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OBJECTIVES: To observe the effect of heat-reinforcing needling (HRN) on synovial inflammation, hypoxia-inducible factor-1α (HIF-1α) and glycolytic activity in serum and synovial tissue in rabbits with cold syndrome of rheumatoid arthritis (RA), so as to explore its mechanisms underlying improvement of RA. METHODS: A total of 32 rabbits were randomly divided into normal, model, inhibitor and HRN groups, with 8 rabbits in each group. The RA with cold syndrome model was induced by injecting ovalbumin dry powder and Freund's complete adjuvant combined with cold freezing. Rabbits in the inhibitor group were intraperitoneally injected with 2-methoxyestradiol (2.5 mg/kg), rabbits in the HRN group were received HRN at bilateral "Zusanli" (ST36) for 30 min. The treatments were conducted once daily for 14 consecutive days. After the interventions, the knee circumference and pain threshold were measured. The contents of nicotinamide adenine dinucleotide phosphoric (NADPH), Hexokinase II (HK2) and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) in serum of rabbits were detected by ELISA. The pathological morphology of synovial tissue of the knee joints were observed by HE staining. The positive expressions of tumor necrosis factor (TNF-α), interleukin (IL)-1ß, IL-6 and IL-17 in synovial tissue of knee joint were detected by immunohistochemistry. The content of lactic acid in synovial tissue of rabbit knee joint was detected by spectrophotometry. The expression levels of HIF-1α, pyruvate kinase 2 (PKM2) and lactate dehydrogenase (LDHA) in synovial tissue of knee joint were detected by Western blot. RESULTS: After intervention, compared with the normal group, the knee circumference was significantly enlarged (P<0.05), the pain threshold was significantly decreased (P<0.05)ï¼the synovial tissue of knee joints showed significant cell proliferation and inflammatory infiltration, the pathological score was significantly increased (P<0.05)ï¼positive expressions of TNF-α, IL-1ß, IL-6 and IL-17, the content of lactic acid in synovial tissue, the contents of NADPH, HK2 and PFKFB3 in serum, and the protein expression levels of HIF-1α, PKM2 and LDHA in synovial tissue were increased (all P<0.05) in the model group. Compared with model group, the circumference of knee joint was significantly decreased (P<0.05), the pain threshold was significantly increased (P<0.05)ï¼in synovial tissue, the pathological score was decreased (P<0.05)ï¼the positive expressions of TNF-α, IL-1ß, IL-6 and IL-17 in synovial tissue were decreased (P<0.05), the lactic acid content in synovial tissue was decreased (P<0.05)ï¼the contents of NADPH, HK2 and PFKFB3 in serum and the protein expression levels of HIF-1α, PKM2 and LDHA in synovial tissue were decreased (P<0.05) in inhibitor group and HRN group. Compared with the inhibitor group, the synovial pathological score was significantly increased (P<0.05), positive expressions of TNF-α, IL-1ß, IL-6 and IL-17, the content of lactic acid in synovial tissue, the contents of NADPH, HK2 and PFKFB3 in serum, and the protein expression levels of HIF-1α, PKM2 and LDHA in synovial tissue were increased (all P<0.05) in HRN group. CONCLUSIONS: HRN can increase the pain threshold, reduce the knee circumference and inhibit the inflammatory response in rabbits with cold syndrome of RA. The possible mechanism is related to the down-regulation of HIF-1α and glycolysis activity.
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Terapia por Acupuntura , Artrite Reumatoide , Glicólise , Subunidade alfa do Fator 1 Induzível por Hipóxia , Animais , Coelhos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Humanos , Artrite Reumatoide/terapia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/genética , Masculino , Feminino , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/genética , Pontos de Acupuntura , Interleucina-6/genética , Interleucina-6/metabolismoRESUMO
INTRODUCTION: Panax ginseng and Panax quinquefolium are traditional Chinese herb medicines and similar in morphology and some chemical components but differ in drug properties, so they cannot be mixed. However, the processed products of them are often sold in the form of slices, powder, and capsules, which are difficult to identify by traditional morphological methods. Furthermore, an accurate evaluation of P. ginseng, P. quinquefolium and the processed products have not been conducted. OBJECTIVE: This study aimed to establish a catalysed hairpin assembly (CHA) identification method for authenticating products made from P. ginseng and P. quinquefolium based on single nucleotide polymorphism (SNP) differences. METHOD: By analysing the differences of SNP in internal transcribed spacer 2 (ITS2) in P. ginseng and P. quinquefolium to design CHA-specific hairpins. Establish a sensitive and efficient CHA method that can identify P. ginseng and P. quinquefolium, use the sequencing technology to verify the accuracy of this method in identifying Panax products, and compare this method with high-resolution melting (HRM). RESULTS: The reaction conditions of CHA were as follows: the ratio of forward and reverse primers, 20:1; hairpin concentration, 5 ng/µL. Compared with capillary electrophoresis, this method had good specificity and the limit of detection was 0.5 ng/µL. The result of Panax product identification with CHA method were coincidence with that of the sequencing method; the positive rate of CHA reaction was 100%. CONCLUSION: This research presents an effective identification method for authenticating P. ginseng and P. quinquefolium products, which is helpful to improve the quality of Panax products.
