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Objective: To investigate whether miR-483-5p regulates osteoclast generation by targeting Timp2. miR-483-5p can promote osteoclast differentiation and bone destruction. Methods: Target genes of miR-483-5p were predicted by miRNAs target gene prediction software TargetScan8.0, and wild type and mutant 3' UTR plasmids were constructed. Dual luciferase reporter genes were used to verify whether target genes had a targeted regulatory relationship with miR-483-5p. Western blotting was used to detect the corresponding changes in the expression level of target protein after adjusting the level of miR-483-5p in cells. Cells were transfected or infected with target gene siRNA or target protein lentivirus, and TRAP staining and q-PCR assays were performed. In addition, for osteoclast induction experiment, RAW264.7 cells were co-transfected with ago-miR-483-5p and target protein-overexpressed lentiviruses q-PCR and TRAP staining were performed respectively. Results: Bioinformatics software was used to predict the target gene of miR-483-5p, and the Timp2 gene was found to regulate osteoclasts, and the dual luciferase reporter detection system found that miR-483- 5p could be associated with the 3-UTR of the predicted target gene Timp2 gene. There are complementary loci and targeted regulatory relationship between them. Subsequently, we upregulated miR-483-5p in RAW264.7 cells to reduce the expression of Timp2. Compared with the normal group, the number of osteoclasts and the expression of osteoclast-specific genes increased significantly after the induction of Timp2 in knockdown cells. After co-transfection of target gene and miR-483-5p into cells, the number of osteoclasts and the expression of specific genes decreased significantly compared with the normal group. Conclusion: Timp2 is a downstream target gene of miR-483-5p and is involved in and inhibits osteoclast generation. [ABSTRACT FROM AUTHOR]

Airway epithelial cells, the first barrier of the respiratory tract, play an indispensable role in innate immunity. Integrin β4 (ITGB4) is a structural adhesion molecule that is involved in the pathological progression of acute inflammatory diseases and is downregulated in asthmatic patients. Research has shown that endothelial ITGB4 has proinflammatory properties in acute lung injury (ALI). However, the role of epithelial ITGB4 in a murine ALI model is still unknown. This study investigated the role of ITGB4 in lipopolysaccharide (LPS)‐induced ALI. We found that ITGB4 in the airway epithelium had remarkably increased after the introduction of LPS in vivo and in vitro. Then, we constructed airway epithelial cell‐specific ITGB4 knockout (ITGB4−/−) mice to study its role in ALI. At a time point of 12 h after the tracheal injection of LPS, ITGB4−/− mice showed increased macrophages (mainly M1‐type macrophages) and neutrophil infiltration into the lungs; inflammation‐related proteins including interleukin (IL)‐6, tumor necrosis factor, and IL‐17A were significantly elevated compared to their levels in ITGB4+/+ mice. Furthermore, we investigated the role of ITGB4 in the anti‐inflammatory response. Intriguingly, in the ITGB4−/− + LPS group, we found significantly reduced expression of anti‐inflammatory factors, including IL‐10 messenger RNA (mRNA) and ARG‐1 mRNA. We also observed that monocyte chemotactic protein (MCP‐1) increased significantly both in vivo and in vitro. Airway epithelium activates macrophages, most likely driven by MCP‐1, which we confirmed in the coculture of epithelia and macrophages. These phenomena indicate that ITGB4 in airway epithelial cells plays an important role in the process of inflammation and activation of macrophages in ALI. Overall, these data demonstrated a novel link between airway epithelial ITGB4 and the inflammatory response in LPS‐induced ALI. [ABSTRACT FROM AUTHOR]

A flexible dicarboxylic acid, 4,4'-{[1,3-phenylenebis-(methylene)]bis(oxy) dibenzoic acid (H 2 L), in combination with 1,10-phenanthroline (phen) was used to reacted with Zn(II) ions under hydrothermal conditions, successfully affording a new metal-organic framework of [Zn(L)(phen)(H 2 O)] n (1). Luminescence sensing property investigations indicate that, compound 1 is sensitive detector of Fe3+ ions based on quenching of luminescence. Its treatment activity on the child allergic purpura was assessed and the specific mechanism of the compound was explored at the same time. First of all, the content of the inflammatory cytokine released into the skin tissue was measured with ELISA detection kit after the compound treatment. Apart from this, the activation ability of the AMPK inflammatory signaling pathway was measured with real time RT-PCR. [Display omitted] • A new Zn(II)-based compound has been prepared. • It can be used as a sensor for Fe3+ ​ion. • It has the potential choice for the allergic purpura therapy. [ABSTRACT FROM AUTHOR]

