Publications by authors named "Ghulam Murtaza"

347 Publications

The Role of Oxidative Stress and Antioxidant Balance in Pregnancy.

Mediators Inflamm 2021 27;2021:9962860. Epub 2021 Sep 27.

College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128 Hunan, China.

It has been widely known that oxidative stress disrupts the balance between reactive oxygen species (ROS) and the antioxidant system in the body. During pregnancy, the physiological generation of ROS is involved in a variety of developmental processes ranging from oocyte maturation to luteolysis and embryo implantation. While abnormal overproduction of ROS disrupts these processes resulting in reproductive failure. In addition, excessive oxidative stress impairs maternal and placental functions and eventually results in fetal loss, IUGR, and gestational diabetes mellitus. Although some oxidative stress is inevitable during pregnancy, a balancing act between oxidant and antioxidant production is necessary at different stages of the pregnancy. The review aims to highlight the importance of maintaining oxidative and antioxidant balance throughout pregnancy. Furthermore, we highlight the role of oxidative stress in pregnancy-related diseases.
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http://dx.doi.org/10.1155/2021/9962860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490076PMC
September 2021

Recent strategies driving oral biologic administration.

Expert Rev Vaccines 2021 Oct 6. Epub 2021 Oct 6.

Department of Pharmacy, COMSATS University Islamabad, Lahore Campus, Lahore 54000, Pakistan.

Introduction: : High patient compliance, non-invasiveness, and self-administration are the leading features of vaccine delivery through the oral route. The implementation of swift mass vaccination campaigns in pandemic outbreaks fascinates the use of oral vaccination. This approach can elicit both mucosal and systemic immune responses to protect against infection at the surface of the mucosa.

Area Covered: : As pathogen entry and spread mainly occurs through the gastrointestinal tract (GIT) mucosal surfaces, oral vaccination may protect and limit disease spread. Oral vaccines target various potential mucosal inductive sites in the GIT, such as the oral cavity, gastric area, and small intestine. Orally delivered vaccines having subunit and nucleic acid pass through various GIT-associated risks, such as the biodegradation of biologics and their reduced absorption. This article presents a summarized review of the existing technologies and prospects for oral vaccination.

Expert Opinion: : The intestinal mucosa focuses on current approaches, while future strategies target new mucosal sites, i.e., oral cavity and stomach. Recent developments in biologic delivery through the oral route and their potential use in future oral vaccination are mainly considered.
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http://dx.doi.org/10.1080/14760584.2021.1990044DOI Listing
October 2021

The Adipokine Component in the Molecular Regulation of Cancer Cell Survival, Proliferation and Metastasis.

Pathol Oncol Res 2021 13;27:1609828. Epub 2021 Sep 13.

College of Pharmacy, South-Central University for Nationalities, Wuhan, China.

A hormonal imbalance may disrupt the rigorously monitored cellular microenvironment by hampering the natural homeostatic mechanisms. The most common example of such hormonal glitch could be seen in obesity where the uprise in adipokine levels is in virtue of the expanding bulk of adipose tissue. Such aberrant endocrine signaling disrupts the regulation of cellular fate, rendering the cells to live in a tumor supportive microenvironment. Previously, it was believed that the adipokines support cancer proliferation and metastasis with no direct involvement in neoplastic transformations and tumorigenesis. However, the recent studies have reported discrete mechanisms that establish the direct involvement of adipokine signaling in tumorigenesis. Moreover, the individual adipokine profile of the patients has never been considered in the prognosis and staging of the disease. Hence, the present manuscript has focused on the reported extensive mechanisms that culminate the basis of poor prognosis and diminished survival rate in obese cancer patients.
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http://dx.doi.org/10.3389/pore.2021.1609828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473628PMC
September 2021

Diastolic function grading by American Society of Echocardiography guidelines and prediction of heart failure readmission and all-cause mortality in a community-based cohort.

Echocardiography 2021 Sep 23. Epub 2021 Sep 23.

Department of Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA.

Background: Diastolic function (DF) guidelines have been simplified but lack extensive outcome data. Using a rural university heart failure (HF) database, we assessed whether DF grading could predict HF, HF readmission, and all-cause mortality (ACM).

Methods: In this single-center retrospective study that included 613 patients in sinus rhythm hospitalized for HF (HF with preserved-254 patients, with mid-range-216 patients, and reduced ejection fraction-143 patients), we recorded demographics, Doppler-echo, Framingham HF score, laboratories, HF readmission, and ACM with follow-up to 2167 days.

Results: Diastolic dysfunction (Ddys) parameters (left atrial volume index [LAVI] > 34 ml/m , tricuspid regurgitation [TR] velocity > 2.8 m/sec, and E/e' > 14) had moderate sensitivity (46.2%-65.0%) for predicting HF among all phenotypes combined with DF grading having moderate predictability and additive to a clinical composite for HF prediction (AUC = .677, P < 0.0001; difference = .043, P < 0.001) for combined phenotypes. Ddys parameters and Ddys severity (2016 ASE criteria: grade II and III) were significantly associated with HF readmission for decompensated HF within 60-2167 days of follow-up (LAVI > 34 ml/m : HR 1.56 [1.26-2.19]; E/e' > 14: HR 1.44 [1.21-1.99]; TR > 2.8 m/sec: H1.43 [1.19-1.88]; LV Dys grade II: HR 2.12 [1.42-2.96]; LV Ddys grade III: HR 2.39 [1.57-4.82]).

Conclusion: The findings of this study highlight the clinical and prognostic relevance of determining the severity of LV Ddys in patients with HF with regard to HF verification and HF readmission.
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http://dx.doi.org/10.1111/echo.15206DOI Listing
September 2021

The Role of Polyphenols in Regulation of Heat Shock Proteins and Gut Microbiota in Weaning Stress.

Oxid Med Cell Longev 2021 6;2021:6676444. Epub 2021 Sep 6.

Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125 Hunan, China.

