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1.
Molecules ; 27(23)2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36500597

RESUMO

Three novel Ir(III) complexes, (ppy)2Ir(L-alanine) (Ir1) (ppy = 2-phenylpyridine), (F4ppy)2Ir(L-alanine) (Ir2) (F4ppy = 2-(4-fluorophenyl)pyridine), and (F2,4,5ppy)2Ir(L-alanine) (Ir3) (F2,4,5ppy = 2-(2,4,5-trifluorophenyl)pyridine), based on simple L-alanine as ancillary ligands were synthesized and investigated. Due to the introduction of fluorine substituents on the cyclometalated ligands, complexes Ir1-Ir3 exhibited yellow to sky-blue emissions (λem = 464-509 nm) in acetonitrile solution. The photoluminescence quantum yields (PLQYs) of Ir1-Ir3 ranged from 0.48-0.69, of which Ir3 with sky-blue luminescence had the highest PLQY of 0.69. The electrochemical study and density functional theory (DFT) calculations show that the highest occupied molecular orbital (HOMOs) energy of Ir1-Ir3 are stabilized by the introduction of fluorine substituents on the cyclometalated ligands, while L-alanine ancillary ligand has little contribution to HOMOs and lowest unoccupied molecular orbitals (LUMOs). Moreover, Ir1-Ir3 presented an excellent response to Cu2+ with a high selectivity, strong anti-interference ability, and short response time. Such a detection was based on significant phosphorescence quenching of their emissions, showing the potential application in chemosensors for Cu2+.


Assuntos
Irídio , Compostos Organometálicos , Irídio/química , Ligantes , Compostos Organometálicos/química , Luminescência , Íons , Flúor , Alanina
2.
World J Clin Cases ; 10(35): 13044-13051, 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36568994

RESUMO

BACKGROUND: Whipple's disease is a rare systemic infection caused by Tropheryma whipplei. Most patients present with nonspecific symptoms, and routine laboratory and imaging examination results also lack specificity. The diagnosis often relies on invasive manipulation, pathological examination, and molecular techniques. These difficulties in diagnosing Whipple's disease often result in misdiagnosis and inappropriate treatments. CASE SUMMARY: This paper reports on the case of a 58-year-old male patient who complained of fatigue and decreased exercise capacity. The results of routine blood tests indicated hypochromic microcytic anemia. Results of gastroscopy and capsule endoscopy showed multiple polypoid bulges distributed in the duodenal and proximal jejunum. A diagnosis of small intestinal adenomatosis was initially considered; hence, the Whipple procedure, a pylorus-preserving pancreaticoduodenectomy, was performed. Pathological manifestations showed many periodic acid-Schiff-positive macrophages aggregated in the intestinal mucosa of the duodenum, upper jejunum, and surrounding lymph nodes. Based on comprehensive analysis of symptoms, laboratory findings, and pathological manifestations, the patient was finally diagnosed with Whipple's disease. After receiving 1 mo of antibiotic treatment, the fatigue and anemia were significantly improved. CONCLUSION: This case presented with atypical gastrointestinal manifestations and small intestinal polypoid bulges, which provided new insight on the diagnosis of Whipple's disease.

