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1.
J Asian Nat Prod Res ; 26(7): 803-811, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38721701

RESUMEN

Two new triterpenes mayteneri A (1), mayteneri B (2), and seven known compounds (3-9) were isolated from stems of Maytenus hookeri Loes. The chemical structures of compounds 1 and 2 were established by 1D, 2D NMR, HRESIMS analysis, and calculating electronic circular dichroism (ECD). The structures of known compounds 3-9 were determined by comparison of their spectral with those reported. Compounds 4-7 showed significant inhibitory activity for NLRP3 inflammasome, with the IC50 values of 2.36-3.44 µM.


Asunto(s)
Maytenus , Ácido Oleanólico , Estructura Molecular , Ácido Oleanólico/química , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/aislamiento & purificación , Ácido Oleanólico/farmacología , Maytenus/química , Triterpenos/química , Triterpenos/farmacología , Triterpenos/aislamiento & purificación , Tallos de la Planta/química , Animales , Ratones , Inflamasomas/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores
2.
J Nat Prod ; 86(10): 2348-2359, 2023 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-37737089

RESUMEN

Eleven diterpenoids, wulfenioidins D-N (1-11), classified into five distinct carbon skeletons with one unreported framework, and four modified abietane diterpenoids were isolated from the whole plant of Orthosiphon wulfenioides. The structures and absolute configurations were characterized by spectroscopic methods, single-crystal X-ray diffraction, and electronic circular dichroism analyses. Compounds 3 and 5 exhibited activity against Zika virus (ZIKV) with EC50 values of 8.07 and 8.50 µM, respectively, and showed no significant cytotoxicity toward Vero cells at 100 µM. Western blot and immunofluorescence experiments showed that compounds 3 and 5 interfered with the replication of the ZIKV by inhibiting the expression of the ZIKV envelope (E) protein.


Asunto(s)
Diterpenos , Orthosiphon , Infección por el Virus Zika , Virus Zika , Animales , Chlorocebus aethiops , Células Vero , Diterpenos/química , Estructura Molecular
3.
Chem Biodivers ; 20(3): e202201171, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36691852

RESUMEN

One new alkaloid, picrasine A, two new quassinoids, picralactones A-B, together with eleven known compounds were isolated from Picrasma chinensis P.Y. Chen. The structures of these compounds were determined using 1D and 2D NMR, HR-ESI-MS, and IR spectroscopic data, and by comparison with published data. Some compounds were tested for tyrosinase inhibiting activity, however, none of them exhibited strong inhibitory effects.


Asunto(s)
Alcaloides , Picrasma , Extractos Vegetales , Alcaloides/química , Estructura Molecular , Monofenol Monooxigenasa/antagonistas & inhibidores , Picrasma/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Hojas de la Planta/química
4.
BMC Med ; 20(1): 369, 2022 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-36280874

RESUMEN

BACKGROUND: Circulating tumor DNA (ctDNA) has been proven to be a promising tumor-specific biomarker in solid tumors, but its clinical utility in risk stratification and early prediction of relapse for diffuse large B cell lymphoma (DLBCL) has not been well explored. METHODS: Here, using a lymphoma-specific sequencing panel, we assessed the prognostic and predictive utilities of ctDNA measurements before, during, and after first-line therapy in 73 Chinese DLBCL patients. RESULTS: The pretreatment ctDNA level serving as an independent prognostic factor for both progression-free survival (PFS, adjusted HR 2.47; p = 0.004) and overall survival (OS, adjusted HR 2.49; p = 0.011) was confirmed in our cohort. Furthermore, the patients classified as molecular responders who presented a larger decrease in ctDNA levels after the initial two treatment cycles had more favorable PFS (unreached vs. 6.25 months; HR 5.348; p = 0.0015) and OS (unreached vs. 25.87; HR 4.0; p = 0.028) than non-responders. In addition, interim ctDNA clearance may be an alternative noninvasive method of positron emission tomography and computed tomography (PET-CT) for predicting better PFS (HR 3.65; p = 0.0033) and OS (HR 3.536; p = 0.016). We also demonstrated that posttreatment ctDNA was a sensitive indicator for detecting minimal residual disease (MRD) in patients with a high risk of recurrence (HR 6.471; p = 0.014), who were otherwise claimed to achieve radiographic CR (complete remission). CONCLUSIONS: CtDNA is a promising noninvasive tool for prognosis prediction, response assessment, and early relapse prediction of first-line treatment in DLBCL patients.