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Panax , Panax/genética , Panax/química , Medicina Tradicional Chinesa , Polimorfismo de Nucleotídeo Único , TecnologiaRESUMO
OBJECTIVE: To observe the effect of heat-reinforcing needling (HRN) on inflammatory factors and necrotizing apoptosis of synovial cells in synovial tissues of knee joint in rabbits with cold syndrome rheumatoid arthritis (RA), so as to explore its underlying mechanisms in treating RA. METHODS: By using the random number table method, 40 New Zealand rabbits were randomly divided into normal, model, antagonist(AG), twist-reinforceing needling (TRN) and HRN groups, with 8 rabbits in each group. The model of cold syndrome RA was established by ovalbumin induction combined with Freund's complete adjuvant injection and cryogenic freezing method. In the AG group, the antagonist TAK-632 (25 mg/kg) was administered intragastrically, once every 2 days, for a total of 7 times. Rabbits of TRN and HRN groups were treated with corresponding acupuncture techniques on bilateral "Zusanli" (ST36) for 30 min, once a day for 14 days. After intervention, the changes of knee skin temperature and circumference were measured. Color Doppler ultrasound was used to observe the joint cavity effusion, synovial thickness and internal blood flow signal. The histomorphological changes of synovial tissues were observed after HE staining. ELISA was used to detect the contents of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 in serum. Transmission electron microscope was used to observe the ultrastructure, necrosis and apoptosis of synovial cells. Western blot was used to detect the protein expressions of receptor-interacting protein kinase1 (RIPK1), RIPK3, mixed lineage kinase domain-like protein (MLKL), and phosphorylation ï¼pï¼-MLKL in synovial tissues. RESULTS: Compared with the normal group, the synovial was diffusely hyperplasia, joint cavity effusion and abnormal blood flow signal were obvious, inflammatory cells were clustered, arranged closely and disordered in the model group. The findings of transmission electron microscopy showed disruption of cell membrane integrity, swollen or ruptured mitochondria, obviously ruptured nucleus, condensed and pyknotic chromatin and nucleolus in the model group. Also, the skin temperature of the knee joint was significantly decreased (P<0.01), while the circumference of the knee joint, the contents of TNF-α, IL-1ß and IL-6 in serum, the protein expressions of RIPK1, RIPK3, p-MLKL and MLKL in synovial tissues were significantly increased (P<0.01) in the model group. Compared with the model group, synovial tissue hyperplasia, joint cavity effusion, abnormal blood flow signals, synovial cell proliferation, inflammatory cell infiltration, disruption of cell membrane integrity, cell swelling, cell rupture, and nuclear pyknosis were reduced to different degrees in the AG, TRN and HRN groups. Additionally, the skin temperature of the knee joint was increased (P<0.01, P<0.05), while the circumference of the knee joint, the contents of TNF-α, IL-1ß and IL-6 in serum, the expressions of RIPK1, RIPK3, p-MLKL and MLKL in synovial tissues were decreased (P<0.01, P<0.05) in the AG, TRN and HRN groups. The effects of HRN and AG were notably superior to that of TRN in up-regulating skin temperature of the knee joint, and down-regulating the circumference of the knee joint, the contents of TNF-α, IL-1ß and IL-6 in serum, the expressions of RIPK1, RIPK3, p-MLKL and MLKL in synovial tissues (P<0.01, P<0.05). CONCLUSION: HRN can reduce synovial inflammation of knee joint in rabbits with cold syndrome RA, which may be related to its function in inhibiting the necrotizing apoptosis of synovial cells.
