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1.
J Cell Biochem ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31609014

RESUMO

OBJECTIVE: To further explore the role of BCL-2 associated anthanogen-1 (BAG-1) in neuronal apoptosis and whether the effect of BAG-1 depends on heat shock protein 70 (HSP70). METHODS: RNA interference (RNAi) technology was used to inhibit the expression of BAG-1 in SH-SY5Y cells. Hypoxia-reoxygenation injury model in the SH-SY5Y cells was established. Cell Counting Kit-8 (CCK-8) was performed for cell viability. Annexin V-APC/7-AAD double-staining followed by flow cytometry was used to measure cell apoptosis. Quantitative reverse-transcription polymerase chain reaction and Western blot analysis were used to detect the messenger RNA (mRNA) and protein expression of genes, respectively. RESULTS: BAG-1 gene silencing decreased SH-SY5Y cell viability and promoted SH-SY5Y cell apoptosis after hypoxia-reoxygenation. However, the down-regulation of BAG-1 had no effect on the mRNA and protein expression of HSP70. CONCLUSION: BAG-1 could protect SH-SY5Y cells from the hypoxia-reoxygenation injury without affecting HSP70 expression.

2.
Mol Med Rep ; 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31638223

RESUMO

ß­myosin heavy chain (MHC) 7 (MYH7) is the dominant pathogenic gene that harbors mutations in 20­30% of cases of familial hypertrophic cardiomyopathy (HCM). The aim of this study was to elucidate the distribution and type of genetic variations among Chinese HCM families. From 2013 to 2017, the clinical data of 387 HCM probands and their families were collected. Targeted exome­sequencing technology was used in all probands, and the selected mutations were subsequently verified by Sanger sequencing in the probands, family members and 300 healthy ethnic­matched volunteers. Three­dimensional models were created using Swiss­PdbViewer 4.1, and further genetic analyses were performed to determine sequence conservation and frequency of the mutations. Among the 5 probands with double MYH7 mutations, 4 carried compound heterozygous mutations, and 1 carried monoallelic double mutations (A934V and E1387K). Four family members of the proband with monoallelic double mutations had the same mutation as the proband. Echocardiography and 12­lead electrocardiography revealed abnormalities in the proband and 3 of the 4 carriers. The probands with compound heterozygous mutation had a higher left ventricular mass as revealed by echocardiography and higher QRS, SV1 and RV5+SV1 amplitudes than those with monoallelic double mutations (P<0.05). Simulation of the 3D structure of mutated proteins showed that the replacement of alanine by valine affected the flexibility of the MHC neck domain in case of the A934V mutation, whereas reactivity of the MHC rod domain was affected in the case of the E1387K mutation. In conclusion, we identified several novel HCM­causing MYH7 mutations. More importantly, this is the first study to report a rare HCM family with monoallelic double mutations.

3.
Fitoterapia ; : 104375, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31629050

RESUMO

Picrasamide A (1), a new cinnamamide derivative, together with two new ß-carboline alkaloids (2 and 3) and five known ß-carboline alkaloids (4-8) were isolated from the stems of Picrasma quassioides (D. Don) Benn. Their structures were elucidated by detailed analyses of UV, IR, HRESIMS, and NMR data. Compound 1 was the first case of cinnamamide derivative from genus Picrasma. The AChE inhibitory activity and the antimicrobial activity of 1-8 were assessed. In addition, preliminary structure-activity relationships of these ß-carboline alkaloids on the AChE inhibitory activity and antimicrobial activity were proposed.

