Role of Th17 and IL-17 Cytokines on Inflammatory and Auto-immune Diseases.

BACKGROUND: The IL-17 (interleukin 17) family consists of six structurally related pro-inflammatory cytokines, namely IL-17A to IL-17F. These cytokines have garnered significant scientific interest due to their pivotal role in the pathogenesis of various diseases. Notably, a specific subset of T-cells expresses IL-17 family members, highlighting their importance in immune responses against microbial infections. INTRODUCTION: IL-17 cytokines play a critical role in host defense mechanisms by inducing cytokines and chemokines, recruiting neutrophils, modifying T-cell differentiation, and stimulating the production of antimicrobial proteins. Maintaining an appropriate balance of IL-17 is vital for overall health. However, dysregulated production of IL-17A and other members can lead to the pathogenesis of numerous inflammatory and autoimmune diseases. METHOD: This review provides a comprehensive overview of the IL-17 family and its involvement in several inflammatory and autoimmune diseases. Relevant literature and research studies were analyzed to compile the data presented in this review. RESULTS: IL-17 cytokines, particularly IL-17A, have been implicated in the development of various inflammatory and autoimmune disorders, including multiple sclerosis, Hashimoto's thyroiditis, systemic lupus erythematosus, pyoderma gangrenosum, autoimmune hepatic disorders, rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, osteoarthritis, and graft-versus-host disease. Understanding the role of IL-17 in these diseases is crucial for developing targeted therapeutic strategies. CONCLUSION: The significant involvement of IL-17 cytokines in inflammatory and autoimmune diseases underscores their potential as therapeutic targets. Current treatments utilizing antibodies against IL-17 cytokines and IL-17RA receptors have shown promise in managing these conditions. This review consolidates the understanding of IL-17 family members and their roles, providing valuable insights for the development of novel immunomodulators to effectively treat inflammatory and autoimmune diseases.

Recent advances in the biosynthesis, bioavailability, toxicology, pharmacology, and controlled release of citrus neohesperidin.

Neohesperidin (hesperetin 7-O-neohesperidoside), a well-known flavanone glycoside widely found in citrus fruits, exhibits a variety of biological activities, with potential applications ranging from food ingredients to therapeutics. The purpose of this manuscript is to provide a comprehensive overview of the chemical, biosynthesis, and pharmacokinetics profiles of neohesperidin, as well as the therapeutic effects and mechanisms of neohesperidin against potential diseases. This literature review covers a wide range of pharmacological responses elicited by Neohesperidin, including neuroprotective, anti-inflammatory, antidiabetic, antimicrobial, and anticancer activities, with a focus on the mechanisms of those pharmacological responses. Additionally, the mechanistic pathways underlying the compound's osteoporosis, antiulcer, cardioprotective, and hepatoprotective effects have been outlined. This review includes detailed illustrations of the biosynthesis, biopharmacokinetics, toxicology, and controlled release of neohesperidine. Neohesperidin demonstrated a broad range of therapeutic and biological activities in the treatment of a variety of complex disorders, including neurodegenerative, hepato-cardiac, cancer, diabetes, obesity, infectious, allergic, and inflammatory diseases. Neohesperidin is a promising therapeutic candidate for the management of various etiologically complex diseases. However, further in vivo and in vitro studies on mechanistic potential are required before clinical trials to confirm the safety, bioavailability, and toxicity profiles of neohesperidin.

Caffeoyl-CoA 3-O-methyltransferase gene family in jute: Genome-wide identification, evolutionary progression and transcript profiling under different quandaries.

