Effects of exogenous hydrogen sulfide and honokiol intervention on the proliferation, apoptosis, and calcium signaling pathway of rat enteric glial cells.

Hydrogen sulfide (H2S) is a gaseous signaling molecule that influences digestive and nervous system functions. Enteric glial cells (EGCs) are integral to the enteric nervous system and play a role in regulating gastrointestinal motility. This study explored the dual effects of exogenous H2S on EGCs and the influence of apoptosis-related pathways and ion channels in EGCs. We also administered honokiol for further interventional studies. The results revealed that low-concentration H2S increased the mitochondrial membrane potential (MMP) of EGCs, decreased the whole-cell membrane potential, downregulated BAX and caspase-3, upregulated Bcl2 expression, reduced apoptosis, and promoted cell proliferation. The Ca2+ concentration, Cx43 mRNA, and protein expression were also increased. A high concentration of H2S had the opposite effect. In addition, GFAP mRNA expression was upregulated in the test-low group, downregulated in the test-high group, and upregulated in the test-high + Hon group. Honokiol treatment increased MMP, reduced whole-cell membrane potential, inhibited BAX and caspase-3 expression, increased Bcl2 expression, decreased cell apoptosis, and increased cell proliferation. The Ca2+ concentration, Cx43 mRNA, and protein expression were also upregulated. In conclusion, our study showed that exogenous H2S can bidirectionally regulate EGC proliferation and apoptosis by affecting MMP and cell membrane potential via the Bcl2/BAX/caspase-3 pathway and modulate Cx43-mediated Ca2+ responses in EGCs to regulate colonic motility bidirectionally. Honokiol can ameliorate the damage to EGCs induced by high H2S concentrations through the Bcl2/BAX/caspase-3 pathway and improve colon motility by increasing Cx43 expression and Ca2+ concentration.

Ruthenium-dihydroartemisinin complex: a promising new compound for colon cancer prevention via G1 cell cycle arrest, apoptotic induction, and adaptive immune regulation.

BACKGROUND: Artemisinin (ART) and its derivatives are important antimalaria agents and have received increased attention due to their broad biomedical effects, such as anticancer and anti-inflammation activities. Recently, ruthenium-derived complexes have attracted considerable attention as their anticancer potentials were observed in preclinical and clinical studies. METHODS: To explore an innovative approach in colorectal cancer (CRC) management, we synthesized ruthenium-dihydroartemisinin complex (D-Ru), a novel metal-based artemisinin derivative molecule, and investigated its anticancer, anti-inflammation, and adaptive immune regulatory properties. RESULTS: Compared with its parent compound, ART, D-Ru showed stronger antiproliferative effects on the human CRC cell lines HCT-116 and HT-29. The cancer cell inhibition of D-Ru comprised G1 cell cycle arrest via the downregulation of cyclin A and the induction of apoptosis. ART and D-Ru downregulated the expressions of pro-inflammatory cytokines IL-1ß, IL-6, and IL-8. Although ART and D-Ru did not suppress Treg cell differentiation, they significantly inhibited Th1 and Th17 cell differentiation. CONCLUSIONS: Our results demonstrated that D-Ru, a novel ruthenium complexation of ART, remarkably enhanced its parent compound's anticancer action, while the anti-inflammatory potential was not compromised. The molecular mechanisms of action of D-Ru include inhibition of cancer cell growth via cell cycle arrest, induction of apoptosis, and anti-inflammation via regulation of adaptive immunity.

Metabolomics study identified bile acids as potential biomarkers for gastric cancer: A case control study.

