P66Shc Mediates SUMO2-induced Endothelial Dysfunction.

Sumoylation is a post-translational modification that can regulate different physiological functions. Increased sumoylation, specifically conjugation of SUMO2/3 (small ubiquitin like modifier 2/3), is detrimental to vascular health. However, the molecular mechanism mediating this effect is poorly understood. Here, we demonstrate that SUMO2 modifies p66Shc, which impairs endothelial function. Using multiple approaches, we show that p66Shc is a direct target of SUMO2. Mass spectrometry identified that SUMO2 modified lysine-81 in the unique collagen homology-2 domain of p66Shc. SUMO2ylation of p66Shc increased phosphorylation at serine-36, causing it to translocate to the mitochondria. Notably, sumoylation-deficient p66Shc (p66ShcK81R) was resistant to SUMO2-induced p66ShcS36 phosphorylation and mitochondrial translocation. Ingenuity pathway analysis showed that majority of effects of p66Shc SUMO2ylation were mediated via p66ShcK81. Finally, p66ShcK81R knockin mice were resistant to SUMO2-induced endothelial dysfunction. Collectively, our work uncovers a posttranslational modification of redox protein p66Shc and identifies SUMO2-p66Shc signaling as a regulator of vascular endothelial function.

Unlocking the potential of cotton stalk as a renewable source of cellulose: A review on advancements and emerging applications.

Cotton stalk (CS) is a global agricultural residue, with an annual production of approximately 50 million tons, albeit with limited economic significance. The utilization of cellulose derived from CS has gained significant attention in green nanomaterial technologies. This interest stems from its unique properties, including biocompatibility, low density, minimal thermal expansion, eco-friendliness, renewability, and its potential as an alternative source for chemicals, petroleum, and biofuels. In this review, we delve into various extraction and characterization methods, the physicochemical attributes, recent advancements, and the applications of cellulose extracted from CS. Notably, the steam explosion method has proven to yield the highest cellulose content (82 %) from CS. Moreover, diverse physicochemical properties of cellulose can be obtained through different extraction techniques. Sulfuric acid hydrolysis, for instance, yields nanocrystalline cellulose fibers measuring 10-100 nm in width and 100-850 nm in length. Conversely, the steam explosion method yields cellulose fibers with dimensions of 10.7 µm in width and 1.2 mm in length. CS-derived products, including biochar, aerogel, dye adsorbents, and reinforcement fillers, find applications in various industries, such as environmental remediation and biodegradable packaging. This is primarily due to their ready availability, cost-effectiveness, and sustainable nature.

Exploring apple pectic polysaccharides: Extraction, characterization, and biological activities - A comprehensive review.

Apple (Malus domestica) is a popular and ancient fruit of the Myrtaceae family. Apple fruit is well-known for its great nutritional and phytochemical content consisted of beneficial compounds such as polyphenols, polysaccharides, sterols, and organic acids. Polysaccharides extracted from different parts of the apple fruit, including the peel, pomace, or the whole fruit, have been extensively studied. Researchers have investigated the structural characteristics of these polysaccharides, such as molecular weight, type of monosaccharide unit, type of linkage and its position and arrangement. Besides this, functional properties and physicochemical and of apple polysaccharides have also been studied, along with the effects of extraction procedures, storage, and processing on cell wall polysaccharides. Various extraction techniques, including hot water extraction, enzymatic extraction, and solvent-assisted extraction, have been studied. From the findings, it was evident that apple polysaccharides are mainly composed of (1 â†’ 3), (1 â†’ 6): α-ß-glycosidic linkage. Moreover, the apple polysaccharides were demonstrated to exhibit antioxidant, hepatoprotective, anti-cancer, hypoilipidemic, and enzyme inhibitory properties in vitro and in vivo. The potential applications of apple polysaccharides in the food, cosmetic, pharmaceutical, nutraceutical industries have also been explored in the present review. Overall, the research on apple polysaccharides highlights their significant potential as a source of biologically active compounds with various health benefits and practical applications.

Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats.

