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905 result(s) for "Mu, Rong"
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The Roles of IL-1 Family Cytokines in the Pathogenesis of Systemic Sclerosis
The IL-1 family consists of 11 cytokines, 7 ligands with agonist activity (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, IL-36γ) and four members with antagonistic activities [IL-1 receptor antagonist (IL-1Ra), IL-36Ra, IL-37, IL-38]. Recent articles have described that most members of IL-1 family cytokines are involved in the process of innate and adaptive immunity as well as fibrosis in systemic sclerosis (SSc). IL-1 family gene polymorphisms, abnormal expression of IL-1 and its potential role in the fibrosis process have been explored in SSc. IL-33 and IL-18 have also been discussed in the recent years. IL-33 may contribute to the fibrosis of SSc, while IL-18 remains to be researched to confirm its role in fibrosis process. There is a lack of study on the pathophysiological roles of IL-36, IL-37, and IL-38 in SSc, which might provide us new study area. Here, we aim to give a brief overview of IL-1 family cytokines and discuss their pivotal roles in the pathogenesis of SSc.
Novel approach to integrated DNA adductomics for the assessment of in vitro and in vivo environmental exposures
Adductomics is expected to be useful in the characterization of the exposome, which is a new paradigm for studying the sum of environmental causes of diseases. DNA adductomics is emerging as a powerful method for detecting DNA adducts, but reliable assays for its widespread, routine use are currently lacking. We propose a novel integrated strategy for the establishment of a DNA adductomic approach, using liquid chromatography-triple quadrupole tandem mass spectrometry (LC-QqQ-MS/MS), operating in constant neutral loss scan mode, screening for both known and unknown DNA adducts in a single injection. The LC-QqQ-MS/MS was optimized using a representative sample of 23 modified 2′-deoxyribonucleosides reflecting a range of biologically relevant DNA lesions. Six internal standards (ISTDs) were evaluated for their ability to normalize, and hence correct, possible variation in peak intensities arising from matrix effects, and the quantities of DNA injected. The results revealed that, with appropriate ISTDs adjustment, any bias can be dramatically reduced from 370 to 8.4%. Identification of the informative DNA adducts was achieved by triggering fragmentation spectra of target ions. The LC-QqQ-MS/MS method was successfully applied to in vitro and in vivo studies to screen for DNA adducts formed following representative environmental exposures: methyl methanesulfonate (MMS) and five N-nitrosamines. Interestingly, five new DNA adducts, induced by MMS, were discovered using our adductomic approach—an added strength. The proposed integrated strategy provides a path forward for DNA adductomics to become a standard method to discover differences in DNA adduct fingerprints between populations exposed to genotoxins, and facilitate the field of exposomics.
Fibroblast Growth Factors in Depression
Major depressive disorder (MDD) is one of the most serious diseases and now becomes a major public health problem in the world. The pathogenesis of depression remains poorly understood. Fibroblast growth factors (FGFs) belong to a large family of growth factors that are involved in brain development during early periods as well as maintenance and repair throughout adulthood. In recent years, studies have found a correlation between the members of the FGF system and depression. These signaling molecules may be expected to be biomarkers for the diagnosis and prognosis of MDD, and may provide new drug targets for the treatment of depression. Here, we reviewed the correlation between some members of the FGF system and depression.
Exercise Reduces Insulin Resistance in Type 2 Diabetes Mellitus via Mediating the lncRNA MALAT1/MicroRNA-382-3p/Resistin Axis
Insulin resistance (IR) is the primary pathological mechanism underlying type 2 diabetes mellitus (T2DM). Here, the study aimed to ascertain whether and how exercise mediates IR in T2DM. An in vivo mouse model of high-fat diet-induced IR and an in vitro high-glucose-induced IR model were constructed. High long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression was detected in T2MD and was positively correlated with HOMA-IR and resistin levels. Then, short hairpin RNA targeting MALAT1 (sh-MALAT1) or pcDNA-MALAT1 was delivered into human umbilical vein endothelial cells (HUVECs) to knock down or upregulate its expression, respectively. Silencing of MALAT1 resulted in reduced levels of resistin, Ang II, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelin-1 (ET-1), and p-insulin receptor substrate-1 (p-IRS)/ISR-1, and decreased cell migration, as well as enhanced glucose uptake and levels of nitric oxide (NO) and p-Akt/Akt. In the IR mouse model, exercise was observed to downregulate MALAT1 to reduce resistin, whereby exercise reduced homeostatic model assessment-insulin resistance (HOMA-IR). Besides, exercise also elevated microRNA-382-3p (miR-382-3p) expression in the serum of IR mice. Dual-luciferase reporter and RNA binding protein immunoprecipitation (RIP) assays identified that MALAT1 could bind to miR-382-3p to upregulate resistin. Collectively, the key observations of the study provide evidence that inhibition of MALAT1 elevates miR-382-3p to repress resistin, which consequently underlies the mechanism of exercise protecting against IR, highlighting a direction for T2DM therapy development.
