IGFBP2 function as a novel biomarker for active lupus nephritis
AbstractIn search for new targets for the diagnosis and treatment of lupus nephritis (LN), we employed TMT-liquid chromatography-triple quadrupole mass spectrometry (TMT-LC –MS/MS) combined with RNA-seq and identified a panel of proteins that was dysregulated both at protein level and mRNA level in active LN patients compared with healthy controls. We chose to study the role of IGFBP2 since it is a relatively understudied protein in the context of LN. We further vali dated that IGFBP2 significantly increased and correlated with SLE activity index in active LN patients. The receiver operator characteristic (ROC) curve sug...
Source: Journal of Molecular Medicine - August 25, 2022 Category: Molecular Biology Source Type: research
TGF- β1/Smad3 upregulates UCA1 to promote liver fibrosis through DKK1 and miR18a
AbstractTGF ‐β1 is the strongest cytokine known to promote liver fibrosis. It has been previously demonstrated that the activation of TGF‐β1 initiates a temporary collagen accumulation program, which is important for wound repair in several organs. Furthermore, temporary extracellular matrix enhancement o ften leads to progressive fibrosis, which is accountable for cases of severe morbidity and mortality worldwide. However, its action mechanism has not been fully explored. It was previously reported that UCA1 could promote its occurrence and development in various tumors. Importantly, it was reported that TGF‐β1 c...
Source: Journal of Molecular Medicine - August 24, 2022 Category: Molecular Biology Source Type: research
Predictive value of common genetic variants in idiopathic pulmonary fibrosis survival
AbstractIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia of unknown etiology. The role of genetic risk factors has been the focus of numerous studies probing for associations of genetic variants with IPF. We aimed to determine whether single-nucleotide polymorphisms (SNPs) of four candidate genes are associated with IPF susceptibility and survival in a Portuguese population. A retrospective case –control study was performed with 64 IPF patients and 74 healthy controls. Ten single-nucleotide variants residing in the MUC5B, TOLLIP, SERPINB1, and PLAU genes were analyzed. Singl...
Source: Journal of Molecular Medicine - August 19, 2022 Category: Molecular Biology Source Type: research
X-linked genes exhibit skewed expression in Sjogren ’s disease (SjD): a further step toward understanding the female predominance of autoimmune disease
(Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - August 18, 2022 Category: Molecular Biology Source Type: research
Adhesion G protein-coupled receptor gluing action guides tissue development and disease
AbstractPhylogenetic analysis of human G protein-coupled receptors (GPCRs) divides these transmembrane signaling proteins into five groups: glutamate, rhodopsin, adhesion, frizzled, and secretin families, commonly abbreviated as the GRAFS classification system. The adhesion GPCR (aGPCR) sub-family comprises 33 different receptors in humans. Majority of the aGPCRs are orphan receptors with unknown ligands, structures, and tissue expression profiles. They have a long N-terminal extracellular domain (ECD) with several adhesion sites similar to integrin receptors. Many aGPCRs undergo autoproteolysis at the GPCR proteolysis sit...
Source: Journal of Molecular Medicine - August 15, 2022 Category: Molecular Biology Source Type: research
Protective mechanisms of loquat leaf extract and ursolic acid against diabetic pro-inflammation
AbstractThe pharmacological effectiveness of loquat leaf extract (LE) and its important component, ursolic acid (UA), in the treatment of diabetes mellitus, has been well established in traditional medicine; however, the mechanism underlying their action is still unclear. We evaluated the protective effects of LE and UA against hyperglycemia-induced advanced glycation end product (AGE) formations and hepatic pro-inflammation. Oral administration of UA and LE at a dose of 50 mg/kg/day for 15 days yielded no significant hypoglycemic effect in diabeticdb/db mice. UA and LE suppressed hepatic oxidative stress and AGE format...
Source: Journal of Molecular Medicine - August 13, 2022 Category: Molecular Biology Source Type: research
Towards less invasive molecular diagnostics for endometrial cancer: massively parallel sequencing of endometrial lavage specimens in women attending for an office hysteroscopy
In conclusions, our study provides pilot evidence on the actionability of uterine lavage samples sequencing to detect EC-associated mutations in women with suspected endometrial lesions. In a precision medicine framework, the high mutational concordance between uterine lavage samples and tissue specimens may help inform less invasive diagnostic protocols and the need for ongoing surveillance in patients with EC who wished for fertility-preserving treatment.Key messages• Sequencing of uterine lavage samples collected by office hysteroscopy is feasible.• Most EC mutations identified in lavage were identical to endometri...