Gabapentin (GBP), a GABA analogue, is primarily used as an anticonvulsant for the treatment of partial seizures and neuropathic pain. Whereas a majority of the side effects are associated with the nervous system, emerging evidence suggests there is a high risk of heart diseases in patients taking GBP. In the present study, we first used a preclinical model of rats to investigate, firstly, the acute cardiovascular responses to GBP (bolus i.v. injection, 50 mg/kg) and secondly the effects of chronic GBP treatment (i.p. 100 mg/kg/day × 7 days) on cardiovascular function and the myocardial proteome. Under isoflurane anesthesia, rat blood pressure (BP), heart rate (HR), and left ventricular (LV) hemodynamics were measured using Millar pressure transducers. The LV myocardium and brain cortex were analyzed by proteomics, bioinformatics, and western blot to explore the molecular mechanisms underlying GBP-induced cardiac dysfunction. In the first experiment, we found that i.v. GBP significantly decreased BP, HR, maximal LV pressure, and maximal and minimal dP/dt, whereas it increased IRP-AdP/dt, Tau, systolic, diastolic, and cycle durations (* p < 0.05 and ** p < 0.01 vs. baseline; n = 4). In the second experiment, we found that chronic GBP treatment resulted in hypotension, bradycardia, and LV systolic dysfunction, with no change in plasma norepinephrine. In the myocardium, we identified 109 differentially expressed proteins involved in calcium pathways, cholesterol metabolism, and galactose metabolism. Notably, we found that calmodulin, a key protein of intracellular calcium signaling, was significantly upregulated by GBP in the heart but not in the brain. In summary, we found that acute and chronic GBP treatments suppressed cardiovascular function in rats, which is attributed to abnormal calcium signaling in cardiomyocytes. These data reveal a novel side effect of GBP independent of the nervous system, providing important translational evidence to suggest that GBP can evoke adverse cardiovascular events by depression of myocardial function.

Cortical lesions uniquely predict motor disability accrual and form rarely in the absence of new white matter lesions in multiple sclerosis.

Background and objectives: Cortical lesions (CL) are common in multiple sclerosis (MS) and associate with disability and progressive disease. We asked whether CL continue to form in people with stable white matter lesions (WML) and whether the association of CL with worsening disability relates to pre-existing or new CL. Methods: A cohort of adults with MS were evaluated annually with 7 tesla (T) brain magnetic resonance imaging (MRI) and 3T brain and spine MRI for 2 years, and clinical assessments for 3 years. CL were identified on 7T images at each timepoint. WML and brain tissue segmentation were performed using 3T images at baseline and year 2. Results: 59 adults with MS had ≥1 7T follow-up visit (mean follow-up time 2±0.5 years). 9 had "active" relapsing-remitting MS (RRMS), defined as new WML in the year prior to enrollment. Of the remaining 50, 33 had "stable" RRMS, 14 secondary progressive MS (SPMS), and 3 primary progressive MS. 16 total new CL formed in the active RRMS group (median 1, range 0-10), 7 in the stable RRMS group (median 0, range 0-5), and 4 in the progressive MS group (median 0, range 0-1) (p=0.006, stable RR vs PMS p=0.88). New CL were not associated with greater change in any individual disability measure or in a composite measure of disability worsening (worsening Expanded Disability Status Scale or 9-hole peg test or 25-foot timed walk). Baseline CL volume was higher in people with worsening disability (median 1010µl, range 13-9888 vs median 267µl, range 0-3539, p=0.001, adjusted for age and sex) and in individuals with RRMS who subsequently transitioned to SPMS (median 2183µl, range 270-9888 vs median 321µl, range 0-6392 in those who remained RRMS, p=0.01, adjusted for age and sex). Baseline WML volume was not associated with worsening disability or transition from RRMS to SPMS. Discussion: CL formation is rare in people with stable WML, even in those with worsening disability. CL but not WML burden predicts future worsening of disability, suggesting that the relationship between CL and disability progression is related to long-term effects of lesions that form in the earlier stages of disease, rather than to ongoing lesion formation.

Incidence, Diagnosis and Treatment of Otorhinolaryngological, Head and Neck Tuberculosis: A Prospective Clinical Study.

