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1.
Pestic Biochem Physiol ; 172: 104768, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33518055

RESUMO

The melon aphid, Aphis gossypii, is an important pest of vegetables. Insecticide resistance in A. gossypii has increased due to the frequent use of insecticides. We studied the levels and mechanisms of A. gossypii resistance to imidacloprid, acetamiprid and lambda-cyhalothrin here. The resistance levels of the three insecticides in 20 populations of A. gossypii varied. When compared to the susceptible strain (Lab-SS), there were two moderate resistance (MR) populations and nine low resistance (LR) populations to imidacloprid, respectively, two MR populations and two LR populations to acetamiprid, respectively, and, five MR populations and two LR populations to λ-cyhalothrin, respectively. Gene mutation detection in the MR level populations showed arginine to threonine substitution (R81T) in three populations and lysine to glutamine substitution (K264E) in the nicotinic acetylcholine receptor (nAChR) ß1 subunit in one population, respectively. No valine to isoleucine substitution (V62I) was found in the nAChR ß1 subunit in any of the tested populations. The leucine to phenylalanine substitution (L1014F) in sodium channel α subunit was found in five MR populations. The relative expression of the CYP6CY13 gene was significantly upregulated in the Daiyue and Shenxian populations. The CYP6CY14 gene was significantly upregulated in Daiyue, Dongchangfu, Shenxian, Mengyin and Anqiu populations. The CYP6CY19 gene was significantly upregulated in the Dongchangfu and Mengyin populations. The relative expressions of the esterase E4 or FE4 genes were significantly upregulated in most of the MR populations. These results provide insight into the current insecticide resistance of A. gossypii and may contribute to more effective resistance management strategies.


Assuntos
Afídeos , Cucurbitaceae , Inseticidas , Animais , Afídeos/genética , China , Resistência a Inseticidas/genética , Inseticidas/toxicidade
2.
Anesthesiology ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33592096

RESUMO

BACKGROUND: Recent work suggests that having aortic valve surgery in the morning increases risk for cardiac-related complications. This study therefore explored whether mortality and cardiac complications, specifically low cardiac output syndrome, differ for morning and afternoon cardiac surgeries. METHODS: The study included adults who had aortic and/or mitral valve repair/replacement and/or coronary artery bypass grafting from 2011 to 2018. The components of the in-hospital composite outcome were in-hospital mortality and low cardiac output syndrome, defined by requirement for at least two inotropic agents at 24 to 48h postoperatively or need for mechanical circulatory support. Patients who had aortic cross-clamping between 8 and 11 am (morning surgery) versus between 2 and 5 pm (afternoon surgery) were compared on the incidence of the composite outcome. RESULTS: Among 9,734 qualifying operations, 0.4% (29 of 6,859) died after morning, and 0.7% (20 of 2,875) died after afternoon surgery. The composite of in-hospital mortality and low cardiac output syndrome occurred in 2.8% (195 of 6,859) of morning patients and 3.4% (97 of 2,875) of afternoon patients: morning versus afternoon confounder-adjusted odds ratio, 0.96 (95% CI, 0.75 to 1.24; P = 0.770). There was no evidence of interaction between morning versus afternoon and surgery type (P = 0.965), and operation time was statistically nonsignificant for surgery subgroups. CONCLUSIONS: Patients having aortic valve surgery, mitral valve surgery, and/or coronary artery bypass grafting with aortic cross-clamping in the morning and afternoon did not have significantly different outcomes. No evidence was found to suggest that morning or afternoon surgical timing alters postoperative risk.

