Extracellular vesicles-associated tRNA-derived fragments (tRFs): biogenesis, biological functions, and their role as potential biomarkers in human diseases
AbstractTraditionally, transfer RNAs (tRNAs) specifically decoded messenger RNA (mRNA) and participated in protein translation. tRNA-derived fragments (tRFs), also known as tRNA-derived small RNAs (tsRNAs), are generated by the specific cleavage of pre- and mature tRNAs and are a class of newly defined functional small non-coding RNAs (sncRNAs). Following the different cleavage positions of precursor or mature tRNA, tRFs are classified into seven types, 5 ′-tRNA half, 3′-tRNA half, tRF-1, 5′U-tRF, 3′-tRF, 5′-tRF, and i-tRF. It has been demonstrated that tRFs have a diverse range of biological functions in cellula...
Source: Journal of Molecular Medicine - March 24, 2022 Category: Molecular Biology Source Type: research
Identification of PDXDC1 as a novel pleiotropic susceptibility locus shared between lumbar spine bone mineral density and birth weight
In conclusion, our study provides insights into some shared genetic mechanisms for BMD and BW as well as a novel potential therapeutic target for the prevention of OP in the early stages of the disease development.Key messagesWe investigated pleiotropy-informed enrichment between LS BMD and BW.We identified genetic variants related to both LS BMD and BW by utilizing a cFDR approach.PDXDC1 is a novel pleiotropic gene which may be related to both LS BMD and BW.Elevated expression of PDXDC1 is related to higher BMD and lower ratio n-6/n-3 PUFA indicating a bone protective effect of PDXDC1. (Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - March 22, 2022 Category: Molecular Biology Source Type: research
White and brown adipose tissue functionality is impaired by fine particulate matter (PM2.5) exposure
AbstractChronic exposure to high levels of particulate matter (PM) is correlated to a higher prevalence of cardio-metabolic disturbances. Adipose tissue represents a pivotal regulator of metabolic homeostasis, and its dysfunction is associated with health issues in PM-exposed models. This review discusses the adaptive changes of white (WAT) and brown (BAT) adipose tissue in response to fine particulate matter (PM2.5), investigating the underlying pathophysiology. In exposed models, PM2.5 increases oxidative stress and impairs mitochondria functionality and biogenesis in WAT and BAT. Chronic exposure also upregulates the ma...
Source: Journal of Molecular Medicine - March 14, 2022 Category: Molecular Biology Source Type: research
Deciphering therapeutic options for neurodegenerative diseases: insights from SIRT1
AbstractSilent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD +)-dependent protein deacetylase that exerts biological effects through nucleoplasmic transfer. Recent studies have highlighted that SIRT1 deacetylates protein substrates to exert its neuroprotective effects, including decreased oxidative stress and inflammatory, increases autophagy, increases le vels of nerve growth factors (correlated with behavioral changes), and maintains neural integrity (affects neuronal development and function) in aging or neurological disorder. In this review, we highlight the molecular mechanisms underl...
Source: Journal of Molecular Medicine - March 11, 2022 Category: Molecular Biology Source Type: research
Circular RNAs: regulators of vascular smooth muscle cells in cardiovascular diseases
AbstractThe aberrant expansion and dysfunction of vascular smooth muscle cells (VSMCs) contribute to the occurrence and development of many cardiovascular diseases. Circular RNAs, a new class of non-coding RNAs with the 3 ′ and 5′ ends covalently linked together due to back-splicing, have recently been revealed to function as new regulators of VSMCs. These circular RNAs mainly act as RNA sponge to downregulate other regulatory non-coding RNAs such as microRNAs, influencing the overgrowth and transformation of VSM Cs under pathogenic conditions. The purpose of this review is to summarize how circular RNAs fluctuate thei...
Source: Journal of Molecular Medicine - March 7, 2022 Category: Molecular Biology Source Type: research
High levels of extracellular ATP lead to different inflammatory responses in COVID-19 patients according to the severity
AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has significantly impacted the world and has driven many researchers into the pathophysiology of COVID-19. In the findings, there is a close association between purinergic signaling and the immune response. Then, this study aimed to evaluate alterations in the purinergic signaling in COVID-19 patients according to range severity. We divided the COVID-19 patients into moderate and severe cases following the guideless of NIH and WHO, together with clinical characteristics. The blood samples were collected to obtain PBMCs and platelets. We analy...
Source: Journal of Molecular Medicine - March 6, 2022 Category: Molecular Biology Source Type: research
EV-T synergizes with AZD5582 to overcome TRAIL resistance through concomitant suppression of cFLIP, MCL-1, and IAPs in hepatocarcinoma
This study has rationalized the next development of a combination therapy with AZD5582 and nanosomal TRAIL for cancer treatment. (Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - March 5, 2022 Category: Molecular Biology Source Type: research
Early reduction of SARS-CoV-2-replication in bronchial epithelium by kinin B2 receptor antagonism
This study examines SARS-CoV-2-infection and epithelial mechanisms of the kinin-kallikrein-system at the kinin B2 receptor level in SARS-CoV-2-infection that is of direct translational relevance. From acute SARS-CoV-2-positive study participants and -negative controls, transcriptomes of nasal curettages were analyzed. Primary airway epithelial cells (NHBEs) were infected with SARS-CoV-2 and treated with the approved B2R-antagonist icatibant. SARS-CoV-2 RNA RT-qPCR, cytotoxicity assays, plaque assays, and transcriptome analyses were performed. The treatment effect was further studied in a murine airway inflammation model in...