Introduction Tuberculosis is a disease of diversified presentation. It affects almost all organs in the body, and otorhinolaryngological, head and neck involvement is not an exception. Objective To increase awareness about the different clinical presentations of otorhinolaryngological, head and neck tuberculosis, the techniques employed to diagnose it, and to assess the response to the treatment. Methods We conducted a prospective study of 114 patients who presented primarily with otorhinolaryngological, head and neck tuberculosis. Routine blood investigations, chest radiographs, the tuberculin test, and sputum examination for the presence of acid-fast bacilli were performed in all cases. Site-specific investigations were performed in relevant cases only. The patients were treated according to the antitubercular treatment (ATT) regimen recommended by the Indian Ministry of Health and Family Welfare's National Tuberculosis Elimination Program (NTEP), and they were followed up clinically two and six months after starting the ATT. Results Tubercular cervical lymphadenopathy was the most common clinical presentation (85.96%), followed by deep neck abscess (5.27%). Fine-needle aspiration cytology proved to be a reliable tool for the diagnosis of tubercular lymphadenopathy. Improvement at the end of 2 and 6 months of the ATT was observed in 90.35% and 96.50% of the cases respectively. Conclusion The diagnosis of otorhinolaryngological, head and neck tuberculosis requires a high index of clinical suspicion, and the ATT proved to be very effective in reducing the severity of the disease.

Autoimmune and paraneoplastic neurological disorders: A review of relevant neuroimaging findings.

INTRODUCTION: Paraneoplastic neurologic syndromes (PNS) and autoimmune encephalitis (AIE) are immune-mediated disorders. PNS is linked to cancer, while AIE may not Their clinical manifestations and imaging patterns need further elucidation. OBJECTIVE/AIMS: To investigate the clinical profiles, antibody associations, neuroimaging patterns, treatments, and outcomes of PNS and AIE. METHODS: A systematic review of 379 articles published between 2014 and 2023 was conducted. Of the 55 studies screened, 333 patients were diagnosed with either PNS or AIE and tested positive for novel antibodies. Data on demographics, symptoms, imaging, antibodies, cancer associations, treatment, and outcomes were extracted. RESULTS: The study included 333 patients (mean age 54 years, 67% males) with PNS and AIE positive for various novel antibodies. 84% had central nervous system issues like cognitive impairment (53%), rhombencephalitis (17%), and cerebellar disorders (24%). Neuroimaging revealed distinct patterns with high-risk antibodies associated with brainstem lesions in 98%, cerebellar in 91%, hippocampal in 98%, basal ganglia in 75%, and spinal cord in 91%, while low/intermediate-risk antibodies were associated with medial temporal lobe lesions in 71% and other cortical/subcortical lesions in 55%. High-risk antibodies were associated with younger males, deep brain lesions, and increased mortality of 61%, while low/intermediate-risk antibodies were associated with females, cortical/subcortical lesions, and better outcomes with 39% mortality. Associated cancers included seminomas (23%), lung (19%), ovarian (2%), and breast (2%). Treatments included IVIG, chemotherapy, and plasmapheresis. Overall mortality was 25% in this cohort. CONCLUSION: PNS and AIE have distinct clinical and radiological patterns based on antibody profiles. High-risk antibodies are associated with increased mortality while low/intermediate-risk antibodies are associated with improved outcomes. Appropriate imaging and antibody testing are critical for accurate diagnosis.

Disease modifying therapy and pregnancy outcomes in multiple sclerosis: A systematic review and meta-analysis.

OBJECTIVES: To report pregnancy outcomes among multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs). METHODS: We performed a retrospective chart review of articles published from June 1996 to May 2023. Additional information was acquired from the drug registries of individual pharmaceutical companies. A comparison was also made with pregnancy data of the general population using the World Health Organization database. Summary analysis was achieved using R statistical software (v3.6), and the overall prevalence of outcomes was estimated using a random effects model. RESULTS: A meta-analysis of 44 studies was conducted. Dimethyl fumarate had the highest prevalence of premature births at 0.6667% (SD:0.5236-0.7845). The highest rates of stillbirths and infant deaths (perinatal and neonatal) were observed with interferons at 0.004% (SD:0.001-0.010) and 0.009% (SD:0.005-0.0015), respectively. Cladribine had the majority of ectopic pregnancies (0.0234%, SD:0.0041-1217), while natalizumab had the highest prevalence of spontaneous abortions (0.1177%, SD:0.0931-0.1477) and live birth defects (0.0755%, SD:0.0643-0.0943).None of the outcomes were significantly different from those of the general population (p > 0.05), except ectopic pregnancy and spontaneous abortion (p < 0.001), where the odds were 0.665 (0.061-0.886) and 0.537(0.003-0.786), respectively. The pooled prevalence of MS relapses was 221% for a single episode (SD:0.001-0.714), 0.075% for more than one episode (SD:0.006-0.167), and 0.141% for at least one episode requiring steroids (SD:0.073-0.206) none of these reached clinical significance. CONCLUSION: Existing research suggests that DMT use in MS patients during pregnancy is generally considered safe. This study supports their utilization on a case-by-case basis. However, further primary research on this topic with clinical trials is warranted.