Gut microbiota is the natural residents of the intestinal ecosystem which display multiple functions that provide beneficial effects on host physiology. Disturbances in gut microbiota in weaning stress are regulated by the immune system and oxidative stress-related protein pathways. Weaning stress also alters gut microbiota response, limits digestibility, and influences animal productive performance through the production of inflammatory molecules. Heat shock proteins are the molecular chaperones that perform array functions from physiological to pathological point of view and remodeling cellular stress response. As it is involved in the defense mechanism, polyphenols ensure cellular tolerance against enormous stimuli. Polyphenols are nature-blessed compounds that show their existence in plenty of amounts. Due to their wider availability and popularity, they can exert strong immunomodulatory, antioxidative, and anti-inflammatory activities. Their promising health-promoting effects have been demonstrated in different cellular and animal studies. Dietary interventions with polyphenols may alter the gut microbiome response and attenuate the weaning stress related to inflammation. Further, polyphenols elicit health-favored effects through ameliorating inflammatory processes to improve digestibility and thereby exert a protective effect on animal production. Here, in this article, we will expand the role of dietary polyphenol intervention strategies in weaning stress which perturbs gut microbiota function and also paid emphasis to heat shock proteins in gut health. This review article gives new direction to the feed industry to formulate diet containing polyphenols which would have a significant impact on animal health.
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http://dx.doi.org/10.1155/2021/6676444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440081PMC
September 2021

An Exploration of Knowledge, Attitude, and Practices of Physicians toward Pharmacovigilance at Tertiary Care Hospitals in Khyber-Pakhtunkhwa Province, Pakistan.

Am J Trop Med Hyg 2021 Sep 7. Epub 2021 Sep 7.

Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, Pakistan.

Drug safety assures the effectiveness, safety, and security of drugs, vaccines, and other biologicals to protect public health. Medication-related errors coupled with unjudicial medication practices often cause a catastrophic impact on the healthcare system globally. The present study aimed to assess the knowledge, attitude, and practice of physicians toward pharmacovigilance and barriers to adverse drug reaction (ADR) reporting at tertiary care hospitals in Khyber-Pakhtunkhwa (KP) province, Pakistan. A descriptive cross-sectional study was conducted among registered doctors working in seven tertiary care hospitals from seven administrative divisions of KP province of Pakistan from July 2019 to March 2020. During the study period, 358 physicians who fulfilled the inclusion criteria and agreed to participate completed and returned the validated structured questionnaires. Descriptive and inferential statistics were applied for data analysis. The majority of physicians had poor knowledge (81.3%) regarding pharmacovigilance along with poor reporting practices (94.9%), although (96.5%) had a positive attitude toward ADR reporting. A significant barrier identified was the unavailability of reporting forms (95.9%), whereas mandatory ADR reporting (96.2%) was the major factor to encourage ADR reporting. Physicians aged ≥ 41 and experience ≥ 11 years had significantly more knowledge than other categories (P < 0.001). Significant association (P < 0.001) of physicians' knowledge and practice were found where 77.2% of the participants having poor knowledge reported poor practices. Physicians' understanding of pharmacovigilance was suboptimal, although they have a positive attitude toward ADR reporting. Thus, there is a need for continuous education and training programs to support pharmacovigilance activities that could improve physicians' understanding.
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http://dx.doi.org/10.4269/ajtmh.21-0336DOI Listing
September 2021

Bioassimilation of lead and zinc in rabbits fed on spinach grown on contaminated soil.

Ecotoxicol Environ Saf 2021 Aug 19;224:112638. Epub 2021 Aug 19.

Department of Plant Breeding and Genetics, The University of Haripur, 22620 Pakistan.

Accumulation of heavy metals in the environment can pose a potential risk to living organisms. Ingestion of leafy vegetables, containing heavy metals, is one of the main routes through which these elements enter the human body. The present study was conducted to assess the accumulation of lead (Pb) and zinc (Zn) in spinach grown on metal contaminated soil, and to examine the bioassimilation of these metals in spinach-fed rabbits. Spinach grown in the fields spiked with Pb (1000 mg kg soil) and Zn (150 mg kg soil), was fed to the rabbits for 14 days. Concentrations of Pb and Zn in the leaves of spinach were 39.1 and 113 mg kg, respectively. For the assessment of Pb and Zn concentration, blood samples were collected after 24 h, 7 days and 14 days of feeding, while the essential organs, i.e. liver and kidneys of rabbits were collected at the end of feeding trials. Concentrations (mg L) of Pb (3.28) and Zn (7.10) increased in blood after 24 h compared to control treatment and then decreased (Pb 1.12; Zn 3.32) to a steady state with the passage of time after 7 days. A significant increase in the concentrations of Pb (1.20%, 3.95% and 5.58%) and Zn (10.7%, 6.89% and 18.4%) as compared to control treatment was also found in liver, kidney and bones of the rabbits, respectively, which was further confirmed by multivariate analysis. The highest significant values of correlation coefficient (r) were observed for blood and bones, i.e. 0.992 followed by blood and liver, i.e. 0.989. The bioassimilation of Pb in the body of rabbits was in the order of bone > kidney > liver > blood, while for Zn the order was bone > liver > kidney > blood. The bioassimilation of Pb and Zn in the blood, essential organs and bones depicted the serious health risks associated by consuming the metal contaminated vegetable.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112638DOI Listing
August 2021

Targeting non-pulmonary vein triggers in persistent atrial fibrillation: results from a prospective, multicentre, observational registry.

Europace 2021 Aug 21. Epub 2021 Aug 21.

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, 3000 N. IH-35, Suite 720, Austin, TX 78705, USA.

Aims: We evaluated the efficacy of an ablation strategy empirically targeting pulmonary veins (PVs) and posterior wall (PW) and the prevalence and clinical impact of extrapulmonary trigger inducibility and ablation in a large cohort of patients with persistent atrial fibrillation (PerAF).

Methods And Results: A total of 1803 PerAF patients were prospectively enrolled. All patients underwent pulmonary vein antrum isolation (PVAI) extended to the entire PW. A standardized protocol was performed to confirm persistent PVAI and elicit any triggers originating from non-PV sites. All non-PV triggers initiating sustained atrial tachyarrhythmias were ablated. Ablation of non-PV sites triggering non-sustained runs (<30 s) of atrial tachyarrhythmias or promoting frequent premature atrial complexes (≥10/min) was left to operator's discretion. Overall, 1319 (73.2%) patients had documented triggers from non-PV areas. After 17.4 ± 8.5 months of follow-up, the cumulative freedom from atrial tachyarrhythmias among patients without inducible non-PV triggers (n = 484) was 70.2%. Patients with ablation of induced non-PV triggers had a significantly higher arrhythmia control than those whose triggers were not ablated (67.9% vs. 39.4%, respectively; P < 0.001). After adjusting for clinically relevant variables, patients in whom non-PV triggers were documented but not ablated had an increased risk of arrhythmia relapse (hazard ratio: 2.39; 95% confidence interval: 2.01-2.83; P < 0.001).

