Mild Photothermal-Stimulation Based on Injectable and Photocurable Hydrogels Orchestrates Immunomodulation and Osteogenesis for High-Performance Bone Regeneration.

A photoactivated bone scaffold integrated with minimally invasive implantation and mild thermal-stimulation capability shows great promise in the repair and regeneration of irregularly damaged bone tissues. Developing multifunctional photothermal biomaterials that can simultaneously serve as both controllable thermal stimulators and biodegradable engineering scaffolds for integrated immunomodulation, infection therapy, and impaired bone repair remains an enormous challenge. Herein, an injectable and photocurable hydrogel therapeutic platform (AMAD/MP) based on alginate methacrylate, alginate-graft-dopamine, and polydopamine (PDA)-functionalized Ti3C2 MXene (MXene@PDA) nanosheets is rationally designed for near-infrared (NIR)-mediated bone regeneration synergistic immunomodulation, osteogenesis, and bacterial elimination. The optimized AMAD/MP hydrogel exhibits favorable biocompatibility, osteogenic activity, and immunomodulatory functions in vitro. The proper immune microenvironment provided by AMAD/MP could further modulate the balance of M1/M2 phenotypes of macrophages, thereby suppressing reactive oxygen species-induced inflammatory status. Significantly, this multifunctional hydrogel platform with mild thermal stimulation efficiently attenuates local immune reactions and further promotes new bone formation without the addition of exogenous cells, cytokines, or growth factors. This work highlights the potential application of an advanced multifunctional hydrogel providing photoactivated on-demand thermal cues for bone tissue engineering and regenerative medicine.

GhROP6 GTPase modulates auxin accumulation in cotton fibers by regulating cell-specific GhPIN3a localization.

PIN-FORMED- (PIN) mediated polar auxin transport plays a predominant role in most auxin-triggered organogenesis in plants. Global control of PIN polarity at the plasma membrane contributes to the essential establishment of auxin maxima in most multicellular tissues. However, establishment of auxin maxima in single cells is poorly understood. Cotton fibers, derived from ovule epidermal cells by auxin-triggered cell protrusion, provide an ideal model to explore the underlying mechanism. Here, we report that cell-specific degradation of GhPIN3a, which guides the establishment of the auxin gradient in cotton ovule epidermal cells, is associated with the preferential expression of GhROP6 GTPase in fiber cells. In turn, GhROP6 reduces GhPIN3a abundance at the plasma membrane and facilitates intracellular proteolysis of GhPIN3a. Overexpression and activation of GhROP6 promote cell elongation, resulting in a substantial improvement in cotton fiber length.

The comparative study for survival outcome of locally advanced cervical cancer treated by neoadjuvant arterial interventional chemotherapy or intravenous chemotherapy followed by surgery or concurrent chemoradiation.

OBJECTIVE: This study aimed to compare the survival outcome of 3 different treatment groups (arterial interventional chemotherapy or intravenous chemotherapy or concurrent chemoradiotherapy) for locally advanced cervical cancer. METHODS: A total of 187 patients with pathological stage IB3-IIB cervical cancer (cervical squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma) hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2013 to May 2019 were included. Therefore, this article is a retrospective study. We collected data from all eligible patients. And all according to the treatment methods at that time, they were divided into three subgroups: (1) 40 patients who received neoadjuvant arterial interventional chemotherapy + surgery + postoperative chemotherapy (IA-NAC + RS), (2) 63 patients who received neoadjuvant intravenous chemotherapy + surgery + postoperative chemotherapy (IV-NAC + RS), (3) 84 patients who only received concurrent chemoradiotherapy (CCRT). Notably, 108 of these patients met the 5-year follow-up period, and 187 patients met the 3-year follow-up period only. Consequently, we compared 5-year survival and 3-year survival separately. The prognosis (5-year survival and 3-year survival) of the three groups and the chemotherapy efficacy, intraoperative blood loss, operation time, and postoperative pathological risk factors of different subgroups were compared. RESULTS: (1) There were no significant differences in the 3-year overall survival (OS) rate, 3-year progression-free survival (PFS) rate, 5-year OS rate, and 5-year PFS rate among the three subgroups (p > 0.05). (2) The chemotherapy response rates of IA-NAC+RS group (37.5%) and IV-NAC+RS group (25.4%) were comparable (p > 0.05). (3) The intraoperative blood loss in the IA-NAC+RS group (average 92.13±84.09 mL) was significantly lower than that in the IV-NAC+RS group (average 127.2±82.36 mL) (p < 0.05). (4) The operation time of the IA-NAC+RS group (average 231.43±63.10 min) and the IV-NAC+RS group (average 219.82±49.11 min) were comparable (p > 0.05). (5) There were no significant differences between the IA-NAC+RS group and IV-NAC+RS group in pathological lymph node metastasis, parametrial invasion, and involvement of lymphovascular space (p > 0.05). CONCLUSIONS: Neoadjuvant chemotherapy combined with surgery had the same long-term survival benefit as concurrent chemoradiotherapy.

