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1.
Biochim Biophys Acta Mol Basis Dis ; 1866(1): 165569, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31669422

RESUMO

Understanding how individuals react differently to the same treatment is a major concern in precision medicine. Metabolic challenges such as the one posed by high fructose intake are important determinants of disease mechanisms. We embarked on studies to determine how fructose affects differential metabolic dysfunctions across genetically dissimilar mice, namely, C57BL/6 J (B6), DBA/2 J (DBA) and FVB/NJ (FVB), by integrating physiological and gene regulatory mechanisms. We report that fructose has strain-specific effects, involving tissue-specific gene regulatory cascades in hypothalamus, liver, and white adipose tissues. DBA mice showed the largest numbers of genes associated with adiposity, congruent with their highest susceptibility to adiposity gain and glucose intolerance across the three tissues. In contrast, B6 and FVB mainly exhibited cholesterol phenotypes, accompanying the largest number of adipose genes correlating with total cholesterol in B6, and liver genes correlating with LDL in FVB mice. Tissue-specific network modeling predicted strain-and tissue-specific regulators such as Fgf21 (DBA) and Lss (B6), which were subsequently validated in primary hepatocytes. Strain-specific fructose-responsive genes revealed susceptibility for human diseases such that genes in liver and adipose tissue in DBA showed strong enrichment for human type 2 diabetes and obesity traits. Liver and adipose genes in FVB were mostly related to lipid traits, and liver and adipose genes in B6 showed relevance to most cardiometabolic traits tested. Our results show that fructose induces gene regulatory pathways that are tissue specific and dependent on the genetic make-up, which may underlie interindividual variability in cardiometabolic responses to high fructose consumption.

2.
Mol Oncol ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670863

RESUMO

Hepatocellular carcinoma (HCC), with its ineffective therapeutic options and poor prognosis, represents a global threat. In the present study, we show that RAD52 motif 1 (RDM1), a key regulator of DNA double-strand break repair and recombination, is downregulated in HCC tissues and suppresses tumor growth. In clinical HCC samples, low expression of RDM1 correlates with larger tumor size, poor tumor differentiation and unfavorable survival. In vitro and in vivo data demonstrate that knockdown of RDM1 increases HCC cell proliferation, colony formation and cell population at G2/M phase, whereas RDM1 overexpression results in the opposite phenotypes. Mechanistically, RDM1 binds to the tumor suppressor p53 and enhances its protein stability. In the presence of p53, RDM1 suppresses the phosphorylation of Raf and ERK. Overexpression of p53 or treatment with ERK inhibitor significantly abolishes cell proliferation induced by the depletion of RDM1. In addition, overexpression of methyltransferase-like 3 (METTL3) markedly induces N6-methyladenosine (m6 A) modification of RDM1 mRNA and represses its expression. Taken together, our study indicates that RDM1 functions as a tumor suppressor and may be a potential prognostic and therapeutic factor for HCC.

3.
Genes (Basel) ; 10(12)2019 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-31771247

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a progressive condition of the liver encompassing a range of pathologies including steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. Research into this disease is imperative due to its rapid growth in prevalence, economic burden, and current lack of FDA approved therapies. NAFLD involves a highly complex etiology that calls for multi-tissue multi-omics network approaches to uncover the pathogenic genes and processes, diagnostic biomarkers, and potential therapeutic strategies. In this review, we first present a basic overview of disease pathogenesis, risk factors, and remaining knowledge gaps, followed by discussions of the need and concepts of multi-tissue multi-omics approaches, various network methodologies and application examples in NAFLD research. We highlight the findings that have been uncovered thus far including novel biomarkers, genes, and biological pathways involved in different stages of NAFLD, molecular connections between NAFLD and its comorbidities, mechanisms underpinning sex differences, and druggable targets. Lastly, we outline the future directions of implementing network approaches to further improve our understanding of NAFLD in order to guide diagnosis and therapeutics.

