26 results on '"Ge, Rili"'
Search Results
2. Antibiotic intervention exacerbated oxidative stress and inflammatory responses in SD rats under hypobaric hypoxia exposure
- Author
-
Liao, Yang, Chen, Zheng, Yang, Yingkui, Shen, Di, Chai, Shatuo, Ma, Yan, Ge, Rili, Wang, Xun, Wang, Shuxiang, and Liu, Shujie
- Published
- 2023
- Full Text
- View/download PDF
3. Macrophage-derived inflammation promotes pulmonary vascular remodeling in hypoxia-induced pulmonary arterial hypertension mice
- Author
-
Liu, Hong, Wang, Yuxiang, Zhang, Qingqing, Liu, Chuanchuan, Ma, Yougang, Huang, Pan, Ge, Rili, and Ma, Lan
- Published
- 2023
- Full Text
- View/download PDF
4. Human Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Alleviate Hypoxia-Induced Pulmonary Arterial Hypertension in Mice Via Macrophages.
- Author
-
Liu, Hong, Zhang, Qingqing, Liu, Chuanchuan, Zhang, Yuwei, Wang, Yuxiang, Huang, Pan, Ma, Lan, and Ge, Rili
- Subjects
PULMONARY arterial hypertension ,VASCULAR remodeling ,EXOSOMES ,MACROPHAGES ,MUSCLE cells ,UMBILICAL cord - Abstract
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]
- Published
- 2024
- Full Text
- View/download PDF
5. Tsantan Sumtang attenuated chronic hypoxia-induced right ventricular structure remodeling and fibrosis by equilibrating local ACE-AngII-AT1R/ACE2-Ang1-7-Mas axis in rat
- Author
-
Dang, Zhancui, Su, Shanshan, Jin, Guoen, Nan, Xingmei, Ma, Lan, Li, Zhanqiang, Lu, Dianxiang, and Ge, Rili
- Published
- 2020
- Full Text
- View/download PDF
6. Gain-of-function EGLN1 prolyl hydroxylase (PHD2 D4E:C127S) in combination with EPAS1 (HIF-2α) polymorphism lowers hemoglobin concentration in Tibetan highlanders
- Author
-
Tashi, Tsewang, Scott Reading, N., Wuren, Tanna, Zhang, Xu, Moore, Lorna G., Hu, Hao, Tang, Feng, Shestakova, Anna, Lorenzo, Felipe, Burjanivova, Tatiana, Koul, Parvaiz, Guchhait, Prasenjit, Wittwer, Carl T., Julian, Colleen G., Shah, Binal, Huff, Chad D., Gordeuk, Victor R., Prchal, Josef T., and Ge, RiLi
- Published
- 2017
- Full Text
- View/download PDF
7. Effect of aqueous extract of Sanweitanxiang powder on calcium homeostasis protein expression in ischemic-reperfusion injury rat heart
- Author
-
Yang, Mei, Zhang, Shuna, Ren, Shicun, Wang, Jinjun, Yun, Haixia, Yong, Sheng, Zhang, Dejun, Yang, Quanyu, Kou, Yiying, Lu, Dianxiang, and Ge, Rili
- Published
- 2013
- Full Text
- View/download PDF
8. An integrated systems approach to plateau ecosystem management—a scientific application in Qinghai and Tibet plateau
- Author
-
Liu, Fang, Bi, Zhuming, Xu, Eric L., Ga, Qin, Yang, Quanyu, Yang, Yingzhong, Ma, Lan, Wuren, Tana, and Ge, Rili
- Published
- 2015
- Full Text
- View/download PDF
9. Genetic Evidence for High-Altitude Adaptation in Tibet
- Author
-
Simonson, Tatum S., Yang, Yingzhong, Huff, Chad D., Yun, Haixia, Qin, Ga, Witherspoon, David J., Bai, Zhenzhong, Lorenzo, Felipe R., Xing, Jinchuan, Jorde, Lynn B., Prchal, Josef T., and Ge, RiLi
- Published
- 2010
10. Effects of hypoxia on mRNA expression of housekeeping genes in rat brain tissue and primary cultured neural cells
- Author
-
Yang, Yingzhong, Fan, Wenhong, Zhu, Lingling, Zhao, Tong, Ma, Lan, Wu, Yan, Ge, Rili, and Fan, Ming
- Published
- 2008
- Full Text
- View/download PDF
11. High-altitude Tibetan fermented milk ameliorated cognitive dysfunction by modified gut microbiota in Alzheimer's disease transgenic mice.
