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Isolation of bioactive compounds from plants and their therapeutic evaluation is crucial in the pursuit of novel phytochemicals and contributes an indispensable role in drug discovery and design. The literature has documented the hypolipidemic effect of numerous Onosma species. Taking that into consideration, the current study was designed to isolate, purify and evaluate the antihyperlipidemic potential of leaves of Onosma hispidum Wall. For the first time, the bioassay-guided isolation led to the separation of 3 compounds that were identified by spectroscopic techniques as o-phthalic acid bis-(2-ethyl decyl)-ester (1), bis (2-ethyloctyl) phthalate (2), and 1,2 benzenedicarboxylic acid bis(2-methyl heptyl) ester (3). Lipase inhibition assay was utilized to scrutinize the antihyperlipidemic potential of methanolic extract fractions and subsequently isolated compounds. Further, the isolated compounds were employed for in silico studies via molecular docking, molecular mechanics with generalized born and surface area solvation (MM-GBSA), and MD simulations with Pancreatic Lipase Colipase (PDB ID: 1LPB). Molecular docking and MM-GBSA of isolated compounds were employed to explain the mode of binding between the protein-ligand complex and binding free energy calculation, respectively. Since compound (3) displayed the best docking score of -6.689 kcal/mol as compared to orlistat -5.529 kcal/mol with PDB: 1LPB. So, it was chosen for MD simulations to evaluate ligand stability and flexibility of the complex which was validated by the fluctuation of α-carbon chain, root mean square deviation (RMSD), root mean square fluctuation (RMSF), and type of interactions involved which authenticated the in vitro lipase inhibitory potential. Overall, in silico and in vitro results validated that compound (3) could be exploited as a promising pancreatic lipase inhibitor.Communicated by Ramaswamy H. Sarma.

Heterocyclic compounds with oxazole and imidazole rings in their structure have disclosed momentous biological aptitudes. Taking into account their superlative attributes, the present study was designed to introduce a new synthetic scheme to make new derivatives with tremendous futuristic pharmacological potentialities. Series of Oxazolones were synthesized by using substituted benzaldehyde with benzyl halides to produce respective benzaldehyde derivatives 1 (a-d) which further reacted with hippuric acid to yield oxazolones 2 (a-e). Newly synthesized oxazolones then reacted with 4-chloroaniline to yield corresponding imidazolones 3 (a-e). All the compounds were characterized by using FTIR and NMR spectroscopic techniques. Docking studies of Compounds were conducted using AutoDock Vina and analyzed with PYMOL. All synthesized oxazolone and imidazolone derivatives exhibited antioxidant potential, demonstrated by their IC 50 values compared to ascorbic acid standard. Oxazolone derivatives (2a-2e) exhibited good acetyl cholinesterase inhibitory potential whereas Imidazolone series did not show significant inhibition as shown by their IC 50 values compared to donepezil as a standard. Docking studies of all compounds against acetylcholinesterase demonstrated favorable binding affinity, indicating their potential for further in-vivo studies. It is notable that novel compounds of both oxazolones and Imidazolone series exhibited antioxidant potential with maximum percentage inhibition of 75.9 (IC 50 12.9 ± 0.0573 µM/mL) by compound 2d while compound 2a showed AChE inhibitory potential with maximum %age inhibition of 75.49 (IC 50 7.8 ± 0.0218 µM/mL).Communicated by Ramaswamy H. Sarma.

Cannabis and opioid co-dependence is independently associated with cognitive impairments. We examined neurocognitive dysfunctions in people with concurrent opioid dependence with cannabis dependence (OD+CD) or cannabis use (OD+CU) compared to those with only opioid dependence (OD) and healthy controls (HC). We selected adult participants, any sex, who met the diagnosis of OD ( N  = 268), OD+CU ( N  = 58), and OD + CD ( N  = 115). We recruited 68 education-matched HC. We administeredStandard progressive matrices (SPM), Wisconsin card sorting test (WCST), Iowa gambling task (IGT), Trail making tests A and B (TMT), and verbal and visual working memory 1-, 2-backtests. 496 (97.5%) were men, and 13 (2.5%) were women. In WCST, OD and OD+CD had significantly higher non-perseverative errors than HC. OD+CD group completed significantly lesser categories than HC. In verbal working memory 2-back, HC scored significantly fewer errors than OD and OD +CD. All patient groups, OD, OD+CU, and OD+CD, scored higher commission errors than HC in visual working memory 1-back. OD and OD+CD scored higher commission and total errors than the controls. OD+CU showed lesser error score than HC in TMT B. Cannabis and opioid co-dependence contribute to cognitive impairments, especially in working memory and executive functions.

