Prevalence and determinants of constipation in children in Asia: a systematic review and meta-analysis.

Background: Constipation is prevalent worldwide, significantly increasing healthcare costs and diminishing the quality of life in children affected. Current studies have yielded mixed results regarding the factors associated with constipation, and mainly focusing on patients outside of Asia. Moreover, most of these studies lack focus on the paediatric population. This study aimed to identify the prevalence and associated factors of constipation among children in Asia. Methods: In this systematic review and meta-analysis, we systematically searched PubMed, Scopus, and Cochrane for cohort and cross-sectional studies published from database inception up to October 12, 2022, and continued with manual searching until September 2, 2023. Eligible studies were those that included children in Asia aged 0-18 years old suffering from idiopathic constipation, with prevalence value provided in the English abstract. The analysis included clinical and general population. Children with organic constipation, who had undergone gastrointestinal surgery, or with congenital defects were excluded, as these factors affect the incidence of constipation. Data included in the analysis were extracted from published reports only. The extracted data were pooled using random-effects model to analyse the prevalence of constipation in children in Asia. This study is registered with PROSPERO, CRD42022367122. Findings: Out of 4410 systematically searched studies and 36 manually searched ones, a total of 50 studies were included in the final analysis, encompassing data from 311,660 children residing in Asia. The pooled prevalence of constipation was 12.0% (95% CI 9.3-14.6%, I2 = 99.8%). There was no significant difference in constipation prevalence observed by sex and geographical location. Nonetheless, adolescents and children aged 1-9 years exhibited a significantly higher prevalence constipation compared to infants (p < 0.0001) Additionally, significant differences in constipation rates were observed across various diagnostic methods, population sources, and mental health conditions. Interpretation: Despite the high heterogeneity resulting from varying diagnostic tools or definitions used among studies, our review adds to the literature on constipation among children in Asia. It reveals a notably high prevalence of constipation in this demographic. Diagnostic methods, age, and compromised mental health emerged as significant influencers of constipation among children in Asia, highlighting potential strategies to mitigate constipation prevalence in children in Asia. Funding: The National Science and Technology Council, Taiwan.

Efficacy of laparoscopic inguinal hernia in day surgery mode and inpatient surgery mode in China: A meta-analysis.

BACKGROUND: In China, laparoscopic inguinal hernia repair (LIHR) under the day surgery mode (DSM) has developed rapidly as an important surgical method for inguinal hernia repair, and it has unique advantages in many aspects. Compared with inpatient surgery mode (ISM), there are some differences in intraoperative and postoperative related indicators, hospitalization costs, and patient satisfaction. Many studies have shown that LIHR in DSM can significantly shorten hospital stay, effectively reduce hospitalization costs, and improve patient satisfaction. Accordingly, this study aimed to compare the differences in intraoperative and postoperative related indicators, hospitalization costs, and patient satisfaction of LIHR between DSM and ISM in China. METHODS: The PubMed/Medline, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wan Fang databases were searched for randomized controlled trials, cohort studies from the establishment of the database to July 1, 2022. Odds ratio (OR), mean difference, standardized mean difference (SMD), and 95% confidence interval were selected as the effect scale indices for the evaluation of the difference in hospitalization costs, hospital stay, operation time, recovery time, complications, and patient satisfaction. All of these were compared using RevMan 5.3 Software (The Cochrane Collaboration, Copenhagen, Denmark). RESULTS: Nine studies involving 1176 patients, 590 in the DSM group and 586 in the ISM group, were included. The hospital stay (d) (SMD = -7.27, 95% confidence interval, CI: -8.68 to -5.87, P  < .001), hospitalization costs (SMD = -7.89, 95% CI: -10.25 to -5.53, P  < .001) in DSM group were significantly lower than the ISM group. Additionally, the patient dissatisfaction (OR = 0.05, 95% CI: 0.01-0.17, P < .001) in DSM group was significantly lower than the ISM group. Nevertheless, no significant differences were found in the operation time (minute) (mean difference = -0.32, 95% CI: -1.78 to 1.14, P = .67), recovery time (h) (SMD = -3.27, 95% CI: -6.95 to 0.41, P  = .08), and postoperative complications (OR = 0.80, 95% CI: 0.47-1.36, P = .41) between the 2 groups. CONCLUSION: In China, compared with ISM, LIHR under DSM can significantly shorten hospital stay, greatly reduce hospitalization costs, and significantly improve patient satisfaction. There were no significant differences in operation time, recovery time and postoperative complications.

