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Cardiovascular diseases (CVD) cause significant global morbidity, mortality and public health burden annually. CVD alters richness, diversity, and composition of Gut microbiota along with RAS and histopathological differences. Present study explores Metformin role in mitigating doxorubicin induced cardiovascular toxicity/remodeling. Animals were divided into 4 groups with n=6: Group I (N. Control) free access to diet and water; Group II (MET. Control) on oral Metformin (250 mg/kg) daily; Group III (DOX. Control) alternate day intraperitoneal Doxorubicin (3 mg/kg) totaling 18 mg/kg; Group IV (DOX. MET. Control) received both daily oral Metformin (250 mg/kg) and alternate day Doxorubicin (3 mg/kg). Gut microbial analysis was made from stool before animals were sacrificed for biochemical and histopathological analysis. Significant alterations were observed in ɑ and β-diversity with new genus from Firmicutes, specifically Clostridia&#95;UCG-014, Eubacterium ruminantium, and Tunicibacter, were prevalent in both the DOX. Control and DOX.MET groups. Proteobacteria, represented by Succinivibrio, were absent in all groups. Additionally, Parabacteroides from the Bacteroidia phylum was absent in all groups except the N. control. In the DOX.MET Control group, levels of Angiotensin II ( 7.75± 0.49 nmol/min, p<0.01) and Renin (2.60±0.26 ng/ml/hr) were significantly reduced. Conversely, levels of CK-MB, Fibrinogen, Troponin, CRP ( p < 0.0001), and TNFɑ (p < 0.05) were elevated. Histopathological examination revealed substantial cardiac changes, including Fibrinogen and fat deposition and eosinophilic infiltration, as well as liver damage characterized by binucleated cells and damaged hepatocytes, along with altered renal tissues in the DOX.MET.Control group. The findings suggest that MET. significantly modifies gut microbiota, particularly impacting the Firmicutes and Proteobacteria phyla. The reduction in Angiotensin II levels, alongside increased inflammatory markers and myocardial damage, highlights the complex interactions and potential adverse effects associated with MET therapy on cardiovascular health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interest or personal relationships that could have appeared to influence the work reported in this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

NS1 is an elusive dengue protein, involved in viral replication, assembly, pathogenesis, and immune evasion. Its levels in blood plasm are positively related to disease severity like thrombocytopenia, hemorrhage, and vascular leakage. Despite its pathogenic roles, NS1 is being used in various vaccine formulations due to its sequence conservancy, ability to produce protective antibodies and low risk for inducing antibody-dependent enhancement. In this study, we have used bioinformatics tools and reported literature to develop an NS1 variant (dNS1). Molecular docking studies were performed to evaluate the receptor-binding ability of the NS1 and dNS1 with TLR4. NS1 and dNS1 (153 to 312 amino acid region) genes were cloned, expressed and protein was purified followed by refolding. Docking studies showed the binding of NS1 and dNS1 with the TLR4 receptor which suggests that N and C-terminal sequences of NS1 are not critical for receptor binding. Antibodies against NS1 and dNS1 were raised in rabbits and binding affinity of anti-dNS1 anti-NS1 sera was evaluated against both NS1 and dNS1. Similar results were observed through western blotting which highlight that N and C-terminal deletion of NS1 does not compromise the immunogenic potential of dNS1 hence, supports its use in future vaccine formulations as a substitute for NS1., (© 2024. The Author(s).)

Spermatic cord malignancies are a scarce modality and liposarcoma of spermatic cord is even a rarer condition encountered. Liposarcoma is usually a slowly progressive, non-tender, well circumscribed mass of variable shapes owing to conformity to fascial compartments. We are reporting a case of 65-year-old male, with a two-month history of initially tender and later non-tender mass in the scrotum, above the testis. Ultrasonography showed a right mid inguinal mass measuring 6x3x3 cm at the superior pole of the right testis and small fluid around the right testis. Fine needle aspiration cytology (FNAC) of the right inguinal mass revealed a spindle cell neoplasm. The patient underwent right inguinal radical orchiectomy with local wide excision of the sarcoma of the spermatic cord origin. Final histopathology confirmed dedifferentiated liposarcoma. No adjuvant treatment was offered and the patient was put on surveillance. Follow-up of more than 10 months has not revealed any local recurrence, regional or non-regional lymph nodes, or systemic metastasis.

Objectives: To determine the response of various histological types of locally advanced rectal cancer to neoadjuvant multimodality therapy., Methods: The non-randomised, quasi-experimental retrospective cohort study was conducted at the Combined Military Hospital, Rawalpindi, Pakistan, and comprised data of patients treated between January 1, 2020, to September 30, 2021. The data retrieved related to histologically proven and locally advanced rectal cancer patients aged 18-70 years receiving neoadjuvant chemoradiotherapy. Radiotherapy dose was 45 gray to pelvis with a boost to gross tumour of 5.4 gray in 3 fractions by using volumetric arc therapy concurrently with capecitabine 625mg/m² daily. A magnetic resonance imaging scan of pelvis with contrast was done at 5-10 weeks before surgery. Histological response to neoadjuvant treatment of various histological types was evaluated using the Rectal Cancer Regression Grade. Data was analysed using SPSS 22., Results: Of the 182 patients evaluated, 108(59.34%) were included; 64(59.3%) males and 44(40.7%) females. The overall mean age was 45.4±5.2 years. Regression status was grade 1 in 24(22%) patients, grade 2 in 43(40%) and grade 3 in 41(38%) (p=0.074). There were 12(11.11%) patients with signet ring cell and 10(83.3%) showed pathological tumour regression. There were 17(15.74%) patients with mucinous variant, and 12(70.5%) had tumour regression. There were 79(73.15%) patients with adenocarcinoma, and 59(74.6%) of them showed tumour regression. ., Conclusions: There was less tumour regression in mucinous and signet ring cell variants of adenocarcinoma. Modification and intensification of neoadjuvant therapy may be required in such histologies.

Herein, core double-shell direct dual Z-scheme ZnO-Ce 2 S 3 -MnO 2 nanocomposite was synthesized via a hydrothermal route along with pure ZnO, Ce 2 S 3 , MnO 2 , and characterized by numerous characterization tools for application in synthetic dyes degradation. The XRD, Raman, and FTIR analyses have confirmed the nanocomposite formation. TEM images exhibited the core double-shell morphology with an average particle diameter of 81 nm and stacking of ZnO, Ce 2 S 3 , and MnO 2 . EDX confirmed the existence of desired elements in the grown composition. The varied oxidation states, presence of defects, and fast charge transfer were also revealed from XPS, PL, and EIS. The ZnO-Ce 2 S 3 -MnO 2 nanocomposite has an optical energy bandgap of 2.84 eV, capable of decomposing harmful dyes with excellent efficiency, 99.81% MB, 97.62% MO, 88.5% MR, and 58.9% EY in 40 min sunlight exposure. The effect of several operating parameters is also observed and obtained results showed the optimal catalyst dose was 20 mg, pH of 8, and dye concentration of 10 ppm. The scavenger's experiment suggests that • O 2 - and • OH are the main active radicals in the photodegradation reaction which is also evident in the dual Z-scheme formation. The MnO 2 and ZnO layers covered the Ce 2 S 3 (core) and dual Z-scheme formation allows rapid kinetics of redox reaction and provides plenteous channels for transfer of photo-generated charge carriers during photocatalysis. Thus, core double-shell direct dual Z-scheme photocatalysts having inorganic components could be an excellent choice for photocatalysis at the industrial level, particularly for water purification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Malvidin is a natural, biologically active polyphenol found in several fruits. It exhibits several therapeutic benefits; however, limited studies are available on its effects on neurodegenerative clinical conditions, including Parkinson's disease. The study aimed to investigate the therapeutic properties of malvidin on rotenone-triggered Parkinson's disease in an animal model., Materials and Methods: To determine the effects of malvidin, rotenone (1.5 mg/kg) was injected subcutaneously into Wistar rats for 21 days, followed by a dose of malvidin (200 and 100 mg/kg). Behavioral tests were performed on the experimental animals before sacrifice. On the 22nd day of the experiment, biochemical tests were performed, including superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and catalase (CAT). The activity of neurotransmitters and their metabolites, including acetylcholine (ACh), acetylcholinesterase (AChE), dopamine (DA), norepinephrine (NE), serotonin (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) along with neuroinflammatory markers including interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor- α (TNF-α), and nuclear factor erythroid 2-related factor 2 (Nrf-2) were estimated. Moreover, the level of the apoptotic marker, caspase-3, was also estimated. In addition, molecular docking was performed., Results: The administration of rotenone resulted in oxidative stress, cholinergic imbalances, dopaminergic alternations, and increased expression of inflammatory compounds. The docking analysis revealed that malvidin displayed a favorable binding affinity for AChE, showcasing a binding energy of -9.329 Kcal/mol., Conclusions: The investigation concludes that malvidin exhibits neuroprotective effects due to its curative effects against inflammation and oxidative stress. These findings suggest that malvidin possesses therapeutic potential against rotenone-triggered behavioral, oxidative, and inflammatory abnormalities in rodents.

