Evaluation of the Bioremediation Potential and Antimicrobial Activity of Pseudomonas and Bacillus Bacteria Isolated from Landfills in Brazzaville, Congo

The pollution of ecosystems as a result of urbanization, industrialization and poor agricultural practices is becoming increasingly alarming. This has a major impact on health and the economy. This pollution causes illness in humans and animals, even at low levels of exposure, leading to endocrine disorders, congenital malformations, cardiovascular disease, nervous system damage and cancer. They are a brake on redevelopment because of the threats they pose, generally causing an anaerobic environment by blocking the diffusion of air into the soil pores, thus affecting the microbial communities living there and preventing the infiltration of water necessary for plant growth. In an ecosystem subjected to various disturbances, changes can be observed in ecosystem structure and function, including loss of aesthetic values, changes in biomass or productivity, and changes in species composition. These include loss of aesthetic values, changes in biomass or productivity, and altered species composition, as a result of habitat loss, disruption of food webs and variations in macro- and micro-climatic environmental conditions. Respect for the environment is becoming a major concern in today’s society. To remedy this, the concept of biological control was used as an alternative, with the selection of microorganisms of bioremediator interest. Twenty (20) isolates, including 10 (50%) from the Pseudomonas genus and 10 (50%) from the Bacillus genus, were isolated from landfills, identified and tested to assess their biofertilization (phosphate solubilization) and depollution (hydrocarbon degradation) potential, and to inhibit the growth of certain microorganisms. The results showed that all Pseudomonas and Bacillus isolates solubilized inorganic phosphate, although this activity was higher in Bacillus. All Bacillus inhibited the growth of all the pathogens included in this study, while Pseudomonas only inhibited the growth of E. coli. With regard to their ability to degrade hydrocarbons, these bacteria all showed exponential growth kinetics in the presence of gasoline. These kinetics evolved as a function of the number of days. The results obtained from this work leave no doubt as to the capacity of microorganisms to be used on a large scale as soil biofertilizers to restore soil integrity and promote sustainable agriculture, but also as biodepollutants to purify ecosystems.

Molecular Identification of Isolated Bacteria from Soils in Likouala Peat Bog Area, Republic of Congo

This study aimed to the molecular identification of isolated bacteria from the soils of Likouala (Congo-Brazzaville) peat bog area. Counting and isolation were carried out on Mossel and TSB media enriched with petroleum and vegetable oil;the amplification and sequencing of 16S RNA genes by PCR and Artic Oxford Nanopore Technology. The results showed bacterial loads of (5.81 ± 1.08) × 104;(6.64 ± 1.94) × 104 et (8.56 ± 1.19) × 103 CFU/g on Mossel respectively for samples 1, 2 and 3 against (2.12 ± 4.1) × 108 et (8.15 ± 10.1) × 107 CFU/g respectively on TSB enriched with petroleum and vegetable oil exclusively with sample 2. The analysis of the 16S rRNA of the isolates gene made it possible, after PCR, agarose gel electrophoresis, sequencing and bioinformatics analysis, to identify eight (08) strains with similarities of 99 to 100% whose sequences genes placed in GenBank have made it possible to obtain accession numbers corresponding to: Bacillus thuringiensis strain (ON303633);Bacillus cereus strain (ON350770);Bacillus thuringiensis strain (ON350771);Bacillus thuringiensis strain (ON738723);Priestia megaterium strain (ON738719);Bacillus anthracis strain (ON738720);Bacillus subtilis (ON738721);Enterobacter sp (ON738722). The phylogenetic classification of strains was done and revealed two genuses which are Bacillus and Enterobacteriaceae.