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Artrite Reumatoide , Temperatura Alta , Animais , Coelhos , Apoptose , Artrite Reumatoide/genética , Artrite Reumatoide/terapia , Hiperplasia , Inflamação/genética , Inflamação/terapia , Interleucina-6/genética , Articulação do Joelho , Fator de Necrose Tumoral alfa/genéticaRESUMO
OBJECTIVE: To observe the effects of heat-reinforcing needling on synovial inflammation and microRNA-155 (miR-155)/Toll-like receptor 4 (TLR4)/nuclear transcription factor-κB (NF-κB) signaling axis, so as to investigate its anti-inflammatory mechanism in rabbits with cold syndrome of rheumatoid arthritis (RA). METHODS: A total of 36 rabbits were randomly divided into normal, model, agonist, inhibitor, heat-reinforcing needling (HRN) and agonist+heat-reinforcing needling (A+HRN) groups, with 6 rabbits in each group. The RA with cold syndrome model was induced by injecting ovalbumin dry powder and Freund's complete adjuvant combined with cold freezing. Rabbits in agonist group were intraperitoneally injected with miR-155 agomir 4.5 OD; rabbits in the inhibitor group were intraperitoneally injected with miR-155 antagomir 6.1 OD; rabbits in HRN group received heat-reinforcing needling at bilateral "Zusanli" (ST36) for 30 minï¼rabbits in A+HRN group received the same treatment as agonist group, and 30 min later, received the same treatment as the HRN group; rabbits in the normal and model groups were grasped and fixed in the same way, all groups received continuous treatment once a day for 7 d. After modeling, the knee joints of rabbits were examined by ultrasound, the pain threshold and the circumference were determined. After the interventions, the pain threshold and knee circumference were measured; the pathological morphology of synovial tissue of the knee joints were observed by HE staining; the mRNA levels of miR-155 and suppressor of cytokine signaling protein 1 (SOCS1), the expression levels of SOCS1, TLR4, NF-κB p65, interleukin (IL)-1ß and IL-17A proteins in synovial tissue of knee joints were detected by real-time PCR and Western blot respectively. RESULTS: Compared with the normal group, the pain threshold was significantly decreased (P<0.05), and the knee circumference was significantly increased (P<0.05); the synovial tissue of knee joints showed significant hyperplasia, abundant blood flow signal, joint cavity effusion and obvious inflammatory invasion, the pathological score was significantly increased (P<0.05), the expressions of miR-155 mRNA and IL-1ß, IL-17A, TLR4, NF-κB p65 proteins were significantly increased (P<0.05), the expressions of SOCS1 mRNA and protein were significantly decreased (P<0.05) in the model group. Compared with model group, the pain threshold was significantly increased (P<0.05), the circumference of knee joint was significantly decreased (P<0.05); in synovial tissue, the pathological score was decreased (P<0.05), the expression levels of miR-155 mRNA and IL-1ß, IL-17A, TLR4, NF-κB p65 proteins were significantly decreased (P<0.05), and the expressions of SOCS1 mRNA and protein were significantly increased (P<0.05) in inhibitor group and HRN group, while the above changes in agonist group were reversed (P<0.05). Compared with the agonist group, the pain threshold was significantly increased (P<0.05), the knee circumference was significantly decreased (P<0.05), the synovial pathological score was significantly decreased (P<0.05), the expressions of miR-155 mRNA and IL-1ß, IL-17A, TLR4, NF-κB proteins in synovial tissue were significantly decreased (P<0.05), and the expression levels of SOCS1 mRNA and protein were significantly increased (P<0.05) in A+HRN group. CONCLUSION: The heat-reinforcing needling can increase the pain threshold, reduce the knee circumference and inhibit the inflammatory response in rabbits with RA cold syndrome. The possible mechanism is related to the regulation of miR-155/TLR4/NF-κB signaling axis.
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Artrite Reumatoide , MicroRNAs , Animais , Coelhos , NF-kappa B , Receptor 4 Toll-Like , Interleucina-17 , Temperatura Alta , InflamaçãoRESUMO
Melatonin,an endocrine hormone synthesized by the pineal gland,plays an important role in the reproduction.The growth and development of follicles is the basis of female mammalian fertility.Follicles have a high concentration of melatonin.Melatonin receptors exist on ovarian granulosa cells,follicle cells,and oocytes.It regulates the growth and development of these cells and the maturation and atresia of follicles,affecting female fertility.This paper reviews the protective effects and regulatory mechanisms of melatonin on the development of ovarian follicles,granulosa cells,and oocytes and makes an outlook on the therapeutic potential of melatonin for ovarian injury,underpinning the clinical application of melatonin in the future.
