PARP2 promotes inflammation in psoriasis by modulating estradiol biosynthesis in keratinocytes
In this study, we assessed the role of PARP2 in a Th17-mediated inflammatory skin condition, psoriasis. We found that PARP2 mRNA expression is increased in human psoriatic lesions. Therefore, we studied the functional consequence of decreased PARP2 expression in murine and cellular human models of psoriasis. We observed that the deletion of PARP2 attenuated the imiquimod-induced psoriasis-like dermatitis in mice. Silencing of PARP2 in human keratinocytes prevented their hyperproliferation, maintained their terminal differentiation, and reduced their production of inflammatory mediators after treatment with psoriasis-mimick...
Source: Journal of Molecular Medicine - June 23, 2023 Category: Molecular Biology Source Type: research
TFEB: a double-edged sword for tumor metastasis
AbstractTranscription factor EB, a member of the microphthalmia-associated transcription factor (MiTF/TFE) family, is a master regulator of autophagy, lysosome biogenesis, and TAMs. Metastasis is one of the main reasons for the failure of tumor therapy. Studies on the relationship between TFEB and tumor metastasis are contradictory. On the positive side, TFEB mainly affects tumor cell metastasis via five aspects, including autophagy, epithelial-mesenchymal transition (EMT), lysosomal biogenesis, lipid metabolism, and oncogenic signaling pathways; on the negative side, TFEB mainly affects tumor cell metastasis in two aspect...
Source: Journal of Molecular Medicine - June 17, 2023 Category: Molecular Biology Source Type: research
Lipid metabolism in idiopathic pulmonary fibrosis: From pathogenesis to therapy
AbstractIdiopathic pulmonary fibrosis (IPF) is a chronic irreversible interstitial lung disease characterized by a progressive decline in lung function. The etiology of IPF is unknown, which poses a significant challenge to the treatment of IPF. Recent studies have identified a strong association between lipid metabolism and the development of IPF. Qualitative and quantitative analysis of small molecule metabolites using lipidomics reveals that lipid metabolic reprogramming plays a role in the pathogenesis of IPF. Lipids such as fatty acids, cholesterol, arachidonic acid metabolites, and phospholipids are involved in the o...
Source: Journal of Molecular Medicine - June 8, 2023 Category: Molecular Biology Source Type: research
Transcriptional changes in multiple endocrine organs from lethal cases of COVID-19
AbstractAltered circulating hormone and metabolite levels have been reported during and post-COVID-19. Yet, studies of gene expression at the tissue level capable of identifying the causes of endocrine dysfunctions are lacking. Transcript levels of endocrine-specific genes were analyzed in five endocrine organs of lethal COVID-19 cases. Overall, 116 autoptic specimens from 77 individuals (50 COVID-19 cases and 27 uninfected controls) were included. Samples were tested for the SARS-CoV-2 genome. The adrenals, pancreas, ovary, thyroid, and white adipose tissue (WAT) were investigated. Transcript levels of 42 endocrine-spec...
Source: Journal of Molecular Medicine - May 29, 2023 Category: Molecular Biology Source Type: research
Acid sphingomyelinase expression is associated with survival in resectable pancreatic ductal adenocarcinoma
AbstractPancreatic adenocarcinoma (PDAC) is one of the most common cancers worldwide. Unfortunately, the prognosis of PDAC is rather poor, and for instance, in the USA, over 47,000 people die because of pancreatic cancer annually. Here, we demonstrate that high expression of acid sphingomyelinase in PDAC strongly correlates with long-term survival of patients, as revealed by the analysis of two independent data sources. The positive effects of acid sphingomyelinase expression on long-term survival of PDAC patients were independent of patient demographics as well as tumor grade, lymph node involvement, perineural invasion, ...
Source: Journal of Molecular Medicine - May 29, 2023 Category: Molecular Biology Source Type: research
Acid-sensing ion channel 1a exacerbates renal ischemia –reperfusion injury through the NF-κB/NLRP3 inflammasome pathway
In conclusion, our study suggests that ASIC1a contributes to renal IRI by affecting the NF-κB/NLRP3 inflammasome pathway. Therefore, ASIC1a may be a potential therapeutic target for AKI.Key messagesKnockout of ASIC1a attenuated renal ischemia-reperfusion injury.ASIC1a promoted the NF- κB pathway and NLRP3 inflammasome activation.Inhibition of the NF- κB mitigated the NLRP3 inflammasome activation induced by ASIC1a. (Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - May 29, 2023 Category: Molecular Biology Source Type: research
Loss of CAA interruption and intergenerational CAG instability in Chinese patients with Huntington ’s disease
In conclusion, we present the first document of Asian HD population with LOI variant, and we suggest that for symptomatic individuals with intermediate or reduced penetrance allele or negative family history,HTT gene sequencing should be considered in the clinical practice.Key messagesWe screened the loss of CAA interruption (LOI) variant in a Chinese HD cohort and presented the first document of Asian patients with Huntington ’s disease carrying LOI variant. We identified 6 individuals with LOI variants from 3 families, and all probands presented with earlier motor onset age than predicted onset age.We presented 2 fam...
Source: Journal of Molecular Medicine - May 26, 2023 Category: Molecular Biology Source Type: research
Modulation of cellular transcriptome and proteome composition by azidohomoalanine —implications on click chemistry–based secretome analysis
AbstractThe analysis of the secretome provides important information on proteins defining intercellular communication and the recruitment and behavior of cells in specific tissues. Especially in the context of tumors, secretome data can support decisions for diagnosis and therapy. The mass spectrometry –based analysis of cell-conditioned media is widely used for the unbiased characterization of cancer secretomes in vitro. Metabolic labeling using azide-containing amino acid analogs in combination with click chemistry facilitates this type of analysis in the presence of serum, preventing serum st arvation-induced effects....