3.
Nutr Metab (Lond) ; 19(1): 85, 2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36581855

RESUMO

BACKGROUND: Type 2 diabetes (T2D) combined with hypertension has a higher risk of developing cardiovascular diseases. This study aimed to investigate the relationships between the surrogate indicators of insulin resistance (TyG, TG/HDL, and Mets-IR) with the risk of T2D combined with hypertension. METHODS: This study is based on a functional community cohort from Beijing and the China Health and Retirement Longitudinal Study, comprising 4234 and 4658 participants respectively. Cox proportional hazards models and restricted cubic spline regression were performed to assess the link between TyG, TG/HDL, and Mets-IR with T2D combined with hypertension. The cross-lagged panel analysis and the mediation analysis were used to examine the temporal relationship between insulin resistance and obesity and their temporal relationship with follow-up T2D combined with hypertension. RESULTS: In multivariable-adjusted models, higher TyG was associated with a higher risk of developing T2D combined with hypertension, the hazard ratios (95% confidence interval) were 3.46 (2.43-4.93) and 2.02 (1.67-2.44), in two cohorts respectively. A similar positive association was shown for Mets-IR, the hazard ratios (95% confidence interval) were 1.04 (1.03-1.06) and 1.05 (1.03-1.07), in two cohorts respectively. However, the association between TG/HDL with T2D combined with hypertension was different in two cohorts. The restricted cubic spline regression showed a linear association between TyG and T2D combined with hypertension (P-nonlinear > 0.05). The cross-lagged path coefficient from baseline BMI to follow-up TyG index was significantly greater than the path coefficient from baseline TyG to follow-up BMI. TyG partially mediated the effect of BMI on the risk of T2D combined with hypertension and the percentage of mediated association was estimated at 41.58% and 48.41% in two cohorts, respectively. CONCLUSION: These findings indicated positive associations between TyG and Mets-IR with the risk of T2D combined with hypertension in two cohorts. In addition, BMI change may precede TyG index change, and the TyG index plays a mediating role in BMI induced T2D combined with hypertension.

4.
Obes Res Clin Pract ; 2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36586764

RESUMO

AIM: To assess the relationship between waist-to-height ratio (WHtR) and the incidence of type 2 diabetes (T2D)/impaired fasting glucose (IFG) and to explore to what extent these associations are mediated by blood pressure, lipids and other indicators related to liver and kidney metabolism. MATERIALS AND METHODS: This study was based on a functional community cohort included 6109 participants which were divided into two sub-cohorts. One sub-cohort included participants with normal fasting glucose (n = 5563), another included IFG individuals at baseline (n = 546). Cox regression models were used to evaluate the relationships of WHtR with T2D/IFG. Four-year time-dependent receiver operating characteristic (ROC) curve and area under curve (AUC) were calculated to estimate the discriminatory power of WhtR and other anthropometric indices on T2D. Mediation analysis was performed to estimate which risk factors mediate the association between WHtR and T2D. RESULTS: Significant positive associations were found between WHtR and the incidence of T2D/IFG in both sub-cohort. WhtR was a useful predictor of T2D (P < 0.05). Mediation analysis showed that HOMA-IR (0.45 %), SBP (5.10 %), triglycerides (11.02 %), creatinine (9.36 %) and combined kidney indicators (17.48 %) partly mediated the effect of WHtR on T2D in men. For women, this association was partly mediated by SBP (13.86 %), HDL (24.54 %), ALT (6.29 %), UA (22.58 %) and combined kidney indicators (39.51 %). CONCLUSIONS: WHtR was an independent risk factor for the development of T2D and IFG. This association was partly mediated by HOMA-IR, SBP, lipids and other liver and kidney metabolism indicators.

5.
Transl Cancer Res ; 11(10): 3634-3644, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36388013

RESUMO

Background: Accumulating data have shown that high expression of CD73 is associated with poor prognosis in various cancers, however the role and significance of CD73 in clear-cell renal cell carcinoma (ccRCC) still remain unclear. The present study aims to evaluate the prognostic significance of CD73 in ccRCC and explore the potential function in vitro and in vivo. Methods: Firstly, the expression of CD73 in ccRCC was detected using clinical tissues and verified using TCGA and GEO data. Immunohistochemistry and Kaplan-Meier test were performed for survival analysis. Furthermore, knockdown or overexpression of CD73 was conducted by lentivirus transfection in ccRCC cells. MTT assay, colony formation assay, wound healing assay, transwell assay and xenograft assay were performed in vitro or in vivo. Results: Our results showed that CD73 was highly expressed in ccRCC, and high expression of CD73 was negatively correlated with prognosis. In addition, CD73 promoted cell proliferation and migration in vitro and in vivo. Our data also showed that CD73 played both enzymatic and non-enzymatic functions in the regulation of cell proliferation and migration in ccRCC. Conclusions: These findings suggested that CD73 might promote the growth of ccRCC and contribute to poor prognosis. Taken together, CD73 may be a potential therapeutic target in ccRCC.

