International Journal of Applied and Basic Medical Research最新文献

Solitary fibrous tumors (SFTs) are a rare spindle cell neoplasm arising from mesenchymal cells. It was first described in the pleura. There are numerous reports that document their extrapleural locations. SFT involving the cervix is extremely rare and only a handful of cases have been reported in Indian and western literature. Previously, it was thought that SFT tumor cells differentiated from mesothelial cells into fibroblasts. With the advent of immunohistochemistry, it is revealed that tumor cells in SFT lack mesothelial characteristics but express CD34 and Bcl-2, suggesting that the tumor originates from mesenchymal tissue. Preoperative definitive diagnosis of SFT cervix is difficult.

Background: Chronic heart failure (CHF), characterized by ventricular remodeling and myocardial fibrosis, remains a major therapeutic challenge. This study investigated the cardioprotective effects of quercetin, an Astragalus-derived bioactive compound, focusing on its modulation of the Akt/Bcl-2 pathway.

Methods: This study established both H9C2 cardiomyocyte hypoxia/reoxygenation (H/R) injury models and aortic constriction-induced heart failure (HF) rat models to investigate the cardioprotective effects of quercetin. Cell viability and mitochondrial function were assessed using CCK-8 assay and Mitotracker staining, while apoptosis, reactive oxygen species (ROS) levels, and myocardial fibrosis were measured. Real-time-quantitative polymerase chain reaction and Western blot analyses were performed to examine the expression of key molecules in the Akt/Bcl-2 pathway, elucidating the molecular mechanisms by which quercetin improves ventricular remodeling and myocardial fibrosis through regulation of this signaling pathway.

Results: In H/R-injured H9C2 cells, quercetin significantly enhanced cardiomyocyte survival, inhibited apoptosis, maintained mitochondrial function, and reduced ROS in H/R-injured H9C2 cells. Molecular analysis demonstrated that quercetin regulated the Akt pathway by upregulating Bcl-2 and downregulating P53, thereby reducing apoptosis. In aortic constriction-induced HF rats, quercetin improved cardiac function, attenuated fibrosis, and inhibited ventricular remodeling through activation of the Akt/Bcl-2 signaling pathway.

Conclusion: Quercetin mitigates ventricular remodeling and myocardial fibrosis through Akt/Bcl-2 pathway activation, offering a promising therapeutic strategy for CHF.

Background: Hypertrophic cardiomyopathy (HCM), associated with left ventricular hypertrophy, can lead to significant morbidity. Given the hereditary association, identifying population-specific genetic markers and gender disparities could enable better screening and management strategies.

Aim: The study aimed to observe the genetic patterns of HCM and investigate its gender associations among the Indian population.

Methodology: A prospective analysis was performed based on the medical records of patients with HCM. Genetic testing was conducted among those with a family history of HCM or sudden cardiac death. Genetic testing results, echocardiography, and clinical outcomes were documented. The prevalence of HCM types and genetic abnormalities were estimated in the study population and were compared between the two genders.

Results: The study included 103 patients with a mean age of 56.3 ± 13.9 years. Genetic analysis was conducted in 48/103 individuals based on the hereditary linkage. Only 50% of the 48 individuals had known genes associated with HCM. About 48% had apical or midapical HCM, and 31.1% had reverse curvature HCM. About 38% of apical and 60% of neutral or reverse curvature were associated with genetic abnormalities. The more commonly associated genes were MYBPC3 and MYH7. The current study also identified genetic variants in several emerging genes in Indian HCM patients.

Conclusion: Our study findings indicate that the prevalence of different types of HCM is different in the Indian population. With only 50% of the hereditary HCM linked to known genes, the study calls for further screening of genes associated with HCM in the Indian population.

Background: Aflatoxin B1 (AFB1) is a mycotoxin generated by the fungi Aspergillus flavus and Aspergillus parasiticus, known for its potential to cause liver cancer and has been associated with several adverse health effects. It commonly contaminates cereals, peanuts, corn, and other crops, posing serious risks to both poultry and human health. One promising natural compound that has gained attention for its potential health benefits is resveratrol. The current research aims to explore the possible effect of resveratrol on AFB1-induced kidney damage in rats.

Materials and methods: Forty adult male albino rats were evenly assigned into four groups: a control group, a group treated with resveratrol at a dosage of 10 mg/kg/day orally for 10 days, a group treated with AFB1 at a dosage of 1.5 mg/kg/day orally for 10 days and a group treated with both resveratrol and AFB1. After 10 days of treatment, renal tissues were processed for biochemical, gene expression, histopathological, and immunohistochemical investigations.

Results: Administering resveratrol led to a reduction in serum creatinine, blood urea nitrogen, renal malondialdehyde concentrations, interleukin 6 gene expression, and the immunoreactivity of the proapoptotic protein (Bax). It also restored reduced glutathione levels, increased sirtuin 1 gene expression, and the immunoreactivity of the antiapoptotic protein (Bcl2). Furthermore, resveratrol improved the alterations in the histopathology in AFB1-treated group.

Conclusions: Coadministration of resveratrol in AFB1 toxicity exhibited a significant ability to improve renal function through antioxidant, anti-inflammatory, and antiapoptotic mechanisms in experimentally induced renal damage by AFB1.

Aim: This study aims to design and develop novel lidocaine analogs specific for the Na_v1.7 channel using in silico approaches.

