Publications by authors named "Bhakta P Gaire"

Article Synopsis
  • Pathological tau isoforms, particularly hyperphosphorylated tau at serine 396, and tau oligomers were found in the retinas of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD), indicating a potential link between tauopathy and retinal changes.
  • The study analyzed retinal cross-sections from 25 patients with MCI or AD and 16 cognitively normal controls, revealing a significant reduction in retinal ganglion cells (RGCs) and increased signs of cell distress in MCI and AD patients compared to controls.
  • Findings showed that higher amounts of pS396-tau in RGCs were strongly correlated with decreased RGC integrity and related to severity in cognitive decline, suggesting that retinal
View Article and Find Full Text PDF

Naturally occurring homoisoflavonoids isolated from some Liliaceae plants have been reported to have diverse biological activities (e.g., antioxidant, anti-inflammatory, and anti-angiogenic effects).

View Article and Find Full Text PDF
Article Synopsis
  • Recent advancements in Alzheimer's disease (AD) diagnostics and treatments show promise, but there's still a significant need for effective therapies, indicating that more research is essential.
  • Evidence suggests that microbial infections could play a role in AD, with specific bacteria like Chlamydia pneumoniae (Cp) being frequently found in the brains of AD patients.
  • Despite its presence in AD brains, there is currently no conclusive research proving whether Cp directly causes or contributes to AD progression, prompting a discussion of potential mechanisms connecting Cp to AD pathology.
View Article and Find Full Text PDF
Article Synopsis
  • The retina is being studied as a promising, noninvasive way to diagnose and track Alzheimer's disease (AD) because it shows similar pathological features to those found in the brain, like amyloid and tau protein abnormalities.
  • Research has found that structural and functional issues in the retina, including reduced blood flow and inflammation, correlate with the severity of AD symptoms in patients.
  • Advanced imaging technologies are now capable of detecting AD-related changes in the retina, which could help in early diagnosis and monitoring of the disease, but more studies are needed with larger, diverse groups to confirm these findings and improve screening methods.
View Article and Find Full Text PDF
Article Synopsis
  • - Osteopontin (OPN) is a vital cytokine in bone marrow-derived macrophages (BMMΦ) that influences immune responses by promoting either an anti-inflammatory or pro-inflammatory state depending on its levels; glatiramer acetate (GA) boosts OPN expression to support healing.
  • - Using mass spectrometry for global proteome profiling, researchers found 631 differentially expressed proteins (DEPs) in macrophages with either OPN knockout or GA-induced OPN, many of which are linked to immune functions and include notable proteins such as UCHL1 and HMOX-1.
  • - The study revealed that UCHL1, tied to anti-inflammatory responses, is regulated by OPN in
View Article and Find Full Text PDF
Article Synopsis
  • * Despite their potential long-term effectiveness, the outcomes of ChEI treatment vary due to factors like inconsistent dosing, guidelines, provider attitudes, and a lack of awareness, which can hinder patient care.
  • * Understanding the biological and genetic factors influencing how patients respond to ChEI is essential for developing personalized treatment strategies that enhance the overall effectiveness of therapies in Alzheimer's and related diseases.
View Article and Find Full Text PDF

, popularly known as a miracle tree or tree of life, has been extensively used as a functional food and nutritional asset worldwide. Ethnomedicinal and traditional uses of indicate that this plant might have a pleiotropic therapeutic efficacy against most human ailments. In fact, is reported to have several pharmacological activities, including antioxidant, antibacterial, antifungal, antidiabetic, antipyretic, antiulcer, antispasmodic, antihypertensive, antitumor, hepatoprotective, and cardiac stimulant properties.

View Article and Find Full Text PDF

A typical neuron consists of a soma, a single axon with numerous nerve terminals, and multiple dendritic trunks with numerous branches. Each of the 100 billion neurons in the brain has on average 7,000 synaptic connections to other neurons. The neuronal endolysosomal compartments for the degradation of axonal and dendritic waste are located in the soma region.

View Article and Find Full Text PDF

Microglial activation is considered as the critical pathogenic event in diverse central nervous system disorders including cerebral ischemia. Proinflammatory responses of activated microglia have been well reported in the ischemic brain and neuroinflammatory responses of activated microglia have been believed to be the potential therapeutic strategy. However, despite having proinflammatory roles, microglia can have significant anti-inflammatory roles and they are associated with the production of growth factors which are responsible for neuroprotection and recovery after ischemic injury.

View Article and Find Full Text PDF

Activation of microglia and/or astrocytes often releases proinflammatory molecules as critical pathogenic mediators that can promote neuroinflammation and secondary brain damages in diverse diseases of the central nervous system (CNS). Therefore, controlling the activation of glial cells and their neuroinflammatory responses has been considered as a potential therapeutic strategy for treating neuroinflammatory diseases. Recently, receptor-mediated lysophospholipid signaling, sphingosine 1-phosphate (S1P) receptor- and lysophosphatidic acid (LPA) receptor-mediated signaling in particular, has drawn scientific interest because of its critical roles in pathogenies of diverse neurological diseases such as neuropathic pain, systemic sclerosis, spinal cord injury, multiple sclerosis, cerebral ischemia, traumatic brain injury, hypoxia, hydrocephalus, and neuropsychiatric disorders.

