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1.
Acta Neuropathol Commun ; 11(1): 196, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-38087392

ABSTRACT

Tau (Tubulin associated unit) protein is a major hallmark of Alzheimer's disease (AD) and tauopathies. Tau is predominantly an axonal protein with a crucial role in the stabilization and dynamics of the microtubules. Since the discovery of Tau protein in 1975, research efforts were concentrated on the pathophysiological role of Tau protein in the context of the microtubules. Although, for more than three decades, different localizations of Tau protein have been discovered e.g., in the nuclear compartments. Discovery of the role of Tau protein in various cellular compartments especially in the nucleus opens up a new fold of complexity in tauopathies. Data from cellular models, animal models, and the human brain indicate that nuclear Tau is crucial for genome stability and to cope with cellular distress. Moreover, it's nature of nuclear translocation, its interactions with the nuclear DNA/RNA and proteins suggest it could play multiple roles in the nucleus. To comprehend Tau pathophysiology and efficient Tau-based therapies, there is an urgent need to understand whole repertoire of Tau species (nuclear and cytoplasmic) and their functional relevance. To complete the map of Tau repertoire, understanding of various species of Tau in the nucleus and cytoplasm, identification if specific transcripts of Tau, isoforms and post-translational modifications could foretell Tau's localizations and functions, and how they are modified in neurodegenerative diseases like AD, is urgently required. In this review, we explore the nuclear face of Tau protein, its nuclear localizations and functions and its linkage with Alzheimer's disease.


Subject(s)
Alzheimer Disease , Tauopathies , Animals , Humans , tau Proteins/metabolism , Alzheimer Disease/metabolism , Tauopathies/metabolism , Microtubules/metabolism , Tubulin/metabolism
2.
Cell Biosci ; 13(1): 221, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38041189

ABSTRACT

BACKGROUND: Aberrant stress granules (SGs) are emerging as prime suspects in the nucleation of toxic protein aggregates. Understanding the molecular networks linked with aggregation-prone proteins (prion protein, synuclein, and tau) under stressful environments is crucial to understand pathophysiological cascades associated with these proteins. METHODS: We characterized and validated oxidative stress-induced molecular network changes of endogenous aggregation-prone proteins (prion protein, synuclein, and tau) by employing immunoprecipitation coupled with mass spectrometry analysis under basal and oxidative stress conditions. We used two different cell models (SH-SY5Y: human neuroblastoma and HeLa cell line) to induce oxidative stress using a well-known inducer (sodium arsenite) of oxidative stress. RESULTS: Overall, we identified 597 proteins as potential interaction partners. Our comparative interactome mapping provides comprehensive network reorganizations of three aggregation-prone hallmark proteins, establish novel interacting partners and their dysregulation, and validates that prion protein and synuclein localize in cytoplasmic SGs. Localization of prion protein and synuclein in TIA1-positive SGs provides an important link between SG pathobiology and aggregation-prone proteins. In addition, dysregulation (downregulation) of prion protein and exportin-5 protein, and translocation of exportin-5 into the nucleus under oxidative stress shed light on nucleocytoplasmic transport defects during the stress response. CONCLUSIONS: The current study contributes to our understanding of stress-mediated network rearrangements and posttranslational modifications of prion/prion-like proteins. Localization of prion protein and synuclein in the cytoplasmic SGs provides an important link between stress granule pathobiology and aggregation-prone proteins. In addition, our findings demonstrate nucleocytoplasmic transport defects after oxidative stress via dysregulation and nuclear accumulation of exportin-5.

