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1.
Eur J Pharmacol ; 876: 173049, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32142771

RESUMO

In the beginning stage of heart disease, the blockage of blood flow frequently occurs due to the persistent damage and even death of myocardium. Cicatricial tissue developed after the death of myocardium can affect heart function, which ultimately leads to heart failure. In recent years, several studies carried out about the use of stem cells such as embryonic, pluripotent, cardiac and bone marrow-derived stem cells as well as myoblasts to repair injured myocardium. Current studies focus more on finding appropriate measures to enhance cell homing and survival in order to increase paracrine function. Until now, there is no universal delivery route for mesenchymal stem cells (MSCs) for different diseases. In this review, we summarize the advantages and challenges of the systemic and local pathways of MSC delivery. In addition, we also describe some advanced measures of cell delivery to improve the efficiency of transplantation. The combination of cells and therapeutic substances could be the most reliable method, which allows donor cells to deliver sufficient amounts of paracrine factors and provide long-lasting effects. The cardiac support devices or tissue engineering techniques have the potential to facilitate the controlled release of stem cells on local tissue for a sustained period. A novel promising epicardial drug delivery system is highlighted here, which not only provides MSCs with a favorable environment to promote retention but also increases the contact area and a number of cells recruited in the heart muscle.

2.
Microbiol Res ; 235: 126448, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32114363

RESUMO

Vibrio parahaemolyticus is a common foodborne pathogen in seafood and represents a major threat to human health worldwide. In this study, we identified that PhoR, a histidine kinase, is involved in the regulation of swarming and flagella assembly. RNA sequencing analysis showed that 1122 genes were differentially expressed in PhoR mutant, including 394 upregulated and 728 downregulated genes. KEGG enrichment and heatmap analysis demonstrated that the bacterial secretion system, flagella assembly and chemotaxis pathways were significantly downregulated in PhoR mutant, while the microbial metabolism in diverse environments and carbon metabolism pathways were upregulated in PhoR mutant. qRT-PCR further confirmed that genes responsible for the type III secretion system (T3SS), swarming and the thermostable direct hemolysin were positively regulated by PhoR. Phosphorylation assays suggested that PhoR was highly activated in BHI medium compared to LB medium. Taken together, these data suggested that activated PhoR contributes to the expression of swarming motility and secretion system genes in Vibrio parahaemolyticus.

3.
Int J Mol Med ; 45(2): 353-364, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31789413

RESUMO

Persistent ventricular remodeling following myocardial ischemia/reperfusion (MI/R) injury results in functional decompensation and eventual progression to heart failure. VCP979, a novel small­molecule compound developed in­house, possesses anti­inflammatory and anti­fibrotic activities. In the present study, no significant pathological effect was observed following the administration of VCP979 on multiple organs in mice and no difference of aspartate transaminase/alanine aminotransferase/lactate dehydrogenase levels was found in murine serum. Treatment with VCP979 ameliorated cardiac dysfunction, pathological myocardial fibrosis and hypertrophy in murine MI/R injury models. The administration of VCP979 also inhibited the infiltration of inflammatory cells and the pro­inflammatory cytokine expression in hearts post MI/R injury. Further results revealed that the addition of VCP979 prevented the primary neonatal cardiac fibroblasts (NCFs) from Angiotensin II (Ang II)­induced collagen synthesis and neonatal cardiac myocytes (NCMs) hypertrophy. In addition, VCP979 attenuated the activation of p38­mitogen­activated protein kinase in both Ang II­induced NCFs and hearts subjected to MI/R injury. These findings indicated that the novel small­molecule compound VCP979 can improve ventricular remodeling in murine hearts against MI/R injury, suggesting its potential therapeutic function in patients subjected to MI/R injury.

