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Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver disorders globally and is a major clinical concern that is increasing in both industrialized and developing countries. Purpose: This study aimed to evaluate the ability of Spinacia oleracea dried powder in protecting rabbits from the toxicity caused by oxidized-tallow. Methods: Oxidized tallow and spinach powder were administered to the rabbits. The phenolic profile of spinach was studied using HPLC-DAD. Investigations were conducted on the liver phospholipid composition, liver-histology analysis, levels of antioxidants, liver-associated inflammatory cytokines, and the serum-lipid profile. Results: The findings revealed that the primary constituents of the extracts were gallic acid, luteolin-3-glucoside, kaempferol-3-glucoside, and chlorogenic acid. Histological and biochemical examination of the liver revealed greater fat storage in the OT-group than in the control or therapy groups. The OT-treated rabbits exhibited increased levels of hepatic inflammatory cytokines, decreased antioxidant status, and elevated lipid profiles. After consuming spinach, the levels of proinflammatory cytokines (IL-1, IL-4, IL-6, and TNF-α), PPARs, and antioxidants (CATs, SODs, TBARS, GSH-Px, and GSHs) returned to normal. Conclusion: Dried spinach powder is an excellent dietary source of liver-protective chemicals that ameliorate NAFLD by reducing proinflammatory cytokines and enhancing antioxidant status.

ABSTRACT Objective: To compare the outcomes of Duloxetine and Amitriptyline therapy in fibromyalgia patients regarding change in Symptom Severity Scale (SSS) score and Widespread Pain Index (WPI) from baseline after three months of treatment. Methodology: This quasi-experimental study was done in the Department of Rheumatology, Pakistan Institute of Medical Sciences, Islamabad, from November 2022 to April 2023. One hundred fifty-six fibromyalgia patients of either gender between the ages of 25-70 years were included in the study. They were erratically assigned into two groups. Group A patients were given Duloxetine, while group B patients were given Amitriptyline for 12 weeks with main outcome of change in WPI and SSS scores three months after the therapy. Results: There were 2.6% (n=2/78) males and 97.4% (n=76/78) females in group A and 1.3% (n=1/78) males and 98.7% (n=77/78) females in group B (P=0.560). At baseline, the mean WPI score in group A was 15.8 ± 1.3 SD, and it was 16.1 ± 1.4 SD in group B (P=0.286), and the mean SSS score was 6.6 ± 1.6 SD in group A, and it was 6.8 ± 1.5 SD in group B (P=0.467). At 12 weeks, the mean WPI score in group A was 11.2 ± 2.2 SD, and it was 8.9 ± 3.1 SD in group B (P=0.001), and the mean SSS score was 4.5 ± 1.7 SD in group A, and it was 3.6 ± 1.3 SD in group B (P=0.001). Conclusions: Outcomes were better with Amitriptyline compared to those patients taking Duloxetine in diagnosed cases of fibromyalgia.

This work describes the profiling of phenolic compounds, total phenolic contents, total flavonoid contents, total anthocyanins, and radical scavenging activity of two important cultivars of pears grown in Pakistan. The HPLC-DAD reversed phase chromatography was used to study phenolic compounds. The spectrophotometry was done to measure the total flavonoid contents, total phenolic contents, total anthocyanin contents, and radical scavenging activity. Results showed 21 phenolic compounds in the extract of Comice pears and 16 in Bosc pears. These include 3-caffeoylquinic acid, p-coumaroylhexose-4-hexoside, 5-coumaroylquinic acid, cis-5-coumaroylquinic acid, (+)-catechin-3-glucoside, ellagic acid dihexoside, quercetin-3-rutinoside, eriodictyol-7-rutinoside, 3-hydroxyphloretin-6′-hexoside, (−)-epigallocatechin, quercetin pentosyl hexoside, (−)-epigallocatechin-3-gallate, epicatechin-3-(4-methyl)-gallate, rosmarinic acid, cyanidin-3,5-diglucoside, 4-caffeoyl-5-coumaroylquinic acid were major identified phenolic compounds in both Comice and Bosc pears. Except for total anthocyanin contents, there were significant differences between the selected cultivars in terms of total phenolic contents, total flavonoid contents, and radical scavenging activity values. In conclusion, the selected pear samples contain important phenolic compounds and possess antioxidant properties.

The effect of domestic cooking techniques such as boiling, frying, microwaving, and freezing on the phenolic profile of spinach, and mustard was studied using high performance liquid chromatography with diode array detection (HPLC-DAD). Nitric oxide, superoxide anion scavenging activity, and anti-choline esterase activity were studied using spectroscopic methods. Results showed 12 phenolic compounds in spinach and 13 in mustard leaves. Microwaving significantly enhanced the amounts of most of the phenolic compounds. Conversely, boiling has an enervating effect on the amounts of phenolic compounds. Raw spinach and mustard leaves have the highest nitric oxide inhibition activities of 42.4 and 62.7%, respectively, followed by microwaving and freezing. Similarly, the highest % superoxide anion scavenging activity was determined in raw spinach and mustard. The applied cooking techniques had deleterious effects on anti-cholinesterase activities. In conclusion, different processing conditions affected phenolic availability, and the antioxidant and anti-cholinesterase activities of the selected vegetable leaves.

The purpose of this review is to evaluate the biological compounds present in walnut kernels and also to assess potential human health benefits. Walnuts are one of the most important tree nuts, belonging to the Juglandaceae family. They are cultivated worldwide, primarily in temperate regions. Throughout history, walnut kernels have been utilized to treat various disorders such as diarrhea, diabetes mellitus, thyroid issues, cancer, anorexia, and infectious diseases, in addition to their dietary benefits. Presently, advanced techniques like UHPLC-MS/MS, HPLC-DAD chromatography, and GC–MS are employed to identify key compounds in walnuts. These include phenolic compounds, phenolic acids, tannins and related compounds, flavonoids, phytosterols, fatty acids, triglycerides, tocopherols, vitamins, and carotenoids. The review also demonstrates that walnut kernels possess numerous medicinal properties, including antioxidants, cardiovascular effects, anti-cancer effects, antidiabetic effects, hepatoprotective effects, and antimicrobial effects. The current review also gives details on plant origin, distribution, classification, cultivation, and consumption as food. The review also described the recent medicinal plant profile, identification, and screening of the active ingredients of walnut's kernels. Researchers around the world are taking an interest in the clinical evaluation of walnut's active ingredients. The current review also gives details of the most recent conducted clinical studies. Mostly the reviews of walnuts are focused on walnut cultivars and/or specific types of compounds, although our current review is mostly focused on the active ingredients of walnut kernels and their specified biological role. In conclusion, different varieties of walnuts are abundant in significant bioactive compounds that possess important medicinal properties.