3.
Mol Biol Rep ; 50(9): 7145-7154, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37407802

ABSTRACT

BACKGROUND: The current study was designed to highlight the effects of heterologous platelet-rich plasma (PRP) on deteriorated hepatic tissues and impaired glucose metabolism of alloxan-induced diabetic mice. METHODS: 30 male mice were divided into a control (CG), PRP (PG), diabetic (DG), and two treated groups (T1G and T2G). PG was given PRP treatment (0.5 ml/kg body weight) twice a week for four weeks. DG, T1G and T2G were given alloxan (150 mg/kg) to induce diabetes. After confirmation, PRP treatment was given to T1G and T2G for two and four weeks respectively while DG was left untreated. Upon completion of the said experimental period, liver samples were taken for histological and gene expression analyses. RESULTS: The study found that the liver tissue of the DG group showed signs of damage, including hepatocyte ballooning, sinusoid dilatation, and collagen deposition. However, these changes were significantly reduced in both T1G and T2G groups. The expression of several genes related to liver function was also affected, with upregulation of Fbp1 and Pklr, and downregulation of Pck1 in the DG group. PRP treatment restored Fbp1 expression and also increased the expression of glycolytic pathway genes Hk1 and Gck, as well as Wnt signalling pathway genes Wnt2, Wnt4, and Wnt9a in both treated groups. CONCLUSION: Current study revealed that heterologous PRP may partly alleviate high glucose levels in diabetics possibly by mediating glucose metabolism via inhibition of Wnt signalling pathway.


Subject(s)
Diabetes Mellitus, Experimental , Platelet-Rich Plasma , Mice , Male , Animals , Diabetes Mellitus, Experimental/therapy , Alloxan , Liver/metabolism , Glucose/metabolism , Platelet-Rich Plasma/metabolism
4.
Biomed Res Int ; 2022: 3460792, 2022.
Article in English | MEDLINE | ID: mdl-36425336

ABSTRACT

Idiopathic generalized epilepsy (IGE) is the most prevalent type of epilepsy with genetic origin. Mutations in ion channel genes have been identified as a common cause of IGE. Several studies have reported various epilepsy risk variants of GABRG2 (gamma-aminobutyric acid type A receptor subunit gamma2 subunit) gene in different ethnic groups, but the results are inconsistent. The purpose of this case-control research is to determine if GABRG2 polymorphisms contribute to IGE susceptibility and antiepileptic drug resistance in Pakistani population. For this purpose, we genotyped exon2, exon5 (C540T and C588T), exon7 (T813C), exon8 (K289M), and exon9 of GABRG2 gene by restriction fragment length polymorphism and Sanger's sequencing in 87 drug-responsive idiopathic generalized epilepsy patients, 55 drug-resistant epilepsy patients, and 83 healthy controls. Restriction fragment length polymorphism (RFLP) and sequencing results indicated only C588T polymorphism in the studied subjects. The comparison of genotypic and allelic frequencies showed significant differences between IGE patients and control groups (P = 0.008 and odds ratio = 4.2) and nonsignificant association of C588T polymorphism in antiseizure medication-resistant patients (P = 0.9). Our findings showed that C588T polymorphism of GABRG2 is a risk variant for IGE in Pakistani population. Further studies are required to validate the results.


Subject(s)
Anticonvulsants , Epilepsy , Humans , Anticonvulsants/therapeutic use , Pakistan , Receptors, GABA-A/genetics , Epilepsy/drug therapy , Epilepsy/genetics , Immunoglobulin E
5.
Genet Res (Camb) ; 2022: 9208765, 2022.
Article in English | MEDLINE | ID: mdl-36262248

ABSTRACT

Arthritis is a genetic disorder characterized by bones and joint degradation assisted by severe pain and inflammation. It is evident by the studies that 0 candidate genes variations play vital role in its development and progression. Therefore, we investigated the genetic variation of TLR-8, TNF, and ESR-1α genes in the Pakistani population. A case-control study comprising 300 RA, 316 OA, and 412 control subjects was conducted. PCR-RFLP and direct sequencing methods were used for determining genetic variations. Analysis was performed by using PLINK and MEGA 6.0 software. Allelic and genetic frequencies of polymorphisms identified on rs3764879 (TLR-8), rs3764880 (TLR-8), rs5744080 (TLR-8), rs1800629 (TNF), rs2228480 (ESR-1α), and rs1451501590 (ESR-1α) were significantly varied among RA, OA, and controls. Novel functional mutations SCV000844945 and SCV000844946 on TLR-8 as well as a non-functional SCV000804801 and functional variation SCV000804802 on ESR-1α were also identified and reported for the first time in the studied population. Multiple site analyses indicated that polymorphisms on TLR-8 and ESR-1α genes were significant risk factors in disease onset to the next generation. In conclusion, TLR-08 and ESR-1α were significant in the onset of arthritis whereas the TNF was not found as a significant risk factor in the onset of RA and OA.