High prevalence of multidrug-resistance in Acinetobacter baumannii and dissemination of carbapenemase-encoding genes bla_(OXA-23-like),bla_(OXA-24-like)and bla_(NDM-1) in Algiers hospitals

Objective:To assess and characterize antibiotic resistance in Acinetobacter baumannii strains recovered from 5 health-care facilities in Algiers.Methods:Antibiotic susceptibility testing was performed by agar diffusion and agar dilution methods,resistance genes were identified by PCR and sequencing,and molecular typing of isolates was carried out by enterobacterial repetitive intergenic consensus-PCR(ERIC-PCR).Results:Among 125 tested isolates,117(93.6% ) were multidrug-resistant.of which 94(75.2% ) were imipenem resistant.The bla_(ADC)and bla_(OXA-51-like) genes were detected in all isolates,in association with ISAba I sequence in 84% and 8% (imipenem resistant) of isolates,respectively.The bla_(OXA-23-like) and bla_(OXA-24-like)carbapenemase genes were delected in 67.02% and 20.21% of imipenem-resistant isolates,respectively.The bla_(OXA-23-like) gene is linked to ISAba1 or ISAba4 elements.The metallo-β-lactamase NDM-1 gene was found in 10(10.6% ) imipenem-resisianl strains from three hospitals,it is linked to ISAba125 clement in nine strains.Extended spectrum β-lactamases production was not detected.Imipenem and cefotaxime resistance phenolypes could not be transferred to Escherichia coli by conjugation.Outer membrane protein CarO gene was not delected in four imipenem-resisianl isolates.The aac(6')-1b.sul1,sul2,tetA and tetB genes were present in 5.31% .36.17% .77.65% .1.06% and 65.92% of strains,respectively.Class 1 integrons were detected in 23.4% strains.KRIC-PCR typing showed a genetic diversity among bla_(OXA-23-like) and bla_(OXA-24-like) positive strains,while clonality was observed among bla_(NDM-1)positives.Conclusions:This study highlighted the high prevalence of imipenem resistance in Acinetobacter baumannii in Algiers hospitals mediated mainly by bla_(OXA-23-like),bla_(OXA-24-like),and bla_(NDM-1) genes.

Antihydatic and immunomodulatory effects of Punica granatum peel aqueous extract in a murine model of echinococcosis

Objective:To investigate the effect of pomegranate peel aqueous extract(PGE) on the development of secondary experimental echinococcosis and on the viability of Echinococcux granulosus protoscoleces,and the immunomodulatory properties of PGE.Methods:Swiss mice were inoculated intraperitoneally with viable protoscoleces.Then,PGE was orally administered daily during cystic echinococcosis development.Cyst development and hepatic damage were macroscopically and histologically analyzed.The production of nitric oxide and TNF-α was assessed in plasma and the hepatic expression of iNOS.TNF-α,NF-κB and CD68 was examined.Moreover,protoscoleces were cultured and treated with different concentrations of PGE.Results:It was observed that in vitro treatment of protoscoleces caused a significant decrease in viability in a PGE-dose-dependent manner.In vivo,after treatment of cystic echinococcosis infected mice with PGE,a significant decrease in nitric oxide levels(P<0.000 1)and TNF-α levels(P<0.001) was observed.This decline was strongly related to the inhibition of cyst development(rate of hydatid cyst growth inhibition=63.08%) and a decrease in CD68 expression in both the pericystic layer of hepatic hydatid cysts and liver tissue(P<0.000 1).A significant diminution of iNOS,TNF-α and NF-κB expression was also observed in liver tissue of treated mice(P<0.000 1).Conclusions:Our results indicate an antihydatic scolicidal effect and immunomodulatory properties of PGE,suggesting its potential therapeutic role against Echinococcuss granulosus infection.

In vitro anti-hydatic and immunomodulatory effects of ginger and [6]-gingerol

Objective: To study in vitro anti-hydatic and immunomodulatory effects of ginger and [6]-gingerol as an alternative therapy for Cystic echinococcosis. Methods: Effect of a commonly used herbal product and ginger(Zingiber officinale) towards protoscoleces(PSC) and cyst wall in vitro was studied. The effect of [6]-gingerol, and the pungent constituent of ginger, was also evaluated on PSC culture. Furthermore, the activity of both extracts in association with interferon-gamma(IFN-γ) on PSC co-cultured with mononuclear cells of hydatic patients was evaluated. The nitric oxide(NO) production was measured in each co-culture. Results: Ginger exhibited a concentration- and time-dependent cytotoxic effect against PSC and cyst wall. Interestingly, ginger was more effective than the [6]-gingerol. Moreover, additional parasitic effect between extracts and IFN-γ are also observed in co-cultures. Furthermore, both extracts attenuated the NO production elicited by this infection or by the IFN-γ. Conclusions: Ginger has an important anti-hydatic effect in vitro. This effect is amplified in the presence of IFN-γ. Moreover, this herbal product may protect against host's cell death by reducing the high levels of NO. Ginger may act, at least, through the [6]-gingerol. All our data suggest the promising use of ginger in the treatment of Echinococcus granulosus infection.

