Aim To investigate the anticancer activity of two new cytotoxins from thevenom of Agkistrodon acutus. Methods The venom was isolated by FPLC column chromatography consistingof DEAE Sepharose FF and Source 30S. The cyt...Aim To investigate the anticancer activity of two new cytotoxins from thevenom of Agkistrodon acutus. Methods The venom was isolated by FPLC column chromatography consistingof DEAE Sepharose FF and Source 30S. The cytotoxic activity on tumor cells was detected by MITmethod. Purity and molecular weight were determined by SDS-PAGE (silver staining). Their stabilitiesto temperature and pH were also detected. Results Two pure cytotoxins named ACTX-6 and ACTX-8 wereobtained. Their molecular weights are 98 kDa and 27 kDa, respectively. ACTX-6 consists of twosubunits bonded together by disulfide bonds. Conclusion ACTX-6 and ATCX-8 have highest inhibitoryactivity on lung cancer cell A549. ACTX-6 is stable to heat while ACTX-8 not. ACTX-6 is stablebetween pH 7-9 and ACTX-8 between pH 6 - 9.展开更多
A major problem which is poorly understood in the management of bladder cancer is low sensitivity to chemotherapy and high recurrence after transurethral resection. Insulin-like growth factor 1 receptor (IGF-1R) signa...A major problem which is poorly understood in the management of bladder cancer is low sensitivity to chemotherapy and high recurrence after transurethral resection. Insulin-like growth factor 1 receptor (IGF-1R) signaling plays a very important role in progression, invasion and metastasis of bladder cancer cells. In this study, we investigated whether IGF-1R was involved in the growth stimulating activity and drug resistance of bladder cancer cells. The results showed: The mRNAs of IGF-1, IGF-2 and IGF-1R were strongly expressed in serum-free cultured T24 cell line, whereas normal urothelial cells did not express these factors/receptors or only in trace levels; T24 cell responded far better to growth stimulation by IGF-1 than did normal urothelial cells; blockage of IGF1R by antisense oligodeoxynucleotide (ODN) significantly inhibited the growth of T24 cell and enhanced sensitivity and apoptosis of T24 cells to mitomycin (MMC). These results suggested that blockage of IGF-IR signaling might potentially contribute to the treatment of bladder cancer cells which are insensitive to chemotherapy.展开更多
OBJECTIVE： To investigate analgesic, antidiarrhoeal and cytotoxic activities of the ethanol extract of Passiflora foetida L. （Passifloraceae） by three experimental methods. METHODS： Analgesic activity of the ethan...OBJECTIVE： To investigate analgesic, antidiarrhoeal and cytotoxic activities of the ethanol extract of Passiflora foetida L. （Passifloraceae） by three experimental methods. METHODS： Analgesic activity of the ethanol extract of Passiflora foetida L. （EEPF） was carried out using acetic acid-induced writhing inhibition in mice. The method of castor oil-induced diarrhoea in mice was utilized to evaluate antidiarrhoeal activity. The cytotoxic activity of EEPF was explored with a brine shrimp lethality bioassay. RESULTS： The extract showed 68.75% and 30.00% inhibition of writhe at the doses of 500 and 250 mg/kg body weight, respectively. The extract increased the mean latent period prior to diarrhoeal onset to about 1.55 h and 1.17 h, and decreased the mean number of stools to 4.4 and 5.6 at the doses of 500 and 250 mg/kg body weight. The extract also demonstrated cytotoxic activity in the brine shrimp lethality assay, and the median lethal concentration for brine shrimp nauplii was 80 pg/mL. CONCLUSION： The results suggest that the plant extract has analgesic and antidiarrhoeal activities, supporting its uses in traditional medicine. The results also demonstrate that the plant extract possesses cytotoxic activities.展开更多
OBJECTIVE:To investigate the underlying mechanism of Bailian (Radix Ampelopsis Japonicae,BL) extract action on colorectal cancer (CRC).METHODS:We explored the involvement of β-catenin signaling on the anti-CRC effect...OBJECTIVE:To investigate the underlying mechanism of Bailian (Radix Ampelopsis Japonicae,BL) extract action on colorectal cancer (CRC).METHODS:We explored the involvement of β-catenin signaling on the anti-CRC effects of an BL ethanolic extract (BLE) in cell models by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,immunofluorescent staining,luciferase assay,Western blot analysis and real-time quantitative polymerase chain reaction analysis.Anti-CRC compounds were quantified by high performance liquid chromatography.RESULTS:The contents of gallic acid,catechin,and epicatechin in the BLE were 0.23,1.25,and 0.18 g/kg,respectively.BLE-mediated cytotoxic and apoptotic effects were accompanied by lowered β-catenin/Tcf transcriptional activity,reduced β-catenin nuclear localization,and downregulated protein and mRNA levels of both β-catenin and molecules regulated by β-catenin.CONCLUSION:The mechanism underpinning the anti-CRC effects of BLE may involve inhibition of β-catenin signaling.Further studies are necessary to establish the role of β-catenin signaling in the action of BLE-mediated anti-CRC effects.展开更多
To elucidate potential antioxidant, antidiarrheal, cytotoxic, and antibacterial activities of the ethanol extract of A/ocasia indica Schott tuber in different experimental models established in vitro and in vivo. METH...To elucidate potential antioxidant, antidiarrheal, cytotoxic, and antibacterial activities of the ethanol extract of A/ocasia indica Schott tuber in different experimental models established in vitro and in vivo. METHODS： In vitro antioxidant activity was evaluated by 2, 2-diphenyl-l-picrylhydrazyl （DPPH） radical-scavenging assay. Phenolic content was estimated by using Folin-Ciocalteu＇s reagent while reducing ability was measured by ferric reducing power assay./n vivo antidiarrheal studies were carried out in mice, and the activity was evaluated in castor oil and magnesium sulfate- induced diarrhea. Disk diffusion assay was utilized to determine antibacterial activity against a number of pathogenic bacterial strains. Acute toxicity test was carried out to measure the safe doses for the extract. RESULTS： In DPPH radical-scavenging assay, the extract exhibited strong radical-scavenging activity with the 50% inhibitory concentration value of 42.66 IJg/mL. Total phenolic content was found to be 542.26 mg gallic acid equivalent per 100 g of dried tuber extract, whereas flavonoid content was found to be 4.30 mg quercetin equivalent/g of dried tuber extract. In reducing power assay, the extract showed strong reducing power in a concentration-dependent manner. The extract significantly （P 〈 0.01） enhanced the latent period and decreased defecation in both castor oil- and magnesium sulfate-induced diarrhea. The extract also lessened gastrointestinal motility in mice. Potential antibacterial activity was exhibited by the extract against all the tested bacterial strains in disk diffusion assay. The 50% lethal concentration against brine shrimp nauplii was 81.09 μg/mL. CONCLUSION： The results demonstrated that the ethanol extract of A. inc/ica has potential antioxidant, antidiarrheal, cytotoxic, and antibacterial activity.展开更多
OBJECTIVE: To evaluate biological potential of methanol and n-hexane extracts of aerial parts in seven species of family Poaceae.METHODS: Qualitative phytochemical tests were done by using standard protocols. In vitro...OBJECTIVE: To evaluate biological potential of methanol and n-hexane extracts of aerial parts in seven species of family Poaceae.METHODS: Qualitative phytochemical tests were done by using standard protocols. In vitro antioxidant activity was performed via different assays and antimicrobial potential was observed via disc diffusion method. Cytotoxic activity was carried out using brine shrimps’ assay.RESULTS: Phytochemical studies revealed the presence of alkaloids, flavonoids, glycosides, phenols,steroids, saponins, tannins, anthocyanins and coumarins in most of the plant extracts. Maximum antioxidant and antimicrobial potential were observed in Cymbopogon citratus methanol extract and Cymbopogon citratus n-hexane extract along with significant number of total flavonoids and phenols contents. However, Polypogon monspeliensis methanol extract and Polypogon monspeliensis n-hexane extract showed minimum antioxidant as well as antimicrobial potential. Moreover, methanol extracts showed a cytotoxic effect with their effectiveness ranked Polypogon monspeliensis methanol extract > Cymbopogon citratus methanol extract > Phalaris minor n-hexane extract > Aristida funiculata methanol extract > Stipagrostis plumosa methanol extract > Cenchrus ciliaris methanol extract > Panicum antidotale methanol extract. Similarly, n-hexane plant extracts revealed cytotoxic activity in decreasing order Cenchrus ciliaris n-hexane extract > Stipagrostis plumosa n-hexane extract > Phalaris minor n-hexane extract > Aristida funiculata n-hexane extract > Polypogon monspeliensis n-hexane extract > Panicum antidotale n-hexane extract > Cymbopogon citratus n-hexane extract respectively.CONCLUSION: Methanol extracts exhibit significant antioxidant and antimicrobial potential which can be correlated to their medicinal values. The observed brine shrimp’s lethality of the plant extracts revealed the presence of potent cytotoxic components in these plants.展开更多
