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Pulmonary hypertension (PH) is an intractable, severe, and progressive cardiopulmonary disease. Recent findings suggest that human umbilical cord mesenchymal stromal cells (HUCMSCs) and HUCMSC-derived exosomes (HUCMSC-Exos) possess potential therapeutic value for PH. However, whether they have beneficial effects on hypoxic pulmonary hypertension (HPH) is unclear. Exos are released into the extracellular environment by the fusion of intracellular multivesicular bodies with the cell membrane, and they play an important role in cellular communication. Exos ameliorate immune inflammation levels, alter macrophage phenotypes, regulate mitochondrial metabolic function, and inhibit pulmonary vascular remodeling, thereby improving PH. Macrophages are important sources of cytokines and other transmitters and can promote the release of cytokines, vasoactive molecules, and reactive oxygen species, all of which are associated with pulmonary vascular remodeling. Therefore, the aim of this study was to investigate whether HUCMSC-Exos could improve the lung inflammatory microenvironment and inhibit pulmonary vascular remodeling by targeting macrophages and identifying the underlying mechanisms. The results showed that HUCMSC-Exos promoted M2 macrophage polarization, decreased pro-inflammatory factors, increased IL-10 levels, and inhibited IL-33/ST2 axis expression, thereby inhibiting hypoxia-induced proliferation of pulmonary artery smooth muscle cells and ameliorating HPH. [ABSTRACT FROM AUTHOR]

Exposure to hypoxia, through ascension to high altitudes (HAs), air travel, or human disease, is associated with an increased incidence of thrombosis in some settings. Mechanisms underpinning this increased thrombosis risk remain incompletely understood, and the effects of more sustained hypoxia on the human platelet molecular signature and associated functional responses have never been examined. We examined the effects of prolonged (≥2 months continuously) hypobaric hypoxia on platelets isolated from subjects residing at HA (3,700 meters) and, for comparison, matched subjects residing under normoxia conditions at sea level (50 meters). Using complementary transcriptomic, proteomic, and functional methods, we identified that the human platelet transcriptome is markedly altered under prolonged exposure to hypobaric hypoxia at HA. Among the significantly, differentially expressed genes (mRNA and protein), were those having canonical roles in platelet activation and thrombosis, including membrane glycoproteins (e.g. GP4, GP6, GP9), integrin subunits (e.g. ITGA2B), and alpha-granule chemokines (e.g. SELP, PF4V1). Platelets from subjects residing at HA were hyperactive, as demonstrated by increased engagement and adhesion to fibrinogen, fewer alpha granules by transmission electron microscopy, increased circulating PF4 and ADP, and significantly enhanced clot retraction. In conclusion, we identify that prolonged hypobaric hypoxia exposure due to HA alters the platelet transcriptome and proteome, triggering increased functional activation responses that may contribute to thrombosis. Our findings may also have relevance across a range of human diseases where chronic hypoxia, platelet activation, and thrombosis are increased. [ABSTRACT FROM AUTHOR]