4.
Drug Deliv Transl Res ; 10(1): 23-33, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31240626

RESUMO

We have used a novel active hydraulic ventricular support drug delivery system (ASD) device, which is a non-transplant surgical approach, can adhere to heart surface, and deliver the drug directly into the epicardium. This study is intended to compare the effect of administration of nitroglycerine (NTG) through ASD and intravenous injection on the ischemic injury during acute myocardial infarction (AMI). 30 male SD rats were allocated into five groups (n = 6): sham, AMI, I.V., ASD high dose (ASDH), and ASD low dose (ASDL) respectively. Ligation of the left anterior descending (LAD) coronary artery was performed to induce myocardial infarction. Electrocardiograms were monitored, and serum myoglobin (Mb) was assessed. Hemodynamics was observed on pre- and post-operation. Hematoxylin and eosin (H&E) staining was performed for histological diagnosis. In all model animals, ligation of LAD provoked ST segment elevation and Mb level augmentation. In ASDH group, Mb showed obvious decrease as compared with other treatment groups. Hemodynamic parameters showed significant improvement in ASDH and ASDL groups than the I.V. group. H&E staining showed that AMI group rats had wavy fibers and loss of transverse striations while ASD group rats had obvious improvement. Unlike the I.V. group, ASD group rats showed significant vasodilation. Therefore, delivery of NTG through ASD to the cardiomyocytes could improve the therapeutic efficacy. A novel effective route for local delivery of agents to manage AMI has been proved.

5.
Br J Cancer ; 122(1): 102-110, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31819181

RESUMO

BACKGROUND: 3-Hydroxybutyrate dehydrogenase type 2 (BDH2) is known to catalyse a rate-limiting step in the biogenesis of the mammalian siderophore and regulate intracellular iron metabolism. Here we aim to explore the expression and possible function of BDH2 in nasopharyngeal carcinoma (NPC). METHODS: The transcription and protein expression of BDH2 in NPC were determined by both real-time RT-PCR and immunohistochemistry staining assays. Cell proliferation, migration and invasion were evaluated by MTT assay, wound-healing assay and Transwell assay, respectively. The profile of genes regulated by restoring BDH2 expression in NPC cells was analysed by cDNA microarray. The level of iron in NPC cells was detected by iron colorimetric assay. RESULTS: The expression of BDH2 was significantly downregulated in NPC. Ectopic expression of BDH2 inhibited NPC cell proliferation and colony formation. Meanwhile, BDH2 suppressed the migration and invasion of NPC cells by reversing the epithelial-mesenchymal transition (EMT). In addition, a higher level of BDH2 decreased the growth and metastasis of NPC cells via reducing intracellular iron level. CONCLUSIONS: Our findings suggest that BDH2 may be a candidate tumour-suppressor gene in NPC. Decreasing intracellular iron could be an effective therapeutic approach for NPC.

6.
Adv Nutr ; 11(1): 66-76, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31269204

RESUMO

The gut microbial metabolite trimethylamine N-oxide (TMAO) is increasingly regarded as a novel risk factor for cardiovascular events and mortality. However, little is known about the association between TMAO and hypertension. This meta-analysis was conducted to quantitatively assess the relation between the circulating TMAO concentration and hypertension prevalence. The PubMed, Cochrane Library, and Embase databases were systematically searched up to 17 June 2018. Studies recording the hypertension prevalence in members of a given population and their circulating TMAO concentrations were included. A total of 8 studies with 11,750 individuals and 6176 hypertensive cases were included in the analytic synthesis. Compared with low circulating TMAO concentrations, high TMAO concentrations were correlated with a higher prevalence of hypertension (RR: 1.12; 95% CI: 1.06, 1.17; P < 0.0001; I2 = 64%; P-heterogeneity = 0.007; random-effects model). Consistent results were obtained in all examined subgroups as well as in the sensitivity analysis. The RR for hypertension prevalence increased by 9% per 5-µmol/L increment (RR: 1.09; 95% CI: 1.05, 1.14; P < 0.0001) and 20% per 10-µmol/L increment of circulating TMAO concentration (RR: 1.20; 95% CI: 1.11, 1.30; P < 0.0001) according to the dose-response meta-analysis. To our knowledge, this is the first systematic review and meta-analysis demonstrating a significant positive dose-dependent association between circulating TMAO concentrations and hypertension risk.