Profiling of the ß-glucosidases identified in the genome of Penicillium funiculosum: insights from genomics, transcriptomics, proteomics, and homology-modeling studies.

The enzymatic conversion of lignocellulosic biomass to bioethanol depends on efficient enzyme systems with ß-glucosidase as one of the key components. In this study, we performed in-depth profiling of the various ß-glucosidases present in the genome of the hypercellulolytic fungus Penicillium funiculosum using genomics, transcriptomics, proteomics, and molecular dynamics simulation approaches. Of the eight ß-glucosidase genes identified in the P. funiculosum genome, three were predicted to be extracellular based on signal peptide prediction and abundance in the secretome. Among the three secreted ß-glucosidases, two belonged to the GH3 family and one belonged to the GH1 family. Homology models of these proteins predicted a deep and narrow active site for the GH3 ß-glucosidases (PfBgl3A and PfBgl3B) and a shallow open active site for the GH1 ß-glucosidase (PfBgl1A). The enzymatic assays indicated that P. funiculosum-secreted proteins showed high ß-glucosidase activities with prominent bands on the 4-methylumbelliferyl ß-D-glucopyranoside zymogram. To understand the contributory effects of each of the three secreted ß-glucosidases (PfBgls), the corresponding gene was deleted separately, and the effect of the deletion on the ß-glucosidase activity of the secretome was examined. Although not the most abundant, PfBgl3A was found to be one of the most important ß-glucosidases, as evidenced by a 42% reduction in ß-glucosidase activity in the ΔPfBgl3A strain. Our results advance the understanding of the genetic and biochemical nature of all ß-glucosidases produced by P. funiculosum and pave the way to design a superior biocatalyst for the hydrolysis of lignocellulosic biomass. IMPORTANCE Commercially available cellulases are primarily produced from Trichoderma reesei. However, external supplementation of the cellulase cocktail from this host with exogenous ß-glucosidase is often required to achieve the desired optimal saccharification of cellulosic feedstocks. This challenge has led to the exploration of other cellulase-producing strains. The nonmodel hypercellulolytic fungus Penicillium funiculosum has been studied in recent times and identified as a promising source of industrial cellulases mainly due to its ability to produce a balanced concoction of cellulolytic enzymes, including ß-glucosidases. Various genetic interventions targeted at strain improvement for cellulase production have been performed; however, the ß-glucosidases of this strain have remained largely understudied. This study, therefore, reports profiling of all eight ß-glucosidases of P. funiculosum via molecular and computational approaches. The results of this study provide useful insights that will establish the background for future engineering strategies to transform this fungus into an industrial workhorse.

Tea (Camellia sinensis (L.) Kuntze) as an emerging source of protein and bioactive peptides: A narrative review.

Tea residues represent one of the major agricultural wastes that are generated after the processing of tea. They account for 21-28% of crude protein and are often discarded without the extraction of valuable proteins. Due to various bioactivity and functional properties, tea proteins are an excellent alternative to other plant-based proteins for usage as food supplements at a higher dosage. Moreover, their good gelation capacity is ideal for the manufacturing of dairy products, jellies, condensation protein, gelatin gel, bread, etc. The current study is the first to comprehend various tea protein extraction methods and their amino acid profile. The preparation of tea protein bioactive peptides and hydrolysates are summarized. Several functional properties (solubility, foaming capacity, emulsification, water/oil absorption capacity) and bioactivities (antioxidant, antihypertensive, antidiabetic) of tea proteins are emphasized.

