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1.
J Gene Med ; : e3280, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025678

RESUMO

BACKGROUND: Increasing evidences have proven that long non-coding RNA (lncRNA) has a vital impact on the procession of cervical cancer (CC). This study aims at investigating the clinical significance of LINC01089 in CC and exploring its biological functions and potential molecular mechanisms. METHODS: Quantitative real time polymerase chain reaction (qRT-PCR) was utilized to investigate the expressions of LINC01089 and miR-27a-3p in CC cells and tissues. Analysis of the correlation between the expression level of LINC01089 and the clinical pathological parameters of CC was then conducted. The human CC cell lines HeLa and SiHa were utilized for transfection to establish gain-of-function model and loss-of-function models. Western blot and qRT-PCR were performed to detect B-cell translocation gene-2 (BTG2) expression in CC cells. Cell counting kit-8 (CCK-8) method and 5-Bromo-2-deoxyUridine (BrdU) assay were performed to detect the proliferation of CC cells. Transwell method was employed to evaluate the migration and invasion of CC cells. The interactions between LINC01089 and miR-27a-3p were verified by bioinformatics, dual luciferase reporter gene experiment and RIP experiment, respectively. RESULTS: The expression of LINC01089 in CC was markedly down-regulated. The low expression of LINC01089 in CC was closely associated with larger tumor size and positive lymph node metastasis. Moreover, overexpression of LINC01089 impeded the proliferation and metastasis of CC cells, whereas knockdown of LINC01089 had opposite biological functions. In terms of mechanism, LINC01089 could sponge miR-27a-3p and indirectly up-regulate BTG2 expression. CONCLUSION: LINC01089, as a tumor suppressor, impedes the development of CC by targeting miR-27a-3p to upregulate BTG2 expression.

2.
Int J Biol Macromol ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33068624

RESUMO

Sporisorium reilianum is an active edible and medicinal phytopathogenic fungus. Our study indicated that the S. reilianum polysaccharide WM-NP-60 could inhibit the growth of HCT116 cells in a dose-dependent manner. In addition, WM-NP-60 could trigger the cell cycle of HCT116 arrest at the G1 phase and induce its apoptosis. In order to explore the anti-tumor mechanism of WM-NP-60, TMT-based quantitative proteomic analysis was used. Results indicated that 369 differentially expressed proteins including 240 up-regulated and 129 down-regulated proteins in WM-NP-60 treated HCT116 cells compared with normal HCT116 cells. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that 192 pathways were enriched containing 15 metabolic pathways with significant difference (P < 0.05). The levels of mRNA and protein up-regulated TGFßR1, P107, DP1 and down-regulated THBS1 related to TGF-ß signaling pathway were verified with qRT-PCR and Western Blot (WB). These findings will provide theoretical basis for the important role of fungal polysaccharides in the field of tumor treatment.

3.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(10): 1085-1091, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33059805

RESUMO

OBJECTIVE: To study the duration of automated auditory brainstem response (AABR) test for initial hearing screening and the factors influencing the duration in neonates. METHODS: A total of 472 neonates who were admitted to the neonatal intensive care unit (NICU) were enrolled as the study group and 182 healthy neonates were enrolled as the healthy control group. The influence of the duration of AABR test on the initial screening results was observed in the two groups. The influencing factors for the AABR test duration were analyzed. RESULTS: In the AABR screening of 180, 360, and 540 seconds, the study group had a failure rate of 41.5%, 28.4%, and 24.4% respectively, while the healthy control group had a failure rate of 31.3%, 19.8%, and 15.4% respectively, showing a decreasing trend with the extension of test time in both groups (P<0.05). In the two groups, the screening results of 180-second testing were moderately consistent with those of 360- or 540-second testing (Kappa<0.75, P<0.05), and the screening results of 360-second testing were highly consistent with those of 540-second testing (Kappa>0.75, P<0.05). In the study group, the median duration of AABR test was 108 seconds (95%CI: 97-120 seconds), which was significantly longer than the duration of 75 seconds (95%CI: 65-85 seconds) in the healthy control group (P<0.05). The Cox regression analysis showed that maternal age ≥35 years, anemia, and electrolyte disturbance (RR<1, P<0.05) were independent risk factors for prolonged AABR test duration, while the prolonged continuous positive airway pressure-assisted ventilation was a protective factor (RR>1, P<0.05). CONCLUSIONS: The AABR test time of 360-540 seconds for initial hearing screening helps to reduce false positive results due to environmental and risk factors in neonates. It may be useful to reduce the false positive results of AABR screening before discharge by taking corresponding intervention measures for NICU neonates with high risk factors.