- Author
-
Liu, JunLi, Yu, ChunYang, Li, RunLe, Liu, KunMei, Jin, GuoEn, Ge, RiLi, Tang, Feng, and Cui, Sen
- Published
- 2020
- Full Text
- View/download PDF
12. Chronic Hypoxia-Induced Microvessel Proliferation and Basal Membrane Degradation in the Bone Marrow of Rats Regulated through the IL-6/JAK2/STAT3/MMP-9 Pathway.
- Author
-
Zhu, Mingming, Yang, Min, Yang, Quanyu, Liu, Wenling, Geng, Hui, Pan, Li, Wang, Lu, Ge, Rili, Ji, Linhua, Cui, Sen, and Li, Zhanquan
- Subjects
ANIMAL experimentation ,HYPOXEMIA ,BLOOD vessels ,BONE marrow ,CELLULAR signal transduction ,DIMETHYL sulfoxide ,ELECTRON microscopy ,ENZYME inhibitors ,ENZYME-linked immunosorbent assay ,FLUORESCENT antibody technique ,GENE expression ,INTERLEUKINS ,BASAL lamina ,PHOSPHORYLATION ,POLYMERASE chain reaction ,RATS ,STAINS & staining (Microscopy) ,WESTERN immunoblotting ,REVERSE transcriptase polymerase chain reaction ,STAT proteins ,MATRIX metalloproteinases ,PATHOLOGIC neovascularization ,JANUS kinases ,DISEASE complications ,PHARMACODYNAMICS - Abstract
Chronic hypoxia (CH) is characterized by long-term hypoxia that is associated with microvessel proliferation and basal membrane (BM) degradation in tissues. The IL-6/JAK2/STAT3/MMP-9 pathway has been described in a variety of human cancers and plays an essential role in microvessel proliferation and BM degradation. Therefore, this study investigated the role of the IL-6/JAK2/STAT3/MMP-9 pathway in hypoxia-mediated microvessel proliferation and BM degradation in the rat bone marrow. Eighty pathogen-free Sprague Dawley male rats were randomly divided into four groups (20 per group)—control group, CH group (exposed to hypoxia in a hypobaric chamber at a simulated altitude of 5000 m for 28 d), CH + STAT3 inhibitor group (7.5 mg/kg/d), and CH + DMSO group. Microvessel density (MVD) and BM degradation in the bone marrow were determined by immunofluorescence staining and transmission electron microscopy. Serum IL-6 levels were assessed by enzyme-linked immunosorbent assay (ELISA), and the levels of P-JAK2, P-STAT3, and MMP-9 were assessed by western blot analysis and real-time reverse transcription PCR (RT-PCR). Hypoxia increased serum IL-6 levels, which in turn increased JAK2 and STAT3 phosphorylation, which subsequently upregulated MMP-9. Overexpression of MMP-9 significantly promoted the elevation of MVD and BM degradation. Inhibition of STAT3 using an inhibitor, SH-4-54, significantly downregulated MMP-9 expression and decreased MVD and BM degradation. Surprisingly, STAT3 inhibition also decreased serum IL-6 levels and JAK2 phosphorylation. Our results suggest that the IL-6/JAK2/STAT3/MMP-9 pathway might be related to CH-induced microvessel proliferation and BM degradation in the bone marrow. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
13. The human platelet transcriptome and proteome is altered and pro-thrombotic functional responses are increased during prolonged hypoxia exposure at high altitude.
- Author
-
Shang, Chunxiang, Wuren, Tana, Ga, Qing, Bai, Zhenzhong, Guo, Li, Eustes, Alicia S., McComas, Kyra N., Rondina, Matthew T., and Ge, Rili
- Subjects
HYPOXEMIA ,MEMBRANE glycoproteins ,BLOOD platelets ,BLOOD platelet activation ,THROMBOTIC thrombocytopenic purpura - Abstract
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]
- Published
- 2020
- Full Text
- View/download PDF
14. Tsantan Sumtang Alleviates Chronic Hypoxia-Induced Pulmonary Hypertension by Inhibiting Proliferation of Pulmonary Vascular Cells.