3.
Environ Pollut ; 276: 116707, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33609902

RESUMO

The space-borne measured fine-mode aerosol optical depth (fAOD) is a gross index of column-integrated anthropogenic particulate pollutants, especially over the populated land. The fAOD is the product of the AOD and the fine-mode fraction (FMF). While there exist numerous global AOD products derived from many different satellite sensors, there have been much fewer, if any, global FMF products with a quality good enough to understand their spatiotemporal variations. This is key to understanding the global distribution and spatiotemporal variations of air pollutants, as well as their impacts on global environmental and climate changes. Modifying our newly developed retrieval algorithm to the latest global-scale Moderate Resolution Imaging Spectroradiometer (MODIS) aerosol product (Collection 6.1), a global 10-year FMF product is generated and analyzed here. We first validate the product through comparisons with the FMF derived from Aerosol Robotic Network (AERONET) measurements. Among our 169,313 samples, the satellite-derived FMFs agreed with the AERONET spectral deconvolution algorithm (SDA)-retrieved FMFs with a root-mean-square error (RMSE) of 0.22. Analyzed using this new product are the global patterns and interannual and seasonal variations of the FMF over land. In general, the FMF is large (>0.80) over Mexico, Myanmar, Laos, southern China, and Africa and less than 0.5 in the Sahelian and Sudanian zones of northern Africa. Seasonally, higher FMF values occur in summer and autumn. The linear trend in the satellite-derived and AERONET FMFs for different countries was explored. The upward trend in the FMFs was particularly strong over Australia since 2008. This study provides a new global view of changes in FMFs using a new satellite product that could help improve our understanding of air pollution around the world.

4.
Acta Pharm Sin B ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33614402

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become one major threat to human population health. The RNA-dependent RNA polymerase (RdRp) presents an ideal target of antivirals, whereas nucleoside analogs inhibitor is hindered by the proofreading activity of coronavirus. Herein, we report that corilagin (RAI-S-37) as a non-nucleoside inhibitor of SARS-CoV-2 RdRp, binds directly to RdRp, effectively inhibits the polymerase activity in both cell-free and cell-based assays, fully resists the proofreading activity and potently inhibits SARS-CoV-2 infection with a low 50% effective concentration (EC50) value of 0.13 µmol/L. Computation modeling predicts that RAI-S-37 lands at the palm domain of RdRp and prevents conformational changes required for nucleotide incorporation by RdRp. In addition, combination of RAI-S-37 with remdesivir exhibits additive activity against anti-SARS-CoV-2 RdRp. Together with the current data available on the safety and pharmacokinetics of corilagin as a medicinal herbal agent, these results demonstrate the potential of being developed into one of the much-needed SARS-CoV-2 therapeutics.

5.
Medicine (Baltimore) ; 100(5): e24252, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592868

RESUMO

BACKGROUND: The popularity of dietary supplements for knee osteoarthritis (OA) management is on the rise; however, their effects are still debated. METHODS: This study aimed to investigate the effect of an oral low molecular weight liquid hyaluronic acid supplement in the treatment of knee OA patients with mild knee pain (visual analogue scale [VAS] ≤ 3) in Taiwan population. This was a randomized, double-blind, placebo-controlled study. Forty-seven subjects were enrolled and randomly allocated to either the A+HA or the placebo groups. The subjects were required to drink a bottle contained 20 mL of A+HA or placebo daily throughout an 8-week study period. The efficacy was assessed by using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the 36-item Short Form Survey (SF-36). RESULTS: At Week 8, significant reductions from baseline in the WOMAC pain (-2.6 ±â€Š1.68, P < .0001), stiffness (-1.2 ±â€Š1.50, P = .007), physical function (-5.8 ±â€Š4.39, P < .0001), and total (-9.4 ±â€Š5.82, P < .0001) scores were observed in the A+HA group but not in the placebo group. Significant differences in the mean change of WOMAC scores from baseline at Week 8 between groups were detected (P < .01). At Week 8, the A+HA group also showed significant improvements in SF-36 physical functioning (2.7 ±â€Š3.10, P = .001) and bodily pain (0.7 ±â€Š1.50, P < .05) domains. Although the A+HA group had a higher increase in the SF-36 total score than the placebo group but the difference was not statistically significant (2.1 ±â€Š12.75 vs 0.3 ±â€Š19.66, P = .12). CONCLUSIONS: Oral administration of low molecular weight liquid HA appeared to be effective for knee OA patients with mild knee pain (VAS ≤ 3) in the relief of knee OA symptoms, particularly in pain and physical function.Clinical Trial Registration: NCT04352322.

