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1.
Ann Palliat Med ; 9(1): 8-18, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32005058

RESUMO

BACKGROUND: Recently, intraoperative use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been demonstrated to be associated with improved outcomes after surgery for several cancers; however, the effect of intraoperative NSAIDs use on bladder cancer (BCa) is not known. Therefore, the present study investigated the association between intraoperative NSAIDs use and oncological outcomes after radical cystectomy (RC). METHODS: We retrospectively analyzed 248 patients with BCa who underwent RC. Kaplan-Meier analysis and a Cox regression model were used to evaluate the association between intraoperative NSAIDs (parecoxib) use and oncological outcomes after RC. RESULTS: After excluding 63 patients, 82 of the remaining 185 patients received parecoxib during surgery. In the parecoxib group, the overall recurrence rate did not decrease significantly (P=0.310). Time to recurrence, cancer-specific mortality, and overall mortality were not significantly different between the groups. Kaplan-Meier analysis showed no association of the intraoperative use of parecoxib with an improved recurrence-free survival (RFS) or overall survival (OS) (P=0.431, P=0.185, respectively). Similarly, the multivariate analysis model showed no association between the administration of parecoxib and RFS [hazard ratio (HR), 0.964; 95% confidence interval (CI), 0.599-1.551, P=0.878] or OS (HR, 1.043; 95% CI, 0.621-1.750; P=0.875). In these patients, elevated preoperative neutrophil-lymphocyte ratio (NLR) was demonstrated to be associated with RFS and OS. CONCLUSIONS: The present study found that intraoperative parecoxib use was not associated with improved outcome after BCa surgery. Prospective, randomized trials should be performed to further evaluate the results of this study.

2.
Eur Urol Oncol ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32063492

RESUMO

BACKGROUND: Salvage external beam radiotherapy (RT) with androgen deprivation therapy (ADT) improves survival over RT in men with prostate cancer (PC) and rising prostate-specific antigen (PSA) levels after radical prostatectomy (RP). OBJECTIVE: To investigate the safety and efficacy of enzalutamide concurrent with salvage RT and ADT. DESIGN, SETTING, AND PARTICIPANTS: This was a three-center prospective phase 2 single-arm trial (NCT02057939) of men with Gleason 7-10 PC and PSA recurrence within 4 yr of RP ranging from 0.2 to 4.0 ng/dl, no prior hormonal therapy, and no radiographic evidence of metastases. We enrolled 38 men; 37 completed therapy and were evaluable with testosterone recovery at 2 yr. INTERVENTION: Six months of ADT with 160 mg/d enzalutamide and 66 Gy RT to the prostate bed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was improved 2-yr progression-free survival (PFS) over historical controls. Secondary objectives included 3-yr PFS, safety, and patient-reported quality of life (QOL). RESULTS AND LIMITATIONS: The primary endpoint of 2-yr PFS was 65% (95% confidence interval [CI]: 47, 78) versus 51% (95% CI: 33, 67) in a trial of men with similar eligibility treated with salvage RT and adjuvant docetaxel. The 3-yr PFS was 53%. Eleven (29%) men experienced G3 toxicities, and there were no G4-5 or unexpected toxicities. QOL data suggest modest worsening of bowel, bladder, and hormonal symptoms at 3 mo, with recovery by 24 mo in most men. CONCLUSIONS: Salvage RT with enzalutamide and ADT following RP for men with PSA recurrent high-risk PC is safe and demonstrates encouraging efficacy, warranting prospective controlled phase 3 trials of ADT with or without potent androgen receptor inhibition in this curative-intent setting. PATIENT SUMMARY: Addition of 6 mo of oral daily enzalutamide to standard salvage radiation and hormone therapy is safe and may improve prostate cancer remission rates at 2 and 3 yr.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31982497

