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Isatin or 1H-indole-2,3-dione skeleton has been playing a significant role in drug de-sign and development. Isatin itself and many of its derivatives are widely distributed in naturally occurring bioactive compounds. Various synthetic isatin derivatives were found to possess a broad range of significant pharmacological efficacies especially anti-cancer activity against a wide variety of cancer cell lines. Interestingly, on a few occasions, some isatin-derived scaffolds were reported as more potent than the tested reputed drug molecules. As a result, isatin-derived compounds have been gaining significant attention in cancer-based drug developments. In this re-view, we have summarized literature reported during the last two decades related to the synthesis of structurally diverse isatin-derived scaffolds with promising anti-cancer activities.
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Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutation of the NF1 gene that is associated with various symptoms, including the formation of benign tumors, called neurofibromas, within nerves. Drug treatments are currently limited. The mitogen-activated protein kinase kinase (MEK) inhibitor selumetinib is used for a subset of plexiform neurofibromas (PNs) but is not always effective and can cause side effects. Therefore, there is a clear need to discover new drugs to target NF1-deficient tumor cells. Using a Drosophila cell model of NF1, we performed synthetic lethal screens to identify novel drug targets. We identified 54 gene candidates, which were validated with variable dose analysis as a secondary screen. Pathways associated with five candidates could be targeted using existing drugs. Among these, chloroquine (CQ) and bafilomycin A1, known to target the autophagy pathway, showed the greatest potential for selectively killing NF1-deficient Drosophila cells. When further investigating autophagy-related genes, we found that 14 out of 30 genes tested had a synthetic lethal interaction with NF1. These 14 genes are involved in multiple aspects of the autophagy pathway and can be targeted with additional drugs that mediate the autophagy pathway, although CQ was the most effective. The lethal effect of autophagy inhibitors was conserved in a panel of human NF1-deficient Schwann cell lines, highlighting their translational potential. The effect of CQ was also conserved in a Drosophila NF1 in vivo model and in a xenografted NF1-deficient tumor cell line grown in mice, with CQ treatment resulting in a more significant reduction in tumor growth than selumetinib treatment. Furthermore, combined treatment with CQ and selumetinib resulted in a further reduction in NF1-deficient cell viability. In conclusion, NF1-deficient cells are vulnerable to disruption of the autophagy pathway. This pathway represents a promising target for the treatment of NF1-associated tumors, and we identified CQ as a candidate drug for the treatment of NF1 tumors.
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Protein kinase C (PKC) is a diverse enzyme family crucial for cell signalling in various organs. Its dysregulation is linked to numerous diseases, including cancer, cardiovascular disorders, and neurological problems. In the brain, PKC plays pivotal roles in synaptic plasticity, learning, memory, and neuronal survival. Specifically, PKC's involvement in Alzheimer's Disease (AD) pathogenesis is of significant interest. The dysregulation of PKC signalling has been linked to neurological disorders, including AD. This review elucidates PKC's pivotal role in neurological health, particularly its implications in AD pathogenesis and chronic alcohol addiction. AD, characterised by neurodegeneration, implicates PKC dysregulation in synaptic dysfunction and cognitive decline. Conversely, chronic alcohol consumption elicits neural adaptations intertwined with PKC signalling, exacerbating addictive behaviours. By unravelling PKC's involvement in these afflictions, potential therapeutic avenues emerge, offering promise for ameliorating their debilitating effects. This review navigates the complex interplay between PKC, AD pathology, and alcohol addiction, illuminating pathways for future neurotherapeutic interventions.
