Experts and Doctors on reactive oxygen species in Jinan, Shandong Sheng, China

Summary

Locale: Jinan, Shandong Sheng, China
Topic: reactive oxygen species

Top Publications

  1. Shi L, Yu X, Yang H, Wu X. Advanced glycation end products induce human corneal epithelial cells apoptosis through generation of reactive oxygen species and activation of JNK and p38 MAPK pathways. PLoS ONE. 2013;8:e66781 pubmed publisher
    ..In addition, NAC completely blocked phosphorylation of JNK and p38 MAPK induced by AGE-BSA. Our results indicate that AGE-BSA induced HUCLs apoptosis through generation of intracellular ROS and activation of JNK and p38 MAPK pathways. ..
  2. Lou H, Jing X, Ren D, Wei X, Zhang X. Eriodictyol protects against H(2)O(2)-induced neuron-like PC12 cell death through activation of Nrf2/ARE signaling pathway. Neurochem Int. 2012;61:251-7 pubmed publisher
    ..In conclusion, these results suggest that eriodictyol upregulates HO-1 and ?-GCS expression through the activation of Nrf2/ARE pathway and protects PC12 cells against H(2)O(2)-induced oxidative stress. ..
  3. Yang S, Wang S, Peng N, Xie Z, Wang P, Zhao C, et al. Butyrolactone derivative 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one protects against amyloid-? peptides-induced cytotoxicity in PC12 cells. J Alzheimers Dis. 2012;28:345-56 pubmed publisher
    ..In addition, 3BDO modulated the autophagy progress via a mammalian target of rampamycin-dependent pathway. 3BDO has a protective effect against the cytotoxicity induced by A?(25-35) and might be a promising tool for AD research. ..
  4. Gao N, Li L, Shi Z, Zhang X, Jin W. High-throughput determination of glutathione and reactive oxygen species in single cells based on fluorescence images in a microchannel. Electrophoresis. 2007;28:3966-75 pubmed
    ..For gastric cancer cells, the concentrations of GSH and ROS are in the range 0.35x10(-3)-1.3x10(-3) mol/L and 0.77x10(-) (6)-1.5x10(-6) mol/L, respectively. ..
  5. Song X, Xie L, Wang X, Zeng Q, Chen T, Wang W, et al. Temozolomide-perillyl alcohol conjugate induced reactive oxygen species accumulation contributes to its cytotoxicity against non-small cell lung cancer. Sci Rep. 2016;6:22762 pubmed publisher
  6. Zhao X, Zhang M, Wang F, Zhao Y, Li J, Wang X, et al. CRP enhances soluble LOX-1 release from macrophages by activating TNF-? converting enzyme. J Lipid Res. 2011;52:923-33 pubmed publisher
    ..Thus, CRP might stimulate sLOX-1 release, and the underlying mechanisms possibly involved Fc?RII-mediated p47(phox) phosphorylation, ROS production, and TACE activation. ..
  7. Wang N, Xie K, Huo S, Zhao J, Zhang S, Miao J. Suppressing phosphatidylcholine-specific phospholipase C and elevating ROS level, NADPH oxidase activity and Rb level induced neuronal differentiation in mesenchymal stem cells. J Cell Biochem. 2007;100:1548-57 pubmed
    ..Furthermore, the level of Rb protein was evidently elevated. Our data suggested that PC-PLC mediated neuronal differentiation of rat MSCs by elevating NADPH oxidase activity, ROS level, and up-regulating the expression of Rb protein. ..
  8. Yu W, Chen G, Zhang P, Chen K. Purification, partial characterization and antitumor effect of an exopolysaccharide from Rhizopus nigricans. Int J Biol Macromol. 2016;82:299-307 pubmed publisher
    ..These findings bring new insights into the potential use of EPS1-1 as antitumor drug against human colorectal carcinoma. ..
  9. Wang J, Wang J, Xu C, Liu R, Chen Y. Molecular mechanism of catalase activity change under sodium dodecyl sulfate-induced oxidative stress in the mouse primary hepatocytes. J Hazard Mater. 2016;307:173-83 pubmed publisher
    ..When the sites in the interface is saturated, SDS interacts with VAL 73, HIS 74, ASN 147 and PHE 152, the key residues of the enzyme activity, and leads to the decrease of CAT activity. ..