4.
J Clin Lab Anal ; : e23129, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774215

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is characterized as glucose intolerance of any degree that begins or first diagnosed during pregnancy. It possesses a higher risk of haemorrhage, which may be caused by the coagulation dysfunction. However, there has been no study focus on how coagulation state changes in the progress of GDM pregnancy. Our study is aimed to assess the association of coagulation function and haemorrhage in GDM. METHODS: A total of 662 subjects (273 from a population-based study and 389 from a prospective cohort study) were selected to measure mean platelet volume (MPV), platelet distribution width (PDW), platelet (PLT), thrombocytocrit (PCT), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB). All pregnant individuals were divided into normal glucose tolerance (NGT) controls and GDM patients diagnosed between the 24th and 28th weeks of gestation. RESULTS: Compared with NGT controls, GDM females showed shortened PT, shortened APTT, and increased blood FIB levels, while the platelet parameters MPV, PDW, PLT, and PCT remained unchanged in mid-pregnancy. By late pregnancy, the platelet parameters MPV, PDW, and PCT were increased in the GDM group compared with the NGT group, while PT and APTT were unchanged. CONCLUSIONS: The GDM group was hypercoagulable compared with the NGT group rather than hypocoagulable as predicted, but still within the normal range. Therefore, our findings demonstrate that the variation degree of coagulation function is not responsible for extra risk of hemorrhage in GDM, and prevention of hemorrhage should focus on other causes.

5.
J Vet Sci ; 20(6): e68, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31775195

RESUMO

Viral-encoded microRNAs (miRNAs) have vital roles in the regulation of virus replications and host immune responses. The results of previous studies have indicated that miRNA clusters are involved in the replication and virulence of the pseudorabies virus (PRV), which may potentially lead to immune escape or facilitation of PRV replication. This study's previous research revealed that prv-miR-LLT11a was differentially expressed during PRV infection. The present study's results have demonstrated that prv-miR-LLT11a could significantly inhibit PRV replication. It was further determined that SLA-1 was the target gene of prv-miR-LLT11a, and simultaneously, that overexpression of prv-miR-LLT11a could downregulate the mRNA and protein levels of SLA-1 in a dose-independent manner. Furthermore, the present study also observed that prv-miR-LLT11a can downregulate TAP1 expression. Our findings provide a better understanding of the molecular mechanism involved in the effects of prv-miR-LLT11a on SLA-1 and TAP1 as well as its involvement in immune system evasion of PRV.

6.
Curr Drug Metab ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31749422

RESUMO

BACKGROUND: Exosomes are small extracellular vesicles (EVs) (40-100nm) secreted by living cells and mediate the transmission of information between cells. The number and contents of exosomes are associated with diseases such as inflammatory diseases, cancer, metabolic diseases and what we are focusing in this passage. OBJECTIVE: This review focused on the role of exosomes in oocyte development, declined ovarian function, PCOS, uterine diseases, endometrial receptivity and fallopian tube dysfunction in the female. METHODS: We conducted an extensive search for research articles involving relationships between exosomes and female infertility on bibliographic database. RESULTS: It's reported that exosomes can act as a potential therapeutic device to carry cargoes to treat female infertility. However, the pathophysiological mechanism of exosomes in female infertility has not been entirely elucidated. Further researches are needed to explore the etiology and provide evidence for potential clinical treatment. CONCLUSIONS: This review systematically summarized the role exosomes play in female infertility and its potential as drug delivery.

7.
Chem Commun (Camb) ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31750461

RESUMO

A triple sequential junction by rationally combining anatase/rutile nanoparticle TiO2 heterophase (Ans/R) and rutile/rutile TiO2 homophase (Rns/R) junctions was fabricated as a proof of concept. Such a continuous charge separation and transfer channel resulted in a remarkable enhancement in the separation of photogenerated carriers and the photocatalytic activity.