4.
Biosci Rep ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31661113

RESUMO

BACKGROUND: Previous studies have explored associations between IL-18 promoter polymorphisms and coronary artery disease (CAD). However, the results were controversial. We conducted a meta-analysis to clarify the association between the two polymorphisms and CAD risk. METHODS: We searched English and Chinese databases and calculated the odds ratio (OR) and 95% confidence interval (CI) to estimate whether there are genetic associations between IL-18 promoter polymorphisms and the risk of CAD. All relevant studies were screened and meta-analyzed using STATA 15.0. RESULTS: A total of 15 studies, including 12 studies for-137 G/C and 9 studies for -607 C/A, were identified for the meta-analysis. For -137 G/C, the results showed a significantly reduced risk of CAD in the dominant model (OR=0.85) and heterozygous model (OR=0.88) in the overall analysis. However, in subgroup analysis, decreased CAD risks were only observed in Asian populations for heterozygous genetic models. For -607 C/A, the overall OR revealed a reduced risk of CAD in all five genetic models (allelic, OR=0.78; recessive, OR=0.75; dominant, OR=0.68; homozygous, OR=0.61; heterozygous, OR=0.72). In subgroup analysis, reduced CAD risk was also found in five genetic models of the Asian population. We also found that the IL-18 polymorphisms were correlated with myocardial infarction and multivessel disease. CONCLUSION: Our results suggested that the -137 polymorphism and -607 polymorphism in the IL-18 promoter were negatively associated with CAD, especially in the Asian population. In addition, some genetic models were correlated with the severity of CAD.

5.
Ecotoxicol Environ Saf ; 187: 109831, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31654868

RESUMO

Lead is one of the most hazardous pollutants to both the environment as well as human beings. As one of the approaches to enhance phytoremediation, brassinosteroids are predicted as a potential candidate phytohormone for assisted phytoremediation. Few studies have focused on the physiological regulations of tall fescue plants (Festuca arundinacea Schreb.), a potential phytoremediation species, for its responses to applications of brassinosteroids under lead stress. Therefore, the objectives of this study were to investigate the effects of foliar application of 24-epibrassinolide, a brassinosteroids analogue, on reactive oxygen species accumulation and antioxidative defense systems of tall fescue when exposed to lead, and ultimately its potential to be used in phytoremediation. When exposed to lead (1000 mg/kg) for 80 d, decreases in shoot and root biomass of tall fescue biomass as well as chlorophyll and carotenoid productions were found. Foliar application of 24-epibrassinolide at three rates and five applications every 7 d improved the biomass of both shoots and roots, and increased the photosynthetic pigments. The improved lead tolerance in tall fescue plants after 24-epibrassinolide applications was associated with reduced H2O2 and O2.- accumulations and increased antioxidative enzyme activities including superoxide dismutase, catalase, and guaiacol peroxidase. Additionally, osmoprotectants increased and lipid peroxidation decreased. Ultimately, foliar applications of 24-epibrassinolide enhanced the lead recovery rate of tall fescue plants, proving its potential role in phytoremediation for soil contaminated with heavy metals such as lead.

6.
Chin J Integr Med ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31630361

RESUMO

OBJECTIVE: To analyze the effective components of Chinese medicine (CM) contained in Chaihu Shugan Powder (, CSP) in the treatment of depressive disorders and to predict its anti-depressant mechanism by network pharmacology. METHODS: Absorption, distribution, metabolism, excretion, and toxicity calculation method was used to screen the active components of CSP. Traditional Chinese Medicine System Pharmacological Database Analysis Platform and text mining tool (GoPuMed database) were used to predict and screen the active ingredients of CSP and anti-depressive targets. Through Genetic Association Database, Therapeutic Target Database, and PharmGkb database targets for depression were obtained. Cytoscape3.2.1 software was used to establish a network map of the active ingredients-targets of CSP, and to analyze gene function and metabolic pathways through Database for Annotation, Visualization and Integrated Discovery and the Omicshare database. RESULTS: The 121 active ingredients and 15 depression-related targets which were screened from the database can exert antidepressant effects by improving the neural plasticity, growth, transfer condition and gene expression of neuronal cell, and the raise of the expression of gap junction protein. The 15 targets passed 14 metabolic pathways, mainly involved in the regulation of neurotransmitters (5-hydroxytryptamine, dopamine and epinephrine), inflammatory mediator regulation of TRP channels, calcium signaling pathway, cyclic adenosine monophosphate signaling pathway and neuroactive ligand-receptor interaction and other signal channels to exert anti-depressant effects. CONCLUSION: This article reveals the possible mechanism of CSP in the treatment of depression through network pharmacology research, and lays a foundation for further target studies.

