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Background: Biofilm formation is viewed as a vital mechanism in C. glabrata pathogenesis. Although, it plays a significant role in virulence but transcriptomic architecture and metabolic pathways governing the biofilm growth mode of C. glabrata remain elusive. The present study intended to investigate the genes implicated in biofilm growth phase of C. glabrata through global transcriptomic approach. Results: Functional analysis of Differentially expressed genes (DEGs) using gene ontology and pathways analysis revealed that upregulated genes are involved in the glyoxylate cycle, carbon-carbon lyase activity, pre-autophagosomal structure membrane and vacuolar parts whereas, down- regulated genes appear to be associated with glycolysis, ribonucleoside biosynthetic process, ribosomal and translation process in the biofilm growth condition. The RNA-Seq expression of eight selected DEGs (CgICL1, CgMLS1, CgPEP1, and CgNTH1, CgERG9, CgERG11, CgTEF3, and CgCOF1) was performed with quantitative real-time PCR (RT-qPCR). The gene expression profile of selected DEGs with RT-qPCR displayed a similar pattern of expression as observed in RNA-Seq. Phenotype screening of mutant strains generated for genes CgPCK1 and CgPEP1, showed that Cgpck1∆ failed to grow on alternative carbon substrate (Glycerol, Ethanol, Oleic acid) and similarly, Cgpep1∆ unable to grow on YPD medium supplemented with hydrogen peroxide. Our results suggest that in the absence of glucose, C. glabrata assimilate glycerol, oleic acid and generate acetyl coenzyme-A (acetyl-CoA) which is a central and connecting metabolite between catabolic and anabolic pathways (glyoxylate and gluconeogenesis) to produce glucose and fulfil energy requirements. Conclusions: The study was executed using various approaches (transcriptomics, functional genomics and gene deletion) and it revealed that metabolic plasticity of C. glabrata (NCCPF-100,037) in biofilm stage modulates its virulence and survival ability to counter the stress and may promote its transition from commensal to opportunistic pathogen. The observations deduced from the present study along with future work on characterization of the proteins involved in this intricate process may prove to be beneficial for designing novel antifungal strategies. [ABSTRACT FROM AUTHOR]

The antibacterial, antioxidant and anti-inflammatory potential of Rhodobryum roseum extracts in organic solvents was investigated. The highest contents of total phenols, flavonoids, and antioxidants have been found in methanolic extract. Escherichia coli and Listeria monocytogenes were sensitive to the extracts, while Bacillus subtilis and Klebsiella pneumoniae were resistant. Anti-inflammatory potential of methanolic extract was assessed in the LPS-induced RAW 264.7 macrophage cell lines. The GC-MS of methanolic extract showed the predominance of phenolic acids, fatty acids and phytosterols, while terpenoids and flavonoids were identified by LC-MS analysis. FTIR confirmed the presence of O-H, C-H, C-N, C-F and SCN functional groups. [ABSTRACT FROM AUTHOR]

Evidently proven medicinal benefits of Tinospora cordifolia and the growing demand of functional foods have created scientific interest in the functional beverage. Therefore, an attempt was made to prepare probiotic Lactiplantibacillus pentosus GSSK2 supplemented herbal wine having the benefits of both phytochemical and probiotic. Experimentally, fermentation of Tinospora cordifolia stem was found to be the most effective with ammonium dihydrogen phosphate, potassium phosphate, magnesium sulfate, isoleucine, and thiamine that yielded maximum ethanol (6.8 to 10%), total phenol (419 to 791.5 µg/ml), and antioxidants capacity (98.2 to 160.4 µmol/ml) after optimizing physical parameters, i.e., 20° Brix total soluble solid, pH 4.5, temperature 30 °C, and 10% (v/v) inoculum. Further, prepared herbal wine was supplemented separately with seven different probiotic strains and among these Lactiplantibacillus pentosus GSSK2 had the highest 88.6% survival rate compared with other probiotics and was safe showing 100% survivability of HEK-293 and THP-1 cells. Both herbal- and probiotic-supplemented herbal wine showed the antimicrobial potential against Gram-positive and Gram-negative bacteria as probiotic-supplemented herbal wine had 19–21 mm inhibition zone compared with 18–19 mm with herbal wine. LC–MS analysis of the probiotic-supplemented herbal wine revealed the presence of various phytochemicals such as alkaloids, diterpenoid lactone, glycoside, steroids having anti-bacterial, anti-oxidant, and anti-inflammatory potential. This is the first ever such study to demonstrate the antibacterial, antioxidant potential and safety of probiotic supplemented herbal wine in vitro. [ABSTRACT FROM AUTHOR]