Asunto(s)
ADN Tumoral Circulante , Linfoma de Células B Grandes Difuso , Humanos , ADN Tumoral Circulante/genética , Tomografía Computarizada por Tomografía de Emisión de Positrones , Recurrencia Local de Neoplasia , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Pronóstico , Biomarcadores de Tumor/genética
5.
Mol Biol Evol ; 36(10): 2227-2237, 2019 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-31362306

RESUMEN

A key question in evolutionary biology concerns the relative importance of different sources of adaptive genetic variation, such as de novo mutations, standing variation, and introgressive hybridization. A corollary question concerns how allelic variants derived from these different sources may influence the molecular basis of phenotypic adaptation. Here, we use a protein-engineering approach to examine the phenotypic effect of putatively adaptive hemoglobin (Hb) mutations in the high-altitude Tibetan wolf that were selectively introgressed into the Tibetan mastiff, a high-altitude dog breed that is renowned for its hypoxia tolerance. Experiments revealed that the introgressed coding variants confer an increased Hb-O2 affinity in conjunction with an enhanced Bohr effect. We also document that affinity-enhancing mutations in the ß-globin gene of Tibetan wolf were originally derived via interparalog gene conversion from a tandemly linked ß-globin pseudogene. Thus, affinity-enhancing mutations were introduced into the ß-globin gene of Tibetan wolf via one form of intragenomic lateral transfer (ectopic gene conversion) and were subsequently introduced into the Tibetan mastiff genome via a second form of lateral transfer (introgression). Site-directed mutagenesis experiments revealed that the increased Hb-O2 affinity requires a specific two-site combination of amino acid replacements, suggesting that the molecular underpinnings of Hb adaptation in Tibetan mastiff (involving mutations that arose in a nonexpressed gene and which originally fixed in Tibetan wolf) may be qualitatively distinct from functionally similar changes in protein function that could have evolved via sequential fixation of de novo mutations during the breed's relatively short duration of residency at high altitude.


Asunto(s)
Aclimatación/genética , Altitud , Canidae/genética , Introgresión Genética , Hemoglobinas/fisiología , Sustitución de Aminoácidos , Animales , Conversión Génica , Modelos Moleculares , Mutación
6.
Biochem Biophys Res Commun ; 500(2): 117-123, 2018 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-29626477

RESUMEN

The plateau pika (Ochotona curzoniae), one of the indigenous animals of the Qinghai-Tibet Plateau, is adapted to life in a cold and hypoxic environment. We conducted a series of genomic, proteomic and morphological studies to investigate whether changes in energy metabolism contribute to adaptation of the plateau pika to cold stress by analyzing summer and winter cohorts. The winter group showed strong morphological and histological features of brown adipose tissue (BAT) in subcutaneous white adipose tissue (sWAT). To obtain molecular evidence of browning of sWAT, we performed reverse transcription and quantitative real-time PCR, which revealed that BAT-specific genes, including uncoupling protein 1 (UCP-1) and PPAR-γ coactivator 1α (PGC-1α), were highly expressed in sWAT from the winter group. Compared with the summer group, Western blot analysis also confirmed that UCP-1, PGC-1α and Cox4 protein levels were significantly increased in sWAT from the winter group. Increased BAT mass in the inter-scapular region of the winter group was also observed. These results suggest that the plateau pika adapts to cold by browning sWAT and increasing BAT in order to increase thermogenesis. These changes are distinct from the previously reported adaptation of highland deer mice. Understanding the regulatory mechanisms underlying this adaptation may lead to novel therapeutic strategies for treating obesity and metabolic disorders.


