Guggulsterone selectively modulates STAT-3, mTOR, and PPAR-gamma signalling in a methylmercury-exposed experimental neurotoxicity: Evidence from CSF, blood plasma and brain samples DOI Creative Commons
Sumit Kumar, Sidharth Mehan, Zuber Khan

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 18, 2023

Abstract Amyotrophic lateral sclerosis (ALS) is a paralytic disease that damages the brain and spinal cord motor neurons. Several clinical preclinical studies have found methylmercury (MeHg + ) causes ALS. In ALS, -induced neurotoxicity manifests as oligodendrocyte destruction; myelin basic protein (MBP) deficiency leads to axonal death. ALS development has been connected an increase in signal transducer activator of transcription-3 (STAT-3), mammalian target rapamycin (mTOR), decrease peroxisome proliferator-activated receptor (PPAR)-gamma. Guggulsterone (GST), plant-derived chemical produced from Commiphorawhighitii resin, protect against by modulating these signalling pathways. Vitamin D 3 (VitD related precursor cells (OPC) damage, demyelination, white matter deterioration, which results neuron As result, primary goal this work was investigate therapeutic potential GST altering STAT-3, mTOR, PPAR-gamma levels MeHg -exposed experimental model adult rats. The GST30 60 mg/kg oral treatments significantly improved behavioral, motor, cognitive dysfunctions increased remyelination, proven Luxol Fast Blue stain (LFB), reduced neuroinflammation measured histological examinations. Furthermore, co-administration VitD3 exhibits moderate efficacy when administered combination with GST60. Our show protects neurons decreasing STAT-3 mTOR while increasing

Language: Английский

Immune System Dysregulation in the Progression of Multiple Sclerosis: Molecular Insights and Therapeutic Implications DOI
Zuber Khan, Sidharth Mehan, Ghanshyam Das Gupta

et al.

Neuroscience, Journal Year: 2024, Volume and Issue: 548, P. 9 - 26

Published: April 30, 2024

Language: Английский

Citations

13
Guggulsterone Selectively Modulates STAT-3, mTOR, and PPAR-Gamma Signaling in a Methylmercury-Exposed Experimental Neurotoxicity: Evidence from CSF, Blood Plasma, and Brain Samples DOI
Sumit Kumar, Sidharth Mehan, Zuber Khan

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(8), P. 5161 - 5193

Published: Jan. 3, 2024

Language: Английский

Citations

7
Matrine mediated neuroprotective potential in experimental multiple sclerosis: Evidence from CSF, blood markers, brain samples and in-silico investigations DOI
Swesha Chhabra, Sidharth Mehan, Zuber Khan

et al.

Journal of Neuroimmunology, Journal Year: 2023, Volume and Issue: 384, P. 578200 - 578200

Published: Sept. 16, 2023

Language: Английский

Citations

14
Effect of Natural Adenylcyclase/cAMP/CREB Signalling Activator Forskolin against Intra-Striatal 6-OHDA-Lesioned Parkinson’s Rats: Preventing Mitochondrial, Motor and Histopathological Defects DOI Creative Commons
Metab Alharbi, Abdulrahman Alshammari, Gurpreet Kaur

et al.

Molecules, Journal Year: 2022, Volume and Issue: 27(22), P. 7951 - 7951

Published: Nov. 17, 2022

Parkinson's disease (PD) is characterised by dopaminergic neuronal loss in the brain area. PD a complex that deteriorates patients' motor and non-motor functions. In experimental animals, neurotoxin 6-OHDA induces neuropathological, behavioural, neurochemical mitochondrial abnormalities formation of free radicals, which related to Parkinson-like symptoms after inter-striatal injection. Pathological manifestations disrupt cAMP/ATP-mediated activity transcription factor CREB, resulting Parkinson's-like symptoms. Forskolin (FSK) direct AC/cAMP/CREB activator isolated from

Language: Английский

Citations

19
Disruptions in cellular communication: Molecular interplay between glutamate/NMDA signalling and MAPK pathways in neurological disorders DOI
Sumedha Gupta, Abhishek Gupta, Sidharth Mehan

et al.

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
White Matter Injury in Central Nervous System Disorders DOI Creative Commons
Ling Zheng, Xiaoyu Wang, Peng Li

et al.

Neuropsychiatric Disease and Treatment, Journal Year: 2025, Volume and Issue: Volume 21, P. 107 - 114

Published: Jan. 1, 2025

As the aging process accelerates and living conditions improve, central nervous system (CNS) diseases have become a major public health problem.Diseases of CNS cause not only gray matter damage, which is primarily characterized by loss neurons, but also white damage.However, most previous studies focused on grey injury (GMI), with fewer (WMI).In this article, we will briefly describe structure function matter, summarize pathological changes WMI, focus molecular mechanisms therapeutic research advances in WMI after ischemic stroke, cerebral hemorrhage, Alzheimer's disease, multiple sclerosis diseases.