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Melatonina , Animais , Feminino , Melatonina/farmacologia , Folículo Ovariano , Oócitos , Células da Granulosa/fisiologia , MamíferosRESUMO
OBJECTIVE: To observe the effect of heat-reinforcing needling on the expression of serum inflammatory factors and autophagy of knee synovial tissue in rheumatoid arthritis (RA) rabbits with cold syndrome, so as to explore its mechanism of anti-inflammatory in the treatment of RA. METHODS: Fifty rabbits were randomly divided into normal, model, heat-reinforcing needling, inhibitor and agonist groups (n=10 rabbits in each group). The model of RA with cold syndrome was established by Freund's adjuvant and ovalbumin mixed solution injection combined with freezing and wind-cold dampness method. Heat-reinforcing needling was applied at "Zusanli" (ST36) for 30 min, once a day for 14 days. Rabbits of the inhibitor and agonist groups were given intraperitoneally injected with autophagy inhibitor 3-methyladenine (3-MA) or autophagy agonist rapamycin, once every 2 days for 7 days. The knee circumference and skin temperature of the rabbits in each group were measured. Color doppler ultrasonography was applied to examine the synovial membrane, joint effusion and blood flow signals in the knee joints of the rabbits in each group. Serum tumor necrosis factor (TNF) -α, interleukin (IL)-1ß, IL-6 and C-creactive protein (CRP) were detected by ELISA. Transmission electron microscopy was applied to observe the ultrastructure and autophagosomes of synovial cells. The protein expressions of autophagy-related protein Atg5, serine/threonine protein kinase-dysregulated 51-like kinase 1 (ULK1), microtubule-associated protein light chain 3B (LC3B), and Beclin-1 were detected by Western blot. Fluorescence quantitative PCR was used to detect the mRNA expressions of NOD-like receptor 3 (NLRP3) and nuclear factor-κB (NF-κB). RESULTS: Compared with the normal group, the circumference of the knee joint was increased (P<0.01), the skin temperature was decreased (P<0.01), the knee joint synovium was thickened and the blood flow signal was abundant, the contents of serum TNF-α, IL-1ß, IL-6, and CRP were increased (P<0.01), the protein expressions of Atg5, ULK1, Beclin-1 and LC3Bâ ¡/LC3Bâ of synovial tissue were significantly decreased (P<0.01), the mRNA expressions of NLRP3 and NF-κB were increased (P<0.01) in the model group. In comparison with the model and inhibitor groups, the circumference of the knee joint was decreased (P<0.01), whlie the skin temperature was increased (P<0.01), the synovial membrane became thinner and the blood flow signal was wea-kened, the contents of TNF-α, IL-1ß, IL-6 and CRP were decreased (P<0.01), the protein expressions of Atg5, ULK1, Beclin-1 and LC3B â ¡/LC3B â were increased (P<0.01), and the mRNA expressions of NLRP3 and NF-κB were decreased (P<0.01) in the heat-reinforcing needling and agonist groups. CONCLUSION: Heat-reinforcing needling can alleviate the inflammatory response of the knee joint synovium in RA rabbits with cold syndrome, which may be related to its function in enhancing the autophagy activity of synovial cells and inhibiting the synthesis and release of inflammatory factors TNF-α, IL-1ß, IL-6 and CRP.
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Artrite Reumatoide , NF-kappa B , Animais , Coelhos , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Artrite Reumatoide/terapia , Autofagia/genética , Proteína Beclina-1/metabolismo , Proteína Beclina-1/farmacologia , Adjuvante de Freund/metabolismo , Adjuvante de Freund/farmacologia , Temperatura Alta , Inflamação , Interleucina-6/metabolismo , Articulação do Joelho , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/farmacologia , NF-kappa B/genética , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ovalbumina/metabolismo , Ovalbumina/farmacologia , Proteínas Quinases/metabolismo , Proteínas Quinases/farmacologia , RNA Mensageiro/metabolismo , Serina/metabolismo , Serina/farmacologia , Sirolimo/metabolismo , Sirolimo/farmacologia , Membrana Sinovial/metabolismo , Treonina/metabolismo , Treonina/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
AIMS: Inhibitor of soluble epoxide hydrolase (t-AUCB) has been used in the experimental therapy of hypertension. This study aimed to investigate whether the secretion of submandibular glands (SMGs) altered in renal hypertensive rats, and to explore whether t-AUCB could improve the salivary secretion. MAIN METHODS: 2-kidney 1-clip Sprague-Dawley rats were used as renal hypertensive animals. t-AUCB treatment was given for 1 week after 8 weeks modeling. Blood pressure, blood perfusion and the secretion of SMGs, and endothelium-dependent relaxation of external maxillary artery were measured to investigate the effects of t-AUCB on the vascular tone and the secretion of SMGs in renal hypertensive rats. SMGs were collected for histological evaluation and the internal arteries were dissected for primary endothelial cells culture. KEY FINDINGS: The blood perfusion and flow rate of SMGs in the renal hypertensive rats were significantly lower than those in the controls. Endothelium-dependent relaxation of the external maxillary artery and AMPK/Akt/eNOS signaling was impaired in hypertensive rats. The glandular morphology and the concentration of salivary ions did not change obviously. t-AUCB treatment ameliorated the secretion of SMGs, the blood perfusion, and the dysfunction of endothelium-dependent relaxation of the external maxillary artery by activating the AMPK/Akt/eNOS pathway in hypertensive rats. SIGNIFICANCE: t-AUCB increases the blood perfusion through ameliorating dysfunction of endothelium-dependent relaxation of SMGs arteries and thus improves the hyposecretion of SMGs in hypertensive rats.
