Jiedu Quyu Decoction mitigates monocrotaline-induced right-sided heart failure associated with pulmonary artery hypertension by inhibiting NLRP3 inflammasome in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Right-side heart failure could accelerate mortality in patients of pulmonary hypertension, Jiedu Quyu Decoction (JDQYF) was used to manage pulmonary hypertension, but its right-sided heart protective effect associated with pulmonary artery hypertension is still unclear. AIM OF THE STUDY: Here, we evaluated the therapeutic effect of JDQYF on monocrotaline-induced right-sided heart failure associated with pulmonary arterial hypertension in Sprague-Dawley (SD) rats and investigated the potential mechanism of action. MATERIALS AND METHODS: The main chemical components of JDQYF were detected and analyzed using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. The effects of JDQYF were investigated using a rat model of monocrotaline-induced right-sided heart failure associated with pulmonary arterial hypertension. We assessed the morphology of cardiac tissue using histopathology and the structure and function of the right heart using echocardiography. The biomarkers of heart failure, atrial natriuretic peptide and B-type natriuretic peptide, as well as serum pro-inflammatory markers, interleukin (IL)-1ß, and IL-18, were measured by enzyme-linked immunosorbent assay (ELISA). Furthermore, the mRNA and protein expression levels of NLRP3 (NOD-, LRR-, and pyrin domain-containing 3), capase-1, IL-1ß, and IL-18 in the right heart tissue were examined by real-time quantitative reverse transcription PCR and western blotting. RESULTS: JDQYF improved ventricular function, alleviated pathological lesions in the right cardiac tissue, reduced the expression levels of biomarkers of heart failure and serum pro-inflammatory factors (IL-1ß and IL-18), and downregulated the mRNA and protein expression levels of NLRP3, caspase-1, IL-1ß, and IL-18 in the right cardiac tissue. CONCLUSIONS: JDQYF possesses cardioprotective effect against right heart failure induced by pulmonary arterial hypertension, possibly owing to reduction of cardiac inflammation through the inhibition of NLRP3 inflammasome activation.

Calenduloside e modulates macrophage polarization via KLF2-regulated glycolysis, contributing to attenuates atherosclerosis.

Glycolysis-mediated macrophage polarization plays a crucial role in atherosclerosis. Although it is known that calenduloside E (CE) exerts anti-inflammatory and lipid-lowering effects in atherosclerosis, the underlying mechanism of action is not clearly understood. We hypothesized that CE functions by inhibiting M1 macrophage polarization via regulation of glycolysis. To verify this hypothesis, we determined the effects of CE in apolipoprotein E deficient (ApoE-/-) mice and on macrophage polarization in oxidized low-density lipoprotein (ox-LDL)-induced RAW 264.7 macrophages and peritoneal macrophages. We also determined whether these effects are linked to regulation of glycolysis both in vivo and in vitro. The plaque size was reduced, and serum cytokine levels were decreased in the ApoE-/- +CE group compared with that in the model group. CE decreased lipid droplet formation, inflammatory factor levels, and mRNA levels of M1 macrophage markers in ox-ldl-induced macrophages. CE suppressed ox-ldl-induced glycolysis, lactate levels, and glucose uptake. The relationship between glycolysis and M1 macrophage polarization was demonstrated using the glycolysis inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one. CE substantially upregulated ox-ldl-induced Kruppel-like transcription factor (KLF2) expression, and the effects of CE on ox-ldl-induced glycolysis and inflammatory factor levels disappeared after KLF2 knockdown. Together, our findings suggest that CE alleviates atherosclerosis by inhibiting glycolysis-mediated M1 macrophage polarization through upregulation of KLF2 expression, providing a new strategy for the treatment of atherosclerosis.

Single-cell transcriptome sequencing of macrophages in common cardiovascular diseases.

