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Ferroptosis is a recently recognized form of regulated cell death caused by an iron-dependent accumulation of lipid reactive species. However, little research on ferroptosis and lung cancer, one of the most common tumors, has been carried out. This paper tries to review the research progress of ferroptotic suppression and explain it from the different ways of ferroptosis occurrence. Furthermore, as inducing ferroptosis to treat cancer gets more attention, we introduce four kinds of ferroptosis-inducing compounds and new prospects for lung cancer therapy to provide new ideas for lung cancer treatment.
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Ferroptosis is a recently recognized form of regulated cell death caused by an iron-dependent accumulation of lipid reactive species. However, little research on ferroptosis and lung cancer, one of the most common tumors, has been carried out. This paper tries to review the research progress of ferroptotic suppression and explain it from the different ways of ferroptosis occurrence. Furthermore, as inducing ferroptosis to treat cancer gets more attention, we introduce four kinds of ferroptosis-inducing compounds and new prospects for lung cancer therapy to provide new ideas for lung cancer treatment.
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Objective To explore the pathologic features and distribution characteristics of upper gastrointestinal submucosal tumors (SMT).Methods From January 2013 to December 2017,at Department of Gastroenterology of Taizhou Hospital Affiliated to Wenzhou Medical University,clinical data of 1 182 hospitalized patients with 1 237 upper gastrointestinal SMT who underwent endoscopic therapy and diagnosed by pathology and immunohistochemistry was retrospectively analyzed including the pathological types,tumor of locations,endoscopic findings,layer of origin and tumor size.Results There were 473 esophageal SMT,including 387(81.8％) leiomyomas,located in the mucosal muscularis or muscularis propria;and 59(12.5％)cysts located in the submucosa or mucosal muscularis.There were 138(29.2％) lesions,159(33.6％) lesions and 176(37.2％) lesions in the upper,middle and lower esophagus respectively,and the most common type was leiomyoma.A total of 723 tumors were gastric SMT,among them 284 (39.3％) lesions were gastrointestinal stromal tumors (GIST) and 273(37.8％) lesions were leiomyomas,and all located in the muscularis propria.A total of 69(9.5％) lesions located at cardia,the common types were leiomyoma (55 lesions,79.7％) and GIST (nine lesions,13.0％).A total of 239 (33.1％) lesions located at gastric fundus,the common types were GIST (152 lesions,63.6％) and leiomyoma (79 lesions,33.1％).A total of 280 (38.7％) lesions located at gastric body,the common types were leiomyoma (138 lesions,49.3％) and GIST (111 lesions,39.6％).A total of 127 (17.6％) lesions located at gastric antrum,the common types were heterotopic pancrease (71 lesions,55.9％) and lipoma (26 lesions,20.5％),and all were located in the submucosa,some involved the muscularis propria.There were six (0.8％) lesions at gastric angle,and two (0.3％) at gastrointestinal anastomosis.Forty-one lesions were duodenal SMT,among them 23(56.1％) located at duodenal bulb,the common types were cyst (10 lesions,43.5％),lipoma (five lesions,21.7％) and heterotopic pancrease (five lesions,21.7％).A total of 18(43.9％) lesions located at descending duodenum,the common types were lipoma (nine lesions,50.0％) and cyst (five lesions,27.8％),and all lesions located in the submucosa.Conclusions The most common type of SMT in the esophagus and cardia is leiomyoma,however the SMT in gastric fundus and body are mostly leiomyomas and GIST,while in gastric antrum,most SMT are heterotopic pancreases and lipomas.In duodenal bulb and descending duodenum,the common types of SMT are cyst and lipoma.
