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1.
Altern Ther Health Med ; 29(4): 184-187, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36947652

RESUMO

Context: Researchers have associated insomnia with many disorders, making insomnia a serious public health issue in China. Sleep quality in older adults isn't well characterized in China. Objective: The study intended to explore the sleep quality and subjective duration of sleep in a community-dwelling older population in China and identify potential risk factors for poor sleep. Design: The research team performed a cross-sectional survey using the convenience sampling method. Setting: The study took place in a community in Wuhu, Anhui, China in 2015. Participants: Participants were 1075 members of the community from Wuhu city. Outcome Measures: The research team collected self-reported information on sleep quality. Results: The overall prevalence of self-reported insomnia among older adults were 40.8%. The prevalence of insomnia in females, 259 (59.00%), was significantly higher than in males, 180 (41.00%), with P = .00. For income status, the prevalence of insomnia was significantly higher for participants with less than 10 000 RMB per year income for a family, 191 participants (43.51%), than for participants with higher family incomes, with P = .00. For marital status, the prevalence of insomnia was significantly higher for the widowed participants, 121 participants (24.56%), with P = .01. Conclusions: Sleep quality for females, low-income families, and widowed people were significantly worse than for people in other categories among older adults in China. Older adults in China need proper interventions for the factors causing poor sleep hygiene.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Masculino , Feminino , Humanos , Idoso , Autorrelato , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Qualidade do Sono , Vida Independente , Estudos Transversais , Sono , Fatores de Risco , China/epidemiologia
2.
Front Neurosci ; 16: 820106, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185459

RESUMO

Alcohol use disorders (AUD) is characterized by persistent or intermittent alcohol cravings and compulsive drinking. The functional changes in the central nervous system (CNS) after alcohol consumption are alcohol-associated cognitive impairment and mood disorders, which are major health issues reported in AUDs. Studies have shown that transferring the intestinal microbiota from AUDs patients to germ-free animals causes learning and memory dysfunction, depression and anxiety-like behavior, indicating the vital role of intestinal microbiota in development of neuropsychiatric disorders in AUD. Intestinal flora composition of AUD patients are significantly different from normal people, suggesting that intestinal flora imbalance orchestrate the development of neuropsychiatric disorders in AUD. Studies suggests that gut microbiome links bidirectional signaling network of the enteric nervous system (ENS) to central nervous system (CNS), forming gut-microbe-brain axis (brain-gut axis). In this review, we discussed pathogenesis and possible treatment of AUD-induced cognitive deficits, anxiety, and depression disorders. Further, we described the mechanism of intestinal flora imbalance and dysfunction of hippocampus-amygdala-frontal cortex (gut-limbic circuit system dysfunction). Therefore, we postulate therapeutic interventions of gut-brain axis as novel strategies for treatment of AUD-induced neuropsychiatric disorders.

3.
Entropy (Basel) ; 23(12)2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34945908

RESUMO

Quantum Brownian motion, described by the Caldeira-Leggett model, brings insights to the understanding of phenomena and essence of quantum thermodynamics, especially the quantum work and heat associated with their classical counterparts. By employing the phase-space formulation approach, we study the heat distribution of a relaxation process in the quantum Brownian motion model. The analytical result of the characteristic function of heat is obtained at any relaxation time with an arbitrary friction coefficient. By taking the classical limit, such a result approaches the heat distribution of the classical Brownian motion described by the Langevin equation, indicating the quantum-classical correspondence principle for heat distribution. We also demonstrate that the fluctuating heat at any relaxation time satisfies the exchange fluctuation theorem of heat and its long-time limit reflects the complete thermalization of the system. Our research study justifies the definition of the quantum fluctuating heat via two-point measurements.

4.
Acta Biochim Pol ; 68(2): 317-323, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33860659

RESUMO

Globally, the tenth most common cancer is the oral squamous cell carcinoma (OSCC) and the treatment strategy for improving of OSCC patients survival rate still remains a challenging one. Aberrant regulation of cell to extracellular matrix protein interactions leads to progression of human cancers. The focal adhesion kinase (FAK) and its downstream target paxillin have been implicated in cancer growth, migration, invasion and metastasis of different cancers. However, the clinical significance of FAK and paxillin in OSCC is not well characterized so far. In the present work, we showed that relative mRNA and protein expressions of FAK and paxillin are significantly higher in side population (SP) cells of OSCC cell line SCC-55. Concomitantly, the matrix metalloproteinase-11 (MMP-11) level is also significantly elevated in SP cells. The enhanced expression of paxillin is strongly correlated with increased chemoresistance, proliferation rate, migration and invasion potential of SP cells. In addition, inhibition of paxillin expression by RNAi makes SP cells more sensitive to chemotherapy drugs. Therefore, our results suggest that paxillin over expression might play a significant role in cancer progression, invasion and chemoresistance of OSCC.