Caffeic acid and quercetin exert caspases-independent apoptotic effects on Leishmania major promastigotes, and reactivate the death of infected phagocytes derived from BALB/c mice

Objective: To investigate the leishmanicidal effects of two antioxidants, caffeic acid and quercetin on Leishmania major(L.major) promastigotes in vitro, and their immunomodulatory effects on infected phagocytes derived from susceptible BALB/c mice.Methods: Caffeic acid and quercetin-induced cell death was examined by Pi-Hoechst double staining of L.major promastigotes and MTT assay, in the presence or absence of protease inhibitors in vitro.Caffeic acid or quercetin were administered subcutaneously to BALB/c mice infected with L.major promastigotes through a dorsal air pouch.Nitric oxide and superoxide anion production by phagocytes infiltrating the air pouch and the expression of inducible nitric oxide synthase(i NOS), tumor necrosis factor alpha(TNF-a) and nuclear factor kappa B in the air pouch membrane were therefore evaluated using appropriate methods.Results: Caffeic acid and quercetin displayed a dose-dependent cytotoxic effect against L.major promastigotes, and induced cell death via caspases-independent pathways.In vivo, L.major promastigotes inoculation into air pouch cavity of BALB/c mice leads to a sequential influx of neutrophils(hours), followed by macrophages(days).Results showed that L.major delayed apoptosis of infected neutrophils and macrophages by the cleavage of the nuclear factor kappa B p65^(RelA) subunit, and persisted by inhibiting TNF-a and i NOS expression and reactive oxygen species generation.Caffeic acid or quercetin restored reactive oxygen species production and TNF-a-induced i NOS activity, and abrogate apoptosis delay of infected phagocytes.Conclusions: The leishmanicidal effect of caffeic acid and quercetin on promastigotes and amastigotes, as well as reactivation of infected phagocytes apoptosis, suggested a potential therapeutic role against cutaneous leishmaniasis.

Antihydatic and immunomodulatory effects of Algerian propolis ethanolic extract:In vitro and in vivo study

Objective: To evaluate the in vitro and in vivo effect of the Algerian propolis ethanolic extract(EEP) against Echinococcus granulosus(E. granulosus) infection. Methods: In vitro scolicidal activity of EEP was investigated on the protoscolices of hydatid cyst. This in vitro study was conducted by using an in vivo assay. BALB/c mice were inoculated with E. granulosus and treated with propolis for three months. Hydatid cysts development was assessed. Nitric oxide(NO), tumor necrosis factor alpha(TNF-α) production and inducible NO synthase, NF-κB, and TNF-α spleen expression were estimated by Griess method and immunofluorescence respectively.Results: Our study revealed that EEP has a high scolicidal activity against E. granulosus. Oral administration of EEP decreased TNF-α, NF-κB and inducible NO synthase expression in the spleen tissues in the CE+EEP group, in comparison with the CE group. Concomitantly, EEP treatment caused an important systemic decrease in NO and TNF-α levels. These findings are associated with the reduction of CE development. Conclusions: This is the first report demonstrating with interest the antihydatic and immunomodulatory effects of the Algerian EEP, suggesting its therapeutic potential for the hydatid disease treatment.