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Objective To evaluate the implant-bone interfaces on implants with active Zn coating in a rabbit model.Methods Pure titanium cylinder implants,fabricated by machining,were prepared by surface microarc oxidation (MAO).The MAO-Zn/Ca/P coated (experimental group) and the MAO-Ca/P coated (control group)implants were randomly placed in the rabbit mandible.The samples were harvested at 4 and 12 weeks postoperatively,histological analysis on the implant-bone interfaces of the two implants was performed,and the bone coverage was compared.Results The coatings of MAO presented micro-porous structure with dense and uniform features,in which size of micro-porous increased with zinc element.The histological examination of implant-bone contact interfaces showed that the bone tissues attached on the coatings increased with time.Further,the adhered bone tissue in the experimental group was thicker and denser and had a larger amount compared to that in the control group at 4 and 12 weeks postoperatively.The bone coverage in the experimental group (70.8％±13.6％) at 12 weeks postoperatively was significantly higher than that in the control group (55.9％±13.8％) (P＜0.05).The results of bone interface element showed that the apatite layer was precipitated at 12 weeks.Conclusion The addition of active zinc element can improve the biological activity of the coating,enhance the osteogenesis ability of the coating,and accelerate the osseointegration of implant-bone interfaces.
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Objective To provide the scientific evidence for studying Alzheimer's disease (AD) and decision-making for its management by analyzing the strategic information of hotspots in studies on AD.Methods Citation strategic coordinate diagram was plotted by describing the history of studies on AD with co-citation clustering for further understanding the novelty and concern of hotspots in studies on AD.The current hotspots in studies on AD were discovered by co-words clustering and their strategic coordinates were analyzed to reveal their development periods.Results The current hotspots in studies on AD were substance metabolism in AD patients, etiology of AD and therapies for AD.The diagnosis of AD according to its clinical characteristics and hypothesis on amyloid cascade in AD patients were greatly concerned.Conclusion Citation strategic coordinate analysis and co-words strategic coordinate analysis can display the hotspots in studies on AD and their development history.
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Objective To investigate the effect of non-alcoholic fatty liver disease (NAFLD) on virologic response in chronic hepatitis B patients treated with nucleos(t)ide analogues.Methods Three hundred and thirty-two treatment-naive patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) who visited clinic or hospitalized in the First Affiliated Hospital of Wenzhou Medical College from January 2007 to December 2009 were enrolled and finally 316 patients completed the research.Among them,106 patients were diagnosed with CHB complicated with NAFLD by ultrasonography (NAFLD group),and the remaining 210 patients were diagnosed with simple CHB (CHB group).Patients in both groups were treated with combination therapy of lamivudine (LAM) plus adefovir dipivoxil (ADV) or entecavir (ETV) monotherapy for 96 weeks.Alanine aminotransferase (ALT) levels,virologic response and serological response were compared pre-and post-treatment in both groups.Enumeration data was compared using x2 test,and correlation analysis was performed using Logistic multivariate regression analysis.Results Rates of hepatitis B virus (HBV) DNA clearance in the NAFLD group at week 12,24 and 48 were 46.2％,61.3％ and 74.5％,respectively,which were all significantly lower than those in CHB group (61.9％,73.8％ and 83.8％,x2 =7.051,5.195,3.895,respectively; all P＜0.05).However,rates of HBV DNA clearance were 85.8％ in the NAFLD group and 91.9％ in the CHB group at week 96.This difference did not reach the level of significance (x2 =2.838,P＞0.05).Rates of HBeAg loss in the NAFLD group were 27.4％ at week 48 and 37.7％ at week 96,compared to 33.3％ and 44.8％ in the CHB group.There was no significant difference in these two groups (x2 =1.169,1.424,both P＞0.05).Rate of HBeAg seroconversion in the NAFLD group was significantly lower than that in the CHB group at week 96 (17.9％ vs29.5％,x2=4.972,P＜0.05).Rates of ALT normalization were also found to be significantly lower in the NAFLD group than those in the CHB group at week 48 (69.8％ vs 80.5％,P＜0.05) and at week 96 (82.1％ vs 91.0％,P＜0.05).Multivariate regression analysis demonstrated that serum levels of triacylglycerol (OR=3.725,P=0.000),uric acid (OR=1.005,P=0.040) and fasting blood-glucose (OR=3.067,P=0.000) were independent risk factors associated with NAFLD.NAFLD was found to be a risk factor of virologic response at each time point throughout the treatment.(week 12,OR=2.749,P=0.001; week 24,OR=1.981,P=0.030; week48,OR=2.348,P=0.021; week 96,OR=8.053,P=0.001).Conclusions During antiviral therapy,NAFLD may affect biochemical and serological responses in CHB patients treated with nucleos(t) ide analogues,and may affect early virologic response in these patients.