Momordica charantia L. (MC) is a widely consumed vegetable known for its nutritional benefits, as it is a rich source of carotenoids and phenolic compounds. Various cooking methods are use in domestic settings, including microwave cooking. Therefore, it is crucial to investigate the impact of microwave cooking on the bioactive composition of MC. MC fruits were subjected to microwave heat for 5-, 10-, and 15-min. High performance liquid chromatography was used to identify of carotenoids and phenolic compounds, and total bioactive composition and antioxidant assays were conducted using spectroscopic techniques. There were 17 carotenoids and chlorophylls identified in MC fruit, including lutein, violaxanthin, antheraxanthin, pheophytin a, and all-E-β-carotene. The levels of these compounds significantly increased upon exposure to microwave heating. Similarly, 16 phenolic compounds were identified, and their amounts increased during the treatments, except for 3-hydroxyphloretin-6′-hexoside, quercetin-3-(6″-acetyl)-glucoside, petunidin-3-(6″-acetyl)-glucoside and petunidin-3-(6″-acetyl)-glucoside. The sample subjected to microwave treatment for 15 min exhibited the highest concentration of total phenolic compounds (TPC) at 754.5 mg/100g. The total flavonoid content (TFC) reached 94.6 mg/100g after 10 min of treatment. Additionally, the maximum total anthocyanin content, reported as 54.8 mg/L, was observed in the sample exposed to microwave heating for 15 min.

Non-alcoholic fatty liver disease (NAFLD) is a chronic condition caused by several factors including thermally oxidized tallow. Various strategies have been considered to ameliorate NAFLD. However, the role of milk thistle (MT) in ameliorating NAFLD caused by thermally oxidized tallow has not been reported. The purpose of this study was to evaluate the ability of milk thistle to protect rabbits from the toxicity of oxidized tallow (OT). The rabbits were given OT and an extract of MT. The composition of MT was analyzed using HPLC-DAD, and tallow samples were studied using GC-MS. The study also examined liver histology, antioxidant levels, liver-related inflammatory markers, and serum lipid profile. The results showed that the major components of the MT extract were silybin B, formononetin-glucuronic acid, proanthocyanidin B1, silychristin B, silydianin, and isosilybin A. The group given OT showed elevated lipid profiles, lower antioxidant status, higher levels of hepatic inflammatory markers, and lower levels of anti-inflammatory markers. This group also had higher fat storage in the liver compared to the control or treatment groups. However, when MT was supplemented, the pro-inflammatory cytokines (IL-1, IL-4, IL-6, and TNF-α) and antioxidant status (CAT, SOD, GSH-Px, GSH, and TBARS) of the liver returned to normal. This suggests that MT extract is an excellent source of hepatoprotective compounds. It protects the liver by increasing antioxidant enzymes, decreasing pro-inflammatory cytokines, and increasing anti-inflammatory markers.

This study examined the effects of thermally oxidised high-fat diet (Oxi-HFD) induced toxicity on mice. Biochemical and histological analyses revealed that the Oxi-HFD group had higher levels of fat accumulation in their livers compared to the control groups. Mice fed on Oxi-HFD exhibited higher levels of hepatic inflammatory markers, altered lipid profile, decreased antioxidant status, and increased body weight. Oxidized high-fat diets significantly increased the amounts of hepatic lipase, phospholipids, and lysophospholipids. However, supplementation of walnut extract improved hepatic lipase, phospholipids, and lysophospholipid levels in mice. Additionally, the consumption of walnut extract improved body weight, lipid profiles (TC, TG, HDL, and LDL), and antioxidant status (GSH, CAT, GSH-Px, SOD, and TBARS). Furthermore, walnut extract supplementation down-regulated the expression of pro-inflammatory cytokines (IL-6 and TNF-α). In conclusion, walnut extract is a valuable source of hepatoprotective substances that enhance antioxidant status and reduce hepatic inflammation.

Objective The objective of this study was to determine the effectiveness of task specific virtual reality training for better ambulation in post stokes patients. Methodology This study was a quasi-experimental study (single group) with non-probability convenient sampling. Baseline assessment was taken at start of study and final assessment was done after 8 weeks. SPSS version 23 was used to analyze and record the data. Descriptive statistics was used to calculate mean and SD for all continuous data and percentages were calculated for all categorical data. Paired T test was used to compare mean change in continuous data before and after intervention. Results Although there was some improvement in pre and post scoring on outcome measurement scales applied in this study, still there is no significant difference between pre and post walking speed (P Value 0.702), TUG test (P Value 0.146), MAS scale (P Value 0.227), forward stepping test P Value (0.089) and functional reach test P Value (0.415). Conclusion. This study concluded that, VR based task specific training is an effective treatment for post stroke patients regarding their gait rehabilitation, as for scoring is concerned on different outcome measures but overall results are not statistically significant. Key Words Cerebrovascular Accident, Gait, Gait Disorders, Stroke, Virtual reality

Introduction: Patient satisfaction is an important indicator of the quality of care given to patients in the health care system. It helps the clinician to know about the exact and objective feedback of the services they provide and to improve the quality and outcome of patient care. Patient satisfaction in physical therapy has not been closely monitored, and limited research exists in the field of health services in this area. The purpose of this study was to measure the patient's satisfaction at the physiotherapy OPD of Hayatabad medical complex Peshawar. Material & Methods: A cross-sectional survey was conducted from October 2018 to January 2019 to measure patient satisfaction. MedRisk patient satisfaction questionnaire by Beattie et al (2005) was used for data collection. The questionnaire was distributed among 125 participants at the physiotherapy OPD of Hayatabad medical complex Peshawar by non-probability convenient sampling. SPSS version 20 was used for data analysis. Results: A total of 125 participants were recruited of which more than half were female (n=70, 56%) and male (n=55,44%) with a mean age of 41.88±12.23. The chief complaint participants presented with was shoulder pain (n=29, 23.2%) followed by low back pain (n=24,19.2%). Patients were satisfied and responded positively to all the MedRisk patient satisfaction questionnaire statements. When asked the participants “My therapist treats me respectfully” (n=4,3.2%) disagree, (n=4,3.2%) neutral responses, and (n=117,93.6%) agree. When inquired about the time therapist spend with participants (n=111, 88.8%) disagree, (n=14, 11.2%) agree. “My therapist thoroughly explains the treatment(s) I receive” (n=3,2.4%) disagree, (n=3,2.4%) neutral response and (n=119,95.2%) agree. “Overall, I am completely satisfied with the services I received from my therapist” (n=1,0.8%) disagree, (n=7,5.6%) neutral response, (n=117,93.6%) agree. No significant correlation was found between gender and patient satisfaction as the p-value was greater than 0.05. Conclusion: This cross-sectional survey showed a high level of patient satisfaction with physiotherapy and good quality care to the patient by a professional therapist in physiotherapy OPD of Hayatabad medical complex Peshawar.

AbstractHerein we designed, optimized, and characterized the Metformin Hydrochloride Transethosomes (MTF-TES) and incorporate them into Chitosan gel to develop Metformin Hydrochloride loaded Transethosomal gel (MTF-TES gel) that provides a sustained release, improved transdermal flux and improved antidiabetic response of MTF. Design Expert® software (Ver. 12, Stat-Ease, USA) was applied for the statistical optimization of MTF-TES. The formulation with Mean Particle Size Distribution (MPSD) of 165.4 ± 2.3 nm, Zeta Potential (ZP) of −21.2 ± 1.9 mV, Polydispersity Index (PDI) of 0.169 ± 0.033, and MTF percent Entrapment Efficiency (%EE) of 89.76 ± 4.12 was considered to be optimized. To check the chemical incompatibility among the MTF and other formulation components, Fourier Transform Infrared (FTIR) spectroscopy was performed and demonstrated with no chemical interaction. Surface morphology, uniformity, and segregation were evaluated through Transmission Electron Microscopy (TEM). It was revealed that the nanoparticles were spherical and round in form with intact borders. The fabricated MTF-TES has shown sustained release followed by a more pronounced effect in MTF-TES gel as compared to the plain MTF solution (MTFS) at a pH of 7.4. The MTF-TES has shown enhanced permeation followed by MTF-TES gel as compared to the MTFS at a pH of 7.4. In vivo antidiabetic assay was performed and results have shown improved antidiabetic potential of the MTF-TES gel, in contrast to MTF-gel. Conclusively, MTF-TES is a promising anti-diabetic candidate for transdermal drug delivery that can provide sustained MTF release and enhanced antidiabetic effect.