Assuntos
Carcinoma de Células Escamosas/patologia , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Neoplasias Bucais/patologia , Metástase Neoplásica/patologia , Paxilina/metabolismo , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proteína-Tirosina Quinases de Adesão Focal/genética , Humanos , Metaloproteinase 11 da Matriz/metabolismo , Neoplasias Bucais/metabolismo , Invasividade Neoplásica/patologia , Paxilina/genética , Interferência de RNA , Células da Side Population/metabolismo
5.
Am J Mens Health ; 14(3): 1557988320926743, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32552402

RESUMO

OBJECTIVE: To investigate the distribution of opportunistic infections (OIs) and factors associated with acquiring OIs in human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) in comparison to those of heterosexual patients. METHOD: A cross-sectional study was conducted on 82 HIV-infected MSM and 120 HIV-infected heterosexual men in Bach Mai Hospital, Hanoi, Vietnam. Demographical characteristics and clinical data were collected and analyzed using appropriate statistics (Mann-Whitney, Chi-square, Fisher's exact test, and logistic regression). RESULTS: The prevalence of OIs among MSM and heterosexual patients were 63.4% and 81.7%, respectively. The most frequent OI in the MSM group was human papilloma virus (HPV) (11%), followed by hepatitis B virus (8.5%), mycobacterium tuberculosis (7.3%), and Talaromycosis (2.4%). CONCLUSIONS: Multivariate logistic regression analysis showed that buying sex (odds ratio (OR) = 4, 95% confidence interval (CI): 1.13-14.25) and injecting drugs (OR = 13.05, 95% CI: 2.39-71.21) were associated with increased odds of having OIs in heterosexual patients while increasing age (OR = 1.1, 95% CI: 1.01-1.24) was correlated to increased odd of acquiring OIs in the MSM group. HIV-infected MSM accumulates OIs with increasing age, while heterosexual individuals increase opportunistic infections by buying sex or injecting drugs.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Homossexualidade Masculina , Hospitais , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/etiologia , Adulto , Estudos Transversais , Humanos , Modelos Logísticos , Masculino , Prontuários Médicos , Prevalência , Vietnã/epidemiologia
6.
BMC Complement Altern Med ; 19(1): 176, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315617

RESUMO

BACKGROUND: Snake venoms contain various bioactive constituents which possess potential therapeutic effects. The aim of this work was to investigate the effect of the extract from Agkistrodon halys venom on lipopolysaccharide (LPS)-induced myocardial injury. METHODS: Thirty male Sprague-Dawley rats were randomly assigned to three groups (10 rats per group): control group, LPS group and LPS + extract group. Rats in control and the LPS groups were intravenously injected with sterile saline solution, and rats in the LPS + extract group with the extract. After 2 h, rats of the control group were intraperitoneally injected sterile saline solution, and rats in the LPS and the LPS + extract groups were treated with LPS (20 mg per kg body weight). Levels of creatine kinase (CK) and lactate dehydrogenase (LDH) in serum were determined. Anti-inflammation of the extract was analyzed via determination of TNF-α and IL-6 in serum, and expression of TNF-α, IL-6, COX-2 and p-ERK protein in hearts. Heme oxygenase-1 (HO-1) and p-NF-κB protein expression in hearts, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in serum were used to evaluate the anti-oxidative properties of the extract. RESULTS: Extract pretreatment significantly decreased the level of serum CK and LDH, reduced the generation of inflammatory cytokines such as TNF-α and IL-6, and also reduced serum level of MDA in the LPS + extract group compared with the LPS group. In addition, the extract increased SOD activity in serum, HO-1 protein expression in hearts, and decreased TNF-α, IL-6, COX-2, p-NF-κB and p-ERK1/2 protein expression. CONCLUSION: Our results suggested that beneficial effect of this extract might be associated with an improved anti-oxidation and anti-inflammatory effect via downregulation of NF-κB/COX-2 signaling by activating HO-1/CO in hearts.