More Information

Publications58

  1. Liu X, Zhao J, Xu J, Zhao B, Zhang Y, Zhang S, et al. Protective effects of a benzoxazine derivative against oxidized LDL-induced apoptosis and the increases of integrin beta4, ROS, NF-kappaB and P53 in human umbilical vein endothelial cells. Bioorg Med Chem Lett. 2009;19:2896-900 pubmed publisher
  2. Wang N, Sun C, Huo S, Zhang Y, Zhao J, Zhang S, et al. Cooperation of phosphatidylcholine-specific phospholipase C and basic fibroblast growth factor in the neural differentiation of mesenchymal stem cells in vitro. Int J Biochem Cell Biol. 2008;40:294-306 pubmed
    ..Moreover, basic fibroblast growth factor could contribute to rescuing the differentiated cells from death through decreasing overly high mitochondrial membrane potentials and reactive oxygen species levels. ..
  3. Zhao J, Miao J, Zhao B, Zhang S. Upregulating of Fas, integrin beta4 and P53 and depressing of PC-PLC activity and ROS level in VEC apoptosis by safrole oxide. FEBS Lett. 2005;579:5809-13 pubmed
  4. Hao E, Lang F, Chen Y, Zhang H, Cong X, Shen X, et al. Resveratrol alleviates endotoxin-induced myocardial toxicity via the Nrf2 transcription factor. PLoS ONE. 2013;8:e69452 pubmed publisher
    ..Our data suggest that resveratrol might be developed as a useful prophylactic management for septic cardiomyopathy. ..
  5. Hu J, Yin L, Xu K, Gao J, Tong L, Tang B. Vicinal diaminobenzoacridine used as the fluorescent probe for trace nitric oxide determination by flow injection spectrofluorimetry and macrophage cells imaging. Anal Chim Acta. 2008;606:57-62 pubmed
    ..1 x 10(-7) to 5.0 x 10(-6)M and the detection limit was 3.1 x 10(-8)M. Furthermore, the probe could make cell-derived NO "visible" by using confocal laser scanning microscope. ..
  6. Su L, Zhao B, Lv X, Wang N, Zhao J, Zhang S, et al. Safrole oxide induces neuronal apoptosis through inhibition of integrin beta4/SOD activity and elevation of ROS/NADPH oxidase activity. Life Sci. 2007;80:999-1006 pubmed
    ..Our study thus demonstrates that safrole oxide induces neuronal apoptosis through integrin beta4, ROS, NADPH, and MnSOD. ..
  7. Hou X, Song J, Li X, Zhang L, Wang X, Chen L, et al. Metformin reduces intracellular reactive oxygen species levels by upregulating expression of the antioxidant thioredoxin via the AMPK-FOXO3 pathway. Biochem Biophys Res Commun. 2010;396:199-205 pubmed publisher
    ..These results suggest that metformin reduces ROS levels by inducing Trx expression through activation of the AMPK-FOXO3 pathway. ..
  8. Li P, Zhang L, Zhang M, Zhou C, Lin N. Uric acid enhances PKC-dependent eNOS phosphorylation and mediates cellular ER stress: A mechanism for uric acid-induced endothelial dysfunction. Int J Mol Med. 2016;37:989-97 pubmed publisher
    ..Thus, we concluded that UA induced HUVEC apoptosis and endothelial dysfunction by triggering oxidative and ER stress through PKC/eNOS-mediated eNOS activity and NO production. ..
  9. Wang K, Wang Y, Qi Q, Zhang F, Zhang Y, Zhu X, et al. Inhibitory effects of S-allylmercaptocysteine against benzo(a)pyrene-induced precancerous carcinogenesis in human lung cells. Int Immunopharmacol. 2016;34:37-43 pubmed publisher
    ..SAMC appears to be a novel therapeutic candidate for the prevention and treatment of B(a)P-induced human lung cancer. ..
  10. Wang X, Chen Y, Qin W, Zhang W, Wei S, Wang J, et al. Arginase I attenuates inflammatory cytokine secretion induced by lipopolysaccharide in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2011;31:1853-60 pubmed publisher
    ..The results indicate the antiinflammatory effects of Arg I and suggest an unexpected beneficial role of Arg I in inflammatory disease. ..