Source: Journal of Molecular Medicine - August 12, 2022 Category: Molecular Biology Source Type: research
Chronic social stress disrupts the intracellular redistribution of brain hexokinase 3 induced by shifts in peripheral glucose levels
AbstractChronic stress has the potential to impair health and may increase the vulnerability for psychiatric disorders. Emerging evidence suggests that specific neurometabolic dysfunctions play a role herein. In mice, chronic social defeat (CSD) stress reduces cerebral glucose uptake despite hyperglycemia. We hypothesized that this metabolic decoupling would be reflected by changes in contact sites between mitochondria and the endoplasmic reticulum, important intracellular nutrient sensors, and signaling hubs. We thus analyzed the proteome of their biochemical counterparts, mitochondria-associated membranes (MAMs) from who...
Source: Journal of Molecular Medicine - August 9, 2022 Category: Molecular Biology Source Type: research
New insights into macrophage subsets in atherosclerosis
This article aims to review the content and results of current studies that used RNA-seq to explore the different types of macrophages in AS and the related molecular mechanisms as well as to identify the potential roles of these macrophage types in the pathogenesis of atherosclerotic plaques. Also, this review listed some new therapeutic targets for delaying atherosclerotic lesion progression and treatment based on the experimental results. (Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - August 5, 2022 Category: Molecular Biology Source Type: research
Uremic mouse model to study vascular calcification and “inflamm-aging”
This study aimed to evaluate an adenine-based uremic mouse model for studying medial vessel calcification and senescence-associated secretory phenotype (SASP) changes of aortic tissue to unravel molecular pathogenesis and provide a model for therapy testing. The dietary adenine administration induced a stable and similar degree of chronic uremia in DBA2/N mice with an increase of uremia blood markers such as blood urea nitrogen, calcium, creatinine, alkaline phosphatase, and parathyroid hormone. Also, renal fibrosis and crystal deposits were detected upon adenine feeding. The uremic condition is related to a moderate to se...
Source: Journal of Molecular Medicine - August 2, 2022 Category: Molecular Biology Source Type: research
Serum exosomal coronin 1A and dynamin 2 as neural tube defect biomarkers
In this study, we used proteomics to identify novel proteins specific for NTDs. Our findings revealed three proteins showing differential expression during fetal development. In a rat model of NTDs, we used western blotting to quantify proteins in maternal serum exosomes on gestational days E18, E16, E14, and E12, in serum on E18 and E12, in neural tubes on E18 and E12, and in fetal neural exosomes on E18. The expression of coronin 1A and dynamin 2 was exosome-specific and associated with spina bifida aperta embryogenesis. Furthermore, coronin 1A and dynamin 2 were significantly downregulated in maternal serum exosomes (E1...
Source: Journal of Molecular Medicine - August 1, 2022 Category: Molecular Biology Source Type: research
Dissecting the role of cell signaling versus CD8+ T cell modulation in propranolol antitumor activity
AbstractPreclinical and early clinical mechanistic studies of antitumor activity from the beta-adrenergic receptor ( β-AR) blocker propranolol have revealed both cell signaling and immune function pathway effects. Intertumoral studies were performed using propranolol, a β1-AR selective agent (atenolol), and a β2-AR selective agent (ICI 118,551) in a preclinical in vivo model, as a step to dissect the contribution of cell signaling and CD8+ immunological effects on anticancer activity. We found that repression of β2-AR but not β1-AR signaling selectively suppressed cell viability and inhibited xenograft growth in vivo....
Source: Journal of Molecular Medicine - July 27, 2022 Category: Molecular Biology Source Type: research
mTOR-FABP4 signal is activated in brain arteriovenous malformations in humans
AbstractArteriovenous malformations (AVMs) are the most common types of cerebral vascular malformations, which are dynamic lesions with de novo growth potentials. The dysfunction of endothelial cells has been postulated to play a role in the pathogenesis of brain AVMs. mTOR-FABP4 signal enhances the angiogenic responses of endothelial cells and is not activated in the normal cerebral vasculature. Herein, we investigated the hypothesis that the mTOR-FABP4 signal may be activated in brain AVMs. The abundance of molecules in mTOR-FABP4 signal expression was detected by immunohistochemistry and Western blotting; special expres...
Source: Journal of Molecular Medicine - July 25, 2022 Category: Molecular Biology Source Type: research
Cellular localization of nucleolin determines the prognosis in cancers: a meta-analysis
This study supports the role of subcellular NCL as a poor prognostic cancer biomarker. (Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - July 21, 2022 Category: Molecular Biology Source Type: research
Ataluren suppresses a premature termination codon in an MPS I-H mouse
AbstarctSuppressing translation termination at premature termination codons (PTCs), termed readthrough, is a potential therapy for genetic diseases caused by nonsense mutations. Ataluren is a compound that has shown promise for clinical use as a readthrough agent. However, some reports suggest that ataluren is ineffective at suppressing PTCs. To further evaluate the effectiveness of ataluren as a readthrough agent, we examined its ability to suppress PTCs in a variety of previously untested models. Using NanoLuc readthrough reporters expressed in two different cell types, we found that ataluren stimulated a significant lev...
Source: Journal of Molecular Medicine - July 20, 2022 Category: Molecular Biology Source Type: research