Macrophages are strategically located throughout the body at key sites in the immune system. A key feature in atherosclerosis is the uptake and accumulation of lipoproteins by arterial macrophages, leading to the formation of foam cells. After myocardial infarction, macrophages derived from monocytes infiltrate the infarcted heart. Macrophages are also closely related to adverse remodeling after heart failure. An in-depth understanding of the functions and characteristics of macrophages is required to study heart health and pathophysiological processes; however, the heterogeneity and plasticity explained by the classic M1/M2 macrophage paradigm are too limited. Single-cell sequencing is a high-throughput sequencing technique that enables the sequencing of the genome or transcriptome of a single cell. It effectively complements the heterogeneity of gene expression in a single cell that is ignored by conventional sequencing and can give valuable insights into the development of complex diseases. In the present review, we summarize the available research on the application of single-cell transcriptome sequencing to study the changes in macrophages during common cardiovascular diseases, such as atherosclerosis, myocardial infarction, and heart failure. This article also discusses the contribution of this knowledge to understanding the pathogenesis, development, diagnosis, and treatment of heart diseases.

Basic fibroblast growth factor gel preparation induces angiogenesis during wound healing.

PURPOSE: This study aimed to observe the effect of basic fibroblast growth factor (bFGF) gel preparation on wound repair in a full-thickness skin defect rat model and to further explore its mechanism. METHODS: The full-thickness skin defect model of Wistar rats was created with circular wounds of 20 mm or 10 mm in diameter on both sides of the spine. The animals were divided into the normal, model, control gel, and bFGF gel groups (300 IU/cm2). The effects of the bFGF gel on wound healing were evaluated and compared. Optical coherence tomography (OCT)-based angiography (OCTA) was used to investigate the effects of bFGF on angiogenesis during wound healing. Western blotting, polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) kits were used to detect the effect of the gel preparation on the levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP2 and MMP9) on the wound surface to explore the mechanism. RESULTS: The bFGF gel significantly reduced wound area, promoted the formation of wound granulation tissue, and accelerated wound healing in the bFGF gel group on days 7 and 14, compared with the control gel group. OCTA results showed that bFGF significantly improved wound vascular density, diameter, and circumference. Western blot, PCR, and ELISA results showed that the gel preparation could promote the expression levels of MMP2, MMP9, and VEGF on the wound surface 7 and 14 days after injury. CONCLUSION: bFGF promotes angiogenesis in wound areas. Topical gel preparations of bFGF can be developed for use in wound repair.

Diabetes Mellitus Promotes the Development of Atherosclerosis: The Role of NLRP3.

Atherosclerosis is one of the main complications of diabetes mellitus, involving a variety of pathogenic factors. Endothelial dysfunction, inflammation, and oxidative stress are hallmarks of diabetes mellitus and atherosclerosis. Although the ability of diabetes to promote atherosclerosis has been demonstrated, a deeper understanding of the underlying biological mechanisms is critical to identifying new targets. NLRP3 plays an important role in both diabetes and atherosclerosis. While the diversity of its activation modes is one of the underlying causes of complex effects in the progression of diabetes and atherosclerosis, it also provides many new insights for targeted interventions in metabolic diseases.

Role of glycolysis in the development of atherosclerosis.

Atherosclerosis is a chronic inflammatory vascular disease associated with endothelial dysfunction, inflammation, and atherosclerotic plaque formation. Glycolysis is a conservative and rigorous biological process that decomposes glucose into pyruvate. Its function is to provide the body with energy and intermediate products required for life activities. However, abnormalities in glycolysis flux during the progression of atherosclerosis accelerate the disease progression. Herein, we review the role of glycolysis in the development of atherosclerosis to provide new ideas for devising novel antiatherosclerosis strategies.

Reduning Injection versus Neuraminidase Inhibitors in the Treatment of Influenza: A Systematic Review and Meta-Analysis.