Language: Английский

Citations

0
Molecular Mechanisms of the Effects of Photodynamic Therapy on the Brain: A Review of the Literature DOI Creative Commons
Paweł Woźnicki, Dorota Bartusik‐Aebisher, Agnieszka Przygórzewska

et al.

Photodiagnosis and Photodynamic Therapy, Journal Year: 2025, Volume and Issue: unknown, P. 104536 - 104536

Published: Feb. 1, 2025

Malignant gliomas are the most common primary brain tumors in adults. These have a diverse molecular origin and very poor prognosis. There is lack of effective treatment at WHO grade IV glioma, all glioblastomas progress or recur. Current treatments including surgical intervention, radiation therapy, chemotherapy insufficient can cause damage to healthy tissue neurological deficits. The preservation during therapeutic intervention made extremely difficult by ability malignant diffusely infiltrate surrounding parenchyma. Photodynamic therapy (PDT) modality for glioma that possibly overcome inherent shortcommings traditional therapies. involves use photosensitizer (PS) which, upon absorption light photosensitized tissue, triggers photochemical reactions generating reactive oxygen species (ROS) leading killing tumor cells. Research focusing on PDT already underway with promising results. Clinical studies shown it be safe acceptable levels side effects. However, some adverse sequelae been observed these tumours, such as increased photosensitivity, intracranial pressure transient aphasia worsening pre-existing Although clinical well described, mechanisms PDT's effects not yet thoroughly characterized. In our work, we attempt summarize photosensitization neural vasculature blood-brain barrier (BBB). We also point findings presenting approaches protect from photodynamic damage.

Language: Английский

Citations

0
The proteomic landscape of trophoblasts unravels calcium-dependent syncytialization processes and beta-chorionic gonadotropin (ß-hCG) production DOI Creative Commons

Axel Gehl,

Daniel S. Klawitter,

Ulrich Wissenbach

et al.

Reproductive Biology and Endocrinology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 4, 2025

The syncytiotrophoblast (STB) layer of the placenta is formed by cell fusion cytotrophoblasts, acts as a feto-maternal barrier, required for production pregnancy hormones such chorionic gonadotropin, estradiol and progesterone also responsible mineral exchange calcium. Adequate supply placental hormone are essential maintenance pregnancy, disturbances in trophoblast integrity associated with complications. Since knowledge about identity expression levels proteins cells limited so far, we analyzed proteomes trophoblast-like syncytiotrophoblast-like BeWo under different calcium conditions. investigation protein profiles combination assays can provide better understanding calcium-dependent cellular processes trophoblasts syncytiotrophoblasts. Here, combine human model cultures, assays, antibody-based detection methods high-resolution mass spectrometry analyzes to assess changes during syncytialization. We monitored forskolin induced syncytialization an unbiased manner show that numerous strongly altered. Among them enzymes glucocorticoid sex synthesis pathways cytochrome P450 (CYP) 19A1, CYP11A1, adrenodoxin (FDX1), hydroxysteroid dehydrogenase (HSD) 11β2 HSD17β1, whose beta gonadotropin (ß-hCG), increase syncytialization, while secretion ß-hCG several markers clear dependence. broad applicability semi-quantitative proteome profiling cytotrophoblast- provides new insights into signaling occur cytotrophoblasts /syncytiotrophoblasts pregnancy.

Language: Английский

Citations

0
Dynamics of Cell Fate Decisions during Chemically Induced Multi‐Lineage Trans‐Differentiation at Single‐Cell Level DOI Creative Commons

E Weigao,

Lijiang Fei, Jingjing Wang

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Cell trans-differentiation offers a powerful means to manipulate cell identities. By exposing cells combination of small molecules (SMs), can be induced in simple and cost-effective manner. However, comprehensive atlas detailing chemical-induced across multiple fates has yet established. In this study, the underlying mechanisms is investigated constructed an in-depth single-cell process. The time-course trajectory demonstrated for mouse embryonic fibroblasts (MEFs) into lineages including epithelial, neural, extraembryonic endoderm like (XEN-like) cells, endothelial when by SMs cocktail 6TCF (E616452, tranylcypromine, CHIR99021, forskolin). These trans-differentiated closely resemble various somatic types fetus. It found that marked dynamic shifts entropy cycle during fate transitions. A common intermediate feature revealed characterized high ribosomal gene expression. This study combines high-resolution landscape with comparative analyses dynamics, providing new insights complex driving determination vitro. Future shall explore applicability model human trans-differentiation.

Language: Английский

Citations

0
Therapeutic potential of Baicalin against experimental obsessive compulsive disorder: Evidence from CSF, blood plasma, and brain analysis DOI

Abhinay Dhiman,

Divya Choudhary,

Sidharth Mehan

et al.

Journal of Neuroimmunology, Journal Year: 2025, Volume and Issue: unknown, P. 578598 - 578598

Published: March 1, 2025

Language: Английский

Citations

0