Asunto(s)
Tejido Adiposo Pardo/metabolismo , Frío , Exposición a Riesgos Ambientales , Lagomorpha/metabolismo , Grasa Subcutánea/metabolismo , Adiposidad , Animales , Peso Corporal , Regulación de la Expresión Génica , Glucosa/metabolismo , Insulina/metabolismo , Metabolismo de los Lípidos , Mitocondrias/genética , Estaciones del Año , Tibet
7.
Appl Microbiol Biotechnol ; 102(5): 2143-2154, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29354854

RESUMEN

Alveolar echinococcosis is a zoonotic disease caused by the infection of the larval stage Echinococcus multilocularis with worldwide distribution especially in the northwest China. It is important to develop a well-tolerated immunoprophylaxis against E. multilocularis for alveolar echinococcosis control. In this study, a prokaryotic expression system for recombinant immunogen LTB-EMY162 was established, and the immunological features, sensitized lymphocyte, IL-4/IFN-γ secreted, prophylactic effect, and therapeutic effect were also evaluated. Arctic Express (DE3) system, Ni2+-charged and molecular sieve chromatography were used to obtain a high-purity 29 kDa protein. The ELISA and lymphocyte proliferation assay showed that LTB-EMY162 induced high-titer specific IgG against EMY162 and E. multilocularis protoscoleces protein in BALB/c mice and promoted sensitized T lymphocyte cell proliferation, and LTB-EMY162 stimulated Th cell to secrete IL-4 and IFN-γ and induced a Th1/Th2 mixed type immunological response. We also found that LTB-EMY162 significantly inhibited the cysts formation by challenging with 1000 E. multilocularis protoscoleces. The growth of protoscoleces and cysts were also significantly decreased by treating with LTB-EMY162 in 1000 protoscoleces intraperitoneal injection therapeutic mice model. In conclusion, we have constructed a subunit vaccine LTB-EMY162 which has prevention and therapeutic effect against E. multilocularis infection.


Asunto(s)
Echinococcus multilocularis/inmunología , Vacunas de Subunidad/inmunología , Animales , Anticuerpos Antihelmínticos/inmunología , Antígenos Helmínticos/administración & dosificación , Antígenos Helmínticos/genética , Antígenos Helmínticos/inmunología , Echinococcus multilocularis/genética , Echinococcus multilocularis/crecimiento & desarrollo , Femenino , Humanos , Interferón gamma/inmunología , Interleucina-4/inmunología , Estadios del Ciclo de Vida , Activación de Linfocitos , Ratones , Ratones Endogámicos BALB C , Linfocitos T/inmunología , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/genética , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunología
8.
Zhong Yao Cai ; 37(9): 1640-3, 2014 Sep.
Artículo en Zh | MEDLINE | ID: mdl-25857168

RESUMEN

OBJECTIVE: To investigate the role of Tibetan medicine-Twenty Wei Chenxiang Pill interfering with serum ET-1 level, in order to confirm that ET-1 is involved to the pathogenesis of hypoxic pulmonary hypertension. METHODS: 165 Wistar rats were randomly divided into high altitude control group,Tibetan medicine-Twenty Wei Chenxiang Pill group and plain control group. The physiological signal acquisition system was used to record pulmonary arterial pressure, and RV/(LV + S) ratio were caculated. Serum HIF-1alpha and ET-1 protein levels were determined by the method of ELISA, and ETA protein levels in lung tissue were determined by Western Blot method. RESULTS: Compared with the high altitude group,in the rats of Tibetan medicine-Twenty Wei Chenxiang Pill group,the pulmonary arterial pressure decreased significantly from the seventh day and the seventh day (P < 0.01), the RV/(LV + S) ratio and serum HIF-1alpha levels decreased significantly from the third day (P < 0.05 or P < 0.01), the serum ET-1 levels decreased significantly from the third day (P < 0.05 or P < 0.01), and the expression of ETA protein decreased significantly from the beginning (P < 0.01 or P < 0.001). CONCLUSION: ET-1 is one of the important factors causing pulmonary artery pressure increasing and right ventricular wall thickening, which plays a role in hypoxic pulmonary artery only involved in the early period hypoxia, but not in the later period. Tibetan medicine--twenty Wei Chenxiang Pill can prevent the pulmonary artery hypertension and the right ventricular wall thickening in rats, and its mechanism may be related to the direct inhibition of ET-1 and protein levels of ETA or the indirect downregulation of ET-1 level and ETA through inhibition of HIF-la level.