7.
Chemosphere ; 240: 124898, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31557644

RESUMO

Urinary polycyclic aromatic hydrocarbon (PAH) metabolites, biomarkers of internal PAH exposure, are commonly used to explore the effects of PAH on human health. However, the correlation between environmental PAH exposure and the species or levels of urinary PAH metabolites remains unclear. We collected detailed information on PAH exposure sources, including cigarette smoking, cooking, traffic and diet habits via structured questionnaires, and determined 12 urinary monohydroxylated PAH metabolites (OH-PAHs) among 4092 participants from the Wuhan-Zhuhai cohort. Linear mixed models and generalized linear models were conducted to explore the associations of urinary metabolite levels with single or multiple PAH exposure sources. We also calculated the standardized regression coefficients to further compare the contributions of different sources to urinary OH-PAH levels. Our results showed that increasing levels of urinary 1-, 2-hydroxynaphthalene (1-, 2- OHNa) and 2-hydroxyfluorene (2-OHFlu) were significantly correlated with tobacco smoking (all P < 0.01). The concentrations of 1-, 2- OHNa and 9-hydroxyfluorene (9-OHFlu) were positively correlated with dietary intake (all P < 0.05). Individuals who spent a long time in traffic showed elevated levels of 9-OHFlu and 1-hydroxyphenanthrene (1-OHPh) compared with individuals who spent a short time in traffic (all P < 0.05). Self-cooking was associated only with elevated 1-hydroxypyrene (1-OHP) levels. Moreover, good kitchen ventilation resulted in significantly decreased urinary low-molecular-weight OH-PAH levels. These findings suggested that cigarette smoking, self-cooking, high dietary PAH intake and a long time spent in traffic were associated with increased levels of specific urinary PAH metabolites, and good kitchen ventilation effectively reduced the exposure to low-molecular-weight PAHs in self-cooking participants.

8.
Mol Med Rep ; 20(5): 4315-4322, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545415

RESUMO

Hypoxia is a constant feature of the synovial microenvironment. How synovial mesenchymal stem cells (SMSCs) proliferate and differentiate in a hypoxic environment over a long period of time has aroused the interest of researchers. The aim of the present study was to explore the effects of hypoxia­inducible factor­1α (HIF­1α) on the proliferation and apoptosis of human SMSCs. SMSCs were harvested and cultured under different concentration of oxygen, normoxia (21% O2), hypoxia (5% O2) and severe hypoxia (0.5% O2) to determine its effect on the expression of HIF­1α. Then, the cells were collected and cell proliferation and apoptosis were detected at severe hypoxia (0.5% O2) and hypoxia (5% O2) conditions following HIF­1α siRNA transfection. There were no significant changes in cellular proliferation or apoptosis when cultured in normoxia (21% O2), hypoxia (5% O2) or severe hypoxia (0.5% O2). However, the mRNA and protein expression of HIF­1α were markedly upregulated in the hypoxic conditions. Further experiments suggested that the proliferation of SMSCs was obviously suppressed and apoptosis was markedly increased under severe hypoxic (0.5%) and hypoxic (5% O2) conditions following HIF­1α siRNA transfection. In conclusion, HIF­1α effectively improved the tolerance of SMSCs to hypoxia, which may promote cellular proliferation and prevent the apoptosis of SMSCs under hypoxic conditions.