OBJECTIVE:To estimate the phytochemical composition,antioxidant,antifungal,cytotoxic and phytotoxic activities of three important medicinal plants of Poonch valley,Azad Kashmir Pakistan.METHODS:Phytochemicals were inv...OBJECTIVE:To estimate the phytochemical composition,antioxidant,antifungal,cytotoxic and phytotoxic activities of three important medicinal plants of Poonch valley,Azad Kashmir Pakistan.METHODS:Phytochemicals were investigated for both qualitative(phenols,flavonoids,alkaloids and saponins)and quantitative(total phenolic and flavonoid contents)analysis of plant extracts prepared in ethanol,ethyl acetate and benzene.Moreover,antioxidant potential was investigated by screening botanical extracts against 2,2-diphenyl-1-picrylhydrazyl scavenging assay,phosphomolybdenum and total reducing power assay.While,disc diffusion method was used for determination of antifungal potential of all extracts against four pathogenic strains.Furthermore,brine shrimp cytotoxicity assay was conducted for cytotoxic potential and radish seed germination assay was carried out for estimation of allelopathic potential of plant extracts.RESULTS:Phytochemical evaluation showed the presence of phenolics,flavonoids,alkaloids and saponins in almost all plants.In addition to significant antioxidant potential,Rubia cordifolia(ethanolic extract)revealed highest amount of phenolics and flavonoids.The said plant also exhibited good cytotoxic activity.Among plant extracts highest antifungal activity and allelopathic potential was recorded by Oxalis latifolia(ethyl acetate extract).Ethanol and ethyl acetate were observed to be the best choice of solvents.The best solvents-based results were obtained by Ethanol followed by Ethyl acetate and Benzene.CONCLUSION:For further studies,Rubia cordifolia and Oxalis latifolia are the most promising medicinal plants of Poonch valley,Azad Kashmir Pakistan at molecular level in order to isolate the compounds concerning with pronounced activities.展开更多
OBJECTIVE:To investigate the phytochemicals and in vitro antioxidant,antimicrobial and cytotoxic potential of Rumex dentatus(R.dentatus)leaf extracts.METHODS:The total phenolics and flavonoids content of R.dentatus ex...OBJECTIVE:To investigate the phytochemicals and in vitro antioxidant,antimicrobial and cytotoxic potential of Rumex dentatus(R.dentatus)leaf extracts.METHODS:The total phenolics and flavonoids content of R.dentatus extracts were evaluated by the Folin-Ciocalteu and aluminum chloride colorimetric methods respectively.Antioxidant potential of studied plant extracts was assessed through 2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity,total reducing power and total antioxidant methods.Moreover,antibacterial and antifungal capacity was also evaluated by disc diffusion method against six clinically isolated multi-drug resistant bacterial strains as well as six fungal isolates.Further,cell cytotoxicity was also evaluated through3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay.RESULTS:Ethanol extract showed highest total phenolic[(38.9±1.5)μg gallic acid equivalent/mg]and total flavonoids[(17.2±1.9)μg quercetin equivalent/mg]contents.Antioxidant assays indicated that ethanol and methanol extracts possess potent antioxidant potential.Moreover,it was observed that ethanol and hexane extracts have the potential to inhibit most of the tested multi-drug resistant bacterial strains while methanol,chloroform and hexane extracts could inhibit the growth of pathogenic fungal strains successfully.Among all the studied extracts,ethanolic extract showed highest cytotoxicity against MCF-7 cell line then Hep-2 and DU-145 cell lines by MTT assay with lowest IC50 of 47.3μg/m L.CONCLUSION:These results suggest that R.dentatus could be a potent alternative candidate for treatment of microbial infections and for breast cancer treatment.展开更多
OBJECTIVE:To report the phytochemical composition(flavonoids,phenolics,saponins,tannins,and terpenoids)and biological activities(antioxidant,phytotoxic,cytotoxic,antifungal activities)of medicinally important plants o...OBJECTIVE:To report the phytochemical composition(flavonoids,phenolics,saponins,tannins,and terpenoids)and biological activities(antioxidant,phytotoxic,cytotoxic,antifungal activities)of medicinally important plants of Pothohar region.METHODS:In the current study various qualitative and quantitative phytochemical tests were conducted to investigate the phytochemical composition of plant extracts prepared in benzene,chloroform and methanol.The same extracts were further utilized in different biological activities i.e.,antioxidant[total antioxidant capacity,total reducing power,and 2,2-diphenyl-1-picrylhydrazyl(DPPH)scavenging assay],phytotoxicity(Radish seed bioassay),brine shrimp cytotoxicity and antifungal activities(against four pathogenic fungal strains).RESULTS:Phytochemical analysis indicate flavonoids,phenolics,saponins,tannins and terpenoids were present in almost all plants however,maximum amount of total phenolic and flavonoid contents was reported in of Malva parviflora and Lepidium pinnatifidum.Extracts of Malva parviflora and Lepidium pinnatifidum also depicted the superlative antioxidant activity(total antioxidant capacity,total reducing power,and DPPH scavenging activity).Maximum fungal growth inhibition was demonstrated by extracts of Centaurea calcitropa,Vicia sativa and Malva parviflora.The maximum cytotoxicity was shown by the extracts of Centaurea calcitropa.Moreover,for phytotoxicity assay the highest allelopathic potential was exhibited by extracts of Lepidium pinnatifidum.Solvents prejudiced results;the best results were obtained by Methanol followed by Chloroform and Benzene.CONCLUSION:Centaurea calcitropa,Vicia sativa,Malva parviflora and Lepidium pinnatifidum are most promising medicinal plants of Pothohar region for future studies.展开更多
H py/ori is probably the most prevalent human pathogen worldwide. Since it was initially suggested in 1983 by Marshall and Warren to be implicated in gastritis and peptic ulcer disease, H pylori has also been implicat...H py/ori is probably the most prevalent human pathogen worldwide. Since it was initially suggested in 1983 by Marshall and Warren to be implicated in gastritis and peptic ulcer disease, H pylori has also been implicated in gastric carcinoma and was classified as a class I carcinogen. In the last two decades, a noteworthy body of research has revealed the multiple processes that this gram negative bacterium activates to cause gastroduodenal disease in humans. Most infections are acquired early in life and may persist for the life of the individual. While infected individuals mount an inflammatory response that becomes chronic, along with a detectable adaptive immune response, these responses are ineffective in clearing the infection. Hpylori has unique features that allow it to reside within the harsh conditions of the gastric environment, and also to evade the host immune response. In this review, we discuss the various virulence factors expressed by this bacterium and how they interact with the host epithelium to influence pathogenesis.展开更多