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Epóxido Hidrolases , Hipertensão , Proteínas Quinases Ativadas por AMP , Animais , Benzoatos , Células Endoteliais/metabolismo , Endotélio/metabolismo , Inibidores Enzimáticos/farmacologia , Epóxido Hidrolases/metabolismo , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Proteínas Proto-Oncogênicas c-akt , Ratos , Ratos Sprague-Dawley , Glândulas Salivares/metabolismo , Ureia/análogos & derivadosRESUMO
Background: Most first-year college/university students are adolescents or young adults and therefore are at high risk of developing psychological distress symptoms. Little is known about psychological distress among first-year university students in Taiwan, especially those studying health science-related fields. Objective: To understand the prevalence of psychological distress and its five dimensions (depression and anxiety, self-harm, impulsivity, and psychiatric disturbance) and explore the relationship between student-specific variables (enrollment year, age, sex, program duration, and college) and psychological distress. Methods: A secondary analysis design was adopted. We enrolled 4,212 first-year university students throughout 2016, 2017, and 2018. Health screening data were obtained using the Mental Health Scale for Undergraduate-Screening Assessment (MHSU-SA) for first-year health science students at a private technical-vocational university in northern Taiwan. Results: Many first-year university students were at-risk for depression (4.2%), anxiety (8.2%), self-harm (5.2%), impulsivity (2.6%), psychiatric disturbance (4.4%), and overall psychological distress (4.2%). Students in a four-year program were more than twice as likely to demonstrate psychological distress symptoms compared to their two-year (night) program counterparts (odds ratio = 2.05, 95% confidence interval = 1.20-3.49, p < 0.01). Conclusion: Some first-year health science university students showed psychological distress, including anxiety, self-harm, psychiatric disturbance, depression, and impulsivity. Students in four-year programs were twice as likely to show symptoms of psychological distress than those in two-year (night) programs. Therefore, mental health screenings are recommended to facilitate early detection and timely intervention for at-risk students.
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BACKGROUND: Hyposalivation is one of the common symptoms of diabetes. Although long non-coding RNAs (lncRNAs) have recently been reported to play important roles in the pathogenesis of diabetes, the role of lncRNAs in diabetes-induced hyposalivation remains unknown. METHODS: The present study aimed to explore the function of lncRNA-microRNA-mRNA regulatory network in the submandibular gland (SMGs) under the context of diabetes. LncRNA expression profile of the SMGs was analyzed using microarray technology. Differentially expressed lncRNAs were confirmed using real-time quantitative PCR. Bioinformatics analyses were performed, and Coding-non-coding gene co-expression (CNC) and competing endogenous RNA (ceRNA) networks were constructed to explore the potential mechanisms of diabetes-induced hyposalivation. RESULTS: A total of 1273 differentially expressed lncRNAs (536 up-regulated and 737 downregulated) were identified in the SMGs tissues of db/db mice. CNC and ceRNA network analyses were performed based on five differentially expressed lncRNAs validated by real-time quantitative PCR. Gene Ontology analysis of target genes of CNC network revealed that "calcium ion binding" was a highly enriched molecular function. Kyoto Encyclopedia of Genes and Genomes pathway analysis of target genes of ceRNA network revealed that the "mammalian target of rapamycin signaling pathway" was significantly enriched. CONCLUSIONS: On the whole, the findings of the present study may provide insight into the possible mechanism of diabetes-induced hyposalivation.
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Diabetes Mellitus Experimental , MicroRNAs , RNA Longo não Codificante , Xerostomia , Animais , Diabetes Mellitus Experimental/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Mamíferos/genética , Mamíferos/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Glândula Submandibular/metabolismoRESUMO
OBJECTIVE: Obesity contributes to the dysfunction of salivary gland. To explore the specific underlying mechanism for obesity-induced hyposalivation, a model for high-fat diet-induced obese (DIO) mice were constructed to analyze long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) expression profiles. METHODS: The DIO group and control group were fed a diet containing 60 kcal% fat and a normal chow diet for 16 weeks respectively. Microarray analyses were performed to detect the expression profiles of lncRNA and mRNA in submandibular gland tissues from control group mice and DIO mice. Gene ontology, kyoto encyclopedia of genes and genomes, protein-protein interaction, coding-non-coding gene co-expression, transcription factors and competing endogenous RNA analyses were performed to examine the function of differentially expressed genes. RESULTS: Microarray analyses identified that 624 lncRNAs, along with 297 mRNAs were differentially expressed. Bioinformatic analyses revealed that "complement and coagulation cascades," "glutathione metabolism," "cysteine and methionine metabolism," and "estrogen signaling pathway" were significantly associated with candidate lncRNAs. Transcription factors analysis on candidate lncRNAs revealed several genes such as tribbles pseudokinase 3 may play regulatory roles. CONCLUSIONS: Our results revealed the expression profiles of lncRNAs and mRNAs and provided new insights into the mechanism of obesity-induced hyposalivation using bioinformatic analyses.
