TCF-1 controls Treg cell functions that regulate inflammation, CD8+ T cell cytotoxicity and severity of colon cancer.

The transcription factor TCF-1 is essential for the development and function of regulatory T (Treg) cells; however, its function is poorly understood. Here, we show that TCF-1 primarily suppresses transcription of genes that are co-bound by Foxp3. Single-cell RNA-sequencing analysis identified effector memory T cells and central memory Treg cells with differential expression of Klf2 and memory and activation markers. TCF-1 deficiency did not change the core Treg cell transcriptional signature, but promoted alternative signaling pathways whereby Treg cells became activated and gained gut-homing properties and characteristics of the TH17 subset of helper T cells. TCF-1-deficient Treg cells strongly suppressed T cell proliferation and cytotoxicity, but were compromised in controlling CD4+ T cell polarization and inflammation. In mice with polyposis, Treg cell-specific TCF-1 deficiency promoted tumor growth. Consistently, tumor-infiltrating Treg cells of patients with colorectal cancer showed lower TCF-1 expression and increased TH17 expression signatures compared to adjacent normal tissue and circulating T cells. Thus, Treg cell-specific TCF-1 expression differentially regulates TH17-mediated inflammation and T cell cytotoxicity, and can determine colorectal cancer outcome.

Effect of chlorpyrifos on cypermethrin-induced dopaminergic neurotoxicity in rats.

The study aimed to investigate the combined effects of chlorpyrifos and cypermethrin combined on dopaminergic neurotoxicity, motor behaviours and level of selected inflammatory proteins in rats compared to either alone for delineating an interaction between these two pesticides. The rotarod and grip strength tests were employed to assess neurobehavioural changes. The striatal dopamine content and expression of tyrosine hydroxylase (TH), α-synuclein, cyclooxygenase-2 (COX-2), and tumour necrosis factor-α (TNF-α) proteins in the nigrostriatal tissue were measured. Chlorpyrifos impaired the neurobehavioural indexes, reduced the striatal dopamine level, augmented the level of α-synuclein, COX-2, and TNF-α and attenuated the expression of TH similar to but a little less than cypermethrin. Half the dose of both pesticides together produced additional neurotoxicity compared with the usual (highest employed) dose of either alone. The results showed that chlorpyrifos induced moderately less dopaminergic neurotoxicity than cypermethrin. In the combination, they produced a little higher toxicity than either pesticide alone.

The impact of electronic cigarette use on periodontitis and periodontal outcomes: a systematic review and meta-analysis.

BACKGROUND: Periodontitis, a prevalent inflammatory disease affecting tooth-supporting structures, leads to significant oral health and systemic complications if untreated. While traditional smoking is a well-known risk factor for periodontitis, the impact of electronic cigarettes (e-cigarettes) on periodontal health remains unclear. This systematic review and meta-analysis aim to synthesize existing evidence on the effects of e-cigarette use on periodontitis and other periodontal outcomes. METHODS: A literature search was conducted across PubMed, EMBASE, and Web of Science from their inception up to June 15 2024. Eligible studies included those assessing the impact of e-cigarette use on periodontal outcomes such as bleeding on probing (BOP), plaque index, probing depth, clinical attachment loss, and marginal bone loss. Data were extracted and analyzed using random-effect models to calculate pooled mean differences. R statistical software was used to perform meta-analyses. RESULTS: Twelve studies were included in the meta-analysis. E-cigarette users showed a significantly lower mean BOP score compared to non-users (pooled mean difference: -14.233; 95% CI: -20.424 to -8.043; I² = 99%). For other periodontal outcomes, the findings were as follows: Plaque Index (MD: -0.160; 95% CI: -0.680 to 0.360; I² = 95%), Clinical Attachment Loss (MD: 0.120; 95% CI: -0.045 to 0.285; I² = 90%), Probing Depth (MD: 0.056; 95% CI: -0.070 to 0.182; I² = 85%), and Marginal Bone Loss (MD: -0.052; 95% CI: -0.168 to 0.064; I² = 88%). CONCLUSION: Present studies have not identified a significant link between e-cigarette use and adverse effects on periodontal health, but the available research is limited. Further longitudinal research is necessary to evaluate the long-term effects of e-cigarette use on periodontal health and to clarify any associated risks.