7.
Front Pharmacol ; 10: 1142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31680946

RESUMO

Background: Effective interventions to improve the outcome of patients subjected to myocardial ischemia reperfusion (MI/R) are urgent in clinical settings. Tanshinone IIA (TSA) is reported to attenuate myocardial injury and improve ventricular remodeling post MI/R. Here, we evaluated the efficacy of AFC1 compound that is similar to TSA structure in murine MI/R models. We found that AFC1 had a comparable effect of improving murine cardiac function after MI/R while it was superior to TSA in safety profile. Administration of AFC1 reduced reactive oxygen species (ROS) production, inflammatory cells infiltration, and the expression of platelet derived growth factor receptors (PDGFR) in infarcted myocardium. Treatment with AFC1 also attenuated MI/R-induced cardiac remodeling and contributed to the recovery of cardiac function. Additionally, AFC1 reversed the elevation of PDGFR expression induced by PDGF-AB in both neonatal rat cardiomyocytes (NCMs) and neonatal rat cardiac fibroblasts (NCFs) and suppressed PDGF-AB induced NCM hypertrophy via STAT3 pathway and NCF collagen synthesis through p38-MAPK signaling in vitro. Similarly, AFC1 may contribute to the recovery of cardiac function in mice post MI/R via suppressing STAT signaling. Our results confirmed that AFC1 exerts anti-hypertrophic and anti-fibrotic effects against MI/R-induced cardiac remodeling, and suggest that AFC1 may have a promising potential in improving the outcome of patients who suffered from MI/R.

8.
Sci Rep ; 9(1): 15896, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685877

RESUMO

In this paper, the zonal and meridional sea surface height (SSH) wavenumber spectra are systematically calculated using along-track and gridded altimeter products, and the slopes of the SSH wavenumber spectra over the mesoscale band, which is defined by the characteristic length scale of mesoscale signals, are estimated. The results show that the homogeneous spectral slopes calculated from the along-track and gridded altimeter datasets have a similar spatial pattern, but the spectral slopes from gridded altimeter data are generally steeper than that from the along-track data with an averaged difference of 1.5. Significant differences are found between the zonal and meridional spectra, which suggest that SSH wavenumber spectra are indeed anisotropic. Furthermore, the anisotropy exhibits strong regional contrast: in the equatorial region, the zonal spectrum is steeper than its corresponding meridional spectrum, while in the eastward-flowing high EKE regions the meridional spectrum is steeper than its zonal counterpart. The anisotropy of SSH wavenumber spectral slopes implies that EKE distributes anisotropically in different directions, and this distribution is closely associated with the generation and nonlinear evolution of mesoscale movements.

9.
Theranostics ; 9(26): 8109-8126, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31754384

RESUMO

Rationale: Ascorbate is an essential micronutrient known for redox functions at normal physiologic concentrations. In recent decades, pharmacological ascorbate has been found to selectively kill tumour cells. However, the dosing frequency of pharmacologic ascorbate in humans has not yet been defined. Methods: We determined that among five hepatic cell lines, Huh-7 cells were the most sensitive to ascorbate. The effects of high-dose ascorbate on hepatoma were therefore assessed using Huh-7 cells and xenograft tumour mouse model. Results: In Huh-7 cells, ascorbate induced a significant increase in the percentage of cells in the G0/G1 phase, apoptosis and intracellular levels of ROS. High doses of ascorbate (4.0 pmol cell-1), but not low doses of ascorbate (1.0 pmol cell-1), also served as a pro-drug that killed hepatoma cells by altering mitochondrial respiration. Furthermore, in a Huh-7 cell xenograft tumour mouse model, intraperitoneal injection of ascorbate (4.0 g/kg/3 days) but not a lower dose of ascorbate (2.0 g/kg/3 days) significantly inhibited tumour growth. Gene array analysis of HCC tumour tissue from xenograft mice given IP ascorbate (4.0 g/kg/3 days) identified changes in the transcript levels of 192 genes/ncRNAs involved in insulin receptor signalling, metabolism and mitochondrial respiration. Consistent with the array data, gene expression levels of AGER, DGKK, ASB2, TCP10L2, Lnc-ALCAM-3, and Lnc-TGFBR2-1 were increased 2.05-11.35 fold in HCC tumour tissue samples from mice treated with high-dose ascorbate, and IHC staining analysis also verified that AGER/RAGE and DGKK proteins were up-regulated, which implied that AGER/RAGE and DGKK activation might be related to oxidative stress, leading to hepatoma cell death. Conclusions: Our studies identified multiple mechanisms are responsible for the anti-tumour activity of ascorbate and suggest high doses of ascorbate with less frequency will act as a novel therapeutic agent for liver cancer in vivo.