Expression of genome-wide alternative transcript isoforms and differential transcript isoform usage in different biological conditions (isoform switching) are responsible for the varied proteomic functional diversity in higher eukaryotic organisms. However, these mechanisms have not been studied in Candida glabrata, which is a potent eukaryotic opportunistic pathogen. Biofilm formation is an important virulence factor of C. glabrata that withstands antifungal drug stress and overcomes the host-immune response. Here, we present the genome-wide differential transcript isoform expression (DTE) and differential transcript isoform usage (DTU) in a mature biofilm growth phase of C. glabrata (clinical isolate; NCCPF 100,037) using the RNA sequencing approach. The DTE analysis generated 7837 transcript isoforms from the C. glabrata genome (5293 genes in total), and revealed that transcript isoforms generated from 292 genes showed significant DTU in the mature biofilm cells. Gene ontology, pathway analysis and protein–protein interactions of significant transcript isoforms, further substantiated that their specific expression and differential usage is required for transitioning the planktonic cells to biofilm in C. glabrata. The present study reported the possible role of expression of alternative transcript isoforms and differential transcript isoform usage in the mature biofilms of C. glabrata. The observation derived from the study may prove to be beneficial for making future antifungal therapeutic strategies. [ABSTRACT FROM AUTHOR]

Pseudomonasaeruginosa, a WHO-prioritized multidrug-resistant Gram-negative bacteria, is one of the frequently implicated pathogen in surgical site infection (SSI) due to its virulence phenotypes and biofilm-forming ability. In the present study, cell-free supernatant (CFS) and biogenics (organic acids and precipitated protein fraction) of indigenous potential probiotic, Lactobacillus fermentum PUM both alone and in combination with zingerone were found to inhibit pyocyanin, pyochelin, protease, elastase, the virulence factors, and motility of P. aeruginosa PAO1. Furthermore, scanning electron microscopy indicated that biofilm formation was attenuated maximally by CFS of L. fermentum combined with zingerone. In vivo study revealed reduced P. aeruginosa burden, suppuration at surgical site vis-a-vis reduced levels of oxidants, pro-inflammatory cytokines, ameliorated anti-oxidants, and healed infected surgical site compared with counter controls. In totality, combination of L. fermentum PUM-derived biogenics and zingerone could be employed to treat P. aeruginosa-induced SSI that needs to be correlated clinically. [ABSTRACT FROM AUTHOR]

Metabolic syndrome a lifestyle disease, where diet and gut microbiota play a prodigious role in its initiation and progression. Prophylactic bio-interventions employing probiotics and prebiotics offer an alternate nutritional approach towards attenuating its progression. The present study aimed to evaluate the protective efficacy of a novel synbiotic (Lactiplantibacillus pentosus GSSK2 + isomalto-oligosaccharides) in comparison to orlistat in an experimental model of metabolic syndrome. It was observed that supplementation of synbiotic for 12 weeks to Sprague Dawley rats fed with high fat diet (HFD), ameliorated the morphometric parameters i.e. weight gain, abdominal circumference, Lee's index, BMI and visceral fat deposition along with significantly increased fecal Bacteroidetes to Firmicutes ratio, elevated population of Lactobacillus spp., Akkermansia spp., Faecalibacterium spp., Roseburia spp. and decreased Enterobacteriaceae compared with HFD animals. Additionally, synbiotic administration to HFD animals exhibited improved glucose clearance, lipid biomarkers, alleviated oxidative stress, prevented leaky gut phenotype, reduced serum lipopolysaccharides and modulated the inflammatory, lipid and glucose metabolism genes along with restored histomorphology of adipose tissue, colon and liver compared with HFD animals. Taken together, the study highlights the protective potential of synbiotic in comparison with its individual components in ameliorating HFD-induced metabolic complications. [ABSTRACT FROM AUTHOR]

Biogenics are compounds produced by living organisms such as animals, plants, bacteria, etc. Probiotics and their biogenics are known for their antimicrobial potential. Therefore, the present study was designed to evaluate the antibiofilm potential of probiotic-derived biogenics in conjunction with zingerone against the Pseudomonas aeruginosa PAO1 biofilm. Cell-free supernatant (CFS) of potential probiotics Pediococcus acidilactici BNS5B and Lactobacillus fermentum PUM was found to inhibit the growth of Ps. aeruginosa PAO1 maximally among the nineteen isolated lactic acid bacteria. L. fermentum PUM produced precipitated protein fraction (PP), organic acids (OAs), exopolysaccharides (EPSs), biosurfactants (BSs) and various volatile antimicrobial compounds, while Ped. acidilactici BNS5B was found to produce PP, OA, EPS, BS and fewer volatile antimicrobial compounds only. More specifically, CFS and selected biogenics (OA and PP from L. fermentum PUM; OA from Ped. acidilactici BNS5B) of both potential probiotics showed synergy with zingerone against Ps. aeruginosa growth as observed by FIC index (< 0.5). Interestingly, CFS of both potential probiotics in combination with zingerone led to the formation of a more distorted biofilm compared with OA of L. fermentum PUM and zingerone, OA of Ped. acidilactici BNS5B and zingerone, PP of L. fermentum PUM and zingerone as well as their individual counterparts. Similarly, both confocal laser scanning microscopy and XTT assay showed an increased number of dead and impaired cells along with the decreased viability of biofilm cells. Thus, it can be reckoned that a combination of probiotic-derived biogenics and zingerone can have therapeutic application against Ps. aeruginosa infections which needs to be validated clinically. [ABSTRACT FROM AUTHOR]

