Journal of Molecular Medicine : Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"

TRIM-containing 44 (TRIM44) is a promoter of multiple cancers. However, its role in cardiac hypertrophy has not been elucidated. This study explored the role of TRIM44 on pressure overload-induced cardiac hypertrophy in mice. Mice were subjected to aortic banding to establish an adverse cardiac hypertrophy model, followed by the administration of AAV9-TRIM44 or AAV9shTRIM44 to overexpress or knock down TRIM44. Echocardiography was used to assess cardiac function. H9c2 cells were cultured and transfected with either Ad-TRIM44 or TRIM44 siRNA to overexpress or silence TRIM44...

Multiple sclerosis is an autoimmune neurodegenerative disease of the CNS that causes progressive disabilities, owing to CNS axon degeneration as a late result of demyelination. In the search for the prevention of axonal loss, mitigating inflammatory attacks in the CNS and myelin restoration are two possible approaches. As a result, therapies that target diverse signaling pathways involved in neuroprotection and remyelination have the potential to overcome the challenges in the development of multiple sclerosis treatments...

Hematopoietic stem cells are a group of heterogeneity cells with the potential to differentiate into various types of mature blood cells. Their basic biological properties include quiescence, self-renewal, multilineage differentiation, and homing ability, with the homing of exogenous hematopoietic stem cells after transplantation becoming a new focus, while the first three properties share some similarity in mechanism due to connectivity. In various complex mechanisms, the role of E3 ubiquitin ligases in hematopoietic homeostasis and malignant transformation is receiving increasing attention...

Increasing studies demonstrate the significant contributions of circRNA-related competitive endogenous RNA (ceRNA) regulatory networks to tumorigenesis and cancer progression. Here, we aimed to construct a non-small cell lung cancer (NSCLC)-specific circRNA-miRNA network and evaluate its diagnostic potential in NSCLC. MiRNA deep sequencing was performed to screen differentially-expressed serum miRNAs in NSCLC. Four bioinformatics databases (TargetScan, miRanda, starBase, and RNAhybrid) were used to analyze the integrated circRNA-miRNA interaction network...

Non-coding RNAs (ncRNAs) are significant regulators of gene expression in a wide range of biological processes, such as transcription, RNA maturation, or translation. ncRNAs interplay with proteins or other RNAs through not only classical sequence-based mechanisms but also unique higher-order structures such as RNA G-quadruplexes (rG4s). rG4s are predictably formed in guanine-rich sequences and are closely related to various human diseases, such as tumors, neurodegenerative diseases, and infections. This review focuses on the vital role of rG4s in ncRNAs, particularly lncRNAs and miRNAs...

Copper (Cu) was recently demonstrated to play a critical role in cellular physiological and biochemical processes, including energy production and maintenance, antioxidation and enzymatic activity, and signal transduction. Antioxidant 1 (ATOX1), a chaperone of Cu previously named human ATX1 homologue (HAH1), has been found to play an indispensable role in maintaining cellular Cu homeostasis, antioxidative stress, and transcriptional regulation. In the past decade, it has also been found to be involved in a variety of diseases, including numerous neurodegenerative diseases, cancers, and metabolic diseases...

Cardiovascular disease (CVD) is the leading cause of disease-related death worldwide and a significant obstacle to improving patients' health and lives. Mitochondria are core organelles for the maintenance of myocardial tissue homeostasis, and their impairment and dysfunction are considered major contributors to the pathogenesis of various CVDs, such as hypertension, myocardial infarction, and heart failure. However, the exact roles of mitochondrial dysfunction involved in CVD pathogenesis remain not fully understood...

Rheumatoid arthritis (RA) is a chronic inflammatory disease mediated by an interdependent network of proinflammatory molecules such as chemokines. Prokineticin 2 (PK2) is a chemokine-like peptide that modulates nociceptive threshold and immuno-inflammatory processes via two G-protein-linked receptors, prokineticin receptor 1 and 2 (PKR1 and PKR2). In the present study, we investigated the effects of the prokineticin receptor antagonist PC1 on arthritic pain and the inflammatory response in type II collagen-induced arthritis (CIA) in mice...

Chronic liver disease is a major public health problem with a high and increasing prevalence worldwide. In the progression of chronic liver disease, steatosis drives the progression of the disease to cirrhosis or even liver cancer. Hypoxia-inducible factor 1α (HIF-1α) is central to the regulation of hepatic lipid metabolism. HIF-1α upregulates the expression of genes related to lipid uptake and synthesis in the liver and downregulates the expression of lipid oxidation genes. Thus, it promotes intrahepatic lipid deposition...

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Endocrine therapy (ET), also known as hormone therapy, refers to the treatment of tumors by regulating and changing the endocrine environment and hormone levels. Its related mechanism is mainly through reducing hormone levels and blocking the binding of hormones to corresponding receptors, thus blocking the signal transduction pathway to stimulate tumor growth. However, with the application of ET, some patients show resistance to ET, which is attributed to abnormal accumulation of hormone receptors (HRs) and the production of multiple mutants of HRs...

