Hesperidin mitigates lead-induced neurotoxicity via TFEB-dependent restoration of mitochondrial function, oxidative balance, and neuroinflammation in rats.

Lead (Pb) neurotoxicity remains a global concern, causing irreversible cognitive and motor impairments through mechanisms like mitochondrial dysfunction, oxidative stress and inflammation. Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy that also coordinates mitochondrial function, has emerged as a novel target in neuroprotection. This study evaluated the neuroprotective potential of hesperidin (natural flavonoid) against Pb-induced neurotoxicity, with a focus on the role of TFEB.

Quality Improvement Essentials and Teaching Quality Improvement.

This article explores the key elements of integrating quality improvement (QI) and patient safety (PS) in medical education and throughout physician training. It begins by identifying core requirements for undergraduate and graduate medical education, and then delves into various frameworks for embedding QI initiatives into curricula. Emphasizing experiential learning, the article discusses hands-on approaches that foster practical understanding of QI.

PERK activation mediates neuroprotection against chronic unpredictable stress-induced neurobehavioral changes via the TFEB pathway.

Chronic unpredictable stress (CUS) is a significant contributor to neurobehavioral changes, via disrupted cellular homeostasis, corticosterone and altered neurotransmitter dynamics. The PERK (Protein Kinase RNA-like Endoplasmic Reticulum Kinase)-TFEB (Transcription factor EB) pathway integrates stress responses with autophagy and lysosomal biogenesis to maintain cellular resilience, influencing oxidative stress, neuroinflammation and neurodegeneration. Hence, this study was intended to explore the possible involvement of PERK-TFEB pathway in mediating the neuroprotective effects of SB202190 (a PERK activator) in mitigating neurobehavioral changes induced by CUS.

Piceatannol attenuates chronic unpredictable stress-induced neurobehavioral deficits in mice via SIRT1-mediated modulation of neuroinflammation, oxidative stress, and neurotransmitter imbalance.

Exposure to chronic unpredictable stress (CUS) serves as the major contributor for the neurobehavioral changes. The current study explores the possible involvement of the SIRT1 pathway in mediating the neuroprotective properties of piceatannol in CUS induced neurobehavioral changes. Molecular docking studies showed binding interactions of piceatannol with SIRT1, suggesting that it may modulate SIRT1 activity.

Neurosteroid mitigation of developmental neurological dysfunction, long-term epileptic biomarkers, chronic neuroinflammation, and neurodegeneration in a pediatric rat model of organophosphate exposure.

Children are particularly susceptible to the neurotoxic effects of organophosphates, which can lead to developmental neuronal deficits and associated dysfunction, including cognitive disabilities, epilepsy, and associated comorbidities. Anticonvulsants like benzodiazepines fail to prevent the lasting neurobehavioral and neuropathological effects of organophosphate exposure, emphasizing the need for new anticonvulsants to address these effects. This study evaluated the efficacy of the synthetic neurosteroid ganaxolone (GX) in combating persistent behavioral deficits, electrographic abnormalities, and neuropathological damage induced by diisopropylfluorophosphate (DFP) intoxication in pediatric rats.

Thrombin mediates seizures following cortical injury-induced status epilepticus.

The neurobiological mechanisms underlying acute seizures, status epilepticus (SE), and cerebral edema following cortical insult are unknown. Currently, benzodiazepines are first-line therapy for SE, and mechanistic insight could lead to improved treatment for cortical-injury-related seizures. Cobalt was implanted in the supplementary motor cortex (M2).

Formulation and evaluation of herbal essential oil based nail lacquer for management of onychomycosis.

Introduction: Onychomycosis (Paronychia) is a common fungal nail infection, characterised by thickened, discoloured and brittle nails often accompanied by pain and discomfort. It is one of the most prevalent fungal nail infections with the global incidence of >20 % affected commonly by Candida albicans and Candida parapsilosis. The market today is flooded with various antifungal therapies (Azoles, Imidazoles, Allylamines, etc.

Ehretia laevis mitigates paracetamol- induced hepatotoxicity by attenuating oxidative stress and inflammation in rats.

Hepatotoxicity is caused due to intake of drug or any chemical above the therapeutic range or as overdose. Current therapies for the management of hepatotoxicity are associated with several side effects. The present study was envisaged to explore the hepatoprotective potential of Ehretia laevis (E.

succinate based polyelectrolyte complexes for colon delivery of synbiotic in management of inflammatory bowel disease.

