Macitentan in Adults with Sickle Cell Disease and Pulmonary Hypertension: A Proof-of-Concept Study
Published on: 22nd April, 2024
Pulmonary hypertension (PH) in sickle cell disease (SCD) is associated with a mortality rate of 37%. There is an upregulation of adhesion molecules which leads to the expression of endothelin-1, a potent vasoconstrictor. A prospective, descriptive study was done to determine the safety and efficacy of macitentan in patients with SCD and PH. Continuous variables were reported as mean ± SEM or percentage where appropriate. We screened 13 patients and recruited five. All five patients were adults. Data were analyzed as appropriate by student t - test. Statistical significance was assumed at p < 0.05. Baseline pulmonary hemodynamics obtained by right heart catheterization and systemic hemodynamics were (± SEM): mean pulmonary artery pressure (MPAP) 32 ± 8 mmHg, right atrial pressure (RAP) 9 ± 4 mmHg, pulmonary vascular resistance (PVR) 257 dynes-sec/cm5 and CI 3·7 ± 0.39 l/m2. Of all parameters, only PVR and 6-min walk distance changed significantly. For the group, MPAP decreased by 15.6%, PVR by 22.5% and RAP by 25.5%. The 6-minute walk distance increased over sixteen weeks except in Patient 4 who had a 3% decrease. The mean walk distance increased in the total distance, from 464 ± 158 meters to 477 ± 190 meters (p .123). In four patients, the adverse events were mild to moderate and did not lead to study drug discontinuation. Significant improvement in pulmonary hemodynamics and exercise capacity in patients with SCD-related pulmonary arterial hypertension. We found that macitentan was safe and well tolerated.
Sexual Dimorphism in Autoimmune Disorders
Published on: 25th April, 2024
Sexual dimorphism exists in Homo sapiens in many systems. Lately, it was found that it also exists in autoimmune disorders. Generally, it was known that the two genders in humans have different endocrine systems, and therefore hormone hormone-regulated systems show sexual dimorphism. However, in the case of autoimmune disorders, it is not due to directly on hormonal milieu but depends on X-chromosome inactivation in males. Whereas every cell in a woman’s body produces Xist; this ribonucleoprotein contains about 81 proteins. This chromosomal inactivation in males and formation of Xist ribonucloprotein in females is responsible for sexual dimorphism in autoimmune disorders in humans.
Exploring the Complexity of Protein Structure Determination Through X-ray Diffraction
Published on: 21st November, 2023
The determination of a protein structure by using X-ray diffraction encompasses a series of sequential steps (including gene identification and cloning, protein expression and purification, crystallization, phasing model building, refinement, and validation), which need the application of several methodologies derived from molecular biology, bioinformatics, and physical sciences. This article thoroughly examines the complicated procedure of elucidating protein structures within plant biology, using X-ray diffraction as the primary methodology. Commencing with the gene identification process and progressing toward crystallography, this article explores the many obstacles and achievements in acquiring diffraction pictures and their subsequent conversion into electron density maps. The ensuing phases of model construction, refinement, and structural validation are thoroughly examined, providing insight into the inherent complexity associated with each stage. The paper also discusses the critical component of understanding the resultant model and scrutinizing its biological significance. By comprehensively examining these stages, this article presents a nuanced comprehension of the intricate procedure in ascertaining protein structures within plant biology. It offers valuable insights into the obstacles encountered and the biological importance of the acquired structural data.
Update on the Use of Mesenchymal Stem Cells and their Products in Hematopoietic Stem Cell Transplantation
Published on: 29th November, 2023
Graft Versus Host Disease (GVHD) is a major limitation to the success of allogeneic Hematopoietic Stem Cell Transplantation (HSCT) as Steroid-Refractory (SR) acute GVHD carries poor prognosis due to the absence of an efficacious second-line therapy. Mesenchymal Stem Cells (MSCs) which have immunosuppressive, immunomodulatory, and regenerative properties may become a highly effective therapeutic modality for SR-GVHD in the near future. MSCs have already been approved to treat childhood SR-GVHD in Japan, and they have been conditionally licensed in New Zealand and Canada. It is expected that MSCs will be approved for the treatment of SR-GVHD in adults in Europe, North America, and other parts of the world within a few years. Utilization of the recently introduced techniques including the use of MSC products such as exosomes and Extracellular Vesicles (ECVs) instead of the parent MSCs, robotic manufacturing technology, and genetic engineering of MSCs will ultimately overcome the remaining obstacles facing the widespread utilization of MSCs and their products as therapeutics not only in HSCT but also in other medical fields. The aim of this review is to provide an update on the remarkable progress achieved in the use of MSCs and their products in the field of HSCT.
