Cysteine triggered cascade reaction forming coumarin: Visualization of cysteine fluctuation in alcoholic liver disease by a NIR fluorescent probe.

Alcoholic liver disease (ALD) is a chronic toxic liver injury caused by long-term heavy drinking. Due to the increasing incidence, ALD is becoming one of important medical tasks. Many studies have shown that the main mechanism of liver damage caused by large amounts of alcohol may be related to antioxidant stress. As an important antioxidant, cysteine (Cys) is involved in maintaining the normal redox balance and detoxifying metabolic function of the liver, which may be closely related to the pathogenesis of ALD. Therefore, it is necessary to develop a simple non-invasive method for rapid monitoring of Cys in liver. Thus, a near-infrared (NIR) fluorescent probe DCI-Ac-Cys which undergoes Cys triggered cascade reaction to form coumarin fluorophore is developed. Using the DCI-Ac-Cys, decreased Cys was observed in the liver of ALD mice. Importantly, different levels of Cys were monitored in the livers of ALD mice taking silybin and curcumin with the antioxidant effects, indicating the excellent therapeutic effect on ALD. This study provides the important references for the accurate diagnosis of ALD and the pharmacodynamic evaluation of silybin and curcumin in the treatment of ALD, and support new ideas for the pathogenesis of ALD.

Mesenchymal stem cells-derived exosomes alleviate temporomandibular joint disc degeneration in temporomandibular joint disorder.

Temporomandibular joint (TMJ) disorder (TMD) is a chronic progressive disease that is commonly seen in clinical settings. TMJ disc degeneration is an important manifestation of TMD, and further aggravates the progression of TMD. However, treatments on TMJ disc degeneration are very limited till now. In this study, we first observed the effects of bone marrow stem cells (BMSC) conditioned medium on functions of TMJ disc fibroblasts. Then BMSC-derived small extracellular vesicles (BMSC-EVs) were isolated and exposed to TMJ disc fibroblasts. RNA-sequencing was used to further investigate the mechanisms. BMSC-EVs were finally injected into a rat model with TMD. Results showed that in the transwell co-culture system, the medium derived from BMSC reduced inflammation and enhanced chondrogenesis in TMJ disc fibroblasts. BMSC-EVs promoted proliferation, migration, and chondrogenic differentiation of TMJ disc fibroblasts, and inhibited apoptosis and inflammatory responses. Local injection of BMSC-EVs into the TMD model alleviated TMJ disc degeneration. Therefore, BMSC-EVs were a potentially effective, sustainable and clinically translational-promising option for TMJ disc degeneration, and further reduce the progression of TMD.

miRNA-143 as a potential biomarker in the detection of bladder cancer: a meta-analysis.

Aim: This study aimed to systematically evaluate the value of miRNA-143 in the early detection of bladder cancer (BCa). Methods: CNKI, WanFang, PubMed and Wiley Online Library databases were explored according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. A random-effects model was used to obtain pooled sensitivity, specificity and other related indicates. Results: Six studies were included for analysis. The overall pooled sensitivity and specificity were 0.80 (95% CI: 0.74-0.85) and 0.85 (95% CI: 0.78-0.91), and the area under the curve was 0.88 (95% CI: 0.85-0.91). Coupled with miR-100, it showed better diagnostic power (area under the curve: 0.95). Conclusion: miRNA-143 may serve as a promising noninvasive tool for the early detection of BCa.

Bladder cancer (BCa) is a common and deadly malignant tumor worldwide; however, noninvasive diagnosis can significantly improve the prognosis of patients. Recently, miRNAs have emerged as potential diagnostic biomarkers for BCa. Among them, miRNA-143 has shown promising results in several studies. This meta-analysis aimed to evaluate the overall diagnostic accuracy of miRNA-143 for BCa through a systematic review and meta-analysis of six published articles. Excitingly, the results of this meta-analysis suggest that miRNA-143 has potential diagnostic value in BCa. Particularly, miRNA-143 combined with miRNA-100 maintained better competence. Besides, miRNA-143 in plasma exhibited better diagnostic strength than that in urine. The authors believe that their study provides valuable insights into the use of miRNA-143 as a diagnostic biomarker for BCa.

Exosomes derived from mesenchymal stem cells attenuate NLRP3-related pyroptosis in autoimmune premature ovarian insufficiency via the NF-κB pathway.

RESEARCH QUESTION: What is the effect of exosomes derived from bone marrow mesenchymal stem cells (MSC-Exos) on the pyroptosis and recovery of granulosa cells in autoimmune premature ovarian insufficiency (POI)? DESIGN: In vitro, KGN cells were exposed to interferon-gamma to simulate immune injury. Samples were collected after a 48 h incubation with MSC-Exos (30 µg/ml). The cell viability, secretion of oestrogen and expression of key molecules in pyroptosis and the nuclear factor kappa B (NF-κB) pathway were tested. In vivo, the BALB/c mouse model of autoimmune POI model induced by zona pellucida glycoprotein 3 was used. Fertility testing and sample collection were applied 4 weeks after the ovarian subcapsular injection of MSC-Exos (150 µg for each ovary). Hormone concentration measurements, follicle counting and pyroptotic pathway analyses were conducted for each group. RESULTS: In vitro, MSC-Exos significantly promoted the proliferation rate and secretion of oestrogen, while at the same time suppressing apoptosis and pyroptosis. In vivo, exosomal treatment normalized the irregular oestrous cycles, rescued the follicular loss and increased the pregnancy rate and number of offspring in POI mice. Elevated serum concentrations of oestrogen and anti-Müllerian hormone, as well as decreased concentrations of FSH and interleukin-1ß, were shown. Furthermore, MSC-Exos down-regulated the expression of the NLRP3/Casp1/GSDMD pathway and inhibited activation of the NF-κB pathway. CONCLUSIONS: These findings demonstrate for the first time that MSC-Exos exert a significant effect on restoring ovarian function in autoimmune POI in vivo and in vitro by suppressing the NLRP3/Casp1/GSDMD pathway and pyroptosis. The NF-κB pathway may contribute to the regulation of NLRP3-related pyroptosis.

miR-21-5p-loaded bone mesenchymal stem cell-derived exosomes repair ovarian function in autoimmune premature ovarian insufficiency by targeting MSX1.