RESUMO

PURPOSE: To develop a tradeoff hyperplane model to facilitate tradeoff decision-making before inverse planning. METHODS AND MATERIALS: We propose a model-based approach to determine the tradeoff hyperplanes that allow physicians to navigate the clinically viable space of plans with best achievable dose-volume parameters before planning. For a given case, a case reference set (CRS) is selected using a novel anatomic similarity metric from a large reference plan pool. Then, a regression model is built on the CRS to estimate the expected dose-volume histograms (DVHs) for the current case. This model also predicts the DVHs for all CRS cases and captures the variation from the corresponding DVHs in the clinical plans. Finally, these DVH variations are analyzed using the principal component analysis to determine the tradeoff hyperplane for the current case. To evaluate the effectiveness of the proposed approach, 244 head and neck cases were randomly partitioned into reference (214) and validation (30) sets. A tradeoff hyperplane was built for each validation case and evenly sampled for 12 tradeoff predictions. Each prediction yielded a tradeoff plan. The root-mean-square errors of the predicted and the realized plan DVHs were computed for prediction achievability evaluation. RESULTS: The tradeoff hyperplane with 3 principal directions accounts for 57.8% ± 3.6% of variations in the validation cases, suggesting the hyperplanes capture a significant portion of the clinical tradeoff space. The average root-mean-square errors in 3 tradeoff directions are 5.23 ± 2.46, 5.20 ± 2.52, and 5.19 ± 2.49, compared with 4.96 ± 2.48 of the knowledge-based planning predictions, indicating that the tradeoff predictions are comparably achievable. CONCLUSIONS: Clinically relevant tradeoffs can be effectively extracted from existing plans and characterized by a tradeoff hyperplane model. The hyperplane allows physicians and planners to explore the best clinically achievable plans with different organ-at-risk sparing goals before inverse planning and is a natural extension of the current knowledge-based planning framework.

4.
Blood ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31951650

RESUMO

Chimeric antigen receptor (CAR) T cells have radically improved the treatment of B cell-derived malignancies by targeting CD19. The success has not yet expanded to treat acute myeloid leukemia (AML). We developed a Sequentially Tumor-selected Antibody and antigen Retrieval (STAR) system to rapidly isolate multiple nanobodies (Nbs) that both preferentially bind AML cells and empower CAR T cells with anti-AML efficacy. The STAR-isolated Nb157 specifically bound CD13, which is highly expressed in AML cells, and CD13 CAR T cells potently eliminated AML in vitro and in vivo. CAR T cells bi-specific for CD13 and TIM3, which is upregulated in AML leukemia stem cells, eradicated patient-derived AML, with much reduced toxicity to human bone marrow stem cells and peripheral myeloid cells in mouse models, highlighting a promising approach for developing effective AML CAR T therapy.

5.
Sci Rep ; 10(1): 104, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919399

RESUMO

Ascorbic acid-2-phosphate (A2-P) is an oxidation-resistant derivative of ascorbic acid that has been widely employed in culturing adipose-derived stem cells (ASCs) for faster expansion and cell sheet formation. While high dose ascorbic acid is known to induce cellular apoptosis via metabolic stress and genotoxic effects, potential cytotoxic effects of A2-P at high concentrations has not been explored. In this study, the relationship between ASC seeding density and A2-P-induced cytotoxicity was investigated. Spheroid-derived ASCs with smaller cellular dimensions were generated to investigate the effect of cell-cell contact on the resistance to A2-P-induced cytotoxicity. Decreased viability of ASC, fibroblast, and spheroid-derived ASC was noted at higher A2-P concentration, and it could be reverted with high seeding density. Compared to control ASCs, spheroid-derived ASCs seeded at the same density exhibited decreased viability in the A2-P-supplemented medium. The expression of antioxidant enzymes (catalase, SOD1, and SOD2) was enhanced in ASCs at higher seeding densities. However, their enhanced expression in spheroid-derived ASCs was less evident. Furthermore, we found that co-administration of catalase or N-acetylcysteine nullified the observed cytotoxicity. Collectively, A2-P can induce ASC cytotoxicity at higher concentrations, which can be prevented by seeding ASCs at high density or co-administration of another antioxidant.

