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Background: Primary uterine alveolar soft part sarcoma (ASPS) is a rare, indolent mesenchymal malignancy with less than 40 patients documented in the literature. Case: We report an example of ASPS in a 61-year-old postmenopausal woman. Macroscopically, the uterus showed multiple nodular masses. Microscopic examination revealed tumor arranged in nests and alveolar pattern. The tumor cells were moderately to markedly pleomorphic, epithelioid to polygonal, with eccentrically placed nuclei, vesicular chromatin, prominent macro-nucleoli, and moderate to abundant eosinophilic cytoplasm. PAS-positive and diastase-resistant intracytoplasmic crystals were also seen in some tumor cells. On immunohistochemistry, the tumor cells showed diffuse positivity for vimentin and nuclear positivity for TFE3, a surrogate marker for ASPS. These were negative for SMA, desmin, CD10, h-caldesmon, cyclin D1, EMA, Melan A, and CD34. SMARCB1 expression was retained. Based on the histopathology and IHC, a final diagnosis of uterine ASPS was rendered. Conclusions: Knowledge of the characteristic histopathologic and immunohistochemical features can help accurately diagnose such rare tumors. Knowledge of the characteristic histopathologic and immunohistochemical features can help accurately diagnose such rare sarcoma in an uncommon site with an unusual age. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency has been linked to several major chronic diseases, such as cardiovascular and neurodegenerative diseases, diabetes, and cancer, linked to oxidative stress, inflammation, and aging. Vitamin D deficiency appears to be particularly harmful to the cardiovascular system, as it can cause endothelial dysfunctioning and vascular abnormalities through the modulation of various downstream mechanisms. As a result, new research indicates that therapeutic approaches targeting vitamin D inadequacies or its significant downstream effects, such as impaired autophagy, abnormal pro-inflammatory and pro-oxidant reactions, may delay the onset and severity of major cerebrovascular disorders such as stroke and neurologic malformations. Vitamin D modulates the various molecular pathways, i.e., Nitric Oxide, PI3K-Akt Pathway, cAMP pathway, NF-kB Pathway, Sirtuin 1, Nrf2, FOXO, in cerebrovascular disorder. The current review shows evidence for vitamin D's mitigating or slowing the progression of these cerebrovascular disorders, which are significant causes of disability and death worldwide. [ABSTRACT FROM AUTHOR]

The inflammatory and immunological responses play a significant role after stroke. The innate immune activation stimulated by microglia during stroke results in the migration of macrophages and lymphocytes into the brain and are responsible for tissue damage. The immune response and inflammation following stroke have no defined targets, and the intricacies of the immunological and inflammatory processes are only partially understood. Innate immune cells enter the brain and meninges during the acute phase, which can cause ischemia damage. Activation of systemic immunity is caused by danger signals sent into the bloodstream by injured brain cells, which is followed by a significant immunodepression that encourages life-threatening infections. Neuropsychiatric sequelae, a major source of post-stroke morbidity, may be induced by an adaptive immune response that is initiated by antigen presentation during the chronic period and is directed against the brain. Thus, the current review discusses the role of immune response and inflammation in stroke pathogenesis, their role in the progression of injury during the stroke, and the emerging targets for the modulation of the mechanism of immune response and inflammation that may have possible therapeutic benefits against stroke. [ABSTRACT FROM AUTHOR]

The growth factor brain-derived neurotrophic factor (BDNF), and its receptor tropomyosin-related kinase receptor type B (TrkB) play an active role in numerous areas of the adult brain, where they regulate the neuronal activity, function, and survival. Upregulation and downregulation of BDNF expression are critical for the physiology of neuronal circuits and functioning in the brain. Loss of BDNF function has been reported in the brains of patients with neurodegenerative or psychiatric disorders. This article reviews the BDNF gene structure, transport, secretion, expression and functions in the brain. This article also implicates BDNF in several brain-related disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, major depressive disorder, schizophrenia, epilepsy and bipolar disorder. [ABSTRACT FROM AUTHOR]