6.
Int J Biol Macromol ; 174: 319-329, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33529627

RESUMO

Perfluorooctanoic acid (PFOA) has demonstrated potential toxicity to human health and has been detected in different environmental matrices due to its stable physical and chemical properties. To degrade PFOA under solar light irradiation, we fabricated a lignin/polyvinyl alcohol (PVA)/Co/Fe metal-organic frameworks (lignin/PVA/bi-MOFs) composite membrane via a typical electrospinning and in-situ solvothermal method for the catalytic degradation of PFOA. In the peroxymonosulfate (PMS)/membranes/solar light system, Electron paramagnetic resonance analysis (EPR) demonstrated the sulfate radicals (SO4-) and hydroxyl radicals (OH) were generated by activating PMS with transition metal and solar light irradiation. Lignin/PVA/bi-MOFs showed outstanding performance in that 89.6% of PFOA was degraded within 3 h under optimal conditions. Compared with that in solar light, only 59.6% PFOA was degraded in the dark, and the rate constant of PFOA degradation decreased from 0.0150 min-1 to 0.0046 min-1. Moreover, lignin/PVA/bi-MOFs were reused after simply rinsing with ultra-pure water and the degradation capacity of lignin/PVA/bi-MOFs remained at 77% after 4 cycles. The results might provide a new concept for the design of bimetallic MOFs for applications in organic pollutant removal.

7.
Epidemiol Infect ; 149: e10, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33397520

RESUMO

This study aims to locate the knots of cumulative coronavirus disease 2019 (COVID-19) case number during the first-level response to public health emergency in the provinces of China except Hubei. The provinces were grouped into three regions, namely eastern, central and western provinces, and the trends between adjacent knots were compared among the three regions. COVID-19 case number, migration scale index, Baidu index, demographic, economic and public health resource data were collected from 22 Chinese provinces from 19 January 2020 to 12 March 2020. Spline regression was applied to the data of all included, eastern, central and western provinces. The research period was divided into three stages by two knots. The first stage (from 19 January to around 25 January) was similar among three regions. However, in the second stage, growth of COVID-19 case number was flatter and lasted longer in western provinces (from 25 January to 18 February) than in eastern and central provinces (from 26 February to around 11 February). In the third stage, the growth of COVID-19 case number slowed down in all the three regions. Included covariates were different among the three regions. Overall, spline regression with covariates showed the different change patterns in eastern, central and western provinces, which provided a better insight into regional characteristics of COVID-19 pandemic.


Assuntos
/epidemiologia , China/epidemiologia , Emergências , Humanos , Saúde Pública , Análise de Regressão
8.
Transl Psychiatry ; 11(1): 11, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33414382

RESUMO

Sufficient feeding is essential for animals' survival, which requires a cognitive capability to facilitate food seeking, but the neurobiological processes regulating food seeking are not fully understood. Here we show that stimulation of agouti-related peptide-expressing (AgRP) neurons triggers a long-term depression (LTD) of spontaneous excitatory post-synaptic current (sEPSC) in adjacent pro-opiomelanocortin (POMC) neurons and in most of their distant synaptic targets, including neurons in the paraventricular nucleus of the thalamus (PVT). The AgRP-induced sEPCS LTD can be enhanced by fasting but blunted by satiety signals, e.g. leptin and insulin. Mice subjected to food-seeking tasks develop similar neural plasticity in AgRP-innervated PVT neurons. Further, ablation of the majority of AgRP neurons, or only a subset of AgRP neurons that project to the PVT, impairs animals' ability to associate spatial and contextual cues with food availability during food seeking. A similar impairment can be also induced by optogenetic inhibition of the AgRP→PVT projections. Together, these results indicate that the AgRP→PVT circuit is necessary for food seeking.

9.
Respir Res ; 22(1): 7, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407433

RESUMO

BACKGROUND: Diabetes is a common comorbidity among patients with exacerbation of chronic obstructive pulmonary disease (AECOPD). Diabetes has been reported to be associated with length of stay (LOS), death, and cost among AECOPD patients. However, most studies are retrospective or have small sample sizes. The association for cost has not been researched using diabetes as a main analytic factor. This study aimed to fill gaps mentioned above, to compare basic characteristics between the diabetic and non-diabetic group, and to detect associations between diabetes and clinical outcomes among patients hospitalized with AECOPD. METHODS: A total of 5334 AECOPD patients, classified into diabetic and non-diabetic group, were included from a prospective multicenter patient registry study. Generalized linear regression and logistic regression were separately used for the association between diabetes and direct hospitalization cost and the association between diabetes and LOS. RESULTS: Generally, diabetic patients had a more severe profile, including being older, more overweight or obese, having more former smokers, more emergency room visits in the past 12 months, and more comorbidities occurrence. Diabetic patients also had worse clinical outcomes, including higher cost and longer LOS. Additionally, the generalized linear regression indicated that the marginal mean cost difference between diabetic and non-diabetic patients was RMB (¥) 775.7. CONCLUSIONS: AECOPD patients with comorbid diabetes had a more severe profile and higher direct hospitalization cost. Diabetes screening and integrated care programs might help reduce the heavy comorbidity and economic burden. Moreover, corticosteroids and metformin could be considered in the treatment of these patients. Trial registration Clinicaltrials.gov with the identifier NCT0265752.