6.
Chin Med J (Engl) ; 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31977553

RESUMO

BACKGROUND: Traditional tissue engineering methods to fabricate urinary tract patch have some drawbacks such as compromised cell viability and uneven cell distribution within scaffold. In this study, we combined three-dimensional (3D) bioprinting and tissue engineering method to form a tissue-engineered urinary tract patch, which could be employed for the application on Beagles urinary tract defect mode to verify its effectiveness on urinary tract reconstruction. METHODS: Human adipose-derived stem cells (hADSCs) were dropped into smooth muscle differentiation medium to generate induced microtissues (ID-MTs), flow cytometry was utilized to detect the positive percentage for CD44, CD105, CD45, and CD34 of hADSCs. Expression of vascular endothelial growth factor A (VEGFA) and tumor necrosis factor-stimulated gene-6 (TSG-6) in hADSCs and MTs were identified by Western blotting. Then the ID-MTs were employed for 3D bioprinting. The bioprinted structure was encapsulated by transplantation into the subcutaneous tissue of nude mice for 1 week. After retrieval of the encapsulated structure, hematoxylin and eosin and Masson's trichrome staining were performed to demonstrate the morphology and reveal collagen and smooth muscle fibers, integral optical density (IOD) and area of interest were calculated for further semi-quantitative analysis. Immunofluorescent double staining of CD31 and α-smooth muscle actin (α-SMA) were used to reveal vascularization of the encapsulated structure. Immunohistochemistry was performed to evaluate the expression of interleukin-2 (IL-2), α-SMA, and smoothelin of the MTs in the implanted structure. Afterward, the encapsulated structure was seeded with human urothelial cells. Immunofluorescent staining of cytokeratins AE1/AE3 was applied to inspect the morphology of seeded encapsulated structure. RESULTS: The semi-quantitative assay showed that the relative protein expression of VEGFA was 0.355 ±â€Š0.038 in the hADSCs vs. 0.649 ±â€Š0.150 in the MTs (t = 3.291, P = 0.030), while TSG-6 expression was 0.492 ±â€Š0.092 in the hADSCs vs. 1.256 ±â€Š0.401 in the MTs (t = 3.216, P = 0.032). The semi-quantitative analysis showed that the mean IOD of IL-2 in the MT group was 7.67 ±â€Š1.26, while 12.6 ±â€Š4.79 in the hADSCs group, but semi-quantitative analysis showed that there was no statistical significance in the difference between the two groups (t = 1.724, P = 0.16). The semi-quantitative analysis showed that IOD was 71.7 ±â€Š14.2 in non-induced MTs (NI-MTs) vs. 35.7 ±â€Š11.4 in ID-MTs for collagen fibers (t = 3.428, P = 0.027) and 12.8 ±â€Š1.9 in NI-MTs vs. 30.6 ±â€Š8.9 in ID-MTs for smooth muscle fibers (t = 3.369, P = 0.028); furthermore, the mean IOD was 0.0613 ±â€Š0.0172 in ID-MTs vs. 0.0017 ±â€Š0.0009 in NI-MTs for α-SMA (t = 5.994, P = 0.027), while 0.0355 ±â€Š0.0128 in ID-MTs vs. 0.0035 ±â€Š0.0022 in NI-MTs for smoothelin (t = 4.268, P = 0.013), which indicate that 3D bioprinted structure containing ID-MTs could mimic the smooth muscle layer of native urinary tract. After encapsulation of the urinary tract patch for additional cell adhesion, urothelial cells were seeded onto the encapsulated structures, and a monolayer urothelial cell was observed. CONCLUSION: Through 3D bioprinting and tissue engineering methods, we provided a promising way to fabricate tissue-engineered urinary tract patch for further investigation.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31980176

RESUMO

Mitochondrial dysfunction plays a pivotal role in doxorubicin (DOX)-induced cardiomyopathy. Cytochrome c oxidase subunit 5A (COX5A) is a nuclear-encoded subunit of the terminal oxidase involved in mitochondrial electron transport. Although COX5A appears to play a key role in modulating the physiological activity of COX and involve in energy metabolism, the involvement of COX5A in DOX-induced cardiotoxicity remains unclear. In this study, we showed that COX5A was significantly downregulated by DOX treatment of H9c2 cells. Overexpression of COX5A in H9c2 cells effectively attenuated DOX-induced apoptosis. Meanwhile, DOX-induced decrease in mitochondrial membrane potential could be reserved by COX5A overexpression. Furthermore, COX5A overexpression relieved the DOX-induced suppression of mitochondrial respiration, due an increase in basal respiration, maximal respiration, ATP production, and spare respiratory capacity. These findings indicate that up-regulation of COX5A may inhibit the apoptosis and alleviate the mitochondrial dysfunction of DOX-treated H9c2 cells. Thus, COX5A may have potential for clinical use as a therapeutic target in DOX-induced cardiotoxicity.