Age-Related Macular Degeneration (AMD): Pathophysiology, Drug Targeting Approaches, and Recent Developments in Nanotherapeutics.

The most prevalent reason for vision impairment in aging inhabitants is age-related macular degeneration (AMD), a posterior ocular disease with a poor understanding of the anatomic, genetic, and pathophysiological progression of the disease. Recently, new insights exploring the role of atrophic changes in the retinal pigment epithelium, extracellular drusen deposits, lysosomal lipofuscin, and various genes have been investigated in the progression of AMD. Hence, this review explores the incidence and risk factors for AMD, such as oxidative stress, inflammation, the complement system, and the involvement of bioactive lipids and their role in angiogenesis. In addition to intravitreal anti-vascular endothelial growth factor (VEGF) therapy and other therapeutic interventions such as oral kinase inhibitors, photodynamic, gene, and antioxidant therapy, as well as their benefits and drawbacks as AMD treatment options, strategic drug delivery methods, including drug delivery routes with a focus on intravitreal pharmacokinetics, are investigated. Further, the recent advancements in nanoformulations such as polymeric and lipid nanocarriers, liposomes, etc., intended for ocular drug delivery with pros and cons are too summarized. Therefore, the purpose of this review is to give new researchers an understanding of AMD pathophysiology, with an emphasis on angiogenesis, inflammation, the function of bioactive lipids, and therapy options. Additionally, drug delivery options that focus on the development of drug delivery system(s) via several routes of delivery can aid in the advancement of therapeutic choices.

Incidental detection of rare vascular variation during pyeloplasty and its clinical implication - A case report.

ABSTRACT: Crossing vessels is one of the important causes of pelviureteric junction obstruction (PUJO). Accessory lower polar vessels are commonly seen with congenital PUJO, but they are not always the cause of obstruction. We incidentally encountered a variation in the lower polar crossing vessel while doing laparoscopic pyeloplasty in a patient with congenital PUJO. We encountered a right accessory lower polar artery and vein along with a right gonadal artery arising from the accessory right renal artery and right gonadal vein draining into the right lower polar crossing accessory renal vein. Knowledge of variations in genitourinary vasculature is important in the current era to prevent inadvertent complications.

Impact of Iron Profile and Vitamin D Levels on Clinical Outcomes in Patients with Sepsis and Septic Shock: A Cross-sectional Analysis at a Tertiary Care Center.

Aim and background: Sepsis is a major global health affecting millions worldwide, hence understanding its contributing factors becomes paramount. This cross-sectional study at a tertiary care center explores the relationship between iron profile, vitamin D levels, and outcomes in sepsis and septic shock patients. The primary objective was to explore the prevalence of iron profile and vitamin D parameters during early intensive care unit (ICU) admission and their association with 28-day mortality. Materials and methods: Spanning 18 months, the study enrolled adult patients meeting sepsis or septic shock criteria at the ICU. Data collection included demographic information, clinical characteristics, and blood samples for iron profile and vitamin D levels at admission. Disease severity was assessed using sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) scores, and treatment was administered as per surviving sepsis-3 guidelines. Results: The research involved 142 participants, uncovering prevalent organisms such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Noteworthy connections to mortality were identified for factors including vasopressor support, ICU stay duration, SOFA score, and APACHE-II score. Interestingly, age, gender, and vitamin D levels showed no significant associations. However, the study did reveal a significant association between iron, ferritin, and transferrin saturation levels with increased 28-day mortality. Conclusion: Our study concluded that low Iron, elevated ferritin, and decreased transferrin saturation levels maintained associations with the outcome of interest. While no such relationship was established with vitamin D levels. These results suggest potential implications for patient management and prognosis, warranting further exploration in future research. How to cite this article: Bairwa M, Jatteppanavar B, Kant R, Singh M, Choudhury A. Impact of Iron Profile and Vitamin D Levels on Clinical Outcomes in Patients with Sepsis and Septic Shock: A Cross-sectional Analysis at a Tertiary Care Center. Indian J Crit Care Med 2024;28(6):569-574.

