Publications by authors named "Bellamkonda R"

Objective: To develop an implantable device capable of delivering intracranial cytostatic hypothermia in swine.

Background: Patients with glioblastoma (GBM) require novel approaches to treatment. We have previously demonstrated that intra-tumoral, non-freezing, 'cytostatic' hypothermia, can safely stunt GBM growth and effectively prolong survival in rodents with GBM.

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The blood-brain barrier, essential for protecting the central nervous system, also restricts drug delivery to this region. Thus, delivering drugs across the blood-brain barrier is an active research area in immunology, oncology, and neurology; moreover, novel methods are urgently needed to expand therapeutic options for central nervous system pathologies. While previous strategies have focused on small molecules that modulate blood-brain barrier permeability or penetrate the barrier, there is an increased focus on biomedical devices-external or implanted-for improving drug delivery.

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Article Synopsis
  • The study addresses a key challenge in treating glioblastoma (GBM) by using a new device that offers continuous access to tumors, improving our understanding of tumor progression and treatment responses.
  • Researchers tested an aligned nanofiber device in rodent models and found it to be safe, providing ample high-quality samples for genomic analyses and allowing for the study of tumor behavior over time.
  • The findings suggest that this device could become a valuable tool for monitoring GBM and tailoring clinical treatments based on real-time data from the tumor environment.
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Fatty liver is the earliest response of the liver to excessive alcohol consumption. Previously we identified that chronic alcohol administration increases levels of stomach-derived hormone, ghrelin, which by reducing circulating insulin levels, ultimately contributes to the development of alcohol-associated liver disease (ALD). In addition, ghrelin directly promotes fat accumulation in hepatocytes by enhancing de novo lipogenesis.

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The development of alcohol-associated liver disease (ALD) is associated with disorganized Golgi apparatus and accelerated phagophore formation. While Golgi membranes may contribute to phagophores, association between Golgi alterations and macroautophagy/autophagy remains unclear. GOLGA4/p230 (golgin A4), a dimeric Golgi matrix protein, participates in phagophore formation, but the underlying mechanism is elusive.

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  • The study explored how Salacia reticulata (SR) and simvastatin (SVS) affect oxidative stress and insulin resistance in rats on a high-fat diet.
  • Results showed that both SR and SVS significantly reduced harmful effects of high-fat diets, like elevated triglycerides and LDL cholesterol, while increasing HDL levels and improving antioxidant enzyme activity.
  • SR outperformed SVS, suggesting that these treatments could be a new approach to managing obesity and metabolic disorders.
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  • Fatty liver disease is the initial response to excessive alcohol consumption, making the liver more vulnerable to severe liver issues.
  • The study focused on the effects of GLP-1 agonist exendin-4 on chronic alcohol-induced liver problems in rats, assessing its impact on hormone levels and fat metabolism.
  • Results showed that exendin-4 improved liver health by enhancing insulin signaling and reducing fat accumulation in the liver without affecting overall body weight.
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Thyroid storm is a rare life-threatening condition characterized by severe and exaggerated clinical manifestations of thyrotoxicosis. It can be precipitated by a myriad of acute events and stressors including but not limited to surgery, trauma, or infections. Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily associated with respiratory symptoms, has been reported to be a likely precipitating cause of thyroid storm in a few cases.

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Chimeric antigen receptor (CAR) T cell therapy in glioblastoma faces many challenges including insufficient CAR T cell abundance and antigen-negative tumor cells evading targeting. Unfortunately, preclinical studies evaluating CAR T cells in glioblastoma focus on tumor models that express a single antigen, use immunocompromised animals, and/or pre-treat with lymphodepleting agents. While lymphodepletion enhances CAR T cell efficacy, it diminishes the endogenous immune system that has the potential for tumor eradication.

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Patients with glioblastoma (GBM) have limited options and require novel approaches to treatment. Here, we studied and deployed nonfreezing "cytostatic" hypothermia to stunt GBM growth. This growth-halting method contrasts with ablative, cryogenic hypothermia that kills both neoplastic and infiltrated healthy tissue.

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Introduction: India reported a severe public health challenge not only due to the COVID-19 outbreak but also the increasing number of associated mucormycosis cases since 2021.This study aimed at developing artificial intelligence based models to predict the risk of mucormycosis among the patients at the time of discharge from hospital.

Methods: The dataset included of 1229 COVID-19 positive patients, and additional 214 inpatients, COVID-19 positive as well as infected with mucormycosis.

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Owing to the coronavirus disease 2019 (COVID-19) pandemic, digitalization is booming in all sectors, including health care. This study provides evidence of using a social networking mobile app as a telemedicine tool during the pandemic in India. The data include telemedicine conversations of 318 COVID-19 patients who were consulted over WhatsApp during the period March 31 to April 16, 2021, and monitored during a quarantine period of 17 days.

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The brain processes information by transmitting signals through highly connected and dynamic networks of neurons. Neurons use specific cellular structures, including axons, dendrites and synapses, and specific molecules, including cell adhesion molecules, ion channels and chemical receptors to form, maintain and communicate among cells in the networks. These cellular and molecular processes take place in environments rich of mechanical cues, thus offering ample opportunities for mechanical regulation of neural development and function.