10.
Front Genet ; 10: 1116, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781171

RESUMO

Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), with distinct long-term prognosis and responses to treatment, are two major problems that lead to heart failure (HF) ultimately. In this study, we investigated the long noncoding RNA (lncRNA) and messenger RNA (mRNA) expressions in the plasma of patients with DCM and ICM and analyzed the different lncRNA profile between the two groups. The microarray analysis identified 3,222 and 1,911 significantly differentially expressed lncRNAs and mRNAs between DCM and ICM group. The most enriched upregulated functional terms included positive regulation of I-kappaB kinase/nuclear factor-kappaB signaling and regulation of cellular localization, while the top 10 downregulated genes mainly consisted of acid secretion and myosin heavy chain binding. Furthermore, the Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differentially expressed lncRNA-coexpressed mRNAs between DCM and ICM group were significantly enriched in the natural killer cell mediated cytotoxicity and ras signaling pathway respectively. Quantitative real-time PCR confirmed 8 of 12 lncRNAs were upregulated in DCM group compared to ICM group which was consistent with the initial microarray results. The lncRNA/mRNA coexpression network indicated the possible functions of the validated lncRNAs. These findings revealed for the first time the specific expression pattern of both protein-coding RNAs and lncRNAs in plasma of HF patients due to DCM and ICM which may provide some important evidence to conveniently identify the etiology of myocardial dysfunctions and help to explore a better strategy for future HF prognosis evaluation.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31642541

RESUMO

Prostate cancer and prostatitis are both significant health concerns. A large number of studies have established that the occurrence of the two is closely related. However, the most common prostatitis, type III chronic prostatitis/chronic pelvic pain syndromes (CP/CPPS), is reported to not correlate with the occurrence of prostate cancer. Although the etiology of CP/CPPS is unknown, it may be related to the autoimmune mechanism favored by most studies. Manipulating the immune system and targeting tumor microenvironment are promising new methods for the treatment of prostate cancer. Therefore, this review focuses on the immune cells and cytokines of CP/CPPS and prostate cancer from the perspective of biological immunology and immune microenvironment. We discuss T-regulatory (Treg) and T helper 17 (Th17) cells dysfunction, the abnormal regulation of T helper 1(Th1) and T helper 2 (Th2) cells, macrophages, and their related cytokines as key activators in CP/CPPS. In addition, we discuss the roles of Treg and Th17 cells, Th1 and Th2 cells, and related cytokines in modulating prostate cancer progression. This review highlights the concept that immune cells and cytokines provide a research strategy for the etiology of CP/CPPS and offer potentially promising targets for the treatment of prostate cancer.