6.
Hypertens Res ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357616

RESUMO

Elevated serum uric acid (SUA) is associated with the incidence of hypertension, but whether relevant metabolic factors have mediating effects is not certain. Our study was based on a functional community cohort established in Beijing. In 2015, a total of 7482 individuals without hypertension were recruited and followed up until 2019. Multivariate logistic regression analysis was used to investigate the association between SUA and hypertension. Cross-lagged panel analysis and mediation analysis were used to explore the effects of metabolic factors on the association between SUA and incident hypertension. During the average 4-year follow-up, the cumulative incidence of hypertension was 10.9% (n = 580). SUA was an independent risk factor for hypertension, and the RRs (95% CI) for subjects with baseline SUA levels in quartile 2, quartile 3 and quartile 4 were 1.20 (0.88-1.63), 1.50 (1.10-2.05), and 1.57 (1.11-2.22) compared to those in quartile 1, respectively. The cross-lagged panel analysis showed that the increases in Cr, TG, LDL, ALT, AST and WBC occurred after SUA increased (P < 0.001). Among these factors, TG, WBC and ALT played an intermediary role in both men (TG: 14.76%; WBC: 11.61%; ALT: 15.93%) and women (TG: 14.55%; WBC: 8.55%; ALT: 6.89%). The elevated SUA concentration was an independent risk factor for hypertension in the Chinese population, and TG, WBC and ALT had important mediating effects on the association between SUA and hypertension.

7.
Artigo em Inglês | MEDLINE | ID: mdl-36231508

RESUMO

The Himalayan region is a fragile high mountain landscape where the population experiences acute vulnerability within a complex coupled human-natural system due to environmental, social, and economic linkages. The lack of significant regional and spatial knowledge of multi-faceted vulnerabilities hinders any potential recommendations to address these vulnerabilities. We systematically reviewed the literature to recommend mitigation interventions based on the region's socio-economic and ecological vulnerability research to date. We applied the PRISMA (Preferred Reporting of Items for Systematic Review and Meta-Analysis) criteria to search for results from four comprehensive databases. For our assessment, we compiled a final sample (n = 59) of vulnerability research papers to examine the vulnerability types, spatial variation, assessment methodology, and significant drivers of change. Our study represented all Himalayan countries, namely, India, Nepal, Pakistan, China, and Bhutan. More than half of the vulnerability studies were conducted in the central Himalayan region, a quarter in the western Himalayas, and a few in the eastern Himalayas. Our review revealed that the primary drivers of change were climate change, land use/land cover, and glacial lake formation. The vulnerability assessments in the Himalayan region primarily used social science methods as compared to natural science methods. While the vulnerability studies seldom assessed mitigation interventions, our analysis identified fourteen recommendations. The recommended interventions mainly included policy interventions, livelihood improvement, and adaptation measures. This study emphasized that sustainable development requires cross-sectoral interventions to manage existing resources and mitigate the confronting vulnerabilities of the region.


Assuntos
Mudança Climática , Lagos , Aclimatação , Humanos , Índia , Nepal
8.
Front Endocrinol (Lausanne) ; 13: 947497, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120445