Myeloid Neoplasms: Better Understanding of their Molecular Pathogenesis with Improvised Genomic Testing: A Ray of Hope for Better Clinical Outcomes
Published on: 31st January, 2024
With the increase in incidence and prevalence of myeloid neoplasms in India, it has become a necessity to understand its molecular mechanisms, acquisition of genomic alterations, and understand its primary and secondary resistance pathways which ultimately impact the decision of therapeutics. The objective of this review is to investigate the molecular aspects of this disease type and identify the biomarkers that help with diagnosis, risk assessment, prognosis, and selecting the best line of treatment for a specific myeloid neoplasm. Advancements and innovations in molecular technologies from simplest Real-Time PCR to high throughput next-generation sequencing have played a vital role in screening the most common mutations and fusions to the novel and rare. Molecular technologies have helped to enumerate the genomic landscape of myeloid malignancies. The understanding of both- the mechanisms and the technology is a strong combination as it has helped revolutionize precision oncology and helped in giving better therapeutic choices with better clinical outcomes. The importance of cellular morphology, clinical symptoms, and molecular pathology in assessing the risk of myeloid malignancies is emphasized and summarized in the review. The review concludes that understanding molecular pathogenesis can be improved by using clinical-pathological-molecular strategies for diagnosis and therapy decision-making.
Large Cystic Dilatation of the Common Bile Duct
Published on: 19th March, 2024
Li B, Chen BW, Xia LS. The Initial Experience of Laparoscopic Management for Type VI Choledochal Cyst in Children. J Laparoendosc Adv Surg Tech A. 2024 Mar;34(3):280-283. doi: 10.1089/lap.2023.0229. Epub 2023 Oct 16. PMID: 37844069.
Dumitrascu T, Lupescu I, Ionescu M. The Todani classification for bile duct cysts: an overview. Acta Chir Belg. 2012 Sep-Oct;112(5):340-5. doi: 10.1080/00015458.2012.11680849. PMID: 23175921.
Dutta S, Jain A, Reddy A, Nelamangala Ramakrishnaiah VP. Anomalous Pancreaticobiliary Duct Junction in an Unusual Case of Synchronous Gallbladder and Bile Duct Malignancy. Cureus. 2021 Feb 13;13(2):e13331. doi: 10.7759/cureus.13331. PMID: 33738174; PMCID: PMC7959653.
Xia HT. Standardized Surgical Management for Cystic Dilation of the Bile Ducts Based on Clinical and Pathological Studies: A Narrative Review. Gastroenterol Res Pract. 2020 Sep 15;2020:3432786. doi: 10.1155/2020/3432786. PMID: 33014038; PMCID: PMC7512076.
Study on the Molecular Mechanism of Antioxidant Health Effect of Tuna Dark Meat Enzymatic Polypeptides
Published on: 21st March, 2024
In order to study the molecular mechanism of the antioxidant effect of enzymatically hydrolyzed tuna dark meat peptides, this article uses alkaline protease to enzymatically hydrolyze tuna dark meat, and at the same time performs peptide sequencing using matrix-assisted laser dissociation time-of-flight mass spectrometry (MALDI TOF/TOF). Discovery Studio (DS) performed molecular docking. Finally, the antioxidant effect was verified through DPPH clearance experiments. The results show that the dominant peptide sequences in the tuna dark meat hydrolyzed polypeptides are LAPGQ, GGGDPI, and PLRLP; through molecular simulation methods (Discover Studio, DS), the potential target of the above-mentioned enzymatic polypeptides was screened out to be Keap1, thus predicting antioxidant activity. It provides theoretical support for further research on enzymatic peptides. Through DPPH clearance experiments, it was found that both the enzymatic hydrolysate and LAPGQ, GGGDPI, and PLRLP have antioxidant activity, confirming their effects.
