Maternal gut microbiota influence stem cell function in offspring.

The maternal microbiome influences child health. However, its impact on a given offspring's stem cells, which regulate development, remains poorly understood. To investigate the role of the maternal microbiome in conditioning the offspring's stem cells, we manipulated maternal microbiota using Akkermansia muciniphila.

METTL3/YTHDF1-mediated mA modification stabilizes USP12 to deubiquitinate FOXO3 and promote apoptosis in sepsis-induced myocardial dysfunction.

Sepsis-induced myocardial dysfunction (SIMD) is a life-threatening complication primarily driven by inflammation, yet its molecular mechanisms remain unclear. In this study, we identified significant upregulation of the mA methyltransferase METTL3 (methyltransferase-like 3), the mA reader protein YTHDF1 (YTH N6-methyladenosine RNA binding protein 1), as well as increased expression levels of USP12 (ubiquitin-specific peptidase 12), FOXO3 (forkhead box O3), and key molecules in the intrinsic apoptotic pathway, PUMA (p53 upregulated modulator of apoptosis) and BAX (Bcl-2-associated X), through proteomic profiling in an LPS (Lipopolysaccharide)-induced SIMD mouse model. In vitro and in vivo experiments demonstrated that METTL3 and YTHDF1 regulated USP12 mRNA expression and stability through mA modification.

Known and unknown: Exosome secretion in tumor microenvironment needs more exploration.

Exosomes, extracellular vesicles originating from endosomes, were discovered in the late 1980s and their function in intercellular communication has since garnered considerable interest. Exosomes are lipid bilayer-coated vesicles that range in size from 30 to 150 nm and appear as sacs under the electron microscope. Exosome secretion is crucial for cell-to-cell contact in both normal physiology and the development and spread of tumors.

Evaluation of deep eutectic solvents chiral selectors based on lactobionic acid in capillary electrophoresis.

Recently, deep eutectic solvents (DESs) have attracted considerable interest in analytical chemistry. This work described the enantioseparations of twenty amino alcohol drugs with several DESs based on lactobionic acid (LA) as the sole chiral selector in capillary electrophoresis (CE) firstly. Compared to the single LA system and the ionic liquid/LA synergistic system, the DES system exhibited considerably improved separations.

The upregulation of Annexin A2 by TLR4 pathway facilitates lipid accumulation and liver injury via blocking AMPK/mTOR-mediated autophagy flux during the development of non-alcoholic fatty liver disease.

Background And Aims: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. In this study, we aimed to investigate the role and regulatory mechanism of Annexin A2 (ANXA2) in the pathogenesis of NAFLD.

Methods: Histological analyses and ELISA were used to illuminate the expression of ANXA2 in NAFLD and healthy subjects.

Longer leukocyte telomere length increases cardiovascular mortality in type 2 diabetes patients.

Aims: Leukocyte telomere length (LTL), as a biomarker of biological aging, is associated with the prevalence and complications of diabetes. This study aims to investigate the associations between LTL and all-cause and cause-specific mortality in patients with type 2 diabetes.

Methods: All participants with baseline LTL records were included from the National Health and Nutrition Examination Survey 1999-2002.

A pathway model of chronic pain and frailty in older Chinese cancer patients: The mediating effect of sleep.

This study aimed to explore the association between chronic pain, sleep quality, and frailty, and whether sleep quality will mediate the relationship between chronic pain and frailty. A cross-sectional study was conducted between June 2020 and July 2021 among 308 patients in Nantong city. The relationship between chronic pain and frailty was tested using linear regression.

Extracellular vesicles from Zika virus-infected cells display viral E protein that binds ZIKV-neutralizing antibodies to prevent infection enhancement.

Mosquito-borne flaviviruses including Zika virus (ZIKV) represent a public health problem in some parts of the world. Although ZIKV infection is predominantly asymptomatic or associated with mild symptoms, it can lead to neurological complications. ZIKV infection can also cause antibody-dependent enhancement (ADE) of infection with similar viruses, warranting further studies of virion assembly and the function of envelope (E) protein-specific antibodies.