10.
Adv Healthc Mater ; : e2001658, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33470539

RESUMO

Liquid marbles have recently attracted much interest in various scientific fields because of their isolated environment and robustness. However, conventional liquid marbles lack a reliable heating mechanism, which is critical in many potential applications. Here, the development of iron oxide (Fe3 O4 ) nanocube-coated liquid marbles (iNLMs), which can be homogeneously heated with an alternating magnetic field (AMF) to as high as 86 °C, is reported. Through tuning the power of the AMF, the iNLMs canbe heated to desired temperatures in controllable patterns. Furthermore, multicenter and selective heating is realized based on the unique magnetothermal properties of iNLMs. As heatable miniature reactors, the iNLMs are further demonstrated to facilitate the kinetic study of temperature-dependent chemical reactions. DNA amplification is successfully performed in liquid marbles, achieving a 25% superior amplification rate compared with that in a common thermal cycler. These results confirm the feasibility of coating liquid marbles with Fe3 O4 nanocubes to form delicate magnetothermal miniature reactors, which provides a reliable method of applying liquid marbles in areas such as biosensor technology, point-of-care testing, and theranostics.

11.
Theranostics ; 11(6): 2755-2769, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33456571

RESUMO

Pancreatic cancer (PC), an important cause of cancer-related deaths worldwide, is one of the most malignant cancers characterized by a dismal prognosis. Circular RNAs (circRNAs), a class of endogenous ncRNAs with unique covalently closed loops, have attracted great attention in regard to various diseases, especially cancers. Compelling studies have suggested that circRNAs are aberrantly expressed in different cancer tissues and cell types, including PC. More specifically, circRNAs can modify the proliferation, progression, tumorigenesis and chemosensitivity of PC, and some circRNAs could serve as biomarkers for diagnosis and prognosis. Herein, we summarize what is currently known to be related to the biogenesis, functions and potential roles of human circRNAs in PC and their application prospects for PC clinical treatments.

12.
Colorectal Dis ; 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33497011

RESUMO

AIM: Anastomotic stricture following anterior resection is an uncommon but challenging problem. Endoscopic dilatation and transanal endoscopic surgery (TES) are proven methods of treatment. However, a small proportion of patients repeatedly fail transanal local therapy for underlying reasons of tension, insufficient blood supply or irradiated tissue, eventually necessitating a complete anastomotic excision. We aimed to combine transanal minimally invasive surgery (TAMIS) with an abdominal approach in redo anastomoses for severe refractory anastomotic strictures. METHOD: For the TAMIS phase, we use a Lonestar® retractor with a GelPOINT® Path transanal access platform. A circumferential full thickness rectotomy is performed and the dissection is continued proximally in the mesorectal fascial plane past the strictured segment to meet the abdominal dissection or until the peritoneal cavity is entered, facilitating mobilization of the rectum. The abdominal phase is performed as usual with sufficient mobilization of the left colon to enable tension-free redo anastomosis. An accompanying video demonstrates this technique. RESULTS: Two patients with refractory anastomotic strictures following a previous low anterior resection underwent the procedure. One patient had laparoscopy followed by TAMIS and the other had TAMIS followed by laparotomy. Both cases were performed by surgeons experienced in laparoscopy and TES. One patient had postoperative ileus which resolved conservatively. Both anastomoses were widely patent on follow-up. CONCLUSION: TAMIS combined with a conventional abdominal approach offers significant technical advantages over a totally abdominal approach for the definitive management of patients with severe anastomotic strictures refractory to first-line methods of therapy. The operator should already be proficient with TES.