Polyelectrolyte complexes (PECs) formed by the interaction between oppositely charged polymers have emerged as promising carriers for accomplishing colon-specific release. In this study, we have explored the potential of polyelectrolyte complexes between a succinate derivative of galactomannan and cationic guar gum for colon delivery of synbiotic. The PECs were prepared using a polyelectrolyte complexation method and characterized.

Neutrophil Lymphocyte Ratio as a Predictor of Stroke Severity in Type 2 Diabetes Mellitus: A Single-Center Study.

Introduction: Type 2 diabetes mellitus (T2DM) is associated with various microvascular and macrovascular complications. Stroke, being a vascular complication, is associated with severe morbidity and mortality. Neutrophil lymphocyte ratio (NLR), a crude, inexpensive, and rather easily available modality to detect inflammation, has been utilized to find the extent of inflammation in type 2 diabetes mellitus patients.

Neuroprotectant Activity of Novel Water-Soluble Synthetic Neurosteroids on Organophosphate Intoxication and Status Epilepticus-Induced Long-Term Neurological Dysfunction, Neurodegeneration, and Neuroinflammation.

Organophosphates (OPs) and nerve agents are potent neurotoxic compounds that cause seizures, status epilepticus (SE), brain injury, or death. There are persistent long-term neurologic and neurodegenerative effects that manifest months to years after the initial exposure. Current antidotes are ineffective in preventing these long-term neurobehavioral and neuropathological changes.

Protective Activity of Novel Hydrophilic Synthetic Neurosteroids on Organophosphate Status Epilepticus-induced Chronic Epileptic Seizures, Non-Convulsive Discharges, High-Frequency Oscillations, and Electrographic Ictal Biomarkers.

Nerve agents and organophosphates (OP) are neurotoxic chemicals that induce acute seizures, status epilepticus (SE), and mortality. Long-term neurologic and neurodegenerative effects manifest months to years after OP exposure. Current benzodiazepine anticonvulsants are ineffective in preventing such long-term neurobehavioral and neuropathological changes.

A Pediatric Rat Model of Organophosphate-Induced Refractory Status Epilepticus: Characterization of Long-Term Epileptic Seizure Activity, Neurologic Dysfunction and Neurodegeneration.

Children are highly vulnerable to the neurotoxic effects of organophosphates (OPs), which can cause neuronal developmental defects, including intellectual disability, autism, epilepsy, and related comorbidities. Unfortunately, no specific pediatric OP neurotoxicity model currently exists. In this study, we developed and characterized a pediatric rat model of status epilepticus (SE) induced by the OP diisopropylfluorophosphate (DFP) and examined its impact on long-term neurological outcomes.

Computational Studies to Understand the Neuroprotective Mechanism of Action Basil Compounds.

Neurodegenerative diseases, such as Alzheimer's and Parkinson's, pose a significant global health challenge, emphasizing the need for novel neuroprotective agents. Basil ( spp.) has been recognized for its therapeutic potential, and numerous studies have reported neuroprotective effects.

In Silico Approaches to Developing Novel Glycogen Synthase Kinase 3β (GSK-3β).

Alzheimer's disease (AD) is caused by plaque agglomeration and entanglement in several areas of the neural cells, which leads to apoptosis. The main etiology of AD is senile dementia, which is linked to amyloid-beta (Aβ) deregulation and tau perivascular pathogeny. Hyperphosphorylated tau has a propensity for microtubules, which elevate the instability and tau-protein congregates, leading to accumulation of neurofibrillary tangles (NFTs).

Clinical Significance of Adropin and Afamin in Evaluating Renal Function and Cardiovascular Health in the Presence of CKD-MBD Biomarkers in Chronic Kidney Disease.

Aim: The study aims to test the hypothesis that concentrations of adropin and afamin differ between patients in various stages of chronic kidney disease when compared with healthy controls. The study also investigates the association of the biomarkers (adropin and afamin) with CKD-MBD and traditional cardiovascular risk parameters in CKD patients.