Source: Journal of Molecular Medicine - May 26, 2023 Category: Molecular Biology Source Type: research
Dysregulation of miRNA-30e-3p targeting IL-1 β in an international cohort of systemic autoinflammatory disease patients
This study aimed to investigate the effect of a candidate miRNA, miR-30e-3p, which was identified in our previous study, on the autoinflammation phenotype seen in SAID patients and to analyze its expression in a larger group of European SAID patients. We examined the potential anti-inflammatory effect of miR-30e-3p, which we had defined as one of the differentially expressed miRNAs in microarray analysis involved in inflammation-related pathways. This study validated our previous microarray results of miR-30e-3p in a cohort involving European S AID patients. We performed cell culture transfection assays for miR-30e-3p. T...
Source: Journal of Molecular Medicine - May 22, 2023 Category: Molecular Biology Source Type: research
Mitochondrial transplantation as a possible therapeutic option for sarcopenia
AbstractWith advancing age, the skeletal muscle phenotype is characterized by a progressive loss of mass, strength, and quality. This phenomenon, known as sarcopenia, has a negative impact on quality of life and increases the risk of morbidity and mortality in older adults. Accumulating evidence suggests that damaged and dysfunctional mitochondria play a critical role in the pathogenesis of sarcopenia. Lifestyle modifications, such as physical activity, exercise, and nutrition, as well as medical interventions with therapeutic agents, are effective in the management of sarcopenia and offer solutions to maintain and improve...
Source: Journal of Molecular Medicine - May 20, 2023 Category: Molecular Biology Source Type: research
Dispensable role of Rac1 and Rac3 after cochlear hair cell specification
AbstractRac small GTPases play important roles during embryonic development of the inner ear; however, little is known regarding their function in cochlear hair cells (HCs) after specification. Here, we revealed the localization and activation of Racs in cochlear HCs using GFP-tagged Rac plasmids and transgenic mice expressing a Rac1-fluorescence resonance energy transfer (FRET) biosensor. Furthermore, we employedRac1-knockout (Rac1-KO,Atoh1-Cre;Rac1flox/flox) andRac1 andRac3 double KO (Rac1/Rac3-DKO,Atoh1-Cre;Rac1flox/flox;Rac3−/−) mice, under the control of theAtoh1 promoter. However, bothRac1-KO andRac1/Rac3-DKO mic...
Source: Journal of Molecular Medicine - May 19, 2023 Category: Molecular Biology Source Type: research
The TLR/MyD88 signalling cascade in inflammation and gastric cancer: the immune regulatory network of Helicobacter pylori
AbstractHelicobacter pylori-induced chronic gastritis represents a well-established risk factor for gastric cancer (GC). However, the mechanism by which chronic inflammation caused byH. pylori induces the development of GC is unclear.H. pylori can influence host cell signalling pathways to induce gastric disease development and mediate cancer promotion and progression. Toll-like receptors (TLRs), as pattern recognition receptors (PRRs), play a key role in the gastrointestinal innate immune response, and their signalling has been implicated in the pathogenesis of an increasing number of inflammation-associated cancers. The ...
Source: Journal of Molecular Medicine - May 17, 2023 Category: Molecular Biology Source Type: research
Increased Fusobacterium tumoural abundance affects immunogenicity in mucinous colorectal cancer and may be associated with improved clinical outcome
The objectives of this study were to assess the association ofFusobacterium abundance with immune cell composition and prognosis in mucinous CRC. Our study included two independent colorectal cancer patient cohorts, The Cancer Genome Atlas (TCGA) cohort, and a cohort of rectal cancers from the Beaumont RCSI Cancer Centre (BRCC). Multiplexed immunofluorescence staining of a tumour microarray (TMA) from the BRCC cohort was undertaken using Cell DIVE technology. Our cohorts included 87 cases (13.3%) of mucinous and 565 cases (86.7%) of non-mucinous CRC. Mucinous CRC in the TCGA dataset was associated with an increased proport...
Source: Journal of Molecular Medicine - May 12, 2023 Category: Molecular Biology Source Type: research
Myeloid-specific deletion of chitinase-3-like 1 protein ameliorates murine diet-induced steatohepatitis progression
AbstractChitinase-3-like 1 protein (CHI3L1) is a secreted glycoprotein, strongly correlated with fibrosis severity in chronic liver diseases including non-alcoholic steatohepatitis (NASH). However, the mechanisms by which CHI3L1 contributes to fibrogenesis remain undefined. Here, we showed that infiltrating monocyte-derived liver macrophages represent the main source of CHI3L1 in murine NASH. We developed a floxed CHI3L1 knock-out (KO) mouse to further study the cell-specific role of CHI3L1 ablation. Wildtype (WT) and myeloid cell-specific CHI3L1 KO mice (CreLyz) were challenged with a highly inflammatory and fibrotic diet...
Source: Journal of Molecular Medicine - May 11, 2023 Category: Molecular Biology Source Type: research
Upregulation of glycolytic enzyme PFKFB3 by deubiquitinase OTUD4 promotes cardiac fibrosis post myocardial infarction
AbstractMetabolic dysregulations have emerged as a major mediator of cardiovascular disorders and fibrotic diseases. Metabolic reprogramming contributes a lot to cardiac fibroblast activation and cardiac fibrosis post-myocardial infarction (MI), yet the mechanism remains incompletely understood. Our work aimed to determine whether or not glycolytic reprogramming, regulated by phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3), is a therapeutic target for alleviating post-MI cardiac fibrosis. Here, we showed that cardiac fibroblasts displayed cell energy phenotype toward augmented glycolysis in response to transfo...
Source: Journal of Molecular Medicine - May 10, 2023 Category: Molecular Biology Source Type: research