- Author
-
He, Qilian, Nan, Xingmei, Li, Silin, Su, Shanshan, Ma, Ke, Li, Zhanqiang, Lu, Dianxiang, and Ge, Rili
- Subjects
CELL proliferation ,ANIMAL experimentation ,HYPOXEMIA ,BLOOD pressure ,CELLULAR signal transduction ,GENE expression ,MUSCLE proteins ,NITRIC oxide ,NORADRENALINE ,PROSTAGLANDINS ,PROTEIN kinases ,PULMONARY artery ,PULMONARY hypertension ,RATS ,TRADITIONAL medicine ,VASOCONSTRICTION ,NUCLEAR proteins ,IN vitro studies ,RIGHT ventricular hypertrophy ,VASCULAR remodeling ,IN vivo studies ,DISEASE complications - Abstract
Hypoxia-induced pulmonary hypertension (HPH) is a severe condition associated with significant morbidity and mortality in people living at high altitude. Tsantan Sumtang, a traditional Tibetan medicine, has been routinely used for the treatment of cardiopyretic disease, as well as stenocardia. Interestingly, our previous research found that Tsantan Sumtang improved HPH in rats maintaining in a hypobaric chamber. We performed a series of experiments to test the indexes of vasoconstriction and vascular remodeling, the key pathophysiological characteristics of HPH. Our results showed that Tsantan Sumtang relaxed noradrenaline (NE)-precontracted rat pulmonary artery rings in a concentration-dependent manner in vitro. The PGI2-cAMP (prostaglandin I2-cyclic adenosine monophosphate) pathway, NO-cGMP (nitric oxide-cyclic guanosine monophosphate) pathway, and the opening of K
+ channels (inward rectifier K+ channels, large conductance Ca2+ -activated K+ channels, and voltage-dependent K+ channels) might play major roles in the vasorelaxation effect. In vivo, the administration of Tsantan Sumtang resulted in a substantial decrease in the rat mean pulmonary artery pressure (mPAP) and the right ventricular hypertrophy index (RVHI). The reduction of thickness of small pulmonary arterial wall and the WT% (the ratio of the vascular wall thickness to the vascular diameter) were observed. The smooth muscle muscularization of the arterials was alleviated by Tsantan Sumtang treatment at the same time. Tsantan Sumtang also reduced remodeling of pulmonary arterioles by suppressing the expression of proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (α-SMA), cyclin D1, and cyclin-dependent kinase 4 (CDK4) through inhibition of p27Kip1 degradation. Therefore, Tsantan Sumtang could be applied as a preventative medication for HPH, which would be a new use for this traditional medicine. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
15. Bioinformatics identification of potentially involved microRNAs in Tibetan with gastric cancer based on microRNA profiling.
- Author
-
Yushuang Luo, Chengwu Zhang, Feng Tang, Junhui Zhao, Cunfang Shen, Cheng Wang, Pengjie Yu, Miaozhou Wang, Yan Li, J. I. Di, Rong Chen, and Ge Rili
- Subjects
STOMACH cancer ,MICRORNA genetics ,DISEASE incidence ,GENE expression ,STOMACH cancer treatment ,GENETICS - Abstract
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]
- Published
- 2015
- Full Text
- View/download PDF
16. Srolo Bzhtang, a traditional Tibetan medicine formula, inhibits cigarette smoke induced airway inflammation and muc5ac hypersecretion via suppressing IL-13/STAT6 signaling pathway in rats.
