Baicalein Relieves Ferroptosis-Mediated Phagocytosis Inhibition of Macrophages in Ovarian Endometriosis.

Iron overload and oxidative stress have been reported to contribute to ferroptosis in endometriotic lesions. However, the possible roles of iron overload on macrophages in endometriosis (EMs) remain unknown. Based on recent reports by single-cell sequencing data of endometriosis, here we found significant upregulations of ferroptosis-associated genes in the macrophage of the endometriotic lesion. Additionally, there was an elevated expression of HMOX1, FTH1, and FTL in macrophages of peritoneal fluid in EMs, as well as iron accumulation in the endometriotic lesions. Notably, cyst fluid significantly up-regulated levels of intracellular iron and ferroptosis in Phorbol-12-myristate-13-acetate (PMA)-stimulated THP-1 cells. Additionally, high iron-induced ferroptosis obviously reduced PMA-stimulated THP-1 cells' phagocytosis and increased the expression of angiogenic cytokines, such as vascular endothelial growth factor A (VEGFA) and interleukin 8 (IL8). Baicalein, a potential anti-ferroptosis compound, increased GPX4 expression, significantly inhibited ferroptosis, and restored phagocytosis of THP-1 cells in vitro. Collectively, our study reveals that ferroptosis triggered by high iron in cyst fluid promotes the development of EMs by impairing macrophage phagocytosis and producing more angiogenic cytokines (e.g., IL8 and VEGFA). Baicalein displays the potential for the treatment of EMs, especially in patients with high ferroptosis and low phagocytosis of macrophages.

[Effect of hypoxia on the activation and visfatin expression in rat hepatic stellate cells].

OBJECTIVE: To investigate the effect of hypoxia on the visfatin and the expression of smooth muscle-actin (alpha-SMA) and hypoxia-inducible factor-1alpha (HIF-1alpha) in rat hepatic stellate cells (HSCs). METHODS: Rat primary HSCs were isolated from SD rats by in situ perfusion of collagenase and pronase and single-step Nycodenz density gradient centrifugation, and then cultured and activated. Completely activated primary HSCs were exposed to hypoxic conditions (37 degrees C, 5% CO2, 1% O2, 94% N2), or normoxic conditions (37 degrees C, 5% CO2, 21% O2, 74% N2), for 3, 6, 12 or 24 h respectively. The expression of alpha-SMA, the marker of HSC activation, and visfatin were assessed by Real time-PCR and Western blot. The Expression of HIF-1alpha was detected by Real time-PCR. RESULTS: HIF-1alpha mRNA in rat HSCs was induced after exposed to hypoxia for 3 h, and maintained elevated status up to 24 h. HSCs exposed to 1% O2 hypoxic conditions for 6 h increased alpha-SMA mRNA and protein expression. Visfatin mRNA expression was up-regulated after subjected to hypoxia for 12 h, and protein level was elevated after 6 h hypoxia. A positive linear correlation existed between alpha-SMA and visfatin expression in responsible to hypoxia (r = 0.991 (genes) and r = 0.968 (proteins), P < 0.05). CONCLUSION: Microcirculation impairment could significantly induce alpha-SMA and visfatin expression in rat HSCs, which might potentate the activation process of HSCs.

[Advances in the clinical research of gastro-esophageal reflux disease and functional gastrointestinal diseases].

Gastro-esophageal reflux disease (GERD) and functional gastrointestinal diseases (FGIDs) are common digestive diseases with an increasing concern. Both of them share similar pathogenesis, symptoms overlapping and merged mental psychological factors, which cause lack of standardization in diagnosis and poor response to treatment. The topics of this issue focused on the characteristics of motility dysfunction in different subtype of GERD and treatment priorities, main points of diagnosis and treatment of atypical-GERD with extra-esophageal symptoms as the primary presenting manifestation, status and characteristics of symptom overlapping between GERD and FGIDs, as well as the influence of symptom overlapping and mental psychological factors to life quality of GERD and FGIDs patients. With these advances in clinical research translating into clinical practice, it becomes promising to improve the standardization of diagnosis and to optimize the treatment of these diseases, which could lead to the change of therapeutic goal from simply alleviation of symptoms into the improvement of life quality with more concern of symptoms indicators.

[Association between acid reflux and esophageal dysmotility in patients with gastroesophageal reflux disease].

