Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 48
Filtrar
1.
Int Immunopharmacol ; 131: 111861, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38484665

RESUMO

Glutathione (GSH) depletion, mitochondrial damage, and oxidative stress have been implicated in the pathogenesis of acetaminophen (APAP) hepatotoxicity. Here, we demonstrated that the expression of histone deacetylase 6 (HDAC6) is highly elevated, whereas malate dehydrogenase 1 (MDH1) is downregulated in liver tissues and AML-12 cells induced by APAP. The therapeutic benefits of LT-630, a novel HDAC6 inhibitor on APAP-induced liver injury, were also substantiated. On this basis, we demonstrated that LT-630 improved the protein expression and acetylation level of MDH1. Furthermore, after overexpression of MDH1, an upregulated NADPH/NADP+ ratio and GSH level and decreased cell apoptosis were observed in APAP-stimulated AML-12 cells. Importantly, MDH1 siRNA clearly reversed the protection of LT-630 on APAP-stimulated AML-12 cells. In conclusion, LT-630 could ameliorate liver injury by modulating MDH1-mediated oxidative stress induced by APAP.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas , Desacetilase 6 de Histona , Leucemia Mieloide Aguda , Animais , Humanos , Camundongos , Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Glutationa/metabolismo , Desacetilase 6 de Histona/antagonistas & inibidores , Leucemia Mieloide Aguda/metabolismo , Fígado/patologia , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos
2.
Cancer Cell Int ; 24(1): 98, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443969

RESUMO

Tumor organoids, especially patient-derived organoids (PDOs) exhibit marked similarities in histopathological morphology, genomic alterations, and specific marker expression profiles to those of primary tumour tissues. They are applied in various fields including drug screening, gene editing, and identification of oncogenes. However, CAR-T therapy in the treatment of solid tumours is still at an exploratory stage. Tumour organoids offer unique advantages over other preclinical models commonly used for CAR-T therapy research, which the preservation of the biological characteristics of primary tumour tissue is critical for the study of early-stage solid tumour CAR-T therapies. Although some investigators have used this co-culture model to validate newly targeted CAR-T cells, optimise existing CAR-T cells and explore combination therapy strategies, there is still untapped potential in the co-culture models used today. This review introduces the current status of the application of tumour organoid and CAR-T cell co-culture models in recent years and commented on the limitations of the current co-cultivation model. Meanwhile, we compared the tumour organoid model with two pre-clinical models commonly used in CAR-T therapy research. Eventually, combined with the new progress of organoid technologies, optimization suggestions were proposed for the co-culture model from five perspectives: preserving or reconstructing the tumor microenvironment, systematization, vascularization, standardized culture procedures, and expanding the tumor organoids resource library, aimed at assisting related researchers to better utilize co-culture models.

3.
BMJ Open ; 13(12): e077279, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-38040433

RESUMO

INTRODUCTION: Rectal cancer is one of the top 10 cancers worldwide. Up to 80% of patients with rectal tumours have had sphincter-saving surgery, mainly due to the large expectation of anal preservation. However, patients tend to experience low anterior resection syndrome (LARS) after rectal resection, which is disordered bowel function that includes faecal incontinence, urgency, frequent defecation, constipation and evacuation difficulties. LARS, with an estimated prevalence of 41%, has been reported to substantially decrease the quality of life of patients. However, no comprehensive preventive strategies are currently available for LARS. This systematic review aims to synthesise evidence on the current LARS preventive strategies. METHODS AND ANALYSIS: This protocol is reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) checklist. Literature in PubMed (via Medline), Embase and the Cochrane Library from inception to July 2023 will be searched to identify articles relevant to preventive effectiveness against LARS. The Cochrane Collaboration's risk of bias tool for randomised controlled trials and the Newcastle-Ottawa Scale for clinical controlled trials, cohort studies and case-control studies will be used to assess the risk of bias. We will group the included studies by the type of LARS prevention strategy and present an overview of the main findings in the form of evidence mapping. A meta-analysis is planned if there is no substantial clinical heterogeneity between the included studies. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) will be used to evaluate the quality of the evidence. ETHICS AND DISSEMINATION: Ethical approval is not needed for systematic review of published data. The findings will be published in a peer-reviewed journal and disseminated at scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42023402886.