Construction and validation of a m6A RNA methylation and ferroptosis-related prognostic model for pancreatic cancer by integrated bioinformatics analysis.

Background: Both N6-methyladenosine (m6A) ribonucleic acid (RNA) methylation and ferroptosis regulators are demonstrated to have significant effects on the malignant clinicopathological characteristics of pancreatic adenocarcinoma (PAAD) patients. However, the currently available clinical indexes are not sufficient to predict precise prognostic outcomes pf PAAD patients accurately. This study aims to examine the clinicopathologic features of m6A RNA methylation and ferroptosis regulators in predicting the outcomes of different types of cancer.

Organoids in recapitulating tumorigenesis driven by risk factors: Current trends and future perspectives.

Environmental and exogenous/ endogenous factors, in a setting of individual genetic predisposition, contribute to the cancer development. Over the years, epidemical evidence increasingly highlights the correlations of multiple cancer incentives and genetic alterations with cancer incidence. Unraveling the pivotal carcinogenesis events prompted by particular risk factors remarkably advances early surveillance and oncogenesis intervening.

The biogenesis and secretion of exosomes and multivesicular bodies (MVBs): Intercellular shuttles and implications in human diseases.

Exosomes carry and transmit signaling molecules used for intercellular communication. The generation and secretion of exosomes is a multistep interlocking process that allows simultaneous control of multiple regulatory sites. Protein molecules, mainly RAB GTPases, cytoskeletal proteins and soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE), are specifically regulated in response to pathological conditions such as altered cellular microenvironment, stimulation by pathogenic factors, or gene mutation.

Flap endonuclease 1 Facilitated Hepatocellular Carcinoma Progression by Enhancing USP7/MDM2-mediated P53 Inactivation.

Overexpression of Flap endonuclease 1 (FEN1) has been previously implicated in hepatocellular carcinoma (HCC), while its expression features and mechanisms remain unclear. In the current study, differential expression genes (DEGs) were screened in HCC tissues and normal liver tissues in 4 Gene Expression Omnibus (GEO) datasets. FEN1, one of the hub co-overexpressed genes, was further determined overexpressed in HCC tissues in TCGA, local HCC cohorts, and hepatocarcinogenesis model.

Association Between C-Peptide Level and Subclinical Myocardial Injury.

Background: Previous studies have confirmed an association between C-peptide levels with the risk of cardiometabolic diseases. However, whether circulating C-peptide was related to subclinical myocardial injury (SC-MI) remains unknown.

Methods: A total of 3,752 participants without a history of cardiovascular diseases were included in our study from National Health and Nutrition Examination Survey III (NHANES III).

The endoribonuclease N4BP1 prevents psoriasis by controlling both keratinocytes proliferation and neutrophil infiltration.

Psoriasis is a common chronic skin disease, characterized by abnormal interplay between hyperproliferative epidermal keratinocytes and self-reactive immune cells with not fully addressed molecular mechanism. N4BP1 (NEDD4-binding protein 1) is considered as an immune regulator for a long time but its physiological role is not determined yet. Here, we found that the expression of N4BP1 in skin was highest among all 54 tested tissues, and its expression was further upregulated in psoriatic skin.

Identification and Validation of Ubiquitin-Specific Proteases as a Novel Prognostic Signature for Hepatocellular Carcinoma.

Purpose: Ubiquitin-specific proteases (USPs), as a sub-family of deubiquitinating enzymes (DUBs), are responsible for the elimination of ubiquitin-triggered modification. USPs are recently correlated with various malignancies. However, the expression features and clinical significance of USPs have not been systematically investigated in hepatocellular carcinoma (HCC).

DNA primase subunit 1 deteriorated progression of hepatocellular carcinoma by activating AKT/mTOR signaling and UBE2C-mediated P53 ubiquitination.

Background: DNA primase subunit 1 (PRIM1) has been reported as a novel oncogene in several cancer types. However, its roles in hepatocellular carcinoma (HCC) remain unclear. This study aimed to investigate underlying mechanisms of PRIM1 and identify it as a potential molecular target for HCC.