OBJECTIVE: To investigate the association between esophageal motility and acid reflux in patients with gastroesophageal reflux disease (GERD). METHODS: A total of 94 patients with typical reflux symptoms such as heartburn, regurgitation and chest pain, whose score (Sc) of reflux diagnostic questionnaire (RDQ) was greater than or equal to 12 were enrolled in the study. Each participant was evaluated by upper gastrointestinal endoscopy, high resolution manometry (HRM) of esophagus and 24 h esophageal pH monitoring. The participants were divided into groups of reflux esophagitis (RE) and non-erosive reflux disease (NERD) on the basis of endoscopy findings. The 24 h esophageal pH monitoring categorized participants into physiologic reflux (pH) and pathologic reflux (pH+). The characteristics of esophageal motility and acid reflux were compared between the two groups of participants. RESULTS: Lower but non-significant differences (P > 0.05) were found in pressure of lower esophageal sphincter (LESP), length of lower esophageal sphincter (LESL), esophageal contraction amplitude (CA), distal contractile integral (DCI) and effective peristalsis proportion (EPP) in the participants in the RE group compared with those in the NERD group. Participants in the RE group had significantly higher prevalence of reduced LESP (63.0% vs. 31.7%, P < 0.01) and hiatus hernia (HH) (37.0% vs. 14.3%, P < 0.05) than those in the NERD group, pH+ was more prevalent in the RE group than in the NERD group (63.0% vs. 17.5%, P < 0.01). Indicators of 24 h esophageal pH monitoring were significantly higher in participants in the RE group compared with those in the NERD group (P < 0.05). Participants with pH+ had significantly lower LESP, CA and higher HH and prevalence of reduced LESP compared with those with pH (P < 0.05). LESL, DCI and EPP were lower in those with pH+ compared with those with pH-, but without statistical significance (P > 0.05). CONCLUSION: RE is closely associated with acid reflux and hiatus hernia. Esophageal dysmotility is more likely to appear in patients with pH+. The interaction of acid reflux and esophageal dysmotility may play a role in GERD.

[Comparison of clinical features between gastroesophageal reflux diseases with atypical and typical symptoms].

OBJECTIVE: To study the differences between gastroesophageal reflux disease (GERD) with atypical symptoms (a-GERD) and typical symptoms (t-GERD). METHODS: 30 patients of suspected a-GERD were recruited and examined with upper gastrointestinal endoscopy, high-resolution manometry (HRM), 24 h esophageal multichannel intra-luminal impedance monitoring with pH sensor (MII-pH) and proton pump inhibitor (PPI) trials. The results were compared with those of 33 cases of GERD with typical symptoms. RESULTS: Among the 30 patients of suspected GERD, 24 were confirmed with a-GERD. One third of those patients were over sixty-years old, significantly higher than those with typical GERD (P < 0.05). No significant differences in prevalence of esophageal mucosa breakage and esophageal manometry readings were found between the two groups (P > 0.05). The a-GERD patients had higher data readings in 24 h esophageal MCII-pH monitoring than the t-GERD patients (P < 0.05). Supine type of GER and mixed reflux were predominately seen in the a-GERD patients, while upright type of GER was predominate seen in the t-GERD patients. The response rate of PPI in the a-GERD patients was significantly lower than that in the t-GERD patients when a course of standard dosage of PPI was given (45.8% vs. 78.8%, P < 0.01). But there was no significant difference in PPI response between these two groups when a second course with double standard dosage of PPI combined with pro-motility agents were given (72.7% vs. 88.0%, P < 0.05). CONCLUSION: Compared with patients of t-GERD, older onset age, more severe degree of acid reflux are presented in patients of a-GERD. a-GERD should be considered when it is hard to explain the symptoms of upper part of the chest in clinical practice. 24 h esophageal MII-pH monitoring and/or diagnostic therapy with double standard dosage of PPI helps make a correct diagnosis.

[Clinical features, quality of life and psychological health of patients with irritable bowel syndrome and functional dyspepsia].

OBJECTIVE: To investigate severity of gastrointestinal symptoms, quality of life, and mental health status of patients with irritable bowel syndrome (IBS) and functional dyspepsia (FD). METHODS: IBS patients were enrolled consecutively at the Outpatient Department of Gastroenterology, West China Hospital, Sichuan University from September 2012 to May 2013. The participants were divided into two groups according to their appearance with FD. Ten healthy volunteers served as normal controls. A questionnaire survey was undertaken to measure scores of gastrointestinal symptom rating scale (GSRS), Chinese IBS-quality of life (ChIBS-QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) and medical conditions. RESULTS: Twenty-five (41.7%) IBS patients were overlapped with FD (IBS-FD). The IBS-FD patients had significantly higher scores of GSRS than IBS patients and healthy volunteers (P < 0.05). The IBS-FD patients saw doctors more frequently than IBS patients (P < 0.05). Neither anxiety nor depression were observed in healthy volunteers. The IBS patients were more likely to present mild anxiety and depression, while the IBS-FD patients were more likely to present moderate to severe anxiety and depression. The IBS-FD patients had significantly higher prevalence of anxiety and depression than IBS patients (80.0% vs. 51.4%, 76.0% vs. 48.6% respectively, P < 0.05). Scores of GSRS, ChIBS-QOL and prevalence of anxiety and depression were the highest in the IBS-FD patients with constipation (IBS-C-FD, P < 0.05). CONCLUSION: IBS-FD patients especially those with constipation suffer more gastrointestinal discomforts, and are more likely to suffer from anxiety and depression and poor quality of life compared with those with IBS only.