Background: Following the change of government in August 2021, the social and economic landscape of Afghanistan deteriorated into an economic and humanitarian crisis. Afghans continue to struggle to access basic healthcare services, making Universal Health Coverage (UHC) in the country a major challenge. The aim of this study was to perform a qualitative investigation into the main access to care challenges in Afghanistan and whether these challenges have been influenced by the recent socio-political developments, by examining the perspectives of health professionals and hospital directors working in the country., Methods: Health professionals working in facilities run by an international non-government organisation, which has maintained continuous operations since 1999 and has become a key health reference point for the population, alongside the public health system, and hospital directors working in government hospitals were recruited to participate in an in-depth qualitative study using semi-structured interviews., Results: A total of 43 participants from ten provinces were interviewed in this study. Four issues were identified as critical barriers to achieving UHC in Afghanistan: (1) the lack of quality human resources; (2) the suboptimal management of chronic diseases and trauma; (3) the inaccessibility of necessary health services due to financial hardship; (4) the unequal accessibility of care for different demographic groups., Conclusions: Health professionals and hospital directors shed light on weaknesses in the Afghan health system highlighting chronic issues and issues that have deteriorated as a result of the 2021 socio-political changes. In order to improve access to care, future healthcare system reforms should consider the perspectives of Afghan professionals working in the country, who are in close contact with Afghan patients and communities., (© 2024. The Author(s).)

Background: The Taliban takeover in August 2021 ended a decades-long conflict in Afghanistan. Yet, along with improved security, there have been collateral changes, such as the exacerbation of the economic crisis and brain drain. Although these changes have altered the lives of Afghans in many ways, it is unclear whether they have affected access to care. This study aimed to analyse Afghans' access to care and how this access has changed after August 2021., Methods: The study relied on the collaboration with the non-governmental organisation EMERGENCY, running a network of three hospitals and 41 First Aid Posts in 10 Afghan provinces. A 67-item questionnaire about access to care changes after August 2021 was developed and disseminated at EMERGENCY facilities. Ordinal logistic regression was used to evaluate whether access to care changes were associated with participants' characteristics., Results: In total, 1807 valid responses were returned. Most respondents (54.34%) reported improved security when visiting healthcare facilities, while the ability to reach facilities has remained stable for the majority of them (50.28%). Care is less affordable for the majority of respondents (45.82%). Female respondents, those who are unmarried and not engaged, and patients in the Panjshir province were less likely to perceive improvements in access to care., Conclusions: Findings outline which dimensions of access to care need resource allocation. The inability to pay for care is the most relevant barrier to access care after August 2021 and must therefore be prioritised. Women and people from the Panjshir province may require ad hoc interventions to improve their access to care., (© 2024. The Author(s).)

In the current era, satisfying the appetite of data hungry models is becoming an increasingly challenging task. This challenge is particularly magnified in research areas characterised by sensitivity, where the quest for genuine data proves to be elusive. The study of violence serves as a poignant example, entailing ethical considerations and compounded by the scarcity of authentic, real-world data that is predominantly accessible only to law enforcement agencies. Existing datasets in this field often resort to using content from movies or open-source video platforms like YouTube, further emphasising the scarcity of authentic data. To address this, our dataset aims to pioneer a new approach by creating the first synthetic virtual dataset for violence detection, named the Weapon Violence Dataset (WVD). The dataset is generated by creating virtual violence scenarios inside the photo-realistic video game namely: Grand Theft Auto-V (GTA-V). This dataset includes carefully selected video clips of person-to-person fights captured from a frontal view, featuring various weapons-both hot and cold across different times of the day. Specifically, WVD contains three categories: Hot violence and Cold violence (representing the violence category) as well as No violence (constituting the control class). The dataset is designed and created in a way that will enable the research community to train deep models on such synthetic data with the ability to increase the data corpus if the needs arise. The dataset is publicly available on Kaggle and comprises normal RGB and optic flow videos., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Climate change is among the greatest drivers of biodiversity loss, threatening up to 15-30% of described species by the end of the twenty-first century. We estimated the current suitable habitat and forecasted future distribution ranges of Indian pangolin (Manis crassicaudata) under climate change scenarios. We collected occurrence records of Indian pangolin using burrow counts, remote camera records and previously published literature in Pakistan during 2021-2023. We downloaded bioclimatic data for current (1970-2000) and future (2041-2060, 2061-2080, 2081-2100) climate scenarios from the WorldClim database using the Hadley Global Environment Model (HadGEM3-GC31-LL). We used MaxEnt software to predict current and future distributions of Indian pangolin, then computed the amount of habitat lost, gained, and unchanged across periods. We obtained 560 Indian pangolin occurrences overall, 175 during the study, and 385 from our literature search. Model accuracy was very good (AUC = 0.885, TSS = 0.695), and jackknife tests of variable importance showed that the contribution of annual mean temperature (bio1) was greatest (33.4%), followed by the mean temperature of the coldest quarter (bio-12, 29.3%), temperature seasonality (bio 4, 25.9%), and precipitation seasonality (bio 15, 11.5%). The maxent model predicted that during the current time period (1970-2000) highly suitable habitat for Indian pangolin was (7270 km 2 , 2.2%), followed by moderately suitable (12,418 km 2 , 3.7%), less suitable (49,846 km 2 , 14.8%), and unsuitable habitat (268,355 km 2 , 79.4%). Highly suitable habitat decreased in the western part of the study area under most SSPs and in the central parts it declined under all SSPs and in future time periods. The predicted loss in the suitable habitat of the Indian pangolin was greatest (26.97%) under SSP 585 followed by SSP 126 (23.67%) during the time 2061-2080. The gain in suitable habitat of Indian pangolin was less than that of losses on average which ranged between 1.91 and 13.11% under all SSPs during all time periods. While the stable habitat of the Indian pangolin ranged between 64.60 and 83.85% under all SSPs during all time periods. Our study provides the current and future habitat ranges of Indian pangolin in the face of a changing climate. The findings of our study could be helpful for policymakers to set up conservation strategies for Indian pangolin in Pakistan., (© 2024. The Author(s).)