COVID-19 pandemic has triggered psychological stress such as anxiety and depression among people around the globe. Due to the nature of the job, healthcare professionals (HCPs) are at high risk of infection and are facing social stigma as well. This research was conducted with the objective to evaluate the psychological influence of the COVID-19 pandemic among HCPs in Yemen and the coping strategies adopted thereof. A web-based, as well as face-to-face cross-sectional study was carried out from July to December 2021 among HCPs of Yemen. The generalized anxiety disorder (GAD-7), patient health questionnaire (PHQ-9), and Brief-COPE scales were applied for the evaluation of anxiety, depression, and coping strategies. A total of 197 HCPs participated in the study where 28.4% and 43.1% had anxiety and depression respectively. The prevalence of both anxiety and depression in the majority were found of the minimal to none and mild categories (71.6% vs. 56.9% respectively). The respondents who had received training on COVID-19 had statistically significant lower GAD-7 scores than those who did not (6.32 vs. 8.02 respectively). A significant statistical difference was observed between physicians versus nurses regarding depression based on the working area (p < 0.05). The physician and pharmacist had a significant positive association with brief COPE scores at the 50th centile compared to other HCPs. The female respondents had statistically significant higher mean Brief COPE scores than male respondents (78.11 vs. 69.50 respectively). Our findings illustrate the requirement for efficient policies through administrative, clinical, and welfare perspectives from the regulatory body in preparedness and preventive measures towards such a pandemic that aids HCPs to provide service in a stress-free condition and assurance of a better healthcare system..

Interactions of manganese dioxide nanoparticles (MnO 2 NPs) with vital biomolecules namely deoxyribonucleic acid (DNA) and serum albumin (BSA) have been studied in association with different surfactants by using fluorescence (steady state, synchronous and 3D), UV-visible, resonance light scattering (RLS), dynamic light scattering (DLS), and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The esterase activity of serum albumin was tested in associations with MnO 2 NPs and surfactants. The antioxidant potential of prepared NPs was also evaluated (DPPH method). Gel electrophoresis was carried out to analyze the effect of MnO 2 NPs and surfactants on DNA. Presence of CTAB, Tween 20, DTAB and Tween 80 enhanced nanoparticle-protein binding. Tween 20 based nanoparticle systems showed long-term stability and biocompatibility. The quenching of BSA fluorescence emission in presence of MnO 2 NPs alone and along with Tween 20 revealed stronger association of nanoparticles with proteins. Enhancement in the esterase activity (BSA) was observed in the presence of Tween 20. Furthermore, radical scavenging activity showed highest antioxidant potential in presence of Tween 20. The enthalpy and entropy assessment for protein-NPs association showed the predominance of Vander Waals interactions and hydrogen bonding. The synchronous fluorescence analysis highlighted the involvement of tryptophan (Trp) in the MnO 2 NPs-protein interactions. The study evaluates the influence of surfactant on the associations of MnO 2 NPs with the essential biomolecules. The findings can be crucially utilized in designing biocompatible MnO 2 formulations for long term applications.Communicated by Ramaswamy H. Sarma.