Subject(s)
Arthritis, Rheumatoid , Polymorphism, Single Nucleotide , Toll-Like Receptor 8 , Tumor Necrosis Factor-alpha , Humans , Arthritis, Rheumatoid/genetics , Case-Control Studies , Genetic Predisposition to Disease/genetics , Polymorphism, Single Nucleotide/genetics , Toll-Like Receptor 8/genetics , Tumor Necrosis Factor-alpha/genetics , Estrogen Receptor alpha/genetics
8.
Environ Sci Pollut Res Int ; 29(55): 83711-83722, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35771333

ABSTRACT

Bisphenol S (BPS), an analog of bisphenol A (BPA), has been frequently detected in consumer products, food wrappers, plastics, and thermal papers. Since the liver is a hub of metabolic and detoxification pathways, thus intimately related to BPS presence in the environment and body. The current study was designed to investigate the effects of BPS administration in an animal model. Twenty-five male Wistar rats weighing 175 ± 25 g were randomly divided into control and treated groups. The control group was further divided into group I (no treatment) and group II (corn oil), whereas the treatment group was divided into D-I (40 mg/kg/day), D-II (200 mg/kg/day), and D-III (400 mg/kg/day) groups, getting oral doses of BPS for 15 days. Data analysis showed a significant statistical increase in hepatic enzymes ALT (33.4%), AST (25.4%), and ALP (529.6%) in the D-III group along with the development of hypercholesterolemia and hypertriglyceridemia in all BPS groups. Aberrant mRNA expressions of some key hepatic iron regulatory genes and inflammatory mediators were evident through qRT-PCR. Bisphenol S caused congestion of central vein from mild to moderate in hepatic sections. In conclusion, our investigation insinuates BPS intoxication potential and therefore may not be a safe alternative to BPA.


Subject(s)
Inflammation Mediators , Iron , Rats , Animals , Male , Rats, Wistar , Benzhydryl Compounds/pharmacology , Liver , Genes, Regulator
9.
Saudi J Biol Sci ; 29(4): 2063-2071, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35531155

ABSTRACT

Various types of cancer pose a notable threat to human health globally. To date, many researchers have undertaken the search for anticancer therapies. However, many anticancer therapeutic approaches accompany many undesirable hazards. In this respect, extracellular vesicles as a whole gained excessive attention from the research community owing to their remarkable potential for delivery of anticancer agents since they are involved in distal intercellular communication via biological cargoes. With the discovery of the fact that tumor cells discharge huge quantities of EVs, new insights have been developed in cancer diagnosis and treatment. Tumor-derived extracellular vesicles (TD-EVs) can be distinguished from the normal cell-derived EVs due to the presence of specific labels on their surface. TD-EVs carry specific oncogenic proteins and the nucleic acids on their surface membrane that participate in tumor progression. Moreover, the proportion of these nucleic acids and the protein greatly varies among malignant and healthy cell-derived EVs. The diagnostic potential of TD-EVs can be implied for the more precise and early-stage detection of cancer that was impossible in the past. This review examines the recent progress in prognostic, diagnostic, and therapeutic potential of the EVs derived from the tumor cells.