The crosstalk between gut inflammation and gastrointestinal disorders during acute pancreatitis.

The intestinal inflammation caused by intestinal ischemia reperfusion during acute pancreatitis (AP) often leads to multiple organ dysfunction and aggravation of acute pancreatitis. This review concerns up-date progress of the pathophysiology and molecular mechanism of the excessive production of gut-derived cytokines. The regulation effects of immuno-neuro-endocrine network for pancreatic necrosis are the basis for pharmacological therapeutic in AP. The translation from basic research to clinical trials for the prevention or treatment of severe acute pancreatitis (SAP) is of great value. Early enteral nutrition is necessary for the restitution, proliferation, and differentiation of the intestinal epithelial cells adjacent to the wounded area. Clearance of the excess intestinal bacteria and supplement of probiotics may be helpful to prevent bacterial translocation and infection of pancreas.

Use of pre-, pro- and synbiotics in patients with acute pancreatitis: a meta-analysis.

AIM: To assess the clinical outcomes of pre-, pro- and synbiotics therapy in patients with acute pancreatitis. METHODS: The databases including Medline, Embase, the Cochrane Library, Web of Science and Chinese Biomedicine Database were searched for all relevant randomized controlled trials that studied the effects of pre-, pro- or synbiotics in patients with acute pancreatitis. Main outcome measures were postoperative infections, pancreatic infections, multiple organ failure (MOF), systemic inflammatory response syndrome (SIRS), length of hospital stay, antibiotic therapy and mortality. RESULTS: Seven randomized studies with 559 acute pancreatic patients were included. Pre-, pro- or synbiotics treatment showed no influence on the incidence of postoperative infections [odds ratios (OR) 0.30, 95% confidence interval (CI): 0.09-1.02, P = 0.05], pancreatic infection (OR 0.50, 95% CI: 0.12-2.17, P = 0.36), MOF (OR 0.88, 95% CI: 0.35-2.21, P = 0.79) and SIRS (OR 0.78, 95% CI: 0.20-2.98, P = 0.71). There were also no significant differences in the length of antibiotic therapy (OR 0.75, 95% CI: 0.50 - 1.14, P = 0.18) and the mortality (OR 0.75, 95% CI: 0.25-2.24, P = 0.61). However, Pre-, pro- or synbiotics treatment was associated with a reduced length of hospital stay (OR -3.87, 95% CI: -6.20 to -1.54, P = 0.001). When stratifying for the severity of acute pancreatitis, the main results were similar. CONCLUSION: Pre-, pro- or synbiotics treatment shows no significant influence on patients with acute pancreatitis. There is a lack of evidence to support the use of probiotics/synbiotics in this area.

Hydrothermal syntheses and structural characterizations of organic-inorganic hybrid materials of the M(II)-ligand/vanadium oxide system (M(II) = Mn(II), Cu(II) and Zn(II); ligand = 2,2'-bipyridine and 1,10-phenanthroline).

Three organic-inorganic hybrid compounds [Mn(bpy)V(bpy)V(3)O(11)] (bpy = 2,2'-bipyridine) (1), [Cu(bpy)V(2)O(6)] (2) and [Zn(phen)3][V(2)O(6)].10H(2)O (phen = 1,10-phenanthroline) (3) have been synthesized hydrothermally. Single crystal X-ray diffraction analyses revealed that compound 1 is the first example of bpy units coordinating to different transition metals in one molecule. Compound 2 is a new isomer of [Cu(bpy)V(2)O(6)] which was named the gamma-isomer by us. In compound 3, a 2-D water sheet with big holes filled by the "naked" [V(4)O(12)](4-) clusters is found.

Combined histology and molecular biology for diagnosis of early stage gastric MALT lymphoma.