8.
Thorac Cancer ; 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31679181

RESUMO

BACKGROUND: Previous studies have documented the therapeutic value of computed tomography (CT)-guided percutaneous microwave ablation (MWA) for early-stage non-small cell lung cancer (NSCLC). However, few studies have focused on patients aged 80 years and older. This retrospective study aimed to evaluate the safety and clinical outcomes of CT-guided percutaneous MWA in patients aged 80 years and older with early-stage peripheral NSCLC. METHODS: A retrospective analysis of 63 patients aged 80 years and older with cT1a-2bN0M0 peripheral NSCLC who underwent CT-guided percutaneous MWA was performed between January 2008 and January 2018 at 11 hospitals in Shandong Province, China. RESULTS: The median follow-up time was 21.0 months. The overall median survival time was 50 months. The cancer-specific median survival time was not reached in five years. The one-, two-, three-, four-, and five-year overall survival rates were 97.1%, 92.6%, 63.4%, 54.4%, and 32.6%, respectively. The one-, two-, and three-year cancer-specific survival (CSS) rates were 97.9%, 97.9%, and 69.4%, respectively. The four- and five-year CSS rates were not achieved. A total of 14 patients (22.2%) had local progression. The one-, two-, three-, four-, and five-year local control rates were 88.8%, 78.8%, 70.3%, 63.9%, and 63.9%, respectively. The mortality rate was 0% within 30 days after the procedure. Major complications included pneumothorax requiring drainage (21.1%), pulmonary infection (4.2%), and pleural effusions requiring drainage (2.8%). CONCLUSIONS: CT-guided percutaneous MWA is a safe and effective modality for treating patients aged 80 years and older with early-stage peripheral NSCLC.

9.
J Cell Mol Med ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769590

RESUMO

High-mobility group box 1 (HMGB1) shows pro-inflammatory activity in various inflammatory diseases and has been found up-regulated in chronic obstructive pulmonary disease (COPD). Lung macrophages play an important role in airway inflammation and lung destruction in COPD, yet whether HMGB1 is involved in cigarette smoke (CS)-induced lung macrophage dysfunction is unknown. We sought to evaluate the intracellular localization and release of HMGB1 in lung macrophages from COPD patients and CS-exposed mice, and to investigate the role of HMGB1 in regulating autophagy in CS extract (CSE)-treated lung macrophages (MH-S cells). Our results showed that HMGB1 was highly expressed in lung tissues and sera of COPD patients and CS-exposed mice, along with predominantly cytoplasmic exporting from nuclei in lung macrophages. In vitro experiments revealed that CSE promoted the expression, nucleocytoplasmic translocation and release of HMGB1 partly via the nicotinic acetylcholine receptor (nAChR). Blockade of HMGB1 with chicken anti-HMGB1 polyclonal antibody (anti-HMGB1) or glycyrrhizin (Gly) attenuated the increase of LC3B-II and Beclin1, migration and p65 phosphorylation, suggesting the involvement of HMGB1 in autophagy, migration and NF-κB activation of lung macrophages. Hydroxychloroquine (CQ), an autophagy inhibitor, enhanced the increase of LC3B-II but not Beclin1 in CSE or rHMGB1-treated MH-S cells, and inhibition of autophagy by CQ and 3-methyladenine (3-MA) abrogated the migration and p65 phosphorylation of CSE-treated cells. These results indicate that CS-induced HMGB1 translocation and release contribute to migration and NF-κB activation through inducing autophagy in lung macrophages, providing novel evidence for HMGB1 as a potential target of intervention in COPD.

10.
Clin Chim Acta ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31758933

RESUMO

BACKGROUND: The value of urinary mitochondrial DNA (mtDNA) for assessing kidney injury of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) was investigated. METHODS: Thirty-nine kidney biopsy-proved myeloperoxidase (MPO)-ANCA associated AAV patients were enrolled and analyzed. RESULTS: The average urinary mtDNA of patients was significantly higher than that of normal controls (3372.74±1859.72 vs. 474.90±123.59 copy/nmol creatinine, p<0.001). The patients who needed dialysis at disease onset had the highest levels of urinary mtDNA (5072.23±1302.87 copy/nmol creatinine). Urinary mtDNA positively correlated with urinary neutrophil gelatinase-associated lipocalin (R=0.661, P<0.001) and negatively correlated with estimated glomerular filtration rate (R=-0.515, P=0.001). The urinary mtDNA level of crescentic class (4703.08±1744.31 copy/nmol creatinine) was higher than that of mixed class (3258.14±1158.99 copy/nmol creatinine) and focal class (2268.15±1897.63 copy/nmol creatinine). Univariate correlation analysis showed urinary mtDNA positively correlated with interstitial neutrophils (R=0.471, P=0.048) and glomerular neutrophils (R=0.673, P=0.002) in kidney biopsy. Among 13 patients who needed hemodialysis at disease onset, 10 patients who got renal recovery had higher urinary mtDNA than 3 patients who remained dialysis dependent (5455.20±1174.64 vs. 3795.67±893.34 copy/nmol creatinine, p=0.047). CONCLUSIONS: Urinary mtDNA increases in AAV with kidney injury, and its levels correlate with the severity of kidney injury and neutrophils infiltration in pathology.