Conclusion: Pulmonary vein antrum isolation extended to the entire PW might provide acceptable long-term arrhythmia-free survival in PerAF patients without inducible non-PV triggers. In our population of PerAF patients, non-PV triggers could be elicited in ∼70% of PerAF patients and their elimination significantly improved outcomes.
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http://dx.doi.org/10.1093/europace/euab161DOI Listing
August 2021

Whole-exome sequencing of consanguineous families with infertile men and women identifies homologous mutations in SPATA22 and MEIOB.

Hum Reprod 2021 Sep;36(10):2793-2804

First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, University of Science and Technology of China, Hefei, China.

Study Question: Can whole-exome sequencing (WES) reveal pathogenic mutations in two consanguineous Pakistani families with infertile patients?

Summary Answer: A homozygous spermatogenesis associated 22 (SPATA22) frameshift mutation (c.203del), which disrupts the interaction with meiosis specific with OB-fold (MEIOB), and a MEIOB splicing mutation (c.683-1G>A) that led to loss of MEIOB protein cause familial infertility.

What Is Known Already: MEIOB and SPATA22, direct binding partners and functional collaborators, form a meiosis-specific heterodimer that regulates meiotic recombination. The protein stability and the axial localization of MEIOB and SPATA22 depend on each other. Meiob and Spata22 knockout mice have the same phenotypes: mutant spermatocytes can initiate meiotic recombination but are unable to complete DSB repair, leading to crossover formation failure, meiotic prophase arrest, and sterility.

Study Design, Size, Duration: We performed WES for the patients and controls in two consanguineous Pakistani families to screen for mutations. The pathogenicity of the identified mutations was assessed by in vitro assay and mutant mouse model.

Participants/materials, Setting, Methods: Two consanguineous Pakistani families with four patients (three men and one woman) suffering from primary infertility were recruited. SPATA22 and MEIOB mutations were screened from the WES data, followed by functional verification in cultured cells and mice.

Main Results And The Role Of Chance: A homozygous SPATA22 frameshift mutation (c.203del) was identified in a patient with non-obstructive azoospermia (NOA) from a consanguineous Pakistani family and a homozygous MEIOB splicing mutation (c.683-1G>A) was identified in two patients with NOA and one infertile woman from another consanguineous Pakistani family. The SPATA22 mutation destroyed the interaction with MEIOB. The MEIOB splicing mutation induced Exon 9 skipping, which causes a 32aa deletion in the oligonucleotide-binding domain without affecting the interaction between MEIOB and SPATA22. Furthermore, analyses of the Meiob mutant mice modelling the patients' mutation revealed that the MEIOB splicing mutation leads to loss of MEIOB proteins, abolished SPATA22 recruitment on chromosome axes, and meiotic arrest due to meiotic recombination failure. Thus, our study suggests that SPATA22 and MEIOB may both be causative genes for human infertility.

Limitations, Reasons For Caution: As SPATA22 and MEIOB are interdependent and essential for meiotic recombination, screening for mutations of SPATA22 and MEIOB in both infertile men and women in larger cohorts is important to further reveal the role of the SPATA22 and MEIOB heterodimer in human fertility.

Wider Implications Of The Findings: These findings provide direct clinical and functional evidence that mutations in SPATA22 and MEIOB can cause meiotic recombination failure, supporting a role for these mutations in human infertility and their potential use as targets for genetic diagnosis of human infertility.

Study Funding/competing Interest(s): This work was supported by the National Key Research and Developmental Program of China (2018YFC1003900, 2018YFC1003700, and 2019YFA0802600), the National Natural Science Foundation of China (31890780, 31630050, 32061143006, 82071709, and 31871514), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB19000000). The authors declare no conflicts of interest.

Trial Registration Number: N/A.
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http://dx.doi.org/10.1093/humrep/deab185DOI Listing
September 2021

Radiofrequency Energy Applications Targeting Significant Residual Leaks After Watchman Implantation: A Prospective, Multicenter Experience.

JACC Clin Electrophysiol 2021 Jul 19. Epub 2021 Jul 19.

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA; Interventional Electrophysiology, Scripps Clinic, La Jolla, California, USA; Department of Cardiology, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

Objectives: The aim of this study was to evaluate the efficacy of radiofrequency (RF) energy applications targeting the atrial side of a significant residual leak in patients with acute and chronic evidence of incomplete percutaneous left atrial appendage (LAA) occlusion.

Background: RF applications have been proved to prevent recanalization of intracranial aneurysms after coil embolization, thereby favoring complete sealing. From a mechanistic standpoint, in vitro and in vivo experiments have demonstrated that RF promotes collagen deposition and tissue retraction.

Methods: Forty-three patients (mean age 75 ± 7 years mean CHADS-VASc score 4.6 ± 1.4, mean HAS-BLED score 4.0 ± 1.1) with residual leaks ≥4 mm after Watchman implantation were enrolled. Procedural success was defined as complete LAA occlusion or presence of a mild or minimal (1- to 2-mm) peridevice leak on follow-up transesophageal echocardiography (TEE), which was performed approximately 45 days after the procedure.

Results: RF-based leak closure was performed acutely after Watchman implantation in 19 patients (44.2%) or scheduled after evidence of significant leaks on follow-up TEE in 24 others (55.8%). The median leak size was 5 mm (range: 4-7 mm). On average, 18 ± 7 RF applications per patient (mean maximum contact force 16 ± 3 g, mean power 44 ± 2 W, mean RF time 5.1 ± 2.5 minutes) were performed targeting the atrial edge of the leak. Post-RF median leak size was 0 mm (range: 0-1 mm). A very low rate (2.3% [n = 1]) of major periprocedural complications was observed. Follow-up TEE revealed complete LAA sealing in 23 patients (53.5%) and negligible residual leaks in 15 (34.9%).

Conclusions: RF applications targeting the atrial edge of a significant peri-Watchman leak may promote LAA sealing via tissue remodeling, without increasing complications. (RF Applications for Residual LAA Leaks [REACT]; NCT04726943).
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http://dx.doi.org/10.1016/j.jacep.2021.06.002DOI Listing
July 2021

A Review on Nuclear Imaging as a Promising Modality for Efficient Diagnosis of Tuberculosis.

Curr Med Imaging 2021 Jul 7. Epub 2021 Jul 7.

Department of Pharmacy, COMSATS University Islamabad, Lahore Campus 54000. Pakistan.