4.
Clin Interv Aging ; 15: 1767-1778, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061328

RESUMO

Purpose: Injurious falls seriously threaten the safety of elderly patients. Identifying risk factors for predicting the probability of injurious falls is an important issue that still needs to be solved urgently. We aimed to identify predictors and develop a nomogram for distinguishing populations at high risk of injurious falls from older adults in acute settings. Patients and Methods: A retrospective case-control study was conducted at three hospitals in Shanghai, China. Elderly patients with injurious falls from January 2014 to December 2018 were taken as cases, and control patients who did not have falls were randomly matched based on the admission date and the department. The data were collected through a medical record review and adverse events system. The original data set was randomly divided into a training set and a validation set at a 7:3 ratio. A nomogram was established based on the results of the univariate analysis and multivariate logistic regression analysis, and its discrimination and calibration were verified to confirm the accuracy of the prediction. The cut-off value of risk stratification was determined to help medical staff identify the high-risk groups. Results: A total of 115 elderly patients with injurious falls and 230 controls were identified. History of fractures, orthostatic hypotension, functional status, sedative-hypnotics and level of serum albumin were independent risk factors for injurious falls in elderly patients. The C-indexes of the training and validation sets were 0.874 (95% CI: 0.784-0.964) and 0.847 (95% CI: 0.771-0.924), respectively. Calibration curves were drawn and showed acceptable predictive performance. The cut-off values of the training and validation sets were 146.3 points (sensitivity: 73.7%; specificity: 87.5%) and 157.2 points (sensitivity: 69.2%; specificity: 85.5%), respectively. Conclusion: The established nomogram facilitates the identification of high-risk populations among elderly patients, providing a new assessment tool to forecast the individual risk of injurious falls.

5.
Mikrochim Acta ; 187(11): 607, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052497

RESUMO

A novel non-enzyme electrochemical biosensor for the rapid detection of Gram-positive bacteria has been constructed that relys on a stable and efficient combination between the peptidoglycan layer and platinum-nickel-copper nanocubes (Pt-Ni-Cu NCs). Briefly, bacteria were first captured by a specific antibody. Then, the electrochemical signal materials (Pt-Ni-Cu NCs) were bound to the bacteria peptidoglycan layer using specific structural and surface features. The rapid and sensitive bacterial detection was then achieved using intrinsic electrochemical characteristics and superoxidase-like activity of the Pt-Ni-Cu NCs. Moreover, the nature of peptidoglycan covering the whole bacteria provided the premise for signal amplification. Under optimal conditions, the electrochemical signal variation was proportional to the concentration of bacteria ranging from 1.5 × 102 to 1.5 × 108 CFU/mL with a detection limit of 42 CFU/mL using a working potential of - 0.4 V. This electrochemical biosensor has been successfully applied to detect bacteria concentrations in urine samples, and the recoveries range from 90.4 to 107%. The proposed biosensor could be applied for broad-spectrum detection of Gram-positive bacteria since most Gram-positive bacteria possess a thick peptidoglycan layer. The developed electrochemical biosensing strategy might be used as a potential tool for clinical pathogenic bacteria detection and point-of-care testing (POCT).