Saikosaponin D alleviates cancer cachexia by directly inhibiting STAT3.

Cancer cachexia is a metabolic syndrome that is characterized by progressive loss of skeletal muscle mass, and effective therapeutics have yet to be developed. Saikosaponin D (SSD), a major bioactive component of Radix Bupleuri, exhibits antiinflammatory, anti-tumor, anti-oxidant, anti-viral, and hepatoprotective effects. In this study, we demonstrated that SSD is a promising agent for the treatment of cancer cachexia. SSD could alleviate TCM-induced myotube atrophy and inhibit the expression of E3 ubiquitin ligases muscle RING-finger containing protein-1 (MuRF1) and muscle atrophy Fbox protein (Atrogin-1/MAFbx) in vitro. Moreover, SSD suppressed the progression of cancer cachexia, with significant improvements in the loss of body weight, gastrocnemius muscle, and tibialis anterior muscle mass in vivo. Mechanism investigations demonstrated that SSD could directly bind to STAT3 and specifically inhibit its phosphorylation as well as its transcriptional activity. Overexpression of STAT3 partially abolished the inhibitory effect of SSD on myotube atrophy, indicating that the therapeutic effect of SSD was attributed to STAT3 inhibition. These findings provide novel strategies for treatment of cancer cachexia by targeting STAT3, and SSD may be a promising drug candidate for cancer cachexia.

Curative effect of different drainage methods on laparoscopic inguinal hernia repair: A meta-analysis.

BACKGROUND: Laparoscopic inguinal hernia repair has developed rapidly as an important surgical method for inguinal hernia repair; however, postoperative complications, especially postoperative seroma, are becoming an important factor hindering its development. Many studies have shown that placing a negative-pressure drainage tube in the preperitoneal space can effectively reduce postoperative seromas. Accordingly, this study aimed to compare differences in postoperative seroma between surgical procedures with drainage tubes (DRG) and those without drainage tubes (nonDRG). METHODS: PubMed/Medline, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched from the establishment of the database to May 1, 2021. Odds ratio (OR), mean difference (MD), standardized mean difference (SMD), and 95% confidence interval (CI) were selected as the effect scale indices for the evaluation of the difference in seroma, operation time, hospital stay time, blood loss, and recovery time. All of these were compared using RevMan 5.3 Software. RESULTS: Sixteen studies involving 4369 patients, 2856 in the DRG group and 1513 in the nonDRG group, were included. The incidence of seroma in the DRG group was lower than that in the nonDRG group (OR = 0.16, 95% CI: 0.07-0.35, P < .001). Additionally, the operation time (min) in the DRG group was longer than that in the nonDRG group (MD = 3.67, 95% CI: 2.18-5.17, P < .001). Nevertheless, no significant differences were found in hospital stay (days) (SMD = 0.22, 95% CI: -0.10-0.54, P = .17), blood loss (mL) (MD = 0.28, 95% CI: -0.14-0.69, P = .19), and recovery time (h) (SMD = 0.54, 95% CI: -0.60-1.69, P = .35) between the 2 groups. CONCLUSION: Despite the slightly prolonged operation time, negative pressure drainage in the preperitoneal space during laparoscopic inguinal hernia repair can significantly reduce the occurrence of postoperative seroma without increasing blood loss, recovery, and hospital stay.

Hypermethylation of TMEM240 predicts poor hormone therapy response and disease progression in breast cancer.