Inhibition of Pyk2 Improves Cx43 Intercalated Disc Localization, Infarct Size, and Cardiac Function in Rats With Heart Failure.

BACKGROUND: Heart failure causes changes in Cx43 (Connexin43) regulation that are associated with arrhythmic heart disease. Pyk2 (proline-rich tyrosine kinase 2) is activated in cardiomyopathies and phosphorylates Cx43 to decrease intercellular communication. This study was designed to determine if Pyk2 inhibition improves cardiac function in a myocardial infarction (MI)-induced heart failure model in rats. METHODS: MI (ligation of left anterior descending artery) rats were treated with the Pyk2 inhibitor PF4618433. Hemodynamic and structural parameters were monitored in Sham (n=5), MI-vehicle (n=5), and MI-PF4618433 (n=8) groups. Heart tissues were collected after 6 weeks to assess Pyk2 and Cx43 protein level and localization. RESULTS: PF4618433 produced no observed adverse effects and inhibited ventricular Pyk2. PF4618433 reduced the MI infarct size from 34% to 17% (P=0.007). PF4618433 improved stroke volume (P=0.031) and cardiac output (P=0.009) in comparison to MI-vehicle with values similar to the Sham group. PF4618433 also led to an increase in the ejection fraction (P=0.002) and fractional shortening (P=0.006) when compared with the MI-vehicle (32% and 35% improvement, respectively) yet were lower in comparison with the Sham group. Pyk2 inhibition decreased Cx43 tyrosine phosphorylation (P=0.043) and maintained Cx43 at the intercalated disc in the distal ventricle 6 weeks post-MI. CONCLUSIONS: Unlike other attempts to decrease Cx43 remodeling after MI-induced heart failure, inhibition of Pyk2 activity maintained Cx43 at the intercalated disc. This may have aided in the reduced infarct size (acute time frame) and improved cardiac function (chronic time frame). Additionally, we provide evidence that Pyk2 is activated following MI in human left ventricle, implicating a novel potential target for therapy in patients with heart failure.

Identification of Eight High Yielding Strains via Morpho-Molecular Characterization of Thirty-Three Wild Strains of Calocybe indica.

Calocybe indica, generally referred as milky mushroom, is one of the edible mushroom species suitable for cultivation in the tropical and sub-tropical regions of the world. However, lack of potential high yielding strains has limited its wider adaptability. To overcome this limitation, in this study, the germplasms of C. indica from different geographical regions of India were characterized based on their morphological, molecular and agronomical attributes. Internal transcribed spacers (ITS1 and ITS4)-based PCR amplification, sequencing and nucleotide analysis confirmed the identity of all the studied strains as C. indica. Further, evaluation of these strains for morphological and yield parameters led to the identification of eight high yielding strains in comparison to the control (DMRO-302). Moreover, genetic diversity analysis of these thirty-three strains was performed using ten sequence-related amplified polymorphism (SRAP) markers/combinations. The Unweighted Pair-group Method with Arithmetic Averages (UPGMA)-based phylogenetic analysis categorized the thirty-three strains along with the control into three clusters. Cluster I possesses the maximum number of strains. Among the high yielding strains, high antioxidant activity and phenol content was recorded in DMRO-54, while maximum protein content was observed in DMRO-202 and DMRO-299 as compared with the control strain. The outcome of this study will help the mushroom breeders and growers in commercializing C. indica.

Non-canonical role for the ataxia-telangiectasia-Rad3 pathway in STAT3 activation in human multiple myeloma cells.

PURPOSE: The goal of this study was to characterize the relationship between ATR and STAT3 interactions in human multiple myeloma (MM) cells. METHODS: Various MM cell lines, including IL-6-dependent cells were exposed to ATR inhibitors and effects on STAT3 Tyr705 and Ser727 were monitored by WB analysis and ImageStream analysis. Parallel studies examined induction of cell death, STAT3 DNA binding activity, and expression of STAT3 downstream targets (BCL-XL, MCL-1, c-MYC). Validation was obtained in ATR shRNA knock-down cells, and in cells ectopically expressing BCL-XL, MCL-1, or c-MYC. Analogous studies were performed in primary MM cells and in a MM xenograft model. RESULTS: Multiple pharmacologic ATR inhibitors inhibited STAT3 Tyr705 (but not Ser727) phosphorylation at low uM concentrations and down-regulated BCL-XL, MCL-1, c-MYC in association with cell death induction. Compatible results were observed in ATR shRNA knock-down cells. Cell death induced by ATR inhibitors was significantly attenuated in cells ectopically expressing constitutively active STAT3, BCL-XL, MCL-1, or c-MYC. Concordant results were observed in primary human MM cells and in an in vivo MM xenograft model. CONCLUSIONS: Collectively, these findings argue for a non-canonical role for the ATR kinase in STAT3 activation in MM cells, and suggest that STAT3 inactivation contributes to the lethal actions of ATR inhibitors in MM.