Tuberculosis (TB) is an infectious disease and is declared a global health issue by the World Health Organization in 1993. Due to the complex pathophysiology of Mycobacterium tuberculosis, it remains a global threat. This article reviews the conventional diagnostic modalities for tuberculosis, their limitations to detect latent TB, multiple drug-resistant TB, human immunodeficiency virus co-infected TB lesions, and TB in children. Moreover, this review illustrates the importance of nuclear medicine imaging for early, non-invasive diagnosis of TB to detect disease stages and monitor therapy response. Currently, single-photon emission computed tomography and positron emission tomography with their specific radionuclides have been extensively used for a thorough assessment of TB.
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http://dx.doi.org/10.2174/1573405617666210707150811DOI Listing
July 2021

Correction: A first-principles study of the stability, electronic structure, and optical properties of halide double perovskite RbSnTeI for solar cell applications.

Phys Chem Chem Phys 2021 Jul;23(28):15386

Department of Physics, University of Peshawar, Peshawar 25120, Pakistan.

Correction for 'A first-principles study of the stability, electronic structure, and optical properties of halide double perovskite Rb2Sn1-xTexI6 for solar cell applications' by Muhammad Faizan et al., Phys. Chem. Chem. Phys., 2021, 23, 4646-4657, DOI: 10.1039/D0CP05827K.
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http://dx.doi.org/10.1039/d1cp90137kDOI Listing
July 2021

Optimization of Novel Naproxen-Loaded Chitosan/Carrageenan Nanocarrier-Based Gel for Topical Delivery: Ex Vivo, Histopathological, and In Vivo Evaluation.

Pharmaceuticals (Basel) 2021 Jun 11;14(6). Epub 2021 Jun 11.

Department of Pharmacy, COMSATS University Islamabad, Lahore Campus, Lahore 54000, Pakistan.

Naproxen (NAP) is commonly used for pain, inflammation, and stiffness associated with arthritis. However, systemic administration is linked with several gastrointestinal tract (GIT) side effects. The present work aims to prepare and evaluate NAP nanoparticulate shells of chitosan (CS) and carrageenan (CRG) loaded into a Carbopol 940 (Ca-940) gel system with unique features of sustained drug delivery as well as improved permeation through a topical route. Moreover, this study aims to evaluate its ex vivo, histopathological, and in vivo anti-inflammatory activity in albino Wistar rats. The percentage of ex vivo drug permeation patterns in the optimized formulation (No) was higher (88.66%) than the control gel (36.195%). Oral toxicity studies of developed nanoparticles in albino rabbits showed that the NAP-loaded CS/CRG are non-toxic and, upon histopathological evaluation, no sign of incompatibility was observed compared to the control group. A In Vivo study showed that the optimized gel formulation (No) was more effective than the control gel (Nc) in treating arthritis-associated inflammation. The sustained permeation and the absence of skin irritation make this novel NAP nanoparticle-loaded gel based on CS/CRG a suitable drug delivery system for topical application and has the potential for improved patient compliance and reduced GIT-related side effects in arthritis.
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http://dx.doi.org/10.3390/ph14060557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230576PMC
June 2021

Nicotine smoking is associated with impaired cognitive performance in Pakistani young people.

PeerJ 2021 2;9:e11470. Epub 2021 Jun 2.

Neuroscience Center, King Fahad Specialist Hospital, Dammam, Saudi Arabia.

Nicotine smoking is the most common mode of tobacco smoking among young people. It affects the areas of the brain associated with memory, attention, and learning. This study has investigated the effect of nicotine smoking on cognitive performance. One hundred male volunteers (50 nicotine smokers and 50 nonsmokers) aged 18-30 years with similar socioeconomic backgrounds were recruited for this study. Clinical history of participants was obtained using a questionnaire. Their brain health and handedness were determined using the Mini Mental State Examination (MMSE) and the Edinburgh Handedness Inventory (EHI), respectively. The dependent variables examined in the study were attention-switching tasks (AST), pattern recognition memory (PRM), and choice reaction time (CRT). These parameters were assessed using the Cambridge Neuropsychological Automated Battery (CANTAB). The average ages of participating smokers and nonsmokers were 24.02 ± 3.41 years (mean ± standard deviation) and 22.68 ± 1.87 years, respectively. MMSE and EHI scores of smokers were 28.42 ± 1.09 and 99.75 ± 1.77, respectively; for nonsmokers, these scores were 28.54 ± 1.34 and 98 ± 1.91, respectively. The mean score for AST correct latency/delay was significantly higher ( = 0.050) in smokers (620.26 ± 142.03) than in nonsmokers (570.11 ± 108.39). The percentage of correct AST trials was significantly higher ( = 0.000) in nonsmokers (96.95 ± 2.18) than in smokers (83.75 ± 11.22). The PRM percent correct were significantly higher ( = 0.000) of nonsmokers (93.42 ± 8.34) than of smokers (79.75 ± 13.44). The mean correct latency for CRT was significantly higher ( = 0.009) in smokers (509.87 ± 129.83) than in nonsmokers (455.20 ± 65.73). From this data, it can be concluded that nicotine smoking is linked with impaired cognitive functions in smokers.
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http://dx.doi.org/10.7717/peerj.11470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179217PMC
June 2021

Optimisation of user-selectable volumetric modulated arc therapy (VMAT) planning parameters: VMAT arcs for prostate and head-and-neck cancers.

J Pak Med Assoc 2021 Apr;71(4):1093-1099

Department of Mathematics, NAMAL INSTITUTE Mianwali, Pakistan.

Objective: To evaluate different VMAT planning techniques for a multi-leaf collimator (MLC)providing maximum aperture of 21 × 16 cm².

Methods: A VMAT planning study of nine prostate and nine head-and-neck cancer patients was carried out. The patients were previously treated with Intensity Modulated Radiotherapy (IMRT) technique during 2014-15, at radiation oncology SanBortolo Hospital, Vicenza, Italy. Three VMAT plans for each of prostate and head-and-neck cancer patient were optimized using Pinnacle treatment planning system for 6MV photon beam from ElektaSynergyS®Linac system. Single arc, dual arc and combined two independent-single-arcs were optimized for collimator angle 45°. VMAT treatment planning comparison was made among single-arc dual-arc and combined two independent-single-arcs. The student's t-test (two-sided) with p ≤ 0.05 was applied for significant difference between dose volume indices of plans.

Results: All VMAT techniques produced clinically acceptable plans for prostate, while for head-and-neck, DA and ISAs significantly improved target coverage compared to SA. Single arc is sufficient for prostate, while inefficient in case of head-and-neck dose-planning. In spite of having different VMAT optimization approach dual arc and two combined independent-single-arcs provided very similar target coverage, while dual arc improved sparing of organs-at-risk. Similar treatment delivery times were observed for DA and ISAs VMAT techniques.