RESUMO

Background: Nephrolithiasis is a common complication of primary hyperparathyroidism (PHPT), and the recurrence of nephrolithiasis in patients with PHPT is also an urgent concern. What is worse, there is a scarcity of recommended evaluation to predict the risk of nephrolithiasis recurrence in patients with PHPT. This study was aimed to develop and validate a nomogram to facilitate risk assessment in patients with PHPT. Methods: A total of 197 patients with PHPT were retrospectively included in this study from September 2016 to August 2021. Patients' demographic data, blood test parameters, urinalysis, stone parameters, and surgical intervention were collected. Extracted variables were submitted to a least absolute shrinkage and selection operator (LASSO) regression model. A nomogram was built and validated according to the area under the curve (AUC) value, calibration curve, and decision curve analysis. Results: According to the LASSO regression and logistic regression analyses, five predictors were derived from 22 variables: creatinine, uric acid, bilateral stone, multiplicity, and surgery. The AUC and concordance index of the training cohort and validation cohort were 0.829 and 0.856, and 0.827 and 0.877, respectively. The calibration curve analysis and the decision curve analysis showed that the nomogram had an adequate prediction accuracy. Conclusion: We built a useful nomogram model to predict the risk of nephrolithiasis recurrence in patients with PHPT. This would assist clinicians to provide appropriate advices and managements for these patients.


Assuntos
Hiperparatireoidismo Primário , Nefrolitíase , Creatinina , Humanos , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/cirurgia , Nefrolitíase/complicações , Nefrolitíase/diagnóstico , Nomogramas , Estudos Retrospectivos , Ácido Úrico
9.
Eur Radiol ; 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36136108

RESUMO

OBJECTIVES: A drug-coated balloon (DCB) has potential applications in the treatment of intracranial atherosclerotic disease (ICAD). We aimed to evaluate changes of vessel wall features of ICAD lesions after DCB treatment by using vessel wall MRI (VWMRI). METHODS: We retrospectively included patients with symptomatic ICAD who underwent DCB angioplasty alone. The incidences of stenosis of the lumen area, vessel wall thickening, hyperintense plaques, and prominent wall enhancement were compared between the baseline and follow-up VWMRI. RESULTS: There were 29 ICAD lesions from 29 patients, of which 22 were stenosis and 7 were occlusion. The median interval between DCB treatment and follow-up VWMRI was 4.1 [3.3, 6.7] months. After DCB treatment, follow-up VWMRI showed a significant decrease in the stenosis degree of the lumen area (83% [71%, 96%] vs 15% [3%, 41%], p < 0.001). Thirty-eight percent (11/29) of the patients observed normal appearance of the target vessel wall on follow-up VWMRI. In the stenosis group, the prevalence of hyperintense plaques decreased from 66.7% (14/21) at baseline to 23.8% (5/21) at follow-up, and prominent wall enhancement decreased from 66.7% (14/21) at baseline to 19.0%(4/21) at follow-up. The incidence of hyperintense plaques (p = 0.028) and vessel wall thickening (p = 0.018) tended to decrease with follow-up time. Although not significant (p = 0.106), a similar trend was observed between the incidence of prominent wall enhancement and follow-up time. CONCLUSION: Vascular healing with plaque modification and stabilization occurred following DCB treatment of ICAD lesions. KEY POINTS: • A drug-coated balloon (DCB) has potential applications in the treatment of intracranial atherosclerotic disease (ICAD). • Vascular healing with plaque modification and stabilization occurred following DCB treatment of ICAD lesions.

10.
Artigo em Inglês | MEDLINE | ID: mdl-36112200

RESUMO

The olfactory pathways of the insect brain have been studied comprehensively for more than 40 years, yet the last decade has included a particularly large accumulation of new information relating to this system's structure. In moths, sharp intracellular recording and staining has been used to elucidate the anatomy and physiology of output neurons from the primary olfactory center, the antennal lobe. This review concentrates on the connection patterns characterizing these projection neurons, which follow six separate antennal-lobe tracts. In addition to highlighting the connections between functionally distinct glomerular clusters and higher-order olfactory neuropils, we discuss how parallel tracts in the male convey distinct features of the social signals released by conspecific and heterospecific females. Finally, we consider the current state of knowledge regarding olfactory processing in the moth's protocerebrum and make suggestions as to how the information concerning antennal-lobe output may be used to design future studies.

