Heat shock transcription factor 1 regulates exercise-induced myocardial angiogenesis after pressure overload via HIF-1α/VEGF pathway.

Exercise training is believed to have a positive effect on cardiac hypertrophy after hypertension. However, its mechanism is still not fully understood. Herein, our findings suggest that heat shock transcription factor 1 (HSF1) improves exercise-initiated myocardial angiogenesis after pressure overload. A sustained narrowing of the diagonal aorta (TAC) and moderately- intense exercise training protocol were imposed on HSF1 heterozygote (KO) and their littermate wild-type (WT) male mice. After two months, the cardiac function was assessed using the adaptive responses to exercise training, or TAC, or both of them such as catheterization and echocardiography. The HE stains assessed the area of myocyte cross-sectional. The Western blot and real-time PCR measured the levels of expression for heat shock factor 1 (HSF1), vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 alpha (HIF-1α) in cardiac tissues. The anti-CD31 antibody immunohistochemical staining was done to examine how exercise training influenced cardiac ontogeny. The outcome illustrated that exercise training significantly improved the cardiac ontogeny in TAC mice, which was convoyed by elevated levels of expression for VEGF and HIF-1α and preserved the heart microvascular density. More importantly, HSF1 deficiency impaired these effects induced by exercise training in TAC mice. In conclusion, exercise training encourages cardiac ontogeny by means of HSF1 activation and successive HIF-1α/VEGF up-regulation in endothelial cells during continued pressure overload.

Exploring the Mechanism of Zhishi-Xiebai-Guizhi Decoction for the Treatment of Hypoxic Pulmonary Hypertension Based on Network Pharmacology and Experimental Analyses.

BACKGROUND: Hypoxic Pulmonary Hypertension (HPH), a prevalent disease in highland areas, is a crucial factor in various complex highland diseases with high mortality rates. Zhishi-Xiebai-Guizhi Decoction (ZXGD), traditional Chinese medicine with a long history of use in treating heart and lung diseases, lacks a clear understanding of its pharmacological mechanism. OBJECTIVE: This study aimed to investigate the pharmacological effects and mechanisms of ZXGD on HPH. METHODS: We conducted a network pharmacological prediction analysis and molecular docking to predict the effects, which were verified through in vivo experiments. RESULTS: Network pharmacological analysis revealed 51 active compounds of ZXGD and 701 corresponding target genes. Additionally, there are 2,116 target genes for HPH, 311 drug-disease co-target genes, and 17 core target genes. GO functional annotation analysis revealed that the core target genes primarily participate in biological processes such as apoptosis and cellular response to hypoxia. Furthermore, KEGG pathway enrichment analysis demonstrated that the core targets are involved in several pathways, including the phosphatidylinositol- 3 kinase/protein kinase B (PI3K/Akt) signaling pathway and Hypoxia Inducible Factor 1 (HIF1) signaling pathway. In vivo experiments, the continuous administration of ZXGD demonstrated a significant improvement in pulmonary artery pressure, right heart function, pulmonary vascular remodeling, and pulmonary vascular fibrosis in HPH rats. Furthermore, ZXGD was found to inhibit the expression of PI3K, Akt, and HIF1α proteins in rat lung tissue. CONCLUSION: In summary, this study confirmed the beneficial effects and mechanism of ZXGD on HPH through a combination of network pharmacology and in vivo experiments. These findings provided a new insight for further research on HPH in the field of traditional Chinese medicine.

Tandem fabrication of upconversion nanocomposites enabled by confined protons.

Lanthanide-doped upconversion nanoparticle (UCNP)-based nanocomposites can address the intrinsic limitations associated with UCNPs and bestow new functions on UCNPs, which can facilitate the development and application of UCNPs. However, the fabrication of UCNP-based composites typically suffers from complex operations, long-drawn-out procedures, and even loss or damage of UCNPs. Herein, we report a tandem fabrication strategy for the preparation of UCNP-based nanocomposites, in which protons, confined in the non-aqueous polar solvent, can produce ligand-free UCNPs for the direct fabrication of a composite without further treatment. Our studies show that the confined protons can be generated by diverse materials and can yield different types of ligand-free nanomaterials for desired composites. This versatile strategy enables a simple but scalable fabrication of UCNP-based nanocomposites, and can be extended to other nanomaterial-based composites. These findings should provide a platform for constructing multifunctional UCNP-based materials, and benefit potential applications of UCNPs in varied fields.

Aerobic Exercise Attenuates Pressure Overload-Induced Cardiac Dysfunction through Promoting Skeletal Muscle Microcirculation and Increasing Muscle Mass.

