Anti-fibrotic effects of pharmacologic FGF-2: a review of recent literature
AbstractFibrosis is a process of pathological tissue repair that replaces damaged, formerly functional tissue with a non-functional, collagen-rich scar. Complications of fibrotic pathologies, which can arise in numerous organs and from numerous conditions, result in nearly half of deaths in the developed world. Despite this, therapies that target fibrosis at its mechanistic roots are still notably lacking. The ubiquity of the occurrence of fibrosis in myriad organs emphasizes the fact that there are shared mechanisms underlying fibrotic conditions, which may serve as common therapeutic targets for multiple fibrotic disease...
Source: Journal of Molecular Medicine - April 28, 2022 Category: Molecular Biology Source Type: research
Current and future direction in treatment of HPV-related cervical disease
AbstractHuman papillomavirus (HPV) is the most common sexually transmitted virus in the world. About 70% of cervical cancers are caused by the most oncogenic HPV genotypes of 16 and 18. Since available prophylactic vaccines do not induce immunity in those with established HPV infections, the development of therapeutic HPV vaccines using E6 and E7 oncogenes, or both as the target antigens remains essential. Also, knocking out the E6 and E7 oncogenes in host genome by genome-editing CRISPR/Cas system can result in tumor growth suppression. These methods have shown promising results in both preclinical and clinical trials and...
Source: Journal of Molecular Medicine - April 27, 2022 Category: Molecular Biology Source Type: research
Receptor-interacting protein kinase-1 ablation in liver parenchymal cells promotes liver fibrosis in murine NASH without affecting other symptoms
In conclusion, our results show that RIPK1 in hepatocyte limits the progression of liver fibrosis during NASH. (Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - April 27, 2022 Category: Molecular Biology Source Type: research
Correction to: White and brown adipose tissue functionality is impaired by fine particulate matter (PM2.5) exposure
(Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - April 27, 2022 Category: Molecular Biology Source Type: research
ASK1 is a novel molecular target for preventing aminoglycoside-induced hair cell death
AbstractAminoglycoside antibiotics are lifesaving medicines, crucial for the treatment of chronic or drug resistant infections. However, aminoglycosides are toxic to the sensory hair cells in the inner ear. As a result, aminoglycoside-treated individuals can develop permanent hearing loss and vestibular impairment. There is considerable evidence that reactive oxygen species (ROS) production and the subsequent phosphorylation of c-Jun N-terminal kinase (JNK) and P38 mitogen-activated protein kinase (P38) drives apoptosis in aminoglycoside-treated hair cells. However, treatment strategies that directly inhibit ROS, JNK, or P...
Source: Journal of Molecular Medicine - April 26, 2022 Category: Molecular Biology Source Type: research
Inhibition of p38 MAPK decreases hyperglycemia-induced nephrin endocytosis and attenuates albuminuria
AbstractChronic hyperglycemia, as in diabetes mellitus, may cause glomerular damage with microalbuminuria as an early sign. Noteworthy, even acute hyperglycemia can increase glomerular permeability before structural damage of the glomerular filter can be detected. Despite intensive research, specific antiproteinuric therapy is not available so far. Thus, a deeper understanding of the molecular mechanisms of albuminuria is desirable. P38 MAPK signaling is involved in the development of hyperglycemia-induced albuminuria. However, the mechanism of increased p38 MAPK activity leading to increased permeability and albuminuria r...
Source: Journal of Molecular Medicine - April 22, 2022 Category: Molecular Biology Source Type: research
Nets, pulmonary arterial hypertension, and thrombo-inflammation
AbstractPulmonary arterial hypertension (PAH) is a progressive and fatal vascular disease in which high blood pressure in the pulmonary artery and remodeling of the pulmonary vasculature ensues. This disorder is characterized by the presence of thrombotic lesions, resulting from chronic platelet, coagulation factors, and endothelium activation, which translate into platelet aggregation, vasoconstriction, and medial thickening. Neutrophil extracellular traps (NETs), a network of chromatin and cytoplasmatic enzymes (myeloperoxidase and neutrophil elastase) forming after neutrophil programmed cell death, were described in mul...
Source: Journal of Molecular Medicine - April 20, 2022 Category: Molecular Biology Source Type: research
Possible implication of miR-142-3p in coronary microembolization induced myocardial injury via ATXN1L/HDAC3/NOL3 axis
This study aims to explore the mechanism underlying miR-142-3p regulating myocardial injury induced by coronary microembolization (CME) through ATXN1L. miR-142-3p overexpression or ATXN1L knockout adenovirus vectors were injected into rats before CME treatment. Cardiac functions were examined by echocardiography, and pathologies of myocardial tissues were assessed. Then, serum cTnI and IL-1 β contents and concentrations of IL-1β and IL-18 in cell supernatant were measured. Immunofluorescence determined the localization of histone deacetylase 3 (HDAC3). The interaction between miR-142-3p and ATXN1L as well as the binding ...
