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
The complement factor H-related protein-5 (CFHR5) exacerbates pathological bone formation in ankylosing spondylitis
In this study, we revealed that CFHR5 and proinflammatory cytokines (TNF, IL-6, IL-17A, and IL-23) were elevated in the AS group compared to the HC group. Correlation analysis revealed that CFHR5 levels were not significantly associated with proinflammatory cytokines, while CFHR5 levels in AS were only positively correlated with the high CRP group. Notably, treatment with soluble CFHR5 has no effect on clinical arthritis scores and thickness at hind paw in curdlan-injected SKG, but significantly increased the ectopic bone formation at the calcaneus and tibia bones of the ankle as revealed by micro-CT image and quantificati...
Source: Journal of Molecular Medicine - February 29, 2024 Category: Molecular Biology Source Type: research
The therapeutic effect of mesenchymal stem cells in diabetic kidney disease
AbstractDiabetes mellitus (DM) often causes chronic kidney damage despite best medical practices. Diabetic kidney disease (DKD) arises from a complex interaction of factors within the kidney and the whole body. Targeting specific disease-causing agents using drugs has not been effective in treating DKD. However, stem cell therapies offer a promising alternative by addressing multiple disease pathways and promoting kidney regeneration. Mesenchymal stem cells (MSCs) offer great promise due to their superior accessibility ratio from adult tissues and remarkable modes of action, such as the production of paracrine anti-inflamm...
Source: Journal of Molecular Medicine - February 29, 2024 Category: Molecular Biology Source Type: research
Targeting EphA2: a promising strategy to overcome chemoresistance and drug resistance in cancer
AbstractErythropoietin-producing hepatocellular A2 (EphA2) is a vital member of the Eph tyrosine kinase receptor family and has been associated with developmental processes. However, it is often overexpressed in tumors and correlates with cancer progression and worse prognosis due to the activation of its noncanonical signaling pathway. Throughout cancer treatment, the emergence of drug-resistant tumor cells is relatively common. Since the early 2000s, researchers have focused on understanding the role of EphA2 in promoting drug resistance in different types of cancer, as well as finding efficient and secure EphA2 inhibito...
Source: Journal of Molecular Medicine - February 23, 2024 Category: Molecular Biology Source Type: research
The role of regulated necrosis in diabetes and its complications
AbstractMorphologically, cell death can be divided into apoptosis and necrosis. Apoptosis, which is a type of regulated cell death, is well tolerated by the immune system and is responsible for hemostasis and cellular turnover under physiological conditions. In contrast, necrosis is defined as a form of passive cell death that leads to a dramatic inflammatory response (also referred to as necroinflammation) and causes organ dysfunction under pathological conditions. Recently, a novel form of cell death named regulated necrosis (such as necroptosis, pyroptosis, and ferroptosis) was discovered. Distinct from apoptosis, regul...
Source: Journal of Molecular Medicine - February 23, 2024 Category: Molecular Biology Source Type: research
Emerging therapeutic targets in systemic sclerosis
AbstractSystemic sclerosis is an autoimmune connective tissue disease which is characterised by vascular perturbations, inflammation, and fibrosis. Although huge progress recently into the underlying molecular pathways that are perturbed in the disease, currently no therapy exists that targets the fibrosis element of the disease and consequently there is a huge unmet medical need. Emerging studies reveal new dimensions of complexity, and multiple aberrant pathways have been uncovered that have shed light on disturbed signalling in the disease, primarily in inflammatory pathways that can be targeted with repurposed drugs. P...
Source: Journal of Molecular Medicine - February 22, 2024 Category: Molecular Biology Source Type: research
Novel high-yield potato protease inhibitor panels block a wide array of proteases involved in viral infection and crucial tissue damage
AbstractViruses critically rely on various proteases to ensure host cell entry and replication. In response to viral infection, the host will induce acute tissue inflammation pulled by granulocytes. Upon hyperactivation, neutrophil granulocytes may cause undue tissue damage through proteolytic degradation of the extracellular matrix. Here, we assess the potential of protease inhibitors (PI) derived from potatoes in inhibiting viral infection and reducing tissue damage. The original full spectrum of potato PI was developed into five fractions by means of chromatography and hydrolysis. Individual fractions showed varying inh...
Source: Journal of Molecular Medicine - February 21, 2024 Category: Molecular Biology Source Type: research
Systemic and local effect of oxidative stress on recurrent aphthous stomatitis: systematic review
AbstractRecurrent aphthous stomatitis (RAS) is a chronic and recurrent inflammatory disease of the mouth. It is characterised by the appearance of painful ulcers in the oral mucosa. RAS is believed to be a multifactorial disease with genetic predisposition, environmental factors and alterations in the immune system. Oxidative stress, caused by an imbalance between free radicals and the antioxidant system, also appears to be involved in the pathogenesis of RAS. Several risk factors, such as smoking, iron and vitamin deficiency and anxiety, may contribute to the development of the disease. Understanding the underlying mechan...