Introduction: Cricket is the most commonly played game in Pakistan. Among all the sports hand and wrist injuries are higher in cricket players. Little is known about its prevalence. This study was conducted in order to determine the prevalence of hand and wrist injuries in cricketers at Islamia Cricket Academy (ICA) Peshawar. Material & Methods: This cross-sectional study was conducted at Islamia Cricket Academy (ICA) Peshawar. A total of 200 players, who were willing to participate in the study and were members of the Islamia cricket academy were recruited in the study. After taking consent a self-modified questionnaire was handed over to 200 cricket players, selected through convenience sampling. Data were analyzed through SPSS version 20. Results: A total of 108 (54%) players reported hand injuries, out of these 96 (48%) players reported soft tissue injuries, 8(4%) reported fracture, while 4 (2%) players reported dislocation. In the hand injuries 69 (34.5%) players had got injuries on their right hand, while 39(19.5%) players had got injuries on their left hand. Twenty-three players (11.5%) reported wrist injuries, in which 18 (9%) players reported soft tissue injuries, 4 players (2%) had dislocation, while 1 player (0.5%) had got fracture. In the wrist injuries 17 players (8.5%) got wrist injuries on their right hand, while 6 players (3%) had got wrist injuries on their left hand. Conclusion: The prevalence of hand injuries were more than the wrist injuries and were more common on right side. Most injuries occurred to players during fielding. The ring and little finger were mostly injured in hand. Strategies focused on the little and ring fingers during fielding activities could be used to decrease the load of injuries.

Leafy vegetables are enriched with health-promoting compounds such as carotenoids and polyphenols. Different processing treatments have been shown to affect the amounts of these compounds. In this study, mustard (Brassica campestris) leaves were subjected to various processing treatments, boiling, frying, freezing, sonication, microwaving, and blanching. Carotenoid contents were determined using HPLC-DAD while the total phenolic, flavonoids, anthocyanin, and antioxidant activities were determined using established spectroscopic protocols. It has been found that different processing treatments concentrated the lutein, flavoxanthin, and β-carotene contents of mustard leaves, while frying has been found to have deleterious effects on these compounds. During boiling the concentration of violaxanthin, antheraxanthin, flavoxanthin, and lutein was significantly increased to 87.4, 29.9, 20.4, and 340.8 μg/g respectively versus control. The total anthocyanin and phenolic contents of mustard leaves were better preserved during frying having values of 6.2 mg/L and 1281.2 mg/100g, respectively, whereas the total flavonoid contents (TFC) in the control sample was 111.8 mg/100g. Among the studied treatments the highest TFC was reported in the blanched samples (108.7 mg/100g), followed by sonication (107.1 mg/100g). During microwave and sonication, the antioxidant potential of the treated samples had significantly increased while in other treatments, it was reduced.

The current study explores the potential of melatonin (MLT)-loaded solid lipid nanoparticles (MLT-SLNs) for better neuroprotective effects in ischemic stroke. MLT-SLNs were prepared using lipid matrix of palmityl alcohol with a mixture of surfactants (Tween 40, Span 40, Myrj 52) for stabilizing the lipid matrix. MLT-SLNs were tested for physical and chemical properties, thermal and polymorphic changes, in vitro drug release and in vivo neuroprotective studies in rats using permanent middle cerebral artery occlusion (p-MCAO) model. The optimized MLT-SLNs showed particle size of ∼159 nm, zeta potential of −29.6 mV and high entrapment efficiency ∼92%. Thermal and polymorphic studies showed conversion of crystalline MLT to amorphous form after its entrapment in lipid matrix. MLT-SLNs displayed a sustained release pattern compared to MLT dispersion. MLT-SLNs significantly enhanced the neuroprotective profile of MLT ascertained by reduced brain infarction, recovered behavioral responses, low expression of inflammatory markers and improved oxidation protection in rats. MLT-SLNs also showed reduced hepatotoxicity compared to p-MCAO. From these outcomes, it is evidenced that MLT-SLNs have improved neuroprotection as compared to MLT dispersion and thereby present a promising approach to deliver MLT to the brain for better therapeutic outcomes in ischemic stroke.

Abstract Background Allopurinol (ALP), a xanthine oxidase inhibitor, is a first line drug for the treatment of gout and hyperuricemia. Being the member of BCS class II drugs, ALP has solubility problem, which affects its bioavailability. Also, ALP has shorter half-life and showed GI related problems. In present study, ALP was encapsulated in nanostructured lipid carriers (NLCs) to ensure enhanced bioavailability, improved efficacy and safety in vivo. Methodology ALP-loaded NLCs were fabricated by micro-emulsion technique. The prepared NLCs were optimized via design expert in term of particle size, zeta potential and entrapment efficiency. FTIR, PXRD and TEM analysis were carried out to check chemical interaction, polymorphic form and surface morphology of the optimized formulation. ALP-loaded NLCs were then loaded into HPMC based poloxamer-407 gel and were characterized. In vitro and ex vivo analysis were carried out via dialysis membrane method and franz diffusion cell, respectively. Uric acid was used for induction of gout and the anti-gout activity of ALP-loaded NLCs gel was performed and compared with ALP suspension. Results The optimized formulation had particles in nano-range (238.13 nm) with suitable zeta potential (-31.5 mV), poly-dispersity index (0.115) and entrapment of 87.24%. FTIR results confirmed absence of chemical interaction among formulation ingredients. XRD indicated amorphous nature of ALP-loaded NLCs, whereas TEM analysis confirmed spherical morphology of nanoparticles. The optimized formulation was successfully loaded in to gel and characterized accordingly. The in vitro release and drug release kinetics models showed sustained release of the drug from ALP-loaded NLCs gel. Furthermore, about 28 fold enhanced permeation was observed from ALP-loaded NLCs gel as compared to conventional gel. Skin irritation study disclosed safety of ALP-loaded NLCs gel for transdermal application. Furthermore, ALP-loaded NLCs gel showed significantly enhanced anti-gout activity in Sprague–Dawley rats after transdermal administration as compared to oral ALP suspension. Conclusion ALP-loaded NLCs gel after transdermal administration sustained the drug release, avoid gastrointestinal side effects and enhance the anti-gout performance of ALP. It can be concluded, that NLCs have the potential to deliver drugs via transdermal route as indicated in case of allopurinol.