- Author
-
Jing, Linde, Su, Shanshan, Zhang, Dejun, Li, Zhanqiang, Lu, Dianxiang, and Ge, Rili
- Subjects
- *
ANIMAL experimentation , *BENZOPYRANS , *BRONCHOALVEOLAR lavage , *CELLULAR signal transduction , *CYTOKINES , *ENZYME-linked immunosorbent assay , *GENE expression , *GLYCOPROTEINS , *IMMUNOHISTOCHEMISTRY , *INFLAMMATORY mediators , *INTERLEUKINS , *LUNGS , *MEDICINAL plants , *TIBETAN medicine , *MESSENGER RNA , *MUCUS , *ORAL drug administration , *POLYMERASE chain reaction , *RATS , *SMOKING , *STAINS & staining (Microscopy) , *TRANSCRIPTION factors , *TUMOR necrosis factors , *WESTERN immunoblotting , *PLANT extracts , *REVERSE transcriptase polymerase chain reaction , *DEXAMETHASONE , *INDOLE compounds , *FLUORESCENT dyes , *CHRONIC bronchitis , *PHARMACODYNAMICS - Abstract
Abstract Ethnopharmacological relevance Srolo Bzhtang (SBT), a traditional Tibetan medicine formula, was composed of three herbs, Solms-Laubachia eurycarpa , Bergenia purpurascens , Glycyrrhiza uralensis , and one lac, and was first documented in the ancient Tibetan medical work Four Medical Tantras (rGyud-bzhi) in the eighth century AD. It has been widely used to treat lung "phlegm-heat" syndromes such as chronic bronchitis and chronic obstructive pulmonary disease (COPD). Objective The aim of this study was to evaluate the potential influences of aqueous extract of SBT on airway inflammation and mucus secretion and to reveal the underlying mechanism in a rat model of cigarette smoke (CS)-induced chronic bronchitis (CB). Materials and methods Sixty male Sprague-Dawley rats were randomly divided to six groups: control (room air exposure), model (CS exposure), DEX (CS exposure and 0.2 mg/kg/day dexamethasone), and three SBT (CS exposure and 1.67, 2.50, and 3.34 g/kg/day SBT) groups. DEX and the three doses of SBT were administered by oral gavage every day for eight weeks. Pathological changes and mucus expression in the lung tissue were determined by hematoxylin and eosin (H&E), Alcian blue-periodic acid-Schiff (AB-PAS) and immunohistochemical staining. The levels of cytokines in bronchoalveolar lavage fluid (BALF) were assessed by ELISA. Western blot analysis and qRT-PCR were performed to explore the effects of SBT on the expression of IL-13, STAT6 and MUC5AC. Results Pretreatment with SBT attenuated the TNF-α, IL-8, IL-13 expression levels in BALF and the inflammatory cell infiltration in bronchial walls and peribronchial lung tissue. SBT exhibited a dose-dependent downregulation of MUC5AC expression as assessed by AB-PAS and immunohistochemical staining. The protein and mRNA levels of IL-13, STAT6/p-STAT6 and MUC5AC were also downregulated by SBT preconditioning. Conclusion These results for the first time demonstrated that SBT exhibited protective effects on CS-induced airway inflammation and MUC5AC hypersecretion, which might be related to the downregulation of the IL-13/STAT6 signaling pathway. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
17. Bioactive fraction of Rhodiola algida against chronic hypoxia-induced pulmonary arterial hypertension and its anti-proliferation mechanism in rats.
- Author
-
Nan, Xingmei, Su, Shanshan, Ma, Ke, Ma, Xiaodong, Wang, Ximeng, Zhaxi, Dongzhu, Ge, Rili, Li, Zhanqiang, and Lu, Dianxiang
- Subjects
- *
CELL proliferation , *ANIMAL experimentation , *HYPOXEMIA , *BLOOD pressure , *GENE expression , *RIGHT heart ventricle , *HEMATOCRIT , *HYPERTROPHY , *LIQUID chromatography , *MASS spectrometry , *TIBETAN medicine , *POLYMERASE chain reaction , *PULMONARY artery , *PULMONARY hypertension , *RATS , *WESTERN immunoblotting , *PLANT extracts , *NUCLEAR proteins , *CELL cycle proteins , *DISEASE complications - Abstract
Ethnopharmacological relevance Rhodiola algida var. tangutica (Maxim.) S.H. Fu is a perennial plant of the Crassulaceae family that grows in the mountainous regions of Asia. The rhizome and roots of this plant have been long used as Tibetan folk medicine for preventing high latitude sickness. Aim of the study The aim of this study was to determine the effect of bioactive fraction from R. algida (ACRT) on chronic hypoxia-induced pulmonary arterial hypertension (HPAH) and to understand the possible mechanism of its pharmacodynamic actions. Materials and methods Male Sprague-Dawley rats were separated into five groups: control group, hypoxia group, and