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1.
Nanotechnology ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794509

RESUMO

Elaborating the sensitization effects of different noble metals on In2O3 has a great significance in providing optimum method to improve ethanol sensing performance. In this study, long-range ordered mesoporous In2O3 has been fabricated through replicating the structure of SBA-15. Different noble metals (Au, Ag, Pt and Pd) with the same doping amount (1 at%) have been introduced by in-situ doping routine. The results of gas sensing investigation indicate that the gas responses towards ethanol can be obviously increased by doping different noble metals. Especially, the best sensing performance towards ethanol detection can be achieved through Pd doping, and the sensors based on Pd doped In2O3 not only possess the highest response (39.0 to 100 ppm ethanol) but also have the shortest response and recovery times at the optimal operation temperature of 250oC. The sensing mechanism of noble metal doped materials can be attributed to the synergetic effect combining "catalysis" and "electronic and chemical sensitization" of noble metal. In particular, the chemical state of noble metal also has great influence on gas sensing mechanism. Detail explanation about the enhancement of gas sensing performance through noble metal doping is presented in gas sensing mechanism part of the manuscript.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33870613

RESUMO

Dsk2 is a nuclear-enriched ubiquitin-like polyubiquitin-binding protein that regulates protein degradation in yeast but has not been explored yet in filamentous fungi, such as Beauveria bassiana. Here, we report Beauveria bassiana Dsk2 located both in the nucleus and in cytoplasm of hyphal cells. Deletion of Dsk2 resulted in mild growth defect on scant media with various carbon/nitrogen sources and dramatic attenuation in conidiation capability at optimal condition. Compared to the wild-type, ΔDsk2 strains are much more sensitive to high osmotic and oxidative pressure during vegetative growth. Meanwhile, the mutant strains showed an increased chemical tolerance to Congo red and calcofluor white, two cell wall perturbing agents. The transcriptional changes of genes involved in central development, superoxide dismutase and chitin synthesis pathway indicate that Dsk2 acts as a multi-functional regulator in adapting to environmental changes. Importantly, Dsk2 negatively regulated the ability of thermal resistance in B. bassiana, which makes it a potential target gene for constructing engineering anti-thermal strains in the circumstance of global warming. Altogether, our finding highlights novel roles of Dsk2 involved in the asexual cycle, multi-stress tolerance and pest control potential of B. bassiana.

3.
J Phys Chem Lett ; : 4079-4084, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33881881

RESUMO

Herein, the negative photoconductivity (NPC) effect has been observed in nanodiamonds (NDs) for the first time, and with illumination under a 660 nm laser lamp, the conductivity of the NDs decreases significantly. The NPC effect has been attributed to the trapping of carriers by the absorbed water molecules on the ND surfaces. A humidity sensor has been constructed based on the NPC effect of the NDs, and the sensitivity of the sensor can reach 106%, which is the highest value ever reported for carbon-based humidity sensors.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33880525

RESUMO

OBJECTIVES: This study aimed to evaluate the value of the high-risk-pattern histology (micropapillary and solid components) for predicting distant metastasis in lung adenocarcinoma and to determine the survival benefit with adjuvant targeted therapy for resected non-small cell lung cancer with high-risk-pattern histology. METHODS: Patients receiving surgery for non-small cell lung cancer were included in this retrospective study. Histological classification was performed according to 2015 World Health Organization classification. Tumours with micropapillary and solid components were defined as high-risk-pattern tumours. Univariable and multivariable Cox regression analyses were used for survival analysis. Adjuvant targeted therapy was alternative for patients with epidermal growth factor receptor (EGFR)-mutation and refusing adjuvant chemotherapy, and outcome was evaluated between 2 groups. RESULTS: The 514 patients (78 in high-risk group and 436 in low-risk group) were followed up for a median of 64 months. High-risk-pattern adenocarcinoma was significantly more common in male patients (P < 0.001) and in smokers (P < 0.001). Among patients with EGFR mutation (n = 164), the high-risk pattern was significantly associated with distant metastasis (P = 0.028) including brain metastasis (P = 0.022). In the 42 patients with high-risk pattern plus EGFR mutation, survival was significantly better after treatment with adjuvant targeted therapy than with chemotherapy (5-year overall survival: 56.4 ± 2.6 vs 44.7 ± 3.7 months, P = 0.011; 5-year disease-free survival: 54.0 ± 3.3 vs 41.9 ± 4.5 months, P = 0.006). CONCLUSIONS: High-risk pattern is associated with distant metastasis in non-small cell lung cancer after surgery. Adjuvant targeted therapy may be superior to chemotherapy for treatment of patients with high-risk pattern and EGFR mutation.