10.
Article in English | MEDLINE | ID: mdl-35457770

ABSTRACT

Following the detection of COVID-19 in cold chain aquatic products (CCAP) at Xinfadi Produce Wholesale Market in Beijing, China, in June 2020, novel coronavirus positive tests of CCAP have been reported in such markets of Dalian, Xi'an, Qingdao, Taiyuan, and other places, which has aroused the concern of Chinese consumers. The CCAP outbreak puts tremendous pressure on public health management and threatens customer well-being. This article uses the theoretical model of planned behavior (TPB) to investigate Chinese consumers' purchasing intentions of CCAP under this circumstance. A total of 783 questionnaires were administered in China with empirical analysis through a structural equation model. The results show that attitudes (ATT) towards the safety of CCAP and subjective norms (SN) have significant positive effects on customers' purchasing behavior intention (BI); the emotional response to the health concern (EM) of CCAP has a significant positive impact on SN, ATT, and BI; and BI of CCAP is significantly affected by individual characteristics. The BI of CCAP for those married consumers living in cities and towns with a low monthly consumption frequency is more likely to be affected by the new coronavirus epidemic events. This paper is one of the first studies that contribute to the literature by exploring the influencing factors of the consumption behavior intention over the COVID-19 pandemic in China from a public health perspective. The findings provide significant implications for cold chain operators, market managers, and policymakers to develop guidelines and offer a framework to initiate and support the produce market and boost consumer health confidence in CCAP at the practitioner level.


Subject(s)
COVID-19 , Intention , COVID-19/epidemiology , China/epidemiology , Consumer Behavior , Humans , Pandemics , Refrigeration , Surveys and Questionnaires
11.
Genet Res (Camb) ; 2022: 1168703, 2022.
Article in English | MEDLINE | ID: mdl-35136380

ABSTRACT

Epilepsy affects millions of people worldwide. Although antiepileptic drugs work for the majority of epileptic patients, these drugs do not work for some of the patients, subjecting them to drug-resistant epilepsy (DRE). Voltage-gated sodium channels act as targets for a number of antiepileptic drugs, and the genes encoding these channels can play a crucial role in developing drug-resistant epilepsy. This case-control (100 control: 101patients) study evaluated the association of sodium channel genes SCN1A and SCN2A with drug-resistant epilepsy. The cases were further accounted in two categories, drug-resistant and drug-responsive epileptic patients. The polymorphic sites rs794726754, rs1057518252, rs121918809, rs12191792, rs121917932, c.730 G > T, c.735 G > T, c.736 A > T, rs10167228, and rs2298771 of the SCN1A gene and rs17183814 of SCN2A gene were selected for mutational analysis. The DNA was isolated, amplified by PCR, and then, was run through 1% agarose gel. The sequencing was performed, and the sequences were observed through BioEdit software for any change in DNA sequence. In our study, no polymorphism was observed in the studied SNPs except for rs2298771. For rs2298771, a significant difference existed in the distribution of genotypic and allelic frequencies (p < 0.01) among the case and control group. Furthermore, the genotypic and allelic frequencies of the two categories of cases (drug responder drug resistant) were calculated. The genotypic and allelic frequencies of drug-responsive and drug-resistant epileptic patients did not differ significantly (p > 0.01). Our study indicated that the rs2298771 polymorphism of SCN1A may not be associated with chance of developing DRE in the Pakistani population.


Subject(s)
Epilepsy , NAV1.1 Voltage-Gated Sodium Channel , Anticonvulsants/therapeutic use , Child , Epilepsy/genetics , Humans , NAV1.1 Voltage-Gated Sodium Channel/genetics , Pakistan , Polymorphism, Single Nucleotide/genetics
12.
Genet Res (Camb) ; 2022: 1451007, 2022.
Article in English | MEDLINE | ID: mdl-35136381