9.
Chin J Nat Med ; 17(8): 616-623, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472899

RESUMO

Loureirin A is a major active component of Draconis sanguis, a traditional Chinese medicine. This work aimed to investigate the activity of loureirin A against Candida albicans biofilms. 2, 3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT)reduction assay and scanning electron microscopy were used to investigate the anti-biofilm effect. Minimal inhibitory concentration testing and time-kill curve assay were used to evaluate fungicidal activity. Cell surface hydrophobicity (CSH) assay and hyphal formation experiment were respectively carried out to investigate adhesion and morphological transition, two virulence traits of C. albicans. Real-time RT-PCR was used to investigate gene expression. Galleria mellonella-C. albicans and Caenorhabditis elegans-C. albicans infection models were used to evaluate the in-vivo antifungal effect. Human umbilical vein endothelial cells and C. elegans nematodes were used to evaluate the toxicity ofloureirin A. Our data indicated that loureirin A had a significant effect on inhibiting C. albicans biofilms, decreasing CSH, and suppressing hyphal formation. Consistently, loureirin A down-regulated the expression of some adhesion-related genes and hypha/biofilm-related genes. Moreover, loureirin A prolonged the survival of Galleria mellonella and Caenorhabditis elegans in C. albicans infection models and exhibited low toxicity. Collectively, loureirin A inhibits fungal biofilms, and this effect may be associated with the suppression of pathogenic traits, adhesion and hyphal formation.

10.
Endocrinology ; 160(11): 2692-2708, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31433456

RESUMO

Human prostate stem and progenitor cells express estrogen receptor (ER)α and ERß and exhibit proliferative responses to estrogens. In this study, membrane-initiated estrogen signaling was interrogated in human prostate stem/progenitor cells enriched from primary epithelial cultures and stem-like cell lines from benign and cancerous prostates. Subcellular fractionation and proximity ligation assays localized ERα and ERß to the cell membrane with caveolin-1 interactions. Exposure to 17ß-estradiol (E2) for 15 to 60 minutes led to sequential phosphorylation of signaling molecules in MAPK and AKT pathways, IGF1 receptor, epidermal growth factor receptor, and ERα, thus documenting an intact membrane signalosome that activates diverse downstream cascades. Treatment with an E2-dendrimer conjugate or ICI 182,870 validated E2-mediated actions through membrane ERs. Overexpression and knockdown of ERα or ERß in stem/progenitor cells identified pathway selectivity; ERα preferentially activated AKT, whereas ERß selectively activated MAPK cascades. Furthermore, prostate cancer stem-like cells expressed only ERß, and brief E2 exposure activated MAPK but not AKT cascades. A gene subset selectively regulated by nongenomic E2 signaling was identified in normal prostate progenitor cells that includes BGN, FOSB, FOXQ1, and MAF. Membrane-initiated E2 signaling rapidly modified histone methyltransferases, with MLL1 cleavage observed downstream of phosphorylated AKT and EZH2 phosphorylation downstream of MAPK signaling, which may jointly modify histones to permit rapid gene transcription. Taken together, the present findings document ERα and ERß membrane-initiated signaling in normal and cancerous human prostate stem/progenitor cells with differential engagement of downstream effectors. These signaling pathways influence normal prostate stem/progenitor cell homeostasis and provide novel therapeutic sites to target the elusive prostate cancer stem cell population.

11.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(7): 857-861, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31441410

