke. Results: Of the 500 respondents, 69.4% were females, 53.4% were aged between 18 and 25, and nearly half were students (48.4%). The mean knowledge score was 13.66 (range 2-24). Hypertension (69%), smoking (63.2%), stress (56.4%) obesity/overweight (54.4%), and heart disease (53.6%) were identified as risk factors. Overall, the knowledge of signs/symptoms was suboptimal. The mean attitude score was 4.41 (range, 1-6); 70.2% would call an ambulance if someone were having a stroke. A monthly income of 11,000-50,000 AED and being a student were associated with positive knowledge. Being a non-health worker and lacking access to electronic media sources were associated with worse attitudes. Conclusion: Overall, we identified poor knowledge and suboptimal attitudes toward stroke. These findings reflect the need for effective public health approaches to improve stroke awareness, knowledge, and attitudes for effective prevention in the community. Presently, this is of utmost necessity, given the increased occurrence of stroke and its severity among COVID-19 patients.