Mitigation of letrozole induced polycystic ovarian syndrome associated inflammatory response and endocrinal dysfunction by Vitex negundo seeds.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder in women that necessitates effective and safe treatment alternatives. This study aimed to evaluate the therapeutic efficacy of Vitex negundo seed in a letrozole-induced PCOS rat model. RESULTS: Findings of the present study demonstrated that administration of hydro-ethanolic extract of Vitex negundo (VNE) effectively restored endocrino-metabolic imbalances associated with PCOS, along with correction of antioxidant enzymes level, proinflammatory cytokines, and apoptotic bio-markers. LC-MS analysis confirmed the presence of cinnamic acid, plumbagin and nigundin B as the prominent phytochemicals in VNE. The observed beneficial effects could be attributed to the active compounds in Vitex negundo extract, which exhibited hypoglycemic, hypolipidemic, and catabolic effects on body weight. Additionally, the extract contributed to hormonal balance regulation by modulating the steroidogenic enzymes, specifically by tuning gonadotropins level and correcting the LH:FSH ratio, through the modulation of ERα signalling and downregulation of NR3C4 expression. The antioxidant properties of phytochemicals in Vitex negundo seed were apparent through the correction of SOD and catalase activity. While it's anti-inflammatory and antiapoptotic action were associated with the regulation of mRNA expression of TNF-α, IL-6, BAX, Bcl2. Molecular docking study further indicated the molecular interaction of above mentioned active phytocompounds of VNE with ERα, NR3C4 and with TNFα that plays a critical mechanistic gateway to the regulation of hormone signalling as well as synchronizing the inflammation cascade. Furthermore, the histomorphological improvement of the ovaries supported the ameliorative action of Vitex negundo extract in the letrozole-induced PCOS model. CONCLUSIONS: This study indicates the potential of Vitex negundo seed as a multifaceted therapeutic option for PCOS. VNE offers a holistic strategy for PCOS with antiandrogenic, anti-inflammatory, and antioxidant properties, driven by its major compounds like cinnamic acid, plumbagine, and nigundin B.

Cervical Trident-Shaped Neurofibroma: A Rare Variant.

Spinal nerve root tumors can arise throughout the spine and at multiple levels, likely representing plexiform neurofibromas that grow from the nerve root into the intraspinal space either intradurally or epidurally and exit through the neural foramen, producing a dumbbell-shaped appearance. Although many cases of dumbbell-shaped extramedullary neurofibromas in the cervical spine have been reported, to the best of our knowledge, there are no reports of trident-shaped extramedullary neurofibromas. A 26-year-old woman presented with swelling over the right side of her neck. Diagnostic workup included magnetic resonance imaging (MRI) and contrast-enhanced computed tomography (CECT) of the neck, which revealed an intradural, extramedullary tumor mass at the right C2-C6 level with an extraspinal extension. Spinal cord compression or canal compromise is the most reliable indication for surgery. The solitary cervical neurofibroma was treated surgically in a single stage through laminoplasty and excision of the intradural tumor along with that of the neck component. This was performed without any complications. A single-stage double approach was adopted in this case. After total excision, the shape of the tumor was found to be more like a trident than a dumbbell. Hence, here we would like to suggest a new nomenclature for this neurofibroma, the trident neurofibroma.

Homocysteine, Vitamins B6, B12, and Folate and the Risk of Ischemic and Hemorrhagic Stroke: A Case-control Study from Northeast India.

Background: Stroke is a major leading global health complication. Identification and management of risk factors associated with stroke can help in prior detection, prevention, and improvement in patient care. Purpose: To investigate the prevalence of hyperhomocysteinemia (HHcy) and Vitamins B6, B12, and folate deficiency in stroke patients and also to assess other risk factors associated with ischemic and hemorrhagic stroke. Methods: Detail history of all the subjects in the study including history of hypertension, anemia, fasting glucose, carotid artery thickness, smoking, alcohol, and dietary intake was recorded. Standard assays for homocysteine (Hcy), Vitamins B6, B12, and folate estimation were done. Lipid and renal profile tests were also performed. The prevalence and odds of having HHcy, Vitamins B6, B12, and folate deficiency, and other risk factors in ischemic and hemorrhagic stroke patients were evaluated. Student's t-tests and chi-square tests were done for statistical validation of the data. Results: Prevalence of HHcy and Vitamins B6, B12, and folate deficiency was not observed in ischemic cases. HHcy and folate deficiency was found to be prevalent in hemorrhagic stroke patients. The odds that a person with HHcy and folate deficiency has hemorrhagic stroke was found to be significantly high. Conclusion: In our study, high Hcy and low folate levels emerged as risk factors for hemorrhagic stroke.

