The association between Helicobacter pylori and gastrointestinal disorders during pregnancy: A Multicenter retrospective study.

BACKGROUND: Some gastrointestinal disorders may be associated with Helicobacter pylori infection, which not only affect maternal health, but may also lead to adverse pregnancy outcomes. We aim to explore the association between H. pylori and gastrointestinal disorders in pregnant women. MATERIALS AND METHODS: In total, 503 patients were retrospectively analyzed and divided into the H. pylori-uninfected group, the H. pylori-infected group, or the H. pylori-eradicated group. We analyzed the influence of H. pylori on gastrointestinal diseases during pregnancy among the groups, as well as the severity, symptoms, laboratory tests of the H. pylori-related diseases. RESULTS: Pregnant women with H. pylori infection had higher risk of nausea and vomiting of pregnancy (NVP) (p < 0.001), severe NVP(p = 0.012), hyperemesis gravidarum (p = 0.027), hematemesis (p = 0.018), hyponatremia (p = 0.033), as well as functional dyspepsia symptoms including epigastric pain (p = 0.004), bloating (p = 0.024), and feeling full quickly in a meal (p = 0.031) compared with those without H. pylori infection. While the prevalence of NVP (p = 0.024), severe NVP (p = 0.009), epigastric pain (p = 0.037), and bloating (p = 0.032) were lower in H. pylori-eradicated pregnant women than in H. pylori-infected women. In addition, pregnant women with H. pylori infection had higher risk of spontaneous preterm birth than whom without H. pylori infection (p = 0.033). CONCLUSIONS: Helicobacter pylori infection was associated with higher risks of NVP, severe NVP, hyperemesis gravidarum, functional dyspepsia, and spontaneous preterm birth in pregnant women.

HBx Modulates Drug Resistance of Sorafenib-Resistant Hepatocellular Carcinoma Cells.

BACKGROUND: Approximately 50% of hepatocellular carcinoma (HCC) arises due to the infection by hepatitis B virus X protein (HBx). Sorafenib, a unique targeted oral kinase inhibitor, is the therapeutic agent of choice for advanced HCC. The mechanism of HBx in drug resistance of sorafenib-resistant HCC cells was evaluated in this study. METHODS: Employing a stepwise increase of the sorafenib content, Hep3B and HepG2 cells were iteratively induced to establish drug-resistant cell lines (Hep3B/R and HepG2/R). The survival rate of Hep3B, Hep3B/R, HepG2, and HepG2/R cells was estimated using the cell counting kit-8 (CCK-8) assay. The IC50 values of sorafenib were calculated, exploring its effects under varying concentrations. The HBx content was quantified via quantitative reverse transcription PCR (RT-qPCR) and Western Blot. HBx overexpression and interfering virus vectors were constructed and transfected into Hep3B/R and HepG2/R cells. Cell viability and metastasis were assessed by colony formation, wound healing, and transwell assays. E-cadherin, N-cadherin, Vimentin, Slug, and Snail content was evaluated via Western Blot. RESULTS: HBx content was significantly elevated in Hep3B/R and HepG2/R subgroups compared to Hep3B and HepG2 subgroups. The proliferation, clonogenicity, invasiveness, and migratory abilities of Hep3B/R and HepG2/R cells in the HBx subgroup were markedly enhanced; E-cadherin content was significantly reduced, whereas the content of N-cadherin, Vimentin, Slug, and Snail was significantly elevated in the HBx subgroup. Conversely, in the sh-HBx subgroup, the proliferation, clonogenicity, invasion, and migration of Hep3B/R and HepG2/R cells were significantly reduced, E-cadherin content was markedly increased, and N-cadherin, Vimentin, Slug, and Snail content was significantly reduced, compared to the sh-negative control (NC) subgroup. CONCLUSIONS: HBx knockout may affect the development of HCC by reducing the proliferation, invasion, and migration of Hep3B/R and HepG2/R cells through the inhibition of Epithelial-Mesenchymal Transition (EMT).

The clinicopathological characteristics of gastric cancer and precancerous conditions in gastric DLBCL and MALT lymphoma patients: a multi-center retrospective study.