Renal I/R injury is a severe medical condition contributing to acute kidney injury (AKI), leading to rapid kidney dysfunction and high mortality rates. It is generally observed during renal transplantation, shock, trauma, and urologic and cardiovascular surgery, for which there is no effective treatment. Cell death and damage are commonly linked to I/R. Cell death triggered by iron-dependent lipid peroxidation, such as ferroptosis, has been demonstrated to have a significant detrimental effect in renal IRI models, making it a new type of cell death currently being researched. Ferroptosis is a nonapoptotic type of cell death that occurs when free iron enters the cell and is a critical component of many biological processes. In ferroptosis-induced renal I/R injury, iron chelators such as Deferasirox, Deferiprone, and lipophilic antioxidants are currently suppressed lipid peroxidation Liproxstatin-1 (Lip-1), Ferrostatin-1 along with antioxidants like vitamin and quercetin. Ferroptosis has been considered a potential target for pharmaceutical intervention to alleviate renal IRI-associated cell damage. Thus, this review emphasized the role of ferroptosis and its inhibition in renal IRI. Also, Pharmacological modulation of ferroptosis mechanism in renal I/R injury has been conferred. [ABSTRACT FROM AUTHOR]

It is considered a significant challenge to understand the neuronal cell death mechanisms with a suitable cure for neurodegenerative disorders in the coming years. Calpains are one of the best-considered "cysteine proteases activated" in brain disorders. Calpain is an important marker and mediator in the pathophysiology of neurodegeneration. Calpain activation being the essential neurodegenerative factor causing apoptotic machinery activation, it is crucial to develop reliable and effective approaches to prevent calpain-mediated apoptosis in degenerating neurons. It has been recently seen that the "inhibition of calpain activation" has appeared as a possible therapeutic target for managing neurodegenerative diseases. A systematic literature review of PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was conducted. The present article reviews the basic pathobiology and role of selective calpain inhibitors used in various neurodegenerative diseases as a therapeutic target. [ABSTRACT FROM AUTHOR]

Cerebral ischemia is one of the most devastating brain injuries and a primary cause of acquired and persistent disability worldwide. Despite ongoing therapeutic interventions at both the experimental and clinical levels, options for stroke-related brain injury are still limited. Several evidence suggests that autophagy is triggered in response to cerebral ischemia, therefore targeting autophagy-related signaling pathways can provide a new direction for the therapeutic implications in the ischemic injury. Autophagy is a highly conserved lysosomal-dependent pathway that degrades and recycles damaged or non-essential cellular components to maintain neuronal homeostasis. But, whether autophagy activation promotes cell survival against ischemic injury or, on the contrary, causes neuronal death is still under debate. We performed an extensive literature search from PubMed, Bentham and Elsevier for various aspects related to molecular mechanisms and pathobiology involved in autophagy and several pre-clinical studies justifiable further in the clinical trials. Autophagy modulates various downstream molecular cascades, i.e., mTOR, NF-κB, HIF-1, PPAR-γ, MAPK, UPR, and ROS pathways in cerebral ischemic injury. In this review, the various approaches and their implementation in the translational research in ischemic injury into practices has been covered. It will assist researchers in finding a way to cross the unbridgeable chasm between the pre-clinical and clinical studies. [ABSTRACT FROM AUTHOR]

Introduction: Ischemia–reperfusion injury (IRI) is the inexplicable aggravation of cellular dysfunction that results in blood flow restoration to previously ischemic tissues. COX mediates the oxidative conversion of AA to various prostaglandins and thromboxanes, which are involved in various physiological and pathological processes. In the pathophysiology of I/R injuries, COX has been found to play an important role. I/R injuries affect most vital organs and are characterized by inflammation, oxidative stress, cell death, and apoptosis, leading to morbidity and mortality. Materials and methods: A systematic literature review of Bentham, Scopus, PubMed, Medline, and EMBASE (Elsevier) databases was carried out to understand the Nature and mechanistic interventions of the Cyclooxygenase modulations in ischemic injury. Here, we have discussed the COX Physiology and downstream signalling pathways modulated by COX, e.g., Camp Pathway, Peroxisome Proliferator-Activated Receptor Activity, NF-kB Signalling, PI3K/Akt Signalling in ischemic injury. Conclusion: This review will discuss the various COX types, specifically COX-1 and COX-2, which are involved in developing I/R injury in organs such as the brain, spinal cord, heart, kidney, liver, and intestine. [ABSTRACT FROM AUTHOR]