6.
Eur J Med Chem ; 209: 112860, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33032085

RESUMO

Meroterpenoids are partially derived from the terpenoids, distributing widely in the plants, animals and fungi. The complex structures and diverse bioactivities of meroterpenoids have attracted more attention for chemists and pharmacologists. Since the first review summarized by Geris in 2009, there are absent of systematic reviews reported about meroterpenoids from the higher and lower fungi up to now. In the past decades, myriads of meroterpenoids were discovered, and it is necessary to summarize these meroterpenoids about their unique structures and promising bioactivities. In this review, we use a new classification method based on the non-terpene precursors, and also highlight the structural features, bioactivity of natural meroterpenoids from the higher and lower fungi covering the period of September 2008 to February 2020. A total of 709 compounds were discussed and cited the 182 references. Meanwhile, we also primarily summarize their occurrence, structural diversity, biological activities, and molecular targets.

7.
Int J Obes (Lond) ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33037330

RESUMO

BACKGROUND: Most previous studies on trends in the prevalence of obesity or abdominal obesity in Chinese adults were based on regional data and/or short time intervals, and recent trends are not available. We aimed to examine the secular trends in the prevalence of overweight, obesity, and abdominal obesity among Chinese adults at the national level from 1993 to 2015. METHODS: A total of 70,242 Chinese adults aged 18-80 years were from the cross-sectional surveys conducted from 1993 to 2015. According to the World Health Organization criteria, overweight was defined as body mass index (BMI) ≥23.0 kg/m2 and <27.5 kg/m2, and obesity was defined as BMI ≥27.5 kg/m2. According to the International Diabetes Federation criteria, abdominal obesity was defined as waist circumference (WC) ≥90 cm for men and ≥80 cm for women. Mean values and prevalence of adiposity markers were standardized to the age distribution of the China population in 2010. RESULTS: Between 1993 and 2015, and based on age-standardized values, mean BMI increased from 21.9 kg/m2 in 1993 to 23.9 kg/m2 (+2.0 kg/m2) in 2015 (P for trend < 0.001), and mean WC increased from 76.0 cm to 83.4 cm (+7.4 cm) (P for trend <0.001). From 1993 to 2015, the prevalence increased from 26.6% to 41.3% (+14.7%) for overweight, from 4.2% to 15.7% (+11.5%) for obesity, and from 20.2% to 46.9% (+26.7%) for abdominal obesity (all P for trends < 0.001). In multivariate linear regression analysis, time (calendar years), older age and urban regions were strongly and independently associated with BMI. CONCLUSIONS: The prevalence of overweight, obesity, and abdominal obesity increased markedly among Chinese adults during the past two decades. Weight control programs and public health measures to address the societal causes of obesity should be strengthened.

8.
Eur J Med Chem ; : 112922, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33069436

RESUMO

Magnolol and honokiol are the two major active ingredients with similar structure and anticancer activity from traditional Chinese medicine Magnolia officinalis, and honokiol is now in a phase I clinical trial (CTR20170822) for advanced non-small cell lung cancer (NSCLC). In search of potent lead compounds with better activity, our previous study has demonstrated that magnolol derivative C2, 3-(4-aminopiperidin-1-yl)methyl magnolol, has better activity than honokiol. Here, based on the core of 3-(4-aminopiperidin-1-yl)methyl magnolol, we synthesized fifty-one magnolol derivatives. Among them, compound 30 exhibited the most potent antiproliferative activities on H460, HCC827, H1975 cell lines with the IC50 values of 0.63-0.93 µM, which were approximately 10- and 100-fold more potent than those of C2 and magnolol, respectively. Besides, oral administration of 30 and C2 on an H460 xenograft model also demonstrated that 30 has better activity than C2. Mechanism study revealed that 30 induced G0/G1 phase cell cycle arrest, apoptosis and autophagy in cancer cells. Moreover, blocking autophagy by the autophagic inhibitor enhanced the anticancer activity of 30in vitro and in vivo, suggesting autophagy played a cytoprotective role on 30-induced cancer cell death. Taken together, our study implied that compound 30 combined with autophagic inhibitor could be another choice for NSCLC treatment in further investigation.