Assuntos
Síndrome de Ressecção Anterior Baixa , Neoplasias Retais , Humanos , Neoplasias Retais/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Qualidade de Vida , Revisões Sistemáticas como Assunto , Metanálise como Assunto
4.
Clin Ther ; 45(10): 991-1003, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37690913

RESUMO

PURPOSE: Viral myocarditis (VMC) is a life-threatening disease that can affect all ages and genders, with middle-aged adults being particularly susceptible. Numerous systematic reviews have been conducted to investigate the efficacy and safety of Chinese herbal medicine (CHM) in treating adult viral myocarditis (AVM). The objective of this study was to conduct a comprehensive overview of systematic reviews and meta-analyses of randomized controlled trials (RCTs) regarding the efficacy and safety of CHM for AVM. METHODS: A comprehensive systematic search was conducted across 8 electronic databases from their inception to June 23, 2022, augmented by manual searches of the gray literature. Systematic reviews were independently selected and data extracted in accordance with predetermined criteria by 2 reviewers. Included systematic reviews were assessed for methodologic and reporting quality using Assessing the Methodological Quality of Systematic Reviews 2 and Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The quality of evidence relating to outcome measures was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation tool. Recalculation of effect sizes and subsequent determination of 95% CIs were conducted with either a fixed-effects or random-effects model. FINDINGS: The current overview of systematic reviews included a total of 6 systematic reviews, which reported on 67 RCTs with a participant pool of 5611 individuals. The findings of our study indicate that the combination of CHM and Western medications had positive effects on the effective rate, cure rate, ECG recovery, atrial premature contraction/premature ventricular contraction, left ventricular ejection fraction, myocardial enzymes, and improvement of clinical symptoms for AVM. The adverse drug reactions in the combination therapy group were generally less than or lighter than that in the Western medication group (relative risk = 0.79; 95% CI, 0.44-1.40; P > 0.05, I2 = 0). IMPLICATIONS: Our research results provide evidence that combining CHM with Western medicine could offer potential benefits for patients with AVM. However, the number of studies included in our review is limited and the methodologic quality of these studies is modest. Therefore, there are potential uncertainties regarding the conclusion that CHM with Western medication may benefit patients with AVM. We call for more large-scale, high-quality studies with standardized designs to further verify and support our findings. This would promote a better understanding of the efficacy and safety profile of CHM and provide reliable reference evidence for clinical practice and policy making. Moreover, future research should explore optimal drug combinations, examine therapeutic doses and durations of CHM combination therapy, and evaluate its long-term efficacy and safety.


Assuntos
Medicamentos de Ervas Chinesas , Miocardite , Adulto , Humanos , Pessoa de Meia-Idade , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/efeitos adversos , Miocardite/tratamento farmacológico , Miocardite/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Metanálise como Assunto
5.
Huan Jing Ke Xue ; 44(9): 5204-5213, 2023 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-37699838

RESUMO

To investigate the effects of nano-copper oxide (CuO NPs) on plant growth, physio-biochemical characteristics, and heavy metal content under cadmium stress, a hydroponics experiment was conducted on the effects of single and combined treatments of CuO NPs (0, 10, 20, and 50 mg·L-1) and Cd (0, 1, and 5 µmol·L-1) on the fresh weight, photosynthetic pigment content, MDA content, antioxidant enzyme activity (CAT, POD, SOD, and GR), and Cu and Cd contents in Brassica chinensis L. The results showed that under the single addition of CuO NPs, the fresh weight and activities of CAT, POD, and GR were inhibited as a whole. Photosynthetic pigment content and SOD activity increased first and then decreased with the increase in CuO NPs concentration, whereas MDA content in leaves and roots, and Cu content in subcells of B. chinensis L. increased with the increasing of CuO NPs. As compared with that in the control, CuO NPs promoted the growth of B. chinensis L., and the fresh weight increased by 8.70%-44.87% at 1 µmol·L-1 Cd. When the content of Cd was up to 5 µmol·L-1, a low content (10 mg·L-1) of CuO NPs promoted the growth of B. chinensis L., whereas a high concentration (50 mg·L-1) showed an inhibitory effect. The addition of CuO NPs could increase photosynthetic pigment and MDA contents under different Cd stress, and MDA content in leaves and roots of B. chinensis L. increased by 4.34%-36.27% and 13.43%-131.04%, respectively, than that in the control groups. Under the same concentration of 1 µmol·L-1 Cd, the addition of CuO NPs decreased the activities of CAT and GR, whereas the activity of POD increased. When the content of Cd was up to 5 µmol·L-1, CuO NPs increased the POD activity and inhibited the activity of SOD and GR. The activities of CAT and CAT in the leaves of B. chinensis L. initially showed an increasing and then decreasing trend. CuO NPs and Cd showed antagonistic effects, the maximum reduction of Cd content in leaves and roots of Brassica chinensis L. under 1 µmol·L-1 Cd treatment was 45.64% and 33.39%, and that under 5 µmol·L-1 Cd treatment was 18.25% and 25.35%, respectively. The content of Cu and Cd in subcellular organs of the plants decreased, but the proportion of soluble components increased. These results indicated that CuO NPs at low concentrations promoted plant growth under Cd stress and further inhibited the absorption of Cd but increased the oxidative damage to B. chinensis L.