Prevalence of Virological Markers HIV, HBV and HCV in Homozygous Sickle Cell Patients at Brazzaville University Hospital

In order to evaluate the seroprevalence of major viral markers, a descriptive study was carried out in homozygous sickle cell transfusion patients at the University Hospital of Brazzaville. The profiles were determined in 51 patients, 32 of whom were male and 19 female, with an age range of 17 to 51 years, admitted to the clinical hematology department of the University Hospital and to the National Reference Center for Sickle Cell Disease. The tests were performed on pre- and post-transfusion blood samples. The following reagents were used: GeenscreenTMultraHIVAg-Ab, MonolisaAg-HBs plus, MonolisaHCV Ag-Ab Ultrade Bio-Radot for the detection of HIV, HBV and HCV by fourth generation ELISA tests (serological tests). The results showed that the indications for blood transfusion were: acute crises of anemia due to malaria and in some cases of Vaso-Occlusive Crises (VOC) resistance to analgesic treatment. The prevalence rates of the markers before the new transfusion were respectively: HIV: 0%, HBV: 1.96%, HCV: 3.92%. After transfusion, the final seroprevalence rates of the markers are: HIV: 0%, HBV: 5.88%, HCV: 3.92%. The seroconversion rate for HBV was 3.92%. One case of HBV + HCV co-infection (1.96%). Conclusion: Transfusion safety is achieved through good transfusion practices and the qualification of blood donations. Homozygous sickle cell disease, characterized by frequent anemia attacks, requires a guarantee of efficient transfusion practices in order to limit microbial risks.

Role of metabolic stress for enhancing muscle adaptations: Practical applications

Metabolic stress is a physiological process that occurs during exercise in response to low energy that leads to metabolite accumulation [lactate, phosphate inorganic(Pi) and ions of hydrogen(H^+)] in muscle cells.Traditional exercise protocol(i.e., Resistance training) has an important impact on the increase of metabolite accumulation, which influences hormonal release, hypoxia, reactive oxygen species(ROS) production and cell swelling.Changes in acute exercise routines, such as intensity, volume and rest between sets, are determinants for the magnitude of metabolic stress, furthermore, different types of training, such as lowintensity resistance training plus blood flow restriction and high intensity interval training, could be used to maximize metabolic stress during exercise.Thus, the objective of this review is to describe practical applications that induce metabolic stress and the potential effects of metabolic stress to increase systemic hormonal release, hypoxia, ROS production, cell swelling and muscle adaptations.

Antibiotic Resistance Phenotypes of <i>Enterobacteriaceae</i>Isolated from Household Wastewater in Brazzaville, Republic of Congo

Household wastewater is a source of pollution and can present health risks when discharged into the environment. Thus, samples of household wastewater from a few neighborhoods in Brazzaville were analyzed for microbiological quality. The various samples were cultured for isolation on solid media using conventional microbiological methods. The bacteria isolated were identified by the Enterobacter System gallery. Sensitivity tests were performed using the standard antibiotic susceptibility test by diffusion on Mueller Hinton medium. At the end of the analysis, 51 Enterobacteriaceae were isolated and identified. They included: 8 (15.68%) Escherichia coli, 8 (15.68%) Salmonella spp., 8 (15.68%) Shigella spp., 8 (15.68%) Klebsiella spp., 5 (9.80%) Enterobacter aerogenes, 8 (15.68%) Enterobacter cloacae, 3 (5.90%) Arizona spp., 3 (5.90%) Proteus spp. The results obtained show that the bacteria tested showed total resistance to the following antibiotics: amoxicillin, amoxicillin + clavulanic acid, cloxacillin and nalidixic acid. On the other hand, imipenem, cefuroxime, cefotaxime, cefftriazone and kanamycin were the most active antibiotics with low levels of resistance. The low resistance rates observed for imipenem, cefotaxime, cefuroxime and cefftriazone show that these antibiotics can be used for the treatment of infections caused by household wastewater bacteria.