9.
Mol Pharm ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33074007

RESUMO

Amorphous solid dispersions (ASDs) of class II and IV biopharmaceutics classification system drugs in water-miscible polymers are a well-recognized means of enhancing dissolution, while such dispersions in hydrophobic polymers form the basis of micro- and nanoparticulate technologies. However, drug recrystallization presents significant problems for product development, and the mechanisms and pathways involved are poorly understood. Here, we outline the use of combined differential scanning calorimetry (DSC)-synchrotron X-ray diffraction to monitor the sequential appearance of polymorphs of olanzapine (OLZ) when dispersed in a range of polymers. In a recent study (Cryst. Growth Des. 2019, 19, 2751-2757), we reported a new polymorph (form IV) of OLZ which crystallized from a spray-dried dispersion of OLZ in polyvinylpyrrolidone. Here, we extend our earlier study to explore OLZ dispersions in poly(lactide-co-glycolide) (PLGA), polylactide (PLA), and hydroxypropyl methyl cellulose acetate succinate (HPMCAS), with a view to identifying the sequence of form generation on heating each dispersion. While spray-dried OLZ results in the formation of crystalline form I, the spray-dried material with HPMCAS comprises an ASD, and forms I and IV are generated upon heating. PLGA and PLA result in a product which contains both amorphous OLZ and the dichloromethane solvate; upon heating, the amorphous material converts to forms I, II, and IV and the solvate to forms I and II. Our data show that it is possible to quantitatively assess not only the polymorph generation sequence but also the relative proportions as a function of temperature. Of particular note is that the sequence of form generation is significantly more complex than may be indicated by DSC data alone, with coincident generation of different polymorphs and complex interconversions as the material is heated. We argue that this may have implications not only for the mechanistic understanding of polymorph generation but also as an aid to identifying the range of polymorphic forms that may be produced by a single-drug molecule.

10.
J Infect ; 2020 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-32956725

RESUMO

Human immunodeficiency virus (HIV) infection impairs both cellular and humoral immune system. Follicular regulatory T (Tfr) cells are a recently characterised subset of CD4+T cells. Tfr also exerts an immunosuppressive effect on humoral immune system through interaction with follicular helper T (Tfh) cells, but the role of Tfr in HIV infection needs to be further elucidated. 20 treatment-naïve and 20 antiretroviral therapy (ART)-treated HIV-infected individuals were enrolled for cross-sectional study and nine complete responders (CRs) and eight immune non-responders (INRs) after ART were collected for retrospective cohort study. Tfr phenotypes, cytokine secretions, and apoptosis of those subjects were evaluated by flow cytometry. HIV DNA was measured by reverse transcription-quantitative PCR (RT-qPCR). Significantly increased circulating Tfr was observed in chronic HIV+ patients and the imbalance between Tfr and Tfh17 was associated with CD4+T counts. In addition, an elevated proportion of Tfr was associated with immune reconstruction failure of patients after ART. The IL-10 and CTLA-4 expressions of Tfr cells were up-regulated in treatment-naïve HIV+ patients. Ex vivo experiments showed IL-10 and CTLA-4 expressed by Tfr inhibited IL-21 secretion of Tfh. Tfr harboured a comparable HIV-1 DNA level with Tfh in HIV+ patients. Compared to Tfr of HCs, Tfr cells of HIV+ patients were more insensitive to CD95 and IFN-α induced apoptosis, had a higher proliferation rate, and had more stem-like T cell (Tscm) phenotype. The anti-apoptosis feature, higher proliferation rate, and Tscm-like features of Tfr in HIV+ patients, led to the expansion of Tfr which in turn resulted in dysfunction of Tfh. Tfr cells were also involved in immune reconstruction failure and latent infection of HIV. Tfr cells were a novel, and potentially therapeutic, target for the cure of HIV infection, especially for HIV vaccine development and HIV reservoir elimination.