AIM: To better understand the pathogenic role of Helicobacter pylori (H. pylori) in pre-eclampsia (PE), and whether it is associated or not with fetal growth retardation (FGR). METHODS: Maternal blood samples were col...AIM: To better understand the pathogenic role of Helicobacter pylori (H. pylori) in pre-eclampsia (PE), and whether it is associated or not with fetal growth retardation (FGR). METHODS: Maternal blood samples were collected from 62 consecutive pregnant women with a diagnosis of PE and/or FGR, and from 49 women with uneventful pregnancies (controls). Serum samples were evaluated by immunoblot assay for presence of specific antibodies against H. pylori antigens [virulence: cytotoxin-associated antigen A (CagA); ureases; heat shock protein B; flagellin A; persistence: vacuolating cytotoxin A (VacA)]. Maternal complete blood count and liver enzymes levels were assessed at delivery by an automated analyzer. RESULTS: A significantly higher percentage of H. pyloriseropositive women were found among PE cases (85.7%) compared to controls (42.9%, P < 0.001). There were no differences between pregnancies complicated by FGR without maternal hypertension (46.2%) and controls. Importantly, persistent and virulent infections (VacA/ CagA seropositive patients, intermediate leukocyte blood count and aspartate aminotransferase levels) were exclusively associated with pre-eclampsia complicated by FGR, while virulent but acute infections (CagA positive/ VacA negative patients, highest leukocyte blood count and aspartate aminotransferase levels) specifically correlated with PE without FGR. CONCLUSION: Our data strongly indicate that persistent and virulent H. pylori infections cause or contribute to PE complicated by FGR, but not to PE without feto-placental compromise.展开更多
Many active secretions produced by animals have been employed in the development of new drugs to treat diseases such as hypertension and cancer.Snake venom toxins coutributed significantly to the treatment of many med...Many active secretions produced by animals have been employed in the development of new drugs to treat diseases such as hypertension and cancer.Snake venom toxins coutributed significantly to the treatment of many medical conditions.There are many published studies describing and elucidating the anti-cancer potential of snake venom.Cancer therapy is one of the main areas for the use of protein peptides and enzymes originating from animals of different species.Some of these proteins or peptides and enzymes from snake venom when isolated and evaluated may bind specifically to cancer cell membranes,affecting the migration and proliferation of these cells.Some of substances found in the snake venom present a great potential as anti-tumor agent.In this review,we presented the main results of recent years of research involving the active compounds of snake venom that have anticancer activity.展开更多
Helicobacter pylori(H. pylori) is perhaps the most ubiquitous and successful human pathogen, since it colonizes the stomach of more than half of humankind. Infection with this bacterium is commonly acquired during chi...Helicobacter pylori(H. pylori) is perhaps the most ubiquitous and successful human pathogen, since it colonizes the stomach of more than half of humankind. Infection with this bacterium is commonly acquired during childhood. Once infected, people carry the bacteria for decades or even for life, if not treated. Persistent infection with this pathogen causes gastritis, peptic ulcer disease and is also strongly associated with the development of gastric cancer. Despite induction of innate and adaptive immune responses in the infected individual, the host is unable to clear the bacteria. One widely accepted hallmark of H. pylori is that it successfully and stealthily evades host defense mechanisms. Though the gastric mucosa is well protected against infection, H. pylori is able to reside under the mucus, attach to gastric epithelial cells and cause persistent infection by evading immune responses mediated by host. In this review, we discuss how H. pylori avoids innate and acquired immune response elements, uses gastric epithelial cells as mediators to manipulate host T cell responses and uses virulence factors to avoid adaptive immune responses by T cells to establish a persistent infection. We also discuss in this review how the genetic diversity of this pathogen helps for its survival.展开更多
BACKGROUND Approximately 90%of new cases of noncardiac gastric cancer(GC)are related to Helicobacter pylori(H.pylori),and cytotoxin-associated gene A(CagA)is one of the main pathogenic factors.Recent studies have show...BACKGROUND Approximately 90%of new cases of noncardiac gastric cancer(GC)are related to Helicobacter pylori(H.pylori),and cytotoxin-associated gene A(CagA)is one of the main pathogenic factors.Recent studies have shown that the pharmacological effects of cryptotanshinone(CTS)can be used to treat a variety of tumors.However,the effects of CTS on H.pylori,especially CagA+strain-induced gastric mucosal lesions,on the development of GC is unknown.AIM To assess the role of CTS in CagA-induced proliferation and metastasis of GC cells,and determine if CagA+H.pylori strains causes pathological changes in the gastric mucosa of mice.METHODS The effects of CTS on the proliferation of GC cells were assessed using the Cell Counting Kit-8(CCK-8)assay,and the abnormal growth,migration and invasion caused by CagA were detected by CCK-8 and transwell assays.After transfection with pSR-HA-CagA and treatment with CTS,proliferation and metastasis were evaluated by CCK-8 and transwell assays,respectively,and the expression of Src homology 2(SH2)domain–containing phosphatase 2(SHP2)and phosphorylated SHP2(p-SHP2)was detected using western blotting in AGS cells.The enzymelinked immunosorbent assay was used to determine the immunoglobulin G(IgG)level against CagA in patient serum.Mice were divided into four groups and administered H.pylori strains(CagA+or CagA-)and CTS(or PBS)intragastrically,and establishment of the chronic infection model was verified using polymerase chain reaction and sequencing of isolated strains.Hematoxylin and eosin staining was used to assess mucosal erosion in the stomach and toxicity to the liver and kidney.RESULTS CTS inhibited the growth of GC cells in dose-and time-dependent manners.Overexpression of CagA promoted the growth,migration,and invasion of GC cells.Importantly,we demonstrated that CTS significantly inhibited the CagAinduced abnormal proliferation,migration,and invasion of GC cells.Moreover,the expression of p-SHP2 protein in tumor tissue was related to the expression of IgG against CagA in the serum of GC patients.Additionally,CTS suppressed the protein expression levels of both SHP2 and p-SHP2 in GC cells.CTS suppressed CagA+H.pylori strain-induced mucosal erosion in the stomach of mice but had no obvious effects on the CagA-H.pylori strain group.CONCLUSION CTS inhibited CagA-induced proliferation and the epithelial-mesenchymal transition of GC cells in vitro,and CagA+H.pylori strains caused mucosal erosions of the stomach in vivo by decreasing the protein expression of SHP2.展开更多
AIM; To determine whether Helicobacter pylori （H pylon） vacuolating cytotoxin （VacA） regulates release of proinflammatory cytokines （IL-1β, IL-8, TNF-α, and IL-6） or alters gastric epithelial cell viability an...AIM; To determine whether Helicobacter pylori （H pylon） vacuolating cytotoxin （VacA） regulates release of proinflammatory cytokines （IL-1β, IL-8, TNF-α, and IL-6） or alters gastric epithelial cell viability and to determine whether NaCl affects these VacA-induced changes. METHODS： Vacuolating activity was determined by measuring the uptake of neutral red into vacuoles of VacA-treated human gastric epithelial （AGS） cells. AGS cell viability was assessed by direct cell counting. Specific enzyme-linked immunosorbent assays （ELISA） and reverse transcdptase-polymerase chain reaction（RT-PCR） were performed to examine the effects of H pylori VacA and NaCl on cell pro-inflammatory cytokine production in AGS cells. Immunohistochemical staining of gastric tissue from Mongolian gerbils was used to confirm VacAinduced pro-inflammatory cytokine production and the effects of NaCl on this VacA-induced response. RESULTS： Addition of VacA alone reduced AGS cell viability （P〈 0.05）, and this reduction was enhanced by high doses of NaCl （P〈0.05）. VacA alone induced expression of TNF-α, IL-8 and IL-1β, while NaCl alone induced expression of TNF-α and IL-1β. Changes in mRNA levels in the presence of both VacA and NaCl were more complicated. For the case of TNF-α, expression was dosedependent on NaCl. IL-6 mRNA was not detected. However, low levels of IL-6 were detected by EUSA. Positive immunohistochemical staining of IL-1, IL-6, and TNF-α was found in gastric tissue of H pylori-infected gerbils fed with either a normal diet or a high salt diet. However, the staining of these three cytoldnes was sb＇onger in H pylori-infected animals fed with a 5g/kg NaCl diet. CONCLUSION： VacA decreases the viability of AGS cells, and this effect can be enhanced by NaCl. NaCl also affects the production of pro-inflammatory cytokines in- duced by VacA, suggesting that NaCl plays an important role in Hpylori-induced gastric epithelial cell cytotoxicity.展开更多
