Contribution of GJB2 gene mutations to hearing loss in Pakistani population – A Narrative Review

Pakistan has a unique population for the study of recessive genetic diseases due to a higher consanguinity rate. Hearing impairment is the loss of hearing normal sounds, and it is a common sensory disorder that affects more than 466 million people worldwide. Immuno-genetic and other environmental factors like loud noises, drug usage, and viral infections are the causes of hearing loss. Hearing loss is categorized into a syndromic hearing loss (70%) and non-syndromic hearing loss (30%). GJB2 mutations are one of the main causes of hearing loss in different populations, including Pakistan. The GJB2 gene encodes a gap junction protein involved in the homeostasis of the inner ear through the recycling of potassium ions. The prevalence of GJB2 mutation in the Pakistani population varies from 6.1 to 9.2%. The most common mutations found in the Pakistani population are 71G>A (p.(Trp24*), 231G > A (p. Trp77*), c.35delG (p. Gly11Leufs24*),c.355G>T (p. Glu119*) 457G > A (p.Val153Ile), 598G > A (p.Gly200Arg), 439G > A (p.Glu147Lys), c.377_378insATGCGGA (p.Arg127Cysfs*85). c.1055C>T (p. Pro352Leu), c.6202A>C p.(Thr2068Pro), c.2496_2496delC p.(Tyr832*) and c.355G>T p.(Glu119*).Keywords: Gap junction protein, GJB2 mutations, Hearing loss

Variations in genomic epidemiology and in-silico screening of potential phytochemicals to cure Monkeypox

Monkeypox virus (MPXV) is passed on when people encounter infectious animals. Before April 2022, the Monkeypox virus was reported only in South Africa and its surrounding region but now it has been spread all over the world. This Monkeypox virus consumes an incubation period of five to twenty-one days and can be communicated through direct contact, breathing, contaminated towels, bedding, and so on. The Orthopoxvirus variety is a subfamily of the Poxviridae family that incorporates the Monkeypox infection. Their unique property is to suppress the host defense system and to exploit host immunity. Treatment of Monkeypox involves two vaccines named JYNNEOSTM and ACAM2000. Antiviral medications can be considered for serious diseases, immunocompromised patients, pediatrics, pregnant and lactating ladies, complex sores, and when injuries happen close to the mouth, eyes, and privates. This review article gives a basic information ofA48R, a thymidine kinase, which is involved in DNA replication pathways in the Monkeypox virus. The potential drugs for A48R inhibition like NMCT and rutaecarpine are considered good synthetic drugs. The maximum affinity -18 was shown by phytochemical dictamnine, amentoflavone -7.5, citral -7.8, and naringin – 6.6 which can be isolated from different plants.  The purpose of this review article is to describe variations in genomic epidemiology and in-silico screening of potential phytochemicals to cure Monkeypox.Keywords: Monkeypox virus; Orthopoxvirus; Poxviridae; A48R; Phytochemicals

Physcion and Physcion 8-O-β-D-glucopyranoside: Natural Anthraquinones with Potential Anti-cancer Activities.

Nature has provided prodigious reservoirs of pharmacologically active compounds for drug development since times. Physcion and physcion 8-O-β-D-glucopyranoside (PG) are bioactive natural anthraquinones which exert anti-inflammatory and anti-cancer properties with minimum or no adverse effects. Moreover, physcion also exhibits anti-microbial and hepatoprotective properties while PG is known to have anti-sepsis as well as ameliorative activities against dementia. This review aims to highlight the natural sources and anti-cancer activities of physcion and PG along with asso-ciated mechanisms of actions. On the basis of the literature, physcion and PG regulate multitudinous cell signaling path-ways through the modulation of various regulators of cell cycle, protein kinases, microRNAs, transcriptional factors, and apoptosis linked proteins resulting in the effective killing of cancerous cells in vitro as well as in vivo. Both compounds effectively suppress metastasis, furthermore, physcion acts as inhibitor of 6PGD and also play an important role in chemosensitization. This review article suggests that physcion and PG are potent anti-cancer drug candidates but further investigations on their mechanism of action and pre-clinical trials are mandatory in order to comprehend the full potential of these natural cancer killers in anti-cancer remedies

Risk Factors Associated with Very Low Birth Weight: A Systematic Review and Meta-Analysis