Oxidative stress due to abnormal accumulation of reactive oxygen species (ROS) is an initiator of a large number of human diseases, and thus, the elimination and prevention of excessive ROS are important aspects of preventing the development of such diseases. Nuclear factor erythroid 2-related factor 2 (NRF2) is an essential transcription factor that defends against oxidative stress, and its function is negatively controlled by Kelch-like ECH-associated protein 1 (KEAP1). Therefore, activating NRF2 by inhibiting KEAP1 is viewed as a strategy for combating oxidative stress-related diseases. Here, we generated a cereblon (CRBN)-based proteolysis-targeting chimera (PROTAC), which we named SD2267, that induces the proteasomal degradation of KEAP1 and leads to NRF2 activation. As was intended, SD2267 bound to KEAP1, recruited CRBN, and induced the degradation of KEAP1. Furthermore, the KEAP1 degradation efficacy of SD2267 was diminished by MG132 (a proteasomal degradation inhibitor) but not by chloroquine (an autophagy inhibitor), which suggested that KEAP1 degradation by SD2267 was proteasomal degradation-dependent and autophagy-independent. Following KEAP1 degradation, SD2267 induced the nuclear translocation of NRF2, which led to the expression of NRF2 target genes and attenuated ROS accumulation induced by acetaminophen (APAP) in hepatocytes. Based on in vivo pharmacokinetic study, SD2267 was injected intraperitoneally at 1 or 3 mg/kg in APAP-induced liver injury mouse model. We observed that SD2267 degraded hepatic KEAP1 and attenuated APAP-induced liver damage. Summarizing, we described the synthesis of a KEAP1-targeting PROTAC (SD2267) and its efficacy and mode of action in vitro and in vivo. The results obtained suggest that SD2267 could be used to treat hepatic diseases related to oxidative stress.

Leafy vegetables are considered to have health-promoting potentials, mainly attributed to bioactive phenolic compounds. The antidiabetic effects of spinach, mustard, and cabbage were studied by feeding their phenolic-rich aqueous extracts to alloxan-induced diabetic mice. The antioxidant, biochemical, histopathological, and hematological indices of the control, diabetic, and treated mice were studied. Phenolic compounds present in the extracts were identified and quantified using HPLC-DAD. Results showed ten, nineteen, and eleven phenolic compounds in spinach, mustard, and cabbage leave aqueous extracts, respectively. The body weight, tissue total glutathione (GSH) contents, fasting blood sugar, liver function tests, renal function tests, and lipid profile of the mice were affected by diabetes and were significantly improved by the extract treatments. Likewise, hematological indices and tissues histological studies also showed recovery from diabetic stress in treated mice. The study's findings highlight that the selected leafy vegetables potentially mitigate diabetic complications. Among the studied vegetables, cabbage extract was comparatively more active in ameliorating diabetic stress.

Objectives: To examine and compare problem-focused and positive-coping styles among individuals with varying levels of cannabis use disorder (non-users to mild, moderate, and severe users), providing insights into how coping strategies may differ across these groups. Methods: A cross-sectional study collected data on cannabis use disorder in Rawalpindi and Islamabad. It included moderate and severe cases from rehab centers using purposive convenience sampling, mild users through snowball sampling in educational and recreational settings, and non-users primarily from educational institutes and offices. Only those meeting DSM-V criteria were included. Data was collected using the brief Coping Orientation to Problems Experienced inventory and DSM-5 criteria, analyzed with SPSS 21. Results: Out of all 204 participants, 104 (51%) were cannabis users, average age of 27 years (SD = 5.37), while 100 individuals (49%) were nonusers having average age of 25 years (SD = 5.65). Positive coping did not show significant variation across all three levels of cannabis use disorder (p =.909), but problem-focused coping revealed a significant variation (p =.001). Conclusion: Significant differences exist in the use of problem-focused coping styles between individuals with cannabis use disorder and non-users. [ABSTRACT FROM AUTHOR]

Abstract Background Natural phenolic compounds and Phenolics-rich medicinal plants are also of great interest in the management of diabetes. The current study was aimed to analyze phenolics in P. hydropiepr L extracts via HPLC-DAD analysis and assess their anti-diabetic potentials using in-vitro and in-silico approaches. Methods Plant crude methanolic extract (Ph.Cme) was evaluated for the presence of phenolic compounds using HPLC-DAD analysis. Subsequently, samples including crude (Ph.Cr), hexane (Ph.Hex), chloroform (Ph.Chf), ethyl acetate (Ph.EtAc), butanol (Ph.Bt), aqueous (Ph.Aq) and saponins (Ph.Sp) were tested for α-glucsidase and α-amylase inhibitory potentials and identified compounds were docked against these target enzymes using Molecular Operating Environment (MOE) software. Fractions were also analyzed for the nutritional contents and acute toxicity was performed in animals. Results In HPLC-DAD analysis of Ph.Cme, 24 compounds were indentfied and quantified. Among these, Kaemferol-3-(p-coumaroyl-diglucoside)-7-glucoside (275.4 mg g− 1), p-Coumaroylhexose-4-hexoside (96.5 mg g− 1), Quercetin-3-glucoronide (76.0 mg g− 1), 4-Caffeoylquinic acid (58.1 mg g− 1), Quercetin (57.9 mg g− 1), 5,7,3′-Trihydroxy-3,6,4′,5′-tetramethoxyflavone (55.5 mg g− 1), 5-Feruloylquinic acid (45.8 mg g− 1), Cyanidin-3-glucoside (26.8 mg g− 1), Delphinidin-3-glucoside (24 mg g− 1), Quercetin-3-hexoside (20.7 mg g− 1) were highly abundant compounds. In α-glucosidase inhibition assay, Ph.Sp were most effective with IC50 value of 100 μg mL-1. Likewise in α-amylase inhibition assay, Ph.Chf, Ph.Sp and Ph.Cme were most potent fractions displayed IC50 values of 90, 100 and 200 μg mL-1 respectively. Docking with the α-glucosidase enzyme revealed top ranked conformations for majority of the compounds with Kaemferol-3-(p-coumaroyl-diglucoside)-7-glucoside as the most active compound with docking score of − 19.80899, forming 14 hydrogen bonds, two pi-H and two pi-pi linkages with the Tyr 71, Phe 158, Phe 177, Gln 181, Arg 212, Asp 214, Glu 276, Phe 300, Val 303, Tyr 344, Asp 349, Gln 350, Arg 439, and Asp 408 residues of the enzyme. Likewise, docking with α-amylase revealed that most of the compounds are well accommodated in the active site residues (Trp 59, Tyr 62, Thr 163, Leu 165, Arg 195, Asp 197, Glu 240, Asp 300, His 305, Asp 356) of the enzyme and Cyanidin-3-rutinoside displayed most active compound with docking score of − 15.03757. Conclusions Phytochemical studies revealed the presence of highly valuable phenolic compounds, which might be responsible for the anti-diabetic potentials of the plant samples.