11.
Endocr Relat Cancer ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31705798

RESUMO

Sorafenib, a small molecule tyrosine kinase inhibitor with antiangiogenic activity, has been used in liver cancer and kidney cancer treatment. However, clinical trials with sorafenib for breast cancer were stopped in phase Ⅲ due to limited efficacy. The existence of heterogeneous vasculatures involving tumor cells, such as vessel-like structures formed by vasculogenic mimicry and mosaic vessels, and their resistance to antiangiogenic therapy are thought to be a possible reason for failure of sorafenib therapy. Nevertheless, the features and mechanism of vasculogenesis by tumor cells remain unclear. In the present study, we found that breast cancer stem-like cells (BCSLCs, ALDH1+ cells) were involved in vasculogenic mimicry and mosaic vessel formation in triple-negative breast cancer tissues. Further, only ALDH1+ BCSLCs sorted from MDA-MB-231 could exhibit the tube formation and angiogenesis ability. Sorafenib could inhibit vascularization from endothelial cells rather than that from ALDH1+ cells. α-SMA was identified as a key molecule in vascular formation of BCSLCs. Mechanistically, HIF-1α enhanced the mRNA and protein levels of α-SMA by binding to the HRE element in the promoter directly and meanwhile increased the BCSLCs population. Interestingly, pigment epithelium-derived factor (PEDF), an endogenous angiogenesis inhibitor, could inhibit both endothelial cell-derived and tumor cell-derived angiogenesis by down-regulating HIF-1α in breast cancer. Our finding clarified the possible reason for the poor outcome of anti-angiogenesis therapy and PEDF may have the therapeutic potential.

12.
Res Microbiol ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31676435

RESUMO

The type VI secretion system (T6SS), a multifunctional protein secretion device, plays very important roles in bacterial killing and/or virulence to eukaryotic cells. Although T6SS genes have been found in many Xanthomonas species, the biological function of T6SSs has not been elucidated in most xanthomonads. In this study, we identified two phylogenetically distinct T6SS clusters, T6SS1 and T6SS2, in a newly sequenced Chinese strain GX01 of Xanthomonas oryzea pv. oryzicola (Xoc) which causes bacterial leaf streak (BLS) of rice (Oryza sativa L.). Mutational assays demonstrated that T6SS1 and T6SS2 are not required for the virulence of Xoc GX01 on rice. Nevertheless, we found that T6SS2, but not T6SS1, played an important role in bacterial killing. Transcription and secretion analysis revealed that hcp2 gene is actively expressed and that Hcp2 protein is secreted via T6SS. Moreover, several candidate T6SS effectors were predicted by bioinformatics analysis that might play a role in the antibacterial activity of Xoc. This is the first report to investigate the type VI secretion system in Xanthomonas oryzae. We speculate that Xoc T6SS2 might play an important role in inter-bacterial competition, allowing this plant pathogen to gain niche advantage by killing other bacteria.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31599340