8.
PLoS One ; 15(1): e0228267, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995608

RESUMO

PURPOSE: To investigate changes in intraocular pressure (IOP) and axial length (AL) on the ascent to high altitude from Beijing to Lhasa. PATIENTS AND METHODS: Twenty volunteers (17 men, 3 women) who had been sent to work in Lhasa, Tibet for more than 6 months were enrolled. One of their journeys from Beijing to Lhasa was chosen as the time for the examination. IOP, AL, corneal curvature (K), and blood pressure (BP) were measured in Beijing (altitude 43 m) and Lhasa (altitude 3658 m). Their first examination was conducted at least 1 day before arriving in Lhasa and the second examination after they had stayed in Lhasa for 7 days. The data from the highland and lowland examinations were analyzed with a paired-sample T test and Pearson's correlation coefficient was calculated for the association between IOP and average BP. RESULTS: The mean IOP was 12.65±2.34 mmHg in Beijing and 14.85±3.1 mmHg in Lhasa. The mean AL was 24.61±1.50mm in Beijing, and 24.98±1.45 mm in Lhasa. The IOP and AL showed a significant elevation in highland compared with lowland (P<0.05). The mean K was 43.58±2.25 D in Beijing and 43.56±2.21 D in Lhasa and no significant difference was found in this study (P>0.05). A positive correlation between variance of IOP and ACD was found (r = 0.475, P<0.05) and no correlation between IOP and average BP was noted. CONCLUSIONS: High altitude may lead to a small but significant change in IOP and axial length. However, the shape of the corneal surface was not influenced by the hypobaric and hypoxic conditions.

9.
Acta Physiol (Oxf) ; : e13439, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900976

RESUMO

AIM: To explore the role of the histidine triad nucleotide-binding 2 (HINT2) protein in heart failure. METHODS: Neonatal mouse ventricle myocytes (NMVMs) and myocardial infarction-induced heart failure mice were used for in vitro or in vivo experiments. Adenovirus (ADV) and adeno-associated virus serum type 9 (AAV9) vectors were used to regulate HINT2 expression. The expression of HINT2 was determined by quantifying the mRNA and protein levels. Cell survival was analysed using the CCK-8 kit and TUNEL staining. Mitochondrial function was determined by the mitochondrial membrane potential and oxygen consumption rates. AAV9-HINT2 was injected 24 h post-myocardial infarction following which transthoracic echocardiography and histological analyses were performed after 4 weeks. Positron emission tomography tomography-computed tomography (PET/CT) and targeted metabolomics analyses were used to explore the metabolic status in vivo. NAD levels were measured using a colorimetric kit. Computer-simulated rigid body molecular docking was performed using AUTODOCK4. Molecule binding kinetics assays were performed using biolayer interferometry. RESULTS: HINT2 was down-regulated in NMVMs in hypoxia. ADV-HINT2-induced HINT2 overexpression improved NMVM survival after exposure to hypoxia. Mitochondrial function was preserved in the ADV-HINT2 group under hypoxic conditions. In vivo experiments showed that cardiac function and metabolic status was preserved by HINT2 overexpression. HINT2 overexpression restored mitochondrial NAD levels; this was dependent on nicotinamide mononucleotide (NMN). Using computer-simulated molecular docking analysis and biolayer interferometry, we observed that HINT2 potentially binds and associates with NMN. CONCLUSION: HINT2 overexpression protects cardiac function in adult mice after myocardial infarction by maintaining mitochondrial NAD homeostasis.