5.
Zhongguo Fei Ai Za Zhi ; 24(3): 141-160, 2021 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-33819964

RESUMO

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS: Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

6.
Leuk Lymphoma ; : 1-9, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33904352

RESUMO

Double minute chromosomes (DMs) are rare in hematologic malignancies. We presented the cytogenetic characteristics and clinical features of the largest single-center cohort of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients with DMs. A total of 2576 AML patients and 1642 MDS patients were investigated, and 30 patients (AML = 19; MDS = 11) who had DMs were followed up. DMs were more common in primary AML (94.7%) and MDS (90.9%). Monosomal karyotypes (MK) were also the main cytogenetic characteristics, like complex karyotypes (CK). AML with myelodysplasia-related changes (AML-MRC) and MDS-refractory anemia with excess blasts (MDS-RAEB) was common in this cohort. We conclude that DMs-positive AML and DMs-positive MDS are associated with older age, complex karyotypes, monosomal karyotypes, TP53 deletion and TP53 mutations. DMs are a type of chromothripsis, which can be observed by the karyotype analysis. MYC and KMT2A were the most commonly amplified genes in DMs. Most patients with DMs presented an extremely poor prognosis.

7.
Biol Reprod ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33709118

RESUMO

Zona pellucida (ZP), which is composed of at most four extracellular glycoproteins (ZP1, ZP2, ZP3, and ZP4) in mammals, shelters the oocytes and is vital in female fertility. Several studies have identified the indispensable roles of ZP1-3 in maintaining normal female fertility. However, the understanding of ZP4 is still very poor because only one study on ZP4-associated infertility performed in rabbits has been reported up to date. Here we investigated the function of mammalian Zp4 by creating a knockout (KO) rat strain (Zp4-/- rat) using CRISPR-Cas9 mediated DNA-editing method. The influence of Zp4 KO on ZP morphology and some pivotal processes of reproduction, including oogenesis, ovulation, fertilization and pup production, was studied using periodic acid-Schiff's staining, superovulation, in vitro fertilization, and natural mating. The ZP morphology in Zp4-/- rats was normal and none of these pivotal processes was affected. This study renewed the knowledge of mammalian Zp4 by suggesting that Zp4 was completely dispensable for female fertility.

8.
Thorac Cancer ; 12(9): 1469-1488, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33787090

RESUMO

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.

9.
J Transl Med ; 19(1): 62, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568202

RESUMO

BACKGROUND: Atherosclerosis is a chronic vascular disease posing a great threat to public health. We investigated whether rosuvastatin (RVS) enhanced autophagic activities to inhibit lipid accumulation and polarization conversion of macrophages and then attenuate atherosclerotic lesions. METHODS: All male Apolipoprotein E-deficient (ApoE-/-) mice were fed high-fat diet supplemented with RVS (10 mg/kg/day) or the same volume of normal saline gavage for 20 weeks. The burden of plaques in mice were determined by histopathological staining. Biochemical kits were used to examine the levels of lipid profiles and inflammatory cytokines. The potential mechanisms by which RVS mediated atherosclerosis were explored by western blot, real-time PCR assay, and immunofluorescence staining in mice and RAW264.7 macrophages. RESULTS: Our data showed that RVS treatment reduced plaque areas in the aorta inner surface and the aortic sinus of ApoE-/- mice with high-fat diet. RVS markedly improved lipid profiles and reduced contents of inflammatory cytokines in the circulation. Then, results of Western blot showed that RVS increased the ratio LC3II/I and level of Beclin 1 and decreased the expression of p62 in aortic tissues, which might be attributed to suppression of PI3K/Akt/mTOR pathway, hinting that autophagy cascades were activated by RVS. Moreover, RVS raised the contents of ABCA1, ABCG1, Arg-1, CD206 and reduced iNOS expression of arterial wall, indicating that RVS promoted cholesterol efflux and M2 macrophage polarization. Similarly, we observed that RVS decreased lipids contents and inflammatory factors expressions in RAW264.7 cells stimulated by ox-LDL, accompanied by levels elevation of ABCA1, ABCG1, Arg-1, CD206 and content reduction of iNOS. These anti-atherosclerotic effects of RVS were abolished by 3-methyladenine intervention. Moreover, RVS could reverse the impaired autophagy flux in macrophages insulted by chloroquine. We further found that PI3K inhibitor LY294002 enhanced and agonist 740 Y-P weakened the autophagy-promoting roles of RVS, respectively. CONCLUSIONS: Our study indicated that RVS exhibits atheroprotective effects involving regulation lipid accumulation and polarization conversion by improving autophagy initiation and development via suppressing PI3K/Akt/mTOR axis and enhancing autophagic flux in macrophages.