Modulation of the gut microbiota by probiotics, is emerging as a promising approach for the management of metabolic diseases but due to their species and strain specific response, isolation of new probiotic strains is gaining importance. The present study was designed to assess the effect of isolated and well characterised indigenous probiotics, Lactobacillus pentosus GSSK2, Lactobacillus fermentum PUM and Lactobacillus plantarum GS26A in high fat diet (HFD) induced metabolic syndrome. It was observed that though supplementation of all three probiotics for 12 weeks to Sprague Dawley rats fed with HFD, ameliorated the anthropometric parameters, but L. pentosus GSSK2 showed maximum reduction in weight gain while maximum decrease in abdominal circumference, Lee's index, BMI and visceral fat deposition was observed in L. plantarum GS26A compared with HFD animals. Further, administration of L. plantarum GS26A to HFD animals led to significant increase in lactic acid bacteria count and lipid excretion in feces followed by L. pentosus GSSK2 and L. fermentum PUM compared with counter controls. Additionally, both L. pentosus GSSK2 and L. plantarum GS26A exhibited improved glucose tolerance, liver biomarkers, alleviated oxidative stress and restored the histoarchitechture of adipose tissue, colon and liver compared with HFD animals. The study highlights the prophylactic potential of isolated probiotics in experimental metabolic syndrome model and revealed that amongst all three probiotics, L. pentosus GSSK2 and L. plantarum GS26A were equally effective and more promising than L. fermentum PUM in improving metabolic dysfunctions and may be employed as functional foods but needs to be correlated clinically. [ABSTRACT FROM AUTHOR]

Background and Objective: The cellular microenvironment, diet, and lifestyle play a key role in the occurrence of colorectal cancer. Due to its rising trend, attempts are being made to devise novel biointerventions as adjunct to conventional therapies to prevent this deadly disease. "Metabiotics," the beneficial metabolic signatures of probiotics are emerging as potential anticancer agent due to their ability to alter metabolic processes in the gut lumen and reduce the severity of colon carcinogenesis. Although beneficial attributes of metabiotics have been elucidated in vitro , yet their anticancer mechanism in vivo needs to be explored. Thus, the present study was performed to envisage anticancer potential of metabiotic extract obtained from indigenous probiotic, Lactobacillus rhamnosus MD 14, in early experimental colon carcinogenesis. Materials and Methods: Sprague–Dawley rats were daily administered with low, medium, and high dose of metabiotic extract orally along with a single dose of weekly intraperitoneal injection of 1,2-dimethylhydrazine up to 6 weeks and monitored for the markers of early colon carcinogenesis. Results: It was observed that the medium dose of metabiotic extract attenuated early colon carcinogenesis by reducing fecal procarcinogenic enzymes, oxidants, aberrant crypt foci, vis-à-vis downregulating oncogenes [K-ras, β-catenin, Cox-2, nuclear factor kappa B (NF-κB)] and upregulating tumor suppressor p53 gene leading to almost normal colon histology. Conclusions: It can be suggested that metabiotics modulate experimental colorectal cancer and could be used as a promising alternative of probiotics, particularly in immunocompromised individuals. [ABSTRACT FROM AUTHOR]

Probiotics are known to modulate gut microbiota, intestinal barrier function and host immune response, but due to the species and strain specific response their mechanisms are not clearly understood. Thus, the present study was designed to isolate, assess the anti-inflammatory potential and underlying modulatory mechanisms of indigenous probiotics in murine macrophage cell line, RAW 264.7. Forty lactic acid bacteria (LAB) were isolated from different sources and monitored for their anti-inflammatory potential against lipopolysaccharide (LPS) induced inflammatory stress employing RAW 264.7 cells. Among these isolates, only four LAB isolates exhibited more than 90% nitric oxide inhibition and possessed the probiotic attributes. Further, these selected LAB isolates reduced the level of pro-inflammatory cytokines, TNF-α, IL-1β and IL-6, inhibited the phosphorylation of Mitogen Activated Protein Kinases (MAPKs) i.e. p38 MAPK, ERK1/2 and SAPK/JNK and expression of cyclooxygenase-2 (COX-2) in LPS stimulated RAW 264.7 cells. The in vitro analysis suggested that the selected probiotic isolates attenuated the LPS-induced inflammation by downregulating MAPK pathway vis-a-vis inhibiting COX-2 and can be employed as anti-inflammatory agents in various inflammatory diseases. [ABSTRACT FROM AUTHOR]