RESUMO

OBJECTIVE: To investigate the protective effect of microRNA-181b (miR-181b) on aged rats with sepsis-induced hippocampus injury in vivo. METHODS: Seventy-five male healthy old Sprague-Dawley (SD) rats were randomly divided into five groups (n = 15) using a random number table: sham operation group (Sham group), sepsis group [cecal ligation and puncture (CLP) group], miR-181b Agomir+CLP group (Ag+CLP group), miR-181b Antagomir+CLP group (An+CLP group) and normal saline (NS) control group (NS+CLP group). Rats sepsis model was reproduced by CLP, and in Sham group, the cecum of rats was separated only after abdominal operation without ligation or perforation. The rats in Ag+CLP group were given miR-181b Agomir 10 µL via lateral ventricle at 24 hours before CLP, the rats in An+CLP group were given 10 µL miR-181b Antagomir, and those in NS+CLP group were given 10 µL NS. At 6, 12, 24 hours after CLP, 5 rats of each group were sacrificed randomly, and hippocampus were harvested. The expression of miR-181b in hippocampus was determined by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The expression of nuclear factor-ΚB p65 (NF-ΚB p65) was determined by Western Blot. The contents of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with Sham group, the expression of miR-181b in hippocampus of CLP group was significantly decreased at 6 hours after CLP (2-ΔΔCT: 0.70±0.12 vs. 0.98±0.06, P < 0.05), and the expressions of NF-ΚB p65, IL-1ß and TNF-α were significantly increased [NF-ΚB p65/Histone H3: 0.30±0.03 vs. 0.07±0.01, IL-1ß (ng/L): 120.39±8.02 vs. 50.55±11.12, TNF-α (ng/L): 59.48±4.60 vs. 40.31±3.96, all P < 0.05], this trend was continued till 24 hours, and these results indicated that there was obvious inflammation in hippocampus of sepsis rats. There was no statistical difference in the expression of miR-181b, NF-ΚB p65, IL-1ß or TNF-α in hippocampus between NS+CLP group and CLP group, which indicated that injection of NS into the rat lateral ventricle, had not aggravated the damage degree of hippocampus. Compared with CLP group, the expression of miR-181b in hippocampus of Ag+CLP group was significantly increased at 6 hours after CLP (2-ΔΔCT: 1.87±0.25 vs. 0.70±0.12, P < 0.05), and the expressions of NF-ΚB p65, IL-1ß and TNF-α were significantly lowered [NF-ΚB p65/Histone H3: 0.16±0.03 vs. 0.30±0.03, IL-1ß (ng/L): 73.76±8.17 vs. 120.39±8.02, TNF-α (ng/L): 49.52±4.77 vs. 59.48±4.60, all P < 0.05]. There was no statistical difference in the expression of miR-181b in hippocampus between An+CLP group and CLP group (2-ΔΔCT: 0.80±0.08 vs. 0.70±0.12 at 6 hours, 0.48±0.03 vs. 0.46±0.05 at 12 hours, 0.61±0.09 vs. 0.63±0.07 at 24 hours, all P > 0.05), but the expressions of NF-ΚB p65, IL-1ß and TNF-α in hippocampus at 6 hours after CLP of An+CLP group were significantly higher than those of CLP group [NF-ΚB p65/Histone H3: 0.44±0.02 vs. 0.30±0.03, IL-1ß (ng/L): 134.21±5.78 vs. 120.39±8.02, TNF-α (ng/L): 67.62±5.86 vs. 59.48±4.60, all P < 0.05], this trend was continued till 24 hours after CLP. The above results showed that overexpression of miR-181b might attenuate the inflammation of hippocampus through down-regulation of NF-ΚB, IL-1ß and TNF-α. CONCLUSIONS: The expression of hippocampal miR-181b was significantly decreased in septic rats. Up-regulation of miR-181b could inhibit the activation of NF-ΚB signal pathway and the release of the inflammatory cytokine IL-1ß and TNF-α stimulated by sepsis, and alleviate the inflammatory reaction and hippocampus injury in rat with sepsis.


Assuntos
MicroRNAs , Sepse , Animais , Hipocampo/lesões , Hipocampo/metabolismo , Interleucina-1beta/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-31374945

RESUMO

OBJECTIVE: The China Center for Disease Control and Prevention (CDC) introduced an innovative financing model of tuberculosis (TB) care and control with the aim of standardizing TB treatment and reducing the financial burden associated with patients with TB. This is a study of the pilot implementation of new financing mechanism in Zhenjiang, between 2014-2015. We compared TB hospitalization rates and inpatient service costs before and after implementation to examine the factors associated with hospital admissions. Our goal is to provide evidence-based recommendations for improving TB service provision and cost control. METHODS: We reviewed new policy documents on TB financing. We conducted a patient survey to investigate the utilization of inpatient services, and patients' out-of-pocket payment for inpatient care. We extracted total medical expenditures of inpatient services from inpatient records of TB designated hospitals. FINDINGS: 63.6% (n = 159) of the surveyed patients with TB were admitted for treatment in 2015, which was higher than that in 2013 (54.8%, n = 144). The number of hospital admission was slightly lower in 2015 (1.16 per patient) than in 2013 (1.26 per patient), while the length of hospital stay was longer in 2015 (24 days) than in 2013 (16 days). In 2015, patients from families with low incomes were more likely to be admitted than those from higher income groups (OR = 3.06, 95% CI: 1.12-8.33). The average inpatient service cost in 2015 (3345 USD) was 1.7 times the cost in 2013 (1952 USD). It was found that 96.2% of patients with TB who were from low-income households spent more than 20% of their household income on inpatient care in 2013, versus 100% in 2015. CONCLUSION: The TB hospital admission rate and total inpatient service cost increased over the study period. The majority of patients with TB, particularly poor patient who used inpatient care, continue to suffer from heavy financial burden.