Type A acute aortic dissection, an aggressive and highly fatal disease, is particularly common among pregnant women and foetuses. This disease often occurs during the third trimester of pregnancy and the postpartum period.This case involves a female who was 20 weeks pregnant with type A acute aortic dissection. While maintaining pregnancy, the patient underwent Bentall surgery and Sun’s procedure. The duration of circulatory arrest was a brief 4 min. The patient fully recovered 40 days after surgery and remained pregnant post-discharge. At the 38th gestational week, she delivered a healthy male infant via caesarean section.Gestational morbidity can have a serious impact on the safety of mothers and children. Currently, the shortest time reported for hypothermic circulatory arrest is 5 min. In this case, the lower body circulatory arrest was controlled to approximately 4 min during cardiopulmonary bypass while simultaneously safeguarding both individuals. Ideal strategies for cardiopulmonary bypass to reduce foetal risk include shorter cardiopulmonary bypass times, higher flow rates, and higher perfusion pressures. A reduction in the duration of hypothermic circulatory arrest further increases foetal survival rates.The development of a rational cardiopulmonary bypass plan should be tailored to the physiological characteristics of the pregnant woman to ensure the safety of both the pregnant woman and the foetus, reduce complications, and improve the success rate of the operation. [ABSTRACT FROM AUTHOR]

Background. The interplay among human gut microbiota (GM) composition, osteoarthritis (OA) and OA-related medication use has been extensively discussed. However, to date, there has been no exploration of the genetic correlation among these three factors. Hypothesis/Gap. The potential causal link between GM and OA), and whether medications influence this relationship, remains unclear. Methods. We utilized bidirectional Mendelian randomization (MR) to explore the genetic associations between GM and OA. We leveraged genome-wide association study (GWAS) summary statistics from the MiBioGen and GO consortia, which provided data on GM taxa and OA cases, respectively. We identified outlier single-nucleotide polymorphisms using radial-MR and assessed causal associations using inverse variance weighting (IVW), weighted median and MR-Egger methods. Robust outcomes, consistent across these methods, were reported. We addressed potential biases through tests for horizontal pleiotropy and heterogeneity, supplemented by the Mendelian randomization pleiotropy residual sum and outlier method. Multivariable MR techniques were applied to adjust for OA medication use using UK Biobank data. Results. IVW estimates revealed a significant increase in hip OA risk for Gordonibacter and Eubacterium (brachy group) [odds ratio (OR): 1.09, 95% confidence interval (CI): 1.04-1.15, P =7.82E-04; OR: 1.09, 95% CI: 1.03-1.16, P =4.67E-03, respectively]. Conversely, Senegalimassilia , Slackia and Streptococcus exhibited protective effects (OR: 0.88, P =2.14E-02; OR: 0.88, P =3.33E-02; 0.91, P =4.29E-02). Sutterella increased the risk of knee OA (OR=1.15, 95% CI: 1.07-1.25, P =4.06E-04), while Haemophilus decreased it (OR=0.94, 95% CI: 0.88-1.00, P =4.26E-02). No significant heterogeneity or horizontal pleiotropy was observed in the results. Even after accounting for the potential confounding effect of medication, the results remained consistent. No reverse causation was detected. Conclusions. Our MR study reveals gut microbiome links to OA risk. Associations hold after adjusting for medication, indicating a potential causal connection between GM and OA.