Phytic acid, the main phosphate storage component of plant-based diet, is one of the prime causes of micronutrient deficiency in vegetarians due to the formation of non-degradable cation-phytic acid complex in gastrointestinal tract of monogastric animals that are devoid of phytase enzyme. Therefore, the present study was designed to isolate phytase producing probiotic from neonatal feces which may enhance the bioavailability of phosphorous micronutrient. Experimentally, 13 phytase producing lactic acid bacteria (LAB) were isolated from 28 neonatal fecal samples and characterized both phenotypically and for probiotic attributes. Among these, Isolate 5b exhibited potent probiotic potential with significant (p <.01) phytase activity (4.55 U/mL) and was identified phylogenetically using both 16S rRNA and MALDI-TOF MS analysis as Pediococcus acidilactici BNS5B. Interestingly, it was found that phytase from P. acidilactici BNS5B significantly dephytinized phytic acid from modified diet (96.59%) and brown bread (88.89%) after 15 min of phytase treatment at 37°C. Therefore, this provides an opportunity to develop P. acidilactici BNS5B as a probiotic to be used as a supplement in feed/food of monogastric animals and humans. This also provides the rationale for further in vivo studies to use phytase producing probiotic in relation to maintaining and improving health. [ABSTRACT FROM AUTHOR]

The present study is an attempt to synthesize nanosized guar gum carriers encapsulating celecoxib as the chemopreventive agent for experimental colorectal cancer (CRC). Guar gum nanoparticles without celecoxib (eGGNPs) and celecoxib loaded guar gum nanoparticles (cGGNPs) were prepared by oil-in-water emulsification and in situ polymer crosslinking method. Electron microscopy, zeta potential and fourier transform infrared spectra analysis was used to affirm the size, stability and morphology of the nanoparticles. In-vitro drug release was investigated using dialysis method. Further, the effect of nanoparticles (eGGNPs & cGGNPs) was evaluated on Caco 2 colon cancer cell lines. Spherical guar gum nanoparticles were obtained in the size range of 200±6nm with zeta potential of -32.1mV indicating good stability of the GGNPs with drug loading of 30±3.2%, and drug release following zero order kinetics. The eGGNPs had no effect on Caco2 cell viability whereas the cGGNPs showed time and concentration dependent growth inhibition of Caco 2 cells. These findings suggest the successful preparation of chemopreventive nanoparticles that can be targeted as the prophylactic agent for experimental colorectal cancer. [ABSTRACT FROM AUTHOR]

The present study was designed to envisage the antigiardial efficacy of killed probiotic and probiotic protein (PP) of Lactobacillus rhamnosus GG in murine giardiasis. Experimentally, it was observed that animal administered either with probiotic protein emulsified with adjuvant (PP(E) + Giardia) or killed probiotic (killed probiotic (i/p) + Giardia) had significantly reduced Giardia cycle with respect to observed severity and duration of giardiasis compared with Giardia-infected mice. Further, it was found that animals belonging to PP(E) + Giardia and killed probiotic (i/p) + Giardia had significantly high levels of antigiardial IgA antibody and nitric oxide both in serum and in intestinal fluid compared with Giardia-infected and counter control mice. Histopathologyically, also animals belonging to PP(E) + Giardia and killed probiotic (i/p) + Giardia animals had intact mucosal epithelium lining, basal crypts, and normal villi along with increased goblet cells compared with severe microvillus atrophy, vacuolated epithelial cells, and ileitis in Giardia-infected mice. This is the first-ever study to demonstrate that prior administration of either killed probiotics or probiotic protein of effective probiotic reduced both the severity and the duration of giardiasis mainly by modulating the gut microbiome and morphology along with mucosal immunity, but animals belonging to PP(E) + Giardia had better response than killed probiotic (i/p) + Giardia suggesting that probiotic components do have adjuvant potential and may be used as the vaccine candidate for gastrointestinal diseases. [ABSTRACT FROM AUTHOR]