OBJECTIVE: To perform a systematic review to assess the effectiveness and safety of Reduning Injection versus neuraminidase inhibitors in treatment of influenza. METHODS: The MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Bio-medical Literature and Retrieval System (Sinomed), China National Knowledge Infrastructure Database (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data Knowledge Service Platform and ClinicalTrails.gov were systematically searched from inception dates to May 2021 for randomized controlled trials (RCTs) exploring Reduning Injection alone or in combination with neuraminidase inhibitors in patients with influenza. Statistical analysis was performed using RevMan 5.4 and Stata 15.1. The qualities of the involved studies were assessed by the risk of bias according to the Cochrane handbook. The evidence quality of each outcome was evaluated by GRADEpro GDT. RESULTS: Twelve trials with 1,460 patients were included. The included studies had a certain unclear or high risk of bias. Reduning Injection appeared to be more effective in shortening the fever clearance time (MD: -16.20 h, 95% CI: -19.40 to -12.99, 7 trials, 814 patients, I2=94%, very low certainty), fever alleviation time (MD: -4.09 h, 95% CI: -4.22 to -3.96, 3 trials, 366 patients, I2=0%, low certainty), cough alleviation time (MD: -21.34 h, 95% CI: -41.56 to -1.11, 2 trials, 228 patients, I2=89%, very low certainty), fatigue alleviation time (MD: -31.83 h, 95% CI: -36.88 to -26.77, 2 trials, 270 patients, I2=0%, low certainty), sore throat alleviation time (MD: -28.66 h, 95% CI: -32.23 to -25.10, 1 trial, 150 patients, low certainty), and improving the total effective rate (RR: 1.15, 95% CI: 1.06 to 1.25, 10 trials, 1,074 patients, I2=76%, very low certainty). Besides, Reduning Injection seemed generally safe. CONCLUSIONS: This study provided low or very low evidence indicating Reduning Injection may be effective in the treatment of influenza and might be safe. Further rigorously designed studies are needed to confirm the effectiveness and safety of Reduning Injection and support it as a recommendation for influenza.

Progress of Single-Cell RNA Sequencing Technology in Myocardial Infarction Research.

After myocardial infarction, the heart enters a remodeling and repair phase that involves myocardial cell damage, inflammatory response, fibroblast activation, and, ultimately, angiogenesis. In this process, the proportions and functions of cardiomyocytes, immune cells, fibroblasts, endothelial cells, and other cells change. Identification of the potential differences in gene expression among cell types and/or transcriptome heterogeneity among cells of the same type greatly contribute to understanding the cellular changes that occur in heart and disease conditions. Recent advent of the single-cell transcriptome sequencing technology has facilitated the exploration of single cell diversity as well as comprehensive elucidation of the natural history and molecular mechanisms of myocardial infarction. In this manner, novel putative therapeutic targets for myocardial infarction treatment may be detected and clinically applied.

[Meta-analysis of Xiaoer Xiaoji Zhike Oral Liqud combined with azithromycin in treatment of mycoplasma pneumonia in children].

Systematic evaluation of the effectiveness and safety of Xiaoer Xiaoji Zhike Oral Liqud combined with azithromycin in the treatment of mycoplasma pneumonia in children. Clinical literatures were retrieved from PubMed, Cochrane Library, EMbase, VIP, CNKI, SinoMed, WanFang from inception to September 2019. Two reviewers independently screened out the literatures, extracted data and assessed the risk of bias of the included studies. Then, Meta-analysis was performed by RevMan 5.3 software. A total of 17 RCT were included, involving 1 712 patients. In this study, there were two subgroups by the application approach of azithromycin: oral azithromycin subgroup and intravenous azithromycin subgroup. According to Meta-analysis results, in terms of the alleviation of clinical symptoms and signs, such as shortening of antifebrile time, cough disappeared time, rales disappearance time, and lung X-ray infiltrating shadow disappearance time, Xiaoer Xiaoji Zhike Oral Liquid combined with oral azithromycin or intravenous azithromycin were better than single-dose azithromycin; in the aspect of the improvement of the overall effective rate, the two combination subgroups were better than the single-use azithromycin; In terms of the decline of IgM, the combination subgroups were also more efficient than the single-use azithromycin, with statistically significant differences. In terms of the incidence of adverse reactions, there was no significant difference between the two combination subgroups and the single-use azithromycin in children, and no serious adverse reactions were found. In inclusion, Xiaoer Xiaoji Zhike Oral Liquid combined with azithromycin can improve the clinical efficacy in treating pediatric mycoplasma pneumonia, with a high safety. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.