A series of new antitumor compounds having indolecarbazole structures were designed and synthesized. The methoxy substituted indolecarbazole parent nucleus, which was firstly synthesized, is condensed with bromine sub...A series of new antitumor compounds having indolecarbazole structures were designed and synthesized. The methoxy substituted indolecarbazole parent nucleus, which was firstly synthesized, is condensed with bromine substituted amino acid methyl ester to produce the target compounds. The target compounds were performed with methylthiazolyldiphenyl-tetrazolium bromide（MTT） in vitro cytotoxin activity test and the results showed that compounds CZ-1, CZ-3 and CZ-6 have higher activity against human colon cancer（HT-29） and（HCT-8）, hepatocellular carcinoma（Bel-7402）, NSCLC（A549） and breast cancer（MCF-7） cells as compared to the positive control JDC-108.展开更多
Helicobacter pylori(H.pylori)is a Gram-negative bacterium that infects about half of the world's population.H.pylori infection prevails by several mechanisms of adaptation of the bacteria and by its virulence fact...Helicobacter pylori(H.pylori)is a Gram-negative bacterium that infects about half of the world's population.H.pylori infection prevails by several mechanisms of adaptation of the bacteria and by its virulence factors including the cytotoxin associated antigen A(CagA).CagA is an oncoprotein that is the protagonist of gastric carcinogenesis associated with prolonged H.pylori infection.In this sense,small regulatory RNAs(sRNAs)are important macromolecules capable of inhibiting and activating gene expression.This function allows sRNAs to act in adjusting to unstable environmental conditions and in responding to cellular stresses in bacterial infections.Recent discoveries have shown that nickelregulated small RNA(NikS)is a post-transcriptional regulator of virulence properties of H.pylori,including the oncoprotein CagA.Notably,high concentrations of nickel cause the reduction of NikS expression and consequently this increases the levels of CagA.In addition,NikS expression appears to be lower in clinical isolates from patients with gastric cancer when compared to patients without.With that in mind,this minireview approaches,in an accessible way,the most important and current aspects about the role of NikS in the control of virulence factors of H.pylori and the potential clinical repercussions of this modulation.展开更多
AIM: To investigate age, sex, histopathology and Helicobacter pylori (H. pylori) status, as risk factors for gastroduodenal disease outcome in Brazilian dyspeptic patients.tients submitted to upper gastroscopy at Hosp...AIM: To investigate age, sex, histopathology and Helicobacter pylori (H. pylori) status, as risk factors for gastroduodenal disease outcome in Brazilian dyspeptic patients.tients submitted to upper gastroscopy at Hospital das Clinicas of Marilia, antral biopsy specimens were obtained and subjected to histopathology and H. pylori diagnosis. All patients presenting chronic gastritis (CG) and peptic ulcer (PU) disease localized in the stomach, gastric ulcer (GU) and/or duodenal ulcer (DU) were included in the study. Gastric biopsies (n = 668) positive for H. pylori by rapid urease test were investigated for vacuolating cytotoxin A (vacA ) medium (m) region mosaicism by polymerase chain reaction. Logistic regression analysis was performed to verify the association of age, sex, histopathologic alterations, H. pylori diagnosis and vacA m region mosaicism with the incidence of DU, GU and CG in patients. RESULTS: Of 1466 patients submitted to endoscopy, 1060 (72.3%) presented CG [male/female = 506/554; mean age (year) ± SD = 51.2 ± 17.81], 88 (6.0%) presented DU [male/female = 54/34; mean age (year) ± SD = 51.4 ± 17.14], and 75 (5.1%) presented GU [male/female = 54/21; mean age (year) ± SD = 51.3 ± 17.12] and were included in the comparative analysis. Sex and age showed no detectable effect on CG incidence (overall c 2 = 2.1, P = 0.3423). Sex [Odds ratios (OR) = 1.8631, P = 0.0058] but not age (OR = 0.9929, P = 0.2699) was associated with DU and both parameters had a highly significant effect on GU (overall c 2 = 30.5, P < 0.0001). The histopathological results showed a significant contribution of ageing for both atrophy (OR = 1.0297, P < 0.0001) and intestinal metaplasia (OR = 1.0520, P < 0.0001). Presence of H. pylori was significantly associated with decreasing age (OR = 0.9827, P < 0.0001) and with the incidence of DU (OR = 3.6077, P < 0.0001). The prevalence of m1 in DU was statistically significant (OR = 2.3563, P = 0.0018) but not in CG (OR = 2.678, P = 0.0863) and GU (OR = 1.520, P = 0.2863). CONCLUSION: In our population, male gender was a risk factor for PU; ageing for GU, atrophy and metapla-sia; and H. pylori of vacA m1 genotype for DU.展开更多
Clostridium difficile (CD), specifically its toxins, have been implicated as a risk factor for exacerbation of the inflammatory process in up to 5% of patients with ulcerative colitis or Crohn’s disease. Typical evid...Clostridium difficile (CD), specifically its toxins, have been implicated as a risk factor for exacerbation of the inflammatory process in up to 5% of patients with ulcerative colitis or Crohn’s disease. Typical evidence of colonic changes with CD infection, including pseudomembranous exudate, are often not present; however, a severe clinical course may result, including precipitation of toxic colitis and toxic megacolon. Recently, hypervirulent CD strains have been reported raising concern for a more severe disease process in patients with underlying inflammatory bowel disease.Moreover, small bowel involvement or CD enteritis has been increasingly described, usually in those with a history of a prior colectomy or total proctocolectomy for prior severe and extensive inflammatory bowel disease. Finally, refractory or treatment-resistant pouchitis may occur with CD infection.展开更多
BACKGROUND In recent years,associations between specific virulence markers of Helicobacter pylori(H.pylori)and gastrointestinal disorders have been suggested.AIM To investigate the presence of virulence factors includ...BACKGROUND In recent years,associations between specific virulence markers of Helicobacter pylori(H.pylori)and gastrointestinal disorders have been suggested.AIM To investigate the presence of virulence factors including vacuolating cytotoxin A genotypes(s1m1,s1m2,s2m1,and s2m2),cytotoxin-associated gene A(CagA),and urease activity in H.pylori strains isolated from Arab and Jewish populations in northern Israel and to assess associations between these factors and patients’demographics and clinical outcomes.METHODS Patients(n=108)who underwent gastroscopy at the Baruch Padeh Medical Center,Poriya due to symptomatic gastroduodenal pathologies as part of H.pylori diagnosis were enrolled in the study.Gastric biopsy specimens were collected from the antrum of the stomach.Clinical condition was assessed by clinical pathology tests.Bacteria were isolated on modified BD Helicobacter Agar(BD Diagnostics,Sparks,MD,United States).Bacterial DNA was extracted,and PCR was performed to detect CagA and vacuolating cytotoxin A genes.Urease activity was assessed using a rapid urease test.RESULTS A significant correlation was found between disease severity and patient ethnicity(P=0.002).A significant correlation was found between CagA presence and the s1m1 genotype(P=0.02),which is considered the most virulent genotype.Further,a higher level of urease activity was associated with isolates originating from the Jewish population.Moreover,higher urease activity levels were measured among CagA-/s1m1 and CagA-/s2m2 isolates.CONCLUSION Our study highlights the importance of incorporating molecular methods for detection of virulence markers of H.pylori in order to tailor optimal treatments for each patient.Further investigation should be performed regarding associations between H.pylori virulence factors and ethnicity.展开更多
文摘Aim To investigate the anticancer activity of two new cytotoxins from thevenom of Agkistrodon acutus. Methods The venom was isolated by FPLC column chromatography consistingof DEAE Sepharose FF and Source 30S. The cytotoxic activity on tumor cells was detected by MITmethod. Purity and molecular weight were determined by SDS-PAGE (silver staining). Their stabilitiesto temperature and pH were also detected. Results Two pure cytotoxins named ACTX-6 and ACTX-8 wereobtained. Their molecular weights are 98 kDa and 27 kDa, respectively. ACTX-6 consists of twosubunits bonded together by disulfide bonds. Conclusion ACTX-6 and ATCX-8 have highest inhibitoryactivity on lung cancer cell A549. ACTX-6 is stable to heat while ACTX-8 not. ACTX-6 is stablebetween pH 7-9 and ACTX-8 between pH 6 - 9.