10.
Bioorg Med Chem ; 28(5): 115299, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31980361

RESUMO

Mitochondrial complex II and complex III are two promising targets for the development of numerous pharmaceuticals and pesticides. Although tremendous inhibitors of either complex II or complex III were identified, compounds which are capable of prohibiting the activities of both complexes have been rarely reported. Since multi-target drugs can interact with several drug targets simultaneously, we were keen on discovering new and potent dual-target inhibitors of both complex II and complex III. Therefore, a new series of structurally simplified sulfonamides bearing a diaryl ether scaffold were designed and synthesized in this paper. Afterwards, the biological activities of the newly synthesized compounds were evaluated. The results implied that several compounds demonstrated outstanding potency against succinate-cytochrome c reductase (SCR, a mixture of complex II and complex III). Further studies confirmed that N-(3,5-Dichloro-4-(2,4,6-trichlorophenoxy)phenyl)benzenesulfonamide (3f), a representative compound herein, was identified as a dual-target inhibitor of both complexes. Furthermore, computational simulations were also performed to have a better understanding about binding of 3f to the enzyme complexes, which concluded that 3f should bind to complex II and the Qo site of complex III. Consequently, we harbor the idea that this work can be beneficial for the synthesis and discovery of more dual- or multi-target inhibitors.

11.
Dalton Trans ; 49(1): 114-123, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31793575

RESUMO

A new 1,4,7-triazacyclononane derivative, 4-benzyloxy-benzyl-1,4,7-triazacyclononane (btacn), and three associated cyclen complexes, Cu(btacn)Cl2, Zn(btacn)Cl2 and [Cu(btacn)2]·(ClO4)2, were prepared to serve as DNA synthesis interferents. The compounds were characterized using IR, 1H and 13C NMR, ESI-MS, elemental analysis and X-ray single crystal diffraction methods, and their DNA damage mechanisms and cytotoxicities towards cancer and normal cells were studied. Among them, Cu(btacn)Cl2 and [Cu(btacn)2]·(ClO4)2 exhibit potent anti-proliferation activity in HepG-2 and HeLa cells, but low cytotoxicity in the normal cell models LO2 and HUVEC, giving SI values (IC50 ratios) ranging from 2.45 to 7.09-times higher than that of cisplatin. DNA binding and cleavage studies suggested that [Cu(btacn)2]·(ClO4)2 can more easily intercalate into CT-DNA than Cu(btacn)Cl2, which is consistent with the results of G2/S phase arrest and apoptosis in HepG-2 cells involving the complexes. In contrast, Zn(btacn)Cl2 demonstrated weak DNA binding and no obvious cytotoxicity. The results suggest that Cu(btacn)Cl2 and [Cu(btacn)2]·(ClO4)2 mainly undergo redox processes to produce reactive oxygen species (ROS) that induce DNA degradation and mitochondrial damage.

12.
Dev Comp Immunol ; 104: 103517, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31647941

RESUMO

The employment of traditional feed and medicament in freshwater aquaculture causes the frequent occurrence of environmental pollution and disease. Effluent collected after Rhodopseudomonas-mediated wastewater treatment could be re-utilized as microbial feeds, and aquaculture water to culture Aristichthys nobilis. Therefore, a novel integrated system of wastewater treatment using effluent containing Rhodopseudomonas that improves yield, increases disease resistance, and enhances the quality of aquaculture water for Aristichthys nobilis culture was proposed and investigated. Aristichthys nobilis can grow well in effluent containing Rhodopseudomonas (ER). The survival rate, yield, and whole body composition of the ER group were all increased compared to the control group (CK). The biochemical (B vitamin) and other substances in the effluent of Rhodopseudomonas enhanced the activity of AKP, ACP, phagocytic, SOD, and CAT by upregulating the expression of AKP, ACP, SOD, and CAT genes. Moreover, Rhodopseudomonas and biochemical substances improved mTOR and NF-kB signaling pathway. Furthermore, Rhodopseudomonas inhibited Aeromonas hydrophila that increases resistance against fish disease. Meanwhile, Rhodopseudomonas in the effluent also improved the aquaculture water quality. This technology would save the aquaculture water, reduce water pollution and wastewater discharge, and increase the output and disease resistance of Aristichthys nobilis, simultaneously.