On the Protective Effects of Aplysin on Ethanol-induced Oxidative Damage in Rat Primary Hepatocytes

[Objective] To investigate the protective effects of Aplysin on ethanol-induced oxidative damage in rat primary hepatocytes.[Methods]Rat primary hepatocytes were obtained via the portal vein collagenase IV in situ perfusion technique followed by a Percoll density gradient centrifuge; MTT test was used to determine the optimum dose of Aplysin and ethanol,and detect the cell vitality in primary hepatocytes; supernatants of primary hepatocytes were harvested to measure AST and LDH level,and the SOD,GSH-PX activities and MDA content in primary hepatocytes were observed; flow cytometry was used to detect the cell apoptosis rate; DNA damage in primary hepatocytes were detected by single-cell gel electrophoresis assay; The level of mitochondrial membrane potential in primary hepatocytes was tested by fluorogenic probe JC-1; the CYP2E1 activity in primary hepatocytes were detected by colorimetry; the proteins of CYP2E1 were detected by Western blotting. [Results]300 mmol/L dose of ethanol and 30 mg/L dose of Aplysin were the optimal dosages and were used in the subsequent experiments. Hepatocyte vitality was significantly increased in the Aplysin group relative to that in the ethanol group,and Aplysin inhibited the release of AST and LDH( P < 0. 05). For the Aplysin treatment group,the activities of hepatocyte SOD and GSH were significantly increased and MDA was markedly lowered as compared with those in the ethanol group( P < 0. 05). And Aplysin can alleviate hepatocyte apoptosis significantly,and hepatocyte DNA damage rate of II-III level and IV level were significantly lowered in the Aplysin treatment group as compared with those in the ethanol group,and Aplysin has evidently improved on alcohol induced mitochondria damage of hepatocyte. Primary hepatocytes activities and protein expression of CYP2E1 were markedly lowered in the Aplysin treatment group as compared with those in the ethanol group( P < 0. 05). [Conclusion] Aplysin has protective effects on liver oxidative damage induced by alcohol of primary cultured rat hepatocytes by blocking CYP2E1 activation,relieving oxidative stress,and sharpening the oxidation resistance ability.

Non-Smad pathways in TGF-β signaling

转变生长因素 -- 尾除了 Smads 利用大量的细胞内部的发信号小径调整细胞的功能的一个宽数组。这些不在经典中， non-Smad 小径被占据 ligand 的受体直接激活到增强，稀释，或不那样调制下游地细胞的回答。这些 non-Smad 小径包括地图 kinase 小径，象 Rho 一样 GTPase 发信号小径，和 phosphatidylinositol-3-kinase/AKT 小径的各种各样的分支。这评论在 non-Smad 小径的分子、生物化学的机制的理解集中于最近的进展。另外，这些 non-Smad 小径的功能也被讨论。

Antioxidant and immunomodulatory activities of a polysaccharide from Flammulina velutipes

OBJECTIVE: To evaluate the antioxidant and immunomodulatory activities of a unique polysaccharide from the medicinal fungus Flammulina velutipes in vitro.METHODS: Using water extraction and alcohol precipitation, crude polysaccharides were obtained. After purification by DEAE-cellulose 52 ion exchange chromatography and Sephacryl S-300 HR gel filtration chromatography, High performance liquid chromatography equipped with evaporative light-scattering detector, Infrared radiation and Nuclear magnetic resonance were used to evaluate the structure of the polysaccharide. Its immunomodulatory activity was measured by examining the production of nitric oxide(NO) and cytokine secretion, and via lymphocyte proliferation experiments. Its effects on the scavenging activities of hydroxyl radical, superoxide anion and reducing power were also measured.RESULTS: A water-soluble polysaccharide, Flammulina velutipes polysaccharide I-A(FVP I-A), was obtained with a molecular mass of 8.14×104Da determined by high performance gel permeation chromatography. An in vitro antioxidant assay indicated that FVP I-A could scavenge hydroxyl radical, superoxide anion and possessed reducing power and could largely promote NO production and augment the interleukin-1β, interleukin-6, and tumor necrosis factor-α secretion by RAW264.7 macrophages(P<0.05). Moreover, FVP I-A could promote lymphocyte proliferation(P<0.05), and synergistically enhance the augmentation of the proliferation of mouse lymphocytes by concanavalin A and lipopolysaccharides(P<0.01, P<0.05).CONCLUSION: The FVP I-A obtained from Flammulina velutipes possessed antioxidant activity and could enhance non-specific and specific immune responses in vitro.