Conclusions: Single arc is sufficient for prostate, while inefficient in case of head-and-neck dose-planning. Dual arc and two combined independent-single-arcs provided similar PTV coverage, while DA provided better sparing of organs at risk.
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http://dx.doi.org/10.47391/JPMA.710DOI Listing
April 2021

Biochar mitigates arsenic-induced human health risks and phytotoxicity in quinoa under saline conditions by modulating ionic and oxidative stress responses.

Environ Pollut 2021 Oct 15;287:117348. Epub 2021 May 15.

Department of Environmental Sciences, COMSATS University Islamabad, Vehari Campus, 61100, Pakistan.

Arsenic (As) is a toxic metalloid and its widespread contamination in agricultural soils along with soil salinization has become a serious concern for human health and food security. In the present study, the effect of cotton shell biochar (CSBC) in decreasing As-induced phytotoxicity and human health risks in quinoa (Chenopodium quinoa Willd.) grown on As-spiked saline and non-saline soils was evaluated. Quinoa plants were grown on As contaminated (0, 15 and 30 mg kg) saline and non-saline soils amended with 0, 1 and 2% CSBC. Results showed that plant growth, grain yield, stomatal conductance and chlorophyll contents of quinoa showed more decline on As contaminated saline soil than non-saline soil. The application of 2% CSBC particularly enhanced plant growth, leaf relative water contents, stomatal conductance, pigment contents and limited the uptake of As and Na as compared to soil without CSBC. Salinity in combination with As trigged the production of HO and caused lipid peroxidation of cell membranes. Biochar ameliorated the oxidative stress by increasing the activities of antioxidant enzymes (SOD, POD, CAT). Carcinogenic and non-carcinogenic human health risks were greatly decreased in the presence of biochar. Application of 2% CSBC showed promising results in reducing human health risks and As toxicity in quinoa grown on As contaminated non-saline and saline soils. Further research is needed to evaluate the role of biochar in minimizing As accumulation in other crops on normal as well as salt affected soils under field conditions.
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http://dx.doi.org/10.1016/j.envpol.2021.117348DOI Listing
October 2021

Relationship between gut microbiota and host-metabolism: Emphasis on hormones related to reproductive function.

Anim Nutr 2021 Mar 4;7(1):1-10. Epub 2021 Jan 4.

Faculty of Animal Husbandry and Veterinary Sciences, University of Poonch, Rawalakot, 12350, Pakistan.

It has been well recognized that interactions between the gut microbiota and host-metabolism have a proven effect on health. The gut lumen is known for harboring different bacterial communities. Microbial by-products and structural components, which are derived through the gut microbiota, generate a signaling response to maintain homeostasis. Gut microbiota is not only involved in metabolic disorders, but also participates in the regulation of reproductive hormonal function. Bacterial phyla, which are localized in the gut, allow for the metabolization of steroid hormones through the stimulation of different enzymes. Reproductive hormones such as progesterone, estrogen and testosterone play a pivotal role in the successful completion of reproductive events. Disruption in this mechanism may lead to reproductive disorders. Environmental bacteria can affect the metabolism, and degrade steroid hormones and their relevant compounds. This behavior of the bacteria can safely be implemented to eliminate steroidal compounds from a polluted environment. In this review, we summarize the metabolism of steroid hormones on the regulation of gut microbiota and vice-versa, and also examined the significant influence this process has on various events of reproductive function. Altogether, the evidence suggests that steroid hormones and gut microbiota exert a central role in the modification of host bacterial action and impact the reproductive efficiency of animals and humans.
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http://dx.doi.org/10.1016/j.aninu.2020.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110851PMC
March 2021

Safety and Efficacy of Apixaban versus warfarin in patients with atrial fibrillation or Venous Thromboembolism and End-Stage renal disease on hemodialysis: A systematic review and meta-analysis.

Indian Pacing Electrophysiol J 2021 Jul-Aug;21(4):221-226. Epub 2021 Apr 15.

Division of Cardiac Electrophysiology, The Kansas City Heart Rhythm Institute & Research Foundation, Overland Park, KS, USA. Electronic address:

Background: Warfarin is traditionally the drug of choice for stroke prophylaxis or treatment of venous thromboembolism in patients with end-stage renal disease (ESRD) on hemodialysis as data on apixaban use is scarce. We aimed to assess the safety and efficacy of Apixaban in patients with ESRD on hemodialysis when compared with warfarin.

Methods: A comprehensive literature search in PubMed, Google Scholar, and Cochrane databases from inception until Nov 25, 2019, was performed. Studies reporting clinical outcomes comparing Apixaban (2.5 mg BID or 5 mg BID) versus Warfarin in ESRD patients on hemodialysis were included. Mantel-Haenszel risk ratio (RR) random-effects model was used to summarize data.

Results: Four studies (three retrospective and one randomized) with a total of 9862 patients (apixaban = 2,547, warfarin = 7315) met inclusion criteria. The overall mean age was 66.6 ± 3.9 years and mean CHA2DS2-VASc score 4.56 ± 0.58. Apixaban was associated with lower rates of major bleeding (RR 0.53, 95% CI 0.45-0.64, p < 0.0001], gastrointestinal (GI) bleed (RR 0.65, 95% CI 0.55-0.76, p < 0.0001), intracranial bleed (RR 0.56, 95% CI 0.36-0.89, p = 0.01), and stroke/systemic embolism [RR 0.65, 95% CI 0.52-0.83, p = 0.0004] compared with warfarin in patients with ESRD on hemodialysis. There was no significant increased risk of all-cause mortality with the apixaban vs. warfarin (RR 0.90, 95% CI 0.41-1.96, p = 0.78).

Conclusion: Apixaban had an overall favorable risk-benefit profile, with significant reductions in ischemic stroke, major bleeding, and intracranial bleeding compared to Warfarin in ESRD patients on hemodialysis with non-valvular AF and/or venous thromboembolism.
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http://dx.doi.org/10.1016/j.ipej.2021.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263313PMC
April 2021

Synthesis, Characterization and Safety Evaluation of Sericin-Based Hydrogels for Controlled Delivery of Acyclovir.

Pharmaceuticals (Basel) 2021 Mar 8;14(3). Epub 2021 Mar 8.

College of Pharmacy and Health Sciences, Ajman University, P.O. Box 346, Ajman, United Arab Emirates.