Hyperlipidemia is a key risk factor mainly for hypertension and cardiac abnormalities. Previously eucalyptus plant (river red gum) had been used for its medicinal value for the treatment of many ailments. This study focused on phytochemical examination, investigation of an in vitro potential and in vivo effects in mice fed with high cholesterol diet, GC-MS analysis of extracts of Eucalyptus camaldulensis leaves and further confirmation of anti-hyperlipidemic potential of different constituents of plant extracts by using in silico technique. For in vitro study screening of different extracts of Eucalyptus camaldulensis leaves was performed by using pancreatic lipase enzyme inhibition assay. Ethanolic extract presented the highest potential among all the extracts by inhibiting pancreatic lipase having IC 50 -11.88 µg/mL. For in vivo study mice were fed with high cholesterol diet for induction of Hyperlipidemia. Water extract showed great anti-hyperlipidemic potential by reducing the level of cholesterol, triglycerides, low density lipoproteins and increasing high density lipoproteins level significantly ( p  < 0.05). Moreover, molecular docking and prime MM-GBSA study were applied for screening of compounds having anti-hyperlipidemic potential which showed that Alpha-cadinol was the lead compound for inhibition of pancreatic lipase enzyme having docking score (-6.604). The ADMET properties and toxicity profile of the top docked compounds were also detailed for ensuring their safety aspects. In this way in silico analysis substantiate the experimental findings by showing anti-hyperlipidemic potential in constituents of eucalyptus plant. Thus, there is a need of advanced research for isolation of active constituents having said anti-hyperlipidemic potential in the Eucalyptus camaldulensis plant.Communicated by Ramaswamy H. Sarma.

Vaccine hesitancy (VH) is not a new phenomenon in Pakistan and is regarded as one of the primary causes of unsatisfactory vaccination campaigns. This study determined post-vaccination COVID-19 VH, factors influencing COVID-19 vaccine uptake, and public's intent to receive booster vaccinations. A cross-sectional study was conducted among adult population of Lahore, Pakistan. Participants were recruited via convenience sampling between March and May 2022. SPSS version 22 was used for the data analysis. A total of 650 participants were included in the study (age = 28.1 ± 9.7 years; male-to-female ratio nearly 1: 1). The majority of participants received Sinopharm followed by Sinovac vaccine. The top three reasons of vaccine uptake were "only vaccinated individuals are allowed at the workplace, and educational institutes" (Relative importance index (RII) = 0.749), "only vaccinated people are allowed to go to markets, malls and other public places" (RII = 0.746), and "protect myself from the infection" (RII = 0.742). The mean COVID-19 VH score was 24.5 ± 6.2 (95% CI 23.9-24.9), with not being pro-vaccines and poor economic status were the significant predictors of COVID-19 vaccine hesitancy among immunized individuals ( p  < .05). Acceptance of booster vaccines was negatively associated with younger age and a lower level of education. Furthermore, being pro-vaccine was associated with a greater likelihood of accepting booster vaccines ( p  = .001). The Pakistani public continues to express VH toward COVID-19 vaccines. Therefore, aggressive measures must be taken to combat the community factors that contribute to it.

Human cancer remains a cause of high mortality throughout the world. The conventional methods and therapies currently employed for treatment are followed by moderate-to-severe side effects. They have not generated curative results due to the ineffectiveness of treatments. Besides, the associated high costs, technical requirements, and cytotoxicity further characterize their limitations. Due to relatively higher presidencies, bioactive peptides with anti-cancer attributes have recently become treatment choices within the therapeutic arsenal. The peptides act as potential anti-cancer agents explicitly targeting tumor cells while being less toxic to normal cells. The anti-cancer peptides are isolated from various natural sources, exhibit high selectivity and high penetration efficiency, and could be quickly restructured. The therapeutic benefits of compatible anti-cancer peptides have contributed to the significant expansion of cancer treatment; albeit, the mechanisms by which bioactive peptides inhibit the proliferation of tumor cells remain unclear. This review will provide a framework for assessing anti-cancer peptides' structural and functional aspects. It shall provide appropriate information on their mode of action to support and strengthen efforts to improve cancer prevention. The article will mention the therapeutic health benefits of anti-cancer peptides. Their importance in clinical studies is elaborated for reducing cancer incidences and developing sustainable treatment models.