13.
Cell Rep ; 34(1): 108586, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33406424

RESUMO

The cyclic GMP-AMP (cGAMP) synthase (cGAS) is a key DNA sensor that initiates STING-dependent signaling to produce type I interferons through synthesizing the secondary messenger 2'3'-cGAMP. In this study, we confirm previous studies showing that cGAS is located both in the cytoplasm and in the nucleus. Nuclear accumulation is observed when leptomycin B is used to block the exportin, CRM1 protein. As a result, leptomycin B impairs the production of interferons in response to DNA stimulation. We further identify a functional nuclear export signal (NES) in cGAS, 169LEKLKL174. Mutating this NES leads to the sequestration of cGAS within the nucleus and the loss of interferon response to cytosolic DNA treatment, and it further determines the key amino acid to L172. Collectively, our data demonstrate that the cytosolic DNA-sensing function of cGAS depends on its presence within the cytoplasm, which is warranted by a functional NES.

14.
Chin Med J (Engl) ; Publish Ahead of Print2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33410621

RESUMO

BACKGROUND: Obesity is a fundamental factor in metabolic disorders such as hyperlipidemia, insulin resistance, fatty liver, and atherosclerosis. However, effective preventive measures are still lacking. This study aimed to investigate different surgical protocols for removing partial adipose tissue before the onset of obesity and determine whether, and by which protocol, preliminary adipose removal could exert potent preventive effects against diet-induced metabolic disorders. METHODS: Male low-density lipoprotein receptor (LDL-R) knockout (KO) mice were randomly divided into four groups and subjected to epididymal fat removal (Epi-FR) surgery, subcutaneous fat removal (suQ-FR) surgery, both subcutaneous and epididymal fat removal (Epi + suQ-FR) surgery, or sham-operation. After 1 week of recovery, all mice were given a high-fat diet (HFD) for 10 weeks to induce metabolic disorders. RESULTS: In the Epi-FR group and the sham-operated group, the mean numbers of the residual subcutaneous fat were 28.59 mg/g and 18.56 mg/g, respectively. The expression of relative genes such as Pparg, Cebpa, Dgat2, Fabp4 and Cd36 in the residual subcutaneous fat increased 2.62, 3.90, 3.11, 2.06, 1.78 times in the Epi-FR group compared with that in the sham-operated group. Whereas in the other fat-removal groups, the residual fat depots had no significant change in either size or gene expression, as compared with those of the sham-operated group. Plasma lipid and glucose levels and insulin sensitivity, as detected by the glucose tolerance test, were not significantly alleviated in the three fat removal groups. Liver mass or lipid content was not attenuated in any of the three fat removal groups. The atherosclerosis burdens in the entire inner aorta and aortic root did not decrease in any of the three fat removal groups. CONCLUSIONS: Our data suggest that removal of epididymal adipose or subcutaneous adipose alone or in combination before the onset of obesity did not protect against hyperlipidemia, insulin resistance, fatty liver, or atherosclerosis in LDL-R KO mice fed with a HFD. Hence, adipose removal possibly does not represent a potential approach in preventing obesity-related metabolic disorders in the obesity-susceptible population.

15.
Genet Med ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402738

RESUMO

PURPOSE: To examine the overall genomic copy-number variant (CNV) landscape of Chinese pediatric patients with developmental disorders. METHODS: De-identified chromosomal microarray (CMA) data from 10,026 pediatric patients with developmental disorders were collected for re-evaluating the pathogenic CNV (pCNV) yields of different medical conditions and for comparing the frequency and phenotypic variability of genomic disorders between the Chinese and Western patient populations. RESULTS: The overall yield of pCNVs in the Chinese pediatric patient cohort was 21.37%, with variable yields for different disorders. Yields of pCNVs were positively associated with phenotypic complexity and intellectual disability/developmental delay (ID/DD) comorbidity for most disorders. The genomic burden and pCNV yield in neurodevelopmental disorders supported a female protective effect. However, the stratification analysis revealed that it was seen only in nonsyndromic ID/DD, not in nonsyndromic autism spectrum disorders or seizure. Furthermore, 15 known genomic disorders showed significantly different frequencies in Chinese and Western patient cohorts, and profiles of referred clinical features for 15 known genomic disorders were also significantly different in the two cohorts. CONCLUSION: We defined the pCNV yields and profiles of the Chinese pediatric patients with different medical conditions and uncovered differences in the frequency and phenotypic diversity of genomic disorders between Chinese and Western patients.