BACKGROUND: Approximately 25% of patients with early-stage breast cancer experience cancer progression throughout the disease course. Alterations in TMEM240 in breast cancer were identified and investigated to monitor treatment response and disease progression. METHODS: Circulating methylated TMEM240 in the plasma of breast cancer patients was used to monitor treatment response and disease progression. The Cancer Genome Atlas (TCGA) data in Western countries and Illumina methylation arrays in Taiwanese breast cancer patients were used to identify novel hypermethylated CpG sites and genes related to poor hormone therapy response. Quantitative methylation-specific PCR (QMSP), real-time reverse transcription PCR, and immunohistochemical analyses were performed to measure DNA methylation and mRNA and protein expression levels in 394 samples from Taiwanese and Korean breast cancer patients. TMEM240 gene manipulation, viability, migration assays, RNA-seq, and MetaCore were performed to determine its biological functions and relationship to hormone drug treatment response in breast cancer cells. RESULTS: Aberrant methylated TMEM240 was identified in breast cancer patients with poor hormone therapy response using genome-wide methylation analysis in the Taiwan and TCGA breast cancer cohorts. A cell model showed that TMEM240, which is localized to the cell membrane and cytoplasm, represses breast cancer cell proliferation and migration and regulates the expression levels of enzymes involved in estrone and estradiol metabolism. TMEM240 protein expression was observed in normal breast tissues but was not detected in 88.2% (67/76) of breast tumors and in 90.0% (9/10) of metastatic tumors from breast cancer patients. QMSP revealed that in 54.5% (55/101) of Taiwanese breast cancer patients, the methylation level of TMEM240 was at least twofold higher in tumor tissues than in matched normal breast tissues. Patients with hypermethylation of TMEM240 had poor 10-year overall survival (p = 0.003) and poor treatment response, especially hormone therapy response (p < 0.001). Circulating methylated TMEM240 dramatically and gradually decreased and then diminished in patients without disease progression, whereas it returned and its levels in plasma rose again in patients with disease progression. Prediction of disease progression based on circulating methylated TMEM240 was found to have 87.5% sensitivity, 93.1% specificity, and 90.2% accuracy. CONCLUSIONS: Hypermethylation of TMEM240 is a potential biomarker for treatment response and disease progression monitoring in breast cancer.

Importance of Gedunin in Antagonizing Rheumatoid Arthritis via Activating the Nrf2/ARE Signaling.

Objective: This study assessed the anti-arthritic effect and protection of Gedunin (GDN) on joint tissues and revealed the possible mechanism in suppressing rheumatoid arthritis (RA). Methods: LPS-induced macrophages and TNF-α-stimulated synovial fibroblasts (MH7A) or IL-1ß-stimulated primary rheumatoid arthritis synovial fibroblasts (RASFs) were used to evaluate the antiinflammatory effect of GDN. In addition, CIA-induced arthritis was employed here to evaluate the anti-arthritic effect. MTT and BRDU assays were utilized to evaluate the cell viability and proliferation, Q-PCR was conducted to detect the mRNA expression of cytokines, FACS was adopted to monitor ROS production, while western blotting (WB) and siRNA interference were applied in confirming the anti-arthritic effects of GDN via the Nrf2 signaling. Results. In vitro, cell viability was inhibited in macrophages and MH7A cells, but not in RASFs; but the proliferation of RASFs was significantly suppressed in time- and dose-dependent manners. GDN suppressed cytokine levels in LPS-stimulated macrophages and TNF-α-stimulated MH7A cells or RASFs. GDN suppressed ROS expression. Furthermore, GDN treatment notably dose-dependently decreased the mRNA and protein expression of iNOS in LPS-induced macrophages. sip62 interference results showed that GDN cause the less expression of HO-1 and Keap1 and also fail to inhibit cytokines after sip62 interference. In vivo, GDN effectively inhibited paw swelling, arthritis score, and arthritis incidence and cytokines. Conclusions: Our study suggested that GDN exhibited strong antagonistic effect on arthritis both in vitro and in vivo via activation of Nrf2 signaling. Our work will provide a promising therapeutic strategy for RA.

Will climate warming of terrestrial ecosystem contribute to increase soil greenhouse gas fluxes in plot experiment? A global meta-analysis.