ABSTRACT

Epilepsy is a major global issue. Epilepsy patients are treated with AED (antiepileptic drugs). Interindividual variability in drug response has been documented in several studies. The resistance to drug response may be attributed to genetic polymorphism. The current study was undertaken to investigate the CYP2C9 gene polymorphism associated with antiepileptic drug (AED) resistance in the Pakistani population. The current study included 337 individuals including 100 control subjects, 110 drug-resistant subjects, and 127 drug responders. Genomic DNA was isolated from blood, and amplification of rs1799853 (430C > T) and rs1057910 was carried out by polymerase chain reaction. Genotypes of CYP2C9 SNPs were determined by Sanger's sequencing. Astounding results were observed in the current study that none of the well-known reported SNPs of CYP2C9 was found in our Pakistani cohorts. However, a novel missense variant (c.374G > A) was found only in drug-resistant patients of the current study. According to the in silico analysis performed by PolyPhen-2, it was observed that this nonsynonymous substitution is likely to be pathogenic. The results of our study demonstrated that rs1799853 and rs1057910 may be involved in drug resistance in the Pakistani population. However, some other variants on CYP2C9 may play a critical role in AED resistance that needs to be explored.


Subject(s)
Epilepsy , Pharmaceutical Preparations , Cytochrome P-450 CYP2C9/genetics , Epilepsy/drug therapy , Epilepsy/genetics , Genotype , Humans , Pakistan , Polymorphism, Single Nucleotide/genetics
13.
Seizure ; 93: 88-94, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34740144

ABSTRACT

The GABA receptor is an important epilepsy-associated candidate gene, and has always been a focus in etiology and in the treatment of epilepsy. This study explores the genetic association between GABA receptor gene polymorphisms and epilepsy in a cohort of the Pakistani population. A case-control study was conducted on 150 patients with idiopathic generalized epilepsy (IGE) and 150 controls. Blood samples were collected, and genomic DNA was extracted and amplified using polymerase chain reaction (PCR). The amplified products were subsequently genotyped by Sanger sequencing and the results were analyzed using the chi-square test. Among the five mutational sites observed, two GABRA1 (rs2279020 and novel c.1016_1017insT) and two GABRA6 (rs3219151 and novel c.1344C>G) were found to be significantly associated with IGE. Amino acid alignment showed that a novel insertion mutation, c.1016_1017insT, in GABRA1 disrupted the reading frame and was possibly damaging, whereas c.1344C>G in GABRA6 was responsible for a synonymous mutation. Therefore, both the GABA receptor genes may play critical roles in the development of epilepsy in Pakistani patients.


Subject(s)
Epilepsy, Generalized , Receptors, GABA-A , Case-Control Studies , Epilepsy, Generalized/genetics , Humans , Mutation , Receptors, GABA-A/genetics
14.
Epilepsy Res ; 178: 106814, 2021 12.
Article in English | MEDLINE | ID: mdl-34844091

ABSTRACT

Despite the best possible medication and treatment protocols, one-third of epilepsy patients have drug resistance which is associated with an elevated risk of mortality and debilitating psychological consequences. P-glycogen encoded by ABCB1 is major drug transporter for a wide variety of AED. To evaluate the complex haplotypic association, genetic and allelic frequency distribution of rs1128503, rs1045642, and rs2032582 polymorphisms of ABCB1 gene with drug resistance in Pakistani pediatric epilepsy patients, we performed this study. A total of 337 individuals including 100 healthy control, 110 drug-resistant patients, and 127 drug-responsive patients were enrolled and genotyped for three polymorphisms. PCR and direct sequencing of DNA were done for genotyping. All the studied SNPs showed a statistically significant association with drug-resistant epilepsy at p < 0.01. In addition, we identified a novel variant at c 0.2678C > A (SCV001712095) position. The haplotype analysis indicated strong linkage disequilibrium between three SNPs. The in-silico analysis indicated that rs2032582 polymorphism at c 0.2677T > A is benign while c 0.2677T > G and c 0.2678C > A are possibly damaging. Our findings showed that pharmacogenetic variants play a key role in disease. Our findings shed light on the pharmacogenomic association of ABCB1 with epilepsy which might facilitate study on pharmacokinetics concerning ethnology.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B , Anticonvulsants , Epilepsy , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Anticonvulsants/pharmacology , Child , Drug Resistance/genetics , Epilepsy/drug therapy , Epilepsy/genetics , Genotype , Humans , Pakistan , Polymorphism, Single Nucleotide
15.
Saudi J Biol Sci ; 28(9): 4845-4851, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34466057