文摘A major problem which is poorly understood in the management of bladder cancer is low sensitivity to chemotherapy and high recurrence after transurethral resection. Insulin-like growth factor 1 receptor (IGF-1R) signaling plays a very important role in progression, invasion and metastasis of bladder cancer cells. In this study, we investigated whether IGF-1R was involved in the growth stimulating activity and drug resistance of bladder cancer cells. The results showed: The mRNAs of IGF-1, IGF-2 and IGF-1R were strongly expressed in serum-free cultured T24 cell line, whereas normal urothelial cells did not express these factors/receptors or only in trace levels; T24 cell responded far better to growth stimulation by IGF-1 than did normal urothelial cells; blockage of IGF1R by antisense oligodeoxynucleotide (ODN) significantly inhibited the growth of T24 cell and enhanced sensitivity and apoptosis of T24 cells to mitomycin (MMC). These results suggested that blockage of IGF-IR signaling might potentially contribute to the treatment of bladder cancer cells which are insensitive to chemotherapy.
文摘OBJECTIVE： To investigate analgesic, antidiarrhoeal and cytotoxic activities of the ethanol extract of Passiflora foetida L. （Passifloraceae） by three experimental methods. METHODS： Analgesic activity of the ethanol extract of Passiflora foetida L. （EEPF） was carried out using acetic acid-induced writhing inhibition in mice. The method of castor oil-induced diarrhoea in mice was utilized to evaluate antidiarrhoeal activity. The cytotoxic activity of EEPF was explored with a brine shrimp lethality bioassay. RESULTS： The extract showed 68.75% and 30.00% inhibition of writhe at the doses of 500 and 250 mg/kg body weight, respectively. The extract increased the mean latent period prior to diarrhoeal onset to about 1.55 h and 1.17 h, and decreased the mean number of stools to 4.4 and 5.6 at the doses of 500 and 250 mg/kg body weight. The extract also demonstrated cytotoxic activity in the brine shrimp lethality assay, and the median lethal concentration for brine shrimp nauplii was 80 pg/mL. CONCLUSION： The results suggest that the plant extract has analgesic and antidiarrhoeal activities, supporting its uses in traditional medicine. The results also demonstrate that the plant extract possesses cytotoxic activities.
基金Supported by Food and Health Bureau of Hong Kong:Elucidating the Involvement of IL-17-IL-6-STAT3 Axis in the anti-melanoma Effects of a Herbal Formula Comprising Flos Sophorae and Flos Lonicerae(No.HMRF14150571)Science,Technology and Innovation Commission of Shenzhen:anti-colorectal Cancer Effects of Bailian(Radix Ampelopsis Japonicae)extract(No.JCYJ20140807091945050)+3 种基金Exploring the Mechanisms for the anti-rheumatoid Rrthritis Effects of Chinese Medicinal Herb Based on Targeting the TLR4 Signaling Pathway(No.JCYJ20160229210327924)The Research Grants Council of Hong Kong:Elucidating the role of TLR4/STAT3 Signaling in the Antimelanoma Effects of Atractylenolide Ⅱ(No.12125116)The National Natural Science Foundation of China:Exploring the let-7/IGF1R-related Mechanism of Action for the Anti-melanoma Effects of a Herbal formula Huai Hua Jin Yin Jiu(No.81673649)Guangdong Natural Science Foundation:Evaluating the Involvement of miR-34b in the Anti-melanoma Action of Si-Jun-Zi-Tang(No.2016A030313007)
文摘OBJECTIVE:To investigate the underlying mechanism of Bailian (Radix Ampelopsis Japonicae,BL) extract action on colorectal cancer (CRC).METHODS:We explored the involvement of β-catenin signaling on the anti-CRC effects of an BL ethanolic extract (BLE) in cell models by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,immunofluorescent staining,luciferase assay,Western blot analysis and real-time quantitative polymerase chain reaction analysis.Anti-CRC compounds were quantified by high performance liquid chromatography.RESULTS:The contents of gallic acid,catechin,and epicatechin in the BLE were 0.23,1.25,and 0.18 g/kg,respectively.BLE-mediated cytotoxic and apoptotic effects were accompanied by lowered β-catenin/Tcf transcriptional activity,reduced β-catenin nuclear localization,and downregulated protein and mRNA levels of both β-catenin and molecules regulated by β-catenin.CONCLUSION:The mechanism underpinning the anti-CRC effects of BLE may involve inhibition of β-catenin signaling.Further studies are necessary to establish the role of β-catenin signaling in the action of BLE-mediated anti-CRC effects.
基金grateful to the authorities of Phytochemistry and Pharmacology Laboratory, Pharmacy Discipline, Life Science School, Khulna University, Bangladesh for providingnecessary instrumental and financial support
文摘To elucidate potential antioxidant, antidiarrheal, cytotoxic, and antibacterial activities of the ethanol extract of A/ocasia indica Schott tuber in different experimental models established in vitro and in vivo. METHODS： In vitro antioxidant activity was evaluated by 2, 2-diphenyl-l-picrylhydrazyl （DPPH） radical-scavenging assay. Phenolic content was estimated by using Folin-Ciocalteu＇s reagent while reducing ability was measured by ferric reducing power assay./n vivo antidiarrheal studies were carried out in mice, and the activity was evaluated in castor oil and magnesium sulfate- induced diarrhea. Disk diffusion assay was utilized to determine antibacterial activity against a number of pathogenic bacterial strains. Acute toxicity test was carried out to measure the safe doses for the extract. RESULTS： In DPPH radical-scavenging assay, the extract exhibited strong radical-scavenging activity with the 50% inhibitory concentration value of 42.66 IJg/mL. Total phenolic content was found to be 542.26 mg gallic acid equivalent per 100 g of dried tuber extract, whereas flavonoid content was found to be 4.30 mg quercetin equivalent/g of dried tuber extract. In reducing power assay, the extract showed strong reducing power in a concentration-dependent manner. The extract significantly （P 〈 0.01） enhanced the latent period and decreased defecation in both castor oil- and magnesium sulfate-induced diarrhea. The extract also lessened gastrointestinal motility in mice. Potential antibacterial activity was exhibited by the extract against all the tested bacterial strains in disk diffusion assay. The 50% lethal concentration against brine shrimp nauplii was 81.09 μg/mL. CONCLUSION： The results demonstrated that the ethanol extract of A. inc/ica has potential antioxidant, antidiarrheal, cytotoxic, and antibacterial activity.