Diabetes is a chronic metabolic disorder marked by postprandial hyperglycemia due to several etiologies including abnormal carbohydrate digestion and glycation of hemoglobin. The prolong use of synthetic drugs results in characteristic side effects which necessitates the discovery of safe and cost-effective substitutes. The aim of the current study is to isolate and evaluate the antidiabetic potential of the phenolic compounds from the leaves of Tradescantia pallida . Syringic acid, p -coumaric acid, morin and catechin (compounds 1 - 4 ) were isolated and characterized from Tradescantia pallida leaves using column chromatography and spectroscopic techniques. The in vitro antidiabetic potential of the phenolic compounds were assessed using α-amylase and non-enzymatic glycosylation of hemoglobin protein assays. A mechanistic insight of interactions between phenolic compounds and human α-amylase and hemoglobin protein were scrutinized by employing molecular docking method. Prime Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) calculations were carried out to find the binding energies of the ligand-protein complexes. Morin and catechin were further analyzed to find the dynamic and thermodynamic constraints of the complexes under specific biological conditions using molecular dynamic simulation trajectories. The stability and flexibility of the complexes were justified by fluctuation of α-carbon chain, Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF) and type of interactions involved which authenticated the in vitro inhibitory potential of morin and catechin against enzymatic and non-enzymatic pathways. The current study could be fruitful in rational designing of safe antidiabetic drugs of natural origin.Communicated by Ramaswamy H. Sarma.

Hypoxia, an oxygen-deprived condition of the tumor, is one of the major reasons for resistance to chemotherapy. Carbonic anhydrases are generally involved in pH homeostasis in normal conditions, but in solid tumors having a strong relation with hypoxia, the carbonic anhydrase IX (CA-IX) enzyme is overexpressed and results in an extracellular acidic environment. For most weakly basic anticancer drugs, including doxorubicin (Dox), the ionization in an acidic environment limits their cellular uptake, and consequently, the tumor exposure to the drug at sub-therapeutic concentration comes out as chemoresistance. Herein, a combined drug delivery system of liposomes and mesoporous silica nanoparticles (MSNPs) was developed for the co-delivery of the CA-IX enzyme inhibitor and Dox in hypoxic condition. The unique structure of MSNPs with higher surface area was utilized for higher drug loading and sustained release of Dox. Additionally, the biocompatible nature of liposomal coating as a second loading site for the CA-IX enzyme inhibitor has provided gatekeeping effects at pore opening to avoid premature drug release. Lipid coated MSNPs as a co-delivery system for Dox and the CA-IX inhibitor have synergistic cytotoxic effects against MDA-MB 231 breast cancer cells in hypoxic conditions. These findings assure the potential of this drug delivery system to overcome hypoxia-related chemoresistance.

There are reports of high rates of antibiotic prescribing among hospitalized patients with COVID-19 around the world. To date, however, there are few reports of prescribing in relation to COVID-19 in Pakistan. Herein, we describe a point prevalence survey of antibiotic prescribing amongst patients hospitalized with suspected or proven COVID-19 in Pakistan. A Point Prevalence Survey (PPS) was undertaken in seven tertiary care health facilities in Punjab Provence, Pakistan. Baseline information about antimicrobial use according to the World Health Organization (WHO) standardized methodology was collected on a single day between 5 th and 30 April 2021. A total of 617 patients' records were reviewed and 578 (97.3%) were documented to be receiving an antibiotic on the day of the survey. The majority (84.9%) were COVID-19 PCR positive, 61.1% were male and 34.9% were age 36 to 44 years. One quarter presented with severe disease, and cardiovascular disease was the major comorbidity in 13%. Secondary bacterial infection or co-infection (bacterial infection concurrent with COVID-19) was identified in only 1.4%. On the day of the survey, a mean of 1.7 antibiotics was prescribed per patient and 85.4% antibiotics were recorded as being prescribed for 'prophylaxis'. The most frequently prescribed antibiotics were azithromycin (35.6%), ceftriaxone (32.9%) and meropenem (7.6%). The majority (96.3%) of the antibiotics were empirical and all were from WHO Watch or Reserve categories. Overall, a very high consumption of antibiotics in patients hospitalized with suspected or proven COVID-19 was observed in Pakistan and this is concerning in view of already high rates of antimicrobial resistance in the region. Antimicrobial stewardship programs need to urgently address unnecessary prescribing in the context of COVID-19 infection.