Maternal nicotine exposure during pregnancy and lactation induces brown adipose tissue whitening in female offspring.

Maternal nicotine exposure during pregnancy and lactation is associated with obesity in female offspring. Brown adipose tissue (BAT) is related to energy metabolism and obesity. In this study, we explored the mechanism of maternal nicotine exposure on BAT "whitening" in female offspring. Pregnant rats were randomly assigned to nicotine (1.0 mg/kg twice per day, subcutaneous administration) or control groups. The weight, structure, and microvascular density of interscapular BAT (iBAT) and the expression of PGC-1αUCP1 signals, mitochondrial biogenesis-related genes and angiogenesis-related genes were tested in 4- and 26-week-aged female offspring. In vitro, C3H10T1/2 cells were induced to differentiate into mature brown adipocytes, and 0-50 µM nicotine was treated on cells during the differentiation process. Nicotine-exposed females had higher iBAT weight, white-like adipocytes and abnormal mitochondrial structure in iBAT at 26 weeks rather than 4 weeks. The PGC-1αUCP1 signals and brown-like genes were down-regulated at 26 weeks, but the microvascular density and the expression of pro-angiogenic factors reduced more at 4 weeks in the nicotine group. In vitro, 50 µM nicotine significantly decreased the expression of PGC-1αUCP1 signals and angiogenesis-related genes. In conclusion, maternal nicotine exposure during pregnancy and lactation led to the "whitening" of BAT in adult female offspring: nicotine decreased BAT angiogenesis in the early development stage, and then, the impairment of blood vessels programed for the reduction of BAT phenotype through down-regulating the PGC-1αUCP1 signals in adulthood. This impairment of BAT may be a potential mechanism of nicotine-induced obesity in female offspring.

Prognostic value of the tumor-specific ceRNA network in epithelial ovarian cancer.

Epithelial ovarian cancer is one of the leading causes of cancer-related death worldwide. Growing evidence indicates that multiple complex altered pathways play important regulatory roles in the development and progression of a variety of cancers, including epithelial ovarian cancer. However, the underlying mechanisms remain unclear. First, we identified differentially expressed messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and microRNAs (miRNAs) in epithelial ovarian cancer by comparing the expression profiles between epithelial ovarian cancer samples and normal tissue samples in different GEO datasets. Then, GO- and KEGG-pathway-enrichment analyses were applied to investigate the primary functions of the overlapped differentially expressed mRNAs. Moreover, the primary enriched genes were used to construct the signal-network with Cytoscape software. In addition, we integrated the relationship among lncRNAs-miRNAs-mRNAs to create a competing endogenous RNA network. Finally, mRNAs that were associated with patient prognosis in epithelial ovarian cancer were selected using univariate Cox regression analysis. A total of 2,225 mRNAs, 336 lncRNAs, and 14 miRNAs were shown to be differentially expressed in epithelial ovarian cancer compared with normal tissues. The dysregulated mRNAs were primarily enriched in cell division and signal transduction, according to Gene Ontology, whereas, according to KEGG, they were primarily enriched in metabolic pathways and pathways in cancer. A total of 10 mRNAs were associated with patient prognosis in ovarian cancer. This study identifies a novel lncRNA-miRNA-mRNA network, which may suggest potential molecular mechanisms underlying the development of epithelial ovarian cancer, providing new insights for survival prediction and interventional strategies for epithelial ovarian cancer.