Glu289 residue in the pore-forming motif of Vibrio cholerae cytolysin is important for efficient ß-barrel pore formation.

Vibrio cholerae cytolysin (VCC) is a potent membrane-damaging ß-barrel pore-forming toxin. Upon binding to the target membranes, VCC monomers first assemble into oligomeric prepore intermediates and subsequently transform into transmembrane ß-barrel pores. VCC harbors a designated pore-forming motif, which, during oligomeric pore formation, inserts into the membrane and generates a transmembrane ß-barrel scaffold. It remains an enigma how the molecular architecture of the pore-forming motif regulates the VCC pore-formation mechanism. Here, we show that a specific pore-forming motif residue, E289, plays crucial regulatory roles in the pore-formation mechanism of VCC. We find that the mutation of E289A drastically compromises pore-forming activity, without affecting the structural integrity and membrane-binding potential of the toxin monomers. Although our single-particle cryo-EM analysis reveals WT-like oligomeric ß-barrel pore formation by E289A-VCC in the membrane, we demonstrate that the mutant shows severely delayed kinetics in terms of pore-forming ability that can be rescued with elevated temperature conditions. We find that the pore-formation efficacy of E289A-VCC appears to be more profoundly dependent on temperature than that of the WT toxin. Our results suggest that the E289A mutation traps membrane-bound toxin molecules in the prepore-like intermediate state that is hindered from converting into the functional ß-barrel pores by a large energy barrier, thus highlighting the importance of this residue for the pore-formation mechanism of VCC.

Pore formation-independent cell death induced by a ß-barrel pore-forming toxin.

Vibrio cholerae cytolysin (VCC) is a ß-barrel pore-forming toxin (ß-PFT). It exhibits potent hemolytic activity against erythrocytes that appears to be a direct outcome of its pore-forming functionality. However, VCC-mediated cell-killing mechanism is more complicated in the case of nucleated mammalian cells. It induces apoptosis in the target nucleated cells, mechanistic details of which are still unclear. Furthermore, it has never been explored whether the ability of VCC to trigger programmed cell death is stringently dependent on its pore-forming activity. Here, we show that VCC can evoke hallmark features of the caspase-dependent apoptotic cell death even in the absence of the pore-forming ability. Our study demonstrates that VCC mutants with abortive pore-forming hemolytic activity can trigger apoptotic cell death responses and cytotoxicity, similar to those elicited by the wild-type toxin. VCC as well as its pore formation-deficient mutants display prominent propensity to translocate to the target cell mitochondria and cause mitochondrial membrane damage. Therefore, our results for the first time reveal that VCC, despite being an archetypical ß-PFT, can kill target nucleated cells independent of its pore-forming functionality. These findings are intriguing for a ß-PFT, whose destination is generally expected to remain limited on the target cell membranes, and whose mode of action is commonly attributed to the membrane-damaging pore-forming ability. Taken together, our study provides critical new insights regarding distinct implications of the two important virulence functionalities of VCC for the V. cholerae pathogenesis process: hemolytic activity for iron acquisition and cytotoxicity for tissue damage by the bacteria.

Financial toxicity and mental well-being of the oral cancer survivors residing in a developing country in the era of COVID 19 pandemic - A cross-sectional study.