Asunto(s)
Hipertensión Pulmonar , Hipoxia , Medicina Tradicional Tibetana , Animales , Presión Arterial , Subunidad alfa del Factor 1 Inducible por Hipoxia , Pulmón , Arteria Pulmonar , Ratas , Ratas Wistar
9.
Fitoterapia ; 177: 106094, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38936674

RESUMEN

In the present study, six new compounds namely, picralactones CH (1-6) along with nine known compounds (7-15) were isolated from the branches and leaves of Picrasma chinese P.Y. Chen. Their structures were determined with the help of spectroscopic techniques such as NMR, HR-ESI-MS, UV, IR and CD. Cytotoxicity of all compounds was evaluated against MDA-MB-231, SW-620 and HepG2 human cancer cell lines. Compound 4 showed cytotoxic activities.

10.
Nat Prod Res ; 38(5): 838-847, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37139787

RESUMEN

Three new diterpenoids, named nematocynine A-C (1-3), together with twelve known compounds (4-15) were isolated from the aerial part of Euphorbia nematocypha Hand.-Mazz (Hereinafter referred to E. nematocypha). Their structures were elucidated by detailed spectroscopic analysis and comparison with literature data. In addition, all the compounds were tested for their anti-candida albicans activities used alone or in combination with fluconazole against sensitive strain and resistant strain in vitro. Wherein only compound 11 shows weak activity against candida albicans resistant strain (MIC50 = 128.15 µg/mL) when used alone. Compounds 1, 4, 7, 8, 9, 10, 12, 13 and 15 in combination with fluconazole showed potent anti-fungal activities (MIC50 = 15 ± 5 µg/mL, FICI = 0.05 ± 0.04) against the Candida albicans resistant strain SC5314-FR. The synergistic effects were weaker against the Candida albicans resistant strain SC5314-FR when the compounds 2, 3, 5 and 14 were combined with fluconazole (FICI = 0.16 ± 0.06).


Asunto(s)
Diterpenos , Euphorbia , Fluconazol/farmacología , Euphorbia/química , Candida albicans , Diterpenos/farmacología , Antifúngicos/farmacología , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Fúngica
11.
J Tradit Chin Med ; 33(3): 355-60, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24024332

RESUMEN

OBJECTIVE: To investigate the underlying mechanism of reduced myocardial ischemia-reperfusion (I/R) injury in rats using the traditional Tibetan medicine Sanweitanxiang powder (SWTX). METHODS: Rats were randomly divided into six groups (n = 10) as follows: (a) propranolol dinitrate control group, given propranolol dinitrate 0.02 g/kg for 10 days before I/R, (b) SWTX with a high dose group, given SWTX 1.5 g/kg for 10 days before I/R, (c) SWTX with a medium dose group, given SWTX 1.25 g/kg for 10 days before I/R, (d) sham group (Sham), in which the rat heart was exposed by pericardiotomy but without I/R, (e) SWTX with a low dose group, given SWTX 1.0 g/kg for 10 days before I/R, and (f) I/R injury group. Rats were intragastrically pretreated with propranolol dinitrate or SWTX. After that, the operation to cause ischemia and reperfusion was conducted. The histopathologic changes of rat hearts were observed by hematoxylin and eosin staining and transmission electron microscopy. Ca2+ homeostasis protein expression was determined by western blot. RESULTS: After SWTX pretreatment, the development of ultrastructural pathological changes from IR injury was attenuated. A decrease in the expression of B-cell lymphoma 2 associated X protein, and an increase in the expression of B-cell lymphoma 2 were observed. An increased activation of extracellular signal regulated kinases were found. Compared with the sham group, the expression of sarcoplasmic reticulum calcium-ATPase, phospholamban, and calsequestrin were all up-regulated after pretreatment with SWTX. CONCLUSION: The protective mechanism of SWTX pretreatment on myocardial I/R injury might be related to its effect on maintaining the balance of calcium homeostasis in rat heart.


Asunto(s)
Calcio/metabolismo , Medicamentos Herbarios Chinos/administración & dosificación , Quinasas MAP Reguladas por Señal Extracelular/genética , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/genética , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/genética , Animales , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Homeostasis , Humanos , Masculino , Daño por Reperfusión Miocárdica/enzimología , Daño por Reperfusión Miocárdica/metabolismo , Ratas , Ratas Sprague-Dawley , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo
12.
Nat Prod Res ; 37(11): 1787-1796, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36095038

RESUMEN

Four new norceanothane-type triterpenes, cyclopalin A-D (1-4), and sixteen known compounds (5-20) were obtained from the fruits of Cyclocarya paliurus. Their structures were determined by spectroscopic data, experimental electronic circular dichroism (ECD) and X-ray single crystal analyses. All isolated compounds were assayed for their anti-HIV-1IIIB activity. Compound 18 exhibited potent anti-HIV-1IIIB activity with an EC50 value of 1.32 µM (SI = 151.52).