Biological testing of chitosan-collagen-based porous scaffolds loaded with PLGA/Triamcinolone microspheres for ameliorating endoscopic dissection-related stenosis in oesophagus.

Objectives: Endoscopic submucosal dissection (ESD), a preferential approach for early oesophageal neoplasms, inevitably results in oesophageal strictures in patients. Clinical use of glucocorticoids through submucosal injection is beneficial for inhibiting oesophageal stricture following injury; however, it also has limitations, such as dose loss and perforation. Hence, alternatives to glucocorticoid therapy should be developed.

Targeting the TXNIP-NLRP3 interaction with PSSM1443 to suppress inflammation in sepsis-induced myocardial dysfunction.

Sepsis-induced myocardial dysfunction (SIMD), a deadly symptom in sepsis patients, is mainly caused by cardiovascular inflammation. However, it remains unclear how systemic inflammation triggers and aggravates cardiovascular inflammation in the pathogenesis of SIMD. This study found that proinflammatory cytokines and H O concentrations were significantly induced in SIMD-mice.

EHD2 Overexpression Suppresses the Proliferation, Migration, and Invasion in Human Colon Cancer.

To investigate how EHD2 influences the development of colon cancer. Immunohistochemistry of 90 colon cancer tissue specimens were determined the expression of EHD2. The lentivirus-EHD2-transfected colon cancer cells were conducted to evaluate the biological behaviors.

Identifying cancer-associated fibroblasts as emerging targets for hepatocellular carcinoma.

The tumor microenvironment (TME) is a complex multicellular functional compartment that includes fibroblasts, myofibroblasts, endothelial cells, immune cells, and extracellular matrix (ECM) elements. The microenvironment provides an optimum condition for the initiation, growth, and dissemination of hepatocellular carcinoma (HCC). As one of the critical and abundant components in tumor microenvironment, cancer-associated fibroblasts (CAFs) have been implicated in the progression of HCC.

The small molecule PSSM0332 disassociates the CRL4A E3 ligase complex to decrease the ubiquitination of NcoR1 and inhibit the inflammatory response in a mouse sepsis-induced myocardial dysfunction model.

Sepsis-induced myocardial dysfunction (SIMD) is a life-threatening complication caused by inflammation, but how it is initiated is still unclear. Several studies have shown that extracellular high mobility group box 1 (HMGB1), an important cytokine triggering inflammation, is overexpressed during the pathogenesis of SIMD, but the underlying mechanism regarding its overexpression is still unknown. Herein, we discovered that CUL4A (cullin 4A) assembled an E3 ligase complex with RBX1 (ring-box 1), DDB1 (DNA damage-binding protein 1), and DCAF8 (DDB1 and CUL4 associated factor 8), termed CRL4A, which ubiquitinated and degraded NcoR1 (nuclear receptor corepressor 1) in an LPS-induced SIMD mouse model.

USP7 mediates pathological hepatic de novo lipogenesis through promoting stabilization and transcription of ZNF638.

Aberrant de novo lipogenesis (DNL) results in excessive hepatic lipid accumulation and liver steatosis, the causative factors of many liver diseases, such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC). However, the underlying mechanism of DNL dysregulation remains largely unknown. Ubiquitination of proteins in hepatocytes has been shown to be widely involved in lipid metabolism of liver.

A novel β2-AR/YB-1/β-catenin axis mediates chronic stress-associated metastasis in hepatocellular carcinoma.

β-Adrenergic receptor (β-AR) signalling is strongly associated with tumour progression by the coupling of β-ARs with either a G protein or β-arrestin; however, the related mechanism underlying hepatocellular carcinoma (HCC) metastasis is not clear. Here, we reveal that the transcription factor Y-box binding protein 1 (YB-1) interacts with β2-adrenergic receptor (β2-AR) following stimulation with the agonist isoproterenol (ISO). Clinicopathological analysis demonstrated that β2-AR is significantly correlated with YB-1, which favours the progression of HCC.