13.
Int J Cancer ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31463974

RESUMO

Gastric cancer (GC) is the third leading cause of cancer deaths and the fourth most prevalent malignancy worldwide. The high incidence and mortality rates of gastric cancer result from multiple factors such as ineffective screening, diagnosis, and limited treatment options. In our study, we sought to systematically identify predictive molecular networks and key regulators to elucidate complex interacting signaling pathways in GC. We performed an integrative network analysis of the transcriptomic data in The Cancer Genome Atlas (TCGA) gastric cancer cohort and then comprehensively characterized the predictive subnetworks and key regulators by the matched genetic and epigenetic data. We identified 221 gene subnetworks (modules) in GC. The most prognostic subnetworks captured multiple aspects of the tumor microenvironment in GC involving interactions among stromal, epithelial and immune cells. We revealed the genetic and epigenetic underpinnings of those subnetworks and their key transcriptional regulators. We computationally predicted and experimentally validated specific mechanisms of anticancer effects of GKN2 in gastric cancer proliferation and invasion in vitro. The network models and the key regulators of the tumor microenvironment in GC identified here pave a way for developing novel therapeutic strategies for GC.

14.
J Laparoendosc Adv Surg Tech A ; 29(9): 1152-1162, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31373875

RESUMO

Background: There is no consensus on whether lightweight mesh (LWM) is better than heavyweight mesh (HWM) in laparoscopic inguinal hernia repair (LIHR). This study aims to update the previous reviews and to analyze present randomized controlled studies comparing LWM versus HWM in LIHR systematically. Methods: We searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs), which compared LWM with HWM in adults with LIHR. All eligible data of outcomes were quantitatively analyzed using Revman 5.3 software or qualitatively described. The outcomes included chronic pain, moderate-severe chronic pain, recurrence, foreign body sensation, influence on sexual life and male fertility (pain with ejaculation, testicular pain, etc.). Results: We included 12 RCTs that analyzed 3092 hernias. The difference between LWM and HWM groups at any follow-up time was not significant in chronic pain and foreign body sensation. Compared with HWM group, patients in LWM group had a similar risk of postoperative moderate-severe chronic pain at 3 and 12 months follow-up, a slightly increased risk of developing moderate-severe chronic pain at >12 months follow-up (risk ratio [RR] = 3.20, 95% confidence interval [CI] 1.05-9.75, P = .04), and a higher risk of recurrence rate (RR = 2.28, 95% CI 1.17-4.44, P = .02). At long-term follow-up, the influences of LWM and HWM on sexual life and male fertility were comparable. Conclusion: LWMs do not show advantages in chronic pain, foreign body sensation as well as the influence on sexual life and male fertility, and may increase hernia recurrence rates for LIHR. In addition, a higher incremental cost and lower incremental effect of LWMs make conventional HWMs preferred choice for LIHR.

