The role of annexins in central nervous system development and disease
AbstractAnnexins, a group of Ca2+-dependent phospholipid-binding proteins, exert diverse roles in neuronal development, normal central nervous system (CNS) functioning, neurological disorders, and CNS tumors. This paper reviews the roles of individual annexins (A1-A13) in these contexts. Annexins possess unique structural and functional features, such as Ca2+-dependent binding to phospholipids, participating in membrane organization, and modulating cell signaling. They are implicated in various CNS processes, including endocytosis, exocytosis, and stabilization of plasma membranes. Annexins exhibit dynamic roles in neurona...
Source: Journal of Molecular Medicine - April 19, 2024 Category: Molecular Biology Source Type: research
The role of the immunosuppressive PD-1/PD-L1 checkpoint pathway in the aging process and age-related diseases
AbstractThe accumulation of senescent cells within tissues is a hallmark of the aging process. Senescent cells are also commonly present in many age-related diseases and in the cancer microenvironment. The escape of abnormal cells from immune surveillance indicates that there is some defect in the function of cytotoxic immune cells, e.g., CD8+ T cells and natural killer (NK) cells. Recent studies have revealed that the expression of programmed death-ligand 1 (PD-L1) protein is abundantly increased in senescent cells. An increase in the amount of PD-L1 protein protects senescent cells from clearance by the PD-1 checkpoint r...
Source: Journal of Molecular Medicine - April 11, 2024 Category: Molecular Biology Source Type: research
Abnormal protein SUMOylation in liver disease: novel target for therapy
AbstractSUMOylation is an important protein post-translational modification (PTM) process, in which the small ubiquitin-like modifier (SUMO) protein covalently binds to the target protein and regulates stability, subcellular localization, and protein –protein interaction of the target protein. Protein SUMOylation exerts crucial regulatory function in the liver, and its abnormalities are associated with various liver-related disease processes. This review focuses on the biological functions of protein SUMOylation in liver-related diseases in re cent years, summarizes the molecular mechanisms of SUMOylation in the replicat...
Source: Journal of Molecular Medicine - April 3, 2024 Category: Molecular Biology Source Type: research
Metabolomic profiling of maternal plasma identifies inverse associations of acetate and urea with anti-SARS-CoV-2 antibody titers following COVID-19 vaccination during pregnancy
In conclusion, we identified different metabolic pathways that underlie the diverse humoral responses triggered by COVID-19 mRNA vaccines during pregnancy. Our data hold significant implications for refining COVID-19 vaccination approaches in expectant mothers.Key messagesAnti-SARS-CoV-2 antibody titers decline as the number of days since COVID-19 vaccination increases.Anti-SARS-CoV-2 antibody titers are inversely associated with acetate, a microbial-derived metabolite, and urea.Amino acid metabolism is significantly associated with SARS-CoV-2 antibody titers. (Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - April 3, 2024 Category: Molecular Biology Source Type: research
Pathogenic effects of Leu200Pro and Arg387His VRK1 protein variants on phosphorylation targets and H4K16 acetylation in distal hereditary motor neuropathy
AbstractRare recessive variants in the humanVRK1 gene are associated with several motor neuron diseases (MND), such as amyotrophic lateral sclerosis, spinal muscular atrophy, or distal hereditary motor neuropathies (dHMN). A case with dHMN carrying two novel VRK1 gene variants, expressing Leu200Pro (L200P) and Arg387His (R387H) variant proteins, identified that these protein variants are functionally different. The Leu200Pro variant shares with several variants in the catalytic domain the loss of the kinase activity on different substrates, such as histones, p53, or coilin. However, the distal Arg387His variant and the dis...
Source: Journal of Molecular Medicine - March 30, 2024 Category: Molecular Biology Source Type: research
Ischemic stroke and diabetes: a TLR4-mediated neuroinflammatory perspective
AbstractIschemic stroke is the major contributor to morbidity and mortality in people with diabetes mellitus. In ischemic stroke patients, neuroinflammation is now understood to be one of the main underlying mechanisms for cerebral damage and recovery delay. It has been well-established that toll-like receptor 4 (TLR4) signaling pathway plays a key role in neuroinflammation. Emerging research over the last decade has revealed that, compared to ischemic stroke without diabetes mellitus, ischemic stroke with diabetes mellitus significantly upregulates TLR4-mediated neuroinflammation, increasing the risk of cerebral and neuro...
Source: Journal of Molecular Medicine - March 28, 2024 Category: Molecular Biology Source Type: research
An Hsp70 promoter –based mouse for heat shock–induced gene modulation
In this study, we successfully established a mouse line based on the heat shock protein 70 (Hsp70) promoter, wherein the expression of CreERT2 can be induced by physical stimuli. Following stimulation of the mouse tail, ear, or cultured calvarias with heat shock (generated by heating, ultrasound, or laser), a distinct Cre-mediated excision was observed in cells stimulated by these physical factors with minimal occurrence of leaky reporter expression. The application of heat shock to Hsp70-CreERT2; FGFR2-P253R double transgenic mice or Hsp70-CreERT2 mice infected with AAV-BMP4 at calvarias induced the activation of Cre-depe...
Source: Journal of Molecular Medicine - March 16, 2024 Category: Molecular Biology Source Type: research
Blockade of aryl hydrocarbon receptor restricts omeprazole-induced chronic kidney disease
We described the process of renal injury after exposure to OME in mice; the early renal injury markers were increased in renal tubular epithelial cells (RTECs). And after long-term OME treatment, the OME-induced CKD mice model was established. Herein, aryl hydrocarbon receptor (AHR) translocation appeared after exposure to OME in HK-2 cells. Then for both in vivo and in vitro, we found that Ahr-knockout (KO) and AHR small interfering RNA (siRNA) substantially alleviated the OME-induced renal function impairment and tubular cell damage. Furthermore, our data demonstrate that antagonists of AHR and CYP1A1 could attenuate OME...