NOD2/CARD15 gene mutations in North Algerian patients with inflammatory bowel disease

AIM: To analyse allelic frequency of NOD2 gene variantsand to assess their correlation with inflammatory bowel disease(IBD) in Algeria.METHODS: We studied 132 unrelated patients diagnosed with IBD, 86 with Crohn's disease(CD) and 46 with ulcerative colitis(UC). Data was prospectively collected between January 2011 and December 2013. The demographic and clinical characteristics were recorded for all the patients. A group of 114 healthy unrelated individuals were selected as controls. All groups studied originated from different regions of North Algeria and confirmed the Algerian origin of their parents and grandparents. Informed and written consent was obtained from each of the participants. All individuals were genotyped for the three CDassociated NOD2 variants(p.Arg702 Trp, p.Gly908 Arg and p.Leu1007 fsins C mutations) using the polymerase chain reaction-restriction fragment length polymorphism method. Allele and genotype frequencies in patients and control subjects were compared by χ2 test and Fisher's exact test where appropriate. Odds ratios(OR) and 95% confidence intervals(95%CI) were also estimated. Association analyses were performed to study the influence of these variants on IBD and on clinical phenotypes.RESULTS: The p.Arg702 Trp mutation showed the highest frequency in CD patients(8%) compared to UC patients(2%)(P = 0.09, OR = 3.67, 95%CI: 0.48-4.87) and controls(5%)(P = 0.4, OR = 1.47, 95%CI: 0.65-3.31). In CD patients allelic frequencies of p.Gly908 Arg and p.Leu1007 fsins C variants compared to HC were 3% vs 2%(P = 0.5, OR = 1.67, 95%CI: 0.44-6.34); 2% vs 1%(P = 0.4 OR = 2.69 95%CI: 0.48-14.87 respectively). In UC patients, allelic frequencies of p.Gly908 Arg and p.Leu1007 fsins C variants compared to HC were 1% vs 2%(P = 1, OR = 1.62, 95%CI: 0.17-4.74) and 2% vs 1%(P = 0.32, OR = 0.39, 95%CI: 0.05-2.87). The total frequency of the mutated NOD2 chromosomes was higher in CD(13%), than in HC(8%) and UC(5%). In addition, NOD2 variants were linked to a particular clinical sub-phenotype in CD in this Algerian cohort. As expected, the three NOD2 variants showed a significant association with CD but did not reach statistical significance, despite the fact that the allele frequency of NOD2 variants was in the range found in most of the European populations. This might be due to the non-exposure of the NOD2 carriers to environmental factors, required for the expression of the disease.CONCLUSION: Further analyses are necessary to study genetic and environmental factors in IBD in the Algerian population, using larger patient groups.

A novel PNPLA2 mutation causing total loss of RNA and protein expression in two NLSDM siblings with early onset but slowly progressive severe myopathy

Neutral lipid storage disease with myopathy(NLSDM)is a rare autosomal recessive disorder,due to an enzymatic error of lipid metabolism.Patients present always with skeletal muscle myopathy and variable cardiac and hepatic involvement.NLSDM is caused by mutations in the PNPLA2 gene,which encodes the adipose triglyceride lipase(ATGL).Here we report the molecular characterization and clinical findings of two NLSDM siblings carrying the novel c.187t1G>C homozygous PNPLA2 mutation,localized in the splice site of intron 2.Molecular analyses revealed that neither aberrant PNPLA2 mRNA isoforms,nor ATGL mutated protein were detectable in patient’s cells.Clinically,both patients presented early onset muscle weakness,in particular of proximal upper limb muscles.In almost 15 years,muscle damage affected also distal upper limbs.This is a NLSDM family,displaying a severe PNPLA2 mutation in two siblings with clinical presentation characterized by an early onset,but a slowly evolution of severe myopathy.

A novel ABHD5 mutation in two Chanarin Dorfman siblings with severe and heterogeneous clinical phenotype

Chanarin Dorfman Syndrome(CDS;MIM:275630)is a rare autosomal recessive disorder,characterized by triacylglycerol(TG)accumulation in lipid droplets(LDs)within different tissues including skin,liver,skeletal muscle,bone marrow,eyes,ears,and central nervous system.1 In CDS,the prevalent and always observed clinical feature is a non-bullous congenital ichthyosiform erythroderma(NCIE).