10.
Biol Reprod ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33624742

RESUMO

The zona pellucida (ZP) plays vital roles in reproductive processes including oogenesis, fertilization and preimplantation development. Both human and rat ZP consist of four glycoproteins, called ZP1, ZP2, ZP3 and ZP4. Our previous research reported a novel Zp1 mutation in cases of human infertility, associated with an abnormal phenotype involving the absence of the zona pellucida. Here, we developed a homologous rat strain to investigate the pathogenic effect. The ovaries of homozygous (Zp1MT/MT) females possessed both growing and fully grown oocytes; the oocytes completely lacked a zona pellucida, but ZP1 was detectable inside the cytoplasm. Only 1-2 eggs were recovered from oviducts of superovulated Zp1MT/MT females, while ≈ 21 eggs were recovered from superovulated Zp1WT/WT females. The eggs of Zp1MT/MT females were not surrounded by a zona pellucida and lost their fertilization capacity in vitro. Zp1MT/MT females mated with wild-type males failed to become pregnant. Studies in 293 T cells showed that mutant Zp1 resulted in a truncated ZP1 protein, which might be intracellularly sequestered and interact with wild-type ZP3 or ZP4. Our results suggest that the Zp1 point mutation led to infertility and loss of the ZP in oocytes in rats.

11.
J Mol Recognit ; : e2890, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33620127

RESUMO

The specific regulation of PTPN18 protein to three HER2 phospho-peptides has been studied by molecular dynamics simulations and free energy calculations. The results revealed that the three HER2 phospho-peptides binding to the PTPN18 catalytic domain is energetically favorable due to substrate specificity of PTPN18, and moreover, the PTPN18 protein have significantly higher affinity to pY1248 peptide (-45.22 kcal/mol) than that of pY1112 (-25.3 kcal/mol) and pY1196 (-31.86 kcal/mol) peptides. Further, the binding of HER2 phospho-peptides to PTPN18 have also caused the closure of WPD-loop with the decrease of the centroid distances between the P-loop and the WPD loop. The WPD-loop closure of PTPN18 relates directly to the new hydrogen bond and hydrophobic interaction formations between the residues Tyr62, Asp64, Val65, Ala231, Arg235, and Ala273 in PTPN18 and Tyr(PO3) in the HER2 phospho-peptides, which suggests that these key residues would contribute to the specific regulation of PTPN18 to the substrates. The correlation analysis revealed the allosteric communication networks from the pY binding loop to the WPD loop through the structural change and the residue interactions in PTPN18. These results will be helpful to understand the specific regulation through the allosteric communication network in the PTPN18 catalytic domain.