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Objective To investigate the changes in cytotoxicity of DC-CIK cells to human multiple myeloma RPMI 8226 cells before and after treatment with oridonin. Methods Normal human peripheral blood mononuclear cells were isolated and induced to obtain DC-CIK cells. Cytotoxicity of DC-CIK cells against RPMI 8226 cells which were treated by oridonin was analyzed by LDH releasing assay. The variation for expression of NKG2D ligands on RPMI 8226 cells were measured by flow cytometry. Results DC-CIK cells were successfully induced from the peripheral blood mononuclear cells. At the same effector to target ratio, oridonin obviously enhanced the cytotocixity of DC-CIK cells against RPMI 8226 cells (P<0.01). Flow cytometry showed the expression of NKG2D ligands ULBP1 of RPMI8226 cells was most significantly increased as the cells were treated by oridonin [(9.19 ± 1.85) vs. (15.47 ± 0.67), P<0.01]. Correlation analysis indicated that cytotocixity was positively correlated with changes in ULBP1. Conclusions Oridonin can improve the cytotoxicity of DC-CIK cells against RPMI 8226 cells, which may be related with the increased expressions of NKG2D ligands on the tumor cell surface.
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ObjectiveTo explore the efficacy and safety of bone marrow mesenchymal stem cells (BMSC)in treatment of aplastic anemia(AA). MethodsTwenty-two patients with aplastic anemia were enrolled with median age of 31 (12-70) years old,including 11 severe aplastic anemia (SAA),and 3 of whom were cyclosporine and anti-thymocyte globulin-resistant. BMSC were isolated from bone marrow of healthy donors and cultured.The third to fifth generation cells were administered intravenously in 1×106/kg to patients once or twice a week.After infusion,complete blood count,bone marrow aspiration,bone marrow biopsy,flow cytometry analysis of lymphocyte subsets of CD3+ CD4+ and CD3+ CD8+ and clinical symptoms were involved in outcome measurement.ResultsAll patients finished 16-time median (5-83 times) infusions of BMSC with 13-month median (2-33 months) treatment course and 23-month median (2-34 months) follow-up.The total response rate was 72.7 ％(16/22), including one patient with essential cure, 9 with remission, 3 with remarkably improvement and 3 with transfusion interval extension.Two of three front-line immunosuppressiveresistant SAA patients achieved remission. Ten of 14 patients recovered from inverted ratio of CD4+/C8+ cells after BMSC treatment. There were no treatment-related side effects observed in the course of treatment.ConclusionBMSC are effective and safe for the treatment of AA in our preliminary study and they deserve further research with larger-scale and long-term clinical trials.