One of the main manifestations of global climate change is its profound impact on the emission of greenhouse gases from terrestrial soil. Numerous field warming experiments have explored the effects of different temperature rise intensities and durations on soil greenhouse gas fluxes in the growing season of different terrestrial ecosystems. However, the results were inconsistent due to the variations in vegetation, soil, and climatic conditions in different ecosystems. In the present work, we carried meta-analysis to synthesize 99 datasets from 52 field warming experiments in growing seasons of terrestrial ecosystems to evaluate the response of soil greenhouse gas fluxes to global warming. The results showed that warming greatly stimulated soil CO2 in temperate forest and farmland by 12.64% and 25.57%, respectively, significantly increased soil N2O emissions in grassland (27.23%), farmland (44.33%), and shrubland (223.36%), and increased soil CH4 uptake by 57.81% in grasslands. However, no significant impact on the greenhouse gas fluxes in other ecosystems was observed. Generally, short-and medium-term (≤ 3 years) warming can promote soil greenhouse gas fluxes. Also, low temperature and low-medium temperature (≤ 2 °C) significantly promoted N2O emission and CH4 absorption, and medium temperature (2-4 °C) considerably assisted CO2 flux, but high temperature (> 4 °C) had no significant effect on greenhouse gas flux. Our results demonstrated that soil greenhouse gas fluxes in terrestrial ecosystems during the growing season do not increase linearly with the increasing climate warming, and it is still uncertain whether there is acclimatization to long-term climate warming.

Neobaicalein Inhibits Th17 Cell Differentiation Resulting in Recovery of Th17/Treg Ratio through Blocking STAT3 Signaling Activation.

Huangqin is the dried root of Scutellaria baicalensis Georgi, which has been widely utilized for heat-clearing (Qingre) and dewetting (Zaoshi), heat-killed (Xiehuo) and detoxifying (Jiedu) in the concept of Traditional Chinese Medicine and is used for treating inflammation and cancer in clinical formulas. Neobaicalein (NEO) is of flavonoid isolated from Huangqin and has been reported to possess prominent anti-inflammatory effects in published work. Th17/Treg balance shift to Th17 cells is an essential reason for autoimmune inflammatory diseases. However, the role NEO plays in Th17 and Treg and the underlying mechanism has not been elucidated yet. Network pharmacology-based study revealed that NEO predominantly regulated IL-17 signaling pathway. Moreover, our result shown that NEO (3-30 µmol/L) down-regulated Th17 differentiation and cellular supernatant and intracellular IL-17A level and tumor necrosis factor α production in a concentration-dependent manner. The further mechanism research revealed that NEO also specifically inhibited phosphorylation of STAT3(Tyr725) and STAT4 (Y693) without influence on activation of STAT5 and STAT6 in splenocytes. Immunofluorescence results illuminated that NEO effectively blocked STAT3 translocated into nucleus. Interestingly, NEO at appreciated dose could only inhibit Th17 cell differentiation and have no effect on Treg differentiation. The present study revealed that NEO effectively inhibited Th17 cell differentiation through specifically blocking the activation of STAT3 signaling without inactivation of STAT5 and STAT6. Additional inhibitory effect on activation of STAT4 by NEO also suggested the potential for antagonism against Th1 differentiation. All work suggested that NEO may be a potential candidate for immunoregulation and treating autoimmune inflammatory diseases through inhibiting immune cell viability and T cell differentiation.

Therapeutic cancer vaccine therapy for acute myeloid leukemia.

Antitumor function of the immune system has been harnessed to eradicate tumor cells as cancer therapy. Therapeutic cancer vaccines aim to help immune cells recognize tumor cells, which are difficult to target owing to immune escape. Many attempts at vaccine designs have been conducted throughout the last decades. In addition, as the advanced understanding of immunosuppressive mechanisms mediated by tumor cells, combining cancer vaccines with other immune therapies seems to be more efficient for cancer treatment. Acute myeloid leukemia (AML) is the most common acute leukemia in adults with poor prognosis. Evidence has shown T-cell-mediated immune responses in AML, which encourages the utility of immune therapies in AML. This review discusses cancer vaccines in AML from vaccine design as well as recent progress in vaccination combination with other immune therapies.

Lay abstract Acute myeloid leukemia (AML) is the most common acute leukemia in adults with poor prognosis. Evidence has shown that the immune system can recognize and eradicate AML cells. Immunotherapy, which aims at enhancing this antitumor function, emerges as a powerful cancer therapy. Cancer vaccine, one of the immunotherapies, helps the immune system recognize tumor cells. The treatment strategy has been explored in AML patients throughout the last decades. This review was a brief introduction of the development and design principle of cancer vaccine in AML. Moreover, we also demonstrated recent progress in vaccination combination with other immune therapies.