An assortment of environmental matrices includes arsenic (As) in its different oxidation states, which is often linked to concerns that pose a threat to public health worldwide. The current difficulty lies in addressing toxicological concerns and achieving sustained detoxification of As. Multiple conventional degradation methods are accessible; however, they are indeed labor-intensive, expensive, and reliant on prolonged laboratory evaluations. Molecular interaction and atomic level degradation mechanisms for enzyme-As exploration are, however, underexplored in those approaches. A feasible approach in this case for tackling this accompanying concern of As might be to cope with undertaking multivalent computational methodologies and tools. This work aimed to provide molecular-level insight into the enzyme-aided As degradation mechanism. AutoDock Vina, CABS-flex 2.0, and Desmond high-performance molecular dynamics simulation (MDS) were utilized in the current investigation to simulate multivalent molecular processes on two protein sets: arsenate reductase (ArsC) and laccase (LAC) corresponding arsenate (ART) and arsenite (AST), which served as model ligands to comprehend binding, conformational, and energy attributes. The structural configurations of both proteins exhibited variability in flexibility and structure framework within the range of 3.5-4.5 Å. The LAC-ART complex exhibited the lowest calculated binding affinity, measuring -5.82 ± 0.01 kcal/mol. Meanwhile, active site residues ILE-200 and HIS-206 were demonstrated to engage in H-bonding with the ART ligand. In contrast to ArsC, the ligand binding affinity of this bound complex was considerably greater. Additional validation of docked complexes was carried out by deploying Desmond MDS of 100 ns to capture protein and ligand conformation behavior. The system achieved stability during the 100 ns simulation run, as confirmed by the average P-L RMSD, which was ∼1 Å. As a preliminary test of the enzyme's ability to catalyze As species, corresponding computational insights might be advantageous for bridging gaps and regulatory consideration., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: In Pakistan, the death rate for post-menopausal women with breast cancer is significant due to late detection and delayed referral to proper facilities. There are a few reports on Pakistan's epidemiology and breast cancer risk factors. There are modifiable and non-modifiable risk factors associated with the development of breast carcinoma; of which body mass index (BMI), central obesity, and lipid profile are considered as major risk markers., Methods: This was a cross-sectional analytical study. A total of 384 women constituted the present study sample. Purposive sampling was used to collect 192 confirmed new breast cancer cases throughout the study. By using basic random sampling, an equal number of controls were chosen. Studied parameters included age, fasting blood sugar, cholesterol, triglyceride, serum high-density lipoprotein, cholesterol, serum low-density lipoprotein cholesterol, weight, height, BMI, waist circumference, and waist-to-hip ratio. The inclusion criteria of this study were post-menopausal women (45-65 years) in Pakistan. The confirmation of breast carcinoma was done through histopathology. Breast cancer occurrence was taken as a dependent variable, whereas BMI, central obesity, and lipid profile were taken as independent variables., Results: Studied risk factors (cholesterol, BMI, and central obesity) significantly correlated with breast cancer. Cholesterol has a significantly high positive correlation (0.646) with breast cancer. BMI has a positive significant correlation (0.491) with breast cancer, and central obesity has a low but positive significant correlation (0.266) with breast cancer. Moreover, the binary logistic regression model also showed a significant association between biochemical factors and breast cancer occurrence. Regression analysis depicted a linear relationship between a dependent variable (breast cancer occurrence) and independent variables (central obesity, cholesterol, BMI)., Conclusion: Postmenopausal overweight (central obesity), increased BMI and high cholesterol levels are major risk factors for breast cancer. Moreover, high total cholesterol proved to be the most significant risk marker for the occurrence of breast cancer in post-menopausal women of Pakistan., (© 2024. The Author(s).)

This study explores the neuroprotective potential of hibiscetin concerning memory deficits induced by lipopolysaccharide (LPS) injection in rats. The aim of this study is to evaluate the effect of hibiscetin against LPS-injected memory deficits in rats. The behavioral paradigms were conducted to access LPS-induced memory deficits. Various biochemical parameters such as acetyl-cholinesterase activity, choline-acetyltransferase, antioxidant (superoxide dismutase, glutathione transferase, catalase), oxidative stress (malonaldehyde), and nitric oxide levels were examined. Furthermore, neuroinflammatory parameters such as tumor necrosis factor-α, interleukin-1β (IL-1β), IL-6, and nuclear factor-kappa B expression and brain-derived neurotrophic factor as well as apoptosis marker i.e ., caspase-3 were evaluated. The results demonstrated that the hibiscetin-treated group exhibited significant recovery in LPS-induced memory deficits in rats by using behavioral paradigms, biochemical parameters, antioxidant levels, oxidative stress, neuroinflammatory markers, and apoptosis markers. Recent research suggested that hibiscetin may serve as a promising neuroprotective agent in experimental animals and could offer an alternative in LPS-injected memory deficits in rodent models., Competing Interests: The authors declare that they have no competing interests., (© 2024 Gilani et al.)

Drug repurposing is an emerging field in drug development that has provided many successful drugs. In the current study, paracetamol, a known antipyretic and analgesic agent, was chemically modified to generate paracetamol derivatives as anticancer and anticyclooxygenase-2 (COX-2) agents. Compound 11 bearing a fluoro group was the best cytotoxic candidate with half-maximal inhibitory concentration (IC 50 ) values ranging from 1.51 to 6.31 μM and anti-COX-2 activity with IC 50  = 0.29 μM, compared to the standard drugs, doxorubicin and celecoxib. The cell cycle and apoptosis studies revealed that compound 11 possesses the ability to induce cell cycle arrest in the S phase and apoptosis in colon Huh-7 cells. These results were strongly supported by docking studies, which showed strong interactions with the amino acids of the COX-2 protein, and in silico pharmacokinetic predictions were found to be favorable for these newly synthesized paracetamol derivatives. It can be concluded that compound 11 could block cell growth and proliferation by inhibiting the COX-2 enzyme in cancer therapy., (© 2023 Deutsche Pharmazeutische Gesellschaft.)

Acemannan, the main polysaccharide in Aloe vera, is a -(1, 4)-acetylated polymannose. According to numerous research findings, acemannan is a viable alternative for the treatment of pathological disorders. Streptozotocin (STZ, 60 mg/kg) administered intraperitoneally caused type 2 diabetes in rats. The current study sought to determine the anti-diabetic efficacy of acemannan (25 and 50 mg/kg) in STZ-injected rats. Different biochemical parameters including HbA1C, glucose and serum insulin, lipid profile, inflammatory markers, antioxidant, oxidative balance, liver function test, glycogen and creatinine, and caspase-3 were evaluated. In addition, a molecular docking study was performed to estimate acemannan's binding affinity to inflammatory markers. Acemannan may be a potent anti-diabetic agent for the treatment of diabetic patients, which will aid in future research into alternative diabetes medications., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: The objective of the study was to assess the protective effects of barbigerone in ethanol-induced gastric ulcers in rats., Materials and Methods: Male Wistar rats (180±20 g) were used in the study (n=06). The rats were randomly divided into different groups, i.e., the normal group, ethanol control, and barbigerone 10 and 20 mg/kg group. Various biochemical parameters were assessed - total acidity and pH values, oxidative stress biomarkers such as superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and catalase (CAT) along with markers, i.e., tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, intercellular adhesion molecule-1 (ICAM-1) and expression of B-Cell Leukemia/Lymphoma 2 (Bcl-2). Also, histopathology was performed., Results: Treatment with barbigerone in the ethanol-induced-ulcer rats restored the levels of biochemical parameters such as SOD, GSH, MDA, CAT, and markers expression, including TNF-α, IL-6, IL-1β, ICAM-1, and Bcl-2 with protected against cellular necrosis., Conclusions: Barbigerone protective effects can be attributed to its ability to reduce oxidative stress and inflammation, as well as promote gastroprotection against ethanol-induced ulcers in rats.

Introduction: Polycystic Ovarian Syndrome (PCOS) is a globally prevalent condition that leads to infertility in women. While environmental factors contribute to PCOS, maternal genetics also play a significant role. Currently, there is no definitive test for identifying predisposition to PCOS. Hence, our objective is to discover novel maternal genetic risk factors for PCOS by investigating the genomes of patients from Pakistan., Methods: We utilized Next-Generation Sequencing (NGS) to sequence the complete mitochondrial DNA of three PCOS patients. Subsequently, we employed MitoTIP (Mitochondrial tRNA Informatics Predictor) and PON-mt-tRNA tools to identify variations in the mitochondrial DNA. Our analysis focused on the genes MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB, which displayed common variations in all three genomes. Additionally, we observed individual variations. The D-loop region exhibited the highest frequency of mutations, followed by the non-coding regions of RNR1 and RNR2 genes. Moreover, we detected frameshift mutations in the mitochondrially encoded NADH Dehydrogenase 2 (MT-ND2) and mitochondrially encoded NADH Dehydrogenase 5 (ND5) genes within individual genomes., Results: Our analysis unveiled six regions with common variations in the mitochondrial DNA of all three PCOS patients. Notably, the MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB genes exhibited these variations. Additionally, we identified individual variations in the mitochondrial DNA. The D-loop region displayed the highest mutation frequency, followed by the non-coding regions of RNR1 and RNR2 genes. Furthermore, frameshift mutations were detected in the MT-ND2 and ND5 genes within individual genomes., Conclusion: Through our study, we have identified variations in mitochondrial DNA that may be associated with the development of PCOS and have the potential to serve as predisposition tests. Our findings highlight the presence of novel mutations in the MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB genes, as well as frameshift mutations in the MT-ND2 and ND5 genes. Pathogenicity analysis indicated that most variants were likely to result in benign cysts. However, the frameshift mutations in the ND2 gene were associated with a high risk of complications and pathogenicity in PCOS. This is the first report identifying these mutations and their association with PCOS, contributing to our understanding of the genetic factors underlying the condition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bibi, Abbas, Khan, Nawaz, Ullah, Uddin, Khan, Ghafoor, Nadeem, Tabassum and Zahoor.)

