Hyperthyroidism and severe bradycardia: Report of three cases and review of the literature.

BACKGROUND: Hyperthyroidism often leads to tachycardia, but there are also sporadic reports of hyperthyroidism with severe bradycardia, such as sick sinus syndrome (SSS) and atrioventricular block. These disorders are a challenge for clinicians. CASE SUMMARY: We describe three cases of hyperthyroidism with SSS and found 31 similar cases in a PubMed literature search. Through the analysis of these 34 cases, we found 21 cases of atrioventricular block and 13 cases of SSS, with 67.6% of the patients experiencing bradycardia symptoms. After drug treatment, temporary pacemaker implantation, or anti-hyperthyroidism treatment, the bradycardia of 27 patients (79.4%) was relieved, and the median recovery time was 5.5 (2-8) d. Only 7 cases (20.6%) needed permanent pacemaker implantation. CONCLUSION: Patients with hyperthyroidism should be aware of the risk of severe bradycardia. In most cases, drug treatment or temporary pacemaker placement is recommended for initial treatment. If the bradycardia does not improve after 1 wk, a permanent pacemaker should be implanted.

Research hotspots and development trends of microRNA in ischemia-reperfusion: network analysis of academic journals oriented by bibliometric and visualization.

Background: Ischemia-reperfusion (IR) injury can occur in the heart, brain, liver, lung, kidney, and other important organs, and may greatly increase disease mortality. MicroRNAs (miRNAs) have a variety of functions, including regulating cell differentiation, proliferation, and apoptosis. In the past 10 years, many studies on miRNAs in IR have been conducted. This study involved a visual analysis of these studies, and a discussion of research hotspots, trends, and frontiers of this topic. Methods: A total of 1,518 articles published between 2012 and 2022 on the topic of miRNA and IR and listed in the Web of Science database were analyzed visually using CiteSpace. Cooperative networks, literature citations, and keyword co-occurrence were analyzed. Results: Of the 1,518 articles, most were published after 2018, and a rapid growth in numbers of publications was seen after 2019. Articles from China numbered the highest, followed by the United States and Canada. It has been found that many miRNAs are involved in the occurrence of IR, with various regulatory mechanisms and signaling pathways. The literature clustering generated by literature co-citation analysis and the keyword co-occurrence network showed that the previous miRNA research on IR had mainly focused on the following topics: myocardial infarction, ischemic stroke, acute kidney injury, oxidative stress, and inflammatory response. More attention has been paid to long noncoding RNA (lncRNA) and exosomes, with much exploration having been conducted in these areas. Conclusions: Although miRNA is involved in the occurrence and development of IR, as a clinical intervention target for IR, further research is still needed.

EGCG protects against myocardial I/RI by regulating lncRNA Gm4419-mediated epigenetic silencing of the DUSP5/ERK1/2 axis.

BACKGROUND: Epigallocatechin gallate (EGCG) has attracted increasing attention due to its beneficial effect on cardiovascular health. The aim of this study was to investigate the underlying mechanism by which EGCG protects against myocardial ischaemia/reperfusion injury (I/RI). METHODS: Murine myocardial I/RI and H2O2-induced cardiomyocyte injury models were established to evaluate the therapeutic effects of EGCG. In the myocardial I/RI mouse model, the echocardiographic parameters of ejection fraction (EF) and fraction shortening (FS) levels, infarct size, histological evaluation and transmission electron microscopy (TEM) were used to evaluate cardiac tissue damage and autophagy. MTT assays, TUNEL staining, flow cytometry and immunofluorescence (IF) were used to monitor cell viability, apoptosis and autophagy in vitro. qRT-PCR and western blotting were used to determine the mRNA and protein levels of key molecules, respectively. The epigenetic regulation of DUSP5 was assessed via RNA immunoprecipitation (RIP), RNA pull-down and chromatin immunoprecipitation (ChIP) assays. RESULTS: EGCG significantly improved cardiac function, reduced infarct size, enhanced cell viability and inhibited autophagic activity in both myocardial I/RI mouse models and H2O2-induced cardiomyocyte injury models. Moreover, EGCG suppressed H2O2- or myocardial I/R-increased Gm4419 expression, and Gm4419 overexpression dramatically abolished EGCG-mediated protective effects against myocardial I/RI. Mechanistically, Gm4419 epigenetically suppressed DUSP5 by recruiting EZH2, thus activating ERK1/2 pathway-mediated autophagy. Furthermore, the in vivo experiments further verified that the Gm4419-mediated disruptive effects of EGCG on myocardial I/RI were potentiated by DUSP5 knockdown but attenuated by DUSP5 overexpression. CONCLUSIONS: In conclusion, our findings demonstrated that EGCG protected against myocardial I/RI by modulating Gm4419/DUSP5/ERK1/2-mediated autophagy.