Social Implementation and Measurement Accuracy Verification of Non-contact Biological Monitors
Published on: 25th March, 2024
In this research, for the purpose of social implementation, we conducted a near-miss demonstration experiment using a car driving in the city and a drive-simulator. Next, we conducted a demonstration experiment to evaluate the reliability of biometric information measured on patients in a medical facility's recuperation ward and residents of a special nursing home. NBC-1100 emits radar waves from a distance of up to 3 meters from an object and uses the reflected waves to measure biological information such as pulse waves and breathing waves. The multi-element pyroelectric effect was used to measure body temperature by detecting infrared radiation emitted from distant objects. This device is unique in that it can measure biological information without being restrained while wearing clothes. In the demonstration test, simultaneous measurements were conducted on nine healthy men aged 45 to 65 using a pharmaceutically approved product (μBP-mp) and a prototype non-contact biological monitor (NBC-1100 manufactured by K&S Co., Ltd.). The demonstration experiments at medical institutions and nursing care facilities were conducted with the consent of residents and their families and were conducted on 30 men and women between the ages of 70 and 94 who were undergoing treatment or in need of care. The tests were conducted on residents with chronic diseases such as dilated gastrostomies, symptomatic epilepsy, hypertension, Alzheimer's disease, and progressive supranuclear palsy. The evaluation method was simultaneous measurement using a master meter (μBP-mp) and a test meter (NBC-1100).
A Brief Dig into the Potent Medicinal Plant Phyllanthus Amarus Schum. and Thonn.
Published on: 27th March, 2024
Phyllanthus amarus Schum. and Thonn., a plant of substantial medicinal significance, is known for its usage in the ‘Ayurvedic’ system of medicine for over 2000 years. This herb grows throughout the world including India. P. amarus along with other species of its genus has been a vital part of several herbal formulations available in the Indian market under the trade name Bhuiamlaki. Several pharmacognostic evaluations over the years established the genus Phyllanthus of great commercial value. Ethnopharmacological studies conducted with P. amarus to date have shown its diverse therapeutic usage globally. This owes to the vast array of secondary metabolites present in the herb, substantially in the leaf tissue. Different analytical and phytochemistry studies performed across the globe revealed that P. amarus is a hub of various classes of secondary metabolites viz. lignans like phyllanthin, hypophyllanthin, flavonoids, alkaloids, triterpenes, sterols, volatile oil, ellagitannins including simple and complex tannins, etc. Different analytical techniques have been employed over the past years for isolating and studying these varied secondary metabolites. Further, bioactivities and pharmacological properties of P. amarus that were mainly due to the presence of these wide arrays of secondary metabolites have also been explored extensively across the globe by several research groups. This plant has also been explored at molecular and transcriptome level, although relatively lesser but its extensive molecular and transcriptome analysis have only been performed from our lab. Thus, P. amarus has considerable potential to be explored in the future as a significant therapeutic source not only in the traditional medicinal system but also in the modern pharmaceutical industry.
The Cortisol Connection: Weight Gain and Stress Hormones
Published on: 28th March, 2024
Weight gain can be good or bad for health. Benefits include increased health for overweight people, disease or surgical recovery, and more. Health concerns, joint and musculoskeletal disorders, respiratory issues, metabolic abnormalities, cardiovascular health, psychological impact, reduced mobility, digestive troubles, hormonal changes, and cancer risk are negative impacts. Weight gain outcomes depend on heredity, weight distribution, and health. Maintaining a healthy weight needs a balanced diet, regular exercise, and stress management. A doctor or nutritionist can offer personalized weight management advice. Stress chemicals like cortisol trigger weight gain. ACTH stimulates adrenal glands to release cortisol, which increases hunger, fat storage, insulin resistance, and muscle loss. Understanding how stress hormones like cortisol affect weight gain is vital to reducing chronic stress’s health risks. Stress reduction, a balanced diet, regular exercise, proper sleep, social support, and professional treatment can mitigate these outcomes. Ultimately, stress hormones like cortisol can cause weight gain, but a holistic strategy tackling physical and psychological stress can help people maintain a healthy weight.
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