Asunto(s)
Juglandaceae , Triterpenos , Triterpenos/química , Frutas , Análisis Espectral , Juglandaceae/química , Hojas de la Planta/química
13.
J Ethnopharmacol ; 283: 114734, 2022 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-34648900

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies have shown that the active fraction of Rhodiola tangutica (Maxim.) S.H. Fu (ACRT) dilates pulmonary arteries and thwarts pulmonary artery remodelling. The dilatation effect of ACRT on pulmonary artery vascular rings could be reduced by potassium (K+) channel blockers. However the exact mechanisms of ACRT on ion channels are still unclear. AIM OF THE STUDY: This study aimed to investigate whether the effect of ACRT on K+ channels inhibits cell proliferation after pulmonary artery smooth muscle cells (PASMCs) are exposed to hypoxia. MATERIALS AND METHODS: The whole-cell patch-clamp method was used to clarify the effect of ACRT on the K+ current (IK) of rat PASMCs exposed to hypoxia. The mRNA and protein expression levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. The intracellular calcium (Ca2+) concentration ([Ca2+]i) values in rat PASMCs were detected by laser scanning confocal microscopy. The cell cycle and cell proliferation were assessed using flow cytometry analysis and CCK-8 and EdU assays. RESULTS: ACRT pretreatment alleviated the inhibition of IK induced by hypoxia in rat PASMCs. Compared with hypoxia, ACRT upregulated voltage-dependent K+ channel (Kv) 1.5 and big-conductance calcium-activated K+ channel (BKCa) mRNA and protein expression and downregulated voltage-dependent Ca2+ channel (Cav) 1.2 mRNA and protein expression. ACRT decreased [Ca2+]i, inhibited the promotion of cyclin D1 and proliferating cell nuclear antigen (PCNA) expression, and prevented the proliferation of rat PASMCs exposed to hypoxia. CONCLUSION: In conclusion, the present study demonstrated that ACRT plays a key role in restoring ion channel function and then inhibiting the proliferation of PASMCs under hypoxia, ACRT has preventive and therapeutic potential in hypoxic pulmonary hypertension.


Asunto(s)
Músculo Liso Vascular/efectos de los fármacos , Extractos Vegetales/farmacología , Arteria Pulmonar/efectos de los fármacos , Rhodiola/química , Animales , Calcio/metabolismo , Hipoxia de la Célula , Proliferación Celular/efectos de los fármacos , Hipertensión Pulmonar/tratamiento farmacológico , Masculino , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/efectos de los fármacos , Técnicas de Placa-Clamp , Canales de Potasio/efectos de los fármacos , Canales de Potasio/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Arteria Pulmonar/citología , Ratas , Ratas Sprague-Dawley
14.
Technol Cancer Res Treat ; 20: 15330338211068964, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34939467

RESUMEN

Background: Next generation sequencing (NGS) has systematically investigated the genomic landscape of soft tissue sarcoma (STS) in Western patients, but few reports have described the utility of NGS in identifying pathogenic and targetable mutations in Asian patients. Methods: We review our single center experience of identifying the genomic profile and feasible genetic mutations in 65 Chinese patients with STS by NGS. Results: On average, 3.35 mutations were identified per patient (range, 0-28), and at least one mutation could be detected in 95.4% (62/65) of patients. TP53, MDM2, CDK4, KDR, and NF1 were the most frequent mutation genes in Chinese STS patients. Actionable mutations were discovered in 36.9% (24/65) of patients, and clinical benefit was achieved in 4 patients treated with corresponding molecular targeted therapies. Conclusions: Our study describes the mutation profile of Chinese STS patients by a single center experience. Some patients have achieved improved clinical outcomes by adopting treatment based on the results of genetic testing. NGS may affect clinical decision-making as a routine clinical test for patients with STS.