The impact of a changing climate, particularly global warming, often harms the distribution of pheasants, particularly those with limited endemic ranges. To effectively create plans of action aimed at conserving species facing threats such as the Western Tragopan, ( Tragopan melanocephalus; Gray, 1829; Galliformes, found in the western Himalayas), it is crucial to understand how future distributions may be affected by anticipated climate change. This study utilized MaxEnt modeling to assess how suitable the habitat of the targeted species is likely to be under different climate scenarios. While similar studies have been conducted regionally, there has been no research on this particular endemic animal species found in the western Himalayas throughout the entire distribution range. The study utilized a total of 200 occurrence points; 19 bioclimatic, four anthropogenic, three topographic, and a vegetation variable were also used. To determine the most fitting model, species distribution modeling (SDM) was employed, and the MaxEnt calibration and optimization techniques were utilized. Data for projected climate scenarios of the 2050s and 2070s were obtained from SSPs 245 and SSPs 585. Among all the variables analyzed; aspect, precipitation of coldest quarter, mean diurnal range, enhanced vegetation index, precipitation of driest month, temperature seasonality, annual precipitation, human footprint, precipitation of driest quarter, and temperature annual range were recognized as the most influential drivers, in that order. The predicted scenarios had high accuracy values (AUC-ROC > 0.9). Based on the feedback provided by the inhabitants, it was observed that the livability of the selected species could potentially rise (between 3.7 to 13%) in all projected scenarios of climate change, because this species is relocating towards the northern regions of the elevation gradient, which is farther from the residential areas, and their habitats are shrinking. The suitable habitats of the Tragopan melanocephalus in the Himalayan region will move significantly by 725 m upwards, because of predicted climate change. However, the fact that the species is considered extinct in most areas and only found in small patches suggests that further research is required to avert a further population decline and delineate the reasons leading to the regional extinction of the species. The results of this study can serve as a foundation for devising conservation strategies for Tragopan melanocephalus under the changing climate and provide a framework for subsequent surveillance efforts aimed at protecting the species.

Nowadays, water pollution and energy crises worldwide force researchers to develop multi-functional and highly efficient nanomaterials. In this scenario, the present work reports a dual-functional La 2 O 3 -C 60 nanocomposite fabricated by a simple solution method. The grown nanomaterial worked as an efficient photocatalyst and proficient electrode material for supercapacitors. The physical and electrochemical properties were studied by state-of-the-art techniques. XRD, Raman spectroscopy, and FTIR spectroscopy confirmed the formation of the La 2 O 3 -C 60 nanocomposite with TEM nano-graphs, and EDX mapping exhibits the loading of C 60 on La 2 O 3 particles. XPS confirmed the presence of varying oxidation states of La 3+ /La 2+ . The electrochemical capacitive properties were tested by CV, EIS, GCD, ECSA, and LSV, which indicated that the La 2 O 3 -C 60 nanocomposite can be effectively used as an electrode material for durable and efficient supercapacitors. The photocatalytic test using methylene blue (MB) dye revealed the complete photodegradation of the MB dye under UV light irradiation after 30 min by a La 2 O 3 -C 60 catalyst with a reusability up to 7 cycles. The lower energy bandgap, presence of deep-level emissions, and lower recombination rate of photoinduced charge carriers in the La 2 O 3 -C 60 nanocomposite than those of bare La 2 O 3 are responsible for enhanced photocatalytic activity with low-power UV irradiation. The fabrication of multi-functional and highly efficient electrode materials and photocatalysts such as La 2 O 3 -C 60 nanocomposites is beneficial for the energy industry and environmental remediation applications.

Niche overlap between sympatric species can indicate the extent of interspecific competition. Sympatric competing species can exhibit spatial, temporal, and dietary adjustments to reduce competition. We investigated spatial, temporal, and dietary niche overlap of sympatric Asian palm civet ( Paradoxurus hermaphroditus ) and small Indian civet ( Viverricula indica ), in and around Pir Lasura National Park, Pakistan. We used remote cameras to determine the frequency and timing of detections to estimate spatial and temporal overlap, and prey remains from scats to estimate dietary overlap. We collected scat samples of Asian palm civet ( n = 108) and small Indian civet ( n = 44) for dietary analysis. We found low spatial ( O ij = 0.32) and temporal (Δ = 0.39) overlap, but high dietary niche overlap (0.9) between these two civet species. Both civet species were detected at only 11 camera sites and small Indian civets were detected most frequently during 2:00-5:00 h and 8:00-10:00 h, whereas Asian palm civets detections were greatest during 20:00-2:00 h. The overall niche breadth of Asian palm civet was slightly narrower (L = 9.69, Lst = 0.31) than that of the small Indian civet (L = 10, Lst = 0.52). We identified 27 dietary items (15 plant, 12 animal) from scats of Asian palm civet including Himalayan pear ( Pyrus pashia; 27%), Indian gerbil ( Tatera indica; 10%), Rhesus monkey ( Macaca mulatta ; 4%), and insects (5%). Scat analysis of small Indian civets revealed 17 prey items (eight plant, nine animal) including Himalayan pear (24%), domestic poultry (15%), Indian gerbil (11%), and house mouse ( Mus musculus; 5%). Both civet species consumed fruits of cultivated orchard species. Spatial and temporal partitioning of landscapes containing diverse foods appears to facilitate coexistence between Asian palm civets and small Indian civets., Competing Interests: The authors declare that they have no competing interests., (© 2023 Akrim et al.)

Background: Parkinson's disease (PD) is a common age-related and slowly progressive neurodegenerative disease that affects approximately 1% of the elderly population. In recent years, phytocomponents have aroused considerable interest in the research for PD treatment as they provide a plethora of active compounds including antioxidant and anti-inflammatory compounds. Herein, we aimed to investigate the anti-Parkinson's effect of barbigerone, a natural pyranoisoflavone possessing antioxidant activity in a rotenone-induced rat model of PD., Methods: To evaluate antioxidant activity, a 0.5 mg/kg dose of rotenone was injected subcutaneously into rats. Barbigerone (10 and 20 mg/kg) was administered to rats for 28 days 1 h prior to rotenone. All behavioral parameters were assessed before sacrificing the rats. On the 29th day, all of the rats were humanely killed and assessed for biochemical changes in antioxidant enzymes (superoxide dismutase, glutathione, malondialdehyde, and catalase), neurotransmitter levels (dopamine, 5-hydroxyindoleacetic acid, serotonin, dihydroxyphenylacetic acid, and homovanillic acid levels), and neuroinflammatory cytokines [interleukin (IL)-1β, tumor necrosis factor-α, nuclear factor kappa B, and IL-6]., Results: The data presented in this study has shown that barbigerone attenuated rotenone-induced motor deficits including the rotarod test, catalepsy, akinesia, and open-field test. Additionally, barbigerone has shown improvements in the biochemical and neuroinflammatory parameters in the rotenone-induced rat model of PD., Conclusion: The results demonstrated that barbigerone exhibits antioxidant and anti-inflammatory actions via reducing oxidative stress and inflammatory cytokines. Altogether, these findings suggest that barbigerone could potentially be utilized as a therapeutic agent against PD., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Current research into the role of engineered nanoparticles in drug delivery systems (DDSs) for medical purposes has developed numerous fascinating nanocarriers. This paper reviews the various conventionally used and current used carriage system to deliver drugs. Due to numerous drawbacks of conventional DDSs, nanocarriers have gained immense interest. Nanocarriers like polymeric nanoparticles, mesoporous nanoparticles, nanomaterials, carbon nanotubes, dendrimers, liposomes, metallic nanoparticles, nanomedicine, and engineered nanomaterials are used as carriage systems for targeted delivery at specific sites of affected areas in the body. Nanomedicine has rapidly grown to treat certain diseases like brain cancer, lung cancer, breast cancer, cardiovascular diseases, and many others. These nanomedicines can improve drug bioavailability and drug absorption time, reduce release time, eliminate drug aggregation, and enhance drug solubility in the blood. Nanomedicine has introduced a new era for drug carriage by refining the therapeutic directories of the energetic pharmaceutical elements engineered within nanoparticles. In this context, the vital information on engineered nanoparticles was reviewed and conferred towards the role in drug carriage systems to treat many ailments. All these nanocarriers were tested in vitro and in vivo. In the coming years, nanomedicines can improve human health more effectively by adding more advanced techniques into the drug delivery system.