16.
J Formos Med Assoc ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33422398

RESUMO

BACKGROUND/PURPOSE: This analysis reports safety and effectiveness data from the Taiwanese cohort of the CORRELATE study. METHODS: CORRELATE was a prospective, observational study to assess the safety and effectiveness of regorafenib for the treatment of metastatic colorectal cancer (CRC) in real-world clinical practice that was conducted in 13 different countries in Asia, Europe and Latin America. The primary endpoint of the study was incidence of all treatment-emergent AEs (TEAEs), and secondary endpoints included overall survival (OS), progression-free survival (PFS), and disease control rate (DCR). RESULTS: The global study population (N = 1037) included 128 Taiwanese patients with a median age of 64 years, median weight of 62.02 kg and 66.41% were male. Reduced initiating doses of regorafenib and dose interruptions were common in Taiwanese patients (71.87% and 50.00%, respectively). The safety profile of regorafenib was consistent with that seen in Asian patients in the clinical development trials, including the CORRECT and CONCUR studies, with hand-foot-skin reactions (HFSR) of any grade occurring in 33.59% of patients. Median OS was 11.64 months in the Taiwanese patients (95% confidence interval [CI], 8.36-13.82) and median PFS was 2.17 months (95% CI, 1.97-2.89). CONCLUSIONS: The safety and effectiveness of regorafenib in this real-world study was generally consistent with the known efficacy and safety profile in Asian patients in clinical trials. TRIAL REGISTRATION: NCT02042144.

17.
BMC Endocr Disord ; 21(1): 19, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33499847

RESUMO

BACKGROUND: The present study aimed to evaluate the effect of artesunate (ART) on the reduction of cardiovascular complications in a type 1 diabetes model and to investigate the associated mechanism based on the receptor for advanced glycation end-product (RAGE)/NF-κB signaling pathway. METHODS: A total of 40 male Sprague-Dawley rats were randomly divided into five groups: The healthy, diabetic, 50 mg/kg ART (ig) treatment diabetic, 100 mg/kg ART (ig) treatment diabetic, and 6 U/kg insulin (iH) treatment diabetic groups. The treatment lasted 4 weeks after the diabetic model was established via intraperitoneal injection of streptozotocin. Blood samples were collected, and cardiovascular tissues were harvested and processed to measure various parameters after the animals were sacrificed. The myocardium and aortic arch tissues were evaluated using hematoxylin-eosin and Masson staining. Expression levels of RAGE, NF-κB, matrix metalloproteinase MMP9, MMP1 and CD68 in the myocardium and aortic arch tissues were detected using immunohistochemistry, and mRNA expression was determined using reverse transcription-quantitative PCR. RESULTS: The results of the present study demonstrated that ART treatment may restrain diabetes-induced cardiovascular complications by maintaining heart and body weight while reducing blood glucose, as well as regulating blood lipid indicators to normal level (P < 0.05). The expression levels of NF-κB, CD68, MMP1, MMP9 and RAGE were decreased in the ART-treated diabetic rats (P < 0.05). CONCLUSIONS: ART treatment may have a protective role against diabetes-associated cardiovascular complications in diabetic rats by inhibiting the expression of proteins in the RAGE/NF-κB signaling pathway and downstream inflammatory factors. High concentrations of ART had a hypoglycemic effect, while a low concentration of ART prevented cardiovascular complications.

18.
Endocrinology ; 162(1)2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33034617

RESUMO

AbstractCentral 5-hydroxytryptamine (5-HT), which is primarily synthesized by tryptophan hydroxylase 2 (TPH2) in the dorsal Raphe nuclei (DRN), plays a pivotal role in the regulation of food intake and body weight. However, the physiological functions of TPH2 on energy balance have not been consistently demonstrated. Here we systematically investigated the effects of TPH2 on energy homeostasis in adult male and female mice. We found that the DRN harbors a similar amount of TPH2+ cells in control male and female mice. Adult-onset TPH2 deletion in the DRN promotes hyperphagia and body weight gain only in male mice, but not in female mice. Ablation of TPH2 reduces hypothalamic pro-opiomelanocortin (POMC) neuronal activity robustly in males, but only to a modest degree in females. Deprivation of estrogen by ovariectomy (OVX) causes comparable food intake and weight gain in female control and DRN-specific TPH2 knockout mice. Nevertheless, disruption of TPH2 blunts the anorexigenic effects of exogenous estradiol (E2) and abolishes E2-induced activation of POMC neurons in OVX female mice, indicating that TPH2 is indispensable for E2 to activate POMC neurons and to suppress appetite. Together, our study revealed that TPH2 in the DRN contributes to energy balance regulation in a sexually dimorphic manner.