OBJECTIVES: The primary outcome measures evaluated the financial toxicity and mental well-being of the oral cancer survivors. METHODS: A cross-sectional study of oral cancer survivors who were disease-free for more than 6 months after treatment and visited the hospital for a routine follow-up is included in the study. Mental well-being and financial toxicity were evaluated using the Depression, Anxiety, and Stress Scale - 21 (DASS 21) and Comprehensive Score for financial Toxicity (COST- Functional Assessment of Chronic Illness Therapy) questionnaires. A literature review was done to compare the results with financial toxicity and mental health in cancer patients from the pre-pandemic era. RESULTS: A total of 79 oral cancer survivors were included in the study, predominantly males (M: F = 10:1). The age ranged from 26 to 75 years (The median age is 49). The full-time employment dropped from 83.5% in the pre-treatment period to 21.5% post-treatment. Depression was observed in 58.2% and anxiety in 72.2%. Unemployed survivors were observed to have more depression (OR = 1.3, 95% confidence interval (CI) = 0.3-5.4, p = 0.6), anxiety (OR = 3.5, 95% CI = 0.3-21.2, p = 0.1) and stress (OR = 1.6, 95% CI = 0.3-6.6, p = 0.5) than rest of the cohort. On univariate analysis, unemployed survivors (M = 11.8 ± 3.8, p = 0.01) had significantly poorer financial toxicity scores. Survivors with depression (M = 16.4 ± 7.1, p = 0.06) and stress (M = 14.4 ± 6.8, p = 0.002) had poor financial toxicity scores. On multifactorial analysis of variance, current employment (p = 0.04) and treatment modality (p = 0.05) were significant factors impacting the financial toxicity. CONCLUSION: There is a trend towards increased incidence of depression, anxiety, and stress among oral cancer survivors compared to the literature from the pre-COVID era. There is significant financial toxicity among either unemployed or part-time workers. This calls for urgent public/government intervention to prevent the long-term impact of financial toxicity on survival and quality of life.

Whole Genome Sequencing in Advanced Lung Cancer can be Performed Using Diff-Quik Cytology Smears Derived from Endobronchial Ultrasound, Transbronchial Needle Aspiration (EBUS TBNA).

INTRODUCTION: Maximising alternative sample types for genomics in advanced lung cancer is important because bronchoscopic samples may sometimes be insufficient for this purpose. Further, the clinical applications of comprehensive molecular analysis such as whole genome sequencing (WGS) are rapidly developing. Diff-Quik cytology smears from EBUS TBNA is an alternative source of DNA, but its feasibility for WGS has not been previously demonstrated. METHODS: Diff-Quik smears were collected along with research cell pellets. RESULTS: Tumour content of smears were compared to research cell pellets from 42 patients, which showed good correlation (Spearman correlation 0.85, P < 0.0001). A subset of eight smears underwent WGS, which presented similar mutation profiles to WGS of the matched cell pellet. DNA yield was predicted using a regression equation of the smears cytology features, which correctly predicted DNA yield > 1500 ng in 7 out of 8 smears. CONCLUSIONS: WGS of commonly collected Diff-Quik slides is feasible and their DNA yield can be predicted.

Lymphocytic emperipolesis in breast carcinoma on cytology smears-A curious finding!

In this article, we discuss an intimidating finding of lymphocytic emperipolesis which was observed in breast carcinoma cells on cytology smears.

Radiological tumor thickness as a clinical predictor of pathological depth of invasion in oral squamous cell carcinoma: a retrospective analysis.

PURPOSE: Inclusion of depth of invasion (DOI) in the recent AJCC/UICC TNM staging for oral cancer has incorporated the concept of tumor third dimension and its prognostic importance. However, there is no uniform consensus about measuring DOI at clinical setting at present. For more practical reasons, radiological tumor thickness (rTT) is a simple and practical measurement which can be used as a clinical predictor of pDOI. METHODS: We compared rTT and pathological DOI (pDOI) of 179 patients with OSCC who underwent curative surgery from April 2018 to April 2020 at AIIMS Rishikesh, India. Spearman correlation was used to determine correlation between rTT and pDOI. ROC curve was used to determine inter-group cutoff values. RESULTS: Overall, rTT showed a strong correlation with pDOI (rho = 0.74; 95% CI 0.667-0.8; p < 0.001). The inter-group cutoff value for rTT were 8 mm (Sn 89.1%; Sp 53.2%) between Group A (pDOI ≤ 5 mm) and B (pDOI > 5 mm, ≤ 10 mm), and 14 mm (Sn 89.5%; Sp 78.3%) between Group B and C (pDOI > 10 mm), respectively. CONCLUSIONS: rTT is a clinical predictor of pDOI in OSCC, and may be considered as a surrogate of DOI in the clinical setting.