BACKGROUND: Aerobic exercise has been proven to have a positive effect on cardiac function after hypertension; however, the mechanism is not entirely clarified. Skeletal muscle mass and microcirculation are closely associated with blood pressure and cardiac function. OBJECTIVE: This study was designed to investigate the effects of aerobic exercise on the skeletal muscle capillary and muscle mass, to explore the possible mechanisms involved in exercise-induced mitigation of cardiac dysfunction in pressure overload mice. METHODS: In this study, 60 BALB/C mice aged 8 weeks were randomly divided into 3 groups: control (CON), TAC, and TAC plus exercise (TAE) group and utilized transverse aortic constriction (TAC) to establish hypertensive model; meanwhile, treadmill training is used for aerobic exercise. After 5 days of recovery, mice in the TAE group were subjected to 10-week aerobic exercise. Carotid pressure and cardiac function were examined before mice were executed by Millar catheter and ultrasound, respectively. Muscle mass of gastrocnemius was weighed; cross-sectional area and the number of capillaries of gastrocnemius were detected by HE and immunohistochemistry, respectively. The mRNA and protein levels of VEGF in skeletal muscle were determined by RT-PCR and western blot, respectively. RESULTS: We found that ① 10-week aerobic exercise counteracted hypertension and attenuated cardiac dysfunction in TAC-induced hypertensive mice; ② TAC decreased muscle mass of gastrocnemius and resulted in muscle atrophy, while 10-week aerobic exercise could reserve transverse aortic constriction-induced the decline of muscle mass and muscle atrophy; and ③ TAC reduced the number of capillaries and the protein level of VEGF in gastrocnemius, whereas 10-week aerobic exercise augmented the number of capillaries, the mRNA and protein levels of VEGF in mice were subjected to TAC surgery. CONCLUSIONS: This study indicates that 10-week aerobic exercise might fulfill its blood pressure-lowering effect via improving skeletal muscle microcirculation and increasing muscle mass.

Efficacy and safety of the Chaihuguizhiganjiang-suanzaoren granule on primary insomnia: study protocol for a randomised controlled trial.

INTRODUCTION: Insomnia is a highly prevalent, often debilitating and economically burdensome sleep disorder with limited effective therapies. Few data are available to understand which of the therapeutic alternatives is the most effective for patients with insomnia, especially for Traditional Chinese Medicine (TCM). Chinese herbal medicine, as a typical TCM, is one of the most popular complementary and alternative therapies for insomnia. We aim to evaluate the efficacy and safety of the Chaihuguizhiganjiang-suanzaoren granule (CSG), a Chinese herbal medicine treatment, in patients with primary insomnia. METHODS AND ANALYSIS: This is a multicentre, placebo-controlled, double-blinded, randomised controlled clinical trial. A total of 258 participants are randomly allocated to two groups: the intervention group or the placebo group. The intervention group receives CSG and the placebo group receives a placebo granule. The patients receive either CSG or placebo two times daily for 8 weeks. The primary outcome is the Pittsburgh sleep quality index (PSQI). Secondary outcomes include the Insomnia Severity Index (ISI), Total Sleep Time (TST) and the Short-Form Health Survey (SF-36). The assessment is performed at baseline (before randomisation), 4, 8 and 12 weeks after randomisation. ETHICS AND DISSEMINATION: The protocol has been approved by the Research Ethical Committee of Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University (reference: 2014BL-003-01). The trial will be helpful in identifying the efficacy and safety of CSG in patients with primary insomnia. TRIAL REGISTRATION NUMBER: ISRCTN22001145; Pre-results.

[Case-control study on arthroscopy and manipulation for the treatment of derangement of patellofemoral joint].

OBJECTIVE: To compare the therapeutic effects of arthroscopy and manipulation of Traditional Chinese medicine (TCM) in the treatment of patellofemoral joint disease. METHODS: The patients met with the criteria of patellofemoral joint disease were divided into manipulation of TCM group and arthroscopy group randomly, 31 patients in each group. There were 31 patients in manipulation of TCM group, including 4 males and 27 females, with an average age of (52.83 +/- 5.79) years old; and the patients were treated with manipulation. There were 31 patients in arthroscopy group, including 8 males and 23 females, with an average age of (54.14 +/- 6.12) years old; the patients were treated with arthroscopy. The HSS knee joint score, fitness angle of patellofemoral joint and lateral angle of patellofemoral joint in X-ray were compared in each group and between the two groups before and after treatment respectively. RESULTS: The two therapeutics had equally efficacious in which improved HSS score significantly. After treatment, the HSS scores in manipulation of TCM group and arthroscopy group were 94.80 +/- 7.26 and 88.65 +/- 5.79 separately, the score in manipulation of TCM group was higher than that of arthroscopy group. Comparing with the arthroscopy group, lateral angle of patellofemoral joint with weight-hearing position were improved significantly in manipulation of TCM group. CONCLUSION: Arthroscopy and manipulation of TCM have equally efficacious in the treatment of patellofemoral joint disease, but manipulation has advantage of minimal trauma, and is better to treat patella extraversion.