Probiotics, the beneficial bacteria produce active metabolites which could probably mimic their anticancer effect and prevent the risk associated with live bacteria. Thus, the study was designed to isolate effective lactic acid bacteria (LAB) and monitor anticancerous potential of their metabiotic extracts. Probiotics were isolated from different sources and their cell free supernatants (CFS) were screened for antigenotoxic and cytotoxic potentials using SOS Chromo Test and MTT assay on Caco-2 and HT-29 cells. Organic extracts of CFS were prepared and dissolved in different solvents. The isolate with most effective metabiotic extract in terms of cytotoxicity was classified for probiotic and phylogenetic characters and the metabiotic extract was characterized physiochemically. Among 60 isolated LAB, CFS of only 10 isolates showed antigenotoxicity more than 30% and four exhibited 70–80% cytotoxicity. Further, organic extracts of these four CFS dissolved in carboxymethyl cellulose showed 80–90% cytotoxicity. Interestingly, the most effective isolate was found to possess probiotic attributes and phylogenetic characterization revealed it to be Lactobacillus rhamnosus MD 14. Physiochemical characterization of its metabiotic extract indicated the presence of heat sensitive organic acids and proteins. To conclude, metabiotics produced by isolated probiotic L. rhamnosus MD 14 exhibited both antigenotoxic and cytotoxic potential against colon cancer. [ABSTRACT FROM AUTHOR]

Giardiasis is a re-emerging infectious disease with outbreaks reported globally specially in children and malnourished individuals leading to malabsorption, growth retardation, and severe diarrhea. Thus, in the present study, prophylactic administration of synbiotic as the functional food was used to assess its antigiardial potential in malnourished murine giardiasis. Interestingly, prior administration of synbiotic (Lactobacillus casei + inulin) even to malnourished-Giardia-infected mice led to increased body mass, small intestine mass, lactobacilli counts, and reduced severity of giardiasis as evident by decreased cyst and trophozoite counts. Synbiotic therapy further boosted the innate and acquired immune response resulting into increase in nitric oxide, antigiardial secretory IgA and IgG antibody levels along with IL-6 and IL-10 cytokines, and decreased levels of inflammatory TNF-α cytokine in both serum and intestinal fluid in malnourished-synbiotic-Giardia-infected mice compared with malnourished-Giardia-infected mice. More specifically, histopathological and scanning electron microscopy analysis of the small intestine also confirmed the modulatory potentials of synbiotic in malnourished-synbiotic-Giardia mice which had less cellular and mucosal damage compared with severely damaged, mummified, and blunted villi in malnourished-Giardia-infected mice. Taken together, this is the first experimental study to report that prior supplementation of synbiotic restored the gut morphology and improved the immune status of the malnourished-Giardia-infected mice, and could be considered as the prophylactic adjunct therapy for malnourished individuals. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer has been found to be attenuated either with prophylactic manipulation of gut microbiome with probiotics or celecoxib, a non-steroidal anti-inflammatory drug mainly by suppressing early pro-carcinogenic markers in various experimental studies. Therefore, the present study was designed to assess the prophylactic potential of combinatorial administration of probiotics (Lactobacillus rhamnosus GG, Lactobacillus acidophilus) and celecoxib in experimental colon carcinogenesis.Methods: Six groups of Spraugue Dawely rats received probiotics L.rhamnosus GG or/and L.acidophilus in combination with celecoxib one week prior to the inducement of tumor by 1,2-dimethylhydrazine (DMH) and the treatment continued for 18 weeks. Prophylactic potentials of probiotics and celecoxib were determined by employing various methods such as tumor incidence, tumor burden, tumor multiplicity, apoptosis, caspase activity, expression of proto-oncogene K-ras and tumor suppressor p53 gene in colonic tumors.Results: Interestingly, it was found that one week prior supplementation of both probiotics and celecoxib reduced tumor burden, tumor multiplicity, down-regulated the expression of anti-apoptotic Bcl-2, proto-oncogene K-ras and up-regulated pro-apoptotic Bax as well as tumor suppressor p53 in L.rhamnosus GG + celecoxib+DMH animals compared with counter controls and DMH-treated.Conclusions: It can be concluded that such combinatorial approach may be useful in reducing the burden and severity of disease in highly susceptible individuals but needs to be validated clinically. [ABSTRACT FROM AUTHOR]

Epidemiological and experimental observations have shown that nonsteroidal anti-inflammatory drugs especially selective cyclooxygenase-2 (COX-2) inhibitors and probiotics reduce the incidence risk of colon cancer. Therefore, the present study was designed to assess the prophylactic potentials of probiotics (Lactobacillus acidophilus and Lactobacillus rhamnosus GG) in conjunction with celecoxib, a selective cox-2 inhibitor in 1,2 dimethylhydrazine dihydrochloride (DMH)-induced experimental colon carcinogenesis, a well-established, well appreciated and widely used model for colorectal cancer that shares many similarities to human sporadic colorectal cancer with respect to response to some promotional and preventive agents. More specifically, it was observed that L. rhamnosus GG + celecoxib + DMH-treated animals had significantly reduced aberrant crypt foci (ACF) count and the expression of procarcinogenic molecular markers (β-catenin, NF-κB, and COX-2) in early experimental colon carcinogenesis compared with probiotic-DMH, celecoxib-DMH or DMH-treated animals. This is the first ever such study to demonstrate that probiotic in conjunction with celecoxib can be opted as an alternate prophylactic strategy in highly susceptible individuals to reduce both the incidence and severity of the life style diseases as prevention is better than cure. [ABSTRACT FROM AUTHOR]