Hypermethylation and decreased expression of TMEM240 are potential early-onset biomarkers for colorectal cancer detection, poor prognosis, and early recurrence prediction.

BACKGROUND: Gene silencing by aberrant DNA methylation of promoter regions remains the most dominant phenomenon occurring during tumorigenesis. Improving the early diagnosis, prognosis, and recurrence prediction of colorectal cancer using noninvasive aberrant DNA methylation biomarkers has encouraging potential. The aim of this study is to characterize the DNA methylation of the promoter region of TMEM240, as well as gene expression and its effect on cell biological functions and its applications in early detection and outcome prediction. RESULTS: Highly methylated CpG sites were identified in the TMEM240 gene by Illumina methylation 450K arrays in 26 Taiwanese patient paired samples and 38 paired samples from The Cancer Genome Atlas (TCGA) colorectal cancer dataset. Transient transfection and knockdown of TMEM240 were performed to demonstrate the role of TMEM240 in colorectal cancer cells. The data showed that TMEM240 could lead to G1 cell cycle arrest, repress cancer cell proliferation, and inhibit cancer cell migration. The quantitative methylation-specific real-time polymerase chain reaction (PCR) results revealed that 87.8% (480 of 547) of the colorectal cancer tumors had hypermethylated TMEM240, and this was also found in benign tubular adenomas (55.6%). Circulating cell-free methylated TMEM240 was detected in 13 of 25 (52.0%) Taiwanese colorectal cancer patients but in fewer (28.6%) healthy controls. In 72.0% (85/118) of tissue samples, TMEM240 mRNA expression was lower in Taiwanese CRC tumor tissues than in normal colorectal tissues according to real-time reverse transcription PCR results, and this was also found in benign tubular adenomas (44.4%). The TMEM240 protein was analyzed in South Korean and Chinese CRC patient samples using immunohistochemistry. The results exhibited low protein expression in 91.7% (100/109) of tumors and 75.0% (24/32) of metastatic tumors but exhibited high expression in 75.0% (6/8) of normal colon tissues. Multivariate Cox proportional hazards regression analysis found that mRNA expression of TMEM240 was significantly associated with overall, cancer-specific, and recurrence-free survival (p = 0.012, 0.007, and 0.022, respectively). CONCLUSIONS: Alterations in TMEM240 are commonly found in Western and Asian populations and can potentially be used for early prediction and as poor prognosis and early-recurrence biomarkers in colorectal cancer.

Targeting the Cell Membrane by Charge-Reversal Amphiphilic Pillar[5]arene for the Selective Killing of Cancer Cells.

A charge-reversal amphiphilic pillar[5]arene, P5NH-DCA, bearing 10 charge-reversal headgroups is reported. It targets the cell membrane of cancer cells and selectively destroys the cancer cells by disrupting the membrane. In the acidic tumor microenvironment, the headgroup charge of P5NH-DCA reversed from negative to positive owing to hydrolysis of the acid-labile amide group. The hydrolyzed product bearing multiple positive charges can bind to the cell membrane and then disrupt the membrane of cancer cells with high efficiency. However, under the neutral microenvironment of healthy cells, the negatively charged P5NH-DCA remains stable and the cytotoxicity is considerably reduced. The strategy killing the cancer cells by membrane disruption may represent a new route of cancer chemotherapy.

Bendable Network Built with Ultralong Silica Nanowires as a Stable Separator for High-Safety and High-Power Lithium-Metal Batteries.

Separators are key safety components for electrochemical energy storage systems. However, the intrinsic poor wettability with electrolyte and low thermal stability of commercial polyolefin separators cannot meet the requirements of the ever-expanding market for high-power, high-energy, and high-safety power systems, such as lithium-metal, lithium-sulfur, and lithium-ion batteries. In this study, scalable bendable networks built with ultralong silica nanowires (SNs) are developed as stable separators for both high-safety and high-power lithium-metal batteries. The three-dimensional porous nature (porosity of 73%) and the polar surface of the obtained SNs separators endue a much better electrolyte wettability, larger electrolyte uptake ratio (325%), higher electrolyte retention ratio (63%), and ∼7 times higher ionic conductivity than that of commercial polypropylene (PP) separators. Moreover, the pore-rich structure of the SNs separator can aid in evenly distributing lithium and, in turn, suppress the uncontrollable growth of lithium dendrites to a certain degree. Furthermore, the pure inorganic structure endows the SNs separators with excellent chemical and electrochemical stabilities even at elevated temperatures, as well as excellent thermal stability up to 700 °C. This work underpins the utilization of SNs separators as a rational choice for developing high-performance batteries with a metallic lithium anode.

lncRNA MEG3 inhibits the growth of hepatocellular carcinoma cells by sponging miR-9-5p to upregulate SOX11.