The resilient cotton plant: uncovering the effects of stresses on secondary metabolomics and its underlying molecular mechanisms.

Cotton is an important fiber crop cultivated around the world under diverse climate conditions and generates billions of dollars in annual revenue globally. Biotic and abiotic stresses have caused reduction in yield and productivity of cotton crops. In this review, we comprehensively analyzed and summarized the effect of biotic and abiotic stress on secondary metabolite production in cotton. The development of cotton varieties with improved tolerance against abiotic and biotic stress can play an important role in sustainable cotton production. Under stress conditions, plants develop a variety of defense mechanisms such as initiating signaling functions to upregulate defense responsive genes and accumulation of secondary metabolites. Understanding the impact of stress on secondary metabolite production in cotton is crucial for developing strategies to alleviate the negative effects of stress on crop yield and quality. Further, the potential industrial applications of these secondary metabolites in cotton, such as gossypol, could provide new opportunities for sustainable cotton production and the development of value-added products. Additionally, transgenic and genome-edited cotton cultivars can be developed to provide tolerance to both abiotic and biotic stress in cotton production.

Evaluating the Incidence of Audiological Derangement in Cases of Thyroid Hormone Imbalance.

Thyroid hormone disorders are both congenital as well as acquired. According to a projection from several studies on thyroid diseases, it has been estimated that about 42 million people in India suffer from various kind of thyroid diseases (1) Thyroid hormone is closely associated with the development of the cognitive functions, thus deficiency of this hormone is said to have effect an overall impact on proper functioning of the body. The normal functioning of the thyroid gland and adequate levels in the blood are Needed for the formation and functioning of the middle ear, inner ear and the central auditory pathway. Thus, congenital hypothyroidism (CH) can be a potential risk factor for hearing impairment (2) if the hormones decrease or are absent during the development of the peripheral and central auditory system structures. This study was undertaken with the objective of studying the pattern of hearing loss in patients who have a deranged thyroid profile. The study was conducted among 50 patients who were known cases of thyroid disorder in the Otorhinolaryngology Department of our institute. The study was hospital based observational clinical study. The patients were subjected to thyroid profile test After this, those who satisfied the inclusion and exclusion criteria and were included, after detailed history and examination, patients were subjected to PTA, hearing loss was classified according to WHO guidelines. The age group of the patients was from 30-55 yrs. with the mean age being 42. On the basis of the t3, t4 and tsh levels, in the current study out of 50 patients,40 were hypothyroid (80%),with male to female ratio of 6:4. On pure tone audiometry, 15 patients had decreased hearing. The other 25 had normal hearing. The incidence of hearing loss in hypothyoroid patients in our study is 37.5%. On analaysis the PTA reports of these patients,9 patients (22.5%) had conductive hearing loss of mild variety, the mean value of hearing loss being 26.2 decibels. 2 (5%) patients had mixed variety of hearing loss, with sensorineural hearing loss at higher frequencies. All the remaining patients had sensorineural type of hearing loss, i.e., 10%. Of the 10 patients, that have hyperthyroidism 8 were female and 2 were male. 3 patients (30%) had hearing loss, all these 3 patients reported hearing losses at high frequencies and had moderate type of sensorineural hearing loss. Conclusion- From our current study, we could see that hearing loss is present in both extremes of thyroid hormone imbalance The dominant variety of hearing loss in thyroid disorder is sensorineural type, because thyroid hormone imbalance affects the inner ear function.

Anti-CD20 monoclonal antibody (mAb) therapy and colitis: A case series and review.