13.
Chem Asian J ; 15(1): 129-135, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31762212

RESUMO

2-Aminobenzimidazoles are widely present in a number of bioactive molecules. Generally, the preparation of these molecules could be realized by the mono-substitution of 2-halobenzimidazoles with amines. However, rare examples were reported for the di-substituted products and the selectivity of mono- vs. di-substitution was relatively low. Considering the potential values of the di-substituted products, we accomplished the first selective diheteroarylation of amines with 2-halobenzimidazoles. Notably, this Pd-catalyzed transformation was realized under ligand-free conditions. Accordingly, numerous target products were efficiently produced from various aromatic or aliphatic amines and 2-halobenzimidazoles. It was worth noting that two representative products were further confirmed by X-ray crystallography. More significantly, this catalytic process could be applied to the synthesis and discovery of new bioactive compounds, which demonstrated the synthetic usefulness of this newly developed approach.

15.
Protoplasma ; 257(1): 43-59, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31359223

RESUMO

High temperature (HT) is one of the major environmental factors which limits plant growth and yield. The mitogen-activated protein kinase (MAPK) plays vital roles in environmental stress responses. However, the mechanisms triggered by MAPKs in plants in response to HT are still extremely limited. In this study, the proteomic data of differences between SlMPK1 RNA-interference mutant (SlMPK1i) and wild type and of tomato (Solanum lycopersicum) plants under HT stress using isobaric tags for relative and absolute quantitation (iTRAQ) was re-analyzed in depth. In total, 168 differently expressed proteins (DEPs) were identified in response to HT stress, including 38 DEPs only found in wild type, and 84 DEPs specifically observed in SlMPK1i after HT treatment. The majority of higher expression of 84 DEPs were annotated into photosynthesis, oxidation-reduction process, protein folding, translation, proteolysis, stress response, and amino acid biosynthetic process. More importantly, SlMPK1-mediated photosynthesis was confirmed by the physiological characterization of SlMPK1i with a higher level of photosynthetic capacity under HT stress. Overall, the results reveal a set of potential candidate proteins helping to further understand the intricate regulatory network regulated by SlMPK1 in response to HT.

16.
ACS Appl Mater Interfaces ; 12(2): 2717-2723, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31850735

RESUMO

A pivotal thermally activated delayed-fluorescence (TADF) emitter, DspiroAc-TRZ, was developed, and it exhibits greatly enhanced electroluminescence performance in nondoped organic light-emitting diodes (OLEDs) owing to the concurrent manipulation of aggregation behavior and monomolecular structure. The delicate non-planar packing pattern in the DspiroAc-TRZ crystal can not only lead to highly efficient solid-state luminescence but also form a loose intermolecular packing pattern, greatly decreasing the HOMO or LUMO overlaps in dimers and shortening the triplet exciton diffusion length. In addition, the rigid donor and acceptor moieties in DspiroAc-TRZ can rigidify the molecular backbone, resulting in a tiny geometric vibrational relaxation in the excited state. Impressively, high photoluminescent quantum yields of 78.5 and 83.7% were achieved for the DspiroAc-TRZ single crystal and nondoped film. A high external quantum efficiency (EQE) of 25.7% was achieved in a nondoped sky-blue TADF OLED, which is higher than any reported EQE value of nondoped sky-blue TADF OLEDs so far.