Assuntos
Agkistrodon/metabolismo , Traumatismos Cardíacos/prevenção & controle , Lipopolissacarídeos/efeitos adversos , Substâncias Protetoras/administração & dosagem , Venenos de Serpentes/administração & dosagem , Animais , Coração/efeitos dos fármacos , Traumatismos Cardíacos/induzido quimicamente , Traumatismos Cardíacos/genética , Traumatismos Cardíacos/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Malondialdeído/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
7.
Acta Pharmacol Sin ; 40(7): 971-979, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30643210

RESUMO

Emerging evidence demonstrates that a c-Met antibody-drug conjugate (ADC) has superior efficacy and safety profiles compared with those of currently available small molecules or antibody inhibitors for the treatment of c-Met-overexpressing cancers. Here we described both the in vitro and in vivo efficacies of SHR-A1403, a novel c-Met ADC composed of a humanized IgG2 monoclonal antibody against c-Met conjugated to a novel cytotoxic microtubule inhibitor. SHR-A1403 showed high affinity to c-Met proteins derived from human or monkey and potent inhibitory effects in cancer cell lines with high c-Met protein expression. In mice bearing tumors derived from cancer cell lines or patient HCC tissues with confirmed c-Met overexpression, SHR-A1403 showed excellent anti-tumor efficacy. Antibody binding with c-Met contributed to SHR-A1403 endocytosis; the subsequent translocation to lysosomes and cytotoxicity of the released toxin are speculated to be predominant mechanisms underlying the anti-tumor activity of SHR-A1403. In conclusion, SHR-A1403 showed significant anti-tumor activity in cancer cell lines, xenograft mouse models and an HCC PDX model, which all have high c-Met levels. These data provide references for SHR-A1403 as a potential therapy for the treatment of cancers with c-Met overexpression.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Imunoconjugados/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Moduladores de Tubulina/uso terapêutico , Animais , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/toxicidade , Antineoplásicos/imunologia , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Imunoconjugados/imunologia , Imunoconjugados/toxicidade , Macaca fascicularis , Masculino , Camundongos Endogâmicos BALB C , Microtúbulos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-met/imunologia , Moduladores de Tubulina/imunologia , Moduladores de Tubulina/toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Acta Pharmacol Sin ; 40(2): 268-278, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29777202

RESUMO

BRAF and MEK inhibitors have shown remarkable clinical efficacy in BRAF-mutant melanoma; however, most patients develop resistance, which limits the clinical benefit of these agents. In this study, we found that the human melanoma cell clones, A375-DR and A375-TR, with acquired resistance to BRAF inhibitor dabrafenib and MEK inhibitor trametinib, were cross resistant to other MAPK pathway inhibitors. In these resistant cells, phosphorylation of ribosomal protein S6 (rpS6) but not phosphorylation of ERK or p90 ribosomal S6 kinase (RSK) were unable to be inhibited by MAPK pathway inhibitors. Notably, knockdown of rpS6 in these cells effectively downregulated G1 phase-related proteins, including RB, cyclin D1, and CDK6, induced cell cycle arrest, and inhibited proliferation, suggesting that aberrant modulation of rpS6 phosphorylation contributed to the acquired resistance. Interestingly, RSK inhibitor had little effect on rpS6 phosphorylation and cell proliferation in resistant cells, whereas P70S6K inhibitor showed stronger inhibitory effects on rpS6 phosphorylation and cell proliferation in resistant cells than in parental cells. Thus regulation of rpS6 phosphorylation, which is predominantly mediated by BRAF/MEK/ERK/RSK signaling in parental cells, was switched to mTOR/P70S6K signaling in resistant cells. Furthermore, mTOR inhibitors alone overcame acquired resistance and rescued the sensitivity of the resistant cells when combined with BRAF/MEK inhibitors. Taken together, our findings indicate that RSK-independent phosphorylation of rpS6 confers resistance to MAPK pathway inhibitors in BRAF-mutant melanoma, and that mTOR inhibitor-based regimens may provide alternative strategies to overcome this acquired resistance.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteína S6 Ribossômica/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Linhagem Celular Tumoral , Humanos , Imidazóis/farmacologia , Melanoma/tratamento farmacológico , Melanoma/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Mutação , Oximas/farmacologia , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas/farmacologia , Pirimidinonas/farmacologia
9.
Asian-Australas J Anim Sci ; 32(4): 574-584, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30208690