Assuntos
Brassica , Metais Pesados , Cobre , Cádmio/toxicidade , Metais Pesados/toxicidade , Antioxidantes , Óxidos , Superóxido Dismutase
6.
Pol Arch Intern Med ; 133(11)2023 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-37154798

RESUMO

INTRODUCTION: Gastroesophageal reflux disease (GERD) is a highly prevalent gastrointestinal disorder that causes diverse esophageal and extraesophageal symptoms. Many clinical practice guidelines (CPGs) have been issued around the world to provide practical evidence regarding GERD management. However, some of the recommendations discussed in various CPGs are inconsistent across individual documents. OBJECTIVES: We aimed to summarize the evidence from CPGs on GERD and assess the consistency of the recommendations. PATIENTS AND METHODS: In this scoping review, we identified current CPGs on the clinical management of GERD, which were comprehensively searched for in electronic databases and on relevant scientific websites. The recommendations were extracted using the population­intervention­comparison framework and were subsequently categorized into tables. RESULTS: Ultimately, 24 CPGs were identified. They included 86 recommendations, which were classified into 5 categories: definition, epidemiology, diagnosis, treatment, and complications. Among the identified recommendations, 68 were proposed in at least 2 CPGs, and they were assessed for the consistency of direction and strength. Overall, 32.4% of the recommendations (22/68) were consistent in direction and strength, whereas 60.3% (41/68) were consistent in direction but inconsistent in strength. Moreover, 7.4% (5/68) were inconsistent in direction. These referred to the relationship between GERD and tobacco consumption, Helicobacter pylori infection, diagnostic utility of the 2­week proton pump inhibitor test, cessation of special food, and antireflux surgery for GERD with extraesophageal symptoms. CONCLUSIONS: Most CPG recommendations regarding GERD were consistent in direction, except for 5 discrepancies, for which further well­designed, large­scale research is required to explain the inconsistency.


Assuntos
Refluxo Gastroesofágico , Infecções por Helicobacter , Helicobacter pylori , Humanos , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/terapia , Refluxo Gastroesofágico/complicações , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/complicações , Inibidores da Bomba de Prótons , Guias de Prática Clínica como Assunto
7.
Molecules ; 28(5)2023 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-36903420

RESUMO

The development of an efficient and straightforward method for cyanation of alcohols is of great value. However, the cyanation of alcohols always requires toxic cyanide sources. Herein, an unprecedented synthetic application of an isonitrile as a safer cyanide source in B(C6F5)3-catalyzed direct cyanation of alcohols is reported. With this approach, a wide range of valuable α-aryl nitriles was synthesized in good to excellent yields (up to 98%). The reaction can be scaled up and the practicability of this approach is further manifested in the synthesis of an anti-inflammatory drug, naproxen. Moreover, experimental studies were performed to illustrate the reaction mechanism.

8.
Science ; 379(6633): eade3392, 2023 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-36795806

RESUMO

Hou et al. challenged the giraffoid affinity of Discokeryx and its ecology and behavior. In our response we reiterate that Discokeryx is a giraffoid that, along with Giraffa, shows extreme evolution of head-neck morphologies that were presumably shaped by selective pressure from sexual competition and marginal environments.