Conventional formulations of antiviral drug acyclovir have various limitations such as low bioavailability. The current study was aimed at developing polymeric matrices for the controlled delivery of acyclovir using sericin as polymer and acrylic acid (AA) as a monomer. The free radical polymerization technique was used for hydrogel formulation. Briefly, sericin was chemically cross-linked with acrylic acid. '-'-methylene bis-acrylamide (MBA) and ammonium persulfate (APS) were used as cross-linker and initiator, respectively. FTIR spectra showed that acyclovir was successfully loaded into sericin hydrogel. SEM micrographs revealed that the outer surface was solid-like and smooth. According to DSC thermograms, the developed polymeric network was thermally stable. Amorphous nature of acyclovir was observed in XRD. The pH of medium and reactants' concentration affected swelling dynamics and acyclovir release pattern. In addition, drug release occurred through a diffusion-controlled process. Sericin hydrogel suspension was well tolerable up to 3800 mg/kg of rabbits' body weight. Haematology and serum chemistry results were well within the range signifying normal liver and kidney functions. Similarly, histopathology slides of the rabbit's vital organs were also in normal condition without causing any histopathological change. It was concluded from the findings that sericin-co-AA polymeric matrices are ideal for the pH-dependent delivery of acyclovir.
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http://dx.doi.org/10.3390/ph14030234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000570PMC
March 2021

Electronic and optical properties of vacancy ordered double perovskites ABX (A = Rb, Cs; B = Sn, Pd, Pt; and X = Cl, Br, I): a first principles study.

Sci Rep 2021 Mar 26;11(1):6965. Epub 2021 Mar 26.

Department of Physics, University of Peshawar, Peshawar, 25120, Pakistan.

The highly successful PBE functional and the modified Becke-Johnson exchange potential were used to calculate the structural, electronic, and optical properties of the vacancy-ordered double perovskites ABX (A = Rb, Cs; B = Sn, Pd, Pt; X = Cl, Br, and I) using the density functional theory, a first principles approach. The convex hull approach was used to check the thermodynamic stability of the compounds. The calculated parameters (lattice constants, band gap, and bond lengths) are in tune with the available experimental and theoretical results. The compounds, RbPdBr and CsPtI, exhibit band gaps within the optimal range of 0.9-1.6 eV, required for the single-junction photovoltaic applications. The photovoltaic efficiency of the studied materials was assessed using the spectroscopic-limited-maximum-efficiency (SLME) metric as well as the optical properties. The ideal band gap, high dielectric constants, and optimum light absorption of these perovskites make them suitable for high performance single and multi-junction perovskite solar cells.
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http://dx.doi.org/10.1038/s41598-021-86145-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997874PMC
March 2021

Network Pharmacological Study of Radix Effect on Bone Trauma.

Biomed Res Int 2021 6;2021:5692039. Epub 2021 Mar 6.

Graduate School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.

Purpose: Bone trauma is a clinical condition that afflicts the majority of the world's population. For the management of bone trauma, the underlying mechanisms of the drugs effective for bone healing are deemed necessary. Radix (ABR) is a popular alternative medicine recommended in the treatment of bone trauma and injury, yet its mechanism of action persists to be vague. This study was conducted for the evaluation of the mode of action of ABR through network pharmacology in treating bone trauma.

Methods: An extensive survey of published works led to the development of a drug-target database, after which multiple protein targets for bone trauma were discerned. The protein-protein interaction network was developed by utilizing the STITCH database and gene ontology (GO) enrichment analysis using Cytoscape and ClueGO. Moreover, docking studies were performed for revealing the affinity of various ingredients with IL6.

Results: The extensive literature survey yielded the presence of 176 components in ABR, and 151 potential targets were acquired. Scrutinization of these targets revealed that 21 potential targets were found to be associated with bone trauma. Out of which, some remarkable targets such as IL6, MAPK14, MAPK8, SRC, PTGS2, and MMP2 were observed to be associated in the functional interaction of ABR. According to docking results, several ingredients of ABR such as Baicalien, Copistine, Epiberberine, Kaempferol, and Palmatine have the lowest docking scores (range between -6 and -7).

Conclusions: The results of the study elucidated that ABR can positively be utilized for the management of bone trauma, which can be mediated by multiple molecular mechanisms such as ERBB2 signaling pathway, positive regulation of oxidoreductase activity, JNK cascade pathway, multicellular organism metabolic process, T cell costimulation, and the positive regulation of MAPK activity. The findings also suggest that several ingredients of ABR such as Baicalien, Copistine, Epiberberine, Kaempferol, and Palmatine have good affinity with IL6, suggesting the promising potential of ABR in treating bone trauma, likely through IL6.
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http://dx.doi.org/10.1155/2021/5692039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959927PMC
May 2021

Prognostic role of albumin level in heart failure: A systematic review and meta-analysis.

Medicine (Baltimore) 2021 Mar;100(10):e24785

Cardiology Division, American University of Beirut Faculty of Medicine and Medical Center, Beirut, Lebanon.

Background: Hypoalbuminemia (HA) is common in HF, however, its pathophysiology and clinical implications are poorly understood. While multiple studies have been published in the past decade investigating the role of serum albumin in HF, there is still no consensus on the prognostic value of this widely available measure. The objective of this study is to assess the prognostic role of albumin in heart failure (HF) patient.

Methods: Unrestricted searches of MEDLINE, EMBASE, Cochrane databases were performed. The results were screened for relevance and eligibility criteria. Relevant data were extracted and analyzed using Comprehensive Meta-Analysis software. The Begg and Mazumdar rank correlation test was utilized to evaluate for publication bias.

Results: A total of 48 studies examining 44,048 patients with HF were analyzed. HA was found in 32% (95% confidence interval [CI] 28.4%-37.4%) HF patients with marked heterogeneity (I2 = 98%). In 10 studies evaluating acute HF, in-hospital mortality was almost 4 times more likely in HA with an odds ratios (OR) of 3.77 (95% CI 1.96-7.23). HA was also associated with a significant increase in long-term mortality (OR: 1.5; 95% CI: 1.36-1.64) especially at 1-year post-discharge (OR: 2.44; 95% CI: 2.05-2.91; I2 = 11%). Pooled area under the curve (AUC 0.73; 95% CI 0.67-0.78) was comparable to serum brain natriuretic peptide (BNP) in predicting mortality in HF patients.