Jute (Corchorus sp.), is a versatile, naturally occurring, biodegradable material that holds the promising possibility of diminishing the extensive use of plastic bags. One of the major components of the cell wall, lignin plays both positive and negative roles in fiber fineness and quality. Although it gives mechanical strength to plants, an excess amount of it is responsible for the diminution of fiber quality. Among various gene families involved in the lignin biosynthesis, Caffeoyl-CoA 3-O-methyltransferase (CCoAOMT) is the most significant and has remained mostly unexplored. In this study, an extensive in-silico characterization of the CCoAOMT gene family was carried out in two jute species (C. capsularis L. and C. olitoroius L.) by analyzing their structural, functional, molecular and evolutionary characteristics. A total of 6 CCoAOMT gene members were identified in each of the two species using published reference genomes. These two jute species showed high syntenic conservation and the identified CCoAOMT genes formed four clusters in the phylogenetic tree. Histochemical assay of lignin in both jute species could shed light on the deposition pattern in stems and how it changes in response to abiotic stresses. Furthermore, expression profiling using qPCR showed considerable alteration of CCoAOMT transcripts under various abiotic stresses and hormonal treatment. This study will lay a base for further analysis and exploration of target candidates for overexpression of gene silencing using modern biotechnological techniques to enhance the quality of this economically important fiber crop.

Comprehensive in silico Characterization of Universal Stress Proteins in Rice (Oryza sativa L.) With Insight Into Their Stress-Specific Transcriptional Modulation.

In a world where climate change is real and its consequences are unprecedented, understanding of the plant adaptive capacity and native stress-responsive machinery is crucial. In recent years, universal stress proteins (USPs) have received much attention in the field of plant science due to their stress-specific transcriptional regulation. This study focuses on the extensive characterization of the USP gene family members in the monocot crop rice (Oryza sativa L. var. japonica). Here, we report a total of 44 USP genes in the rice genome. In silico characterization of these genes showed that domain architecture played a major role in the functional diversification of the USP gene family which holds for all plant USPs. On top of that, a higher conservation of OsUSP members has been exhibited with a monocot genome (Zea mays L.) as compared to a dicot genome (Arabidopsis thaliana L.). Expression profiling of the identified genes led to the discovery of multiple OsUSP genes that showed pronounced transcript alteration under various abiotic stress conditions, indicating their potential role as multi-functional stress-specific modules. Furthermore, expression validation of OsUSP genes using qRT-PCR provided a strong evidence for the utility OsUSP genes in building multi-stress tolerant plants. Altogether, this study provides leads to suitable USP candidates that could be targeted for plant breeding and genetic engineering experiments to develop stress resilient crop species.

Role of Withaferin A and Its Derivatives in the Management of Alzheimer's Disease: Recent Trends and Future Perspectives.

Globally, Alzheimer's disease (AD) is one of the most prevalent age-related neurodegenerative disorders associated with cognitive decline and memory deficits due to beta-amyloid deposition (Aß) and tau protein hyperphosphorylation. To date, approximately 47 million people worldwide have AD. This figure will rise to an estimated 75.6 million by 2030 and 135.5 million by 2050. According to the literature, the efficacy of conventional medications for AD is statistically substantial, but clinical relevance is restricted to disease slowing rather than reversal. Withaferin A (WA) is a steroidal lactone glycowithanolides, a secondary metabolite with comprehensive biological effects. Biosynthetically, it is derived from Withania somnifera (Ashwagandha) and Acnistus breviflorus (Gallinero) through the mevalonate and non-mevalonate pathways. Mounting evidence shows that WA possesses inhibitory activities against developing a pathological marker of Alzheimer's diseases. Several cellular and animal models' particulates to AD have been conducted to assess the underlying protective effect of WA. In AD, the neuroprotective potential of WA is mediated by reduction of beta-amyloid plaque aggregation, tau protein accumulation, regulation of heat shock proteins, and inhibition of oxidative and inflammatory constituents. Despite the various preclinical studies on WA's therapeutic potentiality, less is known regarding its definite efficacy in humans for AD. Accordingly, the present study focuses on the biosynthesis of WA, the epidemiology and pathophysiology of AD, and finally the therapeutic potential of WA for the treatment and prevention of AD, highlighting the research and augmentation of new therapeutic approaches. Further clinical trials are necessary for evaluating the safety profile and confirming WA's neuroprotective potency against AD.