Effects and mechanism of arachidonic acid against TNF-α induced apoptosis of endothelial cells.

This study aimed to investigate the effects of arachidonic acid metabolite epoxyeicosatrienoic acid (EETs) in the apoptosis of endothelial cells induced by tumor necrosis factor-alpha (TNF-α). After human umbilical vein endothelial cells were cultured, TNF-α/ActD, 14, 15-EET, and HMR-1098 were added, respectively, into the culture medium. The apoptosis level of endothelial cells was detected by flow cytometry. After TNF-α/ActD induced endothelial cell apoptosis, flow cytometry staining showed that endothelial cell apoptosis increased significantly, and the apoptotic cells were significantly reduced after the addition of 14, 15-EET. However, the apoptotic cells significantly increased after the addition of HMR-1098. Western Blot results showed that the phosphorylation levels of LC3-II and AMPK were increased after TNF-α/ActD induction, and the increase was noticeable after the addition of 14, 15-EET. However, the phosphorylation levels of LC3-II and AMPK significantly decreased after the addition of HMR-1098. The activity of Caspase-8 and -9 decreased significantly after the addition of 14, 15-EET but increased after the addition of HMR-1098. Arachidonic acid can inhibit TNF-α induced endothelial cell apoptosis by upregulating autophagy.

Mechanisms of Macrophage Immunomodulatory Activity Induced by a New Polysaccharide Isolated From Polyporus umbellatus (Pers.) Fries.

Bladder cancer is one of the most malignant tumors closely associated with macrophage immune dysfunction. The Chinese medicine polyporus has shown excellent efficacy in treating bladder cancer, with minimal side effects. However, its material basis and mechanism of action remain unclear. A new water-soluble polysaccharide (HPP) with strong immunomodulatory activity was isolated from the fungus Polyporus umbellatus (Pers.) Fries. HPP had an average molecular weight of 6.88 kDa and was composed mainly of an <-(1 → 4)-linked D-galactan backbone. The immunomodulatory activity of HPP was determined in vitro, and the results revealed that it could obviously increase the secretion of immune factors by IFN-γ-stimulated macrophages, including nitric oxide (NO), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), RANTES and interleukin-23 (IL-23), and the expression of the cell membrane molecule CD80. In addition, HPP was recognized by Toll-like receptor 2 (TLR2) and activated the signaling pathways of NF-κB and NLRP3 in a bladder cancer microenvironment model, indicating that HPP could enhance host immune system function. These findings demonstrated that HPP may be a potential immune modulator in the treatment of immunological diseases or bladder cancer therapy.

Immunotherapy of Bacillus Calmette­Guérin by targeting macrophages against bladder cancer in a NOD/scid IL2Rg­/­ mouse model.