Umbelliferone ameliorates renal function in diabetic nephropathy rats through regulating inflammation and TLR/NF-κB pathway

Diabetic nephropathy(DN) is a leading cause of renal failure, contributing to severe morbidity and mortality in diabetic patients. Umbelliferae(Umb) has been well characterized to exert protective effects in diabetes. However, the action and mechanism of Umb in DN remains unclear. In this work, we studied the effect of Umb in a streptozotocin(STZ)-induced DN rat model and explore its underlying mechanism. DN rats were treated with Umb(20, 40 mg·kg^(-1)) or irbesartan(15 mg·kg^(-1)) for 4 weeks. Levels of serum glucose, insulin, blood uric acid, creatinine, triglycerides(TG) and total cholesterol(TC) were measured by commercial assay kits,respectively. Histopathological changes and inflammatory cytokine levels including IL-6, IL-1β and TNF-α in the kidney were also evaluated. Alterations in the expression of podocin, CD2 AP and TLR/NF-κB were assessed by western blotting. Our results showed that Umb reduced renal injury in DN rat model, as evidenced by the decrease in blood glucose, 24 h urinary protein, serum creatinine,and blood uric acid. Umb also significantly ameliorated the renal histopathological alteration, and down-regulated the expression of epithelial-to-mesenchymal transition-related molecular markers podocin and CD2AP. Moreover, Umb inhibited TLR2, TLR4, MyD88 expressions, NF-κB activation and considerably reduced levels of other downstream inflammatory molecules(TNF-α, IL-6, IL-1β).These findings indicated that Umb improved renal function through regulating inflammation and TLR/NF-κB pathway, suggesting the potential efficacy of Umb in DN treatment.

Identification of a novel PAK1 inhibitor to treat pancreatic cancer

Pancreatic cancer is one of the most aggressive cancers with poor prognosis and a low 5-year survival rate.The family of P21-activated kinases(PAKs)appears to modulate many signaling pathways that contribute to pancreatic carcinogenesis.In this work,we demonstrated that PAK1 is a critical regulator in pancreatic cancer cell growth.PAK1-targeted inhibition is therefore a new potential therapeutic strategy for pancreatic cancer.Our small molecule screening identified a relatively specific PAK1-targeted inhibitor,CP734.Pharmacological and biochemical studies indicated that CP734 targets residue V342 of PAK1 to inhibit its ATPase activity.Further in vitro and in vivo studies elucidated that CP734 suppresses pancreatic tumor growth through depleting PAK1 kinase activity and its downstream signaling pathways.Little toxicity of CP734 was observed in murine models.Combined with gemcitabine or 5-fluorouracil,CP734 also showed synergistic effects on the anti-proliferation of pancreatic cancer cells.All these favorable results indicated that CP734 is a new potential therapeutic candidate for pancreatic cancer.

Inflammatory bowel disease: DCs sense LTB_(4) to drive T_(H)1 and T_(H)17 differentiation

RESEARCH HIGHLIGHT Ulcerative colitis and Crohn’s disease are the two major forms of inflammatory bowel disease(IBD)in humans.1 Chronic human IBD,such as Crohn’s disease,is characterized by features such as intestinal infiltration of immune cells,inflammatory cytokine milieu,intestinal fibrosis and weight loss among others,that lead to chronic and spontaneously recurring intestinal inflammation.2 Several mouse models of IBD have been used by researchers to understand the diverse aspects related to human IBD.1,2 For example,the mouse model of intra-rectal administration of the haptenating agent,2,4,6-trinitrobenzene sulfonic acid(TNBS),which induces mucosal immunity to colonic immunogenic proteins in the host,recapitulates key immunological responses observed in Crohn’s disease,such as cytokine secretion patterns,intestinal fibrosis,and immune intolerance.2 The innate immune response is critical to initiate the cytokines production that prime T-cell differentiation in the TNBS model.The polarized T-cell responses are hallmarks of IBD and in the TNBS model T_(H)1 and T_(H)17-cell responses predominate as is observed with the signature cytokine secretion profile of IL12/IFNγand IL23/IL17,respectively.