  11. Dong W, Wang M, Xu F, Quan T, Peng K, Xiao L, et al. Wheat oxophytodienoate reductase gene TaOPR1 confers salinity tolerance via enhancement of abscisic acid signaling and reactive oxygen species scavenging. Plant Physiol. 2013;161:1217-28 pubmed publisher
    ..Rather than serving purely as an antioxidant, we believe that TaOPR1 acts during episodes of abiotic stress response as a signaling compound associated with the regulation of the ABA-mediated signaling network. ..
  12. Guan Q, Zhang Y, Yu C, Liu Y, Gao L, Zhao J. Hydrogen sulfide protects against high-glucose-induced apoptosis in endothelial cells. J Cardiovasc Pharmacol. 2012;59:188-93 pubmed publisher
    ..These results indicated that the protective effects of H2S on endothelial cells in the condition of high glucose might involve an antioxidative stress mechanism...
  13. Chen L, Liu L, Wang M, Fu J, Zhang Z, Hou J, et al. Hal2p functions in Bdf1p-involved salt stress response in Saccharomyces cerevisiae. PLoS ONE. 2013;8:e62110 pubmed publisher
    ..Our findings shed new light towards our understanding about the molecular mechanism of Bdf1p-involved salt stress response in budding yeast. ..
  14. Meng T, Yu J, Lei Z, Wu J, Wang S, Bo Q, et al. Propofol reduces lipopolysaccharide-induced, NADPH oxidase (NOX 2) mediated TNF- ? and IL-6 production in macrophages. Clin Dev Immunol. 2013;2013:325481 pubmed publisher
    ..Propofol also reduced LPS-induced NOX activity and expression of gp91phox and p47phox. We conclude that propofol modulates LPS signaling in macrophages by reducing NOX-mediated production of TNF-? and IL-6. ..
  15. Li Y, Liu M, Zuo Z, Liu J, Yu X, Guan Y, et al. TLR9 Regulates the NF-?B-NLRP3-IL-1? Pathway Negatively in Salmonella-Induced NKG2D-Mediated Intestinal Inflammation. J Immunol. 2017;199:761-773 pubmed publisher
    ..typhimurium infection and in the protection of intestinal integrity. ..
  16. Liu X, Pang Y, Zhu W, Zhao T, Zheng M, Wang Y, et al. Benazepril, an angiotensin-converting enzyme inhibitor, alleviates renal injury in spontaneously hypertensive rats by inhibiting advanced glycation end-product-mediated pathways. Clin Exp Pharmacol Physiol. 2009;36:287-96 pubmed publisher
    ..4. The results of the present study provide new insights into the regulation by the renin-angiotensin system of AGE-RAGE, oxidative stress and nephropathy, increasing our understanding of the role of the RAS in nephropathy. ..
  17. Liu B, Ma X, Guo D, Guo Y, Chen N, Bi H. Neuroprotective effect of alpha-lipoic acid on hydrostatic pressure-induced damage of retinal ganglion cells in vitro. Neurosci Lett. 2012;526:24-8 pubmed publisher
    ..These findings suggest that there are protective effects of ALA against elevated hydrostatic pressure-induced damage in RGC-5 cells, indicating ALA might be a potential therapeutic agent for glaucomatous optic neuropathy. ..
  18. Liu X, Yang H, Zhang X, Liu L, Lei M, Zhang Z, et al. Bdf1p deletion affects mitochondrial function and causes apoptotic cell death under salt stress. FEMS Yeast Res. 2009;9:240-6 pubmed publisher
    ..These results indicate that the bromodomain-containing protein, Bdf1p, is involved in the regulation of apoptosis in yeast cells. ..
  19. Cheng Y, Zhao Q, Liu X, Araki S, Zhang S, Miao J. Phosphatidylcholine-specific phospholipase C, p53 and ROS in the association of apoptosis and senescence in vascular endothelial cells. FEBS Lett. 2006;580:4911-5 pubmed
    ..The data suggested that PC-PLC was involved in the association of apoptosis and senescence. Its function might be closely related to the level of p53 in VECs. ..
  20. Li B, Li X, Gao H, Zhang J, Cai Q, Cheng M, et al. Grape seed procyanidin B2 inhibits advanced glycation end product-induced endothelial cell apoptosis through regulating GSK3? phosphorylation. Cell Biol Int. 2011;35:663-9 pubmed publisher
    ..GSPB2 therapy could become an effective approach to battling AGEs-induced endothelial apoptosis. ..