19.
Biochim Biophys Acta Mol Basis Dis ; 1867(1): 165989, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33065235

RESUMO

We previously showed that increased epithelial sodium channel (ENaC) activity in endothelial cells induced by oxidized low-density lipoprotein (ox-LDL) contributes to vasculature dysfunction. Here, we investigated whether ENaC participates in the pathological process of atherosclerosis using LDL receptor-deficient (LDLr-/-) mice. Male C57BL/6 and LDLr-/- mice were fed a normal diet (ND) or high fat diet (HFD) for 10 weeks. Our data show that treatment of LDLr-/- mice with a specific ENaC blocker, benzamil, significantly decreased atherosclerotic lesion formation and expression of matrix metalloproteinase 2 (MMP2) and metalloproteinase 9 (MMP9) in aortic arteries. Furthermore, benzamil ameliorated HFD-induced impairment of aortic endothelium-dependent dilation by reducing expression of proinflammatory cytokines, including TNF-α, IL-1ß, and IL-6 and production of adhesion molecules including VCAM-1 and ICAM-1 in both C57BL/6 and LDLr-/- mice fed with HFD. In addition, HFD significantly increased ENaC activity and the levels of serum lipids, including ox-LDL. Our in vitro data further demonstrated that exogenous ox-LDL significantly increased the production of TNF-α, IL-1ß, IL-6, VCAM-1 and ICAM-1. This ox-LDL-induced increase in inflammatory cytokines and adhesion molecules was reversed by γ-ENaC silencing or by treatment with the cyclooxygenase-2 (COX-2) antagonist celecoxib. Benzamil inhibited HFD-induced increase in COX-2 expression in aortic tissue in both C57BL/6 and LDLr-/- mice, and γ-ENaC gene silencing attenuated ox-LDL-induced COX-2 expression in HUVECs. These data together suggest that HFD-induced activation of ENaC stimulates inflammatory signaling, thereby contributes to HFD-induced endothelial dysfunction and atherosclerotic lesion formation. Thus, targeting endothelial ENaC may be a promising strategy to halt atherogenesis.

20.
Liver Transpl ; 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33277780

RESUMO

Living donor liver transplantation (LDLT) is sometimes associated with impaired regeneration and severe ischemia/reperfusion (I/R) injury in the graft, resulting in small-for-size syndrome (SFSS). Platelets were previously reported to stimulate liver regeneration in models of hepatectomy, but the evidence in partial liver transplantation (LT) is lacking. In this study, a rat model of partial LT was used, and the impact of thrombopoietin-induced perioperative thrombocytosis on graft regeneration, I/R injury and survival was investigated. In experiment I, 30% partial LT was performed. Under thrombocytosis, SFSS was attenuated, as shown by decreased levels of serum aminotransferases, bilirubin and ascites. Serum hepatocyte regeneration-related cytokines, including insulin-like growth factor-1, hepatocyte growth factor, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were elevated. Additionally, the proliferative signaling pathways, Ki67-labeling index, PCNA-labeling index, mitotic index and liver/body weight ratio were increased under thrombocytosis. The platelet-induced regeneration was independent of thrombopoietin, as increases in the Ki67-labelling and PCNA-labelling indexes were abolished after reducing platelet counts by anti-platelet serum in rats administered with thrombopoietin. For I/R injury, thrombocytosis did not aggravate oxidative stress, downstream signaling pathways, necrosis or apoptosis in the graft. After Kupffer cell depletion, the platelet-induced attenuation of serum aminotransferases, increased serum levels of IL-6 and TNF-α, and proliferation-related signaling pathways were abolished. Moreover, platelet accumulation in the graft decreased substantially. In experiment II, 20% partial LT was performed, and thrombocytosis improved postoperative survival. In conclusion, our results suggested that thrombocytosis stimulated graft regeneration and prolonged survival without aggregating I/R injury after partial LT, and Kupffer cells vitally contributed to platelet-derived regeneration. Platelet therapies to increase perioperative platelet counts may improve the outcomes after LDLT.

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