11.
Int Immunopharmacol ; 110: 108926, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35728306

RESUMO

BACKGROUND AND OBJECTIVE: Nephrotoxicity induced by the chemotherapeutic drug arsenic trioxide (ATO) is often overlooked, and the underlying mechanisms remain poorly understood. Based on network pharmacology and experimental validation, this study investigates the protection of 6-gingerol (6G) against ATO-induced nephrotoxicity and the potential mechanisms. METHODS: We screened and collected 6G and disease-related targets and then imported the interaction targets into a String database to construct protein-protein interaction (PPI) networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Mice were injected intraperitoneally with ATO (5 mg/kg) for seven days to induce nephrotoxicity, and then the histological morphology of the kidneys, biochemical indices of serum and tissues, and associated protein expressions were observed. RESULTS: The network pharmacology results revealed that the effects of 6G against nephrotoxicity are closely related to apoptosis, and the MAPKs pathway was screened for validation. In animal experiments, 6G improved the histopathological morphology of the kidneys, reduced the levels of renal function markers, enhanced antioxidant activity, and decreased the levels of inflammation. Furthermore, 6G reduced apoptotic cells in kidney tissues, decreased the levels of Bax and c-Caspase-3, and increased the level of Bcl-2. The results of immunohistochemistry and western blotting revealed that 6G significantly inhibited the expressions of p-p38, p-ERK, and p-JNK. CONCLUSION: The results comprehensively demonstrate the protective effects of 6G against ATO-induced nephrotoxicity. The effects are related to anti-oxidant, anti-inflammatory, and anti-apoptotic properties, possibly through inhibition of the MAPKs pathway.


Assuntos
Arsenicais , Animais , Anti-Inflamatórios , Antioxidantes , Trióxido de Arsênio , Arsenicais/farmacologia , Catecóis , Álcoois Graxos , Camundongos , Óxidos
12.
Phytother Res ; 36(9): 3619-3631, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35747908

RESUMO

Liquiritigenin (Lq) offers cytoprotective effects against various cardiac injuries, but its beneficial effects on myocardial ischemic (MI) injury and the related mechanisms remain unclear. In the in vivo study, an animal model of MI was induced by intraperitoneal injection of isoproterenol (Iso, 85 mg/kg). ECG, heart rate, serum levels of CK and CK-MB, histopathological changes, and reactive oxygen species (ROS) levels were all measured. In vitro, H9c2 cells were divided into four groups and treated for 24 hr with liquiritigenin (30 µmol/L and 100 µmol/L) followed with CoCl2 (800 µmol/L) for another 24 hr. Cell viability, apoptosis, mitochondrial membrane potential, and intracellular Ca2+ concentration ([Ca2+ ]i ) were then assessed. The L-type Ca2+ current (ICa-L ) was detected using a patch clamp technique on isolated rat ventricular myocytes. The myocyte contraction and Ca2+ transients were measured using an IonOptix detection system. The remarkable cardiac injury and generation of intracellular ROS induced by Iso were alleviated via treatment with Lq. CoCl2 administration induced cell apoptosis, mitochondrial dysfunction, and Ca2+ overload in H9c2; Lq reduces these deleterious effects of CoCl2 . Meanwhile, Lq blocked ICa-L in a dose-dependent manner. The half-maximal inhibitory concentration of Lq was 110.87 µmol/L. Lq reversibly reduced the amplitude of cell contraction as well as the Ca2+ transients. The results show that Lq protects against MI injury by antioxidation, antiapoptosis, counteraction mitochondrial dysfunction, and inhibition of ICa-L , thus damping intracellular Ca2+ .