The long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3), a tumor suppressor, is critical for the carcinogenesis and progression of different cancers, including hepatocellular carcinoma (HCC). To date, the roles of lncRNA MEG3 in HCC are not well illustrated. Therefore, this study used western blot and qRT-PCR to evaluate the expression of MEG3, miR-9-5p, and Sex determining Region Y-related HMG-box 11 (SOX11) in HCC tissues and cell lines. RNA pull-down and luciferase reporter assay were used to evaluate these molecular interactions. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry detected the viability and apoptosis of HCC cells, respectively. The results showed that MEG3 and SOX11 were poorly expressed but miR-9-5p was highly expressed in HCC. The expression levels of these molecules suggested a negative correlation between MEG3 and miR-9-5p and a positive correlation with SOX11, confirmed by Pearson's correlation analysis and biology experiments. Furthermore, MEG3 could combine with miR-9-5p, and SOX11 was a direct target of miR-9-5p. Moreover, MEG3 over-expression promoted cell apoptosis and growth inhibition in HCC cells through sponging miR-9-5p to up-regulate SOX11. Therefore, the interactions among MEG3, miR-9-5p, and SOX11 might offer a novel insight for understanding HCC pathogeny and provide potential diagnostic markers and therapeutic targets for HCC.

Pancreatic fistula after pancreaticoduodenectomy: Risk factors and preventive strategies.

PURPOSE: Postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) is a worrisome and life-threatening complication. This study aimed to investigate the risk factors and preventive strategies for POPF after PD. MATERIALS AND METHODS: We retrospectively reviewed 301 consecutive patients who underwent PD at our hospitals between January 2011 and December 2017. We analyzed the pancreatic fistula rate according to the clinical characteristics, pathologic and laboratory findings, and the anastomotic methods and summarized the prevention measures. RESULTS: Postoperative morbidities included pancreatic leakage in 10.30% (31/301), delayed gastric emptying in 22.92% (69/301), abdominal infection in 6.98% (21/301), post-PD hemorrhage in 4.65% (14/301), and bile leakage in 4.98% (15/301), and the mortality rate was 2.33% (7/301). POPF was the most prominent factor for preoperative morbidity. Significant risk factors for pancreatic fistula were a soft pancreas, small pancreatic duct, tumor location, and interrupted anastomosis. Of these, soft texture, pancreatic duct <4 mm, and end-to-end anastomosis through hand suture closure were independent risk factors on multivariate analysis, while interrupted anastomosis, internal stent, and somatostatin use were risk factors in the high-risk pancreas subgroup. CONCLUSIONS: Our study demonstrated that pancreatic fistula is related to a soft texture and small pancreatic duct. The surgeon must consider these risk factors when performing PD. Thus, we propose a risk- and indication-adapted choice of anastomosis or an individualized approach for the pancreatic remnant to reduce the pancreatic fistula rate.

lncRNA MEG3 inhibits the growth of hepatocellular carcinoma cells by sponging miR-9-5p to upregulate SOX11

The long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3), a tumor suppressor, is critical for the carcinogenesis and progression of different cancers, including hepatocellular carcinoma (HCC). To date, the roles of lncRNA MEG3 in HCC are not well illustrated. Therefore, this study used western blot and qRT-PCR to evaluate the expression of MEG3, miR-9-5p, and Sex determining Region Y-related HMG-box 11 (SOX11) in HCC tissues and cell lines. RNA pull-down and luciferase reporter assay were used to evaluate these molecular interactions. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry detected the viability and apoptosis of HCC cells, respectively. The results showed that MEG3 and SOX11 were poorly expressed but miR-9-5p was highly expressed in HCC. The expression levels of these molecules suggested a negative correlation between MEG3 and miR-9-5p and a positive correlation with SOX11, confirmed by Pearson's correlation analysis and biology experiments. Furthermore, MEG3 could combine with miR-9-5p, and SOX11 was a direct target of miR-9-5p. Moreover, MEG3 over-expression promoted cell apoptosis and growth inhibition in HCC cells through sponging miR-9-5p to up-regulate SOX11. Therefore, the interactions among MEG3, miR-9-5p, and SOX11 might offer a novel insight for understanding HCC pathogeny and provide potential diagnostic markers and therapeutic targets for HCC.

