G6PD deficiency is a common genetic trait that can protect heterozygotes from dying from malaria

2021

Preprint

Frontotemporal dementia is an uncommon and complex sickness with a wide spectrum of clinical symptoms, making drug development for the condition challenging. Frontal and temporal lobe responsibilities, as well as the level to which these activities are affected in certain diseases, contribute to clinical heterogeneity. Unfortunately, the available data on symptomatic treatments is drawn from limited case studies and RCTs, which include persons with the same FTD diagnosis. Advances in the identification of new FTD treatments demand the construction of huge clinical networks that are built on collaborative, multicenter research. One of the primary drawbacks of the present studies is the variety of the assessment instruments utilized, such as the FBI, Cambridge Behavioral Inventory, NPI, and BEHAVE-AD, some of which were not originally established for FTD but were first validated for other kinds of dementia, such as AD. The FBI was shown to have high sensitivity and specificity in discriminating between bvFTD and non-FTD, whereas the NPI score did not.The new definition of Alzheimer's disease was changed from a clinical diagnostic to a biomarker-based diagnostic, although we are still a long way from providing a scientific description of FTD. In the future, there might be an increased likelihood of recognizing symptoms or signs in clinical studies because of a revision to the criteria of FTD.Treatment techniques should be customized to individual patient subgroups or mutation carriers. Currently, as a treatment for FTD-tau, antisense oligonucleotide inhibition of MAPT, tau phosphorylation inhibition, microtubule stability, and inhibition of tau aggregation are all being investigated. It is possible to inhibit TDP-43 aggregation, enhance progranulin levels, activate the autophagy–lysosome system, or modify the ubiquitin-proteasome system in FTD-TDP. Despite these breakthroughs, the etiology and genetics of FTD remain unclear. Additional genetic pathways and loci associated with immune dysregulation and inflammation have recently been discovered, furthering the search for possible treatment targets. Also, knowing who the mutation carriers are early on allows researchers to test disease-modifying drugs earlier, when cognitive problems may still be reversible.Research gaps in the etiology and clinical characterization of FTD should be resolved, as well as the production of precise biomarkers and specialized evaluation methodologies. Desharnais and colleagues have created a checklist to assist standardize future FTD clinical trials and boost the probability of successful findings.

Section: The Grn Mutation Is Being Targetedmentioning

confidence: 99%

Frontotemporal dementia is a complex disorder with a wide spectrum of clinical symptoms. Personalized medicine and gene therapy are promising strategies for treatment

2021

Preprint

“…The inconsistency of the sRAGE level owing to cigarette smoking was discussed by Prasad et al (80). Smoking, on the other hand, causes a quick and substantial drop in serum sRAGE, according to research (81). Furthermore, smoking has been shown to have an immediate and transient influence on serum sRAGE (81).…”

Section: In Copd the Age-rage Axis And Srage Play A Rolementioning

confidence: 99%

“…Smoking, on the other hand, causes a quick and substantial drop in serum sRAGE, according to research (81). Furthermore, smoking has been shown to have an immediate and transient influence on serum sRAGE (81). Because the results of these studies are inconsistent, various authors have reported and suggested that more research is needed before sRAGE can be considered a potential biomarker for COPD (82).…”

Section: In Copd the Age-rage Axis And Srage Play A Rolementioning

confidence: 99%

Chronic obstructive pulmonary condition (COPD) is a prevalent, preventable, and curable illness with persistent respiratory symptoms and airflow limitation