Background: Neuropathic pain (NP) is defined as chronic pain originating from abnormalities found within the nervous system. Voltage-gated sodium channels play a significant role in enhancing neuronal excitability, thus gained significance as a crucial target for developing drugs to treat NP. It consists of 9 different isoforms, with Na_v1.7 predominantly found in the dorsal root ganglion, playing a crucial role in the pathophysiology of NP. The selective inhibitors targeting the Na_v1.7 channel hold greater potential for treating NP while minimizing interference with the physiological functions of other sodium channel isoforms.

Methods: Atom and field-based three-dimensional (3D) quantitative structure-activity relationship (QSAR) was created using lidocaine analogs to identify the structural features required for the Na_v1.7 inhibitory activities. Further, the molecular interaction of the scaffold with the Na_v1.7 channel VSD4 was studied by docking the molecules with it followed by absorption, distribution, metabolism, and excretion (ADME) analysis.

Results: The 3D QSAR studies revealed that the presence of hydrophobic groups and steric parameters heightened the specificity for Na_v1.7 channel. Docking analysis revealed that 4 compounds, i.e., A15, A14, A6, and A5, exhibited the highest binding affinity in comparison to reference drug lidocaine. Furthermore, ADME predictions indicated that the compounds exhibited favorable characteristics in terms of oral bioavailability and solubility.

Conclusion: This research offers valuable structural insights to improve the specific inhibition of the Na_v1.7 channel, facilitating the design and development of novel, Na_v1.7 channel-specific inhibitors.

The Guillain-Barré syndrome (GBS) outbreak in Pune, India, has raised significant public health concerns, with over 230 reported cases and 12 fatalities in the state of Maharashtra, India. Epidemiological investigations indicate a potential link between the outbreak and contaminated drinking water. This review discusses the outbreak's progression, surveillance efforts, clinical management, and preventive measures implemented. The findings underscore the need for improved water safety measures, enhanced surveillance, and policy interventions to prevent future outbreaks of GBS in India.

Myasthenia gravis (MG) is an autoimmune condition affecting the neuromuscular junction. Juvenile MG (JMG) is a subtype of pediatric MG and is reported to be a rare neurological disorder with variable presentation and difficult diagnosis. MG has been described as a great neurological mimicker having resemblance with a wide spectrum of neurological disorders. The present case is a distinctive and compelling example of JMG that manifested at a young age with a disguised presentation. Bilateral ptosis was the principal presenting symptom with mild facial droop which simulated Bell's palsy initially. The patient was finally diagnosed as JMG based on acetylcholine receptor antibody test along with ophthalmological, electrophysiological, and imaging findings. She was managed for JMG and concurrent hyperthyroidism and is being regularly monitored for the effectiveness of the treatment. This report highlights the relevance of extensive clinical history, meticulous clinical examination, and awareness of similar neurologic disorders with overlapping characteristics in order to facilitate correct diagnosis, appropriate management, and effective treatment of this condition, often described as the "great imitator."

Introduction: Cation exchange high-performance liquid chromatography (HPLC) serves as a rapid, reproducible, and accurate method for diagnosing hemoglobinopathies. This study outlines the diagnostic approach and the challenges faced in the routine diagnosis of hemoglobinopathies through HPLC, particularly in laboratories with limited resources.

Aims and objectives: The aim of the study was to identify the challenges encountered in identifying abnormal hemoglobin (Hb) variants and to determine the significance of HbA2 and/or fetal Hb (HbF) analysis in the HPLC methodology for hemoglobinopathies.

Materials and methods: A total of 1900 samples were analyzed using the ARKRAY ADAMS HA-8180T HPLC automated analyzer for the purpose of hemoglobinopathy testing. The samples were classified into normal or abnormal hemoglobin variants based on the percentage levels of HbA2, HbF, HbA, and the identification of any abnormal peaks. Among these, 113 cases were diagnosed to have thalassemia or hemoglobinopathy. The clinical presentations and red blood cell (RBC) indices were compared with the HPLC findings for each case, thereby contributing to the accuracy of the diagnosis.

Results: The study examined the distribution of Hb variants, revealing that β-thalassemia trait was the most prevalent at 44.2%, followed by sickle cell trait at 13.3% and HbD Punjab trait at 10.6%. There were many challenging cases with elevated HbA2, like HbE thalassemia and Hb Lepore. Furthermore, there was identification of some abnormal peaks which were not exactly in the instrument's predetermined HbA2, HbF, HbA, or sickle windows, like HbJ Meerut. There were a few cases with abnormally elevated HbF, which can be seen in homozygous β-thalassemia, sickle cell disease, compound double heterozygous sickle cell β-thalassemia, δβ-thalassemia, and hereditary persistence of HbF. Carriers of β-thalassemia were generally identified by an HbA2 level of 4% or higher; however, there were nine cases which exhibited borderline HbA2 levels ranging from 3.5% to 3.9%, which might turn out to be β-thalassemia trait, especially in high-prevalence areas like Gujarat.

Conclusion: Any case scenario with abnormally elevated HbA2 is not always β-thalassemia trait. Nor abnormally elevated HbF may always indicate β-thalassemia major. Furthermore, some clinico-pathologically relevant hemoglobinopathies might show an abnormal peak on HPLC at any retention time, which may not be necessarily determined by the machine to be in some specific window. We need to correlate the clinical context, RBC indices, HPLC findings, and family studies to effectively detect most Hb variants.