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Objectives:The aim of the study was to examine the incidence, baseline characteristics, and outcomes of Chimeric Antigen Receptor T-cell (CAR-T) therapy admissions in individuals who developed acute respiratory failure (ARF). The study utilized the National Inpatient Sample (NIS) database for the years 2017 to 2020. Methods: The study identified CAR-T cell therapy hospitalizations through the International Classification of Diseases, Tenth Revision, Procedure Coding System (ICD-10-PCS) codes. Patients with acute respiratory failure (ARF) were further classified using specific International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes. Descriptive statistics were performed to analyze baseline characteristics, comorbidities, complications, and outcomes. Results: Analysis of the NIS Database identified 5545 CAR-T therapy admissions between 2017 and 2020, revealing a rising trend over time. In our study, we found that hypertension (39%), dyslipidemia (21.7%), and venous thromboembolism (13%) were the most frequently observed comorbidities in CAR-T cell therapy admissions. Acute respiratory failure (ARF) was reported in 7.1% of admissions, and they had higher all-cause in-hospital mortality than CAR-T cell therapy admissions without ARF (32.9% vs 1.3%, P < 0.001). ARF admissions that required invasive mechanical ventilation (IMV) also had higher all-cause in-hospital mortality compared to admissions not requiring IMV (48.9% vs 11.8%, P = 0.001). There was no difference in the mortality rate among admissions with non-Hodgkin's Lymphoma, Multiple Myeloma, and Leukemia that utilized CAR-T therapy. Conclusions: In this largest study to date, we illuminate the incidence and outcomes of CAR-T cell therapy admissions with ARF. Higher mortality rates were observed in CAR-T cell therapy admissions with ARF. The study emphasizes the crucial role of interdisciplinary collaboration in CAR-T patient management and calls for additional research to clarify ARF's etiology and inform effective management strategies.
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Atrial myxomas are typically found in the left atrium and are the most common among overall rare cardiac tumors. Herein, we describe the clinical course of a 72-year-old female with non-small cell lung adenocarcinoma found to have an atrial mass during an imaging for evaluation for lung cancer progression. Differentiating between distinct types of masses can pose a challenge to the treatment team especially in the setting of exiting malignancy. This case demonstrates the complex decision making involved in the diagnosis, and timing of intervention to remove atrial mass in patients with frailty and a fast-growing cardiac mass.
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BACKGROUND: Oral Potentially Malignant Disorders (OPMDs) refer to a heterogenous group of clinical presentations with heightened rate of malignant transformation. Identification of risk levels in OPMDs is crucial to determine the need for active intervention in high-risk patients and routine follow-up in low-risk ones. Machine learning models has shown tremendous potential in several areas of dentistry that strongly suggest its application to estimate rate of malignant transformation of precancerous lesions. METHODS: A comprehensive literature search was performed on Pubmed/MEDLINE, Web of Science, Scopus, Embase, Cochrane Library database to identify articles including machine learning models and algorithms to predict malignant transformation in OPMDs. Relevant bibliographic data, study characteristics, and outcomes were extracted for eligible studies. Quality of the included studies was assessed through the IJMEDI checklist. RESULTS: Fifteen articles were found suitable for the review as per the PECOS criteria. Amongst all studies, highest sensitivity (100%) was recorded for U-net architecture, Peaks Random forest model, and Partial least squares discriminant analysis (PLSDA). Highest specificity (100%) was noted for PLSDA. Range of overall accuracy in risk prediction was between 95.4% and 74%. CONCLUSION: Machine learning proved to be a viable tool in risk prediction, demonstrating heightened sensitivity, automation, and improved accuracy for predicting transformation of OPMDs. It presents an effective approach for incorporating multiple variables to monitor the progression of OPMDs and predict their malignant potential. However, its sensitivity to dataset characteristics necessitates the optimization of input parameters to maximize the efficiency of the classifiers.
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Transformação Celular Neoplásica , Aprendizado de Máquina , Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/patologia , Medição de Risco/métodos , AlgoritmosRESUMO
BACKGROUND: Avelumab, a programmed death ligand-1 inhibitor, has shown success in providing durable responses for difficult-to-treat Merkel cell carcinomas (MCCs). OBJECTIVE: Evaluate the efficacy and safety of avelumab in the treatment of advanced MCC. METHODS: Studies reporting the use of avelumab as a monotherapy or in combination with other agents in the treatment of stage III or IV (advanced) MCC were included. The primary outcomes were overall response rate, overall survival (OS), and treatment-related adverse events. RESULTS: A total of 48 studies were included, involving 1,565 patients with advanced MCC. Most patients were male (1,051, 67.3%) with stage IV MCC (517, 97.0%). The overall response rate was 46.1% (partial response-25.4% and complete response-20.7%) after a mean follow-up period of 9.5 months. Kaplan-Meier survival curves for the pooled stage III and IV group demonstrated OS rates of 58% at 1 year, 47% at 2 years, and 28% at 5 years after completion of treatment with avelumab (median OS: 23.1 months). The most common treatment-related adverse events consisted of constitutional (44%), gastrointestinal (19%), and dermatologic (12%) symptoms. CONCLUSION: Avelumab monotherapy and combination therapy have shown success in the overall response rate and survival for patients with advanced MCC.