Source: Journal of Molecular Medicine - March 5, 2022 Category: Molecular Biology Source Type: research
Ziprasidone suppresses pancreatic adenocarcinoma cell proliferation by targeting GOT1 to trigger glutamine metabolism reprogramming
AbstractPancreatic ductal adenocarcinoma (PDAC) is a fatal malignant tumor whose effective treatment has not been found. The redox state and proliferative activity of PDAC cells are maintained by the conversion of aspartic acid in the cytoplasm into oxaloacetate though aspartate aminotransferase 1 (GOT1). Therefore, GOT1 inhibitors as a potential approach for treating PDAC have attracted more attention of researchers. Ziprasidone effectively inhibited GOT1 in a non-competitive manner. The potential cytotoxicity and anti-proliferation effects of ziprasidone against PDAC cells in vitro and in vivo were evaluated. Ziprasidone...
Source: Journal of Molecular Medicine - February 25, 2022 Category: Molecular Biology Source Type: research
c-Met up-regulates the expression of PD-L1 through MAPK/NF- κBp65 pathway
In conclusion, c-Met regulates the transcription of PD-L1 through the MAPK/NF-κBp65 pathway, thereby promoting the progress of HCC. The role of c-Met and PD-L1 in HCC needs to be further studied, but it is a potential target for the treatment of HCC.Graphical abstractKey messagesIn the study, it was found that c-Met is also abnormally highly expressed in Huh-7SR with high PD-L1 expression and can promote the development of HCC in vitro and in vivo. PD-L1 and c-Met expression levels are positively correlated.In the follow-up mechanism study, we found that c-Met activated the MAPK signaling pathway and subsequently activate...
Source: Journal of Molecular Medicine - February 5, 2022 Category: Molecular Biology Source Type: research
Purinergic signaling elements are correlated with coagulation players in peripheral blood and leukocyte samples from COVID-19 patients
AbstractFor over a year, the coronavirus disease 2019 has been affecting the world population by causing severe tissue injuries and death in infected people. Adenosine triphosphate (ATP) and the nicotinamide adenine dinucleotide (NAD +) are two molecules that are released into the extracellular microenvironment after direct virus infection or cell death caused by hyper inflammation and coagulopathy. Also, these molecules are well known to participate in multiple pathways and have a pivotal role in the purinergic signaling pat hway. Thus, using public datasets available on the Gene Expression Omnibus (GEO), we analyzed r...
Source: Journal of Molecular Medicine - January 29, 2022 Category: Molecular Biology Source Type: research
Gaucher disease – more than just a rare lipid storage disease
AbstractGaucher disease (GD), one of the most common lysosomal storage diseases, is caused by mutations in the gene,GBA1, that leads to defective glucocerebrosidase activity resulting in the accumulation and storage of glycosphingolipids. However, the pathophysiology of GD is more complicated leading to various associated conditions such as skeletal manifestations and Parkinson ’s disease (PD). These may result from oxidative stress and inflammatory responses due to complex interconnection of downstream factors such as substrate accumulation, endoplasmic reticulum (ER) stress, unfolded protein response (UPR), calcium dys...
Source: Journal of Molecular Medicine - January 23, 2022 Category: Molecular Biology Source Type: research
Disturbed lipid and amino acid metabolisms in COVID-19 patients
AbstractThe Coronavirus disease 2019 (COVID-19) pandemic is overwhelming the healthcare systems. Identification of systemic reactions underlying COVID-19 will lead to new biomarkers and therapeutic targets for monitoring and early intervention in this viral infection. We performed targeted metabolomics covering up to 630 metabolites within several key metabolic pathways in plasma samples of 20 hospitalized COVID-19 patients and 37 matched controls. Plasma metabolic signatures specifically differentiated severe COVID-19 from control patients. The identified met abolic signatures indicated distinct alterations in both lip...
Source: Journal of Molecular Medicine - January 22, 2022 Category: Molecular Biology Source Type: research
Recapitulating lipid accumulation and related metabolic dysregulation in human liver-derived organoids
This study aims to develop an organoid-based 3D culture model to recapitulate key features of fatty liver disease focusing on intracellular lipid accumulation and metabolic dysregulation. We used human liver-derived intrahepatic cholangiocyte organoids and hepatocyte differentiated organoids. These organoids were exposed to lactate, pyruvate, and octanoic acid (LPO) for inducing lipid accumulation and mitochondrial impairment. Lipid accumulation resulted in alternations of gene transcription with major effects on metabolic pathways, including triglyceride and glucose level increase, which is consistent with metabolic chang...
Source: Journal of Molecular Medicine - January 20, 2022 Category: Molecular Biology Source Type: research
RNA-Seq for the detection of gene fusions in solid tumors: development and validation of the JAX FusionSeq ™ 2.0 assay
AbstractWhole transcriptome sequencing (RNA-Seq) has gained prominence for the detection of fusions in solid tumors. Here, we describe the development and validation of an in-house RNA-Seq-based test system (FusionSeq ™ 2.0) for the detection of clinically actionable gene fusions, in formalin-fixed paraffin-embedded (FFPE) specimens, using seventy tumor samples with varying fusion status. Conditions were optimized for RNA input of 50 ng, shown to be adequate to call known fusions at as low as 20% neoplastic co ntent. Evaluation of assay performance between FFPE and fresh-frozen (FF) tissues exhibited little to no differ...
Source: Journal of Molecular Medicine - January 10, 2022 Category: Molecular Biology Source Type: research