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Objective To investigate the regulation and the mechanism of Melatonin in calcium overload of pancreatic acinar cell in acute necrotizing pancreatitis (ANP). Methods Fifty-four Sprague-Dawley (SD) rats were equally divided into three groups:sham-operation group (SO group),ANP group (created with retrograde cholangiopancreatography injection of sodium taurocholate) and MT group (ANP model made after intra-peritoneal injection MT for 30 mins).Rats were sacrificed at 1,4 and 8hours after operation and pancreas tissues were underwent pathological examination.The free calcium concentration of pancreas tissues was determined by fluorescence minitoring method; and the expression of CaMK Ⅱ in pancreas tissues at mRNA and protein level was tested by real-time PCR and Western Blot.Results Pancreatic pathological injury in ANP groups was progressively severe as time extended,which was obviously ameliorated in MT group compared with ANP group (the t value of compared pathological score at 1,4 and 8 hour was:-7.95,-9.72 and -7.69,all P=0.00).Compared at same time point,the free Ca2+ concentration of pancreas tissues in ANP group was significantly higher than that of SO group (the t value of 1,4 and 8 hour was 13.09,18.58 and 16.56,all P=0.00).It was a little bit higher in MT group compared with that of SO group,however was significantly lower than that of ANP group (the t value of 1,4 and 8 hour was -10.03,-11.75 and -11.02,all P =0.00).Compared with SO group,the expression of CaMK Ⅱ at mRNA and protein level significantly increased in ANP group; MT significantly inhibited its expression.Conclusions The expression of CaMK Ⅱ may be inhibited by MT interfere,and then lower the calcium overload in pancreatic acinar cell,which play a role in pancreas tissue protection.
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Objective To investigate the role of bone marrow mesenchymal stem cells (MSCs) transplantation in repairing injured intestinal mucosa of acute pancreatitis.Methods MSCs were harvested and cultured from femurs of male SD rats.Twenty female SD rats were divided into three groups,and serve acute pancratitis (SAP) model was induced by intraperitoneal injection of L-arginine (2 g/kg) twice.Twelve hours after SAP model established,MSC transplantation group (n=8) were injected MSCs (5 × 106 cell/rat) through tail vein for three days,and SAP group (n=6) were injected the same volume of saline through tail vein as control.Control group (n=6) were only injected the same volume of saline without any treatment.All the rats were sacrificed at 72 hours after model established.The small intestinal tissues were taken for HE staining and pathological score,the TNF-α mRNA and IL-1β mRNA expression level in small intestine and pancreas were tested by RT-PCR.Y chromo-some (Sry) gene in pancreatic and intestinal tissue was examined by polymerase chain reaction (PCR).Results The relative expression quantity of TNF-a mRNA and IL-1β mRNA in pancreas was significant higher in SAP group and MSC transplantation group than in control group (7.22 ± 1.99,3.46± 1.75 vs 1.32 ± 1.04 ; 2.71 ± 0.56,1.92 ± 0.28 vs 0.61 ± 0.45 ),the difference was statistically significant (F=18.375,F=22.701; P＜0.05).Compared with SAP group,the expression quantity of TNF-α mRNA and IL-1β mRNA in pancreas was significantly decreased in MSC transplantation group,the difference was statistically significant (P＜0.05).The relative expression quantity of TNF-α mRNA and IL-1β mRNA in small intestine was significantly higher in SAP group and MSC transplantation group than in control group (3.93 ± 1.08,2.13 ± 0.53 vs 0.68 ± 0.42 ; 2.44 ± 1.54,1.02±0.44 vs 0.60±0.14),the difference was statistically significant (F=21.772,F=6.132; P＜0.05).The expression of TNF-αmRNA and IL-1β mRNA in MSC transplantation group was lower than that in SAP group,the difference was statistically significant (P＜0.05).Compared with SAP group,pathological score indicated that small intestine injure was slighter in MSC transplantation group (3.83±0.28 vs 2.83±0.56),the difference was statistically significant (F=12.013,P＜0.05).Sry gene could be detected in the pancreatic and intestinal tissue of MSC transplantation group.Conclusion Allogeneic MSC transplantation group can inhibit Pro-inflammatory cytokines expression in acute pancreatitis,relieve the intestinal mucosa injury and may involve in the intestinal tissue repair.