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Anticorpos Monoclonais Humanizados , Carcinoma de Célula de Merkel , Neoplasias Cutâneas , Carcinoma de Célula de Merkel/tratamento farmacológico , Carcinoma de Célula de Merkel/patologia , Humanos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/mortalidade , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Estadiamento de Neoplasias , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Resultado do Tratamento , Taxa de SobrevidaRESUMO
Mostly, cardiovascular diseases are blamed for casualties in rheumatoid arthritis (RA) patients. Customarily, dyslipidemia is probably the most prevalent underlying cause of untimely demise in people suffering from RA as it hastens the expansion of atherosclerosis. The engagement of inflammatory cytokines like tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), etc., is crucial in the progression and proliferation of both RA and abnormal lipid parameters. Thus, lipid abnormalities should be monitored frequently in patients with both primary and advanced RA stages. An advanced lipid profile examination, i.e., direct role of apolipoproteins associated with various lipid molecules is a more dependable approach for better understanding of the disease and selecting suitable therapeutic targets. Therefore, studying their apolipoproteins is more relevant than assessing RA patients' altered lipid profile levels. Among the various apolipoprotein classes, Apo A1 and Apo B are primarily being focused. In addition, it also addresses how calculating Apo B:Apo A1 ratio can aid in analyzing the disease's risk. The marketed therapies available to control lipid abnormalities are associated with many other risk factors. Hence, directly targeting Apo A1 and Apo B would provide a better and safer option.
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Apolipoproteínas , Artrite Reumatoide , Doenças Cardiovasculares , Fatores de Risco de Doenças Cardíacas , Humanos , Artrite Reumatoide/metabolismo , Artrite Reumatoide/sangue , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/etiologia , Apolipoproteínas/sangue , Animais , Apolipoproteína A-I , Apolipoproteínas B/sangue , Apolipoproteínas B/metabolismo , Dislipidemias/tratamento farmacológico , Dislipidemias/sangue , Dislipidemias/metabolismoRESUMO
INTRODUCTION: Obesity increases risks of male infertility, but bariatric surgery does not improve semen quality. Recent uncontrolled studies suggest that a low-energy diet (LED) improves semen quality. Further evaluation within a randomized, controlled setting is warranted. METHODS: Men with obesity (18-60 years) with normal sperm concentration (normal count) (n = 24) or oligozoospermia (n = 43) were randomized 1:1 to either 800 kcal/day LED for 16 weeks or control, brief dietary intervention (BDI) with 16 weeks' observation. Semen parameters were compared at baseline and 16 weeks. RESULTS: Mean age of men with normal count was 39.4 ± 6.4 in BDI and 40.2 ± 9.6 years in the LED group. Mean age of men with oligozoospermia was 39.5 ± 7.5 in BDI and 37.7 ± 6.6 years in the LED group. LED caused more weight loss than BDI in men with normal count (14.4 vs 6.3 kg; P < .001) and men with oligozoospermia (17.6 vs 1.8 kg; P < .001). Compared with baseline, in men with normal count total motility (TM) increased 48 ± 17% to 60 ± 10% (P < .05) after LED, and 52 ± 8% to 61 ± 6% (P < .0001) after BDI; progressive motility (PM) increased 41 ± 16% to 53 ± 10% (P < .05) after LED, and 45 ± 8% to 54 ± 65% (P < .001) after BDI. In men with oligozoospermia compared with baseline, TM increased 35% [26] to 52% [16] (P < .05) after LED, and 43% [28] to 50% [23] (P = .0587) after BDI; PM increased 29% [23] to 46% [18] (P < .05) after LED, and 33% [25] to 44% [25] (P < .05) after BDI. No differences in postintervention TM or PM were observed between LED and BDI groups in men with normal count or oligozoospermia. CONCLUSION: LED or BDI may be sufficient to improve sperm motility in men with obesity. The effects of paternal dietary intervention on fertility outcomes requires investigation.