11.
BMC Psychiatry ; 20(1): 465, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32977774

RESUMO

BACKGROUND: The Obsessive Compulsive Drug Use Scale (OCDUS) measures the overall craving level within a period from a multidimensional perspective. However, no studies have addressed the validity of the new OCDUS factor structure, presented in 2016, in China. Additionally, there is lack of evidence on the interaction among risk factors for relapse. We aimed to assess the psychometric properties of the scores of the Chinese version of the OCDUS in patients with heroin dependence receiving methadone maintenance treatment (MMT). Further, we aimed to assess the correlations of the OCDUS scores with withdrawal symptoms, depression, anxiety, and nicotine dependence. METHODS: We enrolled 113 adults (age 32-64 years) and administered them with the OCDUS, Subjective Opioid Withdrawal Scale (SOWS), Beck Depression Inventory-II (BDI-II), State-Trait Anxiety Inventory (STAI), and Fagerstrom Test for Nicotine Dependence (FTND). RESULTS: Exploratory factor analysis identified a 3-dimensional component that included "Frequency of craving," "Inference of heroin," and "Control of heroin." These factors showed acceptable internal consistency, adequate item-total correlations, and significant item-subscale correlations. There was no correlation between the OCUDS scores and age, education, duration of receiving MMT, and MMT dosages. However, there was a significant correlation between the OCDUS total scores and the SOWS, STAI, BDI-II, and FTND scores. The scores of all the subscales were associated with the SOWS scores; further, the scores of the first two subscales were associated with BDI-II scores while only the scores of the first subscale were associated with the FTND scores. CONCLUSIONS: Our findings support the reliability and structure validity of the OCDUS scores. Heroin craving, withdrawal symptoms, negative emotions, and nicotine dependence, which are considered as risk factors for heroin relapse, might interact with each other. There is a need for further studies on the underlying mechanism of these clinical phenomena.

12.
J Nucl Cardiol ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32909240

RESUMO

BACKGROUND: The prognostic value of left ventricular (LV) mechanical dyssynchrony (MD) in patients with LV aneurysm (LVA) is unclear. This study aimed to investigate the long-term prognostic value of LVMD in LVA patients. METHODS: 92 consecutive patients who underwent 99mTc-sestamibi-gated SPECT myocardial perfusion imaging (GSPECT) were retrospectively analyzed and followed-up for a median of 63 months (range, 1-73 months). LV function and histogram bandwidth (BW) were analyzed by QGS software. LVMD was defined by ROC analysis. Cardiac death was defined as the primary endpoint, and the composite of cardiac deaths and severe or acute heart failure (MACE) as the secondary endpoint. RESULTS: The annual cardiac mortality rate of LVA patients with LVMD and treated by surgical therapy was significantly lower than those treated by medical therapy (2.40% vs. 6.40%, P < .05) but not annual MACE rate (6.61% vs. 10.06%, P > .05). In patients without LVMD, no significant difference in survival and MACE-free survival between medical and surgical treatment. In addition, the occurrence of LVMD is related to the worsen cardiac outcome in terms of MACE and cardiac death, independent of the treatment methods. BW was an independent predictor for MACE (HR 1.010, P < .01) and LVEF (HR .928, P < .05) was an independent predictor for cardiac death in all LVA patients. CONCLUSIONS: LVA patients with LVMD might be associated with high risk for cardiac death and surgical treatment might improve cardiac survival compared to medical therapy in these patients.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32888108