Medial tibial bone resorption following total knee arthroplasty comparing a traditional with a kinematic design.

BACKGROUND: New total knee prostheses are being designed to improve clinical outcome, survivorship and patient satisfaction following total knee arthroplasty (TKA). A new knee system was developed with improvements in patellofemoral joint, trochlear geometry, polyethylene formulation and tibial baseplate. Aim of this study was to compare the newer kinematic knee system with its existing predecessor knee system in terms of clinical outcome, revision rates, radiographic outcomes specifically medial tibial bone resorption. METHODS: The prospective matched-pair study included 88 TKA surgeries using newer kinematic design knee prostheses, performed between January 2015 and December 2016, out of which 82 patients were available for final follow-up. The control cohort of 82 traditional TKA prosthesis was matched in terms of age, gender and body mass index. All surgeries were performed by the single surgeon using medial parapatellar arthrotomy and posterior stabilized implants were used. Clinical outcomes were assessed using knee society score, range of motion (ROM), anterior knee pain and crepitation. Radiological examinations included recording of radiolucent lines and medial tibial bone resorption. RESULTS: At the 5-year follow-up, no significant differences were noted in terms of mean knee society score (93.3 ± 6.6 vs 94.2 ± 8.1), knee function score (88.5 ± 10.5 vs 89.1 ± 11.2) and ROM. The incidences of anterior knee pain and crepitation were lower in the newer group (8.5% vs 21.9% and 14.6% vs 32.9%, respectively) compared to the traditional prosthesis group. No cases of aseptic loosening were observed in either cohort. No significant difference was seen in terms of radiolucent lines (29.3% vs 26.8%) and medial tibial resorption (2.43% in each group) incidences. CONCLUSIONS: At the 5 years follow-up no significant differences were noted between the two groups in terms of clinical and radiological outcomes, except the former proved to be better for anterior knee pain and crepitation. LEVEL OF EVIDENCE: II.

Management of proximal tibial stress fracture associated with advanced knee osteoarthritis: A systematic review.

PURPOSE: Tibial stress fracture associated with knee osteoarthritis is an unusual and difficult clinical scenario. There is no clear existing treatment guideline for this uncommon clinical disease. The aim of this study is to review the impact of various treatment options for patients with advanced knee osteoarthritis associated with proximal tibial stress fracture. METHODS: The study was performed using the databases of PubMed and Scopus. Methodological index for non-randomized studies score was used to evaluate the included studies' bias. The concluded data included the treatment approach, reported outcome measure, and time to fracture union. The literature search was started in December 2021 and accomplished at January 2022. A narrative description of the different methods and comparison of their results were done. RESULTS: Out of total assessed 69 studies, 9 studies were included in our review. The commonest treatment approach used was total knee arthroplasty by long tibial stem extension. The mean preoperative knee society score and knee functional score were 30.62 and 23.17, respectively. The mean postoperative knee society knee score was 86.87, while the functional score was 83.52. The average reported time to achieve fracture union was 4 months (ranging 2.07-5.50 months). CONCLUSION: The optimal clinical outcome for treating either acute or mobile tibial stress fracture in patients with advanced knee osteoarthritis can be achieved with long stem total knee arthroplasty. However, due to heterogeneity of data, comparison of different treatment options for chronic proximal tibial stress fracture mal-union/non-union coexisting with knee osteoarthritic and such inferences need to be judged cautiously.