12.
J BUON ; 24(4): 1686-1691, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31646826

RESUMO

PURPOSE: Esculetin is an important bioactive coumarin with amazing potential to suppress the growth of cancer cells. The present study was designed to investigate the anticancer effects of esculetin against the human leukemia HL-60 cells. METHODS: CCK-8 assay was used to assess cell viability. DAPI and annexin V/propidium iodide (PI) staining was performed to investigate the induction of apoptosis. Autophagy was detected by electron microscopic analysis. Flow cytometry was used for cell cycle analysis and Western blotting was used to estimate protein expression. RESULTS: Esculetin suppressed the proliferation of HL-60 cells dose-dependently. The IC50 of esculetin against HL-60 cells was observed to be 20 µM. The anticancer effects of esculetin against HL-60 cells occurred though different mechanisms. Esculetin induced apoptosis and autophagy in leukemia cells, which were accompanied by alteration in the expression of apoptosis as well as autophagy-related proteins. Esculetin also triggered G0/G1 cell cycle arrest in HL-60 cells, which was also accompanied by suppression of Cyclin D1 and D3. Esculetin could also block the Raf/MEK/ERK signalling pathway in leukemia cells in a concentration-dependent manner. CONCLUSION: These results indicate that esculetin inhibits the growth of leukemia cells and hence may prove beneficial for treating leukemia.

13.
Int Immunopharmacol ; 76: 105899, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31518916

RESUMO

The function of histone methyltransferase enhancer of zeste homolog 2 (EZH2) in sepsis remains unknown. We reported here that the expression of EZH2 and H3K27me3 was significantly upregulated in the circulation of septic patients, whereas patients who survived presented downregulated the expression of EZH2 on CD14+ monocytes. We further identified increased expression of EZH2 in the circulation, peritoneal fluid, and septic lungs from CLP mice. 3-DZNeP treated CLP mice improved mortality and protected from organ injury. EZH2 inhibition not only suppressed the activation of inflammatory cells and release of cytokines in the circulation and infectious sites, but also promoted bacteria clearance and replenished the circulating monocyte and neutrophil pool from bone marrow. Blockage of EZH2 also suppressed the progression of lung injury and alleviated inflammation by decreasing the pulmonary cell apoptosis, reducing inflammatory cells infiltration and cytokines release through inhibition of the STAT3 signaling pathway and recovery of PPARγ activation. In addition, EZH2 inhibitor blunted macrophage M1 polarization by SOCS3/STAT1 pathway. Overall, these data suggest that EZH2 could be a potential biomarker predicting clinical outcome and a new target for therapeutic interference in sepsis.

14.
J Cell Mol Med ; 23(10): 7111-7115, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31411002

RESUMO

Circular RNAs (circRNAs) make up a large class of non-coding RNAs and play important roles in the pathology of a variety of diseases. However, their roles in pulmonary macrophage polarization after sepsisinduced lung injury is unknown. In this study, mice were divided into two groups: Sham control group and cecal ligation and puncture (CLP)-induced ALI group. Macrophages were isolated from lung homogenates 24 hours after SCLP/CLP. We started with RNA-seq of circRNA changes in macrophages and validated by RT-PCR in the following experiments. A total of 4318 circRNAs were detected in the two groups. Of these, 11 and 126 circRNAs were found to be significantly upregulated and downregulated, respectively, compared to the control (p≤0.05, Fold Change ≥2). Differentially expressed circRNAs with a high foldchange (fold-change >4, P<0.05) were selected for validation by qRT-PCR, 10 of which were verified. Furthermore, the most differentially expressed circRNAs within all the comparisons were annotated in detail with circRNA/miRNA interaction information using miRNA target prediction software. The network of circRNA-miRNA-mRNA was illustrated by cytoscape software. Gene ontology analyses indicated the upregulated circRNAs were involved in the multiple biological functions such as regulation of mitochondrion distribution and Notch binding, while the down-regulated circRNAs mainly involved in the biological process as histone H3K27 methylation. KEGG pathway analysis revealed TGF-beta signaling pathway was related to the upregulated circRNAs. The present study provides a novel insight into the roles of circRNAs in pulmonary macrophage differentiation and polarization post septic lung injury.