Ischemic heart disease refers to the imbalance between the supply and demand of myocardial blood; it has various causes and results in a class of clinical diseases characterized by myocardial ischemia (MI). In recent years, the incidence of cardiovascular disease has become higher and higher, and the number of patients with ischemic heart disease has also increased year by year. Traditional treatment methods include drug therapy and surgical treatment, both of which have limitations. The former maybe develop risks of drug resistance and has more significant side effects, while the latter may damage blood vessels and risk infection. At this stage, a new cell-free treatment method needs to be explored. Many research results have shown that exosomes from different cell sources can protect the ischemic myocardium via intercellular action methods, such as promoting angiogenesis, inhibiting myocardial fibrosis, apoptosis and pyroptosis, and providing a new basis for the treatment of MI. In this review, we briefly introduce the formation and consequences of myocardial ischemia and the biology of exosomes, and then focus on the role and mechanism of exosomes from different sources in MI. We also discuss the role and mechanism of exosomes pretreated with Chinese and Western medicines on myocardial ischemia. We also discuss the potential of exosomes as diagnostic markers and therapeutic drug for MI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Yan, Ding, Xie, Liu, Yang, Xie, Liu, Liu, Chen and Huang.)

This study aims to investigate the molecular mechanism of tanshinone Ⅱ_(A )(TaⅡ_A) combined with endothelial progenitor cells-derived exosomes(EPCs-exos) in protecting the aortic vascular endothelial cells(AVECs) from oxidative damage via the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt) pathway. The AVECs induced by 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine(POVPC) were randomly divided into model, TaⅡ_A, EPCs-exos, and TaⅡ_A+EPCs-exos groups, and the normal cells were taken as the control group. The cell counting kit-8(CCK-8) was used to examine the cell proliferation. The lactate dehydrogenase(LDH) cytotoxicity assay kit, Matrigel assay, DCFH-DA fluorescent probe, and laser confocal microscopy were employed to examine the LDH release, tube-forming ability, cellular reactive oxygen species(ROS) level, and endothelial cell skeleton morphology, respectively. The enzyme-linked immunosorbent assay was employed to measure the expression of interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α. Real-time fluorescence quantitative PCR(qRT-PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of PI3K and Akt. Compared with the control group, the model group showed decreased cell proliferation and tube-forming ability, increased LDH release, elevated ROS level, obvious cytoskeletal disruption, increased expression of IL-1β, IL-6, and TNF-α, and down-regulated mRNA and protein levels of PI3K and Akt. Compared with the model group, TaⅡ_A or EPCs-exos alone increased the cell proliferation and tube-forming ability, reduced LDH release, lowered the ROS level, repaired the damaged skeleton, decreased the expression of IL-1β, IL-6, and TNF-α, and up-regulated the mRNA and protein levels of PI3K and Akt. TaⅡ_A+EPCs-exos outperformed TaⅡ_A or EPCs-exos alone in regulating the above indexes. The results demonstrated that TaⅡ_A and EPCs-exos exerted a protective effect on POVPC-induced AVECs by activating the PI3K/Akt pathway, and the combination of the two had stronger therapeutic effect.

Preeclampsia (PE) is an important topic in obstetrics. In this study, we used weighted gene co-expression network analysis (WGCNA) to screen the key modules related to immune cell infiltration and to identify the hub genes for the molecular subtyping of PE. We first downloaded a set of PE transcriptional data (GSE75010; 157 samples: 80 PE and 77 non-PE) from the GEO database. We then analyzed the PE samples and non-PE samples for immune cell infiltration and screened cells with differences in such infiltration. Next, we downloaded the immune-related genes from an immune-related database to screen the expression profile of the immune-related genes. Then, we obtained a candidate gene set by screening the immune-related genes differentially expressed between the two groups. We used WGCNA to construct a weighted co-expression network for these candidate genes, mined co-expression modules, and then calculated the correlation between each module and immune cells with differential infiltration. We screened the modules related to infiltrating immune cells, identified the key modules' hub genes, and determined the key module genes that interacted with each other. Finally, we obtained the hub genes related to the infiltrating immune cells. We classified the preeclampsia patients by unsupervised cluster molecular typing, determined the difference of immune cell infiltration among the different PE subtypes, and calculated the expression of hub genes in these different subtypes. In conclusion, we found 41 hub genes that may be closely related to the molecular typing of PE.