RESUMO

Left atrial (LA) adaptive changes associated with pre-eclampsia (PE) have not been adequately addressed. This study aimed to evaluate the usefulness of LA myocardial function indices in detecting early cardiac alterations in PE. Using speckle tracking echocardiography (STE), LA volumetric and myocardial parameters were acquired in PE women with preserved left ventricular (LV) systolic and diastolic function based on standard criteria and normotensive controls. LA compliance was assessed by the ratio of reservoir strain (LASr) to the estimated LA pressure (E/e'). Subtle systolic and diastolic abnormalities were identified as LV global longitudinal strain < 17.8% and mitral tissue e' velocity < 7 cm/s septal or < 10 cm/s lateral, respectively. LASr/(E/e') was prior to other LA measurements in detecting early LA function changes in PE. The rate of LASr/(E/e') < 3 was significantly greater in the patients with subtle systolic impairments than those without (P < 0.05) in spite of similar proportion of LASr < 31% between them. Among PE women with subtle diastolic damages, the frequencies of anomaly and the values in both LASr/(E/e') and LASr were significantly different to those without (P < 0.05). Moreover, the rate of LASr/(E/e') < 3 was markedly higher than that of LASr < 31% in PE cases with subtle cardiac abnormalities (P < 0.05). In the setting of PE with preserved systolic and diastolic function, STE-derived LA strain and estimated LA compliance may be beneficial to identifying earlier cardiac alternations. LA compliance could outperform LASr in detecting cardiac anomalies earlier during a PE pregnancy with preserved LV performance.

14.
Obes Rev ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32875696

RESUMO

The magnitude of the associations between life-course change in weight status and health outcomes in adulthood has been inconsistent. This study aims to examine the associations between weight change from childhood to adulthood and cardiovascular disease (CVD) risk factors and outcomes in adulthood. PubMed, Embase and ISI Web of Science between 1 August 1953 and 13 July 2020 were searched, and a total of 52 eligible articles were included. The systematic review supported significant associations between the life-course increase in BMI and high odds of markers in adulthood. In the meta-analyses, normal weight in childhood but excess weight in adulthood or persistent excess weight was associated with increased odds of adult markers. However, those who had excess weight in childhood but were normal weight in adulthood did not have increased odds of nearly all adult markers. This systematic review and meta-analysis suggest that individuals who developed excess weight in adulthood or had excess weight in both periods had higher odds of developing CVD risk factors and outcomes in adulthood. In contrast, the probability of these adult markers could be limited or eliminated for children with excess weight who are able to become adults with normal weight.

15.
Eur J Hum Genet ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963334

RESUMO

Osteoporosis and obesity are two severe complex diseases threatening public health worldwide. Both diseases are under strong genetic determinants as well as genetically correlated. Aiming to identify pleiotropic genes underlying obesity and osteoporosis, we performed a bivariate genome-wide association (GWA) meta-analysis of hip bone mineral density (BMD) and total body fat mass (TBFM) in 12,981 participants from seven samples, and followed by in silico replication in the UK biobank (UKB) cohort sample (N = 217,822). Combining the results from discovery meta-analysis and replication sample, we identified one novel locus, 17q21.31 (lead SNP rs12150327, NC_000017.11:g.44956910G > A, discovery bivariate P = 4.83 × 10-9, replication P = 5.75 × 10-5) at the genome-wide significance level (ɑ = 5.0 × 10-8), which may have pleiotropic effects to both hip BMD and TBFM. Functional annotations highlighted several candidate genes, including KIF18B, C1QL1, and PRPF19 that may exert pleiotropic effects to the development of both body mass and bone mass. Our findings can improve our understanding of the etiology of osteoporosis and obesity, as well as shed light on potential new therapies.