17.
Emerg Microbes Infect ; 9(1): 42-52, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31873046

RESUMO

Clostridioides difficile causes healthcare-related diarrhoea in high-income countries. Highly resistant spores persist in healthcare facilities, primarily infecting patients who have recently received antimicrobials. C. difficile infection (CDI) has been studied in detail in North America and Europe; however, the epidemiology of CDI elsewhere, including the Asia-Pacific region, is largely unknown. A survey of CDI was performed in 13 Asia-Pacific countries. Epidemiological data on 600 cases were collected and molecular typing undertaken on 414 C. difficile isolates. Healthcare facility-associated CDI comprised 53.6% of cases, while community-associated CDI was 16.5%. The median age of cases was 63.0 years and 45.3% were female, 77.5% had used antibiotics in the previous 8 weeks, most frequently third-generation cephalosporins (31.7%), and 47.3% had used proton pump inhibitors. Recurrence (9.1%) and mortality (5.2%) rates were low, while complications including colitis or pseudomembranous colitis (13.8%), colectomy (0.4%), and toxic megacolon (0.2%) were uncommon. Common C. difficile strains were ribotypes 017 (16.7%), 014/020 (11.1%) and 018 (9.9%), with wide variation between countries. Binary toxin-positive strains of C. difficile were detected rarely. Overall, disease severity appeared mild, and mortality and recurrence were low. Continued education about, and surveillance of, CDI in Asia are required to reduce the burden of disease.

18.
Epilepsy Behav ; 103(Pt A): 106670, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31864943

RESUMO

Evidence indicates that ferrostain-1 (Fer-1), a specific inhibitor of ferroptosis, could ameliorate cognitive dysfunction of rats with kainic acid (KA)-induced temporal lobe epilepsy (TLE) by suppressing ferroptosis processes. Recent studies suggest that P38 mitogen-activated protein kinase (MAPK) pathway could be mediated by ferroptosis processes. The activation of P38 MAPK results in cognitive impairment by suppressing the expression of synaptic plasticity-related proteins. However, it is unclear whether Fer-1 can mitigate cognitive impairment of rats with KA-induced TLE by inhibiting P38 MAPK activation. In the present study, treatment with Fer-1 blocked the activation of P38 MAPK, which resulted in an increased expression of synaptophysin (SYP) and postsynaptic density protein 95 (PSD-95) in the hippocampus of rats with KA-induced TLE, hence, ameliorating their cognitive impairment. Also, P38 MAPK activation in the hippocampus of the rats reduced the expression of both PSD-95 and SYP proteins. Treatment of the rats with SB203580, a P38 MAPK-specific inhibitor, prevented the activation of P38 MAPK, which resulted in an increase in SYP and PSD95 protein levels in the hippocampus. These results suggest that Fer-1 could mitigate the cognitive impairment by suppressing P38 MAPK activation thus restoring the expression of synaptic proteins. Ferroptosis processes might be involved in suppressing synaptic protein expression.

19.
J Endocrinol ; 244(1): 41-52, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31539871

RESUMO

Protein arginine methyltransferase 5 (PRMT5), a symmetric arginine methyltransferase, regulates cell functions by influencing gene transcription through posttranslational modification of histones and non-histone proteins. PRMT5 interacts with multiple partners including menin, which controls beta cell homeostasis. However, the role of Prmt5 in pancreatic islets, particularly in beta cells, remains unclear. A mouse model with an islet-specific knockout (KO) of the Prmt5 gene was generated, and the influence of the Prmt5 excision on beta cells was investigated via morphologic and functional studies. Beta cell function was evaluated by glucose tolerance test (GTT) and glucose-stimulated insulin secretion (GSIS) test. Beta cell proliferation was evaluated by immunostaining. Gene expression change was determined by real-time qPCR. Molecular mechanisms were investigated in beta cells in vitro and in vivo in Prmt5 KO mice. The results show that islet-specific KO of Prmt5 reduced expression of the insulin gene and impaired glucose tolerance and GSIS in vivo. The mechanistic study indicated that PRMT5 is involved in the regulation of insulin gene transcription, likely via histone methylation-related chromatin remodeling. The reduced expression of insulin in beta cells in the Prmt5 KO mice may contribute to impaired glucose tolerance (IGT) and deficient GSIS in the mouse model. These results will provide new insights into exploring novel strategies to treat diabetes caused by insulin insufficiency.