Bacillus Calmette­Guérin (BCG) is considered to be a successful biotherapy for treating bladder cancer (BCa). However, the underlying mechanisms of BCG have not been completely clarified, to date. The role of macrophages in BCG therapy for BCa has still not been determined in vivo. In the present study, the role and potential mechanism of BCG (0.25, 1.25 and 6.25 µg/mouse; intravenous) immunotherapy for BCa was investigated in a NOD/scid IL2Rg­/­ (NSI) mouse model by targeting macrophages in vivo. Notably, it was observed that NSI mice with T24 BCa cells displayed high levels of the macrophage marker CD11b+ F4/80+ after injection via the tail vein of live BCG, as well as a significant reduction in tumor volume. The levels of the inflammatory and macrophage maturation cytokines, such as tumor necrosis factor­α, interleukin (IL)­1ß, IL­6, IL­12P70, TNF superfamily member 11 and monocyte chemotactic protein 1, were significantly increased in the serum and the tumor supernatant compared to that in normal control subjects. Furthermore, BCG promoted the expression of the pro­differential genes Spi­1 proto­oncogene, early growth response protein 1, nuclear factor (NF)­κB and proto­oncogene c­Fos in bone marrow. In conclusion, these observations indicate that the injection of live BCG can target macrophages against bladder tumor growth in vivo. The mechanism is likely related to the promotion of macrophage maturation, immune activation and increased numbers of macrophages infiltrating the bladder tumor.

NF-κB pathways are involved in M1 polarization of RAW 264.7 macrophage by polyporus polysaccharide in the tumor microenvironment.

Bladder cancer is one of the most malignant tumors closely associated with macrophages. Polyporus polysaccharide (PPS) has shown excellent efficacy in treating bladder cancer with minimal side effects. However, the molecular mechanisms underlying the effects of PPS in inhibiting bladder cancer remain unclear. In this study, we used macrophages cultured alone or with T24 human bladder cancer cell culture supernatant as study models. We found that PPS enhanced the activities of IFN-γ-stimulated RAW 264.7 macrophages, as shown by the release of inducible nitric oxide synthase (INOS), secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-6, phagocytosis activity, as well as expression of M1 phenotype indicators, such as CD40, CD284 and CD86. PPS acted upstream in activation cascade of nuclear factor (NF)-κB signaling pathways by interfering with IκB phosphorylation. In addition, PPS regulated NF-κB (P65) signaling by interfering with Toll-like receptor (TLR)-4, INOS and cyclooxygenase (COX)-2. Our results indicate that PPS activates macrophages through TLR4/NF-κB signaling pathways.

[Survey on a new case of visceral leishmaniasis in Shanxi Province].

A new case of visceral leishmaniasis (kala-azar) was reported by Changzhi CDC of Shanxi Province in September 2011. The case was investigated clinically and epidemiologically. The patient was a two-year-old boy who lived in Huangnian Town of Changzhi County in Shanxi Province. Clinical examination showed hepatosplenomegaly, consistent decrease of blood cells and Leishman-Donovan body in the bone marrow smear. The rK39 immune diagnosis test showed strongly positive. The case was diagnosed as kala-azar. After one course treatment of sodium stibogluconate, the patient's condition improved markedly. There were no cases of kala-azar in this region historically. Blood samples of 17 individuals and 5 domestic animals including 3 dogs were all negative in the rK39 immunodiagnostic test. It is speculated that the potential risk of kala-azar transmission exists in this region.

Improving the sensitivity of single-strand conformation polymorphism (SSCP) to study the variability of PLMVd.

Single-strand conformation polymorphism (SSCP) was used to characterize viroids. Eight cDNA clones, which showed identical profiles in preliminary existing SSCP analysis but had different sequences, were chosen to develop a sensitive SSCP technique for identifying the variability of Peach latent mosaic viroid (PLMVd). Polyacrylamide Gel Electrophoresis (PAGE) conditions were optimized to improve the sensitivity of the existing SSCP, and a modified SSCP protocol was developed. The results indicated that the modified SSCP protocol provided an overall sensitivity in identifying the variability of these clones, and showed higher resolution than the existing one and its improved versions. As shown by sequence analyses of cDNA clones of PLMVd and the modified SSCP profiles, there is no close correlation between the number of base changes and variation of the modified SSCP band patterns. The potential use of the modified SSCP analysis is discussed as a tool for viroids characterization.