RESUMO

OBJECTIVE: Research was conducted to test the effect of including fiber-rich feedstuffs in practical pig diets on nutrient digestibility, nitrogen balance and ammonia emissions from slurry. METHODS: Three Vietnamese fiber sources were screened, namely cassava leaf meal (CL), cassava root residue (CR), and tofu by-product (TF). Accordingly, a control diet (Con) with 10% of dietary non-starch polysaccharides (NSP) and three test diets including one of the three fiber-rich feedstuffs to reach 15% of NSP were formulated. All formulated diets had the same level of crude protein (CP), in vitro ileal protein digestible and metabolisable energy, whereas the in vitro hindgut volatile fatty acid (VFA) production of the test diets was 12% to 20% higher than the control diet. Forty growing barrows with initial body weight at 28.6±1.93 kg (mean±standard deviation) were allocated to the four treatments. When pigs reached about 50 kg of body weight, four pigs from each treatment were used for a nitrogen balance trial and ammonia emission assessment, the remaining six pigs continued the second period of the feeding trial. RESULTS: The TF treatment increased fecal VFA by 33% as compared with the control treatment (p = 0.07), suggesting stimulation of the hindgut fermentation. However, urinary N was not significantly reduced or shifted to fecal N, nor was slurry pH decreased. Accordingly, ammonia emissions were not mitigated. CR and CL treatments failed to enhance in vivo hindgut fermentation, as assessed by fecal VFA and purine bases. On the contrary, the reduction of CP digestibility in the CL treatment enhanced ammonia emissions from slurry. CONCLUSION: Dietary inclusion of cassava and tofu byproducts through an increase of dietary NSP from 10% to 15% might stimulate fecal VFA excretion but this does not guarantee a reduction in ammonia emissions from slurry, while its interaction with protein digestibility even might enhance enhanced ammonia emission.

10.
Chin J Nat Med ; 16(8): 572-579, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30197122

RESUMO

Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. As a metabolic regulator, FXR plays key roles in bile acid and cholesterol metabolism and lipid and glucose homeostasis. Therefore, FXR is a potential drug target for several metabolic syndromes, especially those related to lipidemia disorders. In the present study, we identified small molecule SIPI-7623, a derivative of an extract from Oriental wormwood (Artemisia capillaris), and found that it specifically upregulated the expression of cholesterol-7-alpha-hydroxylase (CYP7A1), downregulated the expression of sterol-regulatory element-binding protein 1c (SREBP-1c) in the liver, and inhibited the expression of ileal bile acid binding-protein (IBABP) in the ileum of rats. We found that inhibition of FXR by SIPI-7623 decreased the level of cholesterol and triglyceride. SIPI-7623 reduced the levels of cholesterol and triglyceride in in vitro HepG2 cell models, ameliorated diet-induced atherosclerosis, and decreased the serum lipid content on rats and rabbits model of atherosclerosis in vivo. Furthermore, SIPI-7623 decreased the extent of atherosclerotic lesions. Our resutls demonstrated that antagonism of the FXR pathway can be employed as a therapeutic strategy to treat metabolic diseases such as hyperlipidemia and atherosclerosis. In conclusion, SIPI-7623 could be a promising lead compound for development of drugs to treat hyperlipidemia and atherosclerosis.


Assuntos
Artemisia/química , Aterosclerose/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Animais , Aterosclerose/genética , Aterosclerose/metabolismo , Colesterol/metabolismo , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Humanos , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Coelhos , Ratos , Ratos Sprague-Dawley , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/metabolismo
11.
Biomed Res Int ; 2018: 1547452, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30186848