Assuntos
Miocárdio , Estresse Oxidativo , Animais , Apoptose , Cálcio/metabolismo , Flavanonas , Contração Miocárdica , Miocárdio/patologia , Miócitos Cardíacos , Ratos , Espécies Reativas de Oxigênio/metabolismo
13.
Front Pharmacol ; 13: 868393, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571130

RESUMO

Background and Objective: Arsenic trioxide (As2O3) induced cardiotoxicity to limit the clinical applications of the effective anticancer agent. 6-Gingerol (6G) is the main active ingredient of ginger, a food with many health benefits. The present study aims to investigate the potential pharmacological mechanisms of 6G on As2O3-induced myocardial injury. Methods and Results: Fifty KunMing mice were divided into five groups (n = 10) receiving: 1) physiological saline; 2) 6G (20 mg/kg) alone; 3) As2O3 (5 mg/kg); 4) 6G (10 mg/kg) and As2O3 (5 mg/kg); 5) 6G (20 mg/kg) and As2O3 (5 mg/kg). 6G was given orally and As2O3 was given intraperitoneally once per day for seven consecutive days. Biochemical, histopathological, transmission electron microscopy, ELISA, and western blotting analyses were then performed. Based on the resultant data, As2O3 was found to induce cardiotoxicity in mice. 6G significantly ameliorated As2O3-induced heart injury, histopathological changes, oxidative stress, myocardial mitochondrial damage, inflammation, and cardiomyocyte apoptosis, while reversed As2O3-induced inhibition of the AMPK/SIRT1/PGC-1α pathway. Conclusion: Our experimental results reveal that 6G effectively counteracts As2O3-induced cardiotoxicity including oxidative stress, inflammation and apoptosis, which might be attributed to its activation action on AMPK/SIRT1/PGC-1α signaling pathway.

14.
J Immunol ; 208(11): 2508-2514, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35545292

RESUMO

Observational studies highlight associations of IgG N-glycosylation with rheumatoid arthritis (RA); however, the causality between these conditions remains to be determined. Standard and multivariable two-sample Mendelian randomization (MR) analyses integrating a summary genome-wide association study for RA and IgG N-glycan quantitative trait loci (IgG N-glycan-QTL) data were performed to explore the potentially causal associations of IgG N-glycosylation with RA. After correcting for multiple testing (p < 2 × 10-3), the standard MR analysis based on the inverse-variance weighted method showed a significant association of genetically instrumented IgG N-glycan (GP4) with RA (odds ratioGP4 = 0.906, 95% confidence interval = 0.857-0.958, p = 5.246 × 10-4). In addition, we identified seven significant associations of genetically instrumented IgG N-glycans with RA by multivariable MR analysis (p < 2 × 10-3). Results were broadly consistent in sensitivity analyses using MR_Lasso, MR_weighted median, MR_Egger regression, and leave-one-out analysis with different instruments (all p values <0.05). There was limited evidence of pleiotropy bias (all p values > 0.05). In conclusion, our MR analysis incorporating genome-wide association studies and IgG N-glycan-QTL data revealed that IgG N-glycans were potentially causally associated with RA. Our findings shed light on the role of IgG N-glycosylation in the development of RA. Future studies are needed to validate our findings and to explore the underlying physiological mechanisms in the etiology of RA.


Assuntos
Artrite Reumatoide , Estudo de Associação Genômica Ampla , Artrite Reumatoide/genética , Humanos , Imunoglobulina G/genética , Polimorfismo de Nucleotídeo Único , Polissacarídeos , Locos de Características Quantitativas
15.
Insect Sci ; 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35608046