  21. Wu X, Cheng A, Sun L, Sun S, Lou H. Plagiochin E, an antifungal bis(bibenzyl), exerts its antifungal activity through mitochondrial dysfunction-induced reactive oxygen species accumulation in Candida albicans. Biochim Biophys Acta. 2009;1790:770-7 pubmed publisher
    ..albicans. The effect of PLE on the mitochondria function in C. albicans was assayed for the first time. These results would conduce to elucidate its underlying antifungal mechanism. ..
  22. Zhang L, Han J. Branched-chain amino acid transaminase 1 (BCAT1) promotes the growth of breast cancer cells through improving mTOR-mediated mitochondrial biogenesis and function. Biochem Biophys Res Commun. 2017;486:224-231 pubmed publisher
  23. Fang W, Li H, Zhou L, Su L, Liang Y, Mu Y. Effect of prostaglandin E1 on TNF-induced vascular inflammation in human umbilical vein endothelial cells. Can J Physiol Pharmacol. 2010;88:576-83 pubmed publisher
    ..We concluded that PGE1 suppressed the vascular inflammatory process, which might be closely related to the inhibition of reactive oxygen species and NF-kappaB activation in human umbilical vein endothelial cells. ..
  24. Xia L, Zhang D, Wang C, Wei F, Hu Y. PC-PLC is involved in osteoclastogenesis induced by TNF-? through upregulating IP3R1 expression. FEBS Lett. 2012;586:3341-8 pubmed publisher
    ..However, D609 did not inhibit RANKL-induced osteoclastogenesis. Our data suggest TNF-? promotes RANKL-induced osteoclastogenesis, at least partially, through PC-PLC/IP3R1/NFATc1 pathway...
  25. Sun C, Wang N, Huang J, Xin J, Peng F, Ren Y, et al. Inhibition of phosphatidylcholine-specific phospholipase C prevents bone marrow stromal cell senescence in vitro. J Cell Biochem. 2009;108:519-28 pubmed publisher
    ..Moreover, D609 suppressed the elevated levels of integrin beta4, caveolin-1 and ROS. The data suggest that PC-PLC is involved in senescence of BMSCs, and its function is associated with integrin beta4, caveolin-1 and ROS. ..
  26. Zhao P, Turdi S, Dong F, Xiao X, Su G, Zhu X, et al. Cardiac-specific overexpression of insulin-like growth factor I (IGF-1) rescues lipopolysaccharide-induced cardiac dysfunction and activation of stress signaling in murine cardiomyocytes. Shock. 2009;32:100-7 pubmed publisher
    ..These data collectively suggested a beneficial of IGF-1 in the management of cardiac dysfunction under sepsis. ..
  27. Luo Y, Zhang D, Dong X, Zhao P, Chen L, Song X, et al. Antimicrobial peptaibols induce defense responses and systemic resistance in tobacco against tobacco mosaic virus. FEMS Microbiol Lett. 2010;313:120-6 pubmed publisher
    ..We report on the antivirus mechanism of peptaibols, which sheds light on the potential of peptaibols in plant viral disease control...
  28. Zhao Z, Azadzoi K, Choi H, Jing R, Lu X, Li C, et al. LC-MS/MS Analysis Unravels Deep Oxidation of Manganese Superoxide Dismutase in Kidney Cancer. Int J Mol Sci. 2017;18: pubmed publisher
    ..Thus, LC-MS/MS analysis revealed multiple oxidative modifications of MNSOD at different amino acid residues that might mediate the regulation of the superoxide radicals, mitochondrial ROS scavenging and MNSOD activity in kidney cancer. ..
  29. Shi M, Zhang T, Sun L, Luo Y, Liu D, Xie S, et al. Calpain, Atg5 and Bak play important roles in the crosstalk between apoptosis and autophagy induced by influx of extracellular calcium. Apoptosis. 2013;18:435-51 pubmed publisher
    ..The potential of TK VI is proposed as a promising anticancer agent for its well-characterized activity of Ca(2+) agonist and as a possible novel therapeutic strategy that acts on cancer cell mitochondria. ..