Objective: The incidence of gastric cancer is high in Chinese Tibetan. This study aimed to identify the differentially expressed microRNAs (miRNAs) and further explore their potential roles in Tibetan with gastric cancer so as to predict potential therapeutic targets. Methods: A total of 10 Tibetan patients (male:female = 6:4) with gastric cancer were enrolled for isolation of matched gastric cancer and adjacent non-cancerous tissue samples. Affymetrix GeneChip microRNA 3.0 Array was employed for detection of miRNA expression in samples. Differential expression analysis between two sample groups was analyzed using Limma package. Then, MultiMiR package was used to predict targets for miRNAs. Following, the target genes were put into DAVID (Database for Annotation, Visualization and Integrated Discovery) to identify the significant pathways of miRNAs. Results: Using Limma package in R, a total of 27 differentially expressed miRNAs were screened out in gastric cancer, including 25 down-regulated (e.g. hsa-miR-148a-3p, hsa-miR-148b-3p and hsa-miR-363-3p) and 2 up-regulated miRNAs. According to multiMiR package, a number of 1445 target genes (e.g. Wnt1, KLF4 and S1PR1) of 13 differentially expressed miRNAs were screened out. Among those miRNAs, hsa-miR-148a-3p, hsa-miR-148b-3p and hsa-miR-363-3p were identified with the most target genes. Furthermore, three miRNAs were significantly enriched in numerous common cancer-related pathways, including "Wnt signaling pathway", "MAPK signaling pathway" and "Jak-STAT signaling pathway". Conclusions: The present study identified a downregulation and enrichment in cancer-related pathways of hsa-miR- 148a-3p, hsa-miR-148b-3p and hsa-miR-363-3p in Tibetan with gastric cancer, which can be suggested as therapeutic targets. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Tsantan Sumtang is a traditional Tibetan medicine, which has been traditionally used as medicine for the treatment of cardiopyretic disease which is similar to angina. However, the precise and comprehensive mechanism of it pretreatment remain elusive, so in this study, we used proteomics to systematically analyse the therapeutic mechanism of it. Materal and methods Rats were divided into three groups ( n =6): Tsantan Sumtang group (2 g/kg), the model group, the control group (distilled water, 10 ml/kg). Drugs were treated once a day for 20 days. After the last administration of drug, left anterior descending coronary artery ligation in vivo was performed. 5 days latter, the hearts were harvested and we applied HPLC- MS/MS using an isobaric TMTs proteomics technology to analyse the differentially expressed proteins among groups. Results We comfirmed from the data that 752 proteins were differentially expressed in model group when compared with the control group, 314 proteins showed the recovery of the values by Tsantan Sumtang treatment. The differential proteins were analysed by gene ontology, cellular pathways and clustering analyses, most of them were metabolic enzymes. These included glycolytic enzymes, enzymes implicated in fatty acids oxidation and the tricarboxylic acid cycle, various subunits of different mitochondrial electron transfer chain complexes, as well as enzymes involved in antioxidation system. Conclusion Tsantan Sumtang can target and regulate multiple metabolic perturbed pathways, especially it can partially inhibite fatty acid β-oxidation, stimulate glucose metabolism, oxidative phosphorylation and ATP utilization to protect the injured heart. This helped us to understand the molecular therapeutic mechanisms of Tsantan Sumtang on mycardial ischemia. [ABSTRACT FROM AUTHOR]

Objective: To compare young males' sleep quality and structure between native Tibetans and longtime Han residents., Methods: A total of 14 male Tibetans and 11 male Hans at an altitude of 3 780 m were enrolled in this study. Tibetans were native highlanders with a mean age of (32.0 ± 9.1) years. Han subjects were born and living in high altitude with a mean age of (36.6 ± 7.6) years. All subjects were monitored by Polysomnography(PSG), and the differences of sleep structure and quality between the two groups were compared according to the international standard., Results: The sleep efficiency (93.1% ± 3.9% vs 85.7% ± 4.2%) and nocturnal oxygen saturation (SpO(2)) (89.4% ± 2.0% vs 84.6% ± 4.3%) in Tibetans was significantly higher than those in Hans (both P<0.05). The number of awakening ((1.9 ± 0.8) vs (4.1 ± 1.3)/h) and micro-awakening ((23.4 ± 5.8) vs (28.7 ± 4.1)/h), the oxygen reduction index ((11.7 ± 4.8) vs (16.3 ± 7.5)/h), apnea hypoventilation index (AHI) ((5.8 ± 2.3) vs (9.6 ± 4.2)/h) and average heart rate ((66.9 ± 8.3) vs (79.9 ± 6.7)/min) of Tibetans were significantly lower than Hans (all P<0.05). Tibetans had longer slow wave sleep (20.1% ± 7.2% vs 8.8% ± 3.3%) and the Hans had longer stage 2 of non-rapid eye movement (NREM) (31.1% ± 11.9% vs 18.4% ± 6.7%) and shallow sleep (76.1 ± 11.7 vs 70.8 ± 11.2) (all P<0.05)., Conclusion: Tibetans have better sleep quality and higher sleep efficiency than Han residents at high altitude.

Objective: To test the hypothesis that the polymorphisms in EDNRA gene are associated with the susceptibility to high-altitude polycythemia (HAPC) in Tibetans at the Qinghai-Tibetan Plateau in China., Methods: We enrolled 63 Tibetan HAPC patients and 131 healthy, age-and gender-matched control Tibetans. All subjects came from Yushu area of Qinghai where the altitude was over 3,500 meters. Five SNPs of EDNRA gene (rs10003447, rs1801708, rs2048894, rs5335 and rs6841581) were genotyped by the Sequenom MassARRAY SNP assays., Results: None of five SNPs in EDNRA gene were associated with HAPC risk (P=0.742; P=0.733; P=0.828; P=0.417; P=0.096)., Conclusion: EDNRA gene is likely to have adaptive benefits for high altitude environment. However, it is not protective against HAPC in Tibetans.