hypoxia+ACRT groups (62.5, 125, and 250 mg/kg/day of ACRT). The chronic hypoxic environment was created in a hypobaric chamber by adjusting the inner pressure and oxygen content for 4 weeks. After 4 weeks, major physiological parameters of pulmonary arterial hypertension such as mPAP, right ventricle index (RV/LV+S, RVHI), hematocrit (Hct) levels and the medial vessel thickness (wt%) were measured. Protein and mRNA expression levels of proliferating cell nuclear antigen (PCNA), cyclin D1, p27Kip1 and cyclin-dependent kinase 4 (CDK4)) were detected by western blotting and real time PCR respectively. Chemical profile of ACRT was revealed by ultra performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UHPLC-Q-TOF-MS/MS). Results The results showed that a successful HPAH rat model was established in a hypobaric chamber for 4 weeks, as indicated by the significant increase in mPAP, RV/LV+S, RV/BW and wt%. Compared with the normal group, administration of ACRT reduced mPAP, right ventricular hypertrophy, pulmonary small artery wall thickness, and damage in ultrastructure induced by hypoxia in rats. PCNA, cyclin D1, and CDK4 expression was reduced ( p <0.05), and p27Kip1 expression increased ( p <0.05) in hypoxia+ACRT groups compared to hypoxia. 38 constituents in bioactive fraction were identified by UHPLC-Q-TOF-MS/MS. Conclusion Our results suggest that ACRT could alleviate chronic hypoxia-induced pulmonary arterial hypertension. And its anti-proliferation mechanism in rats based on decreasing PCNA, cyclin D1, CDK4 expression level and inhibiting p27Kip1 degradation. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
18. Proteomics annotate therapeutic properties of a traditonal Tibetan medicine – Tsantan Sumtang targeting and regulating multiple perturbed pathways.
- Author
-
Zhou, Yi, Li, Zhanqiang, Tang, Feng, and Ge, Rili
- Subjects
- *
BIOLOGICAL models , *CLUSTER analysis (Statistics) , *ISCHEMIA , *ASIAN medicine , *MITOCHONDRIA , *PROTEINS , *RATS , *PROTEOMICS , *CONTROL groups - Abstract
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]
- Published
- 2016
- Full Text
- View/download PDF
19. Comparative genomic analysis of high-altitude adaptation for Mongolia Mastiff, Tibetan Mastiff, and Canis Lupus.
- Author
-
Cai, Chunmei, Yang, Yingzhong, Ga, Qin, Xu, Guocai, Ge, Rili, and Tang, Feng
- Subjects
- *
WOLVES , *GENOMICS , *TIBETANS , *DNA repair , *GENE families , *EXTREME environments - Abstract
Tibetan Mastiff has adapted to the extreme environment of the Qinghai-Tibetan Plateau. Yet, the underlying mechanisms of its high-altitude-adaptation and origin remains elusive. Here, we generated the draft genomes of Mongolia Mastiff, Tibetan Mastiff, and Canis Lupus. The phylogenetic tree uncovered that Tibetan Mastiff and Mongolia Mastiff were derived from Canis Lupus species. The comparative genomic analyses identified that the expansion of gene families related to DNA repair and damage response, and contraction related to ATPase activity revealed the genetic adaptations of Tibetan Mastiff and Canis Lupus to high altitude. In addition, the Tibetan Mastiff and Canis Lupus had signals of positive selection for genes involved in fatty-acid α/β- oxidation for highland adaptation. Notably, the positively selected TERT of Tibetan Mastiff should be an adaptive trait for correcting DNA damage. These findings suggested that the Tibetan Mastiff and Canis Lupus evolves basic strategies for adaptation to high altitude. • De novo assembled the genome sequence of Mongolia mastiff, Tibetan mastiff, and Canis Lupus with excellent continuity at the contig and scaffold levels. • Tibetan Mastiff and Mongolia Mastiff were derived from Canis Lupus. • The expansion of gene families related to DNA repair and damage response, as well as the contraction related to ATPase activity revealed the genetic adaptations of Tibetan Mastiff and Canis Lupus to high altitude. • The Tibetan Mastiff and Canis Lupus had signals of positive selection for genes involved in fatty-acid α/β-oxidation for highland adaptation. Notably, the positively selected TERT of Tibetan Mastiff should be an adaptive trait for correcting DNA damage. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
20. Tibetan Mesenchymal Stem Cell-derived Exosomes Alleviate Pulmonary Vascular Remodeling in Hypoxic Pulmonary Hypertension Rats.