15.
J Virol ; 93(20)2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31375583

RESUMO

Early human immunodeficiency virus type 1 (HIV-1) treatment during the acute period of infection can significantly limit the seeding of viral reservoirs and modify the course of disease. However, while a number of HIV-1 broadly neutralizing antibodies (bnAbs) have demonstrated remarkable efficacy as prophylaxis in macaques chronically infected with simian-human immunodeficiency virus (SHIV), intriguingly, their inhibitory effects were largely attenuated in the acute period of SHIV infection. To investigate the mechanism for the disparate performance of bnAbs in different periods of SHIV infection, we used LSEVh-LS-F, a bispecific bnAb targeting the CD4 binding site and CD4-induced epitopes, as a representative bnAb and assessed its potential therapeutic benefit in controlling virus replication in acutely or chronically SHIV-infected macaques. We found that a single infusion of LSEVh-LS-F resulted in rapid decline of plasma viral loads to undetectable levels without emergence of viral resistance in the chronically infected macaques. In contrast, the inhibitory effect was robust but transient in the acutely infected macaques, despite the fact that all macaques had comparable plasma viral loads initially. Infusing multiple doses of LSEVh-LS-F did not extend its inhibitory duration. Furthermore, the pharmacokinetics of the infused LSEVh-LS-F in the acutely SHIV-infected macaques significantly differed from that in the uninfected or chronically infected macaques. Host SHIV-specific immune responses may play a role in the viremia-dependent pharmacokinetics. Our results highlight the correlation between the fast clearance of infused bnAbs and the treatment failure in the acute period of SHIV infection and may have important implications for the therapeutic use of bnAbs to treat acute HIV infections.IMPORTANCE Currently, there is no bnAb-based monotherapy that has been reported to clear the virus in the acute SHIV infection period. Since early HIV treatment is considered critical to restricting the establishment of viral reservoirs, investigation into the mechanism for treatment failure in acutely infected macaques would be important for the therapeutic use of bnAbs and eventually towards the functional cure of HIV/AIDS. Here we report the comparative study of the therapeutic efficacy of a bnAb in acutely and chronically SHIV-infected macaques. This study revealed the correlation between the fast clearance of infused bnAbs and treatment failure during the acute period of infection.

16.
Nat Prod Res ; : 1-7, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307232

RESUMO

Cladosporine A (1), a new indole diterpenoid alkaloid, was isolated from the extract of a fungal strain Cladosporium sp. JNU17DTH12-9-01. Its structure was elucidated by extensive spectroscopic analysis, and the absolute configurations were determined by electronic circular dichroism (ECD) experiments. This is the first report of the presence of indole diterpenoid alkaloid in the genus Cladosporium. The antimicrobial activities against Staphylococcus aureus 209P, Escherichia coli ATCC0111, Aspergillus niger R330, and Candida albicans FIM709 were evaluated. Compound 1 showed MICs of 4 µg/mL and 16 µg/mL against S. aureus 209P and C. albicans FIM709, respectively.

17.
J Photochem Photobiol B ; 197: 111536, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31326846

RESUMO

The latent utilization of biomaterials that are osteo-conducive in the advancement of healing bone fracture has fascinated extensive consideration. This work includes the synthesis of silver nanoparticles (AgNPs) with the help of a Bauhinia acuminate plant flower extract through an ecofriendly synthetic process without any use of harmful reductants. In the fabrication of AgNPs, Bauhinia acuminate plant flower extract bio constituents acts as both stabilizing and reducing agent. The studies of Fourier transform infrared (FTIR) and X-ray diffraction (XRD) techniques confirmed the formation of AgNPS. TEM images revealed that AgNPs are uniform with average particle size of 17 nm. Further, this work explored if silver nanoparticles (AgNPs) might endorse the osteogenesis and proliferation of mesenchymal stem cells (MSCs) and advance the curing of bone fractures. We also exhibited that the prepared AgNPs could promote the in -vitro osteogenic differentiation and proliferation of MSCs'. Also, the prepared AgNps could stimulate the proliferation of mMSCs at specific concentrations of 6-20 µM. Further, cell viability studies showed that AgNPs exhibited no reduction in mouse mesenchymal stem cell viability at <4 µM. Further, these results indicated the induction effects of AgNPs on osteogenic differentiation and proliferation on MSCs, as well as the advancement of meniscus injury healing.