Source: Journal of Molecular Medicine - April 12, 2022 Category: Molecular Biology Source Type: research
Neurovascular abnormalities in retinopathy of prematurity and emerging therapies
AbstractBlood vessels in the developing retina are formed in concert with neural growth, resulting in functional neurovascular network. Disruption of the neurovascular coordination contributes to the pathogenesis of retinopathy of prematurity (ROP), a potentially blinding retinal neovascular disease in preterm infants that currently lacks an approved drug therapy in the USA. Despite vasculopathy as predominant clinical manifestations, an increasing number of studies revealed complex neurovascular interplays among neurons, glial cells and blood vessels during ROP. Coordinated expression of glia-derived vascular endothelial ...
Source: Journal of Molecular Medicine - April 8, 2022 Category: Molecular Biology Source Type: research
The role of the individual TOM subunits in the association of PINK1 with depolarized mitochondria
AbstractMitochondria dysfunction is involved in the pathomechanism of many illnesses including Parkinson ’s disease. PINK1, which is mutated in some cases of familial Parkinsonism, is a key component in the degradation of damaged mitochondria by mitophagy. The accumulation of PINK1 on the mitochondrial outer membrane (MOM) of compromised organelles is crucial for the induction of mitophagy, but the m olecular mechanism of this process is still unresolved. Here, we investigate the association of PINK1 with the TOM complex. We demonstrate that PINK1 heavily relies on the import receptor TOM70 for its association with mitoc...
Source: Journal of Molecular Medicine - April 7, 2022 Category: Molecular Biology Source Type: research
Clinical perspectives on the age-related increase of immunosuppressive activity
AbstractThe aging process is associated with a remodeling of the immune system involving chronic low-grade inflammation and a gradual decline in the function of the immune system. These processes are also called inflammaging and immunosenescence. The age-related immune remodeling is associated with many clinical changes, e.g., risk for cancers and chronic infections increases, whereas the efficiency of vaccination and immunotherapy declines with aging. On the other hand, there is convincing evidence that chronic inflammatory states promote the premature aging process. The inflammation associated with aging or chronic infla...
Source: Journal of Molecular Medicine - April 6, 2022 Category: Molecular Biology Source Type: research
Endothelial glycocalyx degradation in multisystem inflammatory syndrome in children related to COVID-19
This study aims to characterize endothelial glycocalyx degradation in children admitted with MIS-C. We collected blood and urine samples and measured proinflammatory cytokines, myocardial injury markers, and endothelial glycocalyx markers in 17 children admitted with MIS-C, ten of which presented with inflammatory shock requiring intensive care admission and hemodynamic support with vasopressors. All MIS-C patients presented signs of glycocalyx deterioration with elevated levels of syndecan-1 in blood and both heparan sulfate and chondroitin sulfate in the urine. The degree of glycocalyx shedding correlated with tumor necr...
Source: Journal of Molecular Medicine - March 26, 2022 Category: Molecular Biology Source Type: research
Extracellular vesicles-associated tRNA-derived fragments (tRFs): biogenesis, biological functions, and their role as potential biomarkers in human diseases
AbstractTraditionally, transfer RNAs (tRNAs) specifically decoded messenger RNA (mRNA) and participated in protein translation. tRNA-derived fragments (tRFs), also known as tRNA-derived small RNAs (tsRNAs), are generated by the specific cleavage of pre- and mature tRNAs and are a class of newly defined functional small non-coding RNAs (sncRNAs). Following the different cleavage positions of precursor or mature tRNA, tRFs are classified into seven types, 5 ′-tRNA half, 3′-tRNA half, tRF-1, 5′U-tRF, 3′-tRF, 5′-tRF, and i-tRF. It has been demonstrated that tRFs have a diverse range of biological functions in cellula...
Source: Journal of Molecular Medicine - March 24, 2022 Category: Molecular Biology Source Type: research
Identification of PDXDC1 as a novel pleiotropic susceptibility locus shared between lumbar spine bone mineral density and birth weight
In conclusion, our study provides insights into some shared genetic mechanisms for BMD and BW as well as a novel potential therapeutic target for the prevention of OP in the early stages of the disease development.Key messagesWe investigated pleiotropy-informed enrichment between LS BMD and BW.We identified genetic variants related to both LS BMD and BW by utilizing a cFDR approach.PDXDC1 is a novel pleiotropic gene which may be related to both LS BMD and BW.Elevated expression of PDXDC1 is related to higher BMD and lower ratio n-6/n-3 PUFA indicating a bone protective effect of PDXDC1. (Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - March 22, 2022 Category: Molecular Biology Source Type: research
White and brown adipose tissue functionality is impaired by fine particulate matter (PM2.5) exposure
AbstractChronic exposure to high levels of particulate matter (PM) is correlated to a higher prevalence of cardio-metabolic disturbances. Adipose tissue represents a pivotal regulator of metabolic homeostasis, and its dysfunction is associated with health issues in PM-exposed models. This review discusses the adaptive changes of white (WAT) and brown (BAT) adipose tissue in response to fine particulate matter (PM2.5), investigating the underlying pathophysiology. In exposed models, PM2.5 increases oxidative stress and impairs mitochondria functionality and biogenesis in WAT and BAT. Chronic exposure also upregulates the ma...
Source: Journal of Molecular Medicine - March 14, 2022 Category: Molecular Biology Source Type: research