RESUMO

OBJECTIVES: Evidence from multiple clinical trials showed that local consolidative therapy (LCT) improved survival in oligometastatic non-small cell lung cancer (NSCLC) patients. In the present study, we aim to explore the potential role of microwave ablation (MWA) as LCT for epidermal growth factor receptor (EGFR)-mutant advanced NSCLC patients with extracranial oligometastasis. MATERIALS AND METHODS: From January 2015 to December 2018, a total of 86 EGFR-mutant stage IIIB or IV NSCLC patients with extracranial oligometastasis were enrolled for retrospective analysis. MWA was used as LCT for all oligometastatic lesions and/or primary tumors in 34 patients without progression after first-line EGFR-TKIs therapy (consolidation group), while the other 52 patients received only TKIs until disease progression (monotherapy group). We calculated and compared the progression-free survival (PFS) and overall survival (OS) of the two groups. RESULTS AND CONCLUSION: Patients with MWA consolidation therapy had significantly improved PFS (median 16.7 vs. 12.9 months, HR 0.44, 95% CI 0.22-0.88, P = 0.02) and OS (median: 34.8 vs. 22.7 months, HR 0.45, 95% CI 0.24-0.88, P = 0.04) than monotherapy group. MWA for LCT was identified as the independent predictive factor for better PFS (HR 0.46, 95% CI 0.37-0.82, P < 0.01) and OS (HR 0.57, 95% CI 0.33-0.91, P = 0.02). Most toxicities were mild and well tolerated. No patient had to discontinue EGFR-TKIs because of MWA complications. These findings suggest that MWA as local consolidative therapy after first-line EGFR-TKIs treatment leads to better disease control and survival than TKIs monotherapy in EGFR-mutant advanced NSCLC patients with extracranial oligometastasis. MWA as a novel option of LCT might be considered for clinical management of these patients.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31621453

RESUMO

Objective: To evaluate the efficacy of microwave ablation (MWA) and MWA plus monochemotherapy in elderly patients with advanced non-small-cell lung cancer (NSCLC). Material and methods: Patients with advanced NSCLC aged ≥70 years were retrospectively enrolled. MWA was performed at the primary tumor site. The end points included progression-free survival (PFS), response to MWA and overall survival (OS). Results: Fifty-four patients were enrolled; of these, 36 received monochemotherapy. Complete ablation was achieved in 42 patients (77.8%). The median PFS and OS were 4.9 months and 21.8 months, respectively. Univariate analyses showed that female patients had superior PFS (31.9 months [95% confidence interval (CI): 0.8-63.0]) vs. 5.0 months in male patients (95% CI: 2.0-8.0), p = .002). Female sex was associated with better OS (not reached vs. 10.8 months, 95% CI: 9.3-12.3, p = .003). Moreover, patients with primary tumor size <3.5 cm had better OS than those with tumor size ≥3.5 cm (not reached vs. 10.9 months, 95% CI: 8.2-13.6, p = .006). Multivariate analyses showed that no characteristics were independent prognostic factors of PFS, but sex and primary tumor size were independent prognostic factors of OS. Conclusion: MWA was effective in the treatment of elderly patients with advanced NSCLC.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31614952

RESUMO

Background: Smoking is among the most preventable causes of death globally. Tobacco cessation can lessen the number of potential deaths. The China Tobacco Cessation Guidelines encourage medical staff to perform the 5As (Ask, Advise, Assess, Assist, Arrange) when delivering tobacco dependence treatments to patients. Nursing students will develop to be nurses in the future and they have to finish 9 months of clinical practicum study in the last year at hospitals or care centers. However, the frequency of behaviors used to help smokers quit among Chinese nursing internship students is unclear. This study analyzed the rate of nurse interns' performance of the 5As and which demographic characteristics, perceptions of smoking and knowledge predicted higher performance of the 5As. Methods: The cluster sampling method was used to select 13 teaching hospitals among 29. All nursing intern students were expected to finish the questionnaire about their 5As behaviors to help patients quit smoking. Their 5As performances were scored from one to five with 5 being the best and scores were summed. A multivariate linear mixed-effect model was employed to test the differences between their 5As. Results: Participating in the survey were 1358 interns (62.4% response rate). The average scores were as follows-Ask-3.15, Advise-2.75, Assess-2.67, Assist-2.58 and Arrange-2.42. A total of 56.3% students perceived that medical staff should perform the 5As routinely to help patients quit smoking. On the other hand, 52.1% viewed clinical preceptors as role models of the 5As. School education regarding tobacco control, smoking dependence treatment, self-efficacy and positive intentions were predictors of higher performance of the 5As (p < 0.001). Conclusions: Nursing internship students seldom administered tobacco dependence treatments to patients. It is essential to improve the corresponding education, skills and self-efficacy of the 5As. Meanwhile, clinical preceptors should procure more training in the responsibilities and skills related to tobacco cessation. In this way, clinical preceptors can be role models of the 5As and impart positive influences on interns.

