Publications by authors named "Upadhya D"

Double C-2 Like Domain Beta (DOC2B) located at 17q13.3 prevents metastasis by senescence induction and epithelial to mesenchymal transition inhibition in cervical cancer (CC). The extracellular vesicle (EV) mediated trafficking of DOC2B and its impact on tumor suppressive activity are not investigated in CC.

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In response to hyperglycemia, endothelial cells (ECs) release exosomes with altered protein content and contribute to paracrine signalling, subsequently leading to vascular dysfunction in type 2 diabetes (T2D). High glucose reprograms DNA methylation patterns in various cell/tissue types, including ECs, resulting in pathologically relevant changes in cellular and extracellular proteome. However, DNA methylation-based proteome reprogramming in endothelial exosomes and associated pathological implications in T2D are not known.

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Epilepsy, a chronic non-communicable disease of the brain, is one of the most common neurological diseases globally that affects people of all ages. The existence of medical, neurological, psychiatric, and cognitive comorbidities has always undermined the available advanced treatment strategies for epilepsy. New-generation antiepileptic drugs being less successful in completely controlling the seizures and observance of complex diseases, including drug-resistant cases, have provided scope for integrating and incorporating the therapeutic modalities of Ayurveda, the ancient Indian art of holistic medicine, in the effective management of epilepsy.

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The recently published "Minimal information for studies of extracellular vesicles - 2023 (MISEV2023)" in the Journal of Extracellular Vesicles has provided practical solutions to the numerous challenges extracellular vesicles (EVs) researchers face. These guidelines are imperative for novice and experienced researchers and promote unity within the EV community. It is strongly recommended that laboratories working with EVs make MISEV2023 an essential handbook and that researchers actively promote these guidelines during laboratory meetings, journal clubs, seminars, workshops, and conferences.

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Diabetic retinopathy (DR) stands as a prevalent complication in the eye resulting from diabetes mellitus, predominantly associated with high blood sugar levels and hypertension as individuals age. DR is a severe microvascular complication of both type I and type II diabetes mellitus and the leading cause of vision impairment. The critical approach to combatting and halting the advancement of DR lies in effectively managing blood glucose and blood pressure levels in diabetic patients; however, this is seldom achieved.

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Article Synopsis
  • * Researchers isolated and characterized EVs from various cell types (NSCs, MGE cells, and GABAergic interneurons) and loaded them with GABA to test their effectiveness in a rat model of epilepsy induced by kainic acid.
  • * Results indicated that GABA-encapsulated EVs significantly reduced the frequency and severity of seizures in treated rats, suggesting that this method could be a promising alternative for epilepsy management.
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Parkinson's disease (PD) presents with severe motor manifestations and a plethora of non-motor symptoms. Urinary dysfunctions are one of the most common non-motor symptoms of PD patients responsible for reduced quality of life. Urinary extracellular vesicles (EVs) are mostly considered to originate from the cells in the urogenital tract.

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  • The study addresses the limitations of the anticancer drug 5-fluorouracil (5-FU), including its rapid metabolism and drug resistance, by developing a novel topical gel using metal-organic frameworks (MOFs) for skin cancer treatment.
  • This new formulation, 5-FU@ZIF-8-SDG, combines 5-FU with ZIF-8 MOFs and a targeting agent (sonidegib) to enhance skin penetration and retention related to its therapeutic effects.
  • Experimental results show that the gel formulation significantly inhibits cell growth in cancer cells while being biocompatible with normal cells, suggesting its potential as an effective treatment for basal cell carcinoma (BCC).
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Purpose: Polyethylene glycol is known to improve recovery following its use in repair of acute peripheral nerve injury. The duration till which PEG works remains a subject of intense research. We studied the effect of PEG with augmentation of 20Htz of electrical stimulation (ES) following neurorrhaphy at 48 h in a rodent sciatic nerve neurotmesis model.

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Neurodegenerative disorders (NDD) have grabbed significant scientific consideration due to their fast increase in prevalence worldwide. The specific pathophysiology of the disease and the amazing changes in the brain that take place as it advances are still the top issues of contemporary research. Transcription factors play a decisive role in integrating various signal transduction pathways to ensure homeostasis.

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Diabetic retinopathy (DR) is associated with retinal neovascularization, hard exudates, inflammation, oxidative stress and cell death, leading to vision loss. Anti-vascular endothelial growth factor (Anti-VEGF) therapy through repeated intravitreal injections is an established treatment for reducing VEGF levels in the retina for inhibiting neovascularization and leakage of hard exudates to prevent vision loss. Although anti-VEGF therapy has several clinical benefits, its monthly injection potentially causes devastating ocular complications, including trauma, intraocular hemorrhage, retinal detachment, endophthalmitis, etc.

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Astrocytes are important for maintaining cholesterol metabolism, glutamate uptake, and neurotransmission. Indeed, inflammatory processes and neurodegeneration contribute to the altered morphology, gene expression, and function of astrocytes. Astrocytes, in collaboration with numerous microRNAs, regulate brain cholesterol levels as well as glutamatergic and inflammatory signaling, all of which contribute to general brain homeostasis.