The Ethnopharmacological Properties of Green-Engineered Metallic Nanoparticles against Metabolic Disorders.

Metabolic syndrome is a multifaceted pathophysiologic condition that is largely caused by an imbalance between caloric intake and energy expenditure. The pathogenesis of metabolic syndrome is determined by an individual's genetic/epigenetics and acquired factors. Natural compounds, notably plant extracts, have antioxidant, anti-inflammatory, and insulin-sensitizing properties and are considered to be a viable option for metabolic disorder treatment due to their low risk of side effects. However, the limited solubility, low bioavailability, and instability of these botanicals hinder their performance. These specific limitations have prompted the need for an efficient system that reduces drug degradation and loss, eliminates unwanted side effects, and boosts drug bioavailability, as well as the percentage of the drug deposited in the target areas. The quest for an enhanced (effective) drug delivery system has led to the formation of green-engineered nanoparticles, which has increased the bioavailability, biodistribution, solubility, and stability of plant-based products. The unification of plant extracts and metallic nanoparticles has helped in the development of new therapeutics against metabolic disorders such as obesity, diabetes mellitus, neurodegenerative disorders, non-alcoholic fatty liver, and cancer. The present review outlines the pathophysiology of metabolic diseases and their cures with plant-based nanomedicine.

Hypertension in men - An emerging public health challenge for India: Evidence from national family health survey-4.

Background: Men in the 25-54 year age group form the major workforce in developing countries like India. The rising trend of hypertension in this age group is a growing matter of concern. Objectives: This study analyzed secondary data analysis from the National Family Health Survey-4. Methods: Men in the 25-54 age group (n = 76,410) from 640 districts of the country were included in the study. State and district-wise trends in hypertension in men along with selected individual lifestyle characteristics were displayed using a geographic information system. Results: The prevalence of hypertension among men in the age group of 25-54 was found to be 35.6% for the entire country. In urban India, the prevalence of hypertension was 38.4% (uncorrected - 40.2%) compared with 33.8% (uncorrected - 34.9%) in rural India. Among the 27,973 hypertensives, 6984 (25%) were the known hypertensives prior to the survey. Out of these only 2403 (34.4%) were taking medicines. The prevalence of tobacco use in any form among the men in this age group was 45.7% (uncorrected - 49%). Conclusion: In conclusion, the study highlights the burden of hypertension in men in the prime age group along with the alarming burden of tobacco consumption and recommends public health and policy interventions targeting both hypertension and tobacco control. It requires urgent attention and specialized strategies in tiding over this epidemic brewing in the workforce of the country.

Continuous ambulatory peritoneal dialysis catheter insertion by open technique: 20-year experience from a single center.

Introduction: Continuous ambulatory peritoneal dialysis (CAPD) catheter placement is a part of renal replacement therapy. We describe our 20-year experience in using the open technique and assess its safety, efficacy, and outcome in the treatment of end-stage renal disease patients. Methods: In a retrospective study, we analyzed data of all patients who had a CAPD catheter placed using our open dissection technique using local anesthesia over the previous 20 years, with minimum 1 year of follow-up. Intraoperative data, postoperative data, and complications were noted. Results: A total of 1410 cases were included in the study. The mean duration of follow-up was 72 ± 18 months (range 12-120 months). The mean operative time was 19 ± 7.5 min and mean hospital stay was 3 ± 1 days. No major intraoperative complications were noted. We observed a peritonitis rate of 0.49 episodes/patient/year. The most common reason for permanent catheter removal was refractory peritonitis in 21%, followed by flow failure in 7%, and ultrafiltration failure in 6.5%. The death-censored technical survival rate was 94.3%, 83.2%, 75.9%, 69.2%, and 60.6% patients at 1 year, 2 years, 3 years, 4 years, and 5 years, respectively. Conclusions: The open dissection method of peritoneal dialysis catheter insertion using local anesthesia at well-experienced center is a simple, painless, and uncomplicated procedure with excellent outcomes. Optimal exposure, judicious use of energy source, and using appropriate technique provide good technical success rate with lesser complications.