Integrated pharmacokinetic/viral dynamic model for daclatasvir/asunaprevir in treatment of patients with genotype 1 chronic hepatitis C.

In order to develop an integrated pharmacokinetic/viral dynamic (PK/VD) model to predict long-term virological response rates to daclatasvir (DCV) and asunaprevir (ASV) combination therapy in patients infected with genotype 1 (GT1) chronic hepatitis C virus (HCV), a systematic publication search was conducted for DCV and ASV administered alone and/or in combination in healthy subjects or patients with GT1 HCV infection. On the basis of a constructed meta-database, an integrated PK/VD model was developed, which adequately described both DCV and ASV PK profiles and viral load time curves. The IC50 values of DCV and ASV were estimated to be 0.041 and 2.45 µg/L, respectively, in GT1A patients. A sigmoid Emax function was applied to describe the antiviral effects of DCV and ASV, depending on the drug concentrations in the effect compartment. An empirical exponential function revealed that IC50 changing over time described drug resistance in HCV GT1A patients during DCV or ASV monotherapy. Finally, the PK/VD model was evaluated externally by comparing the expected and observed virological response rates during and post-treatment with DCV and ASV combination therapy in HCV GT1B patients. Both the rates were in general agreement. Our PK/VD model provides a useful platform for the characterization of pharmacokinetic/pharmacodynamic relationships and the prediction of long-term virological response rates to aid future development of direct acting antiviral drugs.

Interactions between miRNAs and the Wnt/ß-catenin signaling pathway in endometriosis.

Endometriosis is a disease characterized by the ectopic growth of endometrial tissue (glands and stroma) outside the confines of the uterus and often involves vital organs such as the intestines and urinary system. Endometriosis is considered a refractory disease owing to its enigmatic etiology, propensity for recurrence following conservative or surgical interventions, and the absence of radical treatment and long-term management. In recent years, the incidence of endometriosis has gradually increased, rendering it a pressing concern among women of childbearing age. A more profound understanding of its pathogenesis can significantly improve prognosis. Recent research endeavors have spotlighted the molecular mechanisms by which microRNAs (miRNAs) regulate the occurrence and progression of endometriosis. Many miRNAs have been reported to be aberrantly expressed in the affected tissues of both patients and animal models. These miRNAs actively participate in the regulation of inflammatory reactions, cellular proliferation, angiogenesis, and tissue remodeling. Their capacity to modulate crucial signaling pathways, such as the Wnt/ß-catenin signaling pathway, reinforces their potential utility as diagnostic markers or therapeutic agents for endometriosis. In this review, we provide the latest insights into the role of miRNAs that interact with the Wnt/ß-catenin pathway to regulate the biological behaviors of endometriosis cells and disease-related symptoms, such as pain and infertility. We hope that this review will provide novel insights and promising targets for innovative therapies addressing endometriosis.

Leucyl and Cystinyl Aminopeptidase as a Prognostic-Related Biomarker in OV Correlating with Immune Infiltrates.