12.
Ann Surg Oncol ; 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33389296

RESUMO

BACKGROUND: The International Association for the Study of Lung Cancer (IASLC) N classifications, which depend on the location and involvement of the lymph nodes, provide accurate prognoses. This study validated the efficiency of classifications using a single-institution dataset and proposed a modified system based on 5-level N1 node dissection. METHODS: From January 2005 to December 2014, 1851 patients with completely resected non-small cell lung cancer were reviewed. According to the IASLC recommendations, N1 is further subdivided into N1a (single) and N1b (multiple), N2 is divided into N2a1 (single station without N1), N2a2 (single station with N1), and N2b (multiple station). Additionally, we evaluated dividing N0 into N0a (with level 13/14 examination) and N0b (without level 13/14 examination), and N1 into N1a* (only level 13/14 positive) and N1b* (level 10-12 positive). Overall survival was also compared. RESULTS: Multivariate analysis showed that the N classifications recommended by the IASLC and those proposed and evaluated by this study could both significantly predict the prognoses of patients (p < 0.001, respectively). There was no significant difference in survival between N1b and N1a (hazard ratio [HR] 1.049, p = 0.83) and N2a1 and N1b (HR 1.314, p = 0.261); however, there were significant differences between N0a and N0b (HR 1.778, p < 0.001) and N1a* and N1b* (HR 2.014, p = 0.019). The survival curve of N1a* overlapped N0b (HR 0.997, p = 0.991), and N2a1 overlapped N1b* (HR 0.842, p = 0.444). CONCLUSION: More detailed nodal information is required to facilitate future revisions of N staging.

13.
Phytochemistry ; 183: 112644, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33429352

RESUMO

The genus Corydalis is a botanical source of various pharmaceutically active components. Its member species have been widely used in traditional medicine systems in Southeast Asia, especially in China for thousands of years. They have been administered to treat the common cold, hypertension, hepatitis, hemorrhage, edema, gastritis, cardiovascular and cerebrovascular diseases, and neurological disorders. Analgesia is the most important effect of Corydalis products, which are relatively non-addictive and associated with low tolerance compared with other analgesics. Certain Corydalis species are rich in alkaloids, which have strong biological activity, and also contain coumarins, flavonoids, steroids, organic acids and other chemical components. These constituents have pharmacological efficacy against diseases of the nervous, cardiovascular and digestive systems. Numerous investigations have been performed on these plants and their components. Here, we systemically summarized the chemical constituents of important medicinal member species of Corydalis that have been reported since 1962. A total 381 alkaloids were enumerated, including 117 quaternary isoquinoline type, 60 Benzophenanthridine type, 37 aporphine type, 10 protopine type, 59 phthalide isoquinoline type, 52 simple isoquinoline-type, 25 lignin amides and 21 other alkaloids. Thus, we have provided a basis for further explorations into the pharmacologically active constituents of Corydalissp.(Papaveraceae) to develop medicines that exert strong effects, are relatively non-addictive, and result in few side effects.


Assuntos
Alcaloides , Corydalis , Plantas Medicinais , Alcaloides/farmacologia , China , Medicina Tradicional
14.
J Labelled Comp Radiopharm ; 64(5): 217-224, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33480078

RESUMO

Acylcarnitines are a big family of small molecule metabolites with various acyl groups attached to the hydroxyl moiety of l-carnitine. They are good indicators of multiple metabolic disorders. For instance, the newborn screening panel uses flow injection tandem mass spectrometry to analyze more than 30 different acylcarnitines and amino acids extracted from dried blood spots. A facile approach has been developed for the synthesis of isotope labeled acylcarnitines whose mass shift over their unlabeled counterparts can be any number in the range of 3 to 12 Da. This strategy makes it more convenient to provide authentic internal standards for acylcarnitines profiling analyses, thereby expanding their clinical applications.