Background: Lower respiratory tract infection (LRTI) is one of the triggering factors toward death in children below the age of five years necessitating appropriate antibiotic selection. This study aimed to evaluate antibiotic use among hospitalized children (≤5 years age) with LRTIs., Methods: A retrospective study was conducted in seven health facilities of the central region of Punjab province of Pakistan. The medical records of hospitalized children ≤5 years diagnosed with LRTI were thoroughly evaluated to get information on demographics, clinical characteristics, and details of prescribed antibiotics. The appropriateness of antibiotics was assessed according to guidelines of the British National Formulary due to a lack of indigenous standard treatment guidelines., Results: The medical records of 5926 children were searched with the majority (70.9%) diagnosed with community-acquired pneumonia (CAP) followed by acute bronchitis (14.1%). Ceftriaxone plus ampicillin and ceftriaxone plus ampicillin plus amikacin were prescribed to 39% and 11.7% study population, respectively. One-fourth of children were prescribed the wrong dose, and more than half were encountered with the incorrect route of antibiotic administration. Alarmingly, 90.2% of antibiotic prescriptions were inappropriate in our findings., Conclusions: Current surveillance study revealed a worrying degree of antibiotic misuse among hospitalized LRTI children aged ≤5 years.

This research covers the current status of occupational health and safety (OHS)-related practices in the informal construction segment of Pakistan. Data were collected, through interviews, from 316 construction sites employing 3577 workers. The results of the study reveal that both employers and workers lack knowledge of OHS laws/standards and no practices of this nature are enacted at these construction sites. Alarmingly, work-related accidents, whenever they happen, are not given due attention and there is no formal injury-report system. The informal construction industry employs a huge portion of the informal workforce, and lack of OHS happens at tremendous human cost. These research findings may thus play their role in strengthening the case for reforms in the sector. This study, if properly utilized, may also enable employers of the sector by increasing their knowledge about OHS practices and, as a result, trying to offer safer environments for their workers.

Context: β-Aescin has anti-inflammatory, anti-oxidant and antiedematous properties., Objective: The present study investigated the hepatoprotective effect and underlying mechanisms of β-aescin in CCl 4 -induced liver damage., Materials and Methods: Thirty-five Wistar rats were divided into six groups: normal control, CCl 4 control, silymarin (50 mg/kg, p.o) and β-aescin (0.9, 1.8 and 3.6 mg/kg, i.p.) treatment for 14 d. CCl 4 (1 mL/kg, i.p. for 3 d) was administered to produce hepatic damage. Ponderal changes and liver marker enzymes were estimated. Hepatic oxidative and nitrosative stress was estimated by levels of thiobarbituric acid reactive substances (TBARS), glutathione (GSH) and nitrite/nitrate. Serum TGF-β1 and TNF-α were estimated by ELISA technique. Hepatic collagen and histopathological studies were carried out., Results: β-Aescin (3.6 mg/kg) markedly decreased CCl 4 -induced increased levels of ALT, AST, ALP (71.77 versus 206.7, 71.39 versus 171.82, 121.20 versus 259 IU/L, respectively), total bilirubin (0.41 versus 1.35 mg/dL), TBARS (2.0 versus 8.83 nmol MDA/mg protein), nitrite/nitrate (352.50 versus 745.15 μg/mL) and increased CCl 4 -induced decreased GSH levels (0.095 versus 0.048 μmol/mg protein). β-Aescin (3.6 mg/kg) induced focal regenerative changes in liver and markedly decreased TBARS (2.0 versus 8.83 nmol MDA/mg protein), nitrite/nitrate (352.50 versus 745.15 μg/mL), TGF-β1 (92.28 versus 152.1 pg/mL), collagen content (110.75 versus 301.74 μmol/100 mg tissue) and TNF-α (92.82 versus 170.56 pg/mL) when compared with CCl 4 control., Discussion and Conclusion: The findings suggest that β-aescin has a protective effect on CCl 4 -induced liver injury, exhibited via its anti-inflammatory, antioxidative, antinitrosative and antifibrotic properties inducing repair regeneration of liver. Hence, it can be used as a promising hepatoprotective agent.