2021

Preprint

Global Initiative for Chronic Obstructive Lung Disease (GOLD) research on chronic obstructive pulmonary condition (COPD) characterizes it as a prevalent, preventable, and curable illness with persistent respiratory symptoms and airflow limitation. airway blockage resulting in dyspnoea and air trapping when exercising airflow restriction can be attributed to smoking, ambient tobacco smoke exposure, and the patient's TB history COPD airflow restriction is largely caused by airway tightness, chronic bronchitis, or emphysema. Repeated inhalation of hazardous particles induces chronic inflammatory immune cell infiltration, tissue repair, and airway remodeling, resulting in a 4-to 40-fold increase in airway resistance and bronchiolar constriction. 20% of small airways are bronchi, with the rest being either bronchioles or alveolar ductal gaps. Flow restriction includes alveolar wall disintegration and alveolar support. The modifications worsen the rapid FEV1 fall and contribute to the airway obstruction seen in COPD. COPD, small airway disease (SAD), has been extensively studied. Inflammation, fibrosis, and destruction of bronchioles are all indications of this illness. mixed pulmonary fibrosis and emphysema (CPFE). In fact, fibrosis appears to be involved in the obstruction of small airways.RAGE participates in several intracellular processes by binding to several ligands. RAGE ligand interactions trigger downstream signaling pathways that have been associated with COPD and other disorders. Thus, inhibitors of RAGE and its signaling pathways also have been found to play a function in other disorders, which suggests that they might be used to treat COPD. There are currently no established biomarkers to diagnose COPD. COPD patients are shown to have altered RAGE and some of its ligands. Despite a lack of agreement on how smoking affects sRAGE levels, greater study is needed to discover whether or not this biomarker is stable. It was discovered that among the North Han Chinese,-429T > C is associated with COPD. COPD vulnerability is furthermore associated with the genetics of RAGE. To get a better diagnosis, population-based studies are needed. Finally, RAGE, AGE-RAGE, and sRAGE all impact COPD, and RAGE may be employed as a biomarker for diagnosis and management of COPD patients if more study supports this hypothesis.

“…A large, cohort research comprising 132 participants with CKD discovered that urine ET-1 levels increased in individuals with SLE, even when their GFR was normal (72). Giant mesangial cell proliferation and matrix generation is associated with the presence of ET-1 in SLE patients (73,74). Renal ET-1 and ETB receptors are present in NZB/WF1 mice (34).…”

Section: Glomerulonephritis Renal Lupusmentioning

confidence: 99%

The vasoconstrictor endothelin system involvement in chronic kidney diseases pathogenesis is now the most often employed treatment method

2021

Preprint

Over 30,000 publications have been published about the vasoconstrictor endothelin-1, which was identified by Yanagisawa and co-workers in 1988. While the evidence is quite compelling, scientists can only speculate on how the endothelin (ET) system affects blood pressure and renal function at this time. ET system involvement in chronic kidney diseases (CKD) pathogenesis is now the most often employed treatment method. ET1, ET2, and ET3 are all members of the endothelin family. Endothelium, renal, and smooth muscle cells all generate ET-1, a significant isoform found in both cardiovascular and renal systems.Kidney cells act on, and contain, ET-1. The ETA receptor is found in the brain and medulla, but not in the vasa recta or glomeruli. Epithelial and endothelial cells contain the ETB receptor, which is most prominent in collecting duct cells. 3 In several experiments, ET-1 has been established to be largely a preglomerular vasoconstrictor. Mesangial proliferation, contraction, and collagen production are regulated by ET-1 and ETB receptors in podocytes. The epithelium in the collecting duct cells in the medulla is important in controlling Na excretion and BP. Without the ET-1 gene, the mice have hypertension and reduced natriuresis in response to salt loading. Et-1, ETB receptor, and hypertension are shown in mice that have lost the ETB receptor gene. There is no correlation between blood pressure regulation and natriuresis.Combined disruption of the ETA and ETB receptors has greater effects on blood pressure and Na reabsorption than when ETB receptor activity is missing. It appears that the ETB receptor doesn't work until ETB is present. Collecting duct-derived ET receptors reduces the transport of sodium. Src kinase and MAPK1/2 decrease epidermal Na channel (ENaC) function, decreasing water and salt reabsorption. Moreover, inner medullary collecting duct cells and vasa recta-bearing cells will release NO, which decreases sodium transport.