15.
J Thorac Dis ; 12(10): 5324-5335, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33209366

RESUMO

Background: Although neoadjuvant chemotherapy could improve survival outcome in resectable non-small cell lung cancer (NSCLC), the efficacy of neoadjuvant targeted therapy is still unclear. Methods: We retrospectively reviewed clinical records of stage I-IIIA lung adenocarcinoma patients treated with neoadjuvant targeted therapy or chemotherapy prior to surgery. The collected data were compared between the two groups. Tumor samples were collected and analyzed by sequencing to explore the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance mechanisms. Results: A total of 134 patients were enrolled; of these, 119 (88.8%) had clinical stage II-IIIA disease. Radiographic response rate was significantly higher with neoadjuvant targeted therapy than with chemotherapy among patients harboring EGFR mutation [objective response rate (ORR): 55.8% vs. 32.6%; P=0.030]. EGFR exon 19 deletion achieved better tumor response than those with exon 21 L858R mutation (ORR: 70.0% vs. 40.0%; P=0.057). Postoperative complications, operation time, drainage volume, and postoperative hospital length of stay were comparable between two groups. There was no difference on disease free survival (DFS) between patients receiving neoadjuvant targeted therapy and chemotherapy (P=0.871), but those who continued long-term adjuvant targeted therapy had significantly longer DFS than those only treated with adjuvant chemotherapy postoperatively (P=0.011). A series of potential molecular mechanisms of EGFR-TKI primary resistance were detected; these included BIM deletion polymorphisms, EGFR T790M mutation, and PTEN, TSC1, PIK3CA, or STAT3 mutations. Patients who presented stable disease (SD) response after TKI therapy had significantly lower EGFR mutation abundance than PR response (P=0.032). Conclusions: Neoadjuvant EGFR-TKI appears to be more effective than conventional chemotherapy for EGFR-mutant NSCLC patients. This study provides evidence that needs to be investigated further in randomized controlled trials (RCT).

16.
Polymers (Basel) ; 12(10)2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32987761

RESUMO

A series of linear amphiphilic pentablock terpolymer PAAx-b-PS48-b-PEO46-b-PS48-b-PAAx (AxS48O46S48Ax) with various lengths x of the PAA block (x = 15, 40, 60, and 90) were synthesized via a two-step atom transfer radical polymerization (ATRP) using Br-poly(ethylene oxide)-Br (Br-PEO46-Br) as the macroinitiator, styrene (St) as the first monomer, and tert-butyl acrylate (tBA) as the second monomer, followed with the hydrolysis of PtBA blocks. The AxS48O46S48Ax pentablock terpolymers formed micelles in dilute aqueous solution, of which the morphologies were dependent on the length x of the PAA block. Cryogenic transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), and zeta potential measurement were employed to investigate the morphologies, chain structures, size, and size distribution of the obtained micelles. The morphology of AxS48O46S48Ax micelles changed from spherical vesicles with ordered porous membranes to long double nanotubes, then to long nanotubes with inner modulated nanotubes or short nanotubes, and finally, to spherical micelles or large compound vesicles with spherical micelles inside when x increased from 15 to 90. The hydrophobic PS blocks formed the walls of vesicles and nanotubes as well as the core of spherical micelles. The hydrophilic PEO and PAA block chains were located on the surfaces of vesicle membranes, nanotubes, and spherical micelles. The PAA block chains were partially ionized, leading to the negative zeta potential of AxS48O46S48Ax micelles in dilute aqueous solutions.

17.
Echocardiography ; 37(11): 1838-1843, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32931069

RESUMO

PURPOSE: Lung ultrasonography (LU) is useful to assess lung lesions and variations at bedside. To investigate the results of LU in severe and critical patients with coronavirus disease 2019 (COVID-19), we performed a single-institution study to evaluate the related lung lesions and variations, and prophylactic strategies, in a large referral and treatment center. METHODS: We included 91 adult patients with severe and critical COVID-19, namely 62 males and 29 females, with an average age of 59 ± 11 years, who underwent LU. We collected the following patient information: sex, age, days in hospital, and days in ICU. In the ultrasound examinations, we recorded the presence of discrete B lines, confluent B lines, consolidation, pleural thickening, pleural effusion, and pneumothorax (PTX). RESULTS: Among the 91 severe and critical patients, 59 cases had scattered B lines, 56 cases had confluent B lines, 58 cases had alveolar-interstitial syndrome (AIS), 48 cases had lung consolidation, six cases had pleural thickening, 39 cases had pleural effusion (average depth of the pleural effusion: 1.0 ± 1.5 cm), and 20 patients developed PTX. In the Cox multivariate analysis, there were significant differences in age, hospitalization days, ICU days, and lung consolidation. CONCLUSION: Lung ultrasonography performed at the bedside can detect lung diseases, such as B lines, PTX, pulmonary edema, lung consolidation, pleural effusion, and variations of these findings. Our findings support the use of LU and measurements for estimating factors, and monitoring response to therapy in severe and critical COVID-19 patients.