Membrane Dynamics and Remodelling in Response to the Action of the Membrane-Damaging Pore-Forming Toxins.

Pore-forming protein toxins (PFTs) represent a diverse class of membrane-damaging proteins that are produced by a wide variety of organisms. PFT-mediated membrane perforation is largely governed by the chemical composition and the physical properties of the plasma membranes. The interaction between the PFTs with the target membranes is critical for the initiation of the pore-formation process, and can lead to discrete membrane reorganization events that further aids in the process of pore-formation. Punching holes on the plasma membranes by the PFTs interferes with the cellular homeostasis by disrupting the ion-balance inside the cells that in turn can turn on multiple signalling cascades required to restore membrane integrity and cellular homeostasis. In this review, we discuss the physicochemical attributes of the plasma membranes associated with the pore-formation processes by the PFTs, and the subsequent membrane remodelling events that may start off the membrane-repair mechanisms.

Influence of the Gut Microbiota on the Development of Neurodegenerative Diseases.

Neurodegenerative disorders are marked by neuronal death over time, causing a variety of cognitive and motor dysfunctions. Protein misfolding, neuroinflammation, and mitochondrial and protein clearance system dysfunction have all been identified as common pathways leading to neurodegeneration in recent decades. An altered microbiome of the gut, which is considered to play a central role in diseases as well as health, has recently been identified as another potential feature seen in neurodegenerative disorders. An array of microbial molecules that are released in the digestive tract may mediate gut-brain connections and permeate many organ systems, including the nervous system. Furthermore, recent findings from clinical as well as preclinical trials suggest that the microbiota of the gut plays a critical part in gut-brain interplay and that a misbalance in the composition of the gut microbiome may be linked to the etiology of neurological disorders (majorly neurodegenerative health problems); the underlying mechanism of which is still unknown. The review aims to consider the association between the microbiota of the gut and neurodegenerative disorders, as well as to add to our understanding of the significance of the gut microbiome in neurodegeneration and the mechanisms that underlie it. Knowing the mechanisms behind the gut microbiome's role and abundance will provide us with new insights that could lead to novel therapeutic strategies.

Adverse effects of textile dyes on antioxidant enzymes and cholinesterase activities in Drosophila melanogaster (Oregon R+).

The effluents from textile dyeing industry are causing water pollution and may transform into more toxic and carcinogenic chemical species by environmental conditions. Therefore systemic toxicity of textile dyes is major health concern. Hence, this study sought to examine the toxic effect of disperse textile dyes on important systemic enzymes in the larvae of wild type Drosophila melanogaster (Oregon R+). Drosophila larvae were fed with corn-sugar-yeast diets containing two disperse dyes, Disperse blue-124 and Disperse black-9 (1, 10 and 100 mg/mL) for 2 days (48 h) and subsequent the enzymatic estimations were carried out using larval homogenate. In silico molecular docking studies were also performed to analyze the binding interaction of these dyes with acetyl choline esterase enzyme. Disperse black 9 shows more strong binding by occupying a groove and forming one hydrogen bond with Tyr465 of acetyl choline esterase enzyme while Disperse blue-124 shows surface binding without forming any hydrogen bond. Drosophila larvae fed on these dyes exhibited a dose-dependent increase in acetyl choline esterase enzymatic activity (1.8 fold increase with Disperse black-9, 100 mg/mL) while 4.4-folds Disperse blue-124, 100 mg/mL). Both Disperse Blue and Disperse Black dyes altered the activities of antioxidant enzymes Catalase (CAT, increased more than 2.5 fold), Superoxide dismutase (SOD, increased more than two folds) and showed a dose-dependent increase in Xanthine oxidase and lipid peroxidation (LPO) levels (more than 3 folds). Therefore both the disperse dyes were found to dysregulate the activities of antioxidant enzymes which may be the underlying mechanism for their toxic effects.