Polycystic ovary syndrome (PCOS) in females is an endocrine pathological condition of reproductive age which is usually caused by insulin resistance, hyperlipidemia, and oxidative stress. This research was aimed at evaluating the therapeutic effect of the Centratherum anthelminticum seed extract (CA) against PCOS in rodents as it is traditionally used to treat diabetes, inflammation, and gynecological problems. The CA was chemically characterized by high-performance liquid chromatography-diode array detection (HPLC-DAD). For the induction of PCOS, a high-fat diet (HFD) was given to all female Wistar rats for nine weeks except the normal control group, which was given a normal chow diet. Estradiol valerate was given to all rats except normal control. After the induction of PCOS, oral metformin (300 mg/kg) was given to the standard group, while CA was orally administered to diseased rats at 250, 500, and 750 mg/kg/day for 28 days. HPLC-DAD analysis revealed that kaempferol-3-pcoumaroylglucoside was present in the highest amount (146.8 ± 1.8 mg/g) of the extract followed by ferulic acid and malvidin-3-(6-caffeoyl)-glucoside. The in vivo results revealed a marked reduction in cholesterol and triglyceride levels in CA treatment groups. A significant rise was observed in progesterone and follicle stimulating hormone with a decrease in luteinizing hormone in the treatment groups as compared to disease control, which indicated normalization of the estrus cycle. The decrease in insulin resistance was characterized by low serum insulin levels in treatment groups. Treatment with CA also reduced inflammatory markers, such as IL-6 and NF-κB in PCOS rats. NrF2 and oxidative stress markers such as catalase, superoxide dismutase, malondialdehyde, and reduced glutathione were also improved by CA in the ovary of diseased rats. Histopathological examination showed the different developmental stages of normal follicles in CA-treated diseased rats which were indicative of a normal fertile estrous cycle. Overall, the results confirmed the efficacy of CA against PCOS in treating estradiol-HFD-induced PCOS due to its antidiabetic, anti-inflammatory, antihyperlipidemic, and antioxidant properties.

Purpose: The purpose of this research is to investigate the impact of leadership styles on employee well-being and resilience in private universities in Peshawar during COVID-19. The role of leadership in reducing stress and improving mental and physical health was not investigated in COVID-19, and this area is particularly understudied in the Pakistani context. Methodology: Data has been collected from 203 faculty members of 10 private-sector universities in Peshawar using an adapted questionnaire. The respondents include lecturers, assistant professors, and full professors working in private-sector universities. Findings: Using the partial least square regression, it is found that charismatic leadership, intellectual stimulation, personal recognition, contingent reward, and management by exception have positive and significant relationships with employee well-being and resilience in private sector universities in Peshawar. Conclusion: The conclusion is that leaders should use both transformational and transactional leadership styles in their organizations. They should also pay attention to the well-being and resilience of their employees in the workplace.

Introduction: The increase in sedentary behaviour and decrease in physical activity levels are some of the contributing factors to many of the non-communicable diseases. These non-communicable diseases included obesity, type-II diabetes and cardiovascular problems. Apart from causing financial burden on health care system, these diseases have been reported to cause nearly 1.9 million premature deaths per year. The aim of the study was to measure sedentary behaviour and physical activity levels among employees of Khyber Medical University, Peshawar. Material & Methods: A cross-sectional survey was conducted on employees of Khyber Medical University, Peshawar. The total sample size was 172 and the data was collected through convenience sampling by using International Physical Activity Questionnaire (IPAQ) long form. This questionnaire measures physical activity levels and sedentary behaviour at work. Results: Out of 172 participants, 154 (89.5%) were male and 18 (10.4%) were female with a mean age of 34.4 ± 2 years. According to the levels of physical activity, 49 (28.5%) were less active, 63 (36.6%) were moderately active and 60 (34.9%) were highly active. The average time spent by the participants for sitting was (8.93 ± 2.35) hours per day. A total of 73.8%, 23.3 % and 2.9% participants could be categorised as having high, moderate and low sedentary behaviour, respectively. Conclusion: Majority of the participants (two-thirds of the participants) demonstrated a high sedentary behaviour and therefore, needed modification in their daily routine.

Poor aqueous solubility and dissolution limit the oral bioavailability of Biopharmaceutics Classification System (BCS) class II drugs. In this study, we aimed to improve the aqueous solubility and oral bioavailability of raloxifene hydrochloride (RLX), a BCS class II drug, using a self-microemulsifying drug delivery system (SMEDDS). Based on the solubilities of RLX, Capryol 90, Tween 80/Labrasol ALF, and polyethylene glycol 400 (PEG-400) were selected as the oil, surfactant mixture, and cosurfactant, respectively. Pseudo-ternary phase diagrams were constructed to determine the optimal composition (Capryol 90/Tween 80/Labrasol ALF/PEG-400 in 150/478.1/159.4/212.5 volume ratio) for RLX-SMEDDS with a small droplet size (147.1 nm) and stable microemulsification (PDI: 0.227). Differential scanning calorimetry and powder X-ray diffraction of lyophilized RLX-SMEDDS revealed the loss of crystallinity, suggesting a molecularly dissolved or amorphous state of RLX in the SMEDDS formulation. Moreover, RLX-SMEDDS exhibited significantly higher saturation solubility and dissolution rate in water, simulated gastric fluid (pH 1.2), and simulated intestinal fluid (pH 6.8) than RLX powder. Additionally, oral administration of RLX-SMEDDS to female rats resulted in 1.94- and 1.80-fold higher area under the curve and maximum plasma concentration, respectively, than the RLX dispersion. Collectively, our findings suggest SMEDDS is a promising oral formulation to enhance the therapeutic efficacy of RLX.

Ketoconazole is commonly used in the treatment of topical fungal infections. The therapy requires frequent application for several weeks. Systemic side effects, allergic reactions, and prolonged treatment are often associated with non-compliance and therapy failure. Hence, we developed an optimized topical antifungal gel that can prolong the release of drug, reduce systemic absorption, enhance its therapeutic effect, and improve patient compliance. Ketoconazole-loaded PLGA nanoparticles were prepared by the emulsion/solvent evaporation method and were characterized with respect to colloidal properties, surface morphology, and drug entrapment efficiency. The optimized ketoconazole-loaded PLGA nanoparticles and commercially available silver nanoparticles were incorporated into a Carbopol 934P-NF gel base. This arrangement was characterized and compared with commercially available 2% ketoconazole cream to assess physical characteristics of the gel, in vitro drug release, ex vivo skin permeation and retention, and in vivo studies on Wister male albino rats. The results showed that polymeric PLGA nanoparticles were very effective in extending the release of ketoconazole in our optimized formulation. Nanoparticles were smooth, spherical in shape, and below 200 nm in size which is consistent with the data obtained from light scattering and SEM images. The ex vivo data showed that our gel formulation could strongly reduce drug permeation through the skin, and more than 60% of the drug was retained on the upper surface of the skin in contrast to 38.42% of the commercial cream. The in vivo studies showed that gel formulation could effectively treat the infection. This study demonstrates that our topical gel could be effective in sustaining the release of drug and suggests its potential use as a possible strategy to combat antifungal-resistant Candida albicans.

Ticks are blood-feeding ecto-parasites that have a cosmopolitan distribution in tropical and subtropical regions of the world. Ticks cause economic losses in the form of reduced blood, meat and dairy products, as well as pathogen transmission. Different acaricides such as organochlorines, organophosphates, formamidines (e.g. amitraz), synthetic pyrethroids, macrocyclic lactones, fipronil, and fluazuron are currently used sequentially or simultaneously to control tick infestations. Most acaricide treatments now face increasingly high chances of failure, due to the resistance selection in different tick populations against these drugs. Acaricide resistance in ticks can be developed in different ways, including amino acid substitutions that result in morphological changes in the acaricide target, metabolic detoxification, and reduced acaricide entry through the outer layer of the tick body. The current literature brings a plethora of information regarding the use of different acaricides for tick control, resistance selection, analysis of mutations in target sites, and resistance mitigation. Alternatives such as synergistic use of different acaricides, plant-derived phytochemicals, fungi as biological control agents, and anti-tick vaccines have been recommended to avoid and mitigate acaricide resistance. The purpose of this review was to summarize and discuss different acaricides applied for tick control, their mechanisms of action and resistance selection, genetic polymorphisms in their target molecules, as well as the approaches used for diagnosis and mitigation of acaricide resistance, specifically in Rhipicephalus microplus ticks.