  30. Wang Z, Wei X, Zhang Y, Ma X, Li B, Zhang S, et al. NADPH oxidase-derived ROS contributes to upregulation of TRPC6 expression in puromycin aminonucleoside-induced podocyte injury. Cell Physiol Biochem. 2009;24:619-26 pubmed publisher
    ..Our results provide direct evidence for the first time that NADPH oxidase-derived reactive oxygen species (ROS) is one of critical components of a signal transduction pathway that links PAN nephrosis to TRPC6-mediated Ca(2+) signaling. ..
  31. Zhao J, Zhao B, Wang W, Huang B, Zhang S, Miao J. Phosphatidylcholine-specific phospholipase C and ROS were involved in chicken blastodisc differentiation to vascular endothelial cells. J Cell Biochem. 2007;102:421-8 pubmed
    ..PC-PLC was an important factor in the blastodisc cell survival and differentiation, and it might perform its function associated with ROS. ..
  32. Du J, Yuan F, Zhao L, Zhu J, Huang Y, Zhang G, et al. Suppression of Kv1.5 protects against endothelial apoptosis induced by palmitate and in type 2 diabetes mice. Life Sci. 2017;168:28-37 pubmed publisher
    ..5 may serve as a therapeutic target of treatment for endothelial dysfunction induced by palmitate and lipid metabolism in T2DM patients. ..
  33. Wang F, Wang Z, Zhang Y, Du Z, Zhang X, Liu Q, et al. Protective effect of melatonin on bone marrow mesenchymal stem cells against hydrogen peroxide-induced apoptosis in vitro. J Cell Biochem. 2013;114:2346-55 pubmed publisher
    ..The findings suggest that melatonin may be an effectively protective agent against oxidative stress-induced MSC apoptosis...
  34. Wang Z, Liu D, Wang F, Liu S, Zhao S, Ling E, et al. Saturated fatty acids activate microglia via Toll-like receptor 4/NF-?B signalling. Br J Nutr. 2012;107:229-41 pubmed publisher
    ..In conclusion, the present in vitro study demonstrates that SFA could activate microglia and stimulate the TLR4/NF-?B pathway to trigger the production of pro-inflammatory mediators, which may contribute to neuronal death. ..
  35. Zhao Z, Wang H, Jessup J, Lindsey S, Chappell M, Groban L. Role of estrogen in diastolic dysfunction. Am J Physiol Heart Circ Physiol. 2014;306:H628-40 pubmed publisher
  36. Stine J, Guo H, Sheng X, Han X, Schointuch M, Gilliam T, et al. The HMG-CoA reductase inhibitor, simvastatin, exhibits anti-metastatic and anti-tumorigenic effects in ovarian cancer. Oncotarget. 2016;7:946-60 pubmed publisher
    ..Our findings demonstrate that simvastatin may have therapeutic benefit for ovarian cancer treatment and be worthy of further exploration in clinical trials. ..
  37. Zhang D, Chia C, Jiao X, Jin W, Kasagi S, Wu R, et al. D-mannose induces regulatory T cells and suppresses immunopathology. Nat Med. 2017;23:1036-1045 pubmed publisher
    ..This previously unrecognized immunoregulatory function of D-mannose may have clinical applications for immunopathology. ..
  38. Liu Y, Qiang W, Xu X, Dong R, Karst A, Liu Z, et al. Role of miR-182 in response to oxidative stress in the cell fate of human fallopian tube epithelial cells. Oncotarget. 2015;6:38983-98 pubmed publisher
  39. Wang J, Wang H, Hao P, Xue L, Wei S, Zhang Y, et al. Inhibition of aldehyde dehydrogenase 2 by oxidative stress is associated with cardiac dysfunction in diabetic rats. Mol Med. 2011;17:172-9 pubmed publisher
    ..ALDH2 inhibition may be associated with LV reduced contractility, and mitochondrial impairment aggravated by ALDH2 inhibition might reflect an underlying mechanism which causes cardiac dysfunction in diabetic rats. ..
  40. Liu Y, Chen L, Xu X, Vicaut E, Sercombe R. Both ischemic preconditioning and ghrelin administration protect hippocampus from ischemia/reperfusion and upregulate uncoupling protein-2. BMC Physiol. 2009;9:17 pubmed publisher
    ..The two dissimilar protective strategies, IPC and ghrelin administration, were both associated with upregulated UCP2, suggesting that UCP2 may often represent a final common pathway in protection from I/R. ..