Background: Very Low Birth Weight (VLBW) is due to multiple gestations and reproductive-assisted techniques. Neonatal complications mainly arise in infants with VLBW and Extremely Low Birth Weight (ELBW). The main objective was to study the risk factors associated with VLBW and to conduct a meta-analysis. Methods: A meta-analysis was done to present the most recent risk variables for VLBW. Electronic databases were searched for information on the suggested topic. Using STATA version 14, the relevant data was extracted, and statistical analysis was conducted. Results: A total number of 112 studies have been conducted on the topic of VLBW worldwide from 2000 to 2020. Information from many parts of the world was evaluated in which GDP or per capita income, age, and education were followed in prominent regions of the world. As GDP and education level improved, the nutritional status also improved. Fifteen studies have been identified, with five meeting the inclusion criteria for the metanalysis of VLBW <1500g in developing countries. Illiteracy, poverty, mother occupation, hypocalcemia, and hypoglycemia were the common risk factors of VLBW (<0.05). Conclusion: It was identified that per-capita GDP is inversely proportional to VLBW throughout the world. VLBW in America was found to be significant when compared with central Europe (<0.005), similarly with Southern Europe (<0.03), Northern Europe (<0.00001), Asia (<0.0001), and Africa (<0.0001). Unlike per capita GDP, VLBW was insignificantly related to maternal age in all regions except Africa, where VLBW was significantly associated with maternal age (p<0.0001). In developing countries, illiteracy, poverty, mother occupation, hypocalcemia, and hypoglycemia are the common risk factors for VLBW (<0.05) as the complications related to VLBW are at a high-risk rate, so it is recommended that VLBW babies require special care at the time of birth, especially in poor economic countries

Rheumatoid Arthritis and the Role of VEGF Gene: An Overview

Purpose: The aim of this review study is to outline rheumatoid arthritis and VEGF participation in rheumatoid arthritis disease development and also to help future researchers in this field. Study Design: A Review Study. Subjects and Methods: A number of research articles were systematically reviewed. More sixty research studies related to rheumatoid arthritis and the role of VEGF Gene were examined. The results of these studies are highlighted and compared.  Results: Rheumatoid Arthritis is capable of causing joint damage, moreover, lead to long term disability in severe cases. Mutation in VEGF due to the involvement of multiple factors (environmental, genetic factors etc) lead to severity in RA patients as it has a role in certain inflammatory processes, angiogenesis etc. Further research needs to be done in this field because many of the factors involve in pathogenesis of RA such as factors that cause loss of tolerance and inflammation in joints, are still unclear. Conclusion: Although old diagnostic techniques are optimized, we further need to improve the diagnostic and treatment techniques in order to diagnose the patients at early stage. This will pacify patients’ disease severity and provide certain preventive measure that will assist in preventing the aggravation of disease in family members

Distribution of Human Leukocyte Antigen alleles in Systemic Lupus Erythematosus patients with Angiotensin Converting Enzyme Insertion/Deletion Polymorphism

Systemic Lupus Erythematosus is one of the classic examples of autoimmune diseases among human beings and is a rare disease in Pakistani population. Clinically it is a quite diverse and complicated autoimmune disease in a sense that it involves multiple organs of the body and mimics with other diseases as well. This study focused on the distribution of HLA alleles in SLE patients with ACE I/D Polymorphism. A total of 122 individuals were enrolled in this study, 61 were the SLE patients who fulfilled revised ACR criteria and 61 were the healthy controls. Mean age of SLE patients at diagnosis was 30.35 ± 1.687 years (12-68 years). ACE gene I/D polymorphism was performed by nested PCR and DNA based HLA typing technique was used. ACE gene I/D polymorphism of Intron16 was studied and found to be involved in the activity of SLE. There is high frequency of HLA-A*01, HLA-B*40, HLA-DRB1*01 alleles in SLE patients with ACE DD genotype. The distribution of HLA-A, -B, -DRB1 alleles was analyzed in SLE patients with various disease phenotypes. HLA-A*01 and HLA-B*40 was the most common allele found in SLE patients with the involvement of skin. HLA-A*01, -A*03, HLA-B*13 and -B*46 were common in SLE patients with arthritis while HLA-A*26 and -A*69 were commonly found in Lupus nephritis cases. SLE patients involving both skin and kidney had an allele HLA-DRB1*01 common in them

NH Serological and Molecular Based Diagnosis of Toxoplasma gondii in Galliformes by using ToxPK1 gene