Background: It was indicated that tumor intrinsic heterogeneity and the tumor microenvironment (TME) of ovarian cancer (OV) influence immunotherapy efficacy and patient outcomes. Leucyl and cystinyl aminopeptidase (LNPEP) encodes a zinc-dependent aminopeptidase, which has been proved to participant in the vesicle-mediated transport and class I MHC mediated antigen processing and presentation. However, the function of LNPEP in TME of OV and its potential molecular mechanisms have not been determined. Therefore, we aimed to investigate a prognostic biomarker which may be helpful in identifying TME heterogeneity of ovarian cancer. Methods: In this study, bioinformatics databases were used to explore the expression profile and immune infiltration of LNPEP. Bioinformatics analyses of survival data and interactors of LNPEP were conducted to predict the prognostic value of LNPEP in OV. The protein levels of LNPEP were validated by Western blot and immunohistochemistry. Results: Based on the TCGA data, our data displayed that the mRNA expression of LNPEP was markedly down-regulated in ovarian cancer than that in para-cancer tissues, contrary to the protein level. Importantly, high LNPEP expression was associated with poor prognosis in patients with OV. Furthermore, Cox regression analysis showed that LNPEP was an independent prognostic factor in OV. GO and KEGG pathway analyses indicated the co-expressed genes of LNPEP were mainly related to a variety of immune-related pathways, including Th1 and Th2 cell differentiation, Th17 cell differentiation, and immunoregulatory interaction. Our data also demonstrated that the expression of LNPEP was strongly correlated with immune infiltration levels, immunomodulators, chemokines and chemokine receptors. Conclusion: In our study, we identified and established a prognostic signature of immune-related LNPEP in OV, which will be of great value in predicting the prognosis of clinical trials and may become a new therapeutic target for immunological research and potential prognostic biomarker in OV.

The important roles of RET, VEGFR2 and the RAF/MEK/ERK pathway in cancer treatment with sorafenib.

AIM: To elucidate the roles of receptor tyrosine kinases RET and VEGFR2 and the RAF/MEK/ERK signaling cascade in cancer treatment with sorafenib. METHODS: The cell lines A549, HeLa, and HepG2 were tested. The enzyme activity was examined under cell-free conditions using 384-well microplate assays. Cell proliferation was evaluated using the Invitrogen Alarmar Blue assay. Gene expression was analyzed using the Invitrogen SYBR Green expression assays with a sequence detection system. Protein expression analysis was performed using Western blotting. RESULTS: Sorafenib potently suppressed the activities of cRAF, VEGFR2, and RET with IC(50) values of 20.9, 4 and 0.4 nmol/L, respectively. Sorafenib inhibited cRAF, VEGFR2, and RET via non-ATP-competitive, ATP-competitive and mixed-type modes, respectively. In contrast, sorafenib exerted only moderate cytotoxic effects on the proliferation of the 3 cell lines. The IC(50) values for inhibition of A549, HeLa, and HepG2 cells were 8572, 4163, and 8338 nmol/L, respectively. In the 3 cell lines, sorafenib suppressed the cell proliferation mainly by blocking the MEK/ERK downstream pathway at the posttranscriptional level, which in turn regulated related gene expression via a feed-back mechanism. CONCLUSION: This study provides novel evidence that protein kinases RET and VEGFR2 play crucial roles in cancer treatment with sorafenib.

Alterations of Gut Microbiome and Fecal Fatty Acids in Patients With Polycystic Ovary Syndrome in Central China.

Objective: The purpose of this study was to elucidate the characteristics of the gut microbiome in patients with Polycystic ovary syndrome (PCOS) and analyze the alterations of fecal fatty acid metabolism, so as to further provide the pathogenesis of PCOS. Methods: Fecal samples from the PCOS group (n = 31) and healthy control group (n = 27) were analyzed by 16S rRNA gene sequencing and untargeted metabolomics. Peripheral venous blood was collected to measure serum inflammation and intestinal permeability. Finally, the correlation analysis of intestinal flora, fecal metabolites, and laboratory indicators was carried out. Results: Serum D-lactate content in the PCOS group was higher than that in the control group. There was no significant difference in microbial α diversity and ß diversity between PCOS patients and healthy controls. Peptostreptococcaceae and Bacteroidales S24-7 group existed significant differences between PCOS patients and healthy controls. Based on linear discriminant analysis selection, 14 genera including Klebsiella, Enterobacteriaceae, and Gammaproteobacteria were dominant in patients with PCOS, while 4 genera, including rumenococcus (Ruminocaccaceae UCG 013), prewortella (Prevotellaceae UCG 001), and erysipelas (Erysipelatoclostridium), were dominant in healthy controls. Compared with PCOS with Body mass index (BMI) < 24, patients with BMI ≥ 24 have multiple dominant genera including Abiotrophia and Peptostreptococcaceae. Moreover, serum levels of free testosterone and androstenedione were positively correlated with Megamonas, while total testosterone was negatively correlated with Alistipes. Additionally, fecal contents of acetic acid and propionic acid in patients with PCOS were significantly higher than those in healthy controls. Eubacterium_coprostanoligenes_group and Alistipes were positively correlated with 6 kinds of fatty acids. Conclusion: Specific intestinal flora fecal fatty acids and serum metabolites may mediate the occurrence and development of PCOS. PCOS patients with different body sizes have specific intestinal flora.