ABSTRACT

BACKGROUND: Acute myeloid leukemia (AML) is a bone marrow malignancy having multiple molecular pathways driving its progress. In recent years, the main causes of AML considered all over the world are genetic variations in cancerous cells. The RUNX1 and FLT3 genes are necessary for the normal hematopoiesis and differentiation process of hematopoietic stem cells into mature blood cells, therefore they are the most common targets for point mutations resulting in AML. METHODS: We screened 32 CN-AML patients for FLT3-ITD (by Allele-specific PCR) and RUNX1 mutations (by Sanger sequencing). The FLT3 mRNA expression was assessed in all AML patients and its subgroups. RESULTS: Eight patients (25%) carried RUNX1 mutation (K83E) while three patients (9.37%) were found to have internal tandem duplications in FLT3 gene. The RUNX1 mutation data were correlated with clinical parameters and FLT3 gene expression profile. The RUNX1 mutations were observed to be significantly prevalent in older males. Moreover, RUNX1 and FLT3-mutated patients had lower complete remission rate, event-free survival rate, and lower overall survival rate than patients with wild-type RUNX1 and FLT3 gene. The RUNX1 and FLT3 mutant patients with up-regulated FLT3 gene expression showed even worse prognosis. Bradford Assay showed that protein concentration was down-regulated in RUNX1 and FLT3 mutants in comparison to RUNX1 and FLT3 wild-type groups. CONCLUSION: This study constitutes the first report from Pakistan reporting significant molecular mutation analysis of RUNX1 and FLT3 genes including FLT3 expression evaluation with follow-up. This provides an insight that aforementioned mutations are markers of poor prognosis but the study with a large AML cohort will be useful to further investigate their role in disease biology of AML.

16.
J Dent Educ ; 85(11): 1749-1755, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34319606

ABSTRACT

INTRODUCTION: Dental undergraduate students encounter anxiety in their professional years of study, the impact of which is reflected on their overall performance. Various coping techniques are advocated that help individuals to deal effectively with the adverse effects of anxiety. OBJECTIVE/AIMS: The objectives of this study were to determine the level of anxiety encountered by dental undergraduate students during clinical rotations, the clinical procedures precipitating it and the number of different coping strategies (problem solving, social seeking support, and avoidance) used by students for anxiety management. METHODS: A descriptive, questionnaire-based, cross-sectional study was conducted on the third and fourth-year undergraduate dental students from six colleges of Islamabad and Rawalpindi. A total of 353 students were included in the study, and their participation in the study was anonymous and voluntary. The administered questionnaire consisted of three parts: Part 1: Moss and McManus Scale (MMM) for anxiety-provoking situations; part 2: Hamilton Anxiety Rating Scale (HAM-A) for the level of anxiety, and Part 3: Coping Strategy Indicator Scale (CSI scale) to determine the frequency of coping strategies used by students. The data were collected and analyzed using SPSS version 22.0. RESULTS: A majority of participants (96.3%) felt mild to moderate levels of anxiety in the clinical settings. Students felt more anxious about getting infected by the patient (62%), extracting the wrong tooth (46.5%), and getting a wrong diagnosis (43.1%). A significant number of participants (47%) used problem-solving mechanisms to overcome their anxiety. CONCLUSION: Mild to moderate levels of clinical anxiety prevailed in most dental undergraduate students. The top clinical situations precipitating anxiety were getting infected by patients and extracting the wrong tooth. Measures should be taken to encourage a vigorous, confidence-enhancing environment for students. This will reduce their levels of clinical anxiety along with training and foster healthy coping strategies to deal with unavoidable anxiety.