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RNA Longo não Codificante , Xerostomia , Animais , Dieta Hiperlipídica , Camundongos , Camundongos Obesos , Obesidade , RNA Longo não Codificante/genética , RNA Mensageiro/metabolismo , Glândula Submandibular/metabolismo , Fatores de Transcrição/genéticaRESUMO
Objectives: This study aimed to compare and rank the therapeutic effects of antivirals in treating hearing loss using a network meta-analysis approach. Methods: We searched the PubMed, Embase, and Cochrane Library databases to identify eligible randomized controlled trials (RCTs) through April 2022. Placebo-controlled or head-to-head RCTs of three categories of antivirals for hearing loss were included, and pooled relative risks (RRs) with 95% confidence interval (CI) were calculated using pairwise and network meta-analyses. Results: Six RCTs with 405 patients were included in the final analysis. The results showed that ganciclovir had relatively better effects on the incidence of hearing recovery (surface under the cumulative ranking: 88.8%) compared with other antivirals. However, pairwise comparison analyses found that the use of antivirals significantly increased the incidence of hearing recovery compared with the use of a placebo (RR: 1.27; 95% CI: 1.04-1.54; P = 0.017), while no significant difference was observed between any two categories of antivirals. Finally, the use of antivirals did not increase the risk of adverse events compared with the use of a placebo (RR: 1.27; 95% CI: 0.82-1.98; P = 0.285). Conclusion: Antivirals are more efficacious than placebos for hearing recovery in patients with hearing loss, and ganciclovir is the most likely to increase the incidence of hearing recovery.
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Ischemia-reperfusion (I/R) injury is a multifactorial process triggered when an organ is subjected to transiently reduced blood supply. The result is a cascade of pathological complications and organ damage due to the production of reactive oxygen species following reperfusion. The present study aims to evaluate the role of activated calcium-sensing receptor (CaR)-cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway in I/R injury. Firstly, an I/R rat model with CSE knockout was constructed. Transthoracic echocardiography, TTC and HE staining were performed to determine the cardiac function of rats following I/R Injury, followed by TUNEL staining observation on apoptosis. Besides, with the attempt to better elucidate how CaR-CSE/H2S affects I/R, in-vitro culture of human coronary artery endothelial cells (HCAECs) was conducted with gadolinium chloride (GdCl3, a CaR agonist), H2O2, siRNA against CSE (siCSE), or W7 (a CaM inhibitor). The interaction between CSE and CaM was subsequently detected. Plasma oxidative stress indexes, H2S and CSE, and apoptosis-related proteins were all analyzed following cell apoptosis. We found that H2S elevation led to the improvement whereas CSE knockdown decreased cardiac function in rats with I/R injury. Moreover, oxidative stress injury in I/R rats with CSE knockout was aggravated, while the increased expression of H2S and CSE in the aortic tissues resulted in alleviated the oxidative stress injury. Moreover, increased H2S and CSE levels were found to inhibit cell apoptotic ability in the aortic tissues after I/R injury, thus attenuating oxidative stress injury, accompanied by inhibited expression of apoptosis-related proteins. In HCAECs following oxidative stress treatment, siCSE and CaM inhibitor were observed to reverse the protection of CaR agonist. Coimmunoprecipitation assay revealed the interaction between CSE and CaM. Taken together, all above-mentioned data provides evidence that activation of the CaR-CSE/H2S pathway may confer a potent protective effect in cardiac I/R injury.
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Cistationina gama-Liase/metabolismo , Sulfeto de Hidrogênio/metabolismo , Substâncias Protetoras/metabolismo , Receptores de Detecção de Cálcio/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Apoptose , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Humanos , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologiaRESUMO
Current interdisciplinary medical training calls for reforms and innovations in the assessment of pathophysiology education. Formative assessment is used to monitor student learning to provide ongoing feedback that can improve both learning and teaching. Beginning in 2016, we implemented a formative assessment composed of case-based multiple-choice questions (MCQs) for all students in all majors. In 2017, case study questions began to be employed in the formative assessment, and student-set, case-based questions were further introduced. Aiming to gather the students' suggestions and feedback on the mixed-method assessment, we conducted a survey on aspects such as the effectiveness of the assessment, assessment content and completion, opinions on student-set questions, and the impact on pathophysiology learning for students from 2017 to 2019. In addition, we compared students' semesterly final scores with those of previous students and evaluated the relationship between formative and summative assessment scores. The results for 1,277 students clearly showed that the reformed formative assessment system was well received by the students. The students thought that the formative assessment not only allowed for the provision of real-time feedback on the effectiveness of teaching and learning but also nurtured self-motivation, the development of analytical and problem-solving skills, and collaborative efforts. Both the semesterly final scores and the proportions of students scoring in higher score ranges increased after the implementation of the formative assessment, and the summative assessment scores were positively related to the formative assessment scores. Consequently, the reformed formative assessment system significantly improved the quality of pathophysiology education.