Temporary Internal Iliac Artery Blockage versus Uterine Artery Embolization in Patients After Laparoscopic Pregnancy Tissue Removal Due to Cesarean Scar Pregnancy.

OBJECTIVE: This study aims to evaluate the clinical value of laparoscopic temporary internal iliac artery blockage (TIIAB) compared with uterine artery embolization (UAE) in type III cesarean scar pregnancy (CSP). METHODS: A total of 76 patients with type III CSP admitted to the Department of Gynecology the First Affiliated Hospital of Zhengzhou University between September 2017 and June 2019 were selected for this retrospective study. Thirty-six of them in the study group received TIIAB, and the rest in control group received UAE. Laparoscopic pregnancy tissue was removed from all patients, and the uterine defects were repaired. The absence of remnants was then confirmed using ultrasonography. Follow-ups were performed in the two groups for six months, and the factors of intraoperative blood loss, operation and menelipsis time, 24-h human chorionic gonadotropin decline rate, postoperative complications, hospitalization days, hospitalization costs, peri-operative hormone levels, and ovarian function indicators were compared between the two groups and within each group. RESULTS: There were statistically significant differences in the hospitalization cost, menelipsis time, and postoperative complication incidence between the two groups (p < 0.05). There were statistically significant differences between ovarian function at one month and three months after surgery (p < 0.05) as well as among the follicle-stimulating hormone, luteinizing hormone, and estradiol levels at one, three, and six months after surgery in the control group (p < 0.05). CONCLUSION: Compared with uterine artery embolization, laparoscopic TIIAB has the advantages of a low hospitalization cost, lower postoperative complication rate, and shorter menelipsis time. Moreover, it avoids ovarian function damage. It is a safe method worthy of clinical popularization.

Four-Way Crossover Phase 1 Thorough QT Study to Assess Cardiac Safety of Domperidone and Consideration for Design and Conduct of QT/QTc Study in China.

This study aimed to evaluate the QT prolongation potential of domperidone in healthy Chinese participants and explore the possibility of a thorough QT (TQT) study in China with a smaller sample size using concentration-QT (C-QT) modeling. Part 1 was a randomized, placebo- and positive-controlled, multiple-dose, 4-way crossover TQT study in healthy Chinese participants; 44 participants were randomized to either domperidone 10/20 mg or placebo 3 times daily, on days 1 to 3, followed by a single dose of either 10/20 mg domperidone/domperidone-placebo/domperidone-placebo plus 400 mg of moxifloxacin, on day 4. Twelve-lead electrocardiograms were recorded in triplicate at predefined time points with pharmacokinetic sampling. The results were that change from baseline in QT interval corrected for heart rate (QTc) using the Fridericia formula (QTcF) between domperidone and placebo was 1.3 milliseconds and 2.7 milliseconds for 10 and 20 mg 3 times daily, and upper limits of 2-sided 90%CI for all time points were below regulatory threshold of 10 milliseconds. In part 2, resampling analysis using C-QT modeling for moxifloxacin showed false-negative rates of <5% with sample sizes ≥6. We could conclude that no clinically relevant effect on corrected QT interval or new safety signals was observed with domperidone. A dedicated TQT study with C-QT modeling could assess drug effects on QT/corrected QT intervals for novel drug development in China.

[Responses of physiological ecology and quality evaluation of Rehmannia gltinosa in continuous cropping].