A synthetic channel that efficiently inserts into mammalian cell membranes and destroys cancer cells.

Despite the fact that a large number of synthetic channels have been developed in the last three decades, few of them can function in mammalian cell membranes because of their weak membrane insertion abilities. This study describes a tubular molecule with terminal positively charged amino groups that displays a strong ability to insert into lipid bilayers composed of phosphatidylcholine and consequently forming unimolecular transmembrane channels. It has been demonstrated that the insertion of the channel into the phosphatidylcholine bilayers was driven by the electrostatic interaction between the positively charged amino groups of the channel molecules and the negatively charged phosphate groups of the lipid molecules. The high affinity of the channels for lipid bilayers led to efficient mammalian cell membrane insertion. The channels showed high effective activity against HepG2 cancer cells at concentrations above 5.1 µM.

[Effect of Compound Zhajin Granule on Toll-like Receptor 4 Signaling Pathway in Nonalcoholic Steatohepatitis Mice].

OBJECTIVE: To observe the effect of Compound Zhajin Granule (CZG) on Toll-like re-ceptor 4 (TLR4) signaling pathway in high-fructose corn syrup induced NASH mice. METHODS: Thirty 6-week-old male C3H mice were divided into the high fat and high fructose (HFHFr) group (n = 20) and the control group (n = 10) according to body weight. Mice in the HFHFr group ate high fat diet and drank 20% fructose water, while those in the control group ate common diet and drank common water. After 8 weeks mice in the HFHFr group were divided into two group according to body weight, the HFHFr group and the CZG group, 10 in each group. Mice in the CZG group were fed with high fat forage and 20% fructose water, and administered with 50 mL/kg 12. 8% CZG (prepared by hawthorn, Radix Curcumae, Alisma Orientale, Fritillaria Thunbergii, Silybum Marianum, peach seed in the ratio of 3:1.5:1.5:2:1.5:2:1) by gastrogavage. Mice in the HFHFr group were fed in the same way and daily administered with equal volume of distilled water by gastrogavage. Sixteen weeks later all mice were sacrificed. Body weight, liver wet weight, liver function, and lipid metabolism were detected. Pathological changes of liver tissues were assessed by HE staining, oil red O staining, and Masson staining. Expressions of TLR4, myeloid differentiation factor 88 (MyD88), tumor necrosis factor-alpha (TNF-α) were detected using immunohistochemical staining and real-time fluorescent quantitative PCR. RESULTS: Body weight, alanine aminotransferase (ALT), aspartate aminotransferase (AST) were obviously lower in the CZG group than in the HFHFr group (P < 0.05); oil red O stained area and density were decreased more in the CZG group than in the control group. HE staining showed ballooning inflammation was reduced more in the CZG group than in the HFHFr group. Masson staining was negative. Positive rates of TLR4 and MyD88 and mRNA expressions were significantly lower in the CZG group than in the HFHFr group (all P < 0.05). CONCLUSION: CZG could significantly inhibit TLR4 signaling pathway of liver in NASH mice.

Optoelectronic Properties and the Electrical Stability of Ga-Doped ZnO Thin Films Prepared via Radio Frequency Sputtering.

In this work, Ga-doped ZnO (GZO) thin films were deposited via radio frequency sputtering at room temperature. The influence of the Ga content on the film's optoelectronic properties as well as the film's electrical stability were investigated. The results showed that the film's crystallinity degraded with increasing Ga content. The film's conductivity was first enhanced due to the replacement of Zn2+ by Ga3+ before decreasing due to the separation of neutralized gallium atoms from the ZnO lattice. When the Ga content increased to 15.52 at %, the film's conductivity improved again. Furthermore, all films presented an average transmittance exceeding 80% in the visible region. Regarding the film's electrical stability, GZO thermally treated below 200 °C exhibited no significant deterioration in electrical properties, but such treatment over 200 °C greatly reduced the film's conductivity. In normal atmospheric conditions, the conductivity of GZO films remained very stable at ambient temperature for more than 240 days.