Assuntos
Aclimatação , Evolução Biológica , Girafas , Seleção Sexual , Seleção Genética , Animais , Girafas/genética , Girafas/fisiologia
9.
Acupunct Med ; 41(4): 235-245, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36046956

RESUMO

OBJECTIVE: Neuroinflammation caused by traumatic brain injury (TBI) can lead to neurological deficits. Acupuncture can inhibit neuroinflammation and promote nerve repair; however, the specific mechanism is still unclear. The purpose of this study was to explore whether acupuncture could modulate the M1 and M2 phenotypic polarization of microglia in a rat model of TBI via the toll-like receptor 4 (TLR4)/intracellular toll-interleukin-1 receptor (TIR) domain-containing adaptor inducing interferon-ß (TRIF)/myeloid differentiation factor 88 (MyD88) pathway. METHODS: A total of 90 adult male Sprague-Dawley (SD) rats, SPF grade, were randomly divided into a normal group, model group and acupuncture group. Each group was further divided into three subgroups (first, third, and fifth day groups) according to the treatment time (n = 10 rats/subgroup). We used the modified neurological severity score (mNSS) method to quantify neurological deficits before and after modeling. We used Nissl staining to observe the pathological changes in brain tissue, flow cytometry to detect the proportion of M1 and M2 polarized microglia in the injured area on the first, third and fifth day, and co-immunoprecipitation (Co-IP) to examine TLR4/TRIF/MyD88 expression in microglia on the first, third and fifth day, as well as expression of the amount of binding of TLR4 with TRIF and MyD88. RESULTS: Compared to the model group, mNSS in the acupuncture group gradually decreased and pathological morphology improved. The proportion of CD11b/CD86 positive cells was decreased, while that of CD11b/CD206 was increased in the acupuncture group. Expression of IP TLR4, IP TRIF and IP MyD88 also decreased in the acupuncture group. CONCLUSION: The results of this study demonstrate that one of the mechanisms through which acupuncture mitigates neuroinflammation and promotes nerve repair in TBI rats may be inhibition of M1 phenotypic polarization and promotion of M2 phenotypic polarization through inhibition of the TLR4/TRIF/MyD88 signaling pathway.


Assuntos
Terapia por Acupuntura , Lesões Encefálicas Traumáticas , Ratos , Animais , Masculino , Microglia , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/farmacologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Ratos Sprague-Dawley , Doenças Neuroinflamatórias , Lesões Encefálicas Traumáticas/genética , Lesões Encefálicas Traumáticas/terapia , Lesões Encefálicas Traumáticas/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/farmacologia
10.
Science ; 376(6597): eabl8316, 2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35653459

RESUMO

The long neck of the giraffe has been held as a classic example of adaptive evolution since Darwin's time. Here we report on an unusual fossil giraffoid, Discokeryx xiezhi, from the early Miocene, which has an unusual disk-shaped headgear and the most complicated head-neck joints in known mammals. The distinctive morphology and our finite element analyses indicate an adaptation for fierce head-butting behavior. Tooth enamel isotope data suggest that D. xiezhi occupied a niche different from that of other herbivores, comparable to the characteristic high-level browsing niche of modern giraffes. The study shows that giraffoids exhibit a higher headgear diversity than other ruminants and that living in specific ecological niches may have fostered various intraspecific combat behaviors that resulted in extreme head-neck morphologies in different giraffoid lineages.


Assuntos
Adaptação Fisiológica , Evolução Biológica , Girafas , Cabeça , Pescoço , Seleção Sexual , Animais , Fósseis , Girafas/anatomia & histologia , Cabeça/anatomia & histologia , Pescoço/anatomia & histologia , Paleontologia
11.
Environ Sci Pollut Res Int ; 29(44): 66960-66978, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35513619

RESUMO

As the competition of tourism industry becomes increasingly white-hot, the sustainability and competitiveness of tourism economies inside a zone gradually gets people's attentions. Based on data of 16 cities from 2010 to 2019, this paper aims to investigate the sustainability and competitiveness of tourism economies in the Chengdu-Chongqing metropolitan area, by constructing a niche evaluation index and four niche models (niche ecostate-ecorole model, niche expansion model, niche breadth model, and niche overlap degree model). The results show that (1) during the sample period, the niche values of tourism competitiveness in most cities of the Chengdu-Chongqing metropolitan area have shown a sustained increasing trend, indicating that the status of these cities in resources, market, environment, social economy, and other dimensions is rising steadily, and their competitive advantages are gradually increasing; (2) the niche values of tourism competitiveness in the core cities of Chengdu-Chongqing metropolitan area (Chengdu and Chongqing) remain stable, while the niche values of tourism competitiveness in the remaining cities vary greatly; the comprehensive niche values of tourism industry competitiveness of the cities in the central area are significantly lower than those of the cities in the peripheral area; (3) the niche overlap of tourism competitiveness in the Chengdu-Chongqing metropolitan area is relatedly high, indicating that the homogenization of tourism in these cities is more serious.