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Sonic hedgehog subtype of medulloblastoma (SHH MB) with metastasis or specific clinical or molecular alteration shas a poor prognosis and current therapy results in long-term cognitive impairment in the majority of survivors. Thus, a great need exists for new targeted therapeutic approaches to more effectively treat SHH MB in children. Imipramine blue (IB), a novel molecule with anti-tumor properties, inhibits the NADPH oxidase (NOX) family of enzymes, which are critical for SHH MB survival and treatment resistance.

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Traumatic brain injury (TBI) by an external physical impact results in compromised brain function via undesired neuronal death. Following the injury, resident and peripheral immune cells, astrocytes, and neural stem cells (NSCs) cooperatively contribute to the recovery of the neuronal function after TBI. However, excessive pro-inflammatory responses of immune cells, and the disappearance of endogenous NSCs at the injury site during the acute phase of TBI, can exacerbate TBI progression leading to incomplete healing.

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Severe traumatic brain injury (sTBI) survivors experience permanent functional disabilities due to significant volume loss and the brain's poor capacity to regenerate. Chondroitin sulfate glycosaminoglycans (CS-GAGs) are key regulators of growth factor signaling and neural stem cell homeostasis in the brain. However, the efficacy of engineered CS (eCS) matrices in mediating structural and functional recovery chronically after sTBI has not been investigated.

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Traumatic brain injury (TBI) triggers multiple biochemical and cellular processes that exacerbate brain tissue damage through a secondary injury. Therapies that prevent or limit the evolution of secondary injury could significantly reduce the neurological deficits associated with TBI. Mesenchymal stem cell (MSC) transplantation after TBI can ameliorate neurological deficits by modulating inflammation and enhancing the expression of neurotrophic factors.

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Background: Appropriately modulating inflammation after traumatic brain injury (TBI) may prevent disabilities for the millions of those inflicted annually. In TBI, cellular mediators of inflammation, including macrophages and microglia, possess a range of phenotypes relevant for an immunomodulatory therapeutic approach. It is thought that early phenotypic modulation of these cells will have a cascading healing effect.

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Objective: Successful application of chronic intracortical electrodes remains highly variable. The biological mechanisms leading to electrode failure are still being explored. Recent work has shown a correlation between blood-brain barrier (BBB) integrity and long-term recordings.

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Treatment of neuroepithelial cancers remains a daunting clinical challenge, particularly due to an inability to address rampant invasion deep into eloquent regions of the brain. Given the lack of access, and the dispersed nature of brain tumor cells, we explore the possibility of electric fields inducing directed tumor cell migration. In this study we investigate the properties of populations of brain cancer undergoing electrotaxis, a phenomenon whereby cells are directed to migrate under control of an electrical field.

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Brain tumors remain a great clinical challenge, in part due to their capacity to invade into eloquent, inoperable regions of the brain. In contrast, inflammation in the central nervous system (CNS) due to injuries activates microglia and astrocytes culminating in an astroglial scar that typically "walls-off" the injury site. Here, the hypothesis is tested that targeting peritumoral cells surrounding tumors to activate them via an inflammatory stimulus that recapitulates the sequelae of a traumatic CNS injury, could generate an environment that would wall-off and contain invasive tumors in the brain.

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In vitro transcribed (IVT) mRNA is an appealing platform for next generation vaccines, as it can be manufactured rapidly at large scale to meet emerging pathogens. However, its performance as a robust vaccine is strengthened by supplemental immune stimulation, which is typically provided by adjuvant formulations that facilitate delivery and stimulate immune responses. Here, we present a strategy for increasing translation of a model IVT mRNA vaccine while simultaneously modulating its immune-stimulatory properties in a programmable fashion, without relying on delivery vehicle formulations.

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Injury to the central nervous system (CNS) can leave patients with devastating neurological deficits that may permanently impair independence and diminish quality of life. Recent insights into how the CNS responds to injury and reacts to critically timed interventions are being translated into clinical applications that have the capacity to drastically improve outcomes for patients suffering from permanent neurological deficits due to spinal cord injury, stroke, or other CNS disorders. The translation of such knowledge into practical and impactful treatments involves the strategic collaboration between neurosurgeons, clinicians, therapists, scientists, and industry.

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In this study we investigated nanoliposome as an approach to tailoring the pharmacology of cerivastatin as a disease-modifying drug for pulmonary arterial hypertension (PAH). Cerivastatin encapsulated liposomes with an average diameter of 98 ± 27 nm were generated by a thin film and freeze-thaw process. The nanoliposomes demonstrated sustained drug-release kinetics in vitro and inhibited proliferation of pulmonary artery (PA) smooth muscle cells with significantly less cellular cytotoxicity as compared with free cerivastatin.

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Traumatic brain injury (TBI) can occur across wide segments of the population, presenting in a heterogeneous manner that makes diagnosis inconsistent and management challenging. Biomarkers offer the potential to objectively identify injury status, severity, and phenotype by measuring the relative concentrations of endogenous molecules in readily accessible biofluids. Through a data-driven, discovery approach, novel biomarker candidates for TBI were identified in the serum lipidome of adult male Sprague-Dawley rats in the first week following moderate controlled cortical impact (CCI).

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