Assuntos
Bauhinia/química , Nanopartículas Metálicas/química , Osteogênese , Extratos Vegetais/química , Prata/química , Animais , Bauhinia/metabolismo , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Flores/química , Flores/metabolismo , Consolidação da Fratura/efeitos dos fármacos , Química Verde , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Nanopartículas Metálicas/toxicidade , Camundongos , Microscopia Eletrônica de Transmissão , Osteogênese/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier
18.
BMC Musculoskelet Disord ; 20(1): 349, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31351472

RESUMO

BACKGROUND: Female patients are more likely to have tendon injuries than males, especially those who has a higher concentration of relaxin. Previous studies have demonstrated that relaxin attenuates extracellular matrix (ECM) formation. However, the mechanism of relaxin on tendon repair remains unclear. We hypothesize that relaxin inhibits tendon healing by disrupting collagen synthesis. METHODS: A patellar tendon window defect model was established using Sprague-Dawley rats. The center of the patellar tendon was removed from the patella distal apex and inserted to the tibia tuberosity in width of 1 mm. Then, the rats were injected with saline (0.2 µg/kg/day) or relaxin (0.2 µg/kg/day) for two and four weeks, which was followed by biomechanical analysis and histological and histochemical examination. RESULTS: Mechanical results indicated that relaxin induces a significant decrease in tear resistance, stiffness, and Young's modulus compared to those rats without relaxin treatment. In addition, it was shown that relaxin activates relaxin family peptide receptor 1(RXFP1), disturbs the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteases (TIMPs), and reduces the deposition of collagen in injury areas. CONCLUSIONS: Relaxin impairs tendon healing in rats. Also, relaxin might lead to tendon injury more commonly for females than males.

19.
BMC Neurol ; 19(1): 175, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331288

RESUMO

BACKGROUND: Elevated levels of plasma D-dimer increase the risk of ischemic stroke, stroke severity, and the progression of stroke status, but the association between plasma D-dimer level and functional outcome is unclear. The aim of this study is to investigate whether plasma D-dimer level is a determinant of short-term poor functional outcome in patients with acute ischemic stroke (AIS). METHODS: This prospective study included 877 Chinese patients with AIS admitted to Renmin Hospital of Wuhan University within 72 h of symptom onset. Patients were categorized by plasma D-dimer level: Quartile 1(≤0.24 mg/L), Quartile 2 (0.25-0.56 mg/L), Quartile 3 (0.57-1.78 mg/L), and Quartile 4 (> 1.78 mg/L). The medical record of each patient was reviewed, and demographic, clinical, laboratory and neuroimaging information was abstracted. Functional outcome at 90 days was assessed with the modified Rankin Scale. RESULTS: Poor outcome was present in 302 (34.4%) of the 877 patients that were included in the study (mean age, 64 years; male, 68.5%). After adjustment for potential confounding variables, higher plasma D-dimer level on admission was associated with poor outcome (adjusted odds ratio 2.257, 95% confidence interval 1.349-3.777 for Q4:Q1; P trend = 0.004). According to receiver operating characteristic (ROC) analysis, the best discriminating factor for poor outcome was a plasma D-dimer level ≥ 0.315 mg/L (area under the ROC curve 0.657; sensitivity 83.8%; specificity 41.4%). CONCLUSION: Elevated plasma D-dimer levels on admission are significantly associated with poor outcome after admission for AIS, suggesting the potential role of plasma D-dimer level as a predictive marker for short-term poor outcome in patients with AIS.

20.
Nat Prod Res ; : 1-8, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31242770

RESUMO

Two new chromones, spororrminone A (1, (S)-5-hydroxy-2-methyl-4-oxo-2-((S)-5-oxotetrahydrofuran-2-yl)chroman-7-carboxylic acid) and 2-epi-spororrminone A (2, (R)-5-hydroxy-2-methyl-4-oxo-2-((S)-5-oxotetrahydrofuran-2-yl)chroman-7-carboxylic acid), were isolated from an EtOAc extract of an endolichenic fungal strain Sporormiella irregularis (No. 71-11-4-1). The structures of these compounds were identified by spectroscopic analyses. The absolute configuration of 1 was established by single-crystal X-ray diffraction. Spororrminone A (1) and 2-epi-spororrminone A (2) represent the first examples of 2-(5-oxotetrahydrofuran-2-yl) chromones with 7-carboxylic group.

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