Microorganisms develop biofilms on indwelling medical devices and are associated with biofilm-related infections, resulting in substantial morbidity and mortality. Therefore, to prevent and control biofilm-associated infections, the present study was designed to assess the anti-biofilm potential of postbiotics derived from probiotic organisms against most prevalent biofilm-forming Pseudomonas aeruginosa PAO1. Eighty lactic acid bacteria isolated from eight neonatal fecal samples possessed antibacterial activity against P. aeruginosa PAO1. Among these, only four lactic acid bacteria produced both bacteriocin and exopolysaccharides but only one isolate was found to maximally attenuate the P. aeruginosa PAO1 biofilm. More specifically, the phenotypic and probiotic characterization showed that the isolated lactic acid bacteria were gram positive, non-motile, and catalase and oxidase negative; tolerated acidic and alkaline pH; has bile salt concentration; showed 53% hydrophobicity; and was found to be non-hemolytic. Phylogenetically, the organism was found to be probiotic Lactobacillus fermentum with accession no. KT998657. Interestingly, pre-coating of a microtiter plate either with bacteriocin or with exopolysaccharides as well as their combination significantly (p < 0.05) reduced the number of viable cells forming biofilms to 41.7% compared with simultaneous coating of postbiotics that had 72.4% biofilm-forming viable cells as observed by flow cytometry and confocal laser scanning microscopy. Therefore, it can be anticipated that postbiotics as the natural biointerventions can be employed as the prophylactic agents for medical devices used to treat gastrointestinal and urinary tract infections. [ABSTRACT FROM AUTHOR]

Colorectal cancer is closely associated with environment, diet and lifestyle. Normally it is treated with surgery, radiotherapy or chemotherapy but increasing systemic toxicity, resistance and recurrence is prompting scientists to devise new potent and safer alternate prophylactic or therapeutic strategies. Among these, probiotics, prebiotics, synbiotics, and metabiotics are being considered as the promising candidates. Metabiotics or probiotic derived factors can optimize various physiological functions of the host and offer an additional advantage to be utilized even in immunosuppressed individuals. Interestingly, anti colon cancer potential of probiotic strains has been attributable to metabiotics that have epigenetic, antimutagenic, immunomodulatory, apoptotic, and antimetastatic effects. Thus, it's time to move one step further to utilize metabiotics more smartly by avoiding the risks associated with probiotics even in certain normal/or immuno compromised host. Here, an attempt is made to provide insight into the adverse effects associated with probiotics and beneficial aspects of metabiotics with main emphasis on the modulatory mechanisms involved in colon cancer. [ABSTRACT FROM AUTHOR]

The current studies entail systematic development of self-nanoemulsifying drug delivery systems (SNEDDS) containing medium-chain triglycerides (MCTs) and long-chain triglycerides (LCTs) for augmenting the biopharmaceutical performance of artemether. Equilibrium solubility and pseudoternary phase diagram studies facilitated selection of Captex 355 and Ethyl oleate as MCTs and LCTs, and Cremophor RH 40 and Tween 80 as surfactants, while Transcutol HP as cosolvent for formulating the SNEDDS. Systematic optimization was performed employing the Box–Behnken design taking concentrations of lipid, surfactant and cosolvent as the critical material attributes (CMAs), while evaluating for globule size, emulsification time, dissolution efficiency and permeation as the critical quality attributes (CQAs).In situsingle pass intestinal perfusion (SPIP) studies in Wistar rats substantiated significant augmentation in the absorption (5- to 6-fold) and permeation (4- to 5-fold) parameters from the optimized MCT and LCT-SNEDDS vis-à-vis the pure drug.In vivopharmacodynamic studies inPlasmodium berghiinfected laca mice exhibited superior reduction in the levels of percent parasitemia, SGOT, SGPT and bilirubin, followed by higher survival rate of the animals by optimized MCT-SNEDDS followed by LCT-SNEDDS vis-à-vis the pure drug, which was subsequently ratified through histopathological examination of liver tissues. Overall, the studies construed successful development of the optimized SNEDDS of artemether with distinctly improved biopharmaceutical and antimalarial potential. [ABSTRACT FROM PUBLISHER]