Purpose: The zoonosis caused by Toxoplasmagondii is known to be the third worldwide parasitic infectious disease. The living life, including human, chickens, cows and goats are at high risk because of its bulky circulation in the universe. The study was conducted to diagnoseT. gondii in Galliformes. The main objective of this study was to compare VetLine Toxoplasma with ToxPK1 gene as a marker for the detection of T. gondii. Study Design: An Experimental study. Subjects and Methods: The study subjects involved were 35 broilers in which 80% were females and 20% were males. Results: It was displayed that the female broilers have a little high rate of prevalence (29.63%) as compared to male broilers (25%). Conclusion: It was concluded that VetLine Toxoplasma in which protein A/G fixes to all IgGs subclasses from various mammalian species and the use of ToxPK1 gene as a molecular marker for the detection of T. gondiiwere100% matched. To eradicate and control this neglected zoonosis, there is an urgency need for risk factors control mechanisms; secondly specific, rapid and inexpensive diagnostic and treatment approaches

Risk Factors Associated with Very Low Birth Weight: A Systematic Review and Meta-Analysis

Background: Very Low Birth Weight (VLBW) is due to multiple gestations and reproductive-assisted techniques. Neonatal complications mainly arise in infants with VLBW and Extremely Low Birth Weight (ELBW). The main objective was to study the risk factors associated with VLBW and to conduct a meta-analysis. Methods: A meta-analysis was done to present the most recent risk variables for VLBW. Electronic databases were searched for information on the suggested topic. Using STATA version 14, the relevant data was extracted, and statistical analysis was conducted. Results: A total number of 112 studies have been conducted on the topic of VLBW worldwide from 2000 to 2020. Information from many parts of the world was evaluated in which GDP or per capita income, age, and education were followed in prominent regions of the world. As GDP and education level improved, the nutritional status also improved. Fifteen studies have been identified, with five meeting the inclusion criteria for the metanalysis of VLBW <1500g in developing countries. Illiteracy, poverty, mother occupation, hypocalcemia, and hypoglycemia were the common risk factors of VLBW (<0.05). Conclusion: It was identified that per-capita GDP is inversely proportional to VLBW throughout the world. VLBW in America was found to be significant when compared with central Europe (<0.005), similarly with Southern Europe (<0.03), Northern Europe (<0.00001), Asia (<0.0001), and Africa (<0.0001). Unlike per capita GDP, VLBW was insignificantly related to maternal age in all regions except Africa, where VLBW was significantly associated with maternal age (p<0.0001). In developing countries, illiteracy, poverty, mother occupation, hypocalcemia, and hypoglycemia are the common risk factors for VLBW (<0.05) as the complications related to VLBW are at a high-risk rate, so it is recommended that VLBW babies require special care at the time of birth, especially in poor economic countries

Rheumatoid Arthritis and the Role of VEGF Gene: an Overview

Purpose: The aim of this review study is to outline rheumatoid arthritis and VEGF participation in rheumatoid arthritis disease development and also to help future researchers in this field. Study Design: A Review Study. Subjects and Methods: A number of research articles were systematically reviewed. More sixty research studies related to rheumatoid arthritis and the role of VEGF Gene were examined. The results of these studies are highlighted and compared. Results: Rheumatoid Arthritis is capable of causing joint damage, moreover, lead to long term disability in severe cases. Mutation in VEGF due to the involvement of multiple factors (environmental, genetic factors etc) lead to severity in RA patients as it has a role in certain inflammatory processes, angiogenesis etc. Further research needs to be done in this field because many of the factors involve in pathogenesis of RA such as factors that cause loss of tolerance and inflammation in joints, are still unclear. Conclusion: Although old diagnostic techniques are optimized, we further need to improve the diagnostic and treatment techniques in order to diagnose the patients at early stage. This will pacify patients' disease severity and provide certain preventive measure that will assist in preventing the aggravation of disease in family members

Elucidating the role of diet in maintaining gut health to reduce the risk of obesity, cardiovascular and other age-related inflammatory diseases: recent challenges and future recommendations

ABSTRACTA healthy balanced diet is crucial in protecting the immune system against infections and diseases. Poor diets, such as the Western diet, contribute to the development of metabolic diseases, hypertension, and obesity. Microbiota, primarily composed of different microorganisms and residing in the gastrointestinal tract (GIT), also play a significant role in maintaining gut health. Polyphenols and probiotics found in fruits, vegetables, whole grains, legumes, nuts, and seeds promote gut health and support the growth of beneficial bacteria. Different types of diets, their categories, and their impact on health are also mentioned. The relationship between diet, gut health, and the risk of developing obesity, cardiovascular diseases, and inflammatory diseases is discussed in this review article. The rationale behind the review concludes future recommendations for maintaining gut health and reducing the occurrence of obesity, cardiometabolic diseases, and other inflammatory diseases. There is also the need for standardized research methods, long-term studies, and translating scientific knowledge into practical dietary recommendations