Inhibition of invasion and metastasis of human liver cancer HCCLM3 cells by portulacerebroside A.

CONTEXT: Portulacerebroside A (PCA) is a novel cerebroside compound isolated from Portulaca oleracea L. (Portulacaceae), an edible and medicinal plant distributed in the temperate and tropical zones worldwide. OBJECTIVE: This study investigates the effects of PCA in human liver cancer HCCLM3 cells on metastasis and invasion. MATERIALS AND METHODS: After the cells were treated with PCA (2.5, 5, and 10 µg/ml) for 6, 12, 24, or 48 h, adhesion, transwell invasion, and scratch tests were conducted and cell functions were evaluated. Western blot and FQ-RT-PCR assays explored the mechanism of PCA-inhibited invasion and metastasis in the cells. RESULTS: The adhesion rate of the cells was suppressed at 0.5 h (79.4 ± 1.0, 68.7 ± 1.3, and 58.1 ± 1.3%, versus 100 ± 1.5% in the control), 1 h (78.2 ± 1.2, 70.9 ± 1.6, and 55.4 ± 1.9%, versus 100 ± 1.2% in the control), and 1.5 h (71.6 ± 1.1, 62.3 ± 0.9, and 50.4 ± 0.9%, versus 100 ± 1.1% in the control). The 24 h invasion ability was decreased (356.6 ± 11.2, 204.0 ± 17.6, and 113.0 ± 9.5%, versus 443.6 ± 15.4% in the control). The migration capability was also restrained by PCA for 24 h (324.8 ± 25.4, 250.4 ± 21.0, and 126.3 ± 10.1, versus 381.6 ± 30.6 in the control) and 48 h (470.3 ± 34.3, 404.0 ± 19.7, and 201.0 ± 15.4, versus 752.0 ± 63.6 in the control). There was an increase in the mRNA and protein expression levels of TIMP-2 and nm23-H1, inhibition in the mRNA expression of MTA1, MMP-2, and MMP-9, and suppression in the protein expression of MTA1, RhoA, Rac1/Cdc42, MMP-2, but not RhoC and MMP-9. CONCLUSION: PCA suppresses the invasion and metastasis of HCCLM3 cells possibly by modulation of the mRNA and protein expression of related parameters. This is the first study to reveal a new potential therapeutic application of PCA in antimetastatic therapy for liver cancer.

Triggering of p38 MAPK and JNK signaling is important for oleanolic acid-induced apoptosis via the mitochondrial death pathway in hypertrophic scar fibroblasts.

Hypertrophic scarring is characterized by collagen overproduction and excessive deposition of extracellular matrix. No consensus arises currently about the best therapeutics to produce complete and permanent improvement of scars with few side effects. In the present study, the mechanism of oleanolic acid (OA)-induced apoptosis in hypertrophic scar fibroblasts (HSFs) was investigated for the first time. OA activated the protein phosphorylation of p38 MAPK and JNK but not ERK. OA did not antagonize the inhibitory effects of SB203580 on p38 MAPK pathway activity but sharply enhanced JNK phosphorylation when HSFs were pretreated with SB203580. Similarly, the inhibition of JNK signal pathway activation by pretreatment with SP600125 facilitated the protein phosphorylation of p38 MAPK caused by OA. Inhibition of p38 MAPK and/or JNK by inhibitors significantly enhanced cell viability and OA only partially depressed the increased cell viability. Moreover, OA increased Bax translocation, MMP loss, mitochondrial cytochrome c and AIF release, Bax and caspase-3 protein expression and the ratio of Bax to Bcl-2, decreased Bcl-2 protein expression, and elevated the mRNA expression of Apaf-1, caspase-9, and capase-3. These results suggest that OA elicits apoptosis through triggering of p38 MAPK and JNK signaling and activation of the mitochondrial death pathway. OA might be a good and useful natural drug against hypertrophic scars.