Virtual screenings of the bioactive constituents of tea, prickly chaff, catechu, lemon, black pepper, and synthetic compounds with the main protease (Mpro) and human angiotensin-converting enzyme 2 (ACE 2) of SARS-CoV-2.

BACKGROUND: COVID-19 has mutation capability, and there are no specific drug therapies that are available to fight or inhibit the proteins of this virus. The present study aims to investigate the binding affinity of the bioactive and synthetic compounds with the main protease (Mpro) enzymes and angiotensin-converting enzyme 2 (ACE 2) by computational approach. PASS prediction, pharmacokinetics, and toxicological properties prediction studies were performed through the Google PASS prediction and Swiss ADME/T website. Besides, molecular docking studies were accomplished by BIOVIA Discovery Studio 2020, UCSF Chimera, and PyRx autodock vina. RESULTS: The docking scores were inferred and the selected compounds showed results varying from -3.2 to -9.8 (kcal/mol). Theaflavin scored the highest docking score to the 5REB, 6VW1, and 1R42 enzymes and showed the binding affinity as -6.3 kcal/mol, -9.8 kcal/mol, and -8.6 kcal/mol, respectively. Again, kaempferol showed the best binding affinity to the 7BQY (-7.1 kcal/mol) and 6Y2FB (-6.6 kcal/mol) enzymes. All the chemical constituents showed better probability in action in pass prediction analysis. Besides, no ligands (except theaflavin) have any conflict with Lipinski's rules of five, which authorized the drug probability of these ligands. CONCLUSION: Therefore, the selected compounds could be considered a potential herbal treatment source against SARS-CoV-2.

Standard factors predicting success of Non-invasive ventilation are useful in treating Patients with POST Tuberculosis sequel.

OBJECTIVE: The aim was to access the effectiveness of Bilevel Positive Airway Pressure (BiPAP) in patients with type II respiratory failure secondary to Post Tuberculosis (TB) sequelae and determine the factors that can predict its success. PostTB pulmonary sequelae are complications after healing of TB and type II respiratory failure is frequently encountered in this group. . METHODS: This prospective study was carried out in the department of Chest Medicine, Jinnah Postgraduate Medical Center Karachi. (JPMC) Total 78 patients, between 20-80 years of age having hypercapnic respiratory failure, were included. Patients were given BiPAP along with standard treatment. RESULTS: Among 78 patients, 45 (56.3%) were males and 33 (43.7%) were females. Patients mean age was 50.6 } 15.76 years. The BiPAP success rate was 70.5% (55/78). There is significant difference in age (p=0.008), duration of disease (p=0.021), baseline pH (p=0.00), PaCO2 (p=0.004), Glasgow Coma Score (p=0.031), Chest X-ray (p<0.05) and systolic blood pressure (p=0.007) between responders and non-responders. Improvement in Abgs and vitals was observed among responders following 3 hours of therapy while pH drops significantly at 3 hours in non-responders. CONCLUSIONS: This study reveals that BiPAP is also efficacious method in patients with Type II respiratory failure post TB sequelae. Potential non responders can be identified relatively early in course of treatment and considered for ventilator.

Assessment and comparison of APACHE II (Acute Physiology and Chronic Health Evaluation), SOFA (Sequential Organ Failure Assessment) score and CURB 65 (Confusion; Urea; Respiratory Rate; Blood Pressure), for prediction of inpatient mortality in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