Source: Journal of Molecular Medicine - March 8, 2024 Category: Molecular Biology Source Type: research
How calorie restriction slows aging: an epigenetic perspective
AbstractGenomic instability and epigenetic alterations are some of the prominent factors affecting aging. Age-related heterochromatin loss and decreased whole-genome DNA methylation are associated with abnormal gene expression, leading to diseases and genomic instability. Modulation of these epigenetic changes is crucial for preserving genomic integrity and controlling cellular identity is important for slowing the aging process. Numerous studies have shown that caloric restriction is the gold standard for promoting longevity and healthy aging in various species ranging from rodents to primates. It can be inferred that del...
Source: Journal of Molecular Medicine - March 8, 2024 Category: Molecular Biology Source Type: research
Exploiting the therapeutic potential of contracting skeletal muscle-released extracellular vesicles in cancer: Current insights and future directions
AbstractThe health benefits of exercise training in a cancer setting are increasingly acknowledged; however, the underlying molecular mechanisms remain poorly understood. It has been suggested that extracellular vesicles (EVs) released from contracting skeletal muscles play a key role in mediating the systemic benefits of exercise by transporting bioactive molecules, including myokines. Nevertheless, skeletal muscle-derived vesicles account for only about 5% of plasma EVs, with the immune cells making the largest contribution. Moreover, it remains unclear whether the contribution of skeletal muscle-derived EVs increases af...
Source: Journal of Molecular Medicine - March 7, 2024 Category: Molecular Biology Source Type: research
Physiological and pathological effects of phase separation in the central nervous system
AbstractPhase separation, also known as biomolecule condensate, participates in physiological processes such as transcriptional regulation, signal transduction, gene expression, and DNA damage repair by creating a membrane-free compartment. Phase separation is primarily caused by the interaction of multivalent non-covalent bonds between proteins and/or nucleic acids. The strength of molecular multivalent interaction can be modified by component concentration, the potential of hydrogen, posttranslational modification, and other factors. Notably, phase separation occurs frequently in the cytoplasm of mitochondria, the nucleu...
Source: Journal of Molecular Medicine - March 5, 2024 Category: Molecular Biology Source Type: research
Decreased circulating CTRP3 levels in acute and chronic cardiovascular patients
This study aimed to investigate CTRP3 levels in chronic and acute settings such as chronic coronary syndrome (CCS) and acute coronary syndrome (ACS). A total of 206 patients were classified into three groups: CCS (n = 64), ACS having a first acute event (ACS-1, n = 75), and ACS having a recurrent acute event (ACS-2, n = 67). The control group consisted of 49 healthy individuals. ELISA measurement in peripheral blood revealed decreased CTRP3 levels in all patient groups (p < 0.001) without significant differences between the groups. This effect was exclusively observed in male patients. Females generall...
Source: Journal of Molecular Medicine - March 4, 2024 Category: Molecular Biology Source Type: research
NLRC3 attenuates osteoclastogenesis by limiting TNF α+ Th17 cell response in osteoporosis
In this study, we transferred the wild-type and NLRC3−/− CD4+ cells into Rag1−/− mice. Consequently, we evidenced the effects of NLRC3 in CD4+ T cells on inhibiting the accumulation of TNF α + Th17 cells, thus restricting bone loss in the OVX mice. Simultaneously, NLRC3−/− CD4+ T cells promoted the recruitment of osteoclast precursors and inflammatory monocytes into the OVX mouse bone marrow. Mechanism-wise, NLRC3 reduced the secretion of TNF α + Th17 cells of RANKL, MIP1α, and MCP1, depending on the T cells. In addition, NLRC3 negatively regulated the Th17 osteoclastogenesis promoting functions via ...
Source: Journal of Molecular Medicine - March 4, 2024 Category: Molecular Biology Source Type: research
Systematic and quantitative analysis of stop codon readthrough in Rett syndrome nonsense mutations
AbstractRett syndrome (RTT) is a neurodevelopmental disorder resulting from genetic mutations in themethyl CpG binding protein 2 (MeCP2) gene. Specifically, around 35% of RTT patients harbor premature termination codons (PTCs) within theMeCP2 gene due to nonsense mutations. A promising therapeutic avenue for these individuals involves the use of aminoglycosides, which stimulate translational readthrough (TR) by causing stop codons to be interpreted as sense codons. However, the effectiveness of this treatment depends on several factors, including the type of stop codon and the surrounding nucleotides, collectively referred...
Source: Journal of Molecular Medicine - March 2, 2024 Category: Molecular Biology Source Type: research
Macrophage activation contributes to diabetic retinopathy
AbstractDiabetic retinopathy (DR) is recognized as a neurovascular complication of diabetes, and emerging evidence underscores the pivotal role of inflammation in its pathophysiology. Macrophage activation is increasingly acknowledged as a key contributor to the onset and progression of DR. Different populations of macrophages originating from distinct sources contribute to DR-associated inflammation. Retinal macrophages can be broadly categorized into two main groups based on their origin: intrinsic macrophages situated within the retina and vitreoretinal interface and macrophages derived from infiltrating monocytes. The ...
Source: Journal of Molecular Medicine - March 2, 2024 Category: Molecular Biology Source Type: research