文摘OBJECTIVE: To evaluate biological potential of methanol and n-hexane extracts of aerial parts in seven species of family Poaceae.METHODS: Qualitative phytochemical tests were done by using standard protocols. In vitro antioxidant activity was performed via different assays and antimicrobial potential was observed via disc diffusion method. Cytotoxic activity was carried out using brine shrimps’ assay.RESULTS: Phytochemical studies revealed the presence of alkaloids, flavonoids, glycosides, phenols,steroids, saponins, tannins, anthocyanins and coumarins in most of the plant extracts. Maximum antioxidant and antimicrobial potential were observed in Cymbopogon citratus methanol extract and Cymbopogon citratus n-hexane extract along with significant number of total flavonoids and phenols contents. However, Polypogon monspeliensis methanol extract and Polypogon monspeliensis n-hexane extract showed minimum antioxidant as well as antimicrobial potential. Moreover, methanol extracts showed a cytotoxic effect with their effectiveness ranked Polypogon monspeliensis methanol extract > Cymbopogon citratus methanol extract > Phalaris minor n-hexane extract > Aristida funiculata methanol extract > Stipagrostis plumosa methanol extract > Cenchrus ciliaris methanol extract > Panicum antidotale methanol extract. Similarly, n-hexane plant extracts revealed cytotoxic activity in decreasing order Cenchrus ciliaris n-hexane extract > Stipagrostis plumosa n-hexane extract > Phalaris minor n-hexane extract > Aristida funiculata n-hexane extract > Polypogon monspeliensis n-hexane extract > Panicum antidotale n-hexane extract > Cymbopogon citratus n-hexane extract respectively.CONCLUSION: Methanol extracts exhibit significant antioxidant and antimicrobial potential which can be correlated to their medicinal values. The observed brine shrimp’s lethality of the plant extracts revealed the presence of potent cytotoxic components in these plants.
文摘OBJECTIVE:To estimate the phytochemical composition,antioxidant,antifungal,cytotoxic and phytotoxic activities of three important medicinal plants of Poonch valley,Azad Kashmir Pakistan.METHODS:Phytochemicals were investigated for both qualitative(phenols,flavonoids,alkaloids and saponins)and quantitative(total phenolic and flavonoid contents)analysis of plant extracts prepared in ethanol,ethyl acetate and benzene.Moreover,antioxidant potential was investigated by screening botanical extracts against 2,2-diphenyl-1-picrylhydrazyl scavenging assay,phosphomolybdenum and total reducing power assay.While,disc diffusion method was used for determination of antifungal potential of all extracts against four pathogenic strains.Furthermore,brine shrimp cytotoxicity assay was conducted for cytotoxic potential and radish seed germination assay was carried out for estimation of allelopathic potential of plant extracts.RESULTS:Phytochemical evaluation showed the presence of phenolics,flavonoids,alkaloids and saponins in almost all plants.In addition to significant antioxidant potential,Rubia cordifolia(ethanolic extract)revealed highest amount of phenolics and flavonoids.The said plant also exhibited good cytotoxic activity.Among plant extracts highest antifungal activity and allelopathic potential was recorded by Oxalis latifolia(ethyl acetate extract).Ethanol and ethyl acetate were observed to be the best choice of solvents.The best solvents-based results were obtained by Ethanol followed by Ethyl acetate and Benzene.CONCLUSION:For further studies,Rubia cordifolia and Oxalis latifolia are the most promising medicinal plants of Poonch valley,Azad Kashmir Pakistan at molecular level in order to isolate the compounds concerning with pronounced activities.
文摘OBJECTIVE:To investigate the phytochemicals and in vitro antioxidant,antimicrobial and cytotoxic potential of Rumex dentatus(R.dentatus)leaf extracts.METHODS:The total phenolics and flavonoids content of R.dentatus extracts were evaluated by the Folin-Ciocalteu and aluminum chloride colorimetric methods respectively.Antioxidant potential of studied plant extracts was assessed through 2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity,total reducing power and total antioxidant methods.Moreover,antibacterial and antifungal capacity was also evaluated by disc diffusion method against six clinically isolated multi-drug resistant bacterial strains as well as six fungal isolates.Further,cell cytotoxicity was also evaluated through3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay.RESULTS:Ethanol extract showed highest total phenolic[(38.9±1.5)μg gallic acid equivalent/mg]and total flavonoids[(17.2±1.9)μg quercetin equivalent/mg]contents.Antioxidant assays indicated that ethanol and methanol extracts possess potent antioxidant potential.Moreover,it was observed that ethanol and hexane extracts have the potential to inhibit most of the tested multi-drug resistant bacterial strains while methanol,chloroform and hexane extracts could inhibit the growth of pathogenic fungal strains successfully.Among all the studied extracts,ethanolic extract showed highest cytotoxicity against MCF-7 cell line then Hep-2 and DU-145 cell lines by MTT assay with lowest IC50 of 47.3μg/m L.CONCLUSION:These results suggest that R.dentatus could be a potent alternative candidate for treatment of microbial infections and for breast cancer treatment.
基金the Higher Education Commission for Pakistan for its support
文摘OBJECTIVE:To report the phytochemical composition(flavonoids,phenolics,saponins,tannins,and terpenoids)and biological activities(antioxidant,phytotoxic,cytotoxic,antifungal activities)of medicinally important plants of Pothohar region.METHODS:In the current study various qualitative and quantitative phytochemical tests were conducted to investigate the phytochemical composition of plant extracts prepared in benzene,chloroform and methanol.The same extracts were further utilized in different biological activities i.e.,antioxidant[total antioxidant capacity,total reducing power,and 2,2-diphenyl-1-picrylhydrazyl(DPPH)scavenging assay],phytotoxicity(Radish seed bioassay),brine shrimp cytotoxicity and antifungal activities(against four pathogenic fungal strains).RESULTS:Phytochemical analysis indicate flavonoids,phenolics,saponins,tannins and terpenoids were present in almost all plants however,maximum amount of total phenolic and flavonoid contents was reported in of Malva parviflora and Lepidium pinnatifidum.Extracts of Malva parviflora and Lepidium pinnatifidum also depicted the superlative antioxidant activity(total antioxidant capacity,total reducing power,and DPPH scavenging activity).Maximum fungal growth inhibition was demonstrated by extracts of Centaurea calcitropa,Vicia sativa and Malva parviflora.The maximum cytotoxicity was shown by the extracts of Centaurea calcitropa.Moreover,for phytotoxicity assay the highest allelopathic potential was exhibited by extracts of Lepidium pinnatifidum.Solvents prejudiced results;the best results were obtained by Methanol followed by Chloroform and Benzene.CONCLUSION:Centaurea calcitropa,Vicia sativa,Malva parviflora and Lepidium pinnatifidum are most promising medicinal plants of Pothohar region for future studies.
基金the National Institutes of Health Grants DK50669and DK56338 EB was a recipient of a fellowship under NationaInstitutes of Health T32 AI007536-06 Training Grant. The costs ofpublication of this article were defrayed in part by the payment ofpage charges. The article must therefore be marked advertisemenin accordance with 18 U.S.C. section 1734 solely to indicate thisfact
文摘H py/ori is probably the most prevalent human pathogen worldwide. Since it was initially suggested in 1983 by Marshall and Warren to be implicated in gastritis and peptic ulcer disease, H pylori has also been implicated in gastric carcinoma and was classified as a class I carcinogen. In the last two decades, a noteworthy body of research has revealed the multiple processes that this gram negative bacterium activates to cause gastroduodenal disease in humans. Most infections are acquired early in life and may persist for the life of the individual. While infected individuals mount an inflammatory response that becomes chronic, along with a detectable adaptive immune response, these responses are ineffective in clearing the infection. Hpylori has unique features that allow it to reside within the harsh conditions of the gastric environment, and also to evade the host immune response. In this review, we discuss the various virulence factors expressed by this bacterium and how they interact with the host epithelium to influence pathogenesis.