Attenuation of fluoride-induced hepatorenal oxidative stress by ferulic acid in vivo: An approach with in-silico analysis and interaction informatics of ferulic acid.

BACKGROUND: Chronic fluoride toxicity induces oxidative strain and lipid peroxidation and imparts deleterious effects on human metabolic organs. AIM: The present study aimed to expose the defensive impact of ferulic acid against sodium fluoride (NaF) induced hepatorenal dysfunction at the biochemical and antioxidative systems. METHODS: In-vivo. Rats were arbitrarily separated into five groups as control, sodium fluoride-treated (200 ppm kg -1), vitamin C -as a positive control, and FA co-administered groups with 10 mg kg -1 and 20 mg kg -1 body weight for 56 days. In the present investigation, we measured antioxidant enzymes, superoxide dismutase, catalase, and lactate dehydrogenase by electrozymographic and spectrophotometric methods. Biochemical assessment of TBARS, conjugated diene, and different serum biomarkers was done for liver and kidney functionality tests. In-silico. An in-silico study was conducted through a molecular docking experiment to evaluate the binding potentiality of FA by employing AutoDock Vina [version 1.5.6] to overcome the abnormality in the activities of catalase, and superoxide dismutase in NaF promoted toxicity of hepatorenal system. In-vitro. An in vitro biochemical experiment was conducted to support the in-silico study. RESULTS: Superoxide dismutase and catalase were decreased in the intoxicated rat. Ferulic acid (FA) as an antioxidant remarkably defended the NaF-mediated deterioration of the antioxidative status in the hepatorenal system, lowering lipid peroxidation products, malondialdehyde, and conjugated diene. Serum biomarkers, ALT, AST, ALP, urea, and creatinine increased in the intoxicated group than in control. Ferulic acid significantly neutralized the ill effects of NaF on serum lipid profile. In-silico analysis hypothesized the strong interaction of FA with the active side of catalase and superoxide dismutase that prevented the binding of NaF at the active site of these mentioned enzymes and this was further validated by in-vitro assay. CONCLUSION: However, FA modulates free radical generation and protected these metabolic organs against sodium fluoride-induced injury.

A Five-Year Retrospective Cohort Study of Survivality and Functional Outcomes of Stroke Patients Following Hospital Admission.

Background: Stroke is the fourth leading cause of death in India. Data on long-term outcomes of patients with stroke in India are relatively sparse. Objective: To document survival and long-term functional outcomes of patients with acute stroke and to assess the measures taken for secondary prevention of stroke. Methods and Material: A five-year retrospective cohort study involving 118 patients with acute stroke was conducted. Details about five years' survival, functional outcomes (modified Rankin Scale [mRS], Barthel index [BI], and Hamilton Depression Rating Scale [HDRS]), and secondary prevention measures were investigated. Results: Among the patients, 38.1% were diagnosed with ischemic stroke and 61.8% were diagnosed with hemorrhagic stroke. Hypertension was observed to be the predominant risk factor in a majority of the admitted patients. About 30.5% of patients died in the hospital within zero to four weeks after the index event, while 27.1% died during the follow-up period of five years. Approximately 21.1% of patients experienced a recurrent stroke over the next five years which turned out fatal. The quality of life was seriously affected in 32.4% of survivors. It was seen that 40.5% of survivors were fully independent and 45.9% were able to return to their occupation after five years poststroke. Prevalence of severe and very severe depression was observed in 3.4% and 1.7% of survivors, respectively. The majority of the survivors (93.9%) were aware of the risk of recurrent stroke. Physical activities as measures for the prevention of stroke were undertaken by 60.6% of survivors. Conclusion: Effective strategies for secondary prevention and also for long-term survival after stroke should be initiated as early as possible after the onset of the initial stroke. Stroke survivors should be closely monitored for their functional recovery and behavioral and emotional improvement poststroke.

Identification and characterization of fungi associated with blister blight lesions of tea (Camellia sinensis L. Kuntze) isolated from Meghalaya, India.