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Objective To investigate the effect and the potential mechanism of splenic artery coarctation on the expression of iNOS and Th1/Th2 cytokines in spleen of cirrhotic rats with portal hypertension (PHT). Methods Cirrhotic rats were randomized into 3 groups (n= 10):sham operation group (SOG), splenic artery coarctation group (SAC) and splenic artery ligation group (SAL). Ten normal rats treated with sham operation were employed to serve as normal control group (NCG). Immunohistochemial staining was used to observe iNOS. RT-PCR was used to detect IFN-γ and IL-4mRNA. The Pearson's correlation analysis was used to investigate the relationship between iNOS and IFN-γ or IL-4. Results The expression of iNOS was increased significantly in spleen of cirrhotic rats as compared with NCG(P＜0. 01). It was decreased after SAC and SAL compared with SOG (P＜0. 01). The expression of IFN-γmRNA and IFN-γ/IL-4 of SOG were decreased but IL-4mRNA increased significantly than that of NCG(P＜0.01). IFN-γmRNA was increased after SAC compared with SOG (P＜0.05). IL-4mRNA was decreased and IFN-γ/IL-4 increased after SAC and SAL compared with SOG (P＜0. 05). The expression of iNOS was negatively correlated with the expression of IFN-γmRNA(r=-0.672, P＜ 0.01 ) and positively correlated with the expression of IL-4 mRNA (r=0.634,P＜0. 01). Conclusion The expression of iNOS is decreased and IFN-γ/IL-4 increased after SAC in spleen of cirrhotic rats with PHT and it may improve Th1/Th2 polarization by reducing the expression of iNOS.
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Objective To explore the effect of prevention of hemorrhagic cystitis (HC) after hematopoietic stem cell transplantation (HSCT) with hyperhydration, forced diuresis and alkalinizing plus infusion mesna. Methods 32 cases of patients receiving HSCT were included in this study. 2 cases of severe aplastic anemia (SAA) received total body irradiation (TBI)+cyclophosphamide(CTX)(TBI-CTX) regimen,and the remaining 30 patients were using the classic busulfan+CTX (BU+CTX) regimen. All patients were treated with mesna combined with hydration, forced diuresis and alkalization to prevent HC. Ganciclovir and acyclovir were used to prevent cytomegalovirus (CMV) and other viral infections and monitor CMV-IgM levels of the blood. Encourage patients to urinate every hour, testing urine pH value and the calculation of urine output, every 6 h review and testing of urine routine,central venous pressure (CVP), each of 8 h of serum electrolytes. Results Only 1 patient at 6 months after transplantation appeared delayed grade Ⅱ HC after hydration, alkalization, diuretic, hemostatic, anti-graft-versus-host disease (GVHD), and ganciclovir antiviral therapy. The HC patients cured at 35 d. The remaining patients did not suffer HC. Adverse effects such as acid-base balance disturbance did not appear clear. Conclusion Mesna joint hydration, forced diuresis and alkalization was effective and safe to prevent HC.
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AIM: To explore the effects of ethanol on replication and expression of HBV, so as to effectively guide the anti HBV treatment in clinic. METHODS: 2.2.15 cells were cultured in vitro. Ethanol of different concentrations was added into the supernatant and 3TC was used as the positive control. And there was no drug added in the negative control group. Effect of ethanol on HBV expression and replication was examined and the expression of antiviral gene MxA was also tested. RESULTS: Ethanol promoted the expression of intracellular HBsAg, HBeAg and intracellular HBcAg. But 3TC revealed no significant effect on all of them. Southern blotting showed that ethanol at 200 mmol?L -1 enhance the replication of HBV DNA, but 3TC inhibited the replication of HBV DNA at 2 ?mol?L -1 .Ethanol at 40 mmol?L -1 promoted the expression of MxA, while 3TC at 2 ?mol?L -1 also stimulated the expression of MxA. CONCLUSION: Ethanol can induce the overexpression of HBsAg, HBeAg and HBcAg, and enhance the expression of antiviral gene MxA which may increase the activity of enzymes of synthetic metabolism. Ethanol can promote replication of HBV DNA, but the mechanism is unclear and need to be studied.