18.
Front Pharmacol ; 11: 1255, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922293

RESUMO

Background: Metabolic remodeling plays a vital role in the development of heart failure. The trimetazidine can optimize fatty acid and glucose oxidation via inhibition of long-chain 3-ketoacyl CoA thiolase in the heart. So, trimetazidine commonly used in cardiovascular therapy as a myocardial metabolic drug. This study was conducted to assess the effects and mechanisms of trimetazidine on ketone body metabolism in heart failure rats. Methods: A rat model of heart failure was established by continuous subcutaneous injection of isoproterenol in 10 mg/kg/d. We examined body weight, heart weight index, and tested B-type natriuretic peptide by kit. We detected the structure and function of the heart. Hematoxylin-eosin staining and Masson's trichrome staining was performed to assess myocardial tissue morphology. To evaluate apoptosis, we used Tunel staining. Metabolic substrate contents of glucose, free fatty acid, ketone bodies, lactic acid, and pyruvate and ATP levels in myocardial tissues were measured with the corresponding kit. We detected the levels of protein expressions related to myocardial substrate uptake and utilization by Western blot. Results: Trimetazidine remarkably reduced the heart weight index and B-type natriuretic peptide levels. Besides, trimetazidine increased the level of blood pressure and decreased heart rate. Moreover, trimetazidine inhibited decreases in left ventricular ejection fraction and left ventricular fractional shortening. Further, trimetazidine decreased the levels of collagen volume fraction and promoted ATP production in myocardial tissues. Trimetazidine also reduced the levels of free fatty acid, ketone bodies, lactic acid, and increased glucose and pyruvate levels in myocardial tissues. Furthermore, trimetazidine markedly inhibited apoptosis. More importantly, the protein expression levels related to myocardial substrate uptake and utilization increased dramatically in the trimetazidine group. In particular, the protein expressions related to ketone body utilization were prominent. Conclusions: Trimetazidine could attenuate metabolic remodeling and improve cardiac function in heart failure rats. The potential mechanism for the cardioprotective effect of trimetazidine may be highly associated with its regulation of adenosine monophosphate-activated protein kinase, and peroxisome proliferator activated receptor α expressions. Along with the regulation, myocardial substrate utilization was improved, especially the utilization of ketone bodies.

19.
Adv Parasitol ; 110: 1-62, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32563322

RESUMO

Being a zoonotic parasitic disease, schistosomiasis was widely spread in 12 provinces of Southern China in the 1950s, severly harming human health and hindering economic development. The National Institute of Parasitic Diseases at the Chinese Center for Diseases Control and Prevention, and Chinese Center for Tropical Diseases Research (NIPD-CTDR), as the only professional institution focussing on parasitic diseases at the national level, has played an important role in schistosomiasis control in the country. In this article, we look back at the changes of schistosomiasis endemicity and the contribution of NIPD-CTDR to the national schistosomiasis control programme. We review NIPD-CTDR's activities, including field investigations, design of control strategies and measures, development of diagnostics and drugs, surveillance-response of endemic situation, and monitoring & evaluation of the programme. The NIPD-CTDR has mastered the transmission status of schistosomiasis, mapped the snail distribution, and explored strategies and measures suitable for different types of endemic areas in China. With a good understanding of the life cycle of Schistosoma japonicum and transmission patterns of the disease, advanced research carried out in the NIPD-CTDR based on genomics and modern technology has made it possible to explore highly efficient and soft therapeutic drugs and molluscicides, making it possible to develop new diagnostic tools and produce vaccine candidates. In the field, epidemiological studies, updated strategies and targeted intervention measures developed by scientists from the NIPD-CTDR have contributed significantly to the national schistosomiasis control programme. This all adds up to a strong foundation for eliminating schistosomiasis in China in the near future, and recommendations have been put forward how to reach this goal.

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