Malnutrition induces a state of growth retardation and immunologic depression, enhancing the host susceptibility to various infections. In the present study, it was observed that prebiotic supplementation either prior or simultaneously with Giardia infection in malnourished mice significantly reduced the severity of giardiasis and increased the body and small intestine mass, along with increased lactobacilli counts in faeces compared with malnourished- Giardia-infected mice. More specifically, prebiotic supplementation significantly increased the levels of anti-giardial IgG and IgA antibodies and anti-inflammatory cytokines IL-6 and IL-10 and reduced the pro-inflammatory cytokine TNF-α, along with increased levels of nitric oxide in both the serum and intestinal fluid of malnourished-prebiotic- Giardia-infected mice compared with malnourished- Giardia-infected mice. Histopathology and scanning electron microscopy of the small intestine also revealed less cellular and mucosal damage in the microvilli of prebiotic-supplemented malnourished- Giardia-infected mice compared with severely damaged mummified and blunted villi of malnourished- Giardia-infected mice. This is the first study to report that prebiotic supplementation modulated the gut morphology and improved the immune status even in malnourished- Giardia-infected mice. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is emerging as a serious nosocomial pathogen with multidrug resistance that has made it difficult to cure and development of efficacious treatment against this pathogen is direly needed. This has led to investigate vaccine approach to prevent and treat A. baumannii infections. In this work, an outer membrane putative pilus assembly protein, FilF, was predicted as vaccine candidate by in silico analysis of A. baumannii proteome and was found to be conserved among the A. baumannii strains. It was cloned and expressed in E. coli BL21(DE3) and purified by Ni-NTA chromatography. Immunization with FilF generated high antibody titer (>64,000) and provided 50% protection against a standardized lethal dose (108 CFU) of A. baumannii in murine pneumonia model. FilF immunization reduced the bacterial load in lungs by 2 and 4 log cycles, 12 and 24 h post infection as compared to adjuvant control; reduced the levels of pro-inflammatory cytokines TNF-α, IL-6, IL-33, IFN-γ, and IL-1ß significantly and histology of lung tissue supported the data by showing considerably reduced damage and infiltration of neutrophils in lungs. These results demonstrate the in vivo validation of immunoprotective efficacy of a protein predicted as a vaccine candidate by in silico proteomic analysis and open the possibilities for exploration of a large array of uncharacterized proteins. [ABSTRACT FROM AUTHOR]

Various antiprotozoal drugs have been used to counteract the spread of giardiasis. However, due to increase in resistance to these compounds, there is an urgent need to find a natural biocompatible product to fight the pathogen in more healthy and effective way. The present study was designed to compare the therapeutic effect of probiotic Lactobacillus casei alone and in conjunction with antiprotozoal drugs on the outcome of giardiasis in murine model. BALB/c mice were challenged with Giardia intestinalis trophozoites, and 1 day after infection, these mice were treated with either probiotic alone or in conjunction with antiprotozoal drugs. Cyst, trophozoite, and lactobacilli counts were monitored vis-a-vis histopathological alterations in the small intestine. It was found that albendazole administered orally 1 day after Giardia infection was the most effective antiprotozoal drug among albendazole, tinidazole, metronidazole, and nitazoxanide. It reduced both the severity and duration of giardiasis. More specifically, oral administration of the probiotic L. casei in conjunction with albendazole further reduced the Giardia infection as was evident by the restored normal gut morphology. This suggests that probiotics and antiprotozoal drugs in combination may be the better alternative therapy for treatment of gastrointestinal diseases and enhanced recovery. [ABSTRACT FROM AUTHOR]

The present study describes the in vivo modulatory potential of Lactobacillus rhamnosus GG (LGG), an effective probiotic, in Giardia intestinalis-infected BALB/c mice. Experimentally, it was observed that oral administration of lactobacilli prior or simultaneous with Giardia trophozoites to mice, efficiently ( p < 0.05) reduced both the severity and duration of giardiasis. More specifically, probiotics fed, Giardia-infected mice, showed a significant increase in the levels of antioxidants [reduced glutathione (GSH) and superoxide dismutase (SOD)] and intestinal disaccharidases [sucrase and lactase] and decreased levels of oxidants in the small intestine, in comparison with Giardia-infected mice. Histopathological findings also revealed almost normal cellular morphology of the small intestine in probiotic-fed Giardia-infected mice compared with fused enterocytes, villous atrophy and increased infiltration of lymphocytes in Giardia-infected mice. The results of the present study has shed new light on the anti-oxidative properties of LGG in Giardia mediated tissue injury, thereby suggesting that the effects of probiotic LGG are biologically plausible and could be used as an alternative microbial interference therapy. [ABSTRACT FROM AUTHOR]