Poor aqueous solubility of eplerenone (EPL) is a major obstacle to achieve sufficient bioavailability after oral administration. In this study, we aimed to develop and evaluate eplerenone nanocrystals (EPL-NCs) for solubility and dissolution enhancement. D-optimal combined mixture process using Design-Expert software was employed to generate different combinations for optimization. EPL-NCs were prepared by a bottom-up, controlled crystallization technique during freeze-drying. The optimized EPL-NCs were evaluated for their size, morphology, thermal behavior, crystalline structure, saturation solubility, dissolution profile, in vivo pharmacokinetics, and acute toxicity. The optimized EPL-NCs showed mean particle size of 46.8 nm. Scanning electron microscopy revealed the formation of elongated parallelepiped shaped NCs. DSC and PXRD analysis confirmed the crystalline structure and the absence of any polymorphic transition in EPL-NCs. Furthermore, EPL-NCs demonstrated a 17-fold prompt increase in the saturation solubility of EPL (8.96 vs. 155.85 µg/mL). The dissolution rate was also significantly higher as indicated by ∼95% dissolution from EPL-NCs in 10 min compared to only 29% from EPL powder. EPL-NCs improved the oral bioavailability as indicated by higher AUC, Cmax, and lower Tmax than EPL powder. Acute oral toxicity study showed that EPL-NCs do not pose any toxicity concern to the blood and vital organs. Consequently, NCs prepared by controlled crystallization technique present a promising strategy to improve solubility profile, dissolution velocity and bioavailability of poorly water-soluble drugs.

The short release half-life of carbon monoxide (CO) is a major obstacle to the effective therapeutic use of carbon monoxide-releasing molecule-2 (CORM-2). The potential of CORM-2-entrapped ultradeformable liposomes (CORM-2-UDLs) to enhance the release half-life of CO and alleviate skin inflammation was investigated in the present study. CORM-2-UDLs were prepared by using soy phosphatidylcholine to form lipid bilayers and Tween 80 as an edge activator. The deformability of CORM-2-UDLs was measured and compared with that of conventional liposomes by passing formulations through a filter device at a constant pressure. The release profile of CO from CORM-2-UDLs was evaluated by myoglobin assay. In vitro and in vivo anti-inflammatory effects of CORM-2-UDLs were assessed in lipopolysaccharide-stimulated macrophages and TPA-induced ear edema model, respectively. The deformability of the optimized CORM-2-UDLs was 2.3 times higher than conventional liposomes. CORM-2-UDLs significantly prolonged the release half-life of CO from 30 s in a CORM-2 solution to 21.6 min. CORM-2-UDLs demonstrated in vitro anti-inflammatory activity by decreasing nitrite production and pro-inflammatory cytokine levels. Furthermore, CORM-2-UDLs successfully ameliorated skin inflammation by reducing ear edema, pathological scores, neutrophil accumulation, and inflammatory cytokines expression. The results demonstrate that CORM-2-UDLs could be used as promising therapeutics against acute skin inflammation.

Objective: Sheep farming is an important source of livelihood in the southern Khyber Pakhtun Khwa province of Pakistan where they are reared under extensive system (ES). This system has limitations of improper feeding, rearing, and management which negatively affect their productivity. The pres¬ent study compares different rearing systems and their stresses on fertility, behavior, and growth rate potential of two sheep breeds of Pakistan. Materials and Methods: Eighty ewes were selected; forty each from Damani and Balkhi breeds reared in semi-intensive system (SIS) and ES at Paharpur district, Dera Ismail Khan. Blood samples were collected in triplicate on days 0, 14, and 28 of May, and the molecular and behavioral stress, growth, and fertility rates were recorded. Results: The highest growth and fertility rate were observed in both the breeds in SIS than in ES (p < 0.01). The values of stress indicators (cortisol, heat shock protein (HSP-70)) and behavioral stress parameters were found lower in Damani breed as compared to Balkhi breed in both rearing systems (p < 0.01). All the molecular stress and behavioral stress parameters were negatively associated with metabolic hormones (T3 and T4) (p < 0.01). A positive correlation was observed among all the molecular stress and behavioral stress parameters (p < 0.01). Similarly, T3 and T4 were positively interlinked to one another (p < 0.01). Conclusion: It was concluded that both Damani and Balkhi sheep showed lower stress levels and better fertility and growth parameter in SIS than ES system of rearing. Local Damani breed exhibited well tolerant ability and genetic adaptation to the local environment as compared to Balkhi breed. [J Adv Vet Anim Res 2020; 7(1.000): 170-176]

Regional carbon emissions related to forest cover change (FCC) and wood harvest (WH) are critical for the accurate estimates of global carbon balance over an extended time period. Using remote sensing and inventory data, this study provides a comprehensive record of FCC, WH, and their integrated carbon emissions between 1908 and 2015 in the dry temperate regions of Pakistan. Results demonstrate a significant decline in forest area (21,034 ha) at an annual rate of 0.56% from 1973 to 2015. The total WH was 24.84 million m3 (0.23 million m3 yr−1) between 1908 and 2015. Deforestation was responsible for a net loss of 1.39 million Mg C (0.018 million Mg C yr−1), while WH-related carbon emissions accounted for 11.29 million Mg C (0.52 million Mg C yr−1). The present results indicate that under the existing FCC and WH harvest scenario, the forests are acting as a net source of 0.29 million Mg C yr−1. Agriculture expansion and the heavy dependency of local communities on the forest’s resources, exclusion of conservation and local communities from forest management, insufficient monitoring, and weak law-enforcement were the striking drivers of FCC, WH, and their related emissions. These findings suggest that to maintain forest carbon and meet the communities’ requirements, counter approaches such as agriculture incentives, agroforestry, trophy hunting, alternative energy sources, and inclusion of conservation and secure community-based management are needed.