Conclusion: Our results suggest that HA is associated with significantly higher in-hospital mortality as well as long-term mortality with a predictive accuracy comparable to that reported for serum BNP. These findings suggest that serum albumin may be useful in determining high-risk patients.
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http://dx.doi.org/10.1097/MD.0000000000024785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969328PMC
March 2021

Management of Arrhythmias After Heart Transplant: Current State and Considerations for Future Research.

Circ Arrhythm Electrophysiol 2021 03 9;14(3):e007954. Epub 2021 Mar 9.

Kansas City Heart Rhythm Institute and Research Foundation, Overland Park, KS (G.M., D.L., R.G.).

Orthotropic heart transplantation remains the most effective therapy for patients with end-stage heart failure, with a median survival of ≈13 years. Yet, a number of complications are observed after orthotropic heart transplantation, including atrial and ventricular arrhythmias. Several factors contribute to arrhythmias, such as autonomic denervation, effect of the surgical technique, acute and chronic rejection, and transplant vasculopathy among others. To minimize risk of future arrhythmias, the bicaval technique and minimizing ischemic time are current surgical standards. Sinus node dysfunction is the most common indication for early (within 30 days) pacemaker implantation, whereas atrioventricular block incidence increases as time from transplant increases. Atrial fibrillation can occur in the first few weeks following transplantation but is uncommon in the long term unless secondary to a precipitant such as acute rejection. The most common atrial arrhythmias are atrial flutters, which are mainly typical, but atypical circuits can be observed such as those that involve the remnant donor atrium in regions immediately adjacent to the atrioatrial anastomosis suture line. Choosing the appropriate pharmacological therapy requires careful consideration due to the potential interaction with immunosuppressive agents. Despite historical concerns, adenosine is effective and safe at reduced doses if administered under cardiac monitoring. Catheter ablation has emerged as an effective treatment strategy for symptomatic supraventricular tachycardias, including ablation of atypical flutter circuits. Cardiac allograft vasculopathy is an important risk factor for sudden cardiac death, yet the role of prophylactic implantable cardioverter-defibrillator implant for sudden death prevention is unclear. Current indications for implantable cardioverter-defibrillator implantation are as in the nontransplant population. A number of questions for future research are posed.
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http://dx.doi.org/10.1161/CIRCEP.120.007954DOI Listing
March 2021

Potential Role of Molecular Imaging with F-FDG in Diagnostic Triage and Follow-Up of Suspects with COVID-19 Infection.

Indian J Nucl Med 2020 Oct-Dec;35(4):381-383. Epub 2020 Oct 21.

Department of Bioinformatics, Hazara University, Dhodial, Mansehra, Khyber Pakhtunkhwa, Pakistan.

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http://dx.doi.org/10.4103/ijnm.IJNM_76_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905264PMC
October 2020

Efficacy of Oral Vitamin D Therapy in Patients Suffering from Diffuse Hair Loss (Telogen Effluvium).

J Nutr Sci Vitaminol (Tokyo) 2021 ;67(1):68-71

Department of Pharmacy, COMSATS University Islamabad.

The aim of the present study was to estimate the prevalence of telogen effluvium (TE) and to evaluate the efficacy of vitamin D in the treatment of this problem in women belonging to various cities of south Punjab, Pakistan. In the present study, 40 adult women suffering from the problem of TE were included. Each woman was treated with oral vitamin D (200,000 IU) therapy fortnightly and a total of 6 doses were given to each patient. After 15 d of the last dose, the condition of patients was assessed clinically. The mean age of female patients was 32.2±1.5 y, 42.5% of the patients between 21-30 y of age were found to be more frequently affected with TE compared to 35% females of 31-40 y of age. Results showed significant improvement in hair growth in young (r=0.457 p<0.003) women and in those, which do not use sunscreen (r=-0.331 p<0.037) but commonly utilize milk or milk protein (r=-0.311 p<0.051). Vitamin D therapy resulted in the improvement of the condition in 82.5% (p<0.001) patients of TE. The use of oral vitamin D (200,000 IU, fortnightly) for 3 mo resulted in significant improvement in hair regrowth in the patient of TE. Results showed improvement in hair growth in young women those do not use sunscreen but commonly utilize milk or milk protein.
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http://dx.doi.org/10.3177/jnsv.67.68DOI Listing
August 2021

A first-principles study of the stability, electronic structure, and optical properties of halide double perovskite RbSnTeI for solar cell applications.

Phys Chem Chem Phys 2021 Feb 15;23(8):4646-4657. Epub 2021 Feb 15.

Department of Physics, University of Peshawar, Peshawar 25120, Pakistan.

Owing to their emerging role in solar cell technology, lead halide perovskites have aroused significant research interest in the recent past. However, due to its obvious toxicity, looking for a potential alternative to lead is becoming one of the most important pursuits in present times. We present our work based on density functional theory (DFT) investigating lead free defect perovskites (RbSnTeI (0 ≤x≤ 1)). In particular, we explore the crystal structure, thermodynamic stability, electronic structure, and optical properties of RbSnTeI (0 ≤x≤ 1) as a function of increasing Te concentration. Our results show that the Sn-Te alloyed perovskites exhibit considerable stability, a suitable band gap, small effective mass, and excellent light absorption. Especially, RbSnTeI and RbSnTeI have a direct band gap of 1.35 and 1.44 eV, respectively, which is highly favorable for use in a single-junction photovoltaic cell. We hope that our work will arouse the interest of experimental as well as theoretical scientists for synthesizing new materials and/or exploring the Sn-Te mix as a potential substitute for lead in photovoltaic materials.
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http://dx.doi.org/10.1039/d0cp05827kDOI Listing
February 2021

A tree-based multiclassification of breast tumor histopathology images through deep learning.

Comput Med Imaging Graph 2021 04 27;89:101870. Epub 2021 Jan 27.