Asunto(s)
Biomarcadores de Tumor , Variación Genética , Secuenciación de Nucleótidos de Alto Rendimiento , Neoplasias de los Tejidos Blandos/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Biología Computacional/métodos , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Mutación , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/terapia , Adulto Joven
15.
Brain Behav ; 10(10): e01804, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32841552

RESUMEN

OBJECTIVES: Sequelae of stroke were mainly caused by neuronal injury. Oxygen is a key factor affecting the microenvironment of neural stem cells (NSCs), and oxygen levels are used to promote NSC neurogenesis. In this study, effects of intermittent hypoxic preconditioning (HPC) on neurogenesis were investigated in a rat model of middle cerebral artery occlusion (MCAO). METHODS: SD rats were used to establish the MCAO model. Nissl staining and Golgi staining were used to confirm the neuronal injury status in the MCAO model. Immunofluorescence, transmission electron microscopy, Western blot, and qPCR were used to observe the effects of HPC on neurogenesis. At the same time, the hypothesis that HPC could affect proliferation, apoptosis, differentiation, and migration of NSC was verified in vitro. RESULTS: Hypoxic preconditioning significantly ameliorated the neuronal injury induced by MCAO. Compared with MCAO group, the dendrites, Edu+ /SOX2+ , Edu+ /DCX+ , Edu+ /NeuN+ , Edu+ /GFAP+ , and Edu+ /Tubulin+ positive cells in the HPC + MCAO group exhibited significantly difference. Similarly, axonal and other neuronal injuries in the HPC + MCAO group were also ameliorated. In the in vitro experiments, mild HPC significantly enhanced the viability of NSCs, promoted the migration of differentiated cells, and reduced apoptosis. CONCLUSIONS: Our results showed that HPC significantly promotes neurogenesis after MCAO and ameliorates neuronal injury.


Asunto(s)
Isquemia Encefálica , Células-Madre Neurales , Animales , Proteína Doblecortina , Infarto de la Arteria Cerebral Media , Neurogénesis , Neuronas , Ratas , Ratas Sprague-Dawley
16.
Biomed Res Int ; 2020: 9204708, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32047820

RESUMEN

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.


Asunto(s)
Médula Ósea/metabolismo , Proliferación Celular/fisiología , Hipoxia/metabolismo , Interleucina-6/metabolismo , Janus Quinasa 2/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Microvasos/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Enfermedad Crónica , Modelos Animales de Enfermedad , Regulación hacia Abajo , Hipoxia/patología , Masculino , Microvasos/patología , Fosforilación , Ratas , Ratas Sprague-Dawley , Factor de Transcripción STAT3/efectos de los fármacos , Regulación hacia Arriba
17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 29(1): 165-8, 2009 Jan.
Artículo en Zh | MEDLINE | ID: mdl-19385230

RESUMEN

Goldview marked DNA fluorescence capillary biosensor was studied in the present paper. Based on fluorescence capillary analysis (FCA), the DNA biosensor uses capillary as immobilization carrier and detection carrier of DNA probe. Probes (20-mer-ssDNA) were immobilized on the inner wall of capillary by poly-l-lysine, and DNA fluorescence capillary biosensor (DNA-FCB) was made. After being hybridized with complementary target DNA and dyed by Goldview, the target DNA was qualified or quantified by detecting the fluorescence density of the Goldview using F-4500 spectrofluorometer. The sample volume was 12 microL. The concentration of the target DNA showed good linearity with the fluorescence intensity in the range of 0. 4-4 micromol x L(-1) (2.4-24 mg x L(-1)) (y = 65.911x + 3.9944, r = 0.9989). The RSD was lower than 3.5%. The concentration detection limit of the target DNA was 0.39 micromol x L(-1) (2.2 mg x L(-1)). The DNA-FCB can be used to qualify or quantify the target DNA. It's advantages are simplicity of manipulation, thimbleful of sample and reagent volumes, repeated use of capillary, and the lowest test cost. By using DNA-FCB to qualify the target DNA, we can consumedly decrease the pollution of the environment.