The Gram-positive bacterium Romboutsia ilealis harbors a polysaccharide synthase that can produce (1,3;1,4)-β-d-glucans
(1,3;1,4)-β- d -Glucans are widely distributed in the cell walls of grasses (family Poaceae) and closely related families, as well as some other vascular plants. Additionally, they have been found in other organisms, including fungi, lichens, brown algae, charophycean green algae, and the bacterium Sinorhizobium meliloti . Only three members of the Cellulose Synthase-Like ( CSL ) genes in the families CSLF , CSLH , and CSLJ are implicated in (1,3;1,4)-β- d -glucan biosynthesis in grasses. Little is known about the enzymes responsible for synthesizing (1,3;1,4)-β- d -glucans outside the grasses. In the present study, we report the presence of (1,3;1,4)-β- d -glucans in the exopolysaccharides of the Gram-positive bacterium Romboutsia ilealis CRIB T . We also report that RiGT2 is the candidate gene of R. ilealis that encodes (1,3;1,4)-β- d -glucan synthase. Ri GT2 has conserved glycosyltransferase family 2 (GT2) motifs, including D, D, D, QXXRW, and a C -terminal PilZ domain that resembles the C -terminal domain of bacteria cellulose synthase, BcsA. Using a direct gain-of-function approach, we insert RiGT2 into Saccharomyces cerevisiae , and (1,3;1,4)-β- d -glucans are produced with structures similar to those of the (1,3;1,4)-β- d -glucans of the lichen Cetraria islandica . Phylogenetic analysis reveals that putative (1,3;1,4)-β- d -glucan synthase candidate genes in several other bacterial species support the finding of (1,3;1,4)-β- d -glucans in these species. (1,3;1,4)-β- d -Glucans are widely distributed in many organisms, but little is known about the enzymes responsible for their synthesis outside the grasses. Here, the authors report on the presence of (1,3;1,4)-β- d -glucans in the exopolysaccharides of the Gram-positive bacterium Romboutsia ilealis and identify and characterize the (1,3;1,4)-β- d -glucan synthase Ri GT2.
Shared immunological pathways in rheumatoid arthritis-related interstitial lung disease
Interstitial lung disease (ILD) is a significant extra-articular complication of rheumatoid arthritis (RA), characterized by high prevalence and mortality rates. Although advancements have been made in understanding its potential mechanisms, the pathogenesis of RA-associated ILD remains incompletely understood. Recent research has shed light on roles of various disease-related signaling pathways, including TGF-β/SMAD, JAK/STAT, PI3K–Akt, Wnt/β-catenin, and NF-κB, which are implicated in development of both RA and lung fibrosis. These shared pathways, which drive inflammatory cytokine production and fibroblast proliferation, offer promising opportunities for therapeutic intervention, including pathway-specific inhibition and drug repurposing. Furthermore, the growing identification of potential biomarkers for early detection and severity assessment in RA-ILD patients holds promise for improving clinical management and guiding treatment strategies. Current treatments fall short in effectively halting the progression of lung fibrosis. This highlights the potential of advancements in signaling pathways and targeted therapies as promising alternatives with significant opportunities for improvement.