Diseases in plants are mostly caused by fungi. Fungal interactions with the host can be either biotrophic, necrotrophic or hemibiotrophic. Synergistic polymicrobial interactions have been recently recognized that can also attribute to the occurrence of complex plant diseases. Tea is one of the most widely consumed beverages worldwide, although tea plants are affected by many different diseases causing a significant reduction in global tea production. Blister blight is one such serious and damaging leaf disease of tea. An assessment of blister blight disease was carried out at the tea development center in Umsning, Meghalaya. A considerable number of tea varieties showed characteristic blister blight symptoms that ranged from preliminary yellow spots in the upper leaf surface, matured white sporulating blisters in the lower leaf surface, and delayed brown necrotic lesions throughout the surfaces of the leaves. A total of 42 isolates, 15 from initial, 15 from mature, and 12 from necrotic stages were isolated from the symptomatic leaf samples. Pestalotiopsis and Nigrospora were the two fungi incessantly isolated from the diseased leaves. Colony characteristics that included colony, hyphal, and spore morphologies were examined and mycelial accumulation, sporulation, and sporal germination were determined for all the isolates of Pestalotiopsis and Nigrospora. Molecular analysis based on ITS-RFLP was performed for identification and genetic variability. In vitro pathogenicity assay revealed that Pestalotiopsis spp. and Nigrospora sp. developed distinct characteristics symptoms on greenhouse acclimated TV17 tea clones. To our knowledge, this is the first report of the prevalence of tea blister blight disease in Meghalaya and it is an initial attempt to identify fungal pathogens during different stages of blister blight disease.

Phospholipases play multiple cellular roles including growth, stress tolerance, sexual development, and virulence in fungi.

Phospholipases are ubiquitous enzymes that hydrolyze phospholipids. Based on the cleavage site of the ester linkage in the substrate phospholipids, phospholipases are classified into four major types, phospholipase A (PLA), phospholipase B (PLB), phospholipase C (PLC), and phospholipase D (PLD), which are further classified into various subtypes. Phospholipases hydrolyze phospholipids into various signaling products including phosphatidic acid (PA), diacylglycerol (DAG), free fatty acids (FFAs), and lyso-phospholipids (LPLs). These signaling products regulate numerous processes such as cytoskeletal dynamics, growth, homeostasis, membrane remodeling, nutrient acquisition, secretion, signal transduction, stress tolerance, sexual development, and virulence in various organisms including fungi. Due to these key cellular roles, phospholipases are also promising targets in diagnostic and therapeutic applications. In this review, we discuss current knowledge about the cellular roles of different classes of phospholipases in fungi.

The pleiotropic vegetative and sexual development phenotypes of Neurospora crassa arise from double mutants of the calcium signaling genes plc-1, splA2, and cpe-1.

We investigated phenotypes of the double mutants of the calcium (Ca2+) signaling genes plc-1, splA2, and cpe-1 encoding for a phospholipase C1 (PLC-1), a secretory phospholipase A2 (sPLA2), and a Ca2+/H+ exchanger (CPE-1), respectively, to understand the cell functions regulated by their genetic interactions. Mutants lacking plc-1 and either splA2 or cpe-1 exhibited numerous defects including reduced colonial growth, stunted aerial hyphae, premature conidiation on plates with delayed germination, inappropriate conidiation in submerged culture, and lesser mycelial pigmentation. Moreover, the ∆plc-1; ∆splA2 and ∆plc-1; ∆cpe-1 double mutants were female-sterile when crossed with wild type as the male parent. In addition, ∆plc-1, ∆splA2, and ∆cpe-1 single mutants displayed higher carotenoid accumulation and an increased level of intracellular reactive oxygen species (ROS). Therefore, the pleiotropic phenotype of the double mutants of plc-1, splA2, and cpe-1 suggested that the genetic interaction of these genes plays a critical role for normal vegetative and sexual development in N. crassa.

Multiple cellular roles of Neurospora crassa plc-1, splA2, and cpe-1 in regulation of cytosolic free calcium, carotenoid accumulation, stress responses, and acquisition of thermotolerance.

Phospholipase C1 (PLC1), secretory phospholipase A2 (sPLA2) and Ca(2+)/H(+) exchanger proteins regulate calcium signaling and homeostasis in eukaryotes. In this study, we investigate functions for phospholipase C1 (plc-1), sPLA2 (splA2) and a Ca(2+)/H(+) exchanger (cpe-1) in the filamentous fungus Neurospora crassa. The Δplc-1, ΔsplA2, and Δcpe-1 mutants exhibited a growth defect on medium supplemented with the divalent ionophore A23187, suggesting that these genes might play a role in regulation of cytosolic free Ca(2+) concentration ([Ca(2+)](c)) in N. crassa. The strains lacking plc-1, splA2, and cpe-1 possessed higher carotenoid content than wild type at 8°C, 22°C, and 30°C, and showed increased ultraviolet (UV)-survival under conditions that induced carotenoid accumulation. Moreover, Δplc-1, ΔsplA2, and Δcpe-1 mutants showed reduced survival rate under hydrogen peroxide-induced oxidative stress and induced thermotolerance after exposure to heat shock temperatures. Thus, this study revealed multiple cellular roles for plc-1, splA2, and cpe-1 genes in regulation of [Ca(2+)](c), carotenoid accumulation, survival under stress conditions, and acquisition of thermotolerance induced by heat shock.