RESUMO

OBJECTIVES: Protein arginine methyltransferase 2 (PRMT2) protects against vascular injury-induced intimal hyperplasia; however, little is known about the role of PRMT2 in angiotensin II (Ang II)-induced VSMCs proliferation and inflammation. This research aims to determine whether PRMT2 inhibits Ang II-induced proliferation and inflammation of vascular smooth muscle cells (VSMCs). MATERIALS AND METHODS: PRMT2 overexpression was used to elucidate the role of PRMT2 in Ang II-induced VSMCs proliferation and inflammation. Western blotting and reverse transcriptional PCR were adopted to detect protein and mRNA expression severally. Cell viability was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay and cell cycle distribution by flow cytometry. RESULTS: Ang II significantly reduced mRNA and protein levels of PRMT2 in VSMCs in time-dependent and dose-dependent manner. Results of PRMT2 overexpression indicated that PRMT2 inhibited proliferation of VSMCs stimulated with 100 nmol/L Ang II for 24 hours. Furthermore, overexpression of PRMT2 reduced Ang II-induced production of proinflammatory cytokines such as interleukin 6 (IL-6) and interleukin 1ß (IL-1ß) in VSMCs. CONCLUSIONS: These findings suggest that PRMT2 alleviates Ang II-induced VSMCs proliferation and inflammation, providing a new mechanism about how Ang II mediated VSMCs proliferation and inflammation.


Assuntos
Proliferação de Células/fisiologia , Inflamação , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Músculo Liso Vascular/fisiologia , Proteína-Arginina N-Metiltransferases/fisiologia , Angiotensina II , Células Cultivadas , Humanos , Miócitos de Músculo Liso
12.
Orthop Surg ; 10(1): 47-55, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29424098

RESUMO

OBJECTIVE: To establish a logistic regression model using surface electromyography (SEMG) parameters for diagnosing the compressed nerve root at L5 or S1 level in patients with lumbar disc herniation (LDH). METHODS: This study recruited 24 patients with L5 nerve root compression and 23 patients with S1 nerve root compression caused by LDH from May 2014 to May 2016. SEMG signals from the bilateral tibialis anterior and lateral gastrocnemius were measured. The root mean square (RMS), the RMS peak time, the mean power frequency (MPF), and the median frequency (MF) were analyzed. The accuracy, sensitivity, and specificity values were calculated separately. The areas under the curve (AUC) of the receiver-operating characteristic (ROC) curve and the kappa value were used to evaluate the accuracy of the SEMG diagnostic model. RESULTS: The accuracy of the SEMG model ranged from 85.71% to 100%, with an average of 93.57%. The sensitivity, specificity, AUC, and kappa value of the logistic regression model were 0.98 ± 0.05, 0.92 ± 0.09, 0.95 ± 0.04 (P = 0.006), and 0.87 ± 0.11, respectively (P = 0.001). The final diagnostic model was: P=1-11+ey; y = 10.76 - (5.95 × TA_RMS Ratio) - (0.38 × TA_RMS Peak Time Ratio) - (5.44 × 44 × LG_RMS Peak Time Ratio). L5 nerve root compression is diagnosed when P < 0.5 and S1 nerve root compression when P ≥ 0.5. CONCLUSIONS: The logistic regression model developed in this study showed high diagnostic accuracy in detecting the compressed nerve root (L5 and S1 ) in these patients with LDH.


Assuntos
Eletromiografia/métodos , Degeneração do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/complicações , Radiculopatia/diagnóstico , Radiculopatia/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Vértebras Lombares , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Curva ROC , Sacro , Sensibilidade e Especificidade , Processamento de Sinais Assistido por Computador
13.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-773584

RESUMO

Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. As a metabolic regulator, FXR plays key roles in bile acid and cholesterol metabolism and lipid and glucose homeostasis. Therefore, FXR is a potential drug target for several metabolic syndromes, especially those related to lipidemia disorders. In the present study, we identified small molecule SIPI-7623, a derivative of an extract from Oriental wormwood (Artemisia capillaris), and found that it specifically upregulated the expression of cholesterol-7-alpha-hydroxylase (CYP7A1), downregulated the expression of sterol-regulatory element-binding protein 1c (SREBP-1c) in the liver, and inhibited the expression of ileal bile acid binding-protein (IBABP) in the ileum of rats. We found that inhibition of FXR by SIPI-7623 decreased the level of cholesterol and triglyceride. SIPI-7623 reduced the levels of cholesterol and triglyceride in in vitro HepG2 cell models, ameliorated diet-induced atherosclerosis, and decreased the serum lipid content on rats and rabbits model of atherosclerosis in vivo. Furthermore, SIPI-7623 decreased the extent of atherosclerotic lesions. Our resutls demonstrated that antagonism of the FXR pathway can be employed as a therapeutic strategy to treat metabolic diseases such as hyperlipidemia and atherosclerosis. In conclusion, SIPI-7623 could be a promising lead compound for development of drugs to treat hyperlipidemia and atherosclerosis.