RESUMO

The mechanism of sex pheromone reception in the male cotton bollworm Helicoverpa armigera has been extensively studied because it has become an important model system for understanding insect olfaction. However, the pathways of pheromone processing from the antenna to the primary olfactory center in H. armigera have not yet been clarified. Here, the physiology and morphology of male H. armigera olfactory sensory neurons (OSNs) were studied using single sensillum recording along with anterograde filling and intracellular recording with retrograde filling. OSNs localized in type A sensilla responded to the major pheromone component cis-11-hexadecenal, and the axonal terminals projected to the cumulus (Cu) of the macroglomerular complex (MGC). The OSNs in type B sensilla responded to the behavioral antagonist cis-9-tetradecenal, and the axonal terminals projected to the dorsomedial anterior (DMA) unit of the MGC. In type C sensilla, there were 2 OSNs: one that responded to cis-9-tetradecenal and cis-11-hexadecenol with the axonal terminals projecting to the DMA, and another that responded to the secondary pheromone components cis-9-hexadecenal and cis-9-tetradecenal with the axonal terminals projecting to the dorsomedial posterior (DMP) unit of the MGC. Type A and type B sensilla also housed the secondary OSNs, which were silent neurons with axonal terminals projected to the glomerulus G49 and DMP. Overall, the neural pathways that carry information on attractiveness and aversiveness in response to female pheromone components in H. armigera exhibit distinct projections to the MGC units.

16.
J Pharm Pharmacol ; 74(8): 1133-1139, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35511715

RESUMO

OBJECTIVES: Gingerols are bioactive compounds derived from ginger, our experiment investigates the effects of 6-, 8- and 10-Gin on the human ether-à-go-go-related gene (hERG) K+ channels by using patch clamp technology. KEY FINDINGS: hERG K+ currents were suppressed by 6-, 8- and 10-Gin in a concentration-dependent manner. The IC50 values of 6-, 8- and 10-Gin were 41.5, 16.1 and 86.5 µM for the hERG K+ currents, respectively. The maximum inhibitory effects caused by 6-, 8- and 10-Gin were 44.3% ± 2.0%, 88.6% ± 1.3% and 63.1% ± 1.1%, respectively, and the effects were almost completely reversible. CONCLUSION: These findings suggest that 8-Gin is the most potent hERG K+ channel inhibitor among gingerol components and may offer a new approach for understanding and treating cancer.


Assuntos
Canais de Potássio Éter-A-Go-Go , Gengibre , Catecóis , Canais de Potássio Éter-A-Go-Go/genética , Éteres , Álcoois Graxos , Células HEK293 , Humanos , Bloqueadores dos Canais de Potássio/farmacologia
17.
Transl Stroke Res ; 2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35460456

RESUMO

Patients with medically refractory non-acute intracranial artery occlusion (ICAO) are difficult to treat. The optimal intervention for these patients is not known. We evaluated the feasibility and safety of drug-coated balloon (DCB) treatment for non-acute ICAO. Consecutive patients with symptomatic medically refractory atherosclerotic non-acute ICAO from January 2015 to July 2021 who underwent DCB treatment were retrospectively analyzed. The rates of stroke, transient ischemic attack, and death within 30 days and the follow-up results were evaluated. A total of 148 patients were enrolled in this study. The 30-day rate of stroke, transient ischemic attack, and death was 8.8%. During the 25.8 ± 15.8-month clinical follow-up period, the rate of outcome beyond 30 days was 4.7%. In the 66 patients with vessel imaging follow-up, 13.6% (9/66) had restenosis. The present study suggests that DCB dilatation is a feasible and effective alternative in carefully selected patients with symptomatic non-acute ICAO.

18.
Insects ; 13(3)2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35323582

RESUMO

The present study was dedicated to investigating the anatomical organization of distinct neuropils within the two brain hemispheres of a gynandromorphic moth of the species Helicoverpa armigera. High quality confocal imaging of a synapsin immuno-stained preparation combined with three-dimensional reconstructions made it possible to identify several brain structures involved in processing odor input and to measure their volumes in the male and female hemispheres. Thus, in addition to reconstructing the antennal lobes, we also made digital models of the mushroom body calyces, the pedunculus, and the vertical and medial lobes. As previously reported, prominent sexual dimorphism was demonstrated in the antennal lobes via the identification of a male-specific macroglomerular complex (MGC) and a female-specific complex (Fc) in each of the two brain hemispheres of the gynandromorph. Additionally, sex-specific differences were found in volume differences for three other neuropil structures-the calyces, pedunculus, and vertical lobe. The putative purpose of larger volumes of three mushroom body neuropils in females as compared to males is discussed.