OBJECTIVE: The objective of this study is to explore the clinicopathological characteristics of gastric cancer and precancerous conditions in patients with primary gastric lymphoma. METHODS: We analyzed 474 cases of primary gastric lymphoma, mainly DLBCL and MALT, from three clinical centres retrospectively, and compared the clinicopathological parameters of primary gastric lymphoma patients complicated with gastric cancer, precancerous conditions, or with no complications. RESULTS: A total of 5.1% of the patients with primary gastric lymphoma were diagnosed with gastric cancer, including metachronous gastric adenocarcinoma (3.2%) and synchronous gastric adenocarcinoma (1.9%). Of the patients with gastric lymphoma, 14.6% had precancerous conditions including atrophy (14.6%), intestinal metaplasia (8.9%), and low-grade intraepithelial neoplasia (1.9%). Primary gastric lymphoma patients with an ulcerative type (p = 0.009) and Lugano classification stage IIE + IV (p < 0.001) lymphoma had a higher risk of complicating with gastric cancers or precancerous conditions. The rate of infection of Helicobacter pylori (Hp) was 68.4% in patients with primary gastric lymphoma, which was higher in patients with MALT lymphoma (p < 0.001), Lugano classification stage I + II (p < 0.001), and patients complicated with precancerous conditions and gastric cancer (p < 0.001), especially gastric cancer of the intestinal type (p = 0.04). Gastric cancer (95.8%) and precancerous conditions (91.3%) occurred mostly in Hp-infected primary gastric lymphoma patients, with a minor subset of Hp-eradicated patients. Primary gastric lymphoma patients had a higher detection rate of early gastric cancer (25.0%) and a five-year survival rate (40.0%) than the general Chinese population. CONCLUSIONS: Patients with primary gastric lymphoma have a high risk of developing gastric cancer and precancerous conditions, and this risk may be related to Helicobacter pylori infection. Follow-up of primary gastric lymphoma provides an opportunity for the detection of early gastric cancer.Key messages5.1% of the patients with primary gastric lymphoma were diagnosed with gastric cancer.14.6% of the patients with gastric lymphoma had premalignant lesions including atrophy (14.6%), intestinal metaplasia (8.9%), and low-grade intraepithelial neoplasia (1.9%).Primary gastric lymphoma patients complicating with gastric cancer had a higher infection rate of Helicobacter pylori (100.0%), a detection rate of early gastric cancer (25.0%) and a five-year survival rate (40.0%) than the general Chinese population.

Association between sarcopenia and cardiovascular disease among middle-aged and older adults: Findings from the China health and retirement longitudinal study.

BACKGROUND: Little is known about the association between sarcopenia and cardiovascular disease (CVD) among middle-aged and older adults. Using the nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted cross-sectional and longitudinal analyses to investigate the association between sarcopenia status and CVD in middle-aged and older Chinese population. METHODS: The sample comprised 15,137 participants aged at least 45 years from the CHARLS 2015. Sarcopenia status was defined according to the Asian Working Group for Sarcopenia 2019 (AWGS 2019) criteria. CVD was defined as the presence of physician-diagnosed heart disease and/or stroke. A total of 11,863 participants without CVD were recruited from the CHARLS 2015 and were followed up in 2018. Cox proportional hazards regression models were conducted to examine the effect of sarcopenia on CVD. FINDINGS: The pre valence of CVD in total populations, no-sarcopenia, possible sarcopenia and sarcopenia individuals were 12.6% (1905/15,137), 10.0% (1026/10,280), 18.1% (668/3685), 18.0% (211/1172), respectively. Both possible sarcopenia [OR (95% CI): 1.29 (1.13-1.48)] and sarcopenia [1.72 (1.40-2.10)] were associated with CVD in total populations. During the 3.6 years of follow-up, 1,273 cases (10.7%) with incident CVD were identified. In the longitudinal analysis, individuals with the diagnosis of possible sarcopenia (HR:1.22, 95% CI: 1.05-1.43) and sarcopenia participants (HR:1.33, 95% CI: 1.04-1.71) were more likely to have new onset CVD than no-sarcopenia peers. INTERPRETATION: Both possible sarcopenia and sarcopenia, assessed using the AWGS 2019 criteria, were associated with higher CVD risk among middle-aged and older Chinese adults. FUNDING: None.