The US Food and Drug Administration (FDA) recently issued a warning regarding ocrelizumab due to reports of colitis among patients taking this medication. Since it is the only FDA-approved therapy for primary progressive multiple sclerosis (PPMS), further research on this adverse event is necessary, and healthcare professionals should be informed of potential treatment options. In this review, we summarize the available data on the incidence of inflammatory colitis associated with anti-CD20 monoclonal antibodies (mAbs), such as ocrelizumab and rituximab, used in MS treatment. Although the exact pathophysiology of anti-CD20-induced colitis remains unknown, immunological dysregulation through treatment-mediated B-cell depletion has been proposed as a possible mechanism. Our study highlights the importance of clinicians being aware of this potential side effect, and patients taking these medications should be closely monitored for any new-onset gastrointestinal symptoms or diarrheal illness. Research indicates that prompt intervention with endoscopic examination and medical or surgical therapies can ensure timely and effective management, thus improving patient outcomes. However, large-scale studies are still needed to determine the associated risk factors and to establish definitive guidelines for the clinical evaluation of MS patients on anti-CD20 medications.

Assessing farmer's exposure to pesticides and the risk for non-communicable diseases: A biomonitoring study.

This cross-sectional study aimed to assess the adverse effects of pesticide use in humans, such as non-communicable diseases, using acetylcholinesterase (AChE) and pesticide concentrations in blood samples. A total of 353 samples (290 case and 63 control) were collected from participants with >20 years of experience in agricultural pesticide use. The pesticide and AChE concentrations were determined using Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) and Reverse Phase High Performance Liquid Chromatography (RP-HPLC). Various health risks from pesticide exposure were assessed, including dizziness or headache, tension, anxiety, confusion, loss of appetite, loss of balance, concentration difficulties, irritability, anger, and depression. These risks may be influenced by the duration and intensity of exposure, the type of pesticide, and environmental factors in the affected areas. A total of 26 pesticides were detected in the blood samples from the exposed population, including 16 insecticides, three fungicides, and seven herbicides. Pesticide concentrations ranged from 0.20 to 12.12 ng/mL, and were statistically significant between the case and control groups (p < 0.05, p < 0.01, and p < 0.001). A correlation analysis was performed to determine statistically significance between pesticide concentration and symptoms of non-communicable diseases, such as Alzheimer's, Parkinson's, obesity, and diabetes. The estimated AChE levels in case and control blood samples were 21.58 ± 2.31 and 24.13 ± 1.08 U/mL, respectively (mean ± SD). The AChE levels were significantly lower in case samples than in controls (p < 0.001), which is considered to be an effect of long-term pesticide exposure, and is the cause of Alzheimer's disease (p < 0.001), Parkinson's disease (p < 0.001), and obesity (p < 0.01). Chronic exposure to pesticides and low levels of AChE are somewhat related to non-communicable diseases.

Identification and morpho-molecular characterization of low spore strain in oyster mushroom.

BACKGROUND: Sporocarps of oyster mushroom liberate enormous spores and cause allergic reactions to workers involved in its cultivation. These spore-related allergies include stiffness or pain in the forearms, limbs, itchy throat, grogginess, and respiratory problems and are major problems during oyster mushroom cultivation. METHODS AND RESULTS: In this study, we have generated seven hybrids using single-spore isolates (SSIs) of Pleurotus ostreatus var. florida (DMRP-49) and P. ostreatus (DMRP-30). Chimera was observed during cultivation trial of these hybrids and led to the development of low spore-producing/sporeless strain (DMRP-395) as evident from spore print and microscopic analysis. Further, the cultivation trial of this sporeless strain revealed a bunchy fruiting pattern and required 20-24 °C temperature for fruiting. At par yield was observed in sporeless strain. Notably, a prominent infundibuliform-shaped pileus along with central attachment of stipe was observed in the sporeless strain. Moreover, genetic diversity and principal component biplot analysis revealed resemblance of sporeless strain with one of the parental strain, i.e., P. ostreatus var. florida (DMRP-49). CONCLUSIONS: The developed sporeless strain (DMRP-395) contains high protein and at par yield as compared with the control (DMRP-136). This sporeless strain will be helpful to reduce spore-related allergic responses in mushroom growers.