Gastric cancer (GC) is a common lethal malignancy worldwide. Gastroscopy is an effective screening technique for decreasing mortality. However, there are still limited useful non-invasive markers for early detection of GC. Bile acids are important molecules for the modulation of energy metabolism. With an in-depth targeted method for accurate quantitation of 80 bile acids (BAs), we aimed to find potential biomarkers for the early screening of GC. A cohort with 280 participants was enrolled, including 113 GC, 22 benign gastric lesions (BGL) and 145 healthy controls. Potential markers were identified using a random forest machine algorithm in the discovery cohort (n=180), then validated in an internal validation cohort (n=78) and a group with 22 BGL. The results represented significant alterations in the circulating BA pool between GC and the controls. BAs also exhibited significant correlations with various clinical traits. Then, we developed a diagnostic panel that comprised six BAs or ratios for GC detection. The panel showed high accuracy for the diagnosis of GC with AUC of 1 (95%CI: 1.00-1.00) and 0.98 (95%CI: 0.93-1.00) in the discovery and validation cohort, respectively. This 6-BAs panel was also able to identify early GC with AUC of 1 (95%CI: 0.999-1.00) and 0.94 (95%CI: 0.83-1.00) in the discovery and validation cohort, respectively. Meanwhile, this panel achieved a good differential diagnosis between GC and BGL and the AUC was 0.873 (95%CI: 0.812-0.934). The alternations of serum bile acids are characteristic metabolic features of GC. Bile acids could be promising biomarkers for the early diagnosis of GC.

The efficacy of endoscopic stenting combined with laparoscopy in the treatment of left colon cancer with obstruction.

CONTEXT: Endoscopic self-expandable metal stents (SEMSs) are the bridge of obstructive colorectal cancer surgery. The debate is still open on whether the procedure and effects can be the same between the SEMS combined obstructive colon cancer resection and nonobstructive colon cancer resection, both of which were under laparoscopic. AIMS: This retrospective study was designed to compare whether the same effects could be achieved in both resections. SETTINGS AND DESIGN: The retrospective analysis was from September 2016 to November 2017. In the observation group (OG), 20 patients hospitalized for obstruction of the left colon cancer were included, who received obstructive colon cancer laparoscopic resection (LR) combined with SEMS insertion. In control group (CG), 20 patients were randomly selected, who underwent nonobstructive colon cancer LR during this period. SUBJECTS AND METHODS: The differences between the two groups were compared, including operation time, intraoperative blood loss, the number of removed lymph nodes, postoperative anal exhaust time, and hospital stay. RESULTS: Both groups were comparable in the age, gender, weight, the distribution of tumor, lymph node metastasis, tumor, node, and metastasis staging, operation time, intraoperative blood loss, the number of removed lymph nodes, and postoperative anal exhaust time. The hospital stay was 15.2 ± 1.3 days and 14.2 ± 1.5 days in OG and CG, respectively, and it was longer in OG than that of in CG (P = 0.032). CONCLUSIONS: Obstructive colon cancer LR combined with SEMS insertion was a safe and feasible radical treatment strategy. The same level of procedure and effects could be achieved, compared to that of nonobstructive colon cancer LR.

Therapeutic effect of a temporary transpyloric stent in refractory post-surgical gastroparesis: a case report.

BACKGROUND: Gastroparesis is a syndrome characterized by delayed gastric emptying with associated symptoms. It was reported that the symptoms of diabetic gastroparesis had been greatly improved by transpyloric stent placement. However, the use of stents in benign conditions is considered to be contraindicated because of the increasing risk of complications, such as stent migration, reflux, perforation, bleeding, and, most importantly, new strictures caused by stent-induced tissue hyperplasia. While temporary placement of a self-expanding metallic stent (SEMC) can drastically reduce the risk of complications, few reports are available on the treatment of refractory PSG by temporary transpyloric stent. Does it have a long-term clinical effect after the stent being retrieved? CASE PRESENTATION: After accepting partial resection of the lesser curvature in another hospital, a patient developed refractory gastroparesis. The symptoms hadn't been improved after long-term drug therapy and balloon dilation therapy. Four months after surgery, a fully covered SEMC was placed by endoscopy in our hospital. Gastroparesis had been greatly improved. Two weeks later, the transpyloric stent was retrieved and the patient didn't show recurrent symptoms. Follow-ups were arranged at 3 months, 6 months and 1 year respectively, and there was no evidence of recurrence was found. CONCLUSIONS: This case indicates that temporary transpyloric SEMC is a safe, effective and less invasive alternative for post-surgical gastroparesis patients.

Primary angiosarcoma of the small intestine with metastasis to the liver: a case report and review of the literature.