Assuntos
Animais , Humanos , Masculino , Coelhos , Ratos , Artemisia , Química , Aterosclerose , Tratamento Farmacológico , Genética , Metabolismo , Colesterol , Metabolismo , Colesterol 7-alfa-Hidroxilase , Genética , Metabolismo , Medicamentos de Ervas Chinesas , Hiperlipidemias , Tratamento Farmacológico , Genética , Metabolismo , Hipolipemiantes , Fígado , Metabolismo , Ratos Sprague-Dawley , Receptores Citoplasmáticos e Nucleares , Genética , Metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1 , Genética , Metabolismo , Triglicerídeos , Metabolismo
14.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-812373

RESUMO

Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. As a metabolic regulator, FXR plays key roles in bile acid and cholesterol metabolism and lipid and glucose homeostasis. Therefore, FXR is a potential drug target for several metabolic syndromes, especially those related to lipidemia disorders. In the present study, we identified small molecule SIPI-7623, a derivative of an extract from Oriental wormwood (Artemisia capillaris), and found that it specifically upregulated the expression of cholesterol-7-alpha-hydroxylase (CYP7A1), downregulated the expression of sterol-regulatory element-binding protein 1c (SREBP-1c) in the liver, and inhibited the expression of ileal bile acid binding-protein (IBABP) in the ileum of rats. We found that inhibition of FXR by SIPI-7623 decreased the level of cholesterol and triglyceride. SIPI-7623 reduced the levels of cholesterol and triglyceride in in vitro HepG2 cell models, ameliorated diet-induced atherosclerosis, and decreased the serum lipid content on rats and rabbits model of atherosclerosis in vivo. Furthermore, SIPI-7623 decreased the extent of atherosclerotic lesions. Our resutls demonstrated that antagonism of the FXR pathway can be employed as a therapeutic strategy to treat metabolic diseases such as hyperlipidemia and atherosclerosis. In conclusion, SIPI-7623 could be a promising lead compound for development of drugs to treat hyperlipidemia and atherosclerosis.


Assuntos
Animais , Humanos , Masculino , Coelhos , Ratos , Artemisia , Química , Aterosclerose , Tratamento Farmacológico , Genética , Metabolismo , Colesterol , Metabolismo , Colesterol 7-alfa-Hidroxilase , Genética , Metabolismo , Medicamentos de Ervas Chinesas , Hiperlipidemias , Tratamento Farmacológico , Genética , Metabolismo , Hipolipemiantes , Fígado , Metabolismo , Ratos Sprague-Dawley , Receptores Citoplasmáticos e Nucleares , Genética , Metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1 , Genética , Metabolismo , Triglicerídeos , Metabolismo
15.
Exp Ther Med ; 14(5): 5177-5185, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29201234

RESUMO

The efficacy, safety and impact of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) associated with the intra-calf muscular injection of bone marrow mononuclear cells (BMMCs) in the treatment of type 2 diabetes mellitus (T2DM)-induced lower extremity vascular disease (LEVD) were evaluated. Patients with T2DM-LEVD were randomly divided into a control group and BMMCs group to assess the efficacy and safety of the treatment; serum VEGF and bFGF levels were detected. The BMMCs group was divided into superior genicular artery (SGA) and inferior genicular artery (IGA) subgroups as well as low-dose and high-dose subgroups for the comparison of efficacy indices. The BMMCs group exhibited significantly improved indices (P<0.05) compared with the control group and no fatalities or cancer occurred. There were no significant changes in serum VEGF and bFGF levels (P>0.05). The claudication distance in the IGA subgroup was significantly greater that in the SGA subgroup (P<0.05); the low-dose subgroup and the high-dose subgroup did not demonstrate any significant differences in each index (P>0.05). BMMC treatment for T2DM-LEVD was found to be safe and effective and had no significant impact on serum VEGF and bFGF levels in the short term; However, the degree of LEVD may affect its efficacy.