Asunto(s)
Técnicas Biosensibles/métodos , Tecnología de Fibra Óptica/métodos , Fluorescencia , Colorantes Fluorescentes/análisis , Capilares , ADN , Sondas de ADN , Enzimas Inmovilizadas , Fibras Ópticas/estadística & datos numéricos , Investigación , Espectrometría de Fluorescencia
18.
High Alt Med Biol ; 20(2): 112-119, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30192653

RESUMEN

Background/Aims: High-altitude polycythemia is defined by the increase of hematocrit and hemoglobin at high altitudes caused by production of excessive erythrocytes. Eryptosis is a process by which mature erythrocytes undergo self-destruction sharing several features with apoptosis. However, the eryptosis in high-altitude hypobaric hypoxia is unknown. Thus, the main purpose of this study was to investigate whether chronic hypoxia affected eryptosis and, if so, by what mechanisms. Methods: Biotin labeling technology was utilized to study the survival of red blood cells in chronic hypoxia. Flow cytometry was used to determine the volume of mature erythrocytes from forward scatter, phosphatidylserine scrambling from annexin-V-binding, intracellular Ca2+ from Fluo-3-AM, reactive oxygen species (ROS) abundance from ROS-probe, and ceramide and CD47 abundance utilizing specific antibodies. Results: The volume of mature erythrocytes was significantly changed, and the percentage of annexin-V-binding cells was significantly decreased under chronic hypobaric hypoxia. Erythrocyte survival was improved under chronic hypoxia, and chronic hypoxia resulted in a decrease in intracellular Ca2+in vivo and influenced eryptosis which was induced by the Ca2+-ionophore ionomycin (1 µM, 60 minutes) in vitro. Chronic hypoxia also resulted in an increase in CD47 and ceramide abundance, but it had no effect on ROS formation. Conclusions: Chronic hypobaric hypoxia can inhibit eryptosis by decreasing intracellular Ca2+ and increasing integrin-associated protein CD47.


Asunto(s)
Eriptosis , Eritrocitos/citología , Hipoxia/metabolismo , Animales , Antígeno CD47/metabolismo , Calcio/metabolismo , Ionóforos de Calcio , Supervivencia Celular , Células Cultivadas , Ceramidas/metabolismo , Citometría de Flujo , Ionomicina , Modelos Animales , Ratas Sprague-Dawley
19.
Gene ; 533(2): 532-7, 2014 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-24076356

RESUMEN

The Tibetan antelope (Pantholops hodgsonii) is a hypoxia-tolerant species that lives at an altitude of 4,000-5,000 m above sea level on the Qinghai-Tibetan plateau. Myoglobin is an oxygen-binding cytoplasmic hemoprotein that is abundantly expressed in oxidative skeletal and cardiac myocytes. Numerous studies have implicated that hypoxia regulates myoglobin expression to allow adaptation to conditions of hypoxic stress. Few studies have yet looked at the effect of myoglobin on the adaptation to severe environmental stress on TA. To investigate how the Tibetan antelope (TA) has adapted to a high altitude environment at the molecular level, we cloned and analyzed the myoglobin gene from TA, compared the expression of myoglobin mRNA and protein in cardiac and skeletal muscle between TA and low altitude sheep. The results indicated that the full-length myoglobin cDNA is composed of 1154 bp with a 111 bp 5' untranslated region (UTR), a 578 bp 3' UTR and a 465 bp open reading frame (ORF) encoding a polypeptide of 154 amino acid residues with a predicted molecular weight of 17.05 kD. The TA myoglobin cDNA sequence and the deduced amino acid sequence were highly homologous with that of other species. When comparing the myoglobin sequence from TA with the Ovis aries myoglobin sequence, variations were observed at codons 21 (GGT→GAT) and 78 (GAA→AAG), and these variations lead to changes in the corresponding amino acids, i.e., Gly→Asp and Glu→Lys, respectively. But these amino acid substitutions are unlikely to effect the ability of binding oxygen because their location is less important, which is revealed by the secondary structure and 3D structure of TA myoglobin elaborated by homology modeling. However, the results of myoglobin expression in cardiac and skeletal muscles showed that they were both significantly higher than that in plain sheep not only in mRNA but also protein level. We speculated that the higher expression of myoglobin in TA cardiac and skeletal muscles improves their ability to obtain and store oxygen under hypoxic conditions. This study indicated that TA didn't improve the ability of carrying oxygen by changing the molecular structure of myoglobin, but through increasing the expression of myoglobin in cardiac and skeletal muscles.


Asunto(s)
Aclimatación/genética , Altitud , Antílopes/genética , Mioglobina/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Clonación Molecular , Expresión Génica , Datos de Secuencia Molecular , Mioglobina/química , Filogenia , Análisis de Secuencia de ADN , Especificidad de la Especie
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