Subject(s)
Adaptation, Psychological , Anxiety , Anxiety Disorders , Cross-Sectional Studies , Humans , Students
17.
Biomed Res Int ; 2021: 7509825, 2021.
Article in English | MEDLINE | ID: mdl-33969125

ABSTRACT

Juvenile myoclonic epilepsy (JME) is the most prevalent and genetically heterogeneous form of epilepsy and accounts for 10-30% of all the cases worldwide. Ef-hand domain- (c-terminal-) containing protein 1 (EFHC1) encodes for a nonion channel protein and mutations in this gene have been extensively reported in different populations to play a causative role in JME. Linkage between JME and 6p11-12 locus has already been confirmed in Mexican and Dutch families. A case-control study was conducted on Pakistani JME patients for the first time, aimed at finding out EFHC1 mutations that have been reported in different populations. For this purpose, 66 clinically diagnosed JME patients and 108 control subjects were included in the study. Blood samples were collected from all the participants, and DNA was isolated from the lymphocytes by the modified organic method. Total 3 exons of EFHC1, harboring extensively reported mutations, were selected for genotypic analysis. We identified three heterozygous variants, R159W, V460A, P436P, and one insertion in the current study. V460A, an uncommon variant identified herein, has recently been reported in public databases in an unphenotyped American individual. This missense variant was found in 3 Pakistani JME patients from 2 unrelated families. However, in silico analysis showed that V460A may possibly be a neutral variant. While the absence of a majority of previously reported mutations in our population suggests that most of the mutations of EFHC1 are confined to particular ethnicities and are not evenly distributed across the world. However, to imply the causation, the whole gene and larger number of JME patients should be screened in this understudied population.


Subject(s)
Calcium-Binding Proteins/genetics , Myoclonic Epilepsy, Juvenile/genetics , Adolescent , Base Sequence , DNA Mutational Analysis , Exons/genetics , Female , Humans , Male , Mutation/genetics , Pakistan
18.
Immunobiology ; 226(1): 152045, 2021 01.
Article in English | MEDLINE | ID: mdl-33387966

ABSTRACT

Rheumatoid Arthritis (RA) is an autoimmune disorder where multiple cytokines including IL-17A and IL-17F produced by T helper cell 17 (Th17), contribute to its pathogenesis. By initiating inflammatory responses in joints Th17 act as pathogenic driver leading to bone and cartilage destruction in RA patients. Hence, the planned study was aimed to estimate IL-17 gene polymorphism association with RA susceptibility in Pakistani population. The present study included 100 subjects (50 RA patients and 50 healthy controls). Blood samples were taken and DNA was isolated for genotyping purpose. Chi square and Logistic regression analysis was performed to check the association of selected SNPs with RA. For rs2397084 and rs763780 polymorphism T allele acted as significant risk factor as compared to the reference C allele. TT vs. CC comparison in rs2397084 showed that T allele is a risk factor (OR 5.538; 95%Cl 1.757-17.458) in RA susceptibility. In case of rs763780 heterozygous CT (OR 10.80; 95% Cl 3.736-31.218) and homozygous mutant TT (OR 7.50; 95% Cl 2.360-23.831) genotypes proved to be a potential risk for RA patients. The significant differences in allelic and genotypic frequencies were observed for both SNPs. While for rs2275913 significantly varied frequency was observed only for dominant model of inheritance and non significant differences were seen at allelic level. Variation at all these three polymorphic sites substituted mutant amino acids leading to further functional changes in protein structure. Three polymorphic sites rs2275913, rs763780 and rs2397084 positioned on IL-17 gene were significantly strong factors in RA incidence among Pakistani population as they alter normal function of inflammatory cytokine IL-17.