Faculty of Computer Science and Information Technology, University of Malaya, 50603, Kuala Lumpur, Malaysia. Electronic address:

Worldwide, the burden of cancer is drastically increasing over the past few years. Among all types of cancers in women, breast cancer (BrC) is the main cause of unnatural deaths. For early diagnosis, histopathology (Hp) imaging is a gold standard for positive and detailed (at tissue level) diagnosis of breast tumor (BrT) compared to mammogram images. A large number of studies used BrT Hp images to solve binary or multiclassification problems using high computational resources. However, classification models' performance may be compromised due to the high correlation among various types of BrT in Hp images, which raises the misclassification rate. Thus, this paper aims to develop a tree-based BrT multiclassification model via deep learning (DL) to extract discriminative features to solve the multiclassification problem with better performance using less computational resources. The main contributions of this work are to create an ensemble, tree-based DL model that is pre-trained on the BreakHis dataset, and implementation of a misclassification reduction algorithm. The ensemble, tree-based DL model, extracts discriminative BrT features from Hp images. The target dataset (i.e., Bioimaging challenge 2015 breast histology) is small in size; thus, to avoid overfitting of the proposed model, pretraining is performed on the BreakHis dataset. Whereas, misclassification reduction algorithm is implemented to enhance the performance of the classification model. The experimental results show that the proposed model outperformed the existing state-of-the-art baseline studies. The achieved classification accuracy is ranging from 87.50 % to 100 % for four subtypes of BrT. Thus, the proposed model can assist doctors as the second opinion in any healthcare centre.
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http://dx.doi.org/10.1016/j.compmedimag.2021.101870DOI Listing
April 2021

Homozygous mutations in C14orf39/SIX6OS1 cause non-obstructive azoospermia and premature ovarian insufficiency in humans.

Am J Hum Genet 2021 02 27;108(2):324-336. Epub 2021 Jan 27.

Division of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei 230027, China. Electronic address:

Human infertility is a multifactorial disease that affects 8%-12% of reproductive-aged couples worldwide. However, the genetic causes of human infertility are still poorly understood. Synaptonemal complex (SC) is a conserved tripartite structure that holds homologous chromosomes together and plays an indispensable role in the meiotic progression. Here, we identified three homozygous mutations in the SC coding gene C14orf39/SIX6OS1 in infertile individuals from different ethnic populations by whole-exome sequencing (WES). These mutations include a frameshift mutation (c.204_205del [p.His68Glnfs2]) from a consanguineous Pakistani family with two males suffering from non-obstructive azoospermia (NOA) and one female diagnosed with premature ovarian insufficiency (POI) as well as a nonsense mutation (c.958G>T [p.Glu320]) and a splicing mutation (c.1180-3C>G) in two unrelated Chinese men (individual P3907 and individual P6032, respectively) with meiotic arrest. Mutations in C14orf39 resulted in truncated proteins that retained SYCE1 binding but exhibited impaired polycomplex formation between C14ORF39 and SYCE1. Further cytological analyses of meiosis in germ cells revealed that the affected familial males with the C14orf39 frameshift mutation displayed complete asynapsis between homologous chromosomes, while the affected Chinese men carrying the nonsense or splicing mutation showed incomplete synapsis. The phenotypes of NOA and POI in affected individuals were well recapitulated by Six6os1 mutant mice carrying an analogous mutation. Collectively, our findings in humans and mice highlight the conserved role of C14ORF39/SIX6OS1 in SC assembly and indicate that the homozygous mutations in C14orf39/SIX6OS1 described here are responsible for infertility of these affected individuals, thus expanding our understanding of the genetic basis of human infertility.
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http://dx.doi.org/10.1016/j.ajhg.2021.01.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895996PMC
February 2021

Prediction of the Mode of Action of in Diabetes.

Biomed Res Int 2020 31;2020:2768403. Epub 2020 Oct 31.

Department of Pharmacy, COMSATS University Islamabad, Lahore Campus, 54000, Pakistan.

Background: The metabolic syndrome increases the risk of different diseases such as type 2 diabetes. The prevalence of metabolic syndrome has rapidly grown and affected more than 230 million people worldwide. is a traditionally used plant for the treatment of diabetes; however, its mechanism to manage diabetes is still unknown.

Purpose: This study was designed to systematically assess the mechanism of action of in diabetes.

Methods: An extensive literature search was made to establish an ingredient-target database of . Of these, targets related to diabetes were identified and used to develop a protein-protein interaction network (PPIN) by utilizing the STITCH database. The obtained PPIN was assessed through Gene Ontology (GO) enrichment analysis based on ClueGO plugin.

Results: According to the acquired data, there were about 143 chemical constituents present in having 119 protein targets. Of these, 31 targets were established to give the pharmacological effect against diabetes. The UniProt database was used for screening of 31 targets, out of which contained 22 targets. Ultimately, 207 GO terms, grouped into 41 clusters, were found by gene analysis, and most of them were found to be linked with diabetes. According to findings, several proteins including TP53, BCL2, CDKN1A, 1L6, CCND1, CDKN2A, and RB1 have a significant role in the treatment of diabetes by .

Conclusion: The possible activity of in the management of diabetes may be mediated by several molecular mechanisms, including the glutamine metabolic process, IRE1-mediated unfolded protein response, and pentose metabolic process.
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http://dx.doi.org/10.1155/2020/2768403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803256PMC
May 2021

Role of Dietary Amino Acids and Nutrient Sensing System in Pregnancy Associated Disorders.

Front Pharmacol 2020 22;11:586979. Epub 2020 Dec 22.

College of Animal Science and Technology, Hunan Agricultural University, Changsha, China.

Defective implantation is related to pregnancy-associated disorders such as spontaneous miscarriage, intrauterine fetal growth restriction and others. Several factors proclaimed to be involved such as physiological, nutritional, environmental and managemental that leads to cause oxidative stress. Overloading of free radicals promotes oxidative stress, and the internal body system could not combat its ability to encounter the damaging effects and subsequently leading to pregnancy-related disorders. During pregnancy, essential amino acids display important role for optimum fetal growth and other necessary functions for continuing fruitful pregnancy. In this context, dietary amino acids have received much attention regarding the nutritional concerns during pregnancy. Arginine, glutamine, tryptophan and taurine play a crucial role in fetal growth, development and survival while ornithine and proline are important players for the regulation of gene expression, protein synthesis and angiogenesis. Moreover, amino acids also stimulate the mammalian target of rapamycin (mTOR) signaling pathway which plays a central role in the synthesis of proteins in placenta, uterus and fetus. This review article explores the significances of dietary amino acids in pregnancy development, regulation of nutrient-sensing pathways such as mTOR, peroxisome proliferator-activated receptors (PPARs), insulin/insulin-like growth factor signaling pathway (IIS) and 5' adenosine monophosphate-activated protein kinase (AMPK) which exhibit important role in reproduction and its related problems. In addition, the antioxidant function of dietary amino acids against oxidative stress triggering pregnancy disorders and their possible outcomes will also be enlightened. Dietary supplementation of amino acids during pregnancy could help mitigate reproductive disorders and thereby improving fertility in animals as well as humans.
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http://dx.doi.org/10.3389/fphar.2020.586979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783402PMC
December 2020
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