RESEARCH QUESTION: What is the effect of micro-RNA (miR)-21-5p-loaded bone marrow mesenchymal stem cell-derived exosomes (miR-21-Exo) on autoimmune premature ovarian insufficiency (POI)? DESIGN: The Cell Counting Kit 8 (CCK8) assay, fluorescence-activated cell sorting, western blotting, quantitative reverse transcriptase (qRT)-PCR and enzyme-linked immunosorbent assay (ELISA) verified the effect of miR-21-Exo on interferon-γ (IFN-γ)-induced KGN cells. qRT-PCR, western blotting and dual-luciferase reporter gene assays verified that miR-21-Exo mediated Msh homeobox 1 (MSX1) regulation of the Notch signalling pathway and that miR-21 interacted directly with MSX1. The effects of miR-21-Exo on the ovaries were verified by monitoring of the oestrous cycle, haematoxylin and eosin staining, follicle counts, ELISA, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL), western blotting and qRT-PCR. RESULTS: The results showed that miR-21-Exo promoted IFN-γ-induced KGN cell proliferation and hormone synthesis, and inhibited apoptosis. Using dual-luciferase reporter gene assays, miR-21 and MSX1 were shown to have direct interactions. Moreover, the findings elucidated that miR-21-Exo inhibited cell apoptosis and promoted hormone synthesis by mediating MSX1 to regulate the Notch signalling pathway. miR-21-Exo restored the ovarian structure in a mouse model of autoimmune POI, promoted endocrine function and proliferation, and inhibited apoptosis and inflammation in vivo. CONCLUSIONS: This study demonstrates that miR-21-Exo regulates the MSX1-mediated Notch signalling pathway to inhibit granulosa cell apoptosis and improve hormone synthesis function, providing insight into a potential mechanism of molecular therapy for the treatment of autoimmune POI.

Feeding ecology of the short-headed lanternfish Diaphus brachycephalus and Warming's lanternfish Ceratoscopelus warmingii (Myctophidae) in the South China Sea.

We report on the feeding ecology of two species, the short-headed lanternfish Diaphus brachycephalus and Warming's lanternfish Ceratoscopelus warmingii, using data collected over five surveys from 2015 to 2017 in the open South China Sea. D. brachycephalus feed mainly on copepods, with few differences in food composition between different-sized individuals; the diet of C. warmingii is more diverse, including crustacean zooplankton, gelatinous animals, and Mollusca, and differs significantly between fishes >55 mm in body length and smaller fishes. Interspecific competition for food between these two species is not strong, while intraspecific competition may be more intense in D. brachycephalus than in C. warmingii. Trophic levels of D. brachycephalus (3.46) and C. warmingii (3.38) identify both species as third-trophic-level lower carnivores. The diel feeding patterns of D. brachycephalus and C. warmingii differ: the former feeds actively both day and night when food is plentiful, and feeds primarily in the upper layer at night and in the mesopelagic layer during the daytime, and the latter ascends into the upper 100 m at night to feed, but stomach fullness is lower than D. brachycephalus. Dry-body-weight daily ration estimates for D. brachycephalus range from 5.19% to 16.46%, and those for C. warmingii range from 1.38% to 4.39%.

Periodontitis aggravates COPD through the activation of γδ T cell and M2 macrophage.

Chronic obstructive pulmonary disease (COPD) is a chronic systemic inflammatory disease with high morbidity and mortality. Periodontitis exacerbates COPD progression; however, the immune mechanisms by which periodontitis affects COPD remain unclear. Here, by constructing periodontitis and COPD mouse models, we demonstrated that periodontitis and COPD could mutually aggravate disease progression. For the first time, we found that the progression was associated with the activation of γδ T cells and M2 macrophages, and M2 polarization of macrophages was affected by γδ T cells activation. In the lung tissues of COPD with periodontitis, the activation of γδ T cells finally led to the increase of IL 17 and IFN γ expression and M2 macrophage polarization. Furthermore, we found that the periodontitis-associated bacteria Porphyromonas gingivalis (P. gingivalis) promoted the activation of γδ T cells and M2 macrophages ex vivo. The data from clinical bronchoalveolar lavage fluid (BALF) samples were consistent with the in vivo and ex vivo experiments. For the first time, our results identified the crucial role of γδ T-M2 immune mechanism in mediating periodontitis-promoted COPD progression. Therefore, targeting at periodontitis treatment and the γδ T-M2 immune mechanism might provide a new practical strategy for COPD prevention or control.IMPORTANCEPeriodontitis exacerbates chronic obstructive pulmonary disease (COPD) progression. For the first time, the current study identified that the impact of periodontitis on COPD progression was associated with the activation of γδ T cells and M2 macrophages and that M2 polarization of macrophages was affected by γδ T cells activation. The results indicated that targeting at periodontitis treatment and the γδ T-M2 immune mechanism might provide a new practical strategy for COPD prevention or control.