Methodology: The cross-sectional study includes the subjects divided into four groups comprising the control group (healthy volunteers = 50), CKD stages 1-2 patients ( = 50), CKD stages 3-4 patients ( = 50), CKD stage 5 patients ( = 50).

Sex Differences in Organophosphate Model of Benzodiazepine-Refractory Status Epilepticus and Neuronal Damage.

Sex differences are common in human epilepsy. Although men are more susceptible to seizure than women, the mechanisms underlying sex-specific vulnerabilities to seizure are unclear. The organophosphate (OP) diisopropylfluorophosphate (DFP) is known to cause neurotoxicity and status epilepticus (SE), a serious neurologic condition that causes prolonged seizures and brain damage.

Recent Development of Novel Aminoethyl-Substituted Chalcones as Potential Drug Candidates for the Treatment of Alzheimer's Disease.

No drug on the market, as a single entity, participates in different pathways involved in the pathology of Alzheimer's disease. The current study is aimed at the exploration of multifunctional chalcone derivatives which can act on multiple targets involved in Alzheimer's disease. A series of novel aminoethyl-substituted chalcones have been developed using in silico approaches (scaffold morphing, molecular docking, and ADME) and reported synthetic methods.

Scaffold Morphing and In Silico Design of Potential BACE-1 (β-Secretase) Inhibitors: A Hope for a Newer Dawn in Anti-Alzheimer Therapeutics.

Alzheimer's disease (AD) is the prime cause of 65-80% of dementia cases and is caused by plaque and tangle deposition in the brain neurons leading to brain cell degeneration. β-secretase (BACE-1) is a key enzyme responsible for depositing extracellular plaques made of β-amyloid protein. Therefore, efforts are being applied to develop novel BACE-1 enzyme inhibitors to halt plaque build-up.

Anticonvulsant potential of Grewia tiliaefolia in pentylenetetrazole induced epilepsy: insights from in vivo and in silico studies.

Epilepsy, a chronic neurological condition, impacts millions of individuals globally and remains a significant contributor to both illness and mortality. Available antiepileptic drugs have serious side effects which warrants to explore different medicinal plants used for the management of epilepsy reported in Traditional Indian Medicinal System (TIMS). Therefore, we explored the antiepileptic potential of the Grewia tiliaefolia (Tiliaeceae) which is known for its neuroprotective properties.

Atypical Kawasaki Disease in a 16-Month-Old Baby: A Case Report and Literature Review.

Kawasaki illness is an inflammatory condition of small- to medium-sized vessels that primarily affects children. It affects the lymph nodes, skin, mucous membranes, and heart, especially the coronary arteries. Patients who lack the comprehensive clinical manifestations of classic Kawasaki disease (KD) are typically evaluated for incomplete KD.

Experimental Models of Gulf War Illness, a Chronic Neuropsychiatric Disorder in Veterans.

Gulf War illness (GWI) is a chronic multifaceted condition with debilitating pain and fatigue, as well as sleep, behavioral, and cognitive impairments in war veterans. Currently, there is no effective treatment or cure for GWI; therefore, there is a critical need to develop experimental models to help better understand its mechanisms and interventions related to GWI-associated neuropsychiatric disorders. Chemical neurotoxicity appears to be one cause of GWI, and its symptoms manifest as disruptions in neuronal function.

The microbiome-gut-brain axis in epilepsy: pharmacotherapeutic target from bench evidence for potential bedside applications.

The gut-brain axis augments the bidirectional communication between the gut and brain and modulates gut homeostasis and the central nervous system through the hypothalamic-pituitary-adrenal axis, enteroendocrine system, neuroendocrine system, inflammatory and immune pathways. Preclinical and clinical reports showed that gut dysbiosis might play a major regulatory role in neurological diseases such as epilepsy, Parkinson's, multiple sclerosis, and Alzheimer's disease. Epilepsy is a chronic neurological disease that causes recurrent and unprovoked seizures, and numerous risk factors are implicated in developing epilepsy.

Promising biomarkers and therapeutic targets for the management of Parkinson's disease: recent advancements and contemporary research.

Parkinson's disease (PD) is one of the progressive neurological diseases which affect around 10 million population worldwide. The clinical manifestation of motor symptoms in PD patients appears later when most dopaminergic neurons have degenerated. Thus, for better management of PD, the development of accurate biomarkers for the early prognosis of PD is imperative.