16.
Arch Biochem Biophys ; 678: 108116, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31568751

RESUMO

Exposure to ambient particulate matter has been shown to promote a variety of disorders, including cardiovascular diseases predominantly of ischemic etiology. However, the mechanisms linking inhaled particulates with systemic vascular effects, resulting in worsened atherosclerosis, are not well defined. We assessed the potential role of macrophages in translating these effects by analyzing gene expression patterns in response to diesel exhaust particles (DEP) at the average cell level, using Affymetrix microarrays in peritoneal macrophages in culture (in vitro), and at the individual cell level, using single-cell RNA sequencing (scRNA-seq) in alveolar macrophages collected from exposed mice (in vivo). Peritoneal macrophages were harvested from C57BL/6J mice and treated with 25 µg/mL of a DEP methanol extract (DEPe). These cells exhibited significant (FDR < 0.05) differential expression of a large number of genes and enrichment in pathways, especially engaged in immune responses and antioxidant defense. DEPe led to marked upregulation of heme oxygenase 1 (Hmox1), the most significantly upregulated gene (FDR = 1.75E-06), and several other antioxidant genes. For the in vivo work, C57BL/6J mice were subjected to oropharyngeal aspiration of 200 µg of whole DEP. The gene expression profiles of the alveolar macrophages harvested from these mice were analyzed at the single-cell level using scRNA-seq, which showed significant dysregulation of a broad number of genes enriched in immune system pathways as well, but with a large heterogeneity in how individual alveolar macrophages responded to DEP exposures. Altogether, DEP pollutants dysregulated immunological pathways in macrophages that may mediate the development of pulmonary and systemic vascular effects.

17.
Arch Gynecol Obstet ; 300(5): 1445-1459, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31631247

RESUMO

PURPOSE: Recurrent implantation failure (RIF) is a common cause of disappointment and a big challenge after assisted reproduction technology treatments. The objective of this study was to evaluate the existing literature to explore whether peripheral blood mononuclear cells' (PBMCs) instillation could improve pregnancy outcomes among patients with RIF. METHODS: We conducted a comprehensive search including PubMed, EMBASE, Cochrane library and various databases in China. Three randomized controlled trials (RCTs) and three non-randomized controlled trials (non-RCTs) were included. We included subgroup and sensitivity analyses using Stata 12.0. RESULTS: The results of the three RCTs showed that PBMC improved outcomes in all patients compared with placebo or no-treatment [clinical pregnancy rate (CPR): odds ratio (OR) 2.45, 95% confidence interval (CI) 1.53-3.91; implantation rate (IR): OR 2.46, 95% CI 1.48-4.09; live birth rate (LBR): OR 2.43, 95% CI 1.32-4.49]. However, the results of the three non-RCTs indicated that there were no statistically significant differences in the outcomes and that the heterogeneity was higher (I2 > 0%). Subgroup analysis further suggested that PBMCs treatment significantly increased the CPR, IR and LBR in the three or more implantation failure subgroups (CPR: OR 2.83, 95% CI 1.29-6.22; IR: OR 3.74, 95% CI 1.71-8.19; LBR: OR 3.03, 95% CI 1.15-7.98). CONCLUSIONS: Among patients with three or more implantation failures, this treatment improved IR, LBR, and CPR compared to that in controls, due to the limited data available, PBMCs' intrauterine instillation should only be used in the context of clinical trials.