Hyperglycemia is seen in approximately 68 percent of patients admitted to a medical intensive care unit (ICU). In many acute circumstances, such as myocardial infarction, brain, injury and stroke, it is an independent predictor of mortality. Hyperglycemia is induced by a mix of genetic, environmental, and immunologic variables in people with type 1 diabetes. These factors cause pancreatic beta cell death and insulin insufficiency. Insulin resistance and irregular insulin production cause hyperglycemia in type 2 diabetes patients. Hyperglycemia activates a number of complicated interconnected metabolic processes. Hyperglycemia is a major contributor to the onset and progression of diabetes' secondary complications such as neuropathy, nephropathy, retinopathy, cataracts, periodontitis, and bone and joint issues. Studies on the health benefits of ginger and its constituent's impact on hyperglycemia and related disorders have been conducted and gingerol proved to be a potential pharmaceutically active constituent of ginger ( Zingiber officinale ) that has been shown to lower blood sugar levels, because it possesses antioxidant properties and it functions as an antioxidant in the complicated biochemical process that causes hyperglycemia to be activated. Gingerol not only helps in treating hyperglycemia but also shows effectivity against diseases related to it, such as cardiopathy, kidney failure, vision impairments, bone and joint problems, and teeth and gum infections. Moreover, fresh ginger has various gingerol analogues, with 6-gingerol being the most abundant. However, it is necessary to investigate the efficacy of its other analogues against hyperglycemia and associated disorders at various concentrations in order to determine the appropriate dose for treating these conditions.

Nowadays, environmental pollution due to discharge of organic pollutants from food, textile, and pharmaceutical industries into clean water and development of contagious diseases due to pathogenic organisms provide impetus to material researcher to fabricate novel design for efficient photocatalyst and antimicrobial agents. In this regard, designing a core-shell heterojunction catalyst based on metal oxides is considered an auspicious approach. In present study, combating the problems of singular oxides, core-shell PANI-CeO 2 -Fe 2 O 3 -NiO nanocomposite (PCFN) and CeO 2 -Fe 2 O 3 -NiO nanocomposite (CFN) was synthesized through sol-gel and oxidative polymerization route with cetyletrimethylammonium bromide (CTAB) as surfactant. The XRD, FTIR, and Raman confirmed the formation of nanocomposites with core-shell morphology composed of PANI (shell) and oxides (Core) in PCFN with a particle size of 52 nm (TEM). Surprisingly, PCFN has lower band gap, e - /h + recombination, and larger charge transfer character than CFN. The decomposition test using MB and MO dyes showed that PCFN degraded 99%, 98%, while CFN degraded only 73% and 54%, respectively, under 50 min sunlight illumination. The reusability was assessed up to 7th cycle for PCFN. The influence of operational parameters (catalyst dose, dye concentration, pH) was tested for PCFN. Further, the antimicrobial action against S. aureus (gram + ve), E. coli (gram -ve) were also tested. The supreme performance of PCFN has been credited to heterostructure dual Z-scheme formation and core-shell morphology supported with PANI, which suppresses the e - /h + recombination process by promoting their separation. The present finding indicated that the PCFN is a promising modifier for bacterial disinfection and acts as a superb photocatalyst through core-shell formation with PANI support., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In the present work, pristine and transition metal (TM) (W, Ag, Zn)-doped SnO 2 nanocrystals using a facile sol-gel approach were synthesized. The grown products were anchored on graphene oxide (GO) sheets via a simple ultrasonication technique to fabricate binary nanocomposites. The structural, optical, and morphological properties of as-synthesized samples were studied by XRD, FTIR, Raman, EDX, UV-Visible, PL, and FE-SEM. The charge transferability of graphene oxide-based samples was investigated by EIS. The XRD exhibited the TM doping in SnO 2 and the development of GO-based nanocomposite. FTIR data evidenced the existence of the metal-oxygen bonds. Raman spectra presented the optical phonon modes of SnO 2 and the existence of oxygen vacancy defects. FE-SEM images demonstrated the anchoring of particles on the GO sheet, and EDX further approved the existence of desired dopants. The integration of SnO 2 with TM doping remarkably reduced optical bandgap (3.65-3.10 eV), which was further decreased (3.10-2.99 eV) by making composite with GO. The photodegradation results exhibited that GO-based nanocomposites have the higher potential to degrade synthetic dyes (methyl red (MR), and methyl orange (MO) and SnZnO 2 /GO have shown superb photocatalytic performance after 80-min sunlight illumination (99.9% MR and 95.0% MO dyes) with the higher rate constant and superior stability up to 6th cycle against MR dye. The grown samples were tested for bacterial disinfection, and SnZnO 2 /GO sample showed a higher zone of inhibition towards S. aureus and K. pneumoniae bacteria strains. The greater charge transfer rate and lower recombination of charge carriers in GO-based composites were also observed by EIS and PL analysis. Moreover, the present article ascribed that the photocatalytic and antibacterial properties of bare SnO 2 could be improved by TM doping and fabricating their composite with GO., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Emotional stress is believed to be associated with increased tumor progression. Stress-induced epigenetic modifications can contribute to the severity of disease and poor prognosis in cancer patients. The current study aimed to investigate the expression profiles along with the prognostic significance of psychological stress-related genes in metastatic breast cancer patients, to rationalize the molecular link between emotional stress and cancer progression. We profiled the expression of selected stress-associated genes ( 5-HTT, NR3C1, OXTR, and FKBP5 ) in breast cancer including the stress evaluation of all participants using the Questionnaire on Distress in Cancer Patients-short form (QSC-R10). A survival database, the Kaplan-Meier Plotter, was used to explore the prognostic significance of these genes in breast cancer. Our results showed relatively low expressions of 5-HTT ( p = 0.02) and OXTR ( p = 0.0387) in metastatic breast cancer patients as compared to the non-metastatic group of patients. The expression of NR3C1 was low in tumor grade III as compared to grade II ( p = 0.04). Additionally, the expression of NR3C1 was significantly higher in patients with positive estrogen receptor status. However, no significant difference was found regarding FKBP5 expression in breast cancer. The results suggest a potential implication of these genes in breast cancer pathology and prognosis.

Neurodegenerative diseases exert an overwhelming socioeconomic burden all around the globe. They are mainly characterized by modified protein accumulation that might trigger various biological responses, including oxidative stress, inflammation, regulation of signaling pathways, and excitotoxicity. These disorders have been widely studied during the last decade in the hopes of developing symptom-oriented therapeutics. However, no definitive cure has yet been discovered. Tea is one of the world's most popular beverages. The same plant, Camellia Sinensis (L.).O. Kuntze, is used to make green, black, and oolong teas. Green tea has been most thoroughly studied because of its anti-cancer, anti-obesity, antidiabetic, anti-inflammatory, and neuroprotective properties. The beneficial effect of consumption of tea on neurodegenerative disorders has been reported in several human interventional and observational studies. The polyphenolic compounds found in green tea, known as catechins, have been demonstrated to have many therapeutic effects. They can help in preventing and, somehow, treating neurodegenerative diseases. Catechins show anti-inflammatory as well as antioxidant effects via blocking cytokines' excessive production and inflammatory pathways, as well as chelating metal ions and free radical scavenging. They may inhibit tau protein phosphorylation, amyloid beta aggregation, and release of apoptotic proteins. They can also lower alpha-synuclein levels and boost dopamine levels. All these factors have the potential to affect neurodegenerative disorders. This review will examine catechins' neuroprotective effects by highlighting their biological, pharmacological, antioxidant, and metal chelation abilities, with a focus on their ability to activate diverse cellular pathways in the brain. This review also points out the mechanisms of catechins in various neurodegenerative and cognitive diseases, including Alzheimer's, Parkinson's, multiple sclerosis, and cognitive deficit.