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Educação de Graduação em Medicina , Estudantes de Medicina , Avaliação Educacional , Retroalimentação , Humanos , Inquéritos e QuestionáriosRESUMO
Aims: Vascular calcification is associated with cardiovascular death in patients with chronic kidney disease (CKD). Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) plays an important role in various cardiovascular diseases. However, its role in vascular calcification remains unknown. Results: Adenine-induced rat CKD model was used to induce arterial medial calcification. The level of PGC-1α decreased in abdominal aorta of CKD rats. Overexpression of PGC-1α significantly ameliorated calcium deposition in rat abdominal aorta, isolated carotid rings, and cultured vascular smooth muscle cells (VSMCs). Mitochondrial reactive oxygen species (mtROS) increased in calcifying aorta and VSMCs. Upregulation of PGC-1α inhibited, whereas PGC-1α depletion promoted ß-glycerophosphate-induced mtROS production and calcium deposition. Moreover, PGC-1α increased superoxide dismutase 1 (SOD1) and SOD2 contents in vivo and in vitro, whereas SOD2 deletion eliminated PGC-1α-mediated mtROS change and promoted calcium deposition. Mechanistically, sirtuin 3 (SIRT3) expression declined in calcifying aorta and VSMCs, while PGC-1α overexpression restored SIRT3 expression. Inhibition of SIRT3 by 3-TYP or siRNA (small interfering RNA) reduced PGC-1α-induced upregulation of SOD1 and SOD2, and abolished the protective effect of PGC-1α on calcification of VSMCs. Importantly, PGC-1α was reduced in calcified femoral arteries in CKD patients. In phosphate-induced human umbilical arterial calcification, upregulation of PGC-1α attenuated calcium nodule formation, while this protective effect was abolished by SIRT3 inhibitor. Innovation: We showed for the first time that PGC-1α is an important endogenous regulator against vascular calcification. Induction of PGC-1α could be a potential strategy to treat vascular calcification in CKD patients. Conclusions: PGC-1α protected against vascular calcification by SIRT3-mediated mtROS reduction.
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Mitocôndrias/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Insuficiência Renal Crônica/metabolismo , Sirtuína 3/metabolismo , Calcificação Vascular/metabolismo , Adenina/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Animais , Aorta Abdominal/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Estresse Oxidativo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Ratos , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/complicações , Calcificação Vascular/genéticaRESUMO
In this article, we analyze the clinical characteristics of five kinds of traditional Chinese medicine injections in treating heart failure based on Meta-analysis. A total of 24 Meta-analysis papers were included, which involved Shenfu Injection, Shenmai Injection, Shengmai Injection, Danhong Injection and Huangqi Injection. The numbers of literatures of Shenfu Injection, Shenmai Injection and Shengmai Injection are high than the other two injections. The efficiencies of these injections combined with Western medicine are higher than the Western medicine used alone. They can improve 6 minute walk test result, ejection fraction, the level of brain peptide sodium and so on. Shenfu Injection can also improve the living quality of patients' life, heart rate and other indicators. Shenfu Injection can be used for patients with Yin deficiency, while Shenmai Injection can be used for patients with Yin deficiency and Shengmai Injection can be used for patients with Qi and Yin deficiency. From this information, we can see that Western medicine combined with traditional Chinese medicine injections can significantly improve the clinical efficiency. These injections need to be used according to patients' symptom. In the present, as the quality of clinical research literature of traditional Chinese medicine injections is low, the efficiency and safety evaluation of Chinese medicine injections still requires higher level of clinical evidence.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Injeções , Medicina Tradicional Chinesa , Deficiência da Energia YinRESUMO
Traditional Chinese medicine (TCM) prescription is the main therapies for disease prevention and treatment in Chinese medicine. Following the guidance of the theory of TCM and developing drug by composing prescriptions of TCM materials and pieces, it is a traditional application mode of TCM, and still widely used in clinic. TCM prescription has theoretical advantages and rich clinical application experience in dealing with multi-factor complex diseases, but scientific research is relatively weak. The lack of scientific cognition of the effective substances and mechanism of Chinese medicine leads to insufficient understanding of the efficacy regularity, which affects the stability of effect and hinders the improvement of quality of Chinese medicinal products. Component-based Chinese medicine (CCM) is an innovation based on inheritance, which breaks through the tradition of experience-based prescription and realize the transformation of compatibility from herbal pieces to components. CCM is an important achievement during the research process of modernization of Chinese medicine. Under the support of three national "973" projects, in order to reveal the scientific connotation of the prescription compatibility theory and develop innovative Chinese drugs, we have launched theoretical innovation and technological innovation around the "two relatively clear", and opened up the research field of CCM. CCM is an innovation based on inheritance, breaking through the tradition of experience based prescription, and realizing the transformation from compatibility of herbal pieces to component compatibility, which is an important achievement of the modernization of traditional Chinese medicine. In the past more than 10 years, with the deepening of research and the expansion of application, the theory and methods of CCM and efficacy-oriented compatibility have been continuously improved. The value of CCM is not only in developing new drug, more important is to build a communication bridge between traditional Chinese medicine and modern science and construct the system of key technologies which meet the need of innovation and development of TCM. This paper focused on the research progress, related concepts and technology development of CCM, as well as its application prospect in the theory research of Chinese medicine, development of innovative Chinese drugs, secondary development of Chinese patent medicine and upgrading of pharmaceutical technology.
Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa/tendências , PrescriçõesRESUMO
Objectives: To examine the protective effect of Rhynchophylline (Rhy) on vascular endothelial function in spontaneous hypertensive rats (SHRs) and the underlying mechanism. Methods: Intrarenal arteries of SHRs and Wistar rats were suspended in myograph for force measurement. Expression and phosphorylation of endothelial nitric oxide (NO) synthase (eNOS), Akt, and Src kinase (Src) were examined by Western blotting. NO production was assayed by ELISA. Results: Rhy time- and concentration-dependently improved endothelium-dependent relaxation in the renal arteries from SHRs, but had no effect on endothelium-independent relaxation in SHR renal arteries. Wortmannin (an inhibitor of phosphatidylinositol 3-kinase) or PP2 (an inhibitor of Src) inhibited the improvement of relaxation in response to acetylcholine by 12 h-incubation with 300 µM Rhy. Western blot analysis revealed that Rhy elevated phosphorylations of eNOS, Akt, and Src in SHR renal arteries. Moreover, wortmannin reversed the increased phosphorylations of Akt and eNOS induced by Rhy, but did not affect the phosphorylation of Src. Furthermore, the enhanced phosphorylations of eNOS, Akt, and Src were blunted by PP2. Importantly, Rhy increased NO production and this effect was blocked by inhibition of Src or PI3K/Akt. Conclusion: The present study provides evidences for the first time that Rhy ameliorates endothelial dysfunction in SHRs through the activation of Src-PI3K/Akt-eNOS signaling pathway.
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Annexin A1 (ANXA1) acts either as a tumor suppressor or an oncogene in different tumor types. Several clinical studies revealed that the expression of ANXA1 is associated with the pathologic differentiation grade in oral squamous cell carcinoma (OSCC) patients. However, the direct function of ANXA1 in OSCC progression has remained to be fully clarified. The present study was designed to investigate the role of ANXA1 in OSCC cell proliferation and invasion in vitro. Furthermore, whether ANXA1 was involved in transforming growth factor ß1 (TGFß1)/epidermal growth factor (EGF)-induced epithelial-mesenchymal transition (EMT) in OSCC was explored. Tca-8113 and SCC-9 cells were transfected with ANXA1-pcDNA3.1 plasmid to overexpress ANXA1. Subsequently, cell proliferation and invasion were examined using MTT and Transwell-Matrigel invasion assays. TGFß1 and EGF were used to induce EMT in Tca-8113 and SCC-9 cells, and the expression of epithelial (E)-cadherin, neural (N)-cadherin and vimentin was determined by western blot analysis. The results demonstrated that ANXA1 overexpression induced a significant decrease of cell growth and invasiveness in Tca-8113 and SCC-9 cells. The expression of E-cadherin was significantly increased, while the expression of vimentin and N-cadherin was significantly decreased in ANXA1-overexpressing Tca-8113 and SCC-9 cells. ANXA1 expression was significantly decreased in TGFß1/EGF-treated cells. Furthermore TGFß1/EGF-induced EMT in OSCC cell lines was attenuated by ANXA1 overexpression. In conclusion, to the best of our knowledge, the present study was the first to evidence that ANXA1 inhibits OSCC cell proliferation and invasion in vitro. TGFß1/EGF-induced EMT was reversed by ANXA1 in OSCC. ANXA1 was suggested to be a potential marker for OSCC as well as a novel treatment.
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Hypertension is a systemic disorder that affects numerous physiological processes throughout the body. Improper sodium transport is a common comorbidity of hypertension, and sodium transport is also critical for maintaining the secretion of submandibular glands, whether the function of submandibular glands is affected by hypertension remains unclear. To determine whether hypertension induces changes in the protein expression of submandibular glands, we compared the proteome of submandibular glands from 14-week-old spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats using LC-MS/MS. The results revealed that 95 proteins displayed different levels of expression between the submandibular glands from the SHRs and WKYs. Among these, 35 proteins were more abundant, and 60 proteins were less abundant in the SHR compared with the WKY rats. Specifically, aquaporin 5 and parvalbumin, which are correlated with water transport and intracellular Ca2+ signal transduction, were verified to exhibit differences in protein abundance. Impaired Ca2+ response to carbachol was confirmed in the acinar cells from SHRs, and hyposecretion by the submandibular glands was further confirmed by in vivo saliva collection. In conclusion, the proteomic analysis of the submandibular glands of SHRs revealed novel changes in protein abundance that provides possible mechanisms connecting hypertension and hyposecretion in submandibular glands.