OBJECTIVE: To study responses of physiological ecology and quality evaluation of Rehmannia glutinosa in continuous cropping. METHOD: The potted plant R. glutinosa which consists of first cropping, 1 year continuous cropping and 2 year continuous cropping were used as experimental materials. The photosynthetic activity, descending axis vitality, the protective enzymes system and MDA content were measured, the quality was evaluated by FTIR and HPLC. RESULT: Continuous cropping reduced the content of chlorophyll in the non-first cropping R. glutinos, the photosynthetic activity and descending axis vitality were weakened. Because of the increase of the free radical in the R. glutinos due to the continuous cropping, the activity of protective enzymes including POD, SOD and CAT were enhanced and MDA content were increased, more importantly the medical potency declined . And along with the increasing years of the continuous cropping, this effect becomes even stronger. CONCLUSION: Continuous cropping affects the descending axis ability of absorbing water and nutrition and photosynthesis are inhibited R. glutinosa, at the same time, it also causes the disorders of antioxidation systems in R. glutinos, resulting in continuous cropping obstacle and decline of the medicinal materials quality.

Maternal nicotine exposure impairs brown adipose tissue via AMPK-SIRT1-PGC-1α signals in male offspring.

AIMS: Maternal nicotine exposure during pregnancy and lactation is associated with obesity in offspring. Brown adipose tissue (BAT) is correlated with energy metabolism and obesity. In this study, we explored the mechanism of maternal nicotine exposure on BAT changes in male offspring. MAIN METHODS: Pregnant rats were randomly assigned to nicotine (1.0 mg/kg twice per day, subcutaneous administration) or control groups. In vitro, C3H10T1/2 cells were induced to differentiate into mature brown adipocytes, and 0-50 µM nicotine was given to C3H10T1/2 cells during the differentiation process. KEY FINDINGS: Nicotine-exposed males had white-like adipocytes and abnormal mitochondria structure in iBAT at 26 weeks. The expression of mitochondrial genes, UCP1 and AMPK-SIRT1-PGC-1α pathway were downregulated in the nicotine group at 26 weeks rather than 4 weeks. In vitro, 50 µM nicotine decreased the expression of mitochondrial genes, UCP1 and AMPK-SIRT1-PGC-1α pathway in brown adipocytes. SIGNIFICANCE: Maternal nicotine exposure showed the "programming" effect on the decreased brown-like phenotype in BAT of adult male offspring via downregulating AMPK-SIRT1-PGC-1α pathway. This impairment of BAT may be a potential mechanism of nicotine-induced obesity in male offspring.

Targeting of KDM5A by miR-421 in Human Ovarian Cancer Suppresses the Progression of Ovarian Cancer Cells.

PURPOSE: The retinoblastoma binding protein RBP2 (KDM5A) is a histone demethylase that promotes cell growth in many human cancers. A series of functional experiments were conducted to explore the role of miR-421/KDM5A in ovarian cancer cells and their underlying molecular mechanisms. MATERIALS AND METHODS: Public microarray databases were analyzed to assess KDM5A and miR-421 expression in ovarian cancer. KDM5A was predicted to be a target of miR-421 using software analysis. The expression of the miR-421/KDM5A regulatory axis in ovarian cancer and the mechanisms of its effects on proliferation, migration, and invasion of ovarian cancer cell lines were investigated. RESULTS: Compared with normal ovarian tissues, the expression of KDM5A mRNA and protein was elevated (P<0.05), and miR-421 expression was reduced in ovarian cancer tissue (P<0.05). miR-421 was found to bind specifically to the KDM5A gene. Silencing KDM5A or overexpressing miR-421 significantly inhibited proliferation, migration, and invasion of OVCAR-8 and SKOV-3 cells. Similarly, compared with nude mice injected with cells transfected with empty capsids, the in vivo proliferation rate of OVCAR-8 cells after miR-421 overexpression was reduced significantly. CONCLUSION: The miR-421/KDM5A regulatory axis plays an important role in the development and progression of ovarian cancer cells.

Dynamics of HBV surface antigen related end points in chronic hepatitis B infection: a systematic review and meta-analysis.