Assuntos
Turismo , China , Cidades , Humanos
12.
Zhonghua Nan Ke Xue ; 28(4): 326-331, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37477454

RESUMO

OBJECTIVE: To investigate the repairing effect of Yishen Tongluo Prescription (YTP) on sperm DNA fragmentation index (DFI) in male rats exposed to benzo(a)pyrene (BaP) and its possible mechanism. METHODS: Thirty Wistar male rats were equally randomized into a blank control, a BaP-exposure and a YTP intervention group, those in the latter two groups exposed to BaP at 20 mg/kg/d for 60 consecutive days, and those in the YTP intervention group treated intragastrically with YTP from the 31st day of BaP exposure for a total of 30 days. After the last administration, the sperm DFI of the rats was detected by sperm chromatin structure analysis, the levels of FSH, LH and T in the serum and superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) and adenosine triphosphate (ATP) in the testis were measured by ELISA. RESULTS: Compared with the blank controls, the rats in the BaP-exposure group showed significantly increased DFI ( ï¼»4.23 ± 1.40ï¼½% vs ï¼»12.46 ± 3.07ï¼½%, P < 0.05), serum FSH (ï¼»1.76 ± 0.31ï¼½ vs ï¼»2.53 ± 0.28ï¼½ U/L, P < 0.05) and LH (ï¼»30.59 ± 2.14ï¼½ vs ï¼»39.72 ± 2.80ï¼½ U/L, P < 0.05), decreased levels of serum T (ï¼»5.33 ± 0.43ï¼½ vs ï¼»4.42 ± 0.38ï¼½ nmol/L, P < 0.05) and testicular SOD (ï¼»166.18 ± 3.74ï¼½ vs ï¼»113.23 ± 10.76ï¼½ U/ml, P < 0.05) and ATP (ï¼»41.23 ± 2.21ï¼½ vs ï¼»33.48 ± 2.74ï¼½ mol/L, P < 0.05), and elevated contents of MDA (ï¼»7.55 ± 0.93ï¼½ vs ï¼»10.59 ± 1.17ï¼½ nmol/ml, P < 0.05) and NO (ï¼»44.23±4.47ï¼½ vs ï¼»54.49 ± 3.13ï¼½ mol/L, P < 0.05). All the above parameters returned to normal after YTP intervention (DFI: ï¼»5.73 ± 2.46ï¼½%, FSH: ï¼»2.07 ± 0.45ï¼½ U/L, LH: ï¼»33.94 ± 4.44ï¼½ U/L, T: ï¼»4.96 ± 0.24ï¼½ nmol/L, SOD: ï¼»135.22 ± 7.26ï¼½ U/ml, ATP: ï¼»38.26 ± 2.14ï¼½ mol/L, MDA: ï¼»8.37 ± 1.29ï¼½ nmol/ml, NO: ï¼»48.36 ± 3.98ï¼½ mol/L), with statistically significant difference from those in the BaP-exposure group (all P < 0.05). CONCLUSION: Yishen Tongluo Prescription can repair BaP-induced sperm DNA damage in male rats, which may be attributed to its effects of suppressing oxidative damage.

13.
Innovation (Camb) ; 2(2): 100110, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34557760

RESUMO

The evolution of the Asian monsoon from the Late Oligocene to the Early Miocene is poorly understood. Here, we first reconstruct the precipitation data of central Tibet during 26-16 million years ago (Ma), applying the coexistence approach to sedimentary pollen data, and detect an intensified Asian monsoon with ∼1.35 Ma and ∼0.33 Ma cycles. Paleoclimate modeling is used to show the importance of paleogeographic location in the development of the paleomonsoon. In addition, the results of spectral analysis suggest that the fluctuations in the Asian monsoon during 26-16 Ma can be attributed to the long-period cyclicities in obliquity (∼1.2 Ma). These findings provide climate data that can be used to understand the Asian monsoon evolution during the Late Oligocene to Early Miocene and highlight the effects of paleogeographic patterns and long-period orbital forcings on the tectonic-scale evolution of the Asian monsoon.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34422083