Objective: To compare cardiovascular disease risk between Systemic Lupus Erythromatosis (SLE) patients and normal healthy controls. Study Design: Comparative cross-sectional study. Place and Duration of Study: Rheumatology Ward & OPD, PIMS Hospital Islamabad, from Dec 2018 to Feb 2019. Methodology: Patients of age between 18-50 years, both genders having a diagnosis of Systemic Lupus Erythromatosis, were enrolled as cases group and matched healthy controls were picked from the medical out door. All the enrolled patients were selected by non-probability consecutive sampling. The calculation of Framingham risk score for all cases and controls was done using online calculator. It was based upon patients age, blood pressure, lipid parameters (total cholesterol, HDL), history of hypertension, diabetes and smoking. Among SLE cases, this score was further multiplied by a factor 1.5 as per European League against Rheumatism (EULAR) recommendations to find the correct cardiovascular risk. Results: The mean body mass index was noted (22.87 ± 2.55 vs. 23.86 ± 4.02 kg/m2) in control and cases group. There was statistically significant (p-value

Objective: High ambient temperature in poultry is a challenging and fatal stress among environmental factors. It affects the production quality, damages the liver, and increases mortality in broilers. The present study is focused to explore appropriate utilization of Selenium (Se) as a feed additive in broiler chickens against high temperature. Materials and Methods: Day-old male broiler chickens (Ross 308) (n = 200) were grouped according to the supplements used in their basal diets such as: corn-soybean basal diet as control (Con), a basal diet containing sodium selenite, basal diet with probiotics, and a basal diet containing selenium-enriched probiotics (SP). At the end of the experimental period of 42 days, the liver was isolated and was used to determine the antioxidant capacity through a spectrophotometer. Inflammatory and anti-inflammatory cytokines production in the liver was measured through a real-time polymerase chain reaction. Results: Hepatic analyses revealed the decreased level of malondialdehyde, whereas glutathione, glutathione peroxidase (GSH-Px), and superoxide dismutase levels were increased in the SP group. Furthermore, supplementation of SP significantly up-regulated the mRNA expression of glutathione peroxidase 1 (GPx1), GPx4, IL6, and IL10 and down-regulated the expression of pro-inflammatory cytokines. Conclusion: It is thus concluded that SP as a potential nutritive supplement may facilitate hepatic protection by suppressing hepatic oxidation, inflammation, and necrosis during the high ambient temperature of summer. [J Adv Vet Anim Res 2019; 6(3.000): 355-361]

In this study, different aerial parts of Monotheca Buxifolia were screened for their antibacterial, antifungal, and anti-oxidant activity. Extract of the fruit was most active against P. mirabilis, MSSA and M. morganii strains. Moreover, the methanolic fruit extract demonstrated good antibacterial properties against VRSA, S. aureus and Acinetobacter. Despite having good antibacterial properties, Monotheca buxifolia showed low antifungal activity. The cytotoxic activity was the highest in the pet-ether fruit extract, causing 60% of lethality against Artemia salina larvae with LD50 at 3.307. The highest scavenging activity was shown by the methanolic leaf extract in a concentration-dependent pattern. The findings of this study suggest that Monotheca Buxifolia has good antibacterial, antioxidant potential but low antifungal properties.

The present study is aimed to develop and optimize levosulpiride-loaded nanostructured lipid carriers (LSP-NLCs) for improving oral bioavailability and prokinetic activity of LSP. LSP-NLCs were optimized with D-optimal mixture design using solid lipid, liquid lipid and surfactant concentrations as independent variables. The prepared LSP-NLCs were evaluated for physicochemical properties and solid-state characterization. The in vivo oral pharmacokinetics and prokinetic activity of LSP-NLCs were evaluated in rats. LSP-NLCs formulation was optimized at Precirol® ATO 5/Labrasol (80.55/19.45%, w/w) and Tween 80/Span 80 concentration of 5% (w/w) as a surfactant mixture. LSP-NLCs showed a spherical shape with a particle size of 152 nm, a polydispersity index of 0.230 and an entrapment efficiency of 88%. The DSC and PXRD analysis revealed conversion of crystalline LSP to amorphous state after loading into the lipid matrix. LSP-NLCs displayed a 3.42- and 4.38-flods increase in AUC and Cmax after oral administration compared to LSP dispersion. In addition, LSP-NLCs showed enhanced gastric emptying (61.4%), intestinal transit (63.0%), and fecal count (68.8) compared to LSP dispersion (39.7%, 38.0% and 51.0, respectively). Taken together, these results show improved oral bioavailability and prokinetic activity of LSP-NLCs and presents a promising strategy to improve therapeutic activity of LSP for efficient treatment of gastric diseases.

Leishmaniasis is affirmed as a category one disease (most emerging and unmanageable) by the World Health Organization (WHO), affecting 98 countries with an annual global incidence of ~1.2 million cases. Options for chemotherapeutic treatment are limited due to drug resistance and cytotoxicity. Thus, the search for new chemical compounds is instantly desirable. In this study, we used two compounds, i.e., 10-hydroxy chondrofoline and tafenoquine, for their antileishmanial activity against L. tropica (HTD7). First, the cytotoxicity assay of the test compounds against THP-1 cells was carried out, and these compounds were found safe. Intra-THP-1 amastigote activity (in vitro) was performed, which was then followed by the in vivo activity of 10-hydroxy chondrofoline in the murine cutaneous leishmaniasis (CL) model. A total of three concentrations were used, i.e., 25, 50, and 100 µM, to check the in vitro activity of the test compounds against the amastigotes. 10-hydroxy chondrofoline was found to be the most potent compound in vitro (and thus was selected for in vivo studies) with an LD50 value of 43.80 µM after 48 h incubation, whilst tafenoquine had an LD50 value of 53.57 µM. In vivo activity was conducted by injecting 10-hydroxy chondrofoline in the left hind foot of the infected BALB/c mice, where it caused a statistically significant 58.3% (F = 14.18; p = 0.002) reduction in lesion size (0.70 ± 0.03 mm) when compared with negative control (1.2 ± 0.3 mm).

Ticks transmit pathogens to animals and humans more often than any other arthropod vector. The rural economy of Pakistan mainly depends on livestock farming, and tick infestations cause severe problems in this sector. The present study aimed to molecularly characterize the Anaplasma spp. in hard ticks collected from six districts of Khyber Pakhtunkhwa, Pakistan. Ticks were collected from various livestock hosts, including cattle breeds (Holstein-Friesian, Jersey, Sahiwal, and Achai), Asian water buffaloes, sheep, and goats from March 2018 to February 2019. Collected ticks were morphologically identified and subjected to molecular screening of Anaplasma spp. by amplifying 16S rDNA sequences. Six hundred seventy-six ticks were collected from infested hosts (224/350, 64%). Among the nine morphologically identified tick species, the highest occurrence was noted for Rhipicephalus microplus (254, 37.6%), followed by Hyalomma anatolicum (136, 20.1%), Rhipicephalus haemaphysaloides (119, 17.6%), Rhipicephalus turanicus (116, 17.1%), Haemaphysalis montgomeryi (14, 2.1%), Hyalomma dromedarii (11, 1.6%), Haemaphysalis bispinosa (10, 1.5%), Hyalomma scupense (8, 1.2%), and Haemaphysalis kashmirensis (8, 1.2%). The occurrence of tick females was highest (260, 38.5%), followed by nymphs (246, 36.4%) and males (170, 25.1%). Overall, the highest occurrence of ticks was recorded in the Peshawar district (239, 35.3%), followed by Mardan (183, 27.1%), Charsadda (110, 16.3%), Swat (52, 7.7%), Shangla (48, 7.1%), and Chitral (44, 6.5%). Among these ticks, Anaplasma marginale was detected in R. microplus, R. turanicus, and R. haemaphysaloides. The 16S rDNA sequences showed high identity (98–100%) with A. marginale reported from Australia, China, Japan, Pakistan, Thailand, Uganda, and the USA. In phylogenetic analysis, the sequence of A. marginale clustered with the same species reported from Australia, China, Pakistan, Thailand, Uruguay, and the USA. Further molecular work regarding the diversity of tick species and associated pathogens is essential across the country.