- Author
-
Zhang Q, Liu H, Liu C, Wang Y, Huang P, Wang X, Ma Y, Ma L, and Ge R
- Abstract
Hypoxic pulmonary hypertension (HPH) is characterized by progressive pulmonary vasoconstriction, vascular remodeling, and right ventricular hypertrophy, causing right heart failure. This study aimed to investigate the therapeutic effects of exosomes from Tibetan umbilical cord mesenchymal stem cells on HPH via the TGF-β1/Smad2/3 pathway, comparing them with exosomes from Han Chinese individuals. An HPH rat model was established in vivo, and a hypoxia-induced injury in the rat pulmonary artery smooth muscle cells (rPASMCs) was simulated in vitro. Exosomes from human umbilical cord mesenchymal stem cells were administered to HPH model rats or added to cultured rPASMCs. The therapeutic effects of Tibetan-mesenchymal stem cell-derived exosomes (Tibetan-MSC-exo) and Han-mesenchymal stem cell-derived exosomes (Han-MSC-exo) on HPH were investigated through immunohistochemistry, Western blotting, EdU, and Transwell assays. The results showed that Tibetan-MSC-exo significantly attenuated pulmonary vascular remodeling and right ventricular hypertrophy in HPH rats compared with Han-MSC-exo. Tibetan-MSC-exo demonstrated better inhibition of hypoxia-induced rPASMCs proliferation and migration. Transcriptome sequencing revealed upregulated genes (Nbl1, Id2, Smad6, and Ltbp1) related to the TGFβ pathway. Nbl1 knockdown enhanced hypoxia-induced rPASMCs proliferation and migration, reversing Tibetan-MSC-exo-induced downregulation of TGFβ1 and p-Smad2/3. Furthermore, TGFβ1 overexpression hindered the therapeutic effects of Tibetan-MSC-exo and Han-MSC-exo on hypoxic injury. These findings suggest that Tibetan-MSC-exo favors HPH treatment better than Han-MSC-exo, possibly through the modulation of the TGFβ1/Smad2/3 pathway via Nbl1., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
- Full Text
- View/download PDF
21. Mitochondria in hypoxic pulmonary hypertension, roles and the potential targets.
- Author
-
Geng Y, Hu Y, Zhang F, Tuo Y, Ge R, and Bai Z
- Abstract
Mitochondria are the centrol hub for cellular energy metabolisms. They regulate fuel metabolism by oxygen levels, participate in physiological signaling pathways, and act as oxygen sensors. Once oxygen deprived, the fuel utilizations can be switched from mitochondrial oxidative phosphorylation to glycolysis for ATP production. Notably, mitochondria can also adapt to hypoxia by making various functional and phenotypes changes to meet the demanding of oxygen levels. Hypoxic pulmonary hypertension is a life-threatening disease, but its exact pathgenesis mechanism is still unclear and there is no effective treatment available until now. Ample of evidence indicated that mitochondria play key factor in the development of hypoxic pulmonary hypertension. By hypoxia-inducible factors, multiple cells sense and transmit hypoxia signals, which then control the expression of various metabolic genes. This activation of hypoxia-inducible factors considered associations with crosstalk between hypoxia and altered mitochondrial metabolism, which plays an important role in the development of hypoxic pulmonary hypertension. Here, we review the molecular mechanisms of how hypoxia affects mitochondrial function, including mitochondrial biosynthesis, reactive oxygen homeostasis, and mitochondrial dynamics, to explore the potential of improving mitochondrial function as a strategy for treating hypoxic pulmonary hypertension., 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., (Copyright © 2023 Geng, Hu, Zhang, Tuo, Ge and Bai.)