MicroRNA-876-5p represses the cell proliferation and invasion of colorectal cancer through suppressing YAP signalling via targeting RASAL2.

Aberrant expression of microRNA-876-5p (miR-876-5p) is implicated in the progression of multiple human cancers. However, the potential role of miR-876-5p in colorectal cancer remains poorly understood. The purpose of the current study was to investigate the potential role of miR-876-5p in colorectal cancer. miR-876-5p expression was significantly downregulated in colorectal cancer tissues and cell lines compared with normal controls. Gain-of-function assays revealed that miR-876-5p overexpression effectively repressed the malignant behaviours of colorectal cancer cells, including cell proliferation, colony formation, and invasion. Bioinformatics analysis predicted that RAS protein activator like 2 (RASAL2), a potential oncogene for colorectal cancer, is a putative miR-876-5p target gene. A luciferase reporter assay confirmed that miR-876-5p directly binds to the 3'-untranslated region (UTR) of RASAL2. Furthermore, both RASAL2 messenger RNA (mRNA) and protein expression were negatively modulated by miR-876-5p in colorectal cancer cells. Notably, there was an inverse correlation between miR-876-5p and RASAL2 expression in colorectal cancer tissue specimens. Moreover, miR-876-5p was involved in regulating the activation of Yes-associated protein (YAP) signalling through inhibiting RASAL2. However, the miR-876-5p-mediated antitumour effect on colorectal cancer cells was partially reversed by restoring RASAL2 expression. Notably, miR-876-5p upregulation impeded the tumour growth of colorectal cancer cells in vivo in nude mice. Overall, these results demonstrated that miR-876-5p exerts an antitumour function in colorectal cancer by targeting RASAL2 to suppress YAP signalling activation. These findings highlight the importance of the miR-876-5p/RASAL2/YAP axis in colorectal cancer progression and suggest that miR-876-5p is a potential therapeutic target for treating colorectal cancer.

[Downregulation of miR-129-5p alleviates alcohol-induced barrier dysfunction of Caco-2 human intestinal epithelial cells].

Objective To investigate the effect of miR-129-5p on alcohol-induced intestinal epithelial permeability. Methods Real-time quantitative PCR was used to detect the expression level of miR-129-5p in sigmoid colon biopsies and alcohol-induced differentiated Caco-2 cells from patients with alcoholic liver disease and healthy people. Then, the differentiated Caco-2 cells were divided into 4 groups: the control group, the alcohol group (treatment with 50 mmol/L alcohol for 60 minutes), alcohol combined with miR-129-5p inhibitor group (transfection with miR-129-5p inhibitor before alcohol treatment), and alcohol combined with miR-129-5p inhibitor control group (transfection with miR-129-5p inhibitor control before alcohol treatment). After the alcohol treatment, the transepithelial electrical resistance (TER) was analyzed by a resistance meter, and the protein levels relevant to tight junction (occludin and ZO-1) were determined by Western blotting. Results The expression level of miR-129-5p was elevated in the biopsies of the patients with alcoholic liver disease compared with that in the healthy controls. Alcohol treatment increased miR-129-5p expression in the differentiated Caco-2 cells. Compared with the control group, TER and the protein levels of occludin and ZO-1 decreased in the alcohol group. Compared with the alcohol group, TER and the protein levels of occludin and ZO-1 were enhanced in the alcohol combined with miR-129-5p group; however, these changes were not altered in the alcohol combined with miR-129-5p inhibitor control group. Conclusion The miR-129-5p expression is elevated in sigmoid colon biopsies and alcohol-induced differentiated Caco-2 cells from patients with alcoholic liver disease. Inhibition of miR-129-5p can suppress alcohol-induced intestinal epithelial permeability.

Pentoxifylline induces apoptosis of HepG2 cells by reducing reactive oxygen species production and activating the MAPK signaling.