Source: Journal of Molecular Medicine - February 20, 2024 Category: Molecular Biology Source Type: research
Current knowledge of bone-derived factor osteocalcin: its role in the management and treatment of diabetes mellitus, osteoporosis, osteopetrosis and inflammatory joint diseases
AbstractOsteocalcin (OC) is the most abundant non-collagenous and osteoblast-secreted protein in bone. It consists of two forms such as carboxylated OC (cOC) and undercarboxylated OC (ucOC). While cOC promotes bone mineralization and increases bone strength, ucOC is regarded an endocrinologically active form that may have several functions in multiple end organs and tissues. Total OC (tOC) includes both of these forms (cOC and ucOC) and is considered a marker of bone turnover in clinical settings. Most of the data on OC is limited to preclinical studies and therefore may not accurately reflect the situation in clinical con...
Source: Journal of Molecular Medicine - February 16, 2024 Category: Molecular Biology Source Type: research
FDA-approved disulfiram as a novel treatment for aggressive leukemia
This study assessed the biological effects of disulfiram on leukemia cells and evaluated its potential as a treatment strategy. We found that disulfiram inhibits the viability of a diverse panel of acute lymphoblastic and myeloid leukemia cell lines (n = 16) and patient-derived xenograft cells from patients with poor outcome and treatment-resistant disease (n = 15). The drug induced oxidative stress and apoptosis in leukemia cells within hours of treatment and was able to potentiate the effects of daunorubicin, etoposide, topotecan, cytarabine, and mitoxantrone chemotherapy. Upon combining disulfiram with auranofin...
Source: Journal of Molecular Medicine - February 13, 2024 Category: Molecular Biology Source Type: research
High expression of BCAT1 sensitizes AML cells to PARP inhibitor by suppressing DNA damage response
In this study, we investigated the clinical significance and biological insight ofBCAT1 in AML. Using q-PCR, we analyzedBCAT1 mRNAs in bone marrow samples from 332 patients with newly diagnosed AML. HighBCAT1 expression independently predicts poor prognosis in patients with AML. We also establishedBCAT1 knockout (KO)/over-expressing (OE) AML cell lines to explore the underlying mechanisms. We found thatBCAT1 affects cell proliferation and modulates cell cycle, cell apoptosis, and DNA damage/repair process. Additionally, we demonstrated thatBCAT1 regulates histone methylation by reducing intracellularαKG levels in AML cell...
Source: Journal of Molecular Medicine - February 10, 2024 Category: Molecular Biology Source Type: research
Etiopathogenesis of medication-related osteonecrosis of the jaws: a review
This study compiles the main hypotheses involved in the etiopathogenesis of medication-related osteonecrosis of the jaw (MRONJ). A narrative review of the literature was performed. The etiopathogenesis of MRONJ is multifactorial and not fully understood. The main hypothesis considers the disturbance of bone turnover caused by anti-resorptive drugs. Bisphosphonates and denosumab inhibit osteoclast activity through different action mechanisms, accumulating bone microfracture. Other hypotheses also consider oral infection and inflammation, the antiangiogenic effect and soft tissue toxicity of bisphosphonates, and the inhibiti...
Source: Journal of Molecular Medicine - February 2, 2024 Category: Molecular Biology Source Type: research
Ubiquitination and deubiquitination in the regulation of N6-methyladenosine functional molecules
AbstractN6 methyladenosine (m6A) is the most prevalent RNA epigenetic modification, regulated by methyltransferases and demethyltransferases and recognized by methylation-related reading proteins to impact mRNA splicing, translocation, stability, and translation efficiency. It significantly affects a variety of activities, including stem cell maintenance and differentiation, tumor formation, immune regulation, and metabolic disorders. Ubiquitination refers to the specific modification of target proteins by ubiquitin molecule in response to a series of enzymes. E3 ligases connect ubiquitin to target proteins and usually lea...
Source: Journal of Molecular Medicine - January 30, 2024 Category: Molecular Biology Source Type: research
Evidence for alterations in lipid profiles and biophysical properties of lipid rafts from spinal cord in sporadic amyotrophic lateral sclerosis
AbstractAmyotrophic lateral sclerosis (ALS) is an age-dependent neurodegenerative disease affecting motor neurons in the spinal cord and brainstem whose etiopathogenesis remains unclear. Recent studies have linked major neurodegenerative diseases with altered function of multimolecular lipid-protein complexes named lipid rafts. In the present study, we have isolated lipid rafts from the anterior horn of the spinal cords of controls and ALS individuals and analysed their lipid composition. We found that ALS affects levels of different fatty acids, lipid classes and related ratios and indexes. The most significant changes af...
Source: Journal of Molecular Medicine - January 29, 2024 Category: Molecular Biology Source Type: research
Traumatic brain injury-induced disruption of the circadian clock
AbstractDisturbances in the circadian rhythm have been reported in patients following traumatic brain injury (TBI). However, the rhythmic expression of circadian genes in peripheral blood leukocytes (PBL) following TBI has not yet been studied. The messenger ribonucleic acid (mRNA) expression of period 1 (Per1),Per2,Per3, cryptochrome 1 (Cry1),Cry2, brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (Bmal1), and circadian locomotor output cycles kaput (Clock) was quantified in PBLs from sham-operated rats and rats with acute subdural hematoma (ASDH) over a 48-h period. The rectal temperature of the anim...
Source: Journal of Molecular Medicine - January 29, 2024 Category: Molecular Biology Source Type: research