- Published
- 2023
- Full Text
- View/download PDF
22. Novel insights into plasma biomarker candidates in patients with chronic mountain sickness based on proteomics.
- Author
-
Zhang P, Li Z, Yang F, Ji L, Yang Y, Liu C, Liu H, Ma J, Liu J, Dang Z, Wang S, Ge R, and Cui S
- Subjects
- Adult, Altitude Sickness metabolism, Biomarkers blood, China, Chromatography, Liquid methods, Chronic Disease, Ethnicity, Gene Ontology, Humans, Male, Middle Aged, Oxidative Stress, Protein Interaction Maps, Reactive Oxygen Species metabolism, Sequence Analysis, RNA methods, Tandem Mass Spectrometry methods, Altitude Sickness blood, Proteomics methods
- Abstract
Chronic mountain sickness (CMS) is a progressive incapacitating syndrome induced by lifelong exposure to hypoxia. In the present study, proteomic analysis was used to identify the differentially expressed proteins (DEPs) and then evaluate the potential plasma biomarkers between CMS and non-CMS groups. A total of 145 DEPs were detected in CMS Han Chinese people who live in the plateau (CMS-HPu), among which 89 were significantly up-regulated and 56 were significantly down-regulated. GO enrichment analysis showed that various biological processes were enriched, including the hydrogen peroxide metabolic/catabolic process, reactive oxygen species (ROS) metabolic, and acute inflammatory response. Protein-protein interaction analysis showed that antioxidant activity, the hydrogen peroxide catabolic process and peroxidase activity were primarily mapped in interaction proteins. Nine modules showed significantly clustering based on WGCNA analysis, with two being the most significant, and GO analysis showed that proteins of both modules were primarily enriched in oxidative stress-related biological processes. Four DEPs increased in CMS patients were evaluated as the candidate biomarkers, and three showed significant AUC: hemoglobin β chain (HB-β), thioredoxin-1 (TRX1), and phosphoglycerate kinase 1 (PGK1). The present study provides insights into the pathogenesis of CMS and further evaluates the potentially biomarkers for its prevention and treatment of it., (© 2021 The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
23. [Pilot study on the differences of young male's sleep structure and quality between indigenous Tibetans and longtime Han residents in high altitude area].
- Author
-
Li Y, Gao L, Wuren T, Ga Q, Guan W, and Ge R
- Subjects
- Adult, Apnea, Humans, Hypoxia, Male, Pilot Projects, Polysomnography, Altitude, Sleep
- Abstract
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.
- Published
- 2015
24. [Pay attention to research on prevention and treatment of sleep disturbances at high altitude].
- Author
-
Ge R
- Subjects
- Attention, Humans, Altitude, Sleep Wake Disorders
- Published
- 2015
25. [Association between genetic polymorphisms of EDNRA gene and high altitude polycythemia in Tibetans at the Qinghai-Tibetan Plateau].
- Author
-
Xu J, Yang Y, Wang Z, Tang F, Ga Q, and Ge R
- Subjects
- China, Genotype, Humans, Tibet, Altitude Sickness, Polycythemia, Polymorphism, Single Nucleotide
- Abstract
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.
- Published
- 2015
26. Store-operated Ca²⁺ entry mediated regulation of polarization in differentiated human neutrophil-like HL-60 cells under hypoxia.
- Author
-
Ma S, Cai C, Ma Y, Bai Z, Meng X, Yang X, Zou F, and Ge R
- Subjects
- Calcium Channels genetics, Calcium Channels metabolism, Gene Expression Regulation, HL-60 Cells, Humans, Membrane Proteins genetics, Membrane Proteins metabolism, Neoplasm Proteins genetics, Neoplasm Proteins metabolism, Neutrophils metabolism, ORAI1 Protein, Stromal Interaction Molecule 1, Calcium metabolism, Cell Hypoxia physiology, Neutrophils physiology
- Abstract
The regulation of neutrophil polarization by calcium entry is critical for maintaining an effective host response. Hypoxia has a major effect on the apoptosis of neutrophils, however the role of store-operated Ca2+ entry (SOCE) in neutrophil polarization under hypoxia remains to be elucidated. In the present study, we examined the polarization of differentiated human neutrophil-like HL-60 (dHL-60) cells exposed to hypoxia (3% O2) and the results demonstrated that the percentage of polarized cells following exposure to an N-formyl-Met-Leu-Phe (fMLP) gradient in the Zigmond chamber was increased. We examined stromal interaction molecule 1 (STIM1) and Orai1 expression in dHL-60 cells during hypoxia, and it was observed that the expression of STIM1 and Orai1 was significantly reduced at day 2. However, no apparent change was observed on the first day, indicating that this effect is dependent on stimulation time. Fluo-4/acetoxymethyl (AM) ester imaging also demonstrated that SOCE was decreased in dHL-60 cells. The plasmid overexpression assay demonstrated that the response of polarization was returned to the control level. We demonstrated the inhibitory role of SOCE on the polarization of dHL-60 cells under hypoxic conditions, which may be the mechanism for the adaptation of neutrophils to hypoxia. SOCE is also suggested to be a key modulator of immune deficiency under hypoxic conditions and is potentially a therapeutic target.
- Published
- 2014
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.