16.
J Anal Methods Chem ; 2020: 8827925, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32963880

RESUMO

Objective: To establish a method for extraction and determination of antioxidant 264 (2,6-di-tert-butyl-4-methylphenol) in the brominated butyl rubber stopper for injection and migration study in recombinant potent antitumor and antivirus protein injection (Novaferon). Methods: Dichloromethane-ethanol was adopted as the extraction solvent during the process of reflux extraction of antioxidant 264 in the brominated butyl rubber stopper. High-performance liquid chromatography (HPLC) was used for the determination of the migration of antioxidant 264 to Novaferon. The mobile phase consisted of acetonitrile-water (80 : 20, v/v). The flow rate was 1.5 mL/min. The detection wavelength was 280 nm. Results: The linearity range was from 4.003 to 200.150 µg/mL (r 2 = 0.99996), and the average recovery of antioxidant 264 was 97.8%. The applicability of the methodology was good, which can be used for the determination of antioxidant 264. The results indicated that antioxidant 264 was not detected in Novaferon after the accelerated test and three months of long-term test. Conclusion: The established validated method in this study can be used for the determination of antioxidant 264 in the rubber stopper, and the brominated butyl rubber stopper has good compatibility with Novaferon.

17.
Bone ; : 115652, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32971307

RESUMO

Recent studies have demonstrated the important role played by gut microbiota in regulating bone development, but the evidence of such causal relationship is still sparse in human population. The aim of this study is to assess the causal relationship from gut microbiota to bone development and to identify specific causal bacteria taxa via a Mendelian randomization (MR) approach. A genome-wide association study (GWAS) summary statistic based two-sample MR analysis was performed. Summary statistics of microbiome GWAS (MGWAS) in 1126 twin pairs of the TwinsUK study was used as discovery sample, and the MGWAS in 984 Dutch participants from the LifeLines-DEEP cohort was used as replication sample. Estimated heel bone mineral density (eBMD) GWAS in 426,824 participants from the UK biobank (UKB) cohort was used as outcome. Bacteria were grouped into taxa features at both order and family levels. In the discovery sample, a total of 25 bacteria features including 9 orders and 16 families were analyzed. Fourteen features (5 orders + 9 families) were nominally significant, including 5 orders (Bacteroidales, Clostridiales, Lactobacillales, Pasteurellales and Verrucomicrobiales) and 9 families (Bacteroidaceae, Clostridiaceae, Lachnospiraceae, Mogibacteriaceae, Pasteurellaceae, Porphyromonadaceae, Streptococcaceae, Verrucomicrobiaceae and Veillonellaceae). One order Clostridiales and its child taxon, family Lachnospiraceae, were successfully replicated in the replication sample (Clostridiales Pdiscovery = 3.32 × 10-3Preplication = 7.29 × 10-3; Lachnospiraceae Pdiscovery = 0.03 Preplication = 7.29 × 10-3). Our findings provided evidence of causal relationship from microbiota to bone development, as well as identified specific bacteria taxa that regulated bone mass variation, thus providing new insights into the microbiota mediated bone development mechanism.

18.
EBioMedicine ; 60: 103027, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32980696

RESUMO

BACKGROUND: The prefrontal-striatal circuit is a core circuit related to substance dependence. Previous studies have found that repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) (key region of executive network) had limited responses, while inhibiting hyperactivation of ventromedial prefrontal cortex (vmPFC) (key region of limbic network) may be another strategy. However, there is currently no comparison between these two treatment locations. METHODS: Seventy-four methamphetamine-dependent patients were randomly assigned to one of treatment groups with two-week treatment: (1) Group A: intermittent theta-burst stimulation (iTBS) targeting the left DLPFC; (2) Group B: continuous theta-burst stimulation (cTBS) targeting the left vmPFC; (3) Group C: a combination of treatment protocol of Group A and Group B; (4) Group D: sham theta-burst stimulation. The primary endpoint was the change of cue-induced craving. The trial was registered at ClinicalTrials.gov (NCT03736317). FINDINGS: The three real TBS groups had more craving decrease effect than the sham group (p<0.01). The changes of craving were positively correlated with the improvement of anxiety and withdrawal symptom. With the highest respondence rate, group C also had shorter respondence time than Group A (p = 0.03). Group C was effective in improve depression symptoms (p = 0.04) and withdrawal symptom (p = 0.02) compared with Group D. Besides, Group C was significant in improve sleep quality (p = 0.04) compared with Group A. Baseline depression scores and spatial working memory were positively predicting the intervention response. INTERPRETATION: The rTMS paradigms involving vmPFC with cTBS are optimized protocols and well-tolerated for methamphetamine-dependent individuals, and they may have better efficacies compared with DLPFC iTBS. Emotion and cognitive function are rTMS treatment response predictors for methamphetamine-dependent patients. FUNDING: This work was supported by the National Key R&D Program of China (2017YFC1310400), National Natural Science Foundation of China (81,771,436, 81,801,319, 81,601,164), Shanghai Municipal Health and Family Planning Commission (2017ZZ02021), Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai (2017YQ013), Qihang Project of Shanghai Mental Health Center (2019-QH-05), Shanghai Sailing Program (19YF1442100), Shanghai Key Laboratory of Psychotic Disorders (13DZ2260500), Program of Shanghai Academic Research Leader (17XD1403300), Shanghai Municipal Science and Technology Major Project (2018SHZDZX05), and Shanghai Clinical Research Center for Mental Health (19MC1911100).