15.
Dev Psychol ; 55(10): 2147-2158, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31368763

RESUMO

Deficits in executive function have been associated with internalizing problems in children. Yet little is known about the mechanisms that may explain this association. Using longitudinal data across elementary school years (N = 1,364), this study examined the role of peer difficulty and poor academic performance in understanding longitudinal associations between executive function and internalizing problems. Executive function was measured in first grade with observed tasks and standardized tests. Peer difficulty and academic performance were reported by teachers and/or mothers at three waves. Internalizing problems were reported by mothers at four waves. Using structural equation modeling, results demonstrated that peer difficulty and poor academic performance independently mediated longitudinal relations between executive function and internalizing problems. Findings highlighted the importance of children's functioning in key identity domains in understanding the adverse impact of inferior executive function on internalizing problems in school-age children. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Desempenho Acadêmico , Comportamento Infantil/fisiologia , Função Executiva/fisiologia , Grupo Associado , Estudantes/estatística & dados numéricos , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Modelos Estatísticos , Testes Neuropsicológicos , Instituições Acadêmicas
16.
Inflammation ; 42(6): 2086-2094, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31429013

RESUMO

The exact etiology and pathogenesis of chronic prostatitis (CP/CPPS) remain unclear. However, autoimmunity is a widely known theory. Precise treatment of CP/CPPS is not available. Here, we developed a new effective treatment method to prevent the occurrence of CP/CPPS. A total of 40 male C57BL/6 mice were randomly divided into four groups (n = 10): i.e., naive, model, high-dose (500 µg/ml), and low-dose (50 µg/ml) groups. High-dose and low-dose groups were orally given 0.4 ml of T2-containing soybean trypsin inhibitor (STI) at once after every 2 days for a total of 10 days. On day 10 and day 24 all the groups except naïve group were subcutaneously injected with 0.2 ml of T2 peptide along with CFA to make valid CP/CPPS models. Hematoxylin and eosin staining were used to evaluate the variation in CP/CPPS manifestation. Voiding behavior was recorded for the evaluation of urine frequencies. ELISA was used to measure the serum level of TNF-α in each group. The high- and low-dose groups of T2-containing STI displayed a reduction in urine frequencies, and inflammation, and there was a slight inflammatory infiltration as compared to the model group. In contrast, there was no difference observed in the TNF-α concentration of model as well as high- and low-dose groups compared to the naïve group. Our study demonstrates that oral T2-containing STI prevents CP/CPPS and provides an effective approach for the treatment of CP/CPPS.

17.
Int J Cardiol ; 296: 136-140, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31466885

RESUMO

BACKGROUND: Increasing studies indicated the involvement of extracellular vesicles (EVs) in cardiovascular diseases. However, the role of circular RNAs (circRNAs) in cardiac EVs (cEVs) during ischemia/reperfusion (I/R) injury remain unclear. METHODS: We isolated the cEVs from I/R injured hearts and performed RNA sequencing (RNA-seq) to identify the profile of circRNA in cEVs and investigated their potential roles in I/R pathological process. RESULTS: Cardiac I/R induced a significantly elevated release of EVs in heart within 24 h. RNA-seq of cEVs identified 185 significantly differentially expressed (DE) circRNAs including 119 down-regulated and 66 up-regulated circRNAs in I/R group compared with the sham. GO and pathway analysis showed that these DE-circRNAs were associated with protein binding and kinase activator activity and mainly involved in the metabolic process. The circRNA-miRNA analysis exhibited the broad potentials of the DE-circRNAs to regulate target genes by acting on the miRNAs. CONCLUSIONS: These findings revealed for the first time the specific expression pattern of circRNAs in EVs derived from sham and I/R heart tissues and provided some potential targets and pathways involving in I/R injury which may provide important evidences for the role of both circRNA and EVs in the pathology of cardiac I/R.