基金Supported by The Italian Ministry of Health, Programma per la Ricerca Sanitaria 2007, Programma Strategico, Salute della donna/Area materno infantile, No. RFPS-2007-4-638281
文摘AIM: To better understand the pathogenic role of Helicobacter pylori (H. pylori) in pre-eclampsia (PE), and whether it is associated or not with fetal growth retardation (FGR). METHODS: Maternal blood samples were collected from 62 consecutive pregnant women with a diagnosis of PE and/or FGR, and from 49 women with uneventful pregnancies (controls). Serum samples were evaluated by immunoblot assay for presence of specific antibodies against H. pylori antigens [virulence: cytotoxin-associated antigen A (CagA); ureases; heat shock protein B; flagellin A; persistence: vacuolating cytotoxin A (VacA)]. Maternal complete blood count and liver enzymes levels were assessed at delivery by an automated analyzer. RESULTS: A significantly higher percentage of H. pyloriseropositive women were found among PE cases (85.7%) compared to controls (42.9%, P < 0.001). There were no differences between pregnancies complicated by FGR without maternal hypertension (46.2%) and controls. Importantly, persistent and virulent infections (VacA/ CagA seropositive patients, intermediate leukocyte blood count and aspartate aminotransferase levels) were exclusively associated with pre-eclampsia complicated by FGR, while virulent but acute infections (CagA positive/ VacA negative patients, highest leukocyte blood count and aspartate aminotransferase levels) specifically correlated with PE without FGR. CONCLUSION: Our data strongly indicate that persistent and virulent H. pylori infections cause or contribute to PE complicated by FGR, but not to PE without feto-placental compromise.
文摘Many active secretions produced by animals have been employed in the development of new drugs to treat diseases such as hypertension and cancer.Snake venom toxins coutributed significantly to the treatment of many medical conditions.There are many published studies describing and elucidating the anti-cancer potential of snake venom.Cancer therapy is one of the main areas for the use of protein peptides and enzymes originating from animals of different species.Some of these proteins or peptides and enzymes from snake venom when isolated and evaluated may bind specifically to cancer cell membranes,affecting the migration and proliferation of these cells.Some of substances found in the snake venom present a great potential as anti-tumor agent.In this review,we presented the main results of recent years of research involving the active compounds of snake venom that have anticancer activity.
基金Supported by National Institutes of Health grants K22AI68712,R56DK090090-01American Gastroenterological Association Research Scholar Award,NIH 1U54RR02614+3 种基金The University of Texas Medical Branch Clinical and Translational Sciences AwardThe American cancer society RSG-10-159-01-LIB,NIH 8UL1TR000041The University of New Mexico clinical and Translational Science CenterTaslima T Lina is funded by Sealy Centre for Vaccine Development Pre-doctoral fellowship and McLaughlin Pre-doctoral Fellowship,UTMB
文摘Helicobacter pylori(H. pylori) is perhaps the most ubiquitous and successful human pathogen, since it colonizes the stomach of more than half of humankind. Infection with this bacterium is commonly acquired during childhood. Once infected, people carry the bacteria for decades or even for life, if not treated. Persistent infection with this pathogen causes gastritis, peptic ulcer disease and is also strongly associated with the development of gastric cancer. Despite induction of innate and adaptive immune responses in the infected individual, the host is unable to clear the bacteria. One widely accepted hallmark of H. pylori is that it successfully and stealthily evades host defense mechanisms. Though the gastric mucosa is well protected against infection, H. pylori is able to reside under the mucus, attach to gastric epithelial cells and cause persistent infection by evading immune responses mediated by host. In this review, we discuss how H. pylori avoids innate and acquired immune response elements, uses gastric epithelial cells as mediators to manipulate host T cell responses and uses virulence factors to avoid adaptive immune responses by T cells to establish a persistent infection. We also discuss in this review how the genetic diversity of this pathogen helps for its survival.
基金National Natural Science Foundation of China,No.81572350。
文摘BACKGROUND Approximately 90%of new cases of noncardiac gastric cancer(GC)are related to Helicobacter pylori(H.pylori),and cytotoxin-associated gene A(CagA)is one of the main pathogenic factors.Recent studies have shown that the pharmacological effects of cryptotanshinone(CTS)can be used to treat a variety of tumors.However,the effects of CTS on H.pylori,especially CagA+strain-induced gastric mucosal lesions,on the development of GC is unknown.AIM To assess the role of CTS in CagA-induced proliferation and metastasis of GC cells,and determine if CagA+H.pylori strains causes pathological changes in the gastric mucosa of mice.METHODS The effects of CTS on the proliferation of GC cells were assessed using the Cell Counting Kit-8(CCK-8)assay,and the abnormal growth,migration and invasion caused by CagA were detected by CCK-8 and transwell assays.After transfection with pSR-HA-CagA and treatment with CTS,proliferation and metastasis were evaluated by CCK-8 and transwell assays,respectively,and the expression of Src homology 2(SH2)domain–containing phosphatase 2(SHP2)and phosphorylated SHP2(p-SHP2)was detected using western blotting in AGS cells.The enzymelinked immunosorbent assay was used to determine the immunoglobulin G(IgG)level against CagA in patient serum.Mice were divided into four groups and administered H.pylori strains(CagA+or CagA-)and CTS(or PBS)intragastrically,and establishment of the chronic infection model was verified using polymerase chain reaction and sequencing of isolated strains.Hematoxylin and eosin staining was used to assess mucosal erosion in the stomach and toxicity to the liver and kidney.RESULTS CTS inhibited the growth of GC cells in dose-and time-dependent manners.Overexpression of CagA promoted the growth,migration,and invasion of GC cells.Importantly,we demonstrated that CTS significantly inhibited the CagAinduced abnormal proliferation,migration,and invasion of GC cells.Moreover,the expression of p-SHP2 protein in tumor tissue was related to the expression of IgG against CagA in the serum of GC patients.Additionally,CTS suppressed the protein expression levels of both SHP2 and p-SHP2 in GC cells.CTS suppressed CagA+H.pylori strain-induced mucosal erosion in the stomach of mice but had no obvious effects on the CagA-H.pylori strain group.CONCLUSION CTS inhibited CagA-induced proliferation and the epithelial-mesenchymal transition of GC cells in vitro,and CagA+H.pylori strains caused mucosal erosions of the stomach in vivo by decreasing the protein expression of SHP2.
文摘AIM; To determine whether Helicobacter pylori （H pylon） vacuolating cytotoxin （VacA） regulates release of proinflammatory cytokines （IL-1β, IL-8, TNF-α, and IL-6） or alters gastric epithelial cell viability and to determine whether NaCl affects these VacA-induced changes. METHODS： Vacuolating activity was determined by measuring the uptake of neutral red into vacuoles of VacA-treated human gastric epithelial （AGS） cells. AGS cell viability was assessed by direct cell counting. Specific enzyme-linked immunosorbent assays （ELISA） and reverse transcdptase-polymerase chain reaction（RT-PCR） were performed to examine the effects of H pylori VacA and NaCl on cell pro-inflammatory cytokine production in AGS cells. Immunohistochemical staining of gastric tissue from Mongolian gerbils was used to confirm VacAinduced pro-inflammatory cytokine production and the effects of NaCl on this VacA-induced response. RESULTS： Addition of VacA alone reduced AGS cell viability （P〈 0.05）, and this reduction was enhanced by high doses of NaCl （P〈0.05）. VacA alone induced expression of TNF-α, IL-8 and IL-1β, while NaCl alone induced expression of TNF-α and IL-1β. Changes in mRNA levels in the presence of both VacA and NaCl were more complicated. For the case of TNF-α, expression was dosedependent on NaCl. IL-6 mRNA was not detected. However, low levels of IL-6 were detected by EUSA. Positive immunohistochemical staining of IL-1, IL-6, and TNF-α was found in gastric tissue of H pylori-infected gerbils fed with either a normal diet or a high salt diet. However, the staining of these three cytoldnes was sb＇onger in H pylori-infected animals fed with a 5g/kg NaCl diet. CONCLUSION： VacA decreases the viability of AGS cells, and this effect can be enhanced by NaCl. NaCl also affects the production of pro-inflammatory cytokines in- duced by VacA, suggesting that NaCl plays an important role in Hpylori-induced gastric epithelial cell cytotoxicity.