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Infertilidade Masculina , Oligospermia , Masculino , Humanos , Análise do Sêmen , Motilidade dos Espermatozoides , Sêmen , Contagem de Espermatozoides , Infertilidade Masculina/etiologia , Espermatozoides , Obesidade/complicações , Obesidade/cirurgiaRESUMO
BACKGROUND: Spinal cord compression (SCC) in metastatic prostate cancer (MPC) is a critical complication and multiple factors influence the optimal therapeutic strategy. We investigated the differences in practice patterns between teaching hospitals (TH) and non-teaching hospitals (NTH) across the United States. METHOD: Using the National Inpatient Sample Database (NIS), we performed a retrospective study on hospitalizations with MPC and SCC between 2016 and 2020 in US. We compared demographic factors, comorbidities, treatment modalities, duration of hospitalization, financial expenditures, and mortality between TH and NTH. We also examined the patients' characteristics and outcomes in TH and NTH based on their chosen therapeutic strategy. RESULTS: We identified 11,380 admissions with metastatic prostate cancer and SCC; 9610 in TH and 1770 in NTH. The median cost of hospitalization was $21,922 in TH and $15,141 in NTH. Although the median age and Charlson comorbidity score did not differ between two groups, patients in TH were more likely to receive intervention (radiation or surgery) compared to NTH (Surgery: 28.2% in TH vs. 23.0% in NTH & Radiation: 12.1% in TH vs. 8.2% in NTH). Mortality was lower in TH than NTH (4.5% vs. 7.9%). In both TH and NTH, a higher proportion of patients with private insurance underwent surgery (TH: Surgery 25.1% vs. Radiation 18.8% & NTH: Surgery 27.0% vs. 6.9%). Black patients were more likely to receive radiation than surgery in TH (34.2% vs. 26.8%). CONCLUSION: This study showed a greater percentage of patients underwent surgical intervention at TH compared to NTH. Additionally, the type of insurance and racial background were associated with distinctive treatment approaches.
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Hospitais de Ensino , Neoplasias da Próstata , Compressão da Medula Espinal , Humanos , Masculino , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/terapia , Compressão da Medula Espinal/mortalidade , Estados Unidos/epidemiologia , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/mortalidade , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Hospitalização/estatística & dados numéricos , Hospitalização/economia , Idoso de 80 Anos ou maisRESUMO
Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkins lymphoma. After the introduction of rituximab therapy like rituximab, cyclophosphamide, doxorubicin vincristine, prednisolone, there has been considerable improvement in the 5-year overall survival in this group of patients, but the nonresponding patients are a challenge to the clinician. The translesion polymerases are unique polymerases that make cells tolerant to DNA damage. Many point mutations are introduced owing to their inherent property of bypassing the points of lesions, preventing the cell from stalling replication. However, the impaired activity of these polymerases can lead to the development of tumors with aggressive clinical course. In this study, the gene expression levels of polymerase eta ( POLE ) were compared in 2 cohorts of patients with DLBCL: the first cohort, patients who had achieved complete response, and the second cohort, patients who were refractory to the treatment or had relapse within 2 years of treatment. There was a significantly upregulated expression in the refractory/relapse cohort compared with the complete remission cohort ( P = 0.0001). The high POLE expression levels correlated significantly with advanced disease stages (III and IV) and poor disease-free survival in the Kaplan-Meier curve. The high POLE expression levels were correlated with poor disease-free survival in nonresponder patients with DLBCL. The results concluded that patients with DLBCL with a high polymerase gene expression may show nonresponsiveness to chemotherapy; hence the functional impact of upregulated expression of POLE in DLBCL requires an in-depth assessment.
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Linfoma Difuso de Grandes Células B , Recidiva Local de Neoplasia , Humanos , Rituximab/uso terapêutico , Prognóstico , Resultado do Tratamento , Prednisona/uso terapêutico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Intervalo Livre de Doença , RecidivaRESUMO
Introduction-Whole genome sequencing of diffuse large B-cell lymphoma [DLBCL] has identified recurrent mutations involved in pathogenesis and potentially affecting response to therapy. In this pilot study, a targeted gene panel was created to identify mutations associated with relapse/refractoriness. Material and methods- A 14-gene targeted panel was designed to sequence thirteen patients who were in remission and nine eight cases that had relapsed/refractory to treatment. A paired diagnostic biopsy and a relapse biopsy were sequenced to find genes repeatedly altered in relapse. Results- A total of 751 nonsynonymous and truncating mutations were identified. Truncated mutations in NOTCH1, TNFAIP3, and CD58 were associated with poor treatment outcomes. In cases that did not respond to treatment, a high number of mutations were found in the EZH2 gene, followed by the DNA-binding domain of TP53 and MYD88. Termination mutations in the intracellular domain of NOTCH were found in 75% of non-responsive cases. Co-occurrence of loss of function mutations of TNFAIP3 and missense mutations in MYD88 was associated with a non-responsive cohort. Discussion-The study highlights mutations associated with chemotherapeutic response in DLBCL with implications for initial diagnostic biopsy response prediction.