Angiosarcoma is a rare disease with a poor prognosis; significantly, patients with intestinal angiosarcomas who survive over 1 year after diagnosis are extraordinarily rare. This article describes the case of a 33-year-old gentleman who presented with abdominal pain of 4 months duration, which had increased in severity 2 weeks prior to presentation. After a complicated diagnostic and therapeutic process, the diagnosis of primary angiosarcoma of the small intestine with metastasis to the liver was made by pathological and immunohistochemical examinations. We reviewed previous cases of angiosarcoma described in the English literature to determine their risk factors, diagnosis and treatment, and we found that angiosarcoma is extremely rare, especially in the small intestine. To the best of our knowledge, this may be the youngest case of primary angiosarcoma of the small intestine with metastasis to the liver reported in the English literature.

[Hydrolytic property and solution stability of NAMI derivative containing nicotinamide].

OBJECTIVE: To study the influence of ligand structure on hydrolysis and solution stability of NAMI derivatives. METHOD: NAMI type compound 1, trans- [RuCl4 (DMSO) (nica)] Na x 2DMSO (nica, nicotinamide) were prepared. Their hydrolytic mechanism, kinetics and stability were investigated by UV-Vis spectrophotometer. RESULT: Similar to NAMI, compound 1 undergoes two well-separated steps chloro-hydrolysis (I chloro-hydrolysis and II chloro-hydrolysis) (step reaction) in pH 7.4 buffer solution; while dimethyl sulfoxide (DMSO) hydrolyze in pH 5.00 acetic buffer solution. The k(obs) and t1/2 for each hydrolytic reaction were determined. CONCLUSION: The stability of compound 1 in acidic solution is much more stable than that of in neutral solution. Nicotinamide in place of imidazole can decrease chloro hydrolytic rate of NAMI derivatives obviously, while the influence on the DMSO hydrolytic process is not so remarkable.

Morphological changes in network of enteric nerve-interstitial cells of Cajal-smooth muscle cells in rats with multiple organ dysfunction syndrome and therapeutic effects of Dachengqi decoction (大承气汤).

OBJECTIVE: To observe the effects of Dachengqi Decoction (大承气汤, DCQD) on morphological changes in the network of enteric nerve-interstitial cells of Cajal (ICCs)-smooth muscle cells (SMC) of enteric deep muscular plexuses (DMP) in the rats with multiple organ dysfunction syndrome (MODS). METHODS: One hundred Wistar rats of both sexes weighing 200 to 250 g were randomly divided into the control group, MODS group, and DCQD group. The morphologic changes of enteric nerve-ICC-SMC network in the DMP of intestine was observed using c-Kit and vesicular acetylcholine transporter/neuronal nitric oxide synthase immunohistochemical double-staining with whole-mount preparation technique, confocal laser scanning microscopy, and electron microscopy. RESULTS: Compared with the control group, the distribution and densities of cholinergic/nitrergic nerves and ICC in the DMP (ICC-DMP) of intestine in the MODS group were significantly decreased (P<0.01), and the network of cholinergic nerve-ICC-SMC was disrupted; and the ultrastructural features of ICC-DMP, enteric nerve, and SMC were severely damaged. After treatment with DCQD, the damage in the network of enteric nerve-ICC-SMC was significantly recovered. Compared with the MODS group, the distribution and densities of cholinergic/nitrergic nerves and ICC-DMP in the DCQD group were significantly increased (P<0.01); and the ultrastructural features of ICC-DMP, enteric nerve, smooth muscle cells were significantly recovered. CONCLUSIONS: DCQD can improve the gastrointestinal motility in MODS. The mechanism may be related to the effect of repairing the damages in the network of enteric nerve-ICC-SMC.

[Determination of cirsilineol in Herba Artemisiae scopariae collected in autumn by HPLC].

OBJECTIVE: To establish a quantitative method for determination of cirsilineol in Herba Artemisiae Scopariae collected in Autumn. METHOD: Sample was extracted with methanol, and cleaned up with polyamide column. ODS column was used with methanol-acetonitrile-0.5% acetic acid solution (24:19:57) as mobile phase. Detection wavelength was 347 nm. RESULT: Cirsilineol in sample solution was well separated. Linearity of cirsilineol was good (r = 0.9998) in range of 0.1-0.8 microgram. The average recovery was 101.3%, RSD of repeatability was 3.04%. CONCLUSION: This method can be used for quality control of Herba Artemisiae Scopariae collected in autumn and its preparations.