18.
Elife ; 82019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31644425

RESUMO

Immune cells are vital constituents of the adipose microenvironment that influence both local and systemic lipid metabolism. Mice lacking IL10 have enhanced thermogenesis, but the roles of specific cell types in the metabolic response to IL10 remain to be defined. We demonstrate here that selective loss of IL10 receptor α in adipocytes recapitulates the beneficial effects of global IL10 deletion, and that local crosstalk between IL10-producing immune cells and adipocytes is a determinant of thermogenesis and systemic energy balance. Single Nuclei Adipocyte RNA-sequencing (SNAP-seq) of subcutaneous adipose tissue defined a metabolically-active mature adipocyte subtype characterized by robust expression of genes involved in thermogenesis whose transcriptome was selectively responsive to IL10Rα deletion. Furthermore, single-cell transcriptomic analysis of adipose stromal populations identified lymphocytes as a key source of IL10 production in response to thermogenic stimuli. These findings implicate adaptive immune cell-adipocyte communication in the maintenance of adipose subtype identity and function.

19.
Cell Death Dis ; 10(10): 742, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582735

RESUMO

Pigment epithelium-derived factor (PEDF), a classic angiogenic inhibitor, has been reported to function as a tumor suppression protein and to downregulate in many types of solid tumors. However, the expression level of PEDF and its role in hepatocellular carcinoma (HCC) are contradictory. The present study investigates the expression and different activities of secreted and intracellular PEDF during HCC development, as well as the underlying mechanism of PEDF on HCC lipid disorders. We found that PEDF had no association with patients' prognosis, although PEDF was highly expressed and inhibited angiogenesis in HCC tumor tissues. The animal experiments indicated that full-length PEDF exhibited equalizing effects on tumor growth activation and tumor angiogenesis inhibition in the late stage of HCC progression. Importantly, the pro-tumor activity was mediated by the intracellular PEDF, which causes accumulation of free fatty acids (FFAs) in vivo and in vitro. Based on the correlation analysis of PEDF and lipid metabolic indexes in human HCC tissues, we demonstrated that the intracellular PEDF led to the accumulation of FFA and eventually promoted HCC cell growth by inhibiting the activation of AMPK via ubiquitin-proteasome-mediated degradation, which causes increased de novo fatty acid synthesis and decreased FFA oxidation. Our findings revealed why elevated PEDF did not improve the patients' prognosis as the offsetting intracellular and extracellular activities. This study will lead to a comprehensive understanding of the diverse role of PEDF in HCC and provide a new selective strategy by supplement of extracellular PEDF and downregulation of intracellular PEDF for the prevention and treatment of liver cancer.

20.
PLoS One ; 14(10): e0223218, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31574112

RESUMO

OBJECTIVE: To identify risk factors associated with unfavorable outcomes in children with IgA vasculitis with nephritis (Henoch-Schonlein purpura nephritis)(IgA-VN). METHODS: PubMed, Embase, and Web of Science databases were searched for studies, published in English through February 2019. The data were extracted to perform pooled analysis, heterogeneity testing, subgroup analysis, sensitivity analysis, and publication bias analysis. RESULTS: This meta-analysis showed that, older age at onset (WMD 1.77, 95% CI 0.35-3.18, p = 0.014), lower glomerular filtration rate (GFR; WMD -23.93, 95% CI -33.78- -14.09, p<0.0001), initial renal manifestations with nephrotic syndrome (OR 1.74, 95% CI 1.12-2.70, p = 0.013), with nephritic-nephrotic syndrome (OR 4.55, 95% CI 2.89-7.15, p<0.0001) and renal biopsy with crescentic nephritis (International Study of Kidney Disease in Children [ISKDC] grades III-V) (OR 3.85, 95% CI 2.37-6.28, p<0.0001) were significant risk factors associated with poor outcomes in IgA-VN, whereas initial clinical features with hematuria (OR 0.33, 95% CI 0.16-0.69, p = 0.003) and mild proteinuria±hematuria (OR 0.46, 95% CI 0.28-0.75, p<0.0001) were associated with progression to good outcomes. By contrast, gender, hypertension and initial renal manifestations of acute nephritic syndrome were not significantly associated with poor outcomes in IgA-VN. CONCLUSION: This meta-analysis showed that older age at onset, lower GFR, initial renal features of nephrotic syndrome and nephritic-nephrotic syndrome and renal biopsy with crescentic nephritis (ISKDC grades III-V) were predictive of poor prognosis in children with IgA-VN.

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