基金supported by the science and technology support project of Jiangsu Province(No.BY2015057-03)
文摘A series of new antitumor compounds having indolecarbazole structures were designed and synthesized. The methoxy substituted indolecarbazole parent nucleus, which was firstly synthesized, is condensed with bromine substituted amino acid methyl ester to produce the target compounds. The target compounds were performed with methylthiazolyldiphenyl-tetrazolium bromide（MTT） in vitro cytotoxin activity test and the results showed that compounds CZ-1, CZ-3 and CZ-6 have higher activity against human colon cancer（HT-29） and（HCT-8）, hepatocellular carcinoma（Bel-7402）, NSCLC（A549） and breast cancer（MCF-7） cells as compared to the positive control JDC-108.
基金Supported by CNPq Brazil (National Council for Scientific and Technological Development)-FFM,No. 317005/2021-09
文摘Helicobacter pylori(H.pylori)is a Gram-negative bacterium that infects about half of the world's population.H.pylori infection prevails by several mechanisms of adaptation of the bacteria and by its virulence factors including the cytotoxin associated antigen A(CagA).CagA is an oncoprotein that is the protagonist of gastric carcinogenesis associated with prolonged H.pylori infection.In this sense,small regulatory RNAs(sRNAs)are important macromolecules capable of inhibiting and activating gene expression.This function allows sRNAs to act in adjusting to unstable environmental conditions and in responding to cellular stresses in bacterial infections.Recent discoveries have shown that nickelregulated small RNA(NikS)is a post-transcriptional regulator of virulence properties of H.pylori,including the oncoprotein CagA.Notably,high concentrations of nickel cause the reduction of NikS expression and consequently this increases the levels of CagA.In addition,NikS expression appears to be lower in clinical isolates from patients with gastric cancer when compared to patients without.With that in mind,this minireview approaches,in an accessible way,the most important and current aspects about the role of NikS in the control of virulence factors of H.pylori and the potential clinical repercussions of this modulation.
基金Supported by Fundaao de Amparo a Pesquisa do Estado de So Paulo (FAPESP), Research Grant 06/01223-0Fellowship CGF 2001/14509-5
文摘AIM: To investigate age, sex, histopathology and Helicobacter pylori (H. pylori) status, as risk factors for gastroduodenal disease outcome in Brazilian dyspeptic patients.tients submitted to upper gastroscopy at Hospital das Clinicas of Marilia, antral biopsy specimens were obtained and subjected to histopathology and H. pylori diagnosis. All patients presenting chronic gastritis (CG) and peptic ulcer (PU) disease localized in the stomach, gastric ulcer (GU) and/or duodenal ulcer (DU) were included in the study. Gastric biopsies (n = 668) positive for H. pylori by rapid urease test were investigated for vacuolating cytotoxin A (vacA ) medium (m) region mosaicism by polymerase chain reaction. Logistic regression analysis was performed to verify the association of age, sex, histopathologic alterations, H. pylori diagnosis and vacA m region mosaicism with the incidence of DU, GU and CG in patients. RESULTS: Of 1466 patients submitted to endoscopy, 1060 (72.3%) presented CG [male/female = 506/554; mean age (year) ± SD = 51.2 ± 17.81], 88 (6.0%) presented DU [male/female = 54/34; mean age (year) ± SD = 51.4 ± 17.14], and 75 (5.1%) presented GU [male/female = 54/21; mean age (year) ± SD = 51.3 ± 17.12] and were included in the comparative analysis. Sex and age showed no detectable effect on CG incidence (overall c 2 = 2.1, P = 0.3423). Sex [Odds ratios (OR) = 1.8631, P = 0.0058] but not age (OR = 0.9929, P = 0.2699) was associated with DU and both parameters had a highly significant effect on GU (overall c 2 = 30.5, P < 0.0001). The histopathological results showed a significant contribution of ageing for both atrophy (OR = 1.0297, P < 0.0001) and intestinal metaplasia (OR = 1.0520, P < 0.0001). Presence of H. pylori was significantly associated with decreasing age (OR = 0.9827, P < 0.0001) and with the incidence of DU (OR = 3.6077, P < 0.0001). The prevalence of m1 in DU was statistically significant (OR = 2.3563, P = 0.0018) but not in CG (OR = 2.678, P = 0.0863) and GU (OR = 1.520, P = 0.2863). CONCLUSION: In our population, male gender was a risk factor for PU; ageing for GU, atrophy and metapla-sia; and H. pylori of vacA m1 genotype for DU.
文摘Clostridium difficile (CD), specifically its toxins, have been implicated as a risk factor for exacerbation of the inflammatory process in up to 5% of patients with ulcerative colitis or Crohn’s disease. Typical evidence of colonic changes with CD infection, including pseudomembranous exudate, are often not present; however, a severe clinical course may result, including precipitation of toxic colitis and toxic megacolon. Recently, hypervirulent CD strains have been reported raising concern for a more severe disease process in patients with underlying inflammatory bowel disease.Moreover, small bowel involvement or CD enteritis has been increasingly described, usually in those with a history of a prior colectomy or total proctocolectomy for prior severe and extensive inflammatory bowel disease. Finally, refractory or treatment-resistant pouchitis may occur with CD infection.
基金The study was reviewed and approved by the Helsinki Committee of the Baruch Padeh Medical Center,Poriya(Approval No.POR 0007-20).
文摘BACKGROUND In recent years,associations between specific virulence markers of Helicobacter pylori(H.pylori)and gastrointestinal disorders have been suggested.AIM To investigate the presence of virulence factors including vacuolating cytotoxin A genotypes(s1m1,s1m2,s2m1,and s2m2),cytotoxin-associated gene A(CagA),and urease activity in H.pylori strains isolated from Arab and Jewish populations in northern Israel and to assess associations between these factors and patients’demographics and clinical outcomes.METHODS Patients(n=108)who underwent gastroscopy at the Baruch Padeh Medical Center,Poriya due to symptomatic gastroduodenal pathologies as part of H.pylori diagnosis were enrolled in the study.Gastric biopsy specimens were collected from the antrum of the stomach.Clinical condition was assessed by clinical pathology tests.Bacteria were isolated on modified BD Helicobacter Agar(BD Diagnostics,Sparks,MD,United States).Bacterial DNA was extracted,and PCR was performed to detect CagA and vacuolating cytotoxin A genes.Urease activity was assessed using a rapid urease test.RESULTS A significant correlation was found between disease severity and patient ethnicity(P=0.002).A significant correlation was found between CagA presence and the s1m1 genotype(P=0.02),which is considered the most virulent genotype.Further,a higher level of urease activity was associated with isolates originating from the Jewish population.Moreover,higher urease activity levels were measured among CagA-/s1m1 and CagA-/s2m2 isolates.CONCLUSION Our study highlights the importance of incorporating molecular methods for detection of virulence markers of H.pylori in order to tailor optimal treatments for each patient.Further investigation should be performed regarding associations between H.pylori virulence factors and ethnicity.