Due to the high toxicity of endocrine disruptors (EDs), studies are being undertaken to design effective techniques for separation and detection of EDs in various matrices. Recently, research activities in this area have shown that a diverse range of chromatographic techniques are available for the quantification and analysis of EDs. Therefore, on the basis of significant, recent original publications, we aimed at providing an overview of different separation and detection methods for the determination of trace-level concentrations of selected EDs. The biological effects of EDs and current pretreatment techniques applied to EDs are also discussed. Various types of chromatographic techniques are presented for quantification, highlighting time- and cost-effective techniques that separate and quantify trace levels of multiple EDs from various environmental matrices. Reports related to methods for the quantification of EDs from various matrices primarily published since 2008 have been cited.

The transient receptor potential (TRP) channel superfamily is a family of 28 nonselective cation channels expressed on the plasma membrane with a high permeability to calcium. Role of TRP channels, especially TRP vanilloid 1, TRP ankyrin 1 and TRP melastatin 8, is widely documented in nociception. During the last few years, there has been a consistent increase in reports indicating the presence and significance of these channels in different tissues including bladder, skin, respiratory system and brain. Based on calcium permeability of these channels and the much published role of calcium and its signaling in adipogenesis, there is a potential for importance of these ion channels in adipocyte biology. This review provides insight into the involvement of TRP channels in adipocyte differentiation, obesity and associated complications. Furthermore, the authors will focus to evaluate these channels as potential therapeutic targets for the management of obesity.

Background: Information on growth status of a population is essential to establish the health status of the population and administer any health intervention programmes., Aims: The study aimed to examine growth patterns in body, fat and physiological traits during adolescence in the light of various hypotheses and other studies., Subjects and Methods: Cross-sectional data on a sample of 220 Rajput girls aged 11-17 years were collected from Theog tehsil, Shimla District in Himachal Pradesh., Results: Mean body height and weight increased by 11% and 45.5%, respectively, from age 11 to 17 years. The first marked growth in height took place between 11 and 12 years, while the maximum annual increment was witnessed between 13 and 14 years. ANOVA revealed significant differences in anthropometric traits between various adolescent age groups. Waist-hip ratio (WHR) decreased from 0.77 at age 11 to 0.72 at age 17 years to attain gynoid pattern of body fat. Mean systolic and diastolic blood pressure increased from 106.92 and 66.48 mm Hg to 111.74 and 72.89 mm Hg, respectively., Conclusion: Although the girls in the present study did not suffer from any severe malnutrition, they had lower dimensions than their Western counterparts when they entered the adolescence phase and also later on. In contrast to height deficits, increase in weight deficits was greater. There is no indication of any compensatory or catch-up growth during adolescence. The present study does not support the hypothesis that lower nutritional stage during childhood affects the timing of adolescent take-off, age at peak height and weight velocity. The data lend support to the hypothesis of saltatory patterns with intervening periods of stasis. BMI, %fat and FM were significantly correlated with diastolic blood pressure but non-significantly correlated with systolic blood pressure.

Virulence expression of Salmonella enterica serovar Typhimurium under iron limited condition was measured by beta-galactosidase (beta-gal) assay using a hilA-lacZY fusion strain and calculated as Miller units. hilA-lacZY beta-galactosidase assays were performed in brain heart infusion (BHI) and minimal media (M9), after iron chelation with 2, 2-dipridyl and iron-supplementation respectively. Before performing virulence assays, concentrations of iron in the media were estimated using ferrozine. Iron content was found to be more in BHI (42.6 microg dL(-1)) as compared to M9 (10.03 microg dL(-1)). beta-gal activity of Salmonella Typhimurium in BHI was generally less than that observed in M9. After exposure to various combinations of iron chelator in BHI, hilA-lacZY activity only increased at the highest concentration of chelator (2001 microM) but decreased in M9 media for all iron concentrations when compared to controls with no iron amendment. These results indicate that iron availability may influence S. Typhimurium hilA expression.

The relationship of early and late menarche with adult body dimensions has been studied on a sample of 147 young adult women drawn from an urban Punjabi population of Chandigarh and Ludhiana. The results indicate that girls with early menarche (age 10 to 11) have significantly smaller skeletal dimensions (both longitudinal and transverse) and more subcutaneous fat than those with average or late menarche. The girls with late menarche have on average more height for weight than early maturers. Results indicate that there is a biological determinant of the observed association between menarcheal age and fatness and adult body size.