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a kind of disorder of glucose and lipid metabolism with the main clinical manifestation of long-term higher blood glucose level than the normal value. Farnesol X receptor (FXR)/ceramide signaling pathway plays an important role in regulating cholesterol metabolism, lipid homeostasis, and the absorption of fat and vitamins in diet. Gegen Qinlian Decoction (GQD) is a classical herbal formula, which has a good clinical therapeutic effect on diabetes-related metabolic syndrome. OBJECTIVE: To investigate the effect of Gegen Qinlian Decoction (GQD) on hepatic gluconeogenesis in obese T2DM rats based on the FXR/ceramide signaling pathway regulating mitochondrial metabolism and endoplasmic reticulum stress (ERS). METHODS: ZDF (fa/fa) rats were fed with high-fat diet to establish the T2DM model; GQD was given to T2DM model rats by gavage; changes of the general state and body weight of rats were recorded; fasting blood glucose was detected; blood insulin, blood ceramide, glycosylated hemoglobin in blood, acetyl CoA in liver mitochondria, and bile salt lyase in intestinal tissue were detected by ELISA. The content of T-ß-MCA in blood was detected by LC-MS; the content of glycogen in liver tissue was detected by PAS staining; the expression of FXR, Sptlc2, and Smpd3 in ileum tissue, P-PERK, ATF6α, GRP78 BIP, and P-IRE1 in the liver, and CS and PC protein in liver mitochondria was detected by immunohistochemistry and western blot assay. The mRNA expression levels of FXR, Sptlc2, and Smpd3 in the ileum, PERK, ATF6α, GRP78 BIP, and IRE1 in the liver, and CS and PC in liver mitochondria were detected by qRT-PCR. RESULTS: GQD can improve the general state of T2DM rats, slow down their weight gain, reduce the levels of fasting blood glucose, fasting insulin, glycosylated hemoglobin, blood ceramide, bile salt hydrolase in intestinal tissue, and acetyl CoA in liver mitochondria of T2DM rats, and increase the contents of liver glycogen and T-ß-MCA in blood of T2DM rats. At the molecular level, GQD can inhibit the expression levels of FXR, Sptlc2, and Smpd3 in the ileum of T2DM rats and the protein and mRNA expression levels of oxidative stress-related factors in the liver. At the same time, GQD can increase the expression of CS and reduce the expression of PC in liver mitochondria of T2DM rats. CONCLUSION: GQD can inhibit the FXR/ceramide signaling pathway, regulate endoplasmic reticulum stress, enhance the CS activity of liver mitochondria, reduce the acetyl CoA level and PC activity of liver mitochondria, inhibit hepatic gluconeogenesis, protect islet ß-cells, and control blood glucose.

15.
Front Pharmacol ; 12: 682735, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995111

RESUMO

Resibufogenin (RBF), an active compound from Bufo bufonis, has been used for the treatment of multiple malignant cancers, including pancreatic cancer, colorectal cancer, and breast cancer. However, whether RBF could exert its antitumor effect by inhibiting angiogenesis remains unknown. Here, we aimed to explore the antiangiogenic activity of RBF and its underlying mechanism on human umbilical vein endothelial cell (HUVEC), and the therapeutic efficacy with regard to antiangiogenesis in vivo using two triple-negative breast cancer (TNBC) models. Our results demonstrated that RBF can inhibit the proliferation, migration, and tube formation of HUVECs in a dose-dependent manner. Spheroid sprouts were thinner and shorter after RBF treatment in vitro 3D spheroid sprouting assay. RBF also significantly suppressed VEGF-mediated vascular network formation in vivo Matrigel plug assay. In addition, Western blot analysis was used to reveal that RBF inhibited the phosphorylation of VEGFR2 and its downstream protein kinases FAK and Src in endothelial cells (ECs). Molecular docking simulations showed that RBF affected the phosphorylation of VEGFR2 by competitively binding to the ATP-bound VEGFR2 kinase domain, thus preventing ATP from providing phosphate groups. Finally, we found that RBF exhibited promising antitumor effect through antiangiogenesis in vivo without obvious toxicity. The present study first revealed the high antiangiogenic activity and the underlying molecular basis of RBF, suggesting that RBF could be a potential antiangiogenic agent for angiogenesis-related diseases.