Background: Europinidin is a derivative of delphinidin obtained from the plants Plumbago Europea and Ceratostigma plumbaginoides. This herb has wide medicinal applications in treating various diseases but there are very few studies available on this bioactive compound. Considering this background, the present study is designed for the evaluation of Europinidin against Parkinson’s disease. Aim: The investigation aims to assess the effect of Europinidin in the rotenone-activated Parkinson’s paradigm. Methods: To evaluate neuroprotective activity, rotenone (1.5 mg/kg s.c) and europinidin (10 mg/kg and 20 mg/kg) was administered in rats for 21 days. The behavioural parameters were performed before sacrificing the rats. On the 22nd day, all the rats were assessed for biochemical markers (SOD, GSH, MDA, Catalase), neurotransmitter levels (Dopamine, 5-HIAA, DOPAC, and HVA levels), and neuroinflammatory markers (IL-6, IL-1β and TNF-α). Results: It was found that rotenone produced significant (p < 0.001) oxidative damage, a cholinergic deficit, dopaminergic loss, and a rise in neuroinflammatory markers in rats. Conclusion: The study concludes that europinidin possesses anti-oxidant and anti-inflammatory properties. The results suggest the therapeutic role of europinidin against rotenone-activated behavioural, biochemical, and neuroinflammatory alterations in rats.

The mammalian target of rapamycin (mTOR) is the major controller of a number of important cellular activities, including protein synthesis, cell expansion, multiplication, autophagy, lysosomal function, and cellular metabolism. When mTOR interacts with specific adaptor proteins, it forms two complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The mTOR signaling system regulates gene transcription and protein manufacturing to control proliferation of cell, differentiation of immune cell, and tumor metabolism. Due to its vital role in case of microbial infections, inflammations and cancer development and progression, mTOR has been considered as a key therapeutic target for the development of targeted medication. As autophagy dysfunction is linked to changes in both innate and adaptive immune responses, bacterial clearance defects, and goblet and Paneth cell malfunction, all of these changes are linked to inflammatory bowel diseases (IBD) and colorectal cancer (CRC) pathogenesis. Preclinical and clinical data have shown that the inhibition and induction of autophagy have significant potential to be translated into the clinical applications. In IBD and several CRC models, mTORC1 inhibitors have been found effective. In the recent years, a number of novel mTOR inhibitors have been investigated in clinical trials, and a number of drugs have shown considerably enhanced efficacy when combined with mTOR inhibitors. The future developments in the mTOR targeting medications can benefit patients in individualized therapy. Advanced and innovative medicines that are more effective and have lower drug resistance are still in high demand. New findings could be relevant in medicine development, pharmacological modification, or future mTOR inhibitor research. Therefore, the goal of this review is to present a comprehensive account of current developments on the mTOR pathway and its inhibitors, with an emphasis on the management of microbial infections, the treatment of inflammatory bowel disease, and the management of colon cancer.

Background: Eastern Khyber Pakhtunkhwa is home to a vast range of medicinal and edible waterbird species due to its diverse geographical environment. Waterbird species have been used for various ailments and cultural practices since ancient times, while ethno-pharmacological applications and cultural uses of waterbird species in this area have seldom been documented. This study is the first ethnomedicinal and cultural assessment of waterbird species, and the first compilation and listing of all known data on these species in Eastern Khyber Pakhtunkhwa, Pakistan., Methods: Interviews and questionnaires were used to collect data from native respondents (N = 100). To analyze the data, principal component analysis (PCA), relative frequency of citation (RFC), fidelity level (FL%), relative popularity level (RPL), rank order priority, and similarity index were used., Results: In total, 64 waterbird species were utilized in cultural practices, of which 40 species are used to cure different infectious and chronic diseases such as cold, cough, flu, fever, respiratory disorders, asthma, TB, gastric ulcers, kidney stones, male impotency, obesity, paralysis, piles, cancer, arthritis, body pain, and weakness. PCA showed significant differences in the use of waterbird species among the local inhabitants of the study area, separated along the axis-2 (p < 0.05). The FL% of waterbird species varied from 12 to 100%. 100% FL was analyzed for four waterbird species, i.e., Charadrius mongolus (cold), Gallicrex cinerea (asthma), Anas platyrhynchos (cancer), and Esacus recurvirostris (body weakness). In this study, Mallard (Anas platyrhynchos) was the most popular species used in the healthcare system of Eastern Khyber Pakhtunkhwa, with high RFC (4.06), FL% (100), and RPL (1.0) values., Conclusion: We concluded that waterbird species are more used for medicine and food purposes in the study area. However, in vitro/in vivo assessment of biochemical activities of waterbird species with a maximum FL% might be significant to produce novel drugs. Recent research shows important ethno-ornithological information about native people and their links with waterbird species, which might be helpful for the sustainable use of waterbird diversity in the research area., (© 2022. The Author(s).)

The presence of antimicrobial-resistance genes (ARGs) in mobile genetic elements (MGEs) facilitates the rapid development and dissemination of multidrug-resistant bacteria, which represents a serious problem for human health. This is a One Health study which aims to investigate the co-occurrence of antimicrobial resistance determinants among clinical and environmental isolates of K. pneumoniae and E. coli . Various bioinformatics tools were used to elucidate the bacterial strains' ID, resistome, virulome, MGEs, and phylogeny for 42 isolates obtained from hospitalized patients ( n = 20) and environmental sites (including fresh vegetables, fruits, and drinking water) ( n = 22). The multilocus sequence typing (MLST) showed that K. pneumoniae belonged to ten sequence types (STs) while the E. coli belonged to seventeen STs. Multidrug-resistant isolates harbored β-lactam, aminoglycoside resistance determinants, and MGE were detected circulating in the environment (drinking water, fresh vegetables, and fruits) and in patients hospitalized with postoperative infections, neonatal sepsis, and urinary tract infection. Four K. pneumoniae environmental isolates (7E, 16EE, 1KE, and 19KE) were multidrug-resistant and were positive for different beta-lactam and aminoglycoside resistance determinants. bla CTX-M-15 in brackets of ISEc 9 and Tn 3 transposases was detected in isolates circulating in the pediatrics unit of Soba hospital and the environment. This study documented the presence of bacterial isolates harboring a similar pattern of antimicrobial resistance determinants circulating in hospitals and environments. A rapid response is needed from stakeholders to initiate a program for infection prevention and control measures to detect such clones disseminated in the communities and hospitals.

Based on newly provided morphological and previously published genetic data, we describe two new distinctive sympatric lacertid lizards of the genus Eremias (subgenus Aspidorhinus) from the arid mountains of northwestern Balochistan Province, Pakistan. The new species, Eremias killasaifullahi sp. nov. and Eremias rafiqi sp. nov. are distinguished from all other species of the subgenus Aspidorhinus (E. afghanistanica, E. fahimii, E. isfahanica, E. kopetdaghica, E. lalezharica, E. montana, E. nikolskii, E. papenfussi, E. persica, E. regeli, E. roborowskii, E. strauchi, E. suphani, and E. velox) by unique morphological characters and genetic differentiation. In the molecular phylogeny of Aspidorhinus, both new taxa are well-supported lineages differentiated from other species of this subgenus by uncorrected p distances from 8.5% to 21.6%, respectively. Both new species belong to E. persica complex where E. rafiqi sp. nov. is partly similar in dorsal color pattern to E. persica but can be distinguished from this species by unique meristic and morphometric characters. Eremias rafiqi sp. nov. is found in Pakistan, Afghanistan, and eastern Iran. Eremias killasaifullahi sp. nov. can be differentiated from E. persica by its distant distribution, dorsal color and pattern, smaller size, and less number of gulars and ventral scales. Eremias killasaifullahi sp. nov. is only known from the type locality and represents the local microendemism, along with other endemic species of reptiles reported from this part of Pakistan. We, however, expect that E. killasaifullahi sp. nov. could have a broader range in northwestern Pakistan and southeastern Afghanistan, which should be an object of following investigations. Our data show that remote areas between Hindu Kush Mountains and Indus River need attention as they most probably represent possible sources of genetic and species diversity in the region.

Background: Rosinidin is a flavonoid anthocyanin pigmentation found in shrub flowers such as Catharanthus roseus and Primula rosea . The molecular docking studies predicted that rosinidin has adequate structural competency, making it a viable medicinal candidate for the treatment of a wide range of disorders. The current study intends to assess rosinidin nephroprotective efficacy against nephrotoxicity induced by cisplatin in rats., Materials and Methods: Oral acute toxicity tests of rosinidin were conducted to assess potential toxicity in animals, and it was shown to be safe. The nephroprotective effect of rosinidin 10, and 20 mg/kg were tested in rats for 25 days with concurrent administration of cisplatin. Several biochemical parameters were measured to support enzymatic and non-enzymatic oxidative stress such as superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH). Likewise, changes in several non-protein-nitrogenous components and blood chemistry parameters were made to support the theory linked with the pathogenesis of chemical-induced nephrotoxicity., Results: Cisplatin caused significant changes in biochemical, enzymatic, and blood chemistry, which rosinidin efficiently controlled., Conclusions: The present investigation linked rosinidin with nephroprotective efficacy in experimental models.