Medicines derived from plants are preferred over synthetic therapeutic agents in treating different diseases. Ziziphus oxyphylla (a member of Rhamnaceae family) is a medicinal plant used as a remedy of different diseases in Greek and Ayurveda medical systems. Z. oxyphylla roots were shade dried and then subjected to extraction of bioactive compounds using different solvent systems and silica gel. From ethyl acetate fraction, three compounds viz., p-coumaric acid (V), 3,4-dimethoxy benzoic acid (VI), and 4-heptyloxy benzoic acid (VII) were isolated in pure form. The selection of ethyl acetate fraction for isolation was based on HPLC profiling of crude extract and different fractions. These compounds were characterized by different spectroscopic techniques and evaluated for their in vitro antioxidant, anticholinesterase, α–glucosidase, and α-amylase inhibitory potentials. To find out possible binding interactions of V with AChE and BChE crystals, in-silico docking studies were also carried out. Compound V showed maximum scavenging capabilities of DPPH and ABTS free radicals with IC50 values of 69 and 62 μg/mL respectively. Excellent percent inhibition (83.4 ± 0.5% at highest concentration 1000 μg/mL) of acetylcholinesterase (AChE) was exhibited by compound V (IC50 = 80 μg/mL); whereas, for the mentioned concentration, 83.2 ± 1.1% inhibition (IC50 = 90 μg/mL) of butyrylcholinesterase (BChE) was observed as well. The compound VI exhibited highest % inhibition against α-glucosidase (IC50 = 84 μg/mL) whereas α-amylase was more potently inhibited by compound V (% inhibition = 86.8 % and IC50 = 85 μg/mL). Docking scores of -1.391 Kcal/mol (BChE) and –6.253 Kcal/mol (AChE) were recorded using molecular docking software. Compound V exhibited strong free radical scavenging and anticholinesterase potentials suggesting that it can be effectively used to treat oxidative stress and dementia in human.

In this technologically developed scenario, many organizations in developing countries including Pakistan have expanded the enthusiasm for understanding and creating an encouraging administrative and managerial environment. Numerous organizations are struggling for structural changes by deserting the old-fashioned organizational management style and implementing an empowering leadership where leaders give more authority to subordinates in decision making and responsibilities with the aim to increase organizational productivity. Therefore, the study examined the leadership empowering behaviour as a predictor of employees' psychological well-being of the educational institutions at secondary level in Kohat Division, Pakistan. A total sample of 564 secondary school teachers (male n = 379; female n = 185) was carefully chosen through a stratified random sampling technique. In this study, a non-experimental predictive correlational design was adopted. In order to collect data from the participants, two different standardized research tools i.e., the Leader Empowering Behaviour Questionnaire and Ryff's Psychological Well-being Scale were used. After the collection of data, it was analyzed on the basis of mean, standard deviation, Pearson's product-moment correlation, and multiple linear regression model. In conclusion, the study confirmed a significant positive correlation between leadership empowering behaviour and employees' psychological well-being. Leadership empowering behaviours predict employees' psychological well-being positively. Therefore, it was recommended that empowering behaviour might be adopted by the school leaders to improve the employees' psychological well-being for better organizational productivity.

Grewia optiva Drummond ex Burret (Tiliceae) is extensively applied for the treatment of typhoid, diarrhea, malaria, etc., in traditional medication. In this study, four bioactive compounds I (β- sitosterol), II (1, 2, 3 benzene triol), III (7-O-methyl cathachin) and VI (betulinic acid) were isolated from the root of G. optiva. The compounds were characterized through UV, FTIR, NMR, and mass spectroscopic techniques. The isolated compounds were tested for the inhibition of synthetic-free radicals: ABTS and DPPH, and anticholinesterases: AChE and BChE. Compound III demonstrated highest percent free radicals scavenging activities against DPPH and ABTS (86.11 ± 2.20, 85.23 ± 1.61, respectively, for 1000 µg/ml concentrations) with IC50 of 63 µg/ml which were comparable to the IC50 value (35 µg/ml) of ascorbic acid. All isolated compounds also showed excellent inhibitory potential against AChE and BChE. However, β-sitosterol amongst them exhibited highest percent inhibition (87.66 ± 1.93, 85.71 ± 1.17, respectively, at 1000 µg/ml concentration) with IC50 of 62 µg/ml, which was close to the standard galanthamine IC50 values (40 µg/ml). To support the findings of the study silico docking model was applied that predicted possible binding modes of β-sitosterol with AChE and BChE. The para hydroxyl group of the phenolic moiety interacted with the active site water molecule and the side chain carbonyl residues through H-bonding. The remaining part of the active compound packed in a shallow pocket through H-bond.

Stroke is the leading cause of morbidity and mortality worldwide. About 87% of stroke cases are ischemic, which disrupt the physiological activity of the brain, thus leading to a series of complex pathophysiological events. Despite decades of research on neuroprotectants to probe for suitable therapies against ischemic stroke, no successful results have been obtained, and new alternative approaches are urgently required in order to combat this pathological torment. To address these problems, drug repositioning/reprofiling is explored extensively. Drug repurposing aims to identify new uses for already established drugs, and this makes it an attractive commercial strategy. Nuclear factor-kappa beta (NF-κB) is reported to be involved in many physiological and pathological conditions, such as neurodegeneration, neuroinflammation, and ischemia/reperfusion (I/R) injury. In this study, we examined the neuroprotective effects of atorvastatin, cephalexin, and mycophenolate against the NF-κB in ischemic stroke, as compared to the standard NF-κB inhibitor caeffic acid phenethyl ester (CAPE). An in-silico docking analysis was performed and their potential neuroprotective activities in the in vivo transient middle cerebral artery occlusion (t-MCAO) rat model was examined. The percent (%) infarct area and 28-point composite neuro score were examined, and an immunohistochemical analysis (IHC) and enzyme-linked immunosorbent assay (ELISA) were further performed to validate the neuroprotective role of these compounds in stroke as well as their potential as antioxidants. Our results demonstrated that these novels NF-κB inhibitors could attenuate ischemic stroke-induced neuronal toxicity by targeting NF-κB, a potential therapeutic approach in ischemic stroke.

The present investigation was to determine the effect of nano-TiO2 (2 to 6 nm) and waste water on early seedling growth of maize. The suspensions of nano-TiO2 either in deionized water or autoclaved waste water were applied at 100 mg/L, 50 mg/L and 25 mg/L under in vitro conditions. Analyses of waste water showed that it was not suitable for irrigation purposes as it had a higher content of heavy metals (Fe, Mn, Zn, Cd, Cr and Cu) which were above permissible levels for irrigation. The higher concentration of nano-TiO2 (100 mg/L) and waste water significantly inhibited seed germination, seedling growth and caused accumulation of phenolics in maize plants (p < 0.05). The application of nano-TiO2 at 25 mg/L significantly increased shoot fresh weight, shoot dry weight, root fresh weight, root dry weight, root area, chlorophyll a, chlorophyll b and carotenoids content (p < 0.05). The adverse effects of waste water on growth attributes of maize were significantly ameliorated by nano-TiO2 at 25 mg/L (p < 0.05). The treatment of waste water with nano-TiO2 (25 mg/L) is recommended before its utilization for agriculture purposes.