19.
Exp Ther Med ; 23(4): 276, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35317438

RESUMO

Magnesium isoglycyrrhizinate (MgIG) has anti-inflammatory, antioxidative, antiviral and anti-hepatotoxic effects. However, protective effects of MgIG against renal damage caused by arsenic trioxide (ATO) have not been reported. The present study aimed to clarify the protective function of MgIG on kidney damaged induced by ATO. Other than the control group and the group treated with MgIG alone, mice were injected intraperitoneally with ATO (5 mg/kg/day) for 7 days to establish a mouse model of kidney damage. On the 8th day, blood and kidney tissue were collected and the inflammatory factors and antioxidants levels in the kidney tissue and serum were measured. The expression of protein levels of caspase-3, Bcl-2, Bax, Toll-like receptor-4 (TLR4) and nuclear factor-κB (NF-κB) were determined via western blot analysis. In the renal tissue of mice, ATO exposure dramatically elevated markers of oxidative stress, apoptosis and inflammation. However, MgIG could also restore the activities of urea nitrogen and creatinine to normal levels, decrease the malondialdehyde level and reactive oxygen species formation and increase superoxide dismutase, catalase and glutathione activities. MgIG also ameliorated the morphological abnormalities generated by ATO, reduced inflammation and apoptosis and inhibited the TLR4/NF-κB signaling pathway. In conclusion, MgIG may mitigate ATO-induced kidney damage by decreasing apoptosis, oxidative stress and inflammation and its mechanism may be connected to the inhibition of TLR4/NF-κB signaling.

20.
J Nutr Biochem ; 104: 108975, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35245652

RESUMO

Ginger, one of the most widely consumed condiment for various foods and beverages, has many pharmacological effects. 6-gingerol, a naturally occurring phenol, is one of the major pungent constituents of ginger. The purpose of this study was to characterize the effect of 6-gingerol on the p38/Nrf2/HO-1 and p38/NF-κB signaling pathway, as a possible means of combating hypoxia-related oxidative stress. H9c2 cells were chemically induced with CoCl2 to mimic hypoxia-associated cellular damage. Cardiomyocyte injury was assessed by lactate dehydrogenase and creatine kinase. Reactive oxygen species production was assessed by 2',7'-dichlorodihydrofluorescein diacetate. The antioxidative property of 6-gingerol was measured by estimating the activities of superoxide dismutase, catalase, glutathione and glutathione disulfide. Apoptosis was detected by flow cytometry after Annexin V-FITC-propidium iodide double staining. Western blotting was used to evaluate levels of p-p38, p38, cytoplasm p65, nuclear p65, total p65, nuclear Nrf2, total Nrf2, Keap1, HIF-1α, and HO-1. 6-gingerol was able to counter hypoxia-induced cardiomyocyte injury as evidenced by inhibiting the levels of oxidative stress indexes and increasing the percentage of apoptosis. Furthermore, 6-gingerol was able to down-regulate p-p38/p38, nuclear p65, total p65 and Keap1 expression induced by CoCl2 stimulation and increased cytoplasm p65, nuclear Nrf2, total Nrf2, HO-1, and HIF-1α expression. However, treatment with specific Nrf2 inhibitor blunted the activation of Nrf2 signaling and removed the protective effects of 6-gingerol. These experiments provide evidence that 6-gingerol exerts cytoprotective effects, which may be associated with the regulation of oxidative stress and apoptosis, potentially through activating the Nrf2 pathway and inhibiting the p38/NF-κB pathways.


Assuntos
Fator 2 Relacionado a NF-E2 , NF-kappa B , Catecóis , Álcoois Graxos , Heme Oxigenase-1/metabolismo , Humanos , Hipóxia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
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