16.
J Biomech ; 120: 110386, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33794414

RESUMO

There has been no systematic review evaluating the efficacy of electromyography (EMG) biofeedback after knee surgery recently. This meta-analysis aimed to determine whether EMG-biofeedback is effective for improving the range of motion (ROM), physical function, and pain relief in patients after knee. Randomized controlled trials (RCTs) assessing the effect of EMG-biofeedback after any knee surgery were retrieved from EMBASE, PubMed, Cochrane Library, Physiotherapy Evidence Database, ClinicalTrials.gov, ProQuest. This review identified 773 unique studies, and six RCTs were in the final meta-analysis. EMG-Biofeedback treatment has a significant difference compared to other rehabilitation therapy in knee ROM improving (SMD = -0.48, 95% CI = -0.82 to -0.14, p = 0.006, I2 = 37%). Moreover, there was no significant difference in pain (SMD = -0.33, 95% CI = -0.67 to0.02, p = 0.07, I2 = 41%) and physical function scores (MD = 1.83, 95% CI = -3.48 to7.14, p = 0.50, I2 = 0%). The results illustrate that EMG-biofeedback can improve knee ROM in patients after knee surgery. However, it is not superior to other rehabilitation methods for pain relief and physical function improvement.


Assuntos
Biorretroalimentação Psicológica , Articulação do Joelho , Eletromiografia , Humanos , Articulação do Joelho/cirurgia , Dor , Amplitude de Movimento Articular
18.
Zhonghua Nan Ke Xue ; 27(12): 1109-1112, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-37454321

RESUMO

Objective: To explore the repairing effect of Yishen Tongluo Recipe (YTR) on sperm DNA damage and its action mechanism in male rats exposed to benzo(a)pyrene (BaP). METHODS: Thirty-three adult male Wistar rats were equally divided into a normal control, a model control and a YTR intervention group. Sperm DNA damage was induced in the latter two groups of rats by exposing them to BaP at 20 mg/kg/d for 60 days, and the animals in the YTR group received a 30-day gavage administration of YTR suspension at 0.1 ml/10 g/d from the 31 day. Then the testis tissue of the rats was collected for examination of the sperm DNA fragmentation index (DFI) by fluorescence flow cytometry and determination of the expressions of APE1, FEN1, XRCC1 (and phosphorylated) proteins and mRNA in the BER pathway by Western blot and RT-PCR. RESULTS: After intervention, the sperm DFI was significantly decreased (P < 0.05) and the expressions of APE1, FEN1, XRCC1 (and phosphorylated) proteins and mRNA remarkably increased in the YTR group compared with the model controls (P < 0.05). CONCLUSIONS: Yishen Tongluo Recipe can reduce benzo(a)pyrene-induced sperm DFI in male rats by up-regulating the expression levels of APE1, FEN1, XRCC1 (and phosphorylated) proteins and improving the ability of sperm DNA base excision repair.

19.
Geriatr Orthop Surg Rehabil ; 11: 2151459320973196, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240559

RESUMO

BACKGROUND: Osteoarthritis is a degenerative disease that commonly occurs in middle-aged and elderly people. High-quality articles in the field of osteoarthritis rehabilitation have not been studied in detail. OBJECTIVE: To identify and conduct a qualitative and quantitative analysis of the 50 most-cited articles on osteoarthritis rehabilitation and provide valuable scientific information for researchers. METHODS: Fifty articles related to the rehabilitation of individuals with osteoarthritis were retrieved from the Web of Science Core Collection. Basic information, such as the authors, title, number of citations, year of publication, journal, country/territory, and research type, was extracted. CiteSpace was used to visualize the keywords. RESULTS: The average number of citations per article was 244.54. The top 50 articles were published in 27 journals and published by 262 authors. Most of the top 50 articles were published in the United States. The top 50 articles included 23 randomized controlled trials, 21 cohort studies, 2 case series, and 4 expert opinion articles. The most commonly studied topics in osteoarthritis rehabilitation included rehabilitation for pain, gait abnormalities, muscle strength deficiencies, and other functional impairments caused by osteoarthritis in elderly people. CONCLUSIONS: The top articles in the field of osteoarthritis rehabilitation have a high level of evidence. Collaboration between authors was high for highly-cited articles. Moreover, the eminent articles can provide important information for the education of doctors and therapists specializing in osteoarthritis rehabilitation.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...