View Article and Find Full Text PDF

Despite being a major global health concern, cerebral ischemia/stroke has limited therapeutic options. Tissue plasminogen activator (tPA) is the only available medication to manage acute ischemic stroke, but this medication is associated with adverse effects and has a narrow therapeutic time window. Curcumin, a polyphenol that is abundantly present in the rhizome of the turmeric plant (), has shown promising neuroprotective effects in animal models of neurodegenerative diseases, including cerebral ischemia.

View Article and Find Full Text PDF

Tanshinones, lipophilic diterpenes isolated from the rhizome of Salvia miltiorrhiza, have diverse pharmacological activities against human ailments including neurological diseases. In fact, tanshinones have been used to treat heart diseases, stroke, and vascular diseases in traditional Chinese medicine. During the last decade, tanshinones have been the most widely studied phytochemicals for their neuroprotective effects against experimental models of cerebral ischemia and Alzheimer's diseases.

View Article and Find Full Text PDF

Nitric oxide (NO) is a neurotransmitter that mediates the activation and inhibition of inflammatory cascades. Even though physiological NO is required for defense against various pathogens, excessive NO can trigger inflammatory signaling and cell death through reactive nitrogen species-induced oxidative stress. Excessive NO production by activated microglial cells is specifically associated with neuroinflammatory and neurodegenerative conditions, such as Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, ischemia, hypoxia, multiple sclerosis, and other afflictions of the central nervous system (CNS).

View Article and Find Full Text PDF

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19), is a worldwide pandemic, as declared by the World Health Organization (WHO). It is a respiratory virus that infects people of all ages. Although it may present with mild to no symptoms in most patients, those who are older, immunocompromised, or with multiple comorbidities may present with severe and life-threatening infections.

View Article and Find Full Text PDF

The search for novel therapeutic agents for the management of cerebral ischemia/stroke has become an appealing research interest in the recent past. Neuroprotective phytochemicals as novel stroke drug candidates have recently drawn significant interests from stroke scientists due to their strong brain protective effects in animal stroke models. The underlying mechanism of action is likely owing to their anti-inflammatory properties, even though other mechanisms such as anti-oxidation and vasculoprotection have also been proposed.

View Article and Find Full Text PDF

Lysophosphatidic acid receptor 1 (LPA) contributes to brain injury following transient focal cerebral ischemia. However, the mechanism remains unclear. Here, we investigated whether nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation might be an underlying mechanism involved in the pathogenesis of brain injury associated with LPA following ischemic challenge with transient middle cerebral artery occlusion (tMCAO).

View Article and Find Full Text PDF

Stroke is a leading cause of death. Stroke survivors often suffer from long-term functional disability. This study demonstrated neuroprotective effects of BMS-986020 (BMS), a selective lysophosphatidic acid receptor 1 (LPA) antagonist under clinical trials for lung fibrosis and psoriasis, against both acute and sub-acute injuries after ischemic stroke by employing a mouse model with transient middle cerebral artery occlusion (tMCAO).

View Article and Find Full Text PDF

Sphingosine 1-phosphate (S1P) is an important lipid biomolecule that exerts pleiotropic cellular actions as it binds to and activates its five G-protein-coupled receptors, S1P. Through these receptors, S1P can mediate diverse biological activities in both healthy and diseased conditions. S1P is produced by S1P-producing enzymes, sphingosine kinases (SphK1 and SphK2), and is abundantly present in different organs, including the brain.

View Article and Find Full Text PDF

Advanced glycation end products (AGEs) are produced through the binding of glycated protein or lipid with sugar, and they are known to be involved in the pathogenesis of both age-dependent and independent neurological complications. Among dicarbonyl compounds, methylglyoxal (MGO), which is produced from glucose breakdown, is a key precursor of AGE formation and neurotoxicity. Several studies have shown the toxic effects of bovine serum albumin (BSA)-AGE (prepared with glucose, sucrose or fructose) both in in vitro and in vivo.

View Article and Find Full Text PDF

The pathogenesis of psoriasis, an immune-mediated chronic skin barrier disease, is not fully understood yet. Here, we identified lysophosphatidic acid (LPA) receptor 5 (LPA)-mediated signaling as a novel pathogenic factor in psoriasis using an imiquimod-induced psoriasis mouse model. Amounts of most LPA species were markedly elevated in injured skin of psoriasis mice, along with LPA upregulation in injured skin.

View Article and Find Full Text PDF

Tumor necrosis factor-alpha (TNF-α) is a well-known pro-inflammatory cytokine responsible for the modulation of the immune system. TNF-α plays a critical role in almost every type of inflammatory disorder, including central nervous system (CNS) diseases. Although TNF-α is a well-studied component of inflammatory responses, its functioning in diverse cell types is still unclear.

View Article and Find Full Text PDF

Isorhapontigenin (ISO), a tetrahydroxylated stilbenoid, is an analog of resveratrol (Rsv). The various biological activities of Rsv and its derivatives have been previously reported in the context of both cancer and inflammation. However, the anti-cancer effect of ISO against breast cancer has not been well established, despite being an orally bioavailable dietary polyphenol.

View Article and Find Full Text PDF