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The term "neurodegenerative disorders" refers to a group of illnesses in which deterioration of nerve structure and function is a prominent feature. Cognitive capacities such as memory and decision-making deteriorate as a result of neuronal damage. The primary difficulty that remains is safeguarding neurons since they do not proliferate or regenerate spontaneously and are therefore not substituted by the body after they have been damaged. Millions of individuals throughout the world suffer from neurodegenerative diseases. Various pathways lead to neurodegeneration, including endoplasmic reticulum stress, calcium ion overload, mitochondrial dysfunction, reactive oxygen species generation, and apoptosis. Although different treatments and therapies are available for neuroprotection after a brain injury or damage, the obstacles are inextricably connected. Several studies have revealed the pathogenic effects of hypothermia, different breathed gases, stem cell treatments, mitochondrial transplantation, multi-pharmacological therapy, and other therapies that have improved neurological recovery and survival outcomes after brain damage. The present review highlights the use of therapeutic approaches that can be targeted to develop and understand significant therapies for treating neurodegenerative diseases.
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Lesões Encefálicas , Doenças Neurodegenerativas , Humanos , Neuroproteção , Mitocôndrias/metabolismo , Neurônios/metabolismo , Doenças Neurodegenerativas/metabolismo , Estresse do Retículo Endoplasmático , Lesões Encefálicas/metabolismo , Estresse Oxidativo/fisiologiaRESUMO
Biliary adenofibroma (BAF) is an uncommon liver tumor with a high propensity for malignant transformation. The histomorphology of BAF with malignant transformation can show a spectrum of changes ranging from benign, dysplastic to frank malignancy. Thus, the diagnosis of BAF imposes the pursuit of dysplasia/ malignancy focus. We presented a case of intrahepatic cholangiocarcinoma arising from BAF in a 49-year-old woman with detailed histomorphology. We also performed a PubMed database search and tabulated all previously reported cases of BAF with dysplasia/ malignant transformation. A statistic comparison of age, sex ratio, size of the tumor, and survival following complete resection between BAFs with and without dysplasia/ malignancy from the retrieved data is presented. Our analysis did not highlight any statistically significant difference between BAFs with and without dysplasia/ malignancy in age, sex ratio, tumor size, and survival following complete surgical resection. Our study highlights the histopathology and immunohistochemistry of a case of BAF with malignant transformation and highlights the importance of this diagnosis in management. Further longitudinal studies on a larger cohort of patients are required to validate our findings.
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Carcinoid syndrome (CS) is a unique constellation of symptoms caused by release of vasoactive substances from neuroendocrine tumors (Pandit et al., StatPearls, 2022). Neuroendocrine tumors are rare with an annual incidence of 2 in 100,000 people (Ram et al., 46:21-27, 2019). Up to 50% of patients with these tumors will develop carcinoid syndrome, which is characterized by symptoms caused by elevated levels of serotonin and most commonly include fatigue, flushing, wheezing, and non-specific gastrointestinal symptoms such as diarrhea and malabsorption (Pandit et al., StatPearls, 2022) (Fox et.al., 90:1224-1228, 2004). Over time, patients with carcinoid syndrome can develop carcinoid heart disease (CHD). CHD refers to the cardiac complications that occur when the vasoactive substances, such as serotonin, tachykinins, and prostaglandins, secreted from the carcinoid tumors. These complications most commonly include valvular abnormalities, but can also present as coronary artery damage, arrhythmias or direct myocardial injury (Ram et al., 46:21-27, 2019). While CHD is not typically an initial feature of carcinoid syndrome, it does eventually occur in up to 70% of patients with carcinoid tumors (Ram et al., 46:21-27, 2019) (Jin et.al., 146:65-73, 2021) (Macfie et.al., 224:665-669, 2022). CHD is associated with significant morbidity and mortality due to the risk of progressive heart failure (Bober et.al., 14:1179546820968101, 2020). In this case, we describe a 35-year-old Hispanic woman in South Texas with undiagnosed carcinoid syndrome for over 10 years that eventually progressed to severe CHD. In this patient's case, we emphasize how lack of access to healthcare resulted in delay of diagnosis, appropriate treatment, and worsened prognosis in this young patient.