OBJECTIVE: To establish a sequential diagnostic procedure of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and provide evidence for selected optimal cases to be treated in the early stage. METHODS: Thirty-one cases of gastric lymphoid hyperplasia (GLH) were selected and multiple investigations including histology, protein level, DNA and chromosome levels, combined with clinical follow-up were performed. Histological grade was according to Isaacson's criteria of GLH; CD20, UCHL-1 (CD45RO), anti-kappa (kappa), anti-lambda (lambda) and Ki-67 were used for immunohistochemical staining; semi-nested polymerase chain reaction (PCR) was used to detect IgH gene rearrangement and reverse-transcription PCR (RT-PCR) was used to detect API2-MALT1 fusion of the chromosome translocation t(11;18)(q21;q21). Twenty-nine cases underwent eradication therapy for Helicobacter pylori. Changes in histological grade, endoscopic appearance, expression of Ki-67 and IgH gene rearrangement were compared after eradication treatment. RESULTS: Of the 31 cases of GLH with predominant chronic gastritis and gastric ulcer most were histological grade 2 and 3. Only one case had lambda light chain restriction and 10 cases had monoclonal IgH gene rearrangement. Expression of Ki-67 and monoclonal IgH gene rearrangement were significantly increased with increased lymphoid hyperplasia (P < 0.05). Two cases had API2-MALT1 fusion. Helicobacter pylori was eradicated in 25 cases and another course of treatment had to be given in 4 cases. All cases were followed up for 1.5-37 months. Of the 27 successful eradication cases, 18 showed complete regression both histologically and endoscopically, 4 had partial regression and 7 were unchanged. CONCLUSIONS: A sequential diagnostic procedure based on histology, expression of Ki-67 combined with clonality of IgH rearrangement and API2-MALT1 fusion helps to diagnosis of early stage gastric MALT lymphoma and choose the best treatment strategy.

[Expression and function of interleukin-18 in mouse dextran sulfate sodium colitis].

OBJECTIVE: Interleukin-18 (IL-18) is a proinflammatory cytokine that induces Th1 cytokines production and may play a role in the pathogenesis of inflammatory bowel diseases. This study was aimed at detecting the expression and role of IL-18 in colonic mucosa of dextran sulfate sodium (DSS) colitic mice. METHODS: Expression of IL-18 in colon of DSS colitis was determined by immunohistochemistry. Extract and supernatant of intestinal epithelial cells (IEC) from colon of DSS colitis mice were used to stimulate splenic mononuclear cells (SMC); IFN-gamma and IL-2 concentrations in supernatant of SMC were measured by ELISA. The levels of expression of IL-18 in extract or supernatant of IEC were examined by Western blot. RESULTS: Colon epithelial cells and part of lamina propria mononuclear cells were stained positive for IL-18 antibody. Stimulation assay and Western blot indicated that IL-18 positive proteins were present in both IEC extract and supernatant. CONCLUSION: Colon epithelial cells in mice with DSS colitis express and secret pro IL-18 and active IL-18.

[The early diagnosis and treatment of gastric mucosa-associated lymphoma].

OBJECTIVE: To determine the general markers for the diagnosis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and select optimal cases to be interfered in early stage. METHODS: To investigate the changes of histology, Ki-67 expression, monoclonality of IgH gene rearrangement in gastric lymphoid hyperplasia (GLH) cases before and after Helicobacter pylori (Hp) eradication treatment. Histological changes were classified according to Isaacson's criteria of GLH; L26, UCHL-1, anti-Kappa, anti-Lambda and Ki-67 were applied for immunohistochemical staining; semi-nest PCR was used to detect IgH gene rearrangement. RESULTS: Thirty-one cases of GLH with predominant chronic gastritis and gastric ulcer were studied. The ratio of male to female in the 31 cases was 1.8 and the mean course 6.8 years. Twenty-nine cases had Hp infection. Most of the cases belonged to histological grade II and III. Only 1 case had lambda light chain restriction and 10 cases had monoclonal IgH gene rearrangement. Expression of Ki-67 and monoclonal IgH gene rearrangement were significantly increased with the crescendo of lymphoid hyperplasia grading (P < 0.05). 28 cases were given antibiotics with eradication of Hp in 24 cases and 2 cases had to be given another course of treatment. These cases were followed-up on average for 4.6 months. 18 cases showed complete regression both histologically and endoscopically, 4 cases partial regression and 6 cases no change. Four cases with histological grade II, III had the decrease of expression of Ki-67 and reversed to polyclonal IgH gene rearrangement, while there was no change in 4 cases with histological grade IV. CONCLUSIONS: General considerations of histology, expression of Ki-67 and combined clonality of IgH gene rearrangement help to screen cases which need intervention early and make a diagnosis of gastric MALT lymphoma in early stage. Monoclonal IgH gene rearrangement in cases with histological grade III or IV appears to carry more clinical significance.