16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-658893

RESUMO

Objective To investigate the distribution and antimicrobial resistance of pathogens causing bacterial peritonitis,provide laboratorial guidance for rational use of antimicrobial agents.Methods Pathogenic strains iso-lated from peritoneal fluid specimen of patients with peritonitis in the Affiliated Hospital of Xuzhou Medical Univer-sity in 2011-2015 were collected,performed bacterial identification and antimicrobial susceptibility testing,distri-bution of pathogens and antimicrobial resistance were analyzed.Results A total of 491 strains were collected,in-cluding 291(59.26%)strains of gram-negative bacilli,196(39.92%)of gram-positive cocci,and 4 (0.82%)of fun-gi.The top 5 pathogens were Escherichia coli (30.14%),coagulase negative staphylococcus(12.22%),Staphylo-coccus aureus (10.39%),Klebsiella pneumoniae (8.55%),and Enterococcus faecium(6.52%).Antimicrobial re-sistance rates of Escherichia coli ,Klebsiella pneumoniae ,Acinetobacter baumannii ,and Pseudomonas aeruginosa to imipenem were 4.90%,31.04%,77.28% and 26.27% respectively.Methicillin-resistant Staphylococcus aureus (MRSA)and methicillin-resistant coagulase negative staphylococcus(MRNCS)accounted for 56.02% and 70.02%respectively.Conclusion The main pathogens causing bacterial peritonitis are gram-negative bacilli,Escherichia co-li ranks first;resistance of pathogens is serious,standard use of antimicrobial agents should be strengthened to re-duce the emergence of drug-resistant strains.

17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-661812

RESUMO

Objective To investigate the distribution and antimicrobial resistance of pathogens causing bacterial peritonitis,provide laboratorial guidance for rational use of antimicrobial agents.Methods Pathogenic strains iso-lated from peritoneal fluid specimen of patients with peritonitis in the Affiliated Hospital of Xuzhou Medical Univer-sity in 2011-2015 were collected,performed bacterial identification and antimicrobial susceptibility testing,distri-bution of pathogens and antimicrobial resistance were analyzed.Results A total of 491 strains were collected,in-cluding 291(59.26%)strains of gram-negative bacilli,196(39.92%)of gram-positive cocci,and 4 (0.82%)of fun-gi.The top 5 pathogens were Escherichia coli (30.14%),coagulase negative staphylococcus(12.22%),Staphylo-coccus aureus (10.39%),Klebsiella pneumoniae (8.55%),and Enterococcus faecium(6.52%).Antimicrobial re-sistance rates of Escherichia coli ,Klebsiella pneumoniae ,Acinetobacter baumannii ,and Pseudomonas aeruginosa to imipenem were 4.90%,31.04%,77.28% and 26.27% respectively.Methicillin-resistant Staphylococcus aureus (MRSA)and methicillin-resistant coagulase negative staphylococcus(MRNCS)accounted for 56.02% and 70.02%respectively.Conclusion The main pathogens causing bacterial peritonitis are gram-negative bacilli,Escherichia co-li ranks first;resistance of pathogens is serious,standard use of antimicrobial agents should be strengthened to re-duce the emergence of drug-resistant strains.

18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-247655

RESUMO

<p><b>OBJECTIVE</b>To investigate the biological characteristics and genetic features of human placenta mesenchymal stem cells (hPA-MSCs) cultured in vitro in order to assess its safety for clinical use.</p><p><b>METHODS</b>The shapes of the 1st, 3rd, 5th, 7th, 10th, 13th, 17th and 20th generation hPA-MSCs cultured in vitro using serum-free culture medium were observed. Their cell cycle, cell surface markers, and karyotype were analyzed, and relevant genes and cytokines were measured.</p><p><b>RESULTS</b>The shape of hPA-MSCs has remained as fusiform or short fusiform, and there was no significant change. About 93% of hPA-MSCs cells were in G0/G1 phase and remained stable. No obvious chromosomal translocation, loss or inversion was noted by karyotyping analysis. Cytokines expression level remained stable. Related gene expression level as a whole was on the decline, but the gene expression level of the first five generations showed very slight variations, with genetic characteristics remaining stable.</p><p><b>CONCLUSION</b>The hPA-MSCs cultured in vitro with serum-free medium has retained stable in the first five generations.</p>


Assuntos
Feminino , Humanos , Gravidez , Células Cultivadas , Citocinas , Cariotipagem , Células-Tronco Mesenquimais , Fisiologia , Placenta , Biologia Celular
19.
Shanghai Kou Qiang Yi Xue ; 24(1): 30-6, 2015 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-25858366