OBJECTIVE: To assess and compare the role of Acute Physiology and Chronic Health Evaluation, Sequential Organ Failure Assessment, and Confusion Urea Respiratory Rate Blood Pressure scores in predicting inpatient mortality for patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.. DESIGN: The retrospective study was conducted at the Jinnah Post-graduate Medical Centre, Karachi, and comprised data of all consecutive Acute Exacerbation of Chronic Obstructive Pulmonary Disease patients from December 1, 2013, to December 31, 2014. Logistic regression model and non-parametric tests were employed using SPSS 22.. RESULTS: There were 95 patients whose medical records were studied. The overall mean age was 60.79±12.39 years. Mortality rate was of 26(27.6%). Median hospital stay was 11.5 days (interquartile range: 9-17 days) in survivors and 4 days (2-8 days) in non-survivors. Out of the three scales used, Confusion Urea Respiratory Rate Blood Pressure-65 score showed the greatest difference between survivors and non-survivors (p <0.05). Significant higher scores were observed in non survivors with Type 2 than Type 1 respiratory failure (p<0.05). There was significant association of mortality with baseline partial pressure of oxygen and oxygen saturation (p<0.05 each). CONCLUSIONS: Confusion Urea Respiratory Rate Blood Pressure-65score determined at the time of admission had significant ability to predict inpatient mortality..

Knowledge of female doctors about smoking risks and their attitude toward cessation in antenatal clinics - perspective from tertiary care hospitals in Karachi.

OBJECTIVE: To assess the knowledge and attitude of doctors with regard to smoking risks and cessation, and to identify factors associated with self- reported assessment of smoking. METHODS: This cross-sectional survey was performed in 5 hospitals of Karachi from February to April 2014, and comprised doctors providing antenatal care. Data was collected using a questionnaire. SPSS 21 was used for data analysis. RESULTS: Of the 164 respondents,150(91.5%) considered the assessment of smoking an integral part of their medical responsibilities, but only 53(32.4%) reported that they asked regarding smoking habit in 100% of patients and 77(47.3%) inquired about passive smoking. The mean knowledge score for risks and cessation was 2.57±0.278 and 2.12±0.457, respectively. A few misconceptions were also found, such as 94(57.3%) doctors were against the use of nicotine replacement therapy in pregnant females and 114(69.4%) falsely believed that smoking was associated with pre-eclampsia. Factors independently associated with good baseline knowledge were: formal training (p=0.01) and hospital's smoke-free policy (p=0.004). Doctors with formal training more frequently assessed smoking habit of their patients and were more confident while counselling patients for smoking cessation (p=0.05). CONCLUSIONS: Basic misconceptions showed inadequate knowledge among doctors working in antenatal clinics.

Management of community acquired pneumonia by Family Physicians.

BACKGROUND AND OBJECTIVE: Community Acquired Pneumonia (CAP)is a major burden on health systemwith significant mortality and morbidity. Family Physicians(FPs)can play important role. To determine management strategies and prescription of FPs regarding CAP. METHODS: A multicenter cross sectional survey was done in 10 cities of Pakistan from November 2014 to January 2015. Self-administered questionnaire was filled by 110 Family Physicians. RESULTS: Of total 71% of FPs reported to work in high prevalence areas for respiratory ailments. Only 32% of FPs used PSI and 34% CURB 65 for assessment of severity. It was alarming to note that only 58% of FPs treats severe pneumonia with Intravenous antibiotics while rests were comfortable with oral route. The overall use of quinolones to treat CAP, irrespective of severity, in combination or as single agent was > 60%. Duration of antibiotics for severe pneumonia was sub optimal (<10 days). Only 52.8% patients came back for follow-up so true outcome cannot be anticipated. CONCLUSION: Major deficiencies were treatment of severe pneumonia in community, inappropriate use of quinolones and poor knowledge of recent guidelines. This can lead to emergence of resistant bacteria and high mortality and morbidity. List of Abbreviations: FPs: Family Physicians, CAP: Community Acquired Pneumonia.

Primary Pleural Epitheliod Hemangioendothelioma with Lung Involvement.