  41. Li X, Rong Y, Zhang M, Wang X, LeMaire S, Coselli J, et al. Up-regulation of thioredoxin interacting protein (Txnip) by p38 MAPK and FOXO1 contributes to the impaired thioredoxin activity and increased ROS in glucose-treated endothelial cells. Biochem Biophys Res Commun. 2009;381:660-5 pubmed publisher
    ..Taken together, upregulation of Txnip and subsequent impairment of thioredoxin antioxidative system through p38 MAPK and FOXO1 may represent a novel mechanism for glucose-induced increase in intracellular ROS. ..
  42. Lv X, Su L, Yin D, Sun C, Zhao J, Zhang S, et al. Knockdown of integrin beta4 in primary cultured mouse neurons blocks survival and induces apoptosis by elevating NADPH oxidase activity and reactive oxygen species level. Int J Biochem Cell Biol. 2008;40:689-99 pubmed
  43. Guo D, Bi H, Wang D, Wu Q. Zinc oxide nanoparticles decrease the expression and activity of plasma membrane calcium ATPase, disrupt the intracellular calcium homeostasis in rat retinal ganglion cells. Int J Biochem Cell Biol. 2013;45:1849-59 pubmed publisher
    ..Thus, the disrupted calcium homeostasis is involved in the zinc oxide nanoparticle-induced rat retinal ganglion cell death. ..
  44. Li H, Wu S, Mao L, Lei G, Zhang L, Lu A, et al. Human pathogenic fungus Trichophyton schoenleinii activates the NLRP3 inflammasome. Protein Cell. 2013;4:529-38 pubmed publisher
    ..schoenleinii, and suggest that manipulating NLRP3 signaling can be a novel approach for control of diseases caused by T. schoenleinii infection. ..
  45. Guan Q, Wang X, Gao L, Chen J, Liu Y, Yu C, et al. Hydrogen sulfide suppresses high glucose-induced expression of intercellular adhesion molecule-1 in endothelial cells. J Cardiovasc Pharmacol. 2013;62:278-84 pubmed publisher
    ..These findings indicate that H?S might protect against HG-induced vascular damage by down-regulating ICAM-1 expression in endothelial cells...
  46. Xue L, Xu F, Meng L, Wei S, Wang J, Hao P, et al. Acetylation-dependent regulation of mitochondrial ALDH2 activation by SIRT3 mediates acute ethanol-induced eNOS activation. FEBS Lett. 2012;586:137-42 pubmed publisher
    ..Furthermore, activation of ALDH2 by ethanol is due to its hyperacetylation by SIRT3 inactivation. These data suggest that ethanol-induced eNOS activation in HAECs may be dependent on ALDH2 hyperacetylation by SIRT3 inactivation. ..
  47. Fu Q, Chen K, Zhu Q, Wang W, Huang F, Miao L, et al. ?-catenin promotes intracellular bacterial killing via suppression of Pseudomonas aeruginosa-triggered macrophage autophagy. J Int Med Res. 2017;45:556-569 pubmed publisher
    ..Rapamycin/starvation-induced autophagy resulted in reduced bacterial killing following P. aeruginosa infection. Conclusion ?-catenin may promote bacterial killing via suppression of P. aeruginosa-induced macrophage autophagy. ..
  48. Wang D, Yuan X, Liu T, Liu L, Hu Y, Wang Z, et al. Neuroprotective activity of lavender oil on transient focal cerebral ischemia in mice. Molecules. 2012;17:9803-17 pubmed publisher
    ..These results suggested that the neuroprotective effects of lavender oil against cerebral ischemia/reperfusion injury may be attributed to its antioxidant effects. ..
  49. Han W, Lu X, Jia X, Zhou T, Guo C. Soluble mediators released from PI-IBS patients' colon induced alteration of mast cell: involvement of reactive oxygen species. Dig Dis Sci. 2012;57:311-9 pubmed publisher
    ..The study shows that ROS scavenger reverses the SUP of PI-IBS-induced enhancement of PMCs activities, and that these effects may be related to activation of PAR(2). These findings might pave the way to new therapeutic targets in PI-IBS. ..