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Interneuron loss/dysfunction contributes to spontaneous recurrent seizures (SRS) in chronic temporal lobe epilepsy (TLE), and interneuron grafting into the epileptic hippocampus reduces SRS and improves cognitive function. This study investigated whether graft-derived gamma-aminobutyric acid positive (GABA-ergic) interneurons directly regulate SRS and cognitive function in a rat model of chronic TLE. Human pluripotent stem cell-derived medial ganglionic eminence-like GABA-ergic progenitors, engineered to express hM4D(Gi), a designer receptor exclusively activated by designer drugs (DREADDs) through CRISPR/Cas9 technology, were grafted into hippocampi of chronically epileptic rats to facilitate the subsequent silencing of graft-derived interneurons.

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Article Synopsis
  • Persistent cognitive impairment is a common issue for veterans with chronic Gulf War Illness (GWI), linked to neuroinflammation characterized by changes in brain cells and inflammatory markers.
  • Research using rat models has shown elevated levels of leukotrienes (LTs), specifically cysteinyl LTs and LTB4, which are associated with cognitive dysfunction and increased proinflammatory cytokines in specific brain regions.
  • The study suggests that targeted drugs to modify LT signaling may help reduce neuroinflammation and enhance cognitive function in GWI, with potential monitoring of brain inflammation through blood-derived extracellular vesicles.
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Lysosomal storage diseases (LSDs) are inherited metabolic diseases caused by deficiency of lysosomal enzymes, essential for the normal development of the brain and other organs. Approximately two-thirds of the patients suffering from LSD exhibit neurological deficits and impose an escalating challenge to the medical and scientific field. The advent of induced pluripotent stem cell (iPSC) technology has aided researchers in efficiently generating functional neuronal and non-neuronal cells through directed differentiation protocols, as well as in decoding the cellular, subcellular, and molecular defects associated with LSDs using two-dimensional cultures and cerebral organoid models.

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  • Type 2 diabetes mellitus (T2DM) is rapidly rising in India, currently affecting around 77 million people, and it's linked to an increased risk of cognitive issues, particularly mild cognitive impairment (MCI).
  • In a study of 1,278 T2DM patients, higher rates of MCI were found in older age groups, with independent factors for cognitive dysfunction identified as elevated HbA1c levels, longer duration of diabetes, older age, and being female.
  • Lipidomic analyses revealed significant differences in serum lipid profiles between T2DM patients with MCI and those with normal cognition, highlighting particular triglycerides and sphingolipids that may play a role in cognitive decline associated with
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Drug-resistant melanoma is very difficult to treat, and a novel approach is needed to overcome resistance. The present study aims at identifying the alternate pathways utilized in the dual drug-resistant mouse melanoma cells (B16F10R) for their survival and proliferation. The dual drug-resistant mouse melanoma, B16F10R, was established by treating the cells with a combination of U0126 (MEK1/2 inhibitor) and LY294002 (PI3K-AKT kinase inhibitor) in a dose-escalating manner till they attained a resistance fold factor of ≥2.

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Infant and young child feeding is a key area to improve child survival and promote healthy growth and development. Nepal government has developed and implemented different programs to improve infant and young child feeding practice. However, the practice remains poor and is a major cause of malnutrition in Nepal.

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Background: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β superfamily, known to promote the tumor invasion and metastasis. There are continual progresses in understanding the role of BMP signaling pathways in carcinogenesis. However, the biological significance of BMPs in human melanoma has received very little attention.

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Background: Alcohol dependence is a significant public health problem, contributing to the global health burden. Due to its immense socio-economic burden, various psychosocial, psychological, and pharmacological approaches have attempted to alter the behaviour of the patient misusing or abusing alcohol, but their efficacy is modest at best. Therefore, there is a search for newer treatment approaches, including non-invasive brain stimulation in the management of alcohol dependence.

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The pathological alterations that manifest during the early embryonic development due to inherited and acquired factors trigger various neurodevelopmental disorders (NDDs). Besides major NDDs, there are several rare NDDs, exhibiting specific characteristics and varying levels of severity triggered due to genetic and epigenetic anomalies. The rarity of subjects, paucity of neural tissues for detailed analysis, and the unavailability of disease-specific animal models have hampered detailed comprehension of rare NDDs, imposing heightened challenge to the medical and scientific community until a decade ago.

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Enduring brain dysfunction is amid the highly manifested symptoms in veterans with Gulf War Illness (GWI). Animal studies have established that lasting brain dysfunction in GWI is concomitant with augmented oxidative stress, inflammation, and declined neurogenesis in the brain, and systemic inflammation. We hypothesize that drugs capable of restoring redox homeostasis in GWI will improve cognitive and mood function with modulation of neuroinflammation and neurogenesis.

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Extracellular vesicles (EVs) released from cells play vital roles in intercellular communication. Moreover, EVs released from stem cells have therapeutic properties. This review confers the potential of brain-derived EVs in the cerebrospinal fluid (CSF) and the serum as sources of epilepsy-related biomarkers, and the promise of mesenchymal stem cell (MSC)-derived EVs for easing status epilepticus (SE)-induced adverse changes in the brain.

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Extracellular vesicles (EVs) are gaining tremendous importance in comprehending central nervous system (CNS) function and treating neurological disorders because of their role in intercellular communication and reparative processes, and suitability as drug delivery vehicles. Since EVs have lipid membranes, they cross the blood-brain barrier easily and communicate with target neurons and glia even deep inside the brain. EVs from various sources have been isolated, characterized, and tailored for promoting beneficial effects in conditions, such as brain injury and disease.

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