AIMS: Pentoxifylline (PTX) is a methylxanthine derivative and has potent anti-tumor activity. This study aimed at investigating the anti-HCC effects of PTX and associated molecular mechanisms. MAIN METHODS: The effects of varying doses of PTX on viability, cell cycle and apoptosis of HepG2 cells were determined by MTT and flow cytometry, respectively. The effects of PTX on the production of reactive oxygen species (ROS), expression of pro- and anti-apoptotic regulators and activation of the MAPK signaling in HepG2 cells were analyzed by flow cytometry and Western blot assays. The effects of PTX on the growth of implanted HepG2 cells and their apoptosis in mice were examined. KEY FINDINGS: Our results indicated that PTX inhibited proliferation of HepG2 cells and induced HepG2 cell cycle arrest at G0/G1 phase and apoptosis in a dose- and time-dependent manner. Treatment with PTX reduced levels of ROS and Bcl-XL expression, but increased caspase 3 and caspase 9 expression and JNK and ERK1/2 phosphorylation in HepG2 cells. Pre-treatment with n-acetyl-l-cysteine (NAC), a ROS scavenger, enhanced PTX-mediated cell cycle arrest, apoptosis and the JNK and ERK MAPK activation, while pre-treatment with SP600125 or PD98509 attenuated PTX-mediated effects in HepG2 cells. Treatment with PTX inhibited the growth of implanted HCC and promoted HCC apoptosis in mice. SIGNIFICANCE: Our data demonstrate that PTX inhibits proliferation of HepG2 cells and induces HepG2 cell apoptosis by attenuating ROS production and enhancing the MAPK activation in HepG2 cells.

Celecoxib suppresses fibroblast growth factor-2 expression in pancreatic ductal adenocarcinoma PANC-1 cells.

The inhibition of cyclooxygenase (COX)-2 has been reported to suppress growth and induce apoptosis in human pancreatic cancer cells. Nevertheless, the precise biological mechanism of how celecoxib, a selective COX-2 inhibitor, regulates the growth and invasion of pancreatic tumors is not completely understood. It has been shown that fibroblast growth factor-2 (FGF-2) and its receptor levels correlate with the inhibition of cancer cell proliferation, migration and invasion in pancreatic ductal adenocarcinoma (PDAC). Therefore, the aim of the present study was to examine the hypothesis that the antitumor activity of celecoxib in PDAC may be exerted through modulation of FGF-2 function. In the present study, we evaluated the effects of celecoxib on the proliferation, migration, invasion and apoptosis of the PANC-1 cell line. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were used to examine the expression of FGF-2, FGFR-2, ERK1/2 and MMPs. In the present study, FGF-2 and FGFR-2 were expressed in PANC-1 cells and FGF-2 exerted a stimulatory effect on phosphorylated extracellular signal regulated kinase (p-ERK) expression. Celecoxib treatment suppressed FGF-2 and FGFR-2 expression and decreased MMP-2, MMP-9 and p-ERK expression in the PANC-1 cells. Furthermore, celecoxib treatment caused the resistance of PANC-1 cells to FGF-2 induced proliferation, migration and invasion ability, as well as the increase in their apoptotic rate. Our data provide evidence that targeting FGF-2 with celecoxib may be used as an effective treatment in PDAC.

Protective effects of pentoxifylline on acute liver injury induced by thioacetamide in rats.

Pentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor with the effects of antioxidation, anti-inflammation and anti-fibrosis that has been shown to induce damage in liver. The purpose of this study is to investigate the effects and possible mechanisms of PTX on thioacetamide (TAA)-induced acute liver injury in rats. Male Sprague-Dawley (SD) rats were divided into four groups: control, PTX, TAA and PTX+TAA treated groups. Rats were administrated TAA together with or without PTX for a week and sacrificed 24 h after the last intragastric administration of PTX. Histopathological analysis was carried out. The liver function, the indices of oxidative stress including malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) in liver tissues, and pro-inflammatory cytokines expressions were examined. The mRNA level of NF-κB p65 in liver was also determined. PTX significantly attenuated TAA-induced liver injury. The serum transaminase and MDA levels were reduced while the levels of SOD and GSH were increased, as compared with the TAA-treated group. PTX also remarkably suppressed the secretions of pro-inflammatory cytokines and the nuclear factor-κB (NF-κB) activation induced by TAA. In addition, the histopathological analysis showed that the range and degree of liver tissue lesions were improved obviously in PTX treated group. Pentoxifylline could ameliorate the effects of thioacetamide-induced acute liver injury in rats by inhibiting oxidative stress, expressions of pro-inflammatory cytokines and NF-κB activation.