The authors report a case of 50-year man who presented with 2-year history of dry cough, right sided chest pain, and shortness of breath. Chest X-ray revealed right-sided pleural effusion and left-sided opacity. Pleuroscopic pleural biopsy confirmed the diagnosis of primary pleural epitheliod hemangioendothelioma (EHE) with peripheral lung parenchymal invasion. Chest drain was inserted; and significant amount of fluid was drained, but lung failed to expand after 72 hours. Patient was planned for video assisted thoracoscopy (VATS) and also discussed with oncology department for chemotherapy; but he refused any further treatment, and left home against medical advice with chest drain in place. EHE originating from pleura is extremely rare with an aggressive clinical course and poor prognosis. To our knowledge, this is the first reported case of an EHE originating from pleura in South Asia and highlights the heterogeneous geographic distribution of tumor and demonstrates the need for a more systemic approach to all patients with unilateral pleural effusion.

Comparison of end tidal carbon monoxide (eCO) levels in shisha (water pipe) and cigarette smokers.

BACKGROUND: Measuring eCo is rapid, non-invasive and inexpensive tool and correlate correctly with carboxyhemoglobin levels in blood. The aim of this study was to evaluate and compare the increase in end tidal carbon monoxide (eCO) levels in exhaled breath of passive smokers and healthy smokers after cigarette and shisha smoking. FINDINGS: In a cross sectional study eCO levels were measured in 70 subjects (24 cigarette smokers, 20 shisha smoker, 26 passive smokers) by use of portable device. Smokers were asked to smoke shisha for 30 mins in shisha cafe or to smoke 5 cigarettes in 30 mins in a restaurant. eCo levels were measured at baseline (30 mins), 35 mins, 60 mins and 90 mins in all groups after entry to the venue. The baseline mean eCO level among cigarette smokers was 3.5 +/- 0.6 ppm (part per million), passive cigarette smokers 3.7+/-1.0 ppm, shisha smokers 27.7+/-4.9 ppm and passive shisha smokers 18.3+/-8.4 ppm .The mean increase in eCO after 90 min among smokers was 9.4+/-4.6 (p < 0.005), passive cigarette smokers 3.5+/-2.5 (p < 0.05), shisha smokers 57.9+/-27.4 (p <0.005) and passive shisha smokers 13.3+/-4.6 (p = 0.03). CONCLUSION: Exposure to shisha smoke is a cause of elevated eCO in smokers and passive smokers and due to in-door pollution, sitting in shisha bar causes significant increase in eCO levels.

Gender based response to fluoxetine hydrochloride medication in endogenous depression.

OBJECTIVE: To determine the gender based response to fluoxetine HCl medication in relation to tryptophan metabolism in depressed patients. DESIGN: A comparative, analytical study. PLACE AND DURATION OF STUDY: Clinical Biochemistry and Psychopharmacology Research Unit, Department of Biochemistry, University of Karachi during the year 2002 to 2003. SUBJECTS AND METHODS: Sixteen adults depressed patients who were not having any other major comorbidity were selected from the outpatients department of local psychiatric clinic for the study. They were subjected to a semi-structured interview for associated clinical characteristics and diagnosis of depression according to ICD-10 criteria. A control group of normal health male and female individuals was identified for comparison with the depressed group. All the depressed patients were treated with fluoxetine hydrochloride (Prozac 20 mg/day) for four weeks. Healthy individual's data was compared with the depressed group and evaluated for gender based response to fluoxetine HCl medication. RESULTS: Significant decreases were found in total tryptophan concentrations (33 %, p<0.01,56%, p<0.01) in depressed male and female patients respectively, in contrast, serum cortisol levels were increased by 68% and 98% in male and female depressed patients respectively as compared to healthy controls. Significant increases (23%, p<0.05) in albumin levels were found in females only. Four weeks treatment of male and female depressed group by Fluoxetine HCL (Prozac) 20 mg/kg/day, increased serum total tryptophan concentrations significantly by 32% (p<0.05) in males and by 83% (p<0.01) in females. Serum-free tryptophan concentrations were increased by 22% (p<0.05) in males only. In contrast serum cortisol concentrations were decreased by 31% (p<0.01) and 45.35% (p<0.01) in males and females respectively. CONCLUSION: Increases in tryptophan and decreases in cortisol concentrations were greater in females which may contribute to better response of the drug in females.