Subject(s)
Arthritis, Rheumatoid/immunology , Genotype , Interleukin-17/genetics , Adult , Arthritis, Rheumatoid/epidemiology , Arthritis, Rheumatoid/genetics , Case-Control Studies , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Incidence , Male , Middle Aged , Pakistan/epidemiology , Polymorphism, Single Nucleotide , Protein Conformation , Risk , Structure-Activity Relationship
19.
Epilepsy Behav ; 112: 107476, 2020 11.
Article in English | MEDLINE | ID: mdl-33181895

ABSTRACT

The current pandemic of coronavirus disease 2019 (COVID-19) that led to an unprecedented crisis with significant health, social, and economic repercussions presented more serious concerns for those living with some chronic conditions such as epilepsy. This study was aimed to find out impact of the COVID-19 pandemic on management of epilepsy. A cross-sectional study was conducted through telephone interviews, targeting 213 caregivers of pediatric patients with epilepsy, belonging to underserved areas of Faisalabad, Punjab, Pakistan. A simple questionnaire was designed to record the responses of participants relevant to the direct and indirect effects of COVID-19 pandemic and their knowledge about possible ways that can be accessed for the management of epilepsy during an ongoing pandemic. The current study, which holds 77% of the respondents from rural areas and 23% from urban settings, showed that partial measures of lockdown taken to stop or slow the spread of COVID-19 resulted in adverse economic and health outcomes in the said population including cancelation of follow-up visits, worsening of seizures, job loss, burden of antiepileptic drugs (AEDs) costs, and discontinuation of medicines. Furthermore, knowledge about alternative ways to access health facilities was found very poor among caregivers. Income sources of poor people disrupted by lockdown can lead to unintentional nonadherence to medication, which is a clear picture of inequitable distribution of resources. This study highlights the major issues faced by the caregivers during this ongoing pandemic of COVID-19.


Subject(s)
Anticonvulsants , Coronavirus Infections/prevention & control , Coronavirus , Epilepsy/drug therapy , Health Services Accessibility , Pneumonia, Viral/prevention & control , Quarantine/psychology , Social Isolation , Anticonvulsants/economics , Anticonvulsants/supply & distribution , Anticonvulsants/therapeutic use , Betacoronavirus , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/psychology , Cross-Sectional Studies , Epilepsy/epidemiology , Female , Health Resources , Humans , Longitudinal Studies , Male , Medication Adherence , Pakistan , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/psychology , SARS-CoV-2 , Seizures/epidemiology , Surveys and Questionnaires , Telemedicine , Vulnerable Populations
20.
Soc Work Public Health ; 35(7): 569-578, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32970548

ABSTRACT

Awareness and comprehension of disease origin, transmission, and control in a health crisis are mainly affected by the knowledge, attitude, and practices (KAP) of the general public. We conducted the current study to assess KAP among the general population of Jammu and Kashmir (J&K), India, based on an online cross-sectional survey. Participants completed a questionnaire we developed consisting of KAP questions. We also collected sociodemographic information and source of information about disease awareness. The main source of information regarding COVID-19 was Internet social media (66.3%) followed by TV (17.4%). We conducted nonparametric analyses on KAP scores using a Mann-Whitney U and Kruskall-Wallis H tests (P < .05) to find out the association with sociodemographic characteristics. The overall knowledge score (correct answer) was 88.9%, which was significantly associated with gender, age, qualification, and occupation. The positive attitude score was 73.3%, which was significantly associated with gender, age, qualification, marital status, and geographic area. Overall, 93.0% positive practices were observed in the general population based on asked questions. These scores were significantly associated with gender, age, qualification, marital status, area, and occupation. On the basis of the Spearmen correlation test (P < .01), a significant correlation was observed between scores of knowledge and attitude, with rs = +0.28, P = .000, knowledge and practices scores as rs = +0.24, P = .000, and attitude and practices scores as rs = +0.24, P = .000. However, due to the limited sample presentation in the survey, the study is unable to generalize to lower socioeconomic communities.


Subject(s)
Coronavirus Infections/prevention & control , Health Knowledge, Attitudes, Practice , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Adolescent , Adult , Awareness , Betacoronavirus , COVID-19 , Coronavirus Infections/epidemiology , Cross-Sectional Studies , Female , Humans , India/epidemiology , Male , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Surveys and Questionnaires
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