BACKGROUND: In chronic hepatitis B (CHB) treatment, hepatitis B surface antigen (HBsAg) is regarded as a promising clinical end point associated with long-term clinical outcomes. We performed a meta-analysis to characterize the dynamics and influencing factors of HBsAg. METHODS: Literature search was conducted through PubMed from January 1995 to May 2015 for papers reporting HBsAg in patients receiving various antiviral treatments. We conducted weighted linear regression to select for potential influencing factors on maximum HBsAg loss percentage, and subgroup analysis to calculate the pooled estimates of maximum HBsAg loss and seroconversion percentage following treatment of interferon (IFN), nucleoside analogue (NUC) or combination therapies (NUC+IFN), respectively. Study heterogeneity was assessed through sensitivity test and I-square statistics. RESULTS: We collected data from 24 papers involving 6,674 adult CHB patients. In most studies, average HBsAg level decreased during treatment but relapsed after treatment cessation, while HBsAg loss or seroconversion percentage continued to increase or remained stable after treatment cessation. No strong relationship was observed between maximum HBsAg change and its baseline level. The pooled estimates of maximum HBsAg loss percentage for IFN (5.3%, 2.7-7.9%) and NUC+IFN (5.2%, 3.1-7.4%) were significantly higher than that of NUC (0.93%, 0.29-1.6%). Higher maximum HBsAg loss percentage is associated with longer peak time. Pooled maximum HBsAg seroconversion percentage estimates were 1.6%, 0.56% and 6.2% for IFN, NUC and NUC+IFN. CONCLUSIONS: With respect to HBsAg lowering, this meta-analysis confirmed the importance of longer treatment duration and addition of IFN, which revealed the potential value of immune-based therapies.

The association between maternal nicotine exposure and adipose angiogenesis in female rat offspring: A mechanism of adipose tissue function changes.

Maternal smoking during pregnancy and lactation is associated with increased fat mass in the offspring, but the mechanism by which this occurs is not fully understood. Our study focused on the relationships among maternal nicotine exposure, adipose angiogenesis and adipose tissue function in female offspring. Pregnant rats were randomly assigned to nicotine or control groups. Microvascular density, lipid metabolism and α7nAChR-Egr1-FGF2 signaling pathway genes/proteins were tested in 4-, 12- and 26-week female offspring. In vitro, nicotine concentration- and time-response experiments were conducted in 3T3-L1. Lipid metabolism and α7nAChR-Egr1-FGF2 signaling pathway genes/proteins were tested. The conditioned media of differentiated 3T3-L1 treated with nicotine were used to observe tube formation in human umbilical vein endothelial cells (HUVECs). Nicotine-exposed females presented higher adipose microvascular density. The gene expression of α7nAChR, Egr1 and FGF2 was significantly increased in gonadal white adipose tissue (gWAT) and inguinal subcutaneous WAT (igSWAT) of nicotine-exposed females at 4 weeks of age. The protein expression of α7nAChR, Egr1 and FGF2 was increased in gWAT and igSWAT of nicotine-exposed females at 4 weeks of age, and increased in gWAT at 26 weeks. In vitro, nicotine increased the expression of lipid metabolism and α7nAChR-Egr1-FGF2 signaling pathway genes/proteins in a concentration- and time-dependent manner. In the tube formation experiment, adipocytes affected by nicotine promoted HUVEC angiogenesis. Therefore, maternal nicotine exposure promoted the early angiogenesis of adipose tissue via the α7nAChR-Egr1-FGF2 signaling pathway, and this angiogenesis mechanism was associated with increased adipogenesis in adipose tissue of female offspring.

LncRNA GAS5 confers the radio sensitivity of cervical cancer cells via regulating miR-106b/IER3 axis.