19.
Mol Med Rep ; 22(4): 2860-2868, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945408

RESUMO

Hydrogen exhibits therapeutic and preventive effects against various diseases. The present study investigated the potential protective effect and dose­dependent manner of hydrogen inhalation on high fat and fructose diet (HFFD)­induced nonalcoholic fatty liver disease (NAFLD) in Sprague­Dawley rats. Rats were randomly divided into four groups: i) Control group, regular diet/air inhalation; ii) model group, HFFD/air inhalation; iii) low hydrogen group, HFFD/4% hydrogen inhalation; and iv) high hydrogen group, HFFD/67% hydrogen inhalation. After a 10­week experiment, hydrogen inhalation ameliorated weight gain, abdominal fat index, liver index and body mass index of rats fed with HFFD and lowered the total area under the curve in an oral glucose tolerance test. Hydrogen inhalation also ameliorated the increase in liver lipid content and alanine transaminase and aspartate transaminase activities. Liver histopathologic changes evaluated with hematoxylin and eosin as well as Oil Red O staining revealed lower lipid deposition in hydrogen inhalation groups, consistent with the decrease in the expression of the lipid synthesis gene SREBP­1c. The majority of the indicators were affected following treatment with hydrogen in a dose­dependent manner. In conclusion, hydrogen inhalation may play a protective role by influencing the general state, lipid metabolism parameters, liver histology and liver function indicators in the rat model of metabolic syndrome with NAFLD.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32975407

RESUMO

Most of chemiluminescence (CL) substrates exhibit the flash-type light emission. Therefore, the long-lasting CL system is always the crown in the field of CL-based analysis methodology. In this work, we constructed a Dox-ABEI chimeric magnetic DNA hydrogel (MDH) as a novel protease-free long-lasting CL reaction system. The functional MDH can transform flash-type ABEI/H2O2/CO2+ reaction into a glow-type CL system because of its block effect on delaying the diffusion rate of co-reactants, making the CL reaction gradually occur. More importantly, the functional MDH possessed the advantages of biocompatibility and controllability and could be well-designed to incorporate different biosensing strategies. Subsequently, we established a functional MDH-based long-lasting CL immunoassay system for ultrasensitive and highly specific detection of d-dimer and fibrin degradation products (FDPs). The designed CL immunoassay can detect d-dimer and FDP down to 53.7 and 31.6 fg/mL, respectively, with a wide line ranging from 100 fg/mL to 100 ng/mL, which was superior to the previously reported CL biosensing strategies. Moreover, benefiting from the magnetic separation of MDH and excellent CL performance, the developed immunoassaying method was successfully applied in the detection of clinical samples, which showed a close correlation with clinical reference technology. Thus, this functional MDH proved to be an excellent long-lasting CL system and a potential technical platform for clinical bioanalysis applications.

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