20.
Zhongguo Zhen Jiu ; 39(12): 1255-61, 2019 Dec 12.
Artigo em Chinês | MEDLINE | ID: mdl-31820598

RESUMO

OBJECTIVE: To evaluate the clinical effect of acupuncture on smoking cessation and withdrawal symptoms and to explore the influence factors of acupuncture on smoking cessation. METHODS: A total of 500 subjects with tobacco dependence were randomized into an acupuncture group, an auricular therapy group, an acupuncture plus auricular therapy group, a TENS group and a nicotine replacement therapy group (NRT group), 100 cases in each one. In the acupuncture group, acupuncture was applied at Baihui (GV 20), Lieque (LU 7), Hegu (LI 4) and Zusanli (ST 36). The treatment was given 5 times a week, once a day in the first 2 weeks. The treatment was given once every 2 days in the week 3 and 4, 3 times a week, and twice a week, once every 3 days in the week 5 to 8. In the auricular therapy group, the ear point pressure therapy was used at shenmen (TF4), neifenmi (CO18), pizhixia (AT4) and jiaogan (AH6a), 3 times a week. In the acupuncture plus auricular therapy group, acupuncture and auricular therapy were adopted with the same points and manipulation as the previous two groups. Acupuncture was given 3 times a week and the auricular therapy was given twice a week. In the TENS group, SDZ-Ⅱ B type electric acupuncture apparatus was used to stimulate Lieque (LU 7) and Zusanli (ST 36), once a day. In the NRT group, the nicotine patch was used on the chest, back and the upper arms of the subjects, once a day. The duration of treatment was 8 weeks as one course in every group. Afterwards, the 16-week follow-up was conducted. The time-point withdrawal rate was evaluated by the level of urine cotinine in 8 weeks of treatment and in the follow-up in the subjects of 5 groups. The persistent withdrawal rate was evaluated by the self-report of the subjects in 8 weeks of treatment as well as in the follow-up in the 5 groups. The withdrawal effect, the score of the fagerstrom test for nicotine dependence (FTND) and the score of the heaviness of smoking index (HSI) were compared among the groups. Twenty indexes were selected as the potential influence factors, the 72 h withdrawal rate based on the level of urine cotinine in 8 weeks of treatment and in the follow-up was taken as the dependent variable. Using the two categories of Logistic regression analysis, the influence factors of therapeutic effect of acupuncture were screened for smoking cessation. RESULTS: After 8 weeks of treatment, the time-point withdrawal rate in the subjects among the groups was NRT group > acupuncture plus auricular therapy group > auricular therapy group > acupuncture group > TENS group. In the follow-up, the time-point withdrawal rate was acupuncture plus auricular therapy group > NRT group > acupuncture group > TENS group > auricular therapy group, but without statistical significance in comparison (P>0.05). After 8 weeks of treatment, the persistent withdrawal rate in the subjects among the groups was auricular therapy group > TENS group > acupuncture group > acupuncture plus auricular therapy group > NRT group. In the follow-up visit, the persistent withdrawal rate was auricular therapy group > TENS group > acupuncture plus auricular therapy group > acupuncture group > NRT group. The result in the auricular therapy group was better than all of the other 4 groups (P<0.05). Except in the follow-up visit, FTND score in the acupuncture group was lower than the auricular therapy group (P<0.05), FTND score and HSI score were not different significantly in statistics among the groups either in 8 weeks of treatment or in the follow-up (P>0.05). The regression analysis showed that the factors, i.e. nationality, educational background, drinking frequency, pre-treatment FTND score, pre-treatment HSI score and smoking cessation for physical reason in family, were correlated significantly with the withdrawal result after 8-week treatment (P<0.05). The factors, i.e. education background, smoking age, pre-treatment FTND score and different therapeutic methods, were correlated significantly with the withdrawal result in the follow-up (P<0.05). CONCLUSION: Acupuncture combined with auricular therapy effectively reduce nicotine dependence and smoking intensity and relieve withdrawal symptoms. There are many factors that affect the withdrawal effect in smoking cessation. Hence, the influence factors in smoking cessation with acupuncture should be clearly determined so as to develop the individual regimen for smoking cessation and improve the clinical therapeutic effect of acupuncture on smoking cessation.


Assuntos
Terapia por Acupuntura , Abandono do Hábito de Fumar , Humanos , Fumar , Dispositivos para o Abandono do Uso de Tabaco , Resultado do Tratamento
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