Genetic pattern and demographic history of cutlassfish (Trichiurus nanhaiensis) in South China Sea by the influence of Pleistocene climatic oscillations
Trichiurus nanhaiensis is one of the most important commercial fish species in the South China Sea. This study aimed to investigate the level of genetic variation and population genetic structure of T. nanhaiensis in the South China Sea for the first time, using 281 individuals collected from seven locations along the coast of mainland China, Taiwan, and Hainan Island. A high level of haplotype diversity and low nucleotide diversity were detected in the mitochondrial DNA cyt b gene and nuDNA RYR 3 gene. The overall expected heterozygosity (He = 0.693) among the seven populations ranged from 0.681 to 0.706 in microsatellite DNA data, which revealed high levels of genetic diversity. Significant genetic differentiation was found in Taidong populations in Taiwan, revealing the prevention of gene flow caused by the Kuroshio Current. Two major lineages based on the cyt b gene suggested that the Taiwan Strait acted as a geographic barrier for T. nanhaiensis during the glacier periods in the late Pleistocene. The Bayesian skyline plot also revealed that population demographic expansion of T. nanhaiensis was estimated to have occurred in 0.1 Mya. Our results indicated that all populations of T. nanhaiensis had experienced a recent genetic bottleneck following recent expansion based on ABC analysis.
Genetic Structure and Diversity of the Yellowbelly Threadfin Bream Nemipterus bathybius in the Northern South China Sea
The genetic structure and demography of the yellowbelly threadfin bream, Nemipterus bathybius, in the northern South China Sea were examined using the mitochondrial DNA cytochrome b gene (1141 bp). High levels of haplotype and nucleotide diversities (0.98 and 5.26 × 10−3, respectively) showed that all populations exhibited a high level of genetic diversity. Analysis of molecular variance (AMOVA), FST statistics, and haplotype networks suggested the absence of significant genetic differentiation along the coast of the northern South China Sea. Although the results suggested that the lack of differentiation within the population structure of N. bathybius was shaped by ocean currents, our results also showed that the Qiongzhou Strait limited their migration between Beibu Gulf and the northern South China Sea. Neutrality tests and mismatch distributions indicated population expansion, but the Bayesian skyline plots and approximate Bayesian computation approaches suggested that the population sizes recently contracted. The diversification of multiple stocks, which were induced by two ocean current systems, contributed to these discordant results. Although these analyses of demographic history revealed no evidence for recent population bottlenecks, the population demography needs to be evaluated further.
A facile approach towards high-performance poly(thioether-thioester)s with full recyclability
Developing new chemically recyclable polymers is important for a circular plastics economy. Herein, we prepared a class of 1,4-dithian-2-one (DTO) with thioether and thioester functionalities. These sulfur-substituted monomers (DTO) showed excellent reactivity for ring-opening polymerization (turnover frequency (TOF) up to 2.3 × 10 4 h −1 ), which afforded poly(thioether-thioester)s (P(DTO)s) with high air stability, high crystallinity, and commercial high-density polyethylene-like mechanical property ( σ B = 29.59 ± 1.08 MPa and ε B = 749% ± 36%). Intriguingly, chemical recycling of P(DTO) to monomer could be accomplished with excellent efficiency in dilute solution (1 min) at room temperature or even from a commodity plastic waste mixture under catalyst-free thermal bulk condition (180 °C), thus establishing its circular life cycle. P(Me-DTO) could be applied for selective removal of Hg 2+ with >99% removal efficiency. More importantly, Me-DTO could be recovered in high yield after utilization for Hg 2+ adsorption.
Integrin activating molecule-talin1 promotes skin fibrosis in systemic sclerosis
Integrin-dependent cell adhesion and migration play important roles in systemic sclerosis (SSc). The roles of integrin activating molecules including talins and kindlins, however, are unclear in SSc. We aimed to explore the function of integrin activating molecules in SSc. Transcriptome analysis of skin datasets of SSc patients was performed to explore the function of integrin-activating molecules including talin1, talin2, kindlin1, kindlin2 and kindlin3 in SSc. Expression of talin1 in skin tissue was assessed by multiplex immunohistochemistry staining. Levels of talin1 in serum were determined by ELISA. The effects of talin1 inhibition were analyzed in human dermal fibroblasts by real-time PCR, western blot and flow cytometry. We identified that talin1 appeared to be the primary integrin activating molecule involved in skin fibrosis of SSc. Talin1 was significantly upregulated and positively correlates with the modified Rodnan skin thickness score (mRSS) and the expression of pro-fibrotic biomarkers in the skin lesions of SSc patients. Further analyses revealed that talin1 is predominantly expressed in the dermal fibroblasts of SSc skin and promotes fibroblast activation and collagen production. Additionally, talin1 primarily exerts its effects through integrin β1 and β5 in SSc. Overexpressed talin1 is participated in skin fibrosis of SSc, and talin1 appears to be a potential new therapeutic target for SSc.