Severe infections such as viral, bacterial, or fungal sepsis can cause an inflammatory response in the host, leading to organ failure and septic shock-phosphodiesterase-4 (PDE-4) inhibiting related agents from suppressing cyclic adenosine monophosphate (cAMP) degradation. Regulatory organisations have approved some substances in this category to reduce the risk of chronic obstructive pulmonary disease (COPD) exacerbations in patients with chronic bronchitis and a history of COPD exacerbations. Roflumilast has been shown to alleviate inflammatory responses, thus regulating airway inflammation. Additionally, roflumilast therapy dramatically enhanced B-cell lymphoma 2 (Bcl-2) expression, an anti-apoptotic marker lowered in septic animals. Previous research has indicated that roflumilast may help reverse sepsis-induced liver and lung harm, but whether it is also effective in reversing sepsis-induced renal impairment remains unknown. Therefore, this review determines whether roflumilast protects against renal dysfunction, inflammatory response, and apoptosis in sepsis-induced kidney damage. Additionally, we discussed the molecular mechanism through which roflumilast exerts its protective effect to uncover a possible treatment agent for sepsis-induced renal impairment.

Energy-levels well-matched direct Z-scheme ZnNiNdO/CdS heterojunction was successfully fabricated using facile co-precipitation and ultra-sonication techniques and characterized with XRD, FTIR, Raman, PL, UV-vis, and FE-SEM. The XRD diffractograms confirmed the co-doping of Ni-Nd in ZnO and the formation of heterostructured nanocomposite. FTIR and Raman data showed the presence of metal-oxygen vibration and optical phonon modes of ZnO and CdS. FE-SEM images exhibited the network type morphology. The energy bandgap was redshifted by co-doping (3.37-2.9 eV) and was further reduced (2.6 eV) by making a composite with CdS. The ZnNiNdO/CdS catalyst degraded 99.7, 49, 96.6, 98.6, and 98.6% methylene blue (MB), p-nitroaniline (P-Nitro), methyl orange (MO), methyl red (MR), and rhodamine B (RhB) dyes under 50 min sunlight irradiation. Moreover, ZnNiNdO/CdS showed intense inhibition activity towards Staphylococcus aureus, Escherichia coli, Proteus vulgaris, and Pseudomonas aeruginosa bacterial strains with maximum inhibition zone diameters 30, 33, 27, and 31 mm, respectively. The synergistic effects arising from band alignment can lead to efficient vectorial charge separation, transportation, and lower recombination of photoinduced charge carriers, ultimately boosting photocatalytic and antibacterial performance. The ZnNiNdO/CdS photocatalyst has higher stability up to the 7th cycle towards MB dye with ~ 5% deficit in degradation efficiency. The higher generation of superoxide and hydroxyl radical was confirmed by species trapping experiments responsible for photodegradation of dyes molecules. Furthermore, the results showed that the photocatalytic and antibacterial performance of pristine ZnO can be enhanced by co-doping and tuning energy bandgap., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The fustin plant-derived bioflavonoid obtained from a common plant known as lacquer tree from family Anacardiaceae, formally known as Rhus verniciflua Stokes, is known to exert a variety of therapeutic properties. The current investigation proved the anti-ulcerative property of fustin on ethanol-induced gastric ulcers in an experimental animal model. The fustin 50 and 100 mg/kg was studied in an experimental rat model by performing an 8 day protocol. The ulcer index, pH, total acidic content, and biochemical parameters such as glutathione (GSH), superoxide dismutase (SOD), catalase activity (CAT), malondialdehyde (MDA), interleukin-1β, prostaglandin E-2, tumor necrosis factor-α (TNF-α), myeloperoxidase, and nitric oxide (NO) in serum were measured. The gastric parameter such as ulcer index, pH, and acidic content was maintained in the fustin groups compared to the ethanol control group. Clinical presentation of gastric ulcers includes a significant increase in serum levels, GSH, SOD, and CAT and decreased MDA, TNF-α, interleukin-1β, and prostaglandin E-2 parameters in contrast to normal groups. The treatment regimen with fustin has significantly restored all serum parameters in test groups. The current study helps to develop reasonable phytochemical options for the innervations of chemical-induced gastric ulcers., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Staphylococcus epidermidis is part of the normal human flora that has recently become an important opportunistic pathogen causing nosocomial infections and tends to be multidrug-resistant. In this investigation, we aimed to study the genomic characteristics of methicillin-resistant S. epidermidis isolated from clinical specimens. Three isolates were identified using biochemical tests and evaluated for drug susceptibility. Genomic DNA sequences were obtained using Illumina, and were processed for analysis using various bioinformatics tools. The isolates showed multidrug resistance to most of the antibiotics tested in this study, and were identified with three types (III(3A), IV(2B&5), and VI(4B)) of the mobile genetic element SCCmec that carries the methicillin resistance gene ( mecA ) and its regulators ( mecI and mecR1 ). A total of 11 antimicrobial resistance genes (ARGs) was identified as chromosomally mediated or in plasmids; these genes encode for proteins causing decreased susceptibility to methicillin ( mecA ), penicillin ( blaZ ), fusidic acid ( fusB ), fosfomycin ( fosB ), tetracycline ( tet ( K )), aminoglycosides ( aadD , aac ( 6' ) -aph ( 2'' )), fluoroquinolone (MFS antibiotic efflux pump), trimethoprim ( dfrG ), macrolide ( msr ( A )), and chlorhexidine ( qacA )). Additionally, the 9SE strain belongs to the globally disseminated ST2, and harbors biofilm-formation genes ( icaA , icaB , icaC , icaD, and IS256) with phenotypic biofilm production capability. It also harbors the fusidic acid resistance gene ( fusB ), which could increase the risk of device-associated healthcare infections, and 9SE has been identified as having a unique extra SCC gene ( ccrB4 ); this new composite element of the ccr type needs more focus to better understand its role in the drug resistance mechanism.

Genus Tatera is comprised of 12 species, but only one species, Tatera indica , exists in Asia. T. indica is considered an agricultural pest and host of a few zoonotic diseases. However, the data on morphological characteristics are published, but the aspect of molecular characterization is lacking to confirm the status of subspecies in most of the Asian countries including Pakistan. Therefore, the present study is the first study on morphological and molecular characterization of T. indica to get a phylogenetic relationship with the population of T. indica in Pakistan. Almost all the morphometric, cranial, and dental values of T. indica were lower in the present study as compared to the specimen from Iran, Syria, and Turkey. The molecular analysis indicated the presence of sub-species of T. indica . Interestingly, the cytochrome b gene sequence showed more resemblance to the Iranian rat than the previously reported sequence of a Pakistani T. indica. Iran shares a border with Pakistan, and migration between the two countries could be a possible reason. The resembling morphometric data on Iranian rats also explain this phenomenon. The present study found, although minor, evidence of the presence of sub-species even within Pakistan. Unfortunately, the previously submitted sequence from Pakistan was not supplemented with morphometric data and the exact capturing site of the rat. Therefore, further molecular and morphometric data from other regions are required to confirm the presence of sub-species., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2022 Amber Khalid et al., published by De Gruyter.)