RESUMO

PURPOSE: To study the role and mechanism of autophagy in chemotherapy of oral squamous cell carcinoma, and provide theoretical evidence to improve chemotherapeutic efficacy of oral squamous cell carcinoma patients. METHODS: The cell survival rate changes induced by cisplatin (DDP) and chloroquine (CQ) in CAL-27 cells were assayed by methyl thiazolyl tetrazolium method(MTT). The LC3-II expression level was detected by laser scanning confocal microscope; The apoptotic rate was determined by flow cytometry. SPSS17.0 software package was used for statistical analysis. RESULTS: MTT results showed that compared with the control group, the cell survival rate reduced with the increasing time of DDP and CQ treatment; The optimal concentration of CAL-27 cells was 5 mg/L after treatment with CQ. IC50 of the CAL-27 cells was 5 mg/L after treatment with DDP; MTT results showed that the cell survival rate of CQ+DDP group was significantly lower than control group, CQ group and DDP group (P<0.05). With the action of CQ and DDP to CAL-27 cells for 48 hours, immunofluorescence results showed that the average fluorescence intensity of DDP group was significantly higher than the other 3 groups (P<0.05), while it was significantly lower in CQ group than the other 3 groups (P<0.05). With the action of CQ and DDP to CAL-27 cells for 48 hours, flow cytometry results showed that the cell apoptosis rate of DDP group and CQ+DDP group were significantly higher than control group and CQ group. The cell apoptosis rate of CQ+DDP group was significantly higher than DDP group (P<0.05). With the action of CQ and DDP to CAL-27 cells for 48 hours, cells in G1 phase of DDP group and CQ+DDP group increased, indicating G1 phase blockage. The cell count in G1 phase of CQ+DDP group was significantly higher than DDP group (P<0.05). CONCLUSIONS: Inhibition of autophagy can enhance the chemotherapeutic sensitivity of DDP in CAL-27 cells. Autophagy in CAL-27 cells is an important mechanism for chemotherapy resistance of oral squamous cell carcinoma. Autophagy inhibitor may have significant potential to be a novel chemotherapeutic sensitizer for oral squamous cell carcinoma.


Assuntos
Apoptose , Autofagia , Carcinoma de Células Escamosas , Cloroquina , Cisplatino , Proteínas Associadas aos Microtúbulos , Neoplasias Bucais , Antineoplásicos , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos
20.
Sheng Li Xue Bao ; 67(2): 193-200, 2015 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-25896050

RESUMO

Angiotensin II (Ang II) and calcitonin gene-related peptide (CGRP) play important roles in vascular injury and protection. In order to determine the role of CGRP receptor component protein (RCP) in signal transduction whereby CGRP and Ang II mediate the expression of vascular peroxidase-1 (VPO1) in vascular smooth muscle cell (VSMC), mouse derived A10 vascular smooth muscle cell line (A10VSMC) was cultured with CGRP or/and Ang II in vitro. RCP-specific small interference RNA (siRNA-RCP) was used to silence oligonucleotide sequence. Western blot and RT-PCR were used to determine the protein and mRNA expressions of RCP and VPO1, respectively. The results showed that the expressions of RCP and VPO1 were increased in the presence of CGRP or Ang II in the quiescent A10VSMC. But the protein expressions of RCP and VPO1 induced by Ang II were decreased by pretreatment of CGRP (P < 0.05). The expressions of VPO1 were decreased in all the groups treated with siRNA-RCP, compared with those of wide-type counterparts. Meanwhile, the expression of VPO1 was significantly induced by CGRP but not Ang II in the siRNA-RCP treated A10VSMCs. Ang II in combination with CGRP increased the protein expression of VPO1 in the siRNA-RCP-transfected cells, compared with Ang II alone, and this effect could be abolished by catalase. The results suggest that RCP may play an important role in the integration of signal transduction whereby CGRP and Ang II receptors jointly regulate VPO1 expression in VSMC.


Assuntos
Angiotensina II/farmacologia , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Miócitos de Músculo Liso/metabolismo , Peroxidases/metabolismo , Animais , Camundongos , Músculo Liso Vascular/citologia , RNA Interferente Pequeno , Transdução de Sinais
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