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Introduction: Loin pain hematuria syndrome (LPHS) is a rare clinical syndrome with a reported prevalence of 1 in 10,000. The syndrome is characterized by severe pain localized to the kidney in the absence of identifiable urinary tract disease. Because of an inadequate understanding of the pathophysiology of the disease, the goal of management has been limited to symptomatic pain management. Through detailed phenotype and genotype assessment we sought to identify possible underlying etiologies. Methods: We completed a chart review, ultrasound imaging, kidney biopsy, and type IV collagen (COL4A3, COL4A4, and COL4A5) gene sequencing in 14 patients with loin pain hematuria recruited from a single center. Results: Red blood cells and red cell casts were observed within the tubules in 10 of 14 patients. The glomerular basement membrane (GBM) was normal in 11 patients and thickened in 1 patient. Staining for IgA kappa was present in 1 patient. C3 deposition without any inflammation was present in 7 patients. Arteriolar hyalinosis was present in 4 patients and endothelial cell injury was present in 6 patients. No pathogenic COL4A3, COL4A4, or COL4A5 variants were identified. Conclusion: Conventional histopathology and genetic testing for type IV collagen variants failed to identify the cause of hematuria in 14 patients with LPHS.
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Postmenopausal osteoporosis, an epidemic disorder is defined as a loss in bone mineral density and a greater possibility of fractures in older women. It is a multifactorial disease under the control of various genetic, hormonal, and environmental factors. Insufficiency of estrogen hormone, leads to postmenopausal osteoporosis. Hormone replacement therapy (HRT), despite being the most effective treatment, it is associated with the risk of breast cancer and cardiovascular disorders. This review seeks to compile the most recent information on medicinal plants and natural compounds used to treat and prevent postmenopausal osteoporosis. Furthermore, the origin, chemical constituents and the molecular mechanisms responsible for this therapeutic and preventive effect are also discussed. Literature research was conducted using PubMed, Science direct, Scopus, Web of Science, and Google Scholar. Different plant extracts and pure compounds exerts their antiosteoporotic activity by inhibition of RANKL and upregulation of OPG. RANKL signaling regulates osteoclast formation, characterized by increased bone turnover and osteoprotegrin is a decoy receptor for RANKL thereby preventing bone loss from excessive resorption. In addition, this review also includes the chemical structure of bioactive compounds acting on NFκB, TNF α, RUNX2. In conclusion, we propose that postmenopausal osteoporosis could be prevented or treated with herbal products.
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Fraturas Ósseas , Osteoporose Pós-Menopausa , Feminino , Humanos , Idoso , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/prevenção & controle , Densidade Óssea , Estrogênios/farmacologia , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêuticoRESUMO
Recently, much attention has been paid to chronic neuro-inflammatory condition underlying neuropathic pain. It is generally linked with thermal hyperalgesia and tactile allodynia. It results due to injury or infection in the nervous system. The neuropathic pain spectrum covers a variety of pathophysiological states, mostly involved are ischemic injury viral infections associated neuropathies, chemotherapy-induced peripheral neuropathies, autoimmune disorders, traumatic origin, hereditary neuropathies, inflammatory disorders, and channelopathies. In CNS, angiogenesis is evident in inflammation of neurons and pain in bone cancer. The role of chemokines and cytokines is dualistic; their aggressive secretion produces detrimental effects, leading to neuropathic pain. However, whether the angiogenesis contributes and exists in neuropathic pain remains doubtful. In the present review, we elucidated summary of diverse mechanisms of neuropathic pain associated with angiogenesis. Moreover, an overview of multiple targets that have provided insights on the VEGF signaling, signaling through Tie-1 and Tie-2 receptor, erythropoietin pathway promoting axonal growth are also discussed. Because angiogenesis as a result of these signaling, results in inflammation, we focused on the mechanisms of neuropathic pain. These factors are mainly responsible for the activation of post-traumatic regeneration of the PNS and CNS. Furthermore, we also reviewed synthetic and herbal treatments targeting angiogenesis in neuropathic pain.