Hypervirulent K. pneumoniae (hvKP) strains possess distinct characteristics such as hypermucoviscosity, unique serotypes, and virulence factors associated with high pathogenicity. To better understand the genomic characteristics and virulence profile of the isolated hvKP strain, genomic data were compared to the genomes of the hypervirulent and typical K. pneumoniae strains. The K. pneumoniae strain was isolated from a patient with a recurrent urinary tract infection, and then the string test was used for the detection of the hypermucoviscosity phenotype. Whole-genome sequencing was conducted using Illumina, and bioinformatics analysis was performed for the prediction of the isolate resistome, virulome, and phylogenetic analysis. The isolate was identified as hypermucoviscous, type 2 (K2) capsular polysaccharide, ST14, and multidrug-resistant (MDR), showing resistance to ciprofloxacin, ceftazidime, cefotaxime, trimethoprim-sulfamethoxazole, cephalexin, and nitrofurantoin. The isolate possessed four antimicrobial resistance plasmids ( p KPN3-307&#95;type B, p ECW602, p MDR, and p 3K157) that carried antimicrobial resistance genes (ARGs) ( bla OXA-1, bla CTX-M-15 , sul2 , APH(3″)-Ib , APH(6)-Id , and AAC(6')-Ib-cr6 ). Moreover, two chromosomally mediated ARGs ( fosA6 and SHV-28) were identified. Virulome prediction revealed the presence of 19 fimbrial proteins, one aerobactin ( iutA ) and two salmochelin ( iroE and iroN ). Four secretion systems (T6SS-I (13), T6SS-II (9), T6SS-III (12), and Sci-I T6SS (1)) were identified. Interestingly, the isolate lacked the known hypermucoviscous regulators ( rmpA/rmpA2 ) but showed the presence of other RcsAB capsule regulators ( rcsA and rcsB ). This study documented the presence of a rare MDR hvKP with hypermucoviscous regulators and lacking the common capsule regulators, which needs more focus to highlight their epidemiological role.

Pheasants are declining everywhere in the world and therefore updated information about their population and habitats are important for conservation and management. The present study was conducted in the Palas Valley, District Kohistan, Pakistan in late spring (May and June) 2020 and early spring (March and April) 2021 to assess the population and anthropogenic stress. The major focus was on three sympatric pheasant species, including Western Horned Tragopan (Tragopan melanocephalus), Himalayan Monal (Lophophorus impejanus), and Koklass Pheasant (Pucrasia macrolopha). We used the "Call Count Method" for the population assessment in the field, and a questionnaire survey was conducted to document the risk assessment of local residents of the valley. The population assessments revealed that the Koklass Pheasant is more adapted to increasing anthropogenic activities and its population appeared more or less similar as 22 years ago. In the past 22 years, Western Tragopan and Himalayan Monal have lost about 40-50% of their populations. Human interference in the form of illegal hunting, deforestation, and overgrazing was found to be common in the valley. The study concludes that the Palas Valley habitat is ideal for pheasant species; however, human interference in the form of urbanization, habitat fragmentation, illegal hunting, and deforestation is occurring at a rapid pace, causing havoc in the pheasant population.

Apigenin (AGN) is a potent phytochemical with strong antioxidant and anticancer potential. But its therapeutic efficacy is limited due to its high lipophilic characteristics. Therefore, the present investigation aimed to develop AGN-loaded polymer-lipid hybrid nanoparticles (AGN-PLHNPs). Herein, we successfully developed AGN-PLHNPs and optimized them by a 33-Box-Behnken de-sign. The poly (lactic-co-glycolic acid) (PLGA; coded as F1), phospholipon 90 G (PL-90G; coded as F2), and poloxamer 188 (P-188; coded as F3) were considered as the independent factors while particle size (PS; coded as R1), entrapment efficiency (%EE; R2), and cumulative drug release (%CDR; R3) were selected as dependent responses. The average PS, %EE, and %CDR of the AGN-PLHNPs were observed in the range of 101.93 nm to 175.26 nm, 58.35% to 81.14%, and 71.21% to 93.31%, respectively. The optimized AGN-PLHNPs revealed better homogeneity (poly-dispersity index < 0.2) and colloidal stability with high zeta potential (>25 mV). It also exhibited fast release in the initial 4 h after that sustained release up to 48 h of study. Moreover, the results of both DPPH as well as ABTS assays revealed significant improvement in the antioxidant activity. Furthermore, the optimized AGN-PLHNPs exhibited enhanced cytotoxicity efficacy against MCF-7 as well as MDA-MB-231 breast cancer cell lines.

There is emerging evidence exhibiting the strong association of gut microbiota with cardiovascular metabolic functions. Cardiac diseases may alter the richness, diversity, and composition of the gut microbiome. Vitamin C (Vit C) plays an important role in many metabolic activities in cardiovascular diseases. In this study, we induced cardiac remodeling by the forced swim stress model in rats, which resulted in dysbiosis. Adult male Wistar rats were designated into the following groups: (i) normal control (NC), (ii) forced swim induced stress (FSIS) control, (iii) FSIS + Vit C treatment, and (iv) Vit C control. Stool samples were collected for estimation for 90 days, and at the end of the study, the animals were killed and heart tissue was isolated for histochemical analysis. We observed a sharp fall in the operational taxonomic unit in the FSIS control animals as compared to NC animals. Treatment with Vit C exhibited a decrease in Bacteroidetes while raising the abundance of spirochetes. Plasma levels of creatine kinase myocardial band (CKMB) in the treatment group reduced to 175.7 ± 3.41 U/L, from 317.7 ± 34.48 U/L in the diabetic control group. Also, the C-reactive protein level in the disease control group was 18 ± 0.93 mg/dl, which reduced to the normal level of 7.53 ± 0.20 mg/dl on treatment with Vit C administration. Our results suggest that FSIS induced cardiac complication is also associated with changes in gut microbial abundance. Higher doses of Vit C, which strengthens the immunity, have shown some positive outcomes on cardiac complications. The abundance of gut microbiota is also associated with the immune system, which in turn marks the impact of a disease. More the richness and diversity of the gut microbiome, healthier is the composition that can withstand the external threats of disease and other major challenges in the environment. Hence microbiome abundance plays an important role in the therapies or future prospects of disease. Histopathological studies support the serological and microbiome examination and warrant the cardioprotective influence of Vit C in the stress-induced cardiac dysfunction model., (© 2022 Wiley Periodicals LLC.)

Piperine (PPN), one of the most investigated phytochemicals, is known to have excellent therapeutic efficacy against a variety of ailments including breast cancer. However, its physicochemical properties such as poor aqueous solubility restrict its clinical application. Therefore, the present investigation was designed to develop PPN encapsulated lipid polymer hybrid nanoparticles (PPN-LPHNPs) to overcome the limitation. The developed PPN-LPHNPs were optimized by the three-factor, three-level Box−Behnken design (33-BBD). The optimized PPN-LPHNPs were then evaluated for their drug release profile, cytotoxicity assay against MDA-MB-231 and MCF-7 cells, and gastrointestinal stability as well as colloidal stability. In addition, the optimized PPN-LPHNPs were evaluated for ex vivo intestinal permeation and in vivo pharmacokinetic in albino Wistar rats. As per the results, the optimized PPN-LPHNPs showed a small average particles size of <160 nm with a low (<0.3) polydispersity index, and highly positive surface charge (>+20 mV). PPN-LPHNPs revealed excellent gastrointestinal as well as colloidal stability and sustained release profiles up to 24 h. Furthermore, PPN-LPHNPs revealed excellent cytotoxicity against both MDA-MB-231 and MCF-7 cancer cells compared to the free PPN. Moreover, animal studies revealed that the PPN-LPHNPs exhibited a 6.02- and 4.55-fold higher intestinal permeation and relative oral bioavailability, respectively, in comparison to the conventional PPN suspension. Thus, our developed LPHNPs present a strong potential for improved delivery of PPN.

Diabetes is one of the world's most important public health issues, impacting both public health and socioeconomic advancement; moreover, current pharmacotherapy is still insufficient. The natural flavonoid rosinidin has a long history of use in pharmaceuticals and nutritional supplements, but its role in diabetes has been unknown. The current study was intended to confirm the anti-diabetic activity of rosinidin in our laboratory setting, along with its mechanism. Streptozotocin (60 mg/kg, ip) treatment used to induce type II diabetes in rats and the test medication rosinidin was then administered orally (at doses of 10 mg/kg and 20 mg/kg) for biochemical and histopathological analysis. Treatment with rosinidin reduced negative consequences of diabetes. Rosinidin exerted a protective effect on a number of characteristics, including anti-diabetic responses (lower blood glucose, higher serum insulin and improved pancreatic function) and molecular mechanisms (favorable effects on lipid profiles, total protein, albumin, liver glycogen, proinflammatory cytokine, antioxidant and oxidative stress markers, AST, ALT and urea). Furthermore, the improved pancreatic architecture observed in tissues substantiated the favourable actions of rosinidin in STZ-induced diabetic rats.