Ebola virus can trigger a release of pro-inflammatory cytokines with subsequent vascular leakage and impairment of clotting finally leading to multiorgan failure and shock after entering and infecting patients. Ebola virus is known to directly target endothelial cells and macrophages, even without infecting them, through direct interactions with viral proteins. These interactions affect cellular mechanics and immune processes, which are tightly linked to other key cellular functions such as metabolism. However, research regarding metabolic activity of these cells upon viral exposure remains limited, hampering our understanding of its pathophysiology and progression...

Studies showed that SARS-CoV-2 can directly target the kidney and induce renal damage. As the cell surface receptor for SARS-CoV-2 infection, the angiotensin-converting enzyme 2 (ACE2) plays a pivotal role for renal physiology and function. Thus, it is important to understand ACE2 through which pathway influences the pathogenesis of renal damage induced by COVID-19. In this study, we first performed an eQTL mapping for Ace2 in kidney tissues in 53 BXD mice strains. Results demonstrated that Ace2 is highly expressed and strongly controlled by a genetic locus on chromosome 16 in the kidney, with six genes (Dnase1, Vasn, Usp7, Abat, Mgrn1, and Rbfox1) dominated as the upstream modulator, as they are highly correlated with Ace2 expression...

UVB exposure accelerates skin aging and pigmentation. Melatonin effectively regulates tyrosinase (TYR) activity and aging. The purpose of this study was to determine the association between premature senescence and pigmentation, and the mechanism of melanin synthesis effected by melatonin. Primary melanocytes were extracted and identified from the male foreskin. To inhibit TYR expression, primary melanocytes were transduced with the lentivirus pLKD-CMV-EGFP-2A-Puro-U6-TYR. The wild-type TYR(+/+) and TYR(-/-) or TYR(+/-) knockout C57BL/6 J mice were used to determine the role of TYR on melanin synthesis in vivo...

Low-intensity pulsed ultrasound (LIPUS), as a safe and potent physical therapy, has been widely used. It has been demonstrated that LIPUS could induce multiple biological effects, such as relieving pain, accelerating tissue repair/regeneration, and alleviating inflammation. A number of in vitro studies have indicated that LIPUS could significantly reduce the expression of proinflammatory cytokines. This anti-inflammatory effect has also been verified in many in vivo researches. However, the molecular mechanisms underlying LIPUS against inflammation are far from fully elucidated and may differ among different tissues and cells...

As a member of long non-coding RNAs (lncRNAs), LncRNA HLA complex group 18 (HCG18) has recently become the focus of cancer research. As outlined in this review, LncRNA HCG18 has been reported to be dysregulated in various cancers development and appears to be activated in a variety of tumors, including clear cell renal cell carcinoma (ccRCC), colorectal cancer (CRC), gastric cancer (GC), hepatocellular carcinoma (HCC), laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC), lung adenocarcinoma (LUAD), nasopharyngeal cancer (NPC), osteosarcoma (OS), and prostate cancer (PCa)...

The adenovirus-REIC/Dkk-3 expression vector (Ad-REIC) has been the focus of numerous clinical studies due to its potential for the quenching of cancers. The cancer-suppressing mechanisms of the REIC/DKK-3 gene depend on multiple pathways that exert both direct and indirect effects on cancers. The direct effect is triggered by REIC/Dkk-3-mediated ER stress that causes cancer-selective apoptosis, and the indirect effect can be classified in two ways: (i) induction, by Ad-REIC-mis-infected cancer-associated fibroblasts, of the production of IL-7, an important activator of T cells and NK cells, and (ii) promotion, by the secretory REIC/Dkk-3 protein, of dendritic cell polarization from monocytes...

NIMA (never in mitosis, gene A)-related kinase-6 (NEK6), a cell cycle regulatory gene, was found to regulate cardiac hypertrophy. However, its role in diabetes-induced cardiomyopathy has not been fully elucidated. This research was designed to illustrate the effect of NEK6 involved in diabetic cardiomyopathy. Here we used a streptozotocin (STZ)-induced mice diabetic cardiomyopathy model and NEK6 knockout mice to explore the role and mechanism of NEK6 in diabetic-induced cardiomyopathy. NEK6 knockout mice and wild-type littermates were subjected to STZ injection (50 mg/kg/day for 5 days) to induce a diabetic cardiomyopathy model...

Neuroblastoma is the most common malignant tumor in childhood, and metastases occur in more than 30% patients. Recurrent metastasis is the main cause of poor prognosis and high mortality in neuroblastoma. In this regard, there is still a lack of sufficient biomarkers and effective therapies. Therefore, we performed a multi-omics analysis of neuroblastoma patients from Therapeutically Applicable Research To Generate Effective Treatments (TARGET). With clinical relapse site information, tumor samples derived from the primary site were divided into recurrent metastasis and primary tumor groups...

Dyschromatosis universalis hereditaria (DUH) is a pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed randomly over the body. Although Sterile Alpha motif- and SH3 domain-containing protein 1 (SASH1) and ATP-binding cassette subfamily B, member 6 (ABCB6) have been identified as causative genes for this disorder, some cases involve unknown pathogenic genes. In this study, whole-exome sequencing, data analysis, and Sanger sequencing were utilized for a four-generation extended Chinese family with DUH...