OBJECTIVE: The aim of the study was to investigate the biological role of growth arrest special 5 (GAS5) in the radio sensitivity of cervical cancer (CC). METHODS: The expressions of GAS5, miR-106b and immediate early response 3 (IER3) were detected in CC tissues and CC cell lines. RNA immunoprecipitation and RNA pull-down assays were performed to test the interaction of GAS5 and miR-106b. Dual-luciferase reporter assay was used to detect the regulatory relationship between miR-106b and IER3. The nude mouse model of CC was established for verifying the effects of GAS5 on the resistance of CC to radiation therapy in vivo. RESULTS: GAS5 and IER3 were low expressed in the radio-resistant human CC tissues and SiHa cells, while miR-106b expression was highly expressed. Overexpression of IER3 or GAS5 enhanced radio-sensitivity in SiHa cells, while knockdown of IER3 or GAS5 decreased radio-sensitivity in ME180 cells. Moreover, GAS5 served as a miR-106b sponge, and miR-106b negatively regulated IER3 expression. Besides, GAS5 could regulate IER3 expression through miR-106b, and GAS5 enhanced the radio-sensitivity in CC cells through inhibiting miR-106b both in vitro and in vivo. CONCLUSION: Overexpression of GAS5 enhanced the sensitivity of CC cells to radiation treatment via up-regulating IER3 through miR-106b.

MicroRNA-338-3p suppresses ovarian cancer cells growth and metastasis: implication of Wnt/catenin beta and MEK/ERK signaling pathways.

BACKGROUND: Downregulation of microRNA-338-3p (miR-338-3p) was detected in many malignant tumors, which indicated miR-338-3p might serve as a role of antioncogene in those cancers. The present study aimed to explore the roles of miR-338-3p in the growth and metastasis of ovarian cancer cells and elaborate the underlying possible molecular mechanism. METHODS: Multiply biomedical databases query and KEGG pathway enrichment assay were used to infilter possible target genes and downstream pathways regulated by miR-338-3p. Overexpression miR-338-3p lentiviral vectors were transfected into ovarian cancer OVCAR-3 and OVCAR-8 cells, cell proliferation, migration and invasion were analyzed by MTT, colony formation, transwell, Matrigel assay and xenograft mouse model. One 3'-untranslated regions (UTRs) binding target gene of miR-338-3p, MACC1 (MET transcriptional regulator MACC1), and its regulated gene MET and downstream signaling pathway activities were examined by western blot. RESULTS: Biomedical databases query indicated that miR-338-3p could target MACC1 gene and regulate Met, downstream Wnt/Catenin beta and MEK/ERK pathways. Rescue of miR-338-3p could inhibit the proliferation, migration and invasion of ovarian cancer cells, and suppress the growth and metastasis of xenograft tumor. Restoration of miR-338-3p could attenuate MACC1 and Met overexpression induced growth, epithelial to mesenchymal transition (EMT) and activities of Wnt/Catenin beta and MEK/ERK signaling in vitro and in vivo. CONCLUSIONS: The present data indicated that restoration of miR-338-3p could suppress the growth and metastasis of ovarian cancer cells, which might due to the inhibition of proliferation and EMT induced by MACC1, Met and its downstream Wnt/Catenin beta and MEK/ERK signaling pathways.

Age Differences in the Relationship between Secondhand Smoke Exposure and Risk of Metabolic Syndrome: A Meta-Analysis.

Secondhand smoke (SHS), a common environmental exposure factor, has become a serious public health problem. Metabolic syndrome is another worldwide clinical challenge. Our study tried to determine the age differences in the relationship between SHS and the risk of metabolic syndrome. Studies were searched in PubMed and Web of Science from 11 November to 30 November 2018. Eighteen studies were finally included based on inclusion and exclusion criteria. The relationship between SHS and the risk indicators of metabolic syndrome was analyzed. The weighted mean difference (WMD) of fasting plasma glucose (FPG), insulin, body mass index (BMI), and waist circumference (WC), and the standard mean difference (SMD) of total cholesterol, triglycerides, and low- and high-density lipoprotein-cholesterol (LDL-C, HDL-C) were calculated in a meta-analysis. SHS was positively associated with the level of insulin and WC. According to the subgroup analysis based on age difference, SHS was positively associated with FPG in the upper age group, and positively associated with LDL-C and negatively associated with HDL-C in the lower age group. BMI showed a more obvious positive correlation in the adults group than in the children and the teenagers group. In conclusion, the association of metabolic syndrome with SHS varies with age. When exposed to SHS, older people may be more susceptible to glucose metabolic disorder, but younger people may be more susceptible to lipid metabolic disorder.