18.
Int Urol Nephrol ; 51(12): 2093-2106, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31468287

RESUMO

Among one of the four category prostatitis, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is the disease with unknown etiology and having 90-95% prevalence in prostatitis. CP/CPPS poses adverse psychological effects and weakens the quality of life (QoL) of the patients. Due to its multifactorial etiology, various types of treatment are available with different management efficacies. The conventional treatment like anti-inflammatory medications, antibiotics, and alpha-blockers have given the lack of verified efficacy that has turned the patients to alternative therapies such as acupuncture because of its efficacy, safety, and high compliance. Acupuncture is an alternative management accepted in several countries and is commonly used in traditional Chinese medicine for chronic pain. Acupuncture had the effect of immune modulation, anti-inflammatory, and neuromodulation. For chronic prostatitis, acupuncture can improve pain symptoms and can bring better results about National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), and QoL. This review will discuss the efficacy of acupuncture in the treatment of CP/CPPS and effect of acupuncture on NIH-CPSI total score and its domains: pain, voiding, and QoL, as well as its effect on different biomarkers of CPPS.

19.
J Agric Food Chem ; 67(30): 8382-8392, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31271032

RESUMO

Staphylococcus aureus is a common pathogen that can cause life-threatening infections. Treatment of antibiotic-resistant S. aureus infection needs effective antibacterial agents. Thymol, a generally recognized safe natural compound, has potential as an alternative to treat S. aureus infections. However, the targets and mechanisms of action of thymol were not fully understood. Bioinformatics analysis showed that IolS, a predicted aldo-keto reductase (AKR) in S. aureus, could be a potential target of thymol. Isothermal titration calorimetry (ITC) analysis demonstrated that thymol directly binds IolS and amino acid residues (Y30 and L33) are essential for such binding. Deletion of IolS or mutation of Y30A and L33A reduced the bactericidal activity of thymol at the concentration of 200 µg/mL, suggesting that thymol mediates bactericidal activity via binding with IolS. Biochemical analysis showed that addition of thymol significantly increased AKR activity of IolS from 1.6 ± 0.1 to 2.4 ± 0.2 U (p < 0.05). The content of NADPH within S. aureus cells decreased significantly from 105 ± 5 to 72 ± 3 pmol/108 cells (p < 0.05) following thymol treatment at the concentration of 200 µg/mL. Importantly, addition of NADPH could alleviate the bactericidal effect of thymol on S. aureus, indicating that the depletion of NADPH is responsible for thymol-mediated bactericidal activity. Overall, these results demonstrated that thymol could directly bind IolS and increase its AKR activity, leading to the depletion of NADPH and bactericidal effect. AKR activity of IolS could be a promising target for the development of new antimicrobials.


Assuntos
Aldo-Ceto Redutases/antagonistas & inibidores , Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , NADP/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/enzimologia , Timol/farmacologia , Aldo-Ceto Redutases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Humanos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética
20.
Cell Rep ; 28(3): 804-818.e7, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31315056

RESUMO

Toll-like receptors (TLRs) activate innate immunity via interactions between their Toll/interleukin-1 (IL-1) receptor (TIR) domain and downstream adaptor proteins. Here we report that Salmonella Enteritidis produces a secreted protein (TcpS) that contains both a TIR domain and a coiled-coil domain. TcpS blocks MyD88- and TRIF-mediated TLR signaling, inhibits inflammatory responses, and promotes bacterial survival. Early-stage immune evasion by TcpS results in severe tissue damage in the late stage of infection and contributes to Salmonella virulence. TcpS-derived peptides inhibit nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) activation and reduce lipopolysaccharide (LPS)-elicited systemic inflammation. Therapeutic peptide administration alleviates weight loss of mice infected with H1N1 influenza. Importantly, maximal TcpS-mediated TLR inhibition requires the critical TIR-TcpS residues Y191 and I284, as well as TcpS homodimerization via its N-terminal coiled-coil domain. Our study unveils a mechanism in which TcpS suppresses innate immunity via both its homodimerization and interaction with MyD88. TcpS is also a potential therapeutic agent for inflammation-associated diseases.

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