Background: Gut homeostasis can be altered by the oral administration of health-promoting microorganisms, namely probiotics that are known to reinforce the host immune response. Aim: The aim of this study was to elucidate the immunomodulatory effect of orally administered probiotic Lactobacillus rhamnosus GG (LGG) in Giardia-infected mice. Methods: BALB/c mice were fed orally with probiotic LGG either 7 days prior to or simultaneously with the challenge dose of Giardia trophozoites. The administration of the probiotic was continued for 25 days, and immunomodulatory potentials in terms of secretory immunoglobulin A (IgA) levels, CD8+ and CD4+ T lymphocytes, and expression of pro-inflammatory [tumor necrosis factor-alpha, interferon-gamma (INF-γ)] and anti-inflammatory cytokines [interleukin (IL)-4, IL-6, IL-10] were studied. Results: Oral feeding of LGG prior to or simultaneously with the test dose of Giardia seems to have modulated both arms (humoral and cellular) of the mucosal immune system since a significant increase in the levels of specific secretory IgA antibody, IgA+ cells, and CD4+ T lymphocytes were observed in contrast with the decreased percentage of cytotoxic CD8+ T lymphocytes. The stimulated mucosal immune response in probiotic fed Giardia-infected mice was further correlated with the enhanced levels of anti-inflammatory cytokines IL-6 and IL-10 and reduced levels of pro-inflammatory cytokine INF-γ. Conclusions: This is the first study to show that oral administration of the effective probiotic LGG to Giardia infected mice could be used as a bacterio-therapy that restores the normal gut microflora and modulates the mucosal immune response. [ABSTRACT FROM AUTHOR]

Diet makes an important contribution to colorectal cancer (CRC) risk implying risks for CRC are potentially reducible. Therefore, the probiotics have been suggested as the prophylactic measure in colon cancer. In this study, different probiotics were used to compare their protective potential against 1,2 dimethylhydrazine dihydrochloride (DMH)-induced chemical colon carcinogenesis in Sprague Dawley rats. Animals belonging to different probiotic groups were fed orally with 1 × 109lactobacilli daily for 1 week, and then a weekly injection of DMH was given intraperitoneally for 6 wks with daily administration of probiotic.Lactobacillus GGandL.acidophilus+ DMH-treated animals had maximum percent reduction in ACF counts. A significant decrease (P< 0.05) in fecal nitroreductase activity was observed inL.casei+ DMH andL.plantarum+ DMH-treated rats whereas β-glucuronidase activity decreased inL.GG+ DMH andL.acidophilus+ DMH-treated rats. Animals treated withBifidobacterium bifidum+ DMH had significant decreased β-glucosidase activity. However, not much difference was observed in the colon morphology of animals belonging to various probiotic + DMH-treated rats compared with DMH-treated alone. The results indicated that probiotics,L.GG, andL.acidophiluscan be used as the better prophylactic agents for experimental colon carcinogenesis. [ABSTRACT FROM PUBLISHER]

The present study describes the in vivo ameliorating effect of Lactobacillus casei supplementation in renourished Giardia intestinalis infected BALB/c mice. It was observed that daily administration of probiotic 7 days prior to Giardia-infection to renourished mice, efficiently reduced the excretion of Giardia cysts and trophozoite counts, along with significant increased fecal lactobacilli counts compared with Giardia-infected mice. It was also observed that oral feeding of probiotic to renourished- Giardia-infected mice abrogated all the anthropometric and biochemical anomalies. Histologically, morphological and cellular alteration of microvillus membrane integrity revealed that probiotic administration further ameliorated the mucosal damage in renourished-probiotic- Giardia-infected mice compared to severe microvillus atrophy, oedematous, vacuolated epithelial cells and ileitis in renourished- Giardia and Giardia-infected mice. Thus, it is suggested that probiotic used as the functional food helps in restoration of anthropometric, biochemical alterations and atrophied gut by enhancing the goblet cells and reducing the giardiasis. [ABSTRACT FROM AUTHOR]

Placental malaria is a common clinical complication during pregnancy and is associated with abortion, premature delivery, intrauterine growth retardation and low birth weight. The present study was designed to delineate the underlying mechanism of placental pathology during malarial infection with special reference to oxidative stress and apoptosis. Experimentally, pregnant BALB/c mice were infected with Plasmodium berghei infected red blood cells on gestation day 10. The presence of malarial infection in placenta was confirmed by histopathological studies. It was observation that infected placenta had plugged placental sinusoids with parasitized red blood cells and malarial pigments. Interestingly, we found significant increase in the level of malondialdehyde, the index of oxidative stress and decreased activity of catalase, the antioxidant in infected placenta. Furthermore, in infected placenta the oxidative stress mediated apoptosis was determined by DNA fragmentation assay, ethidium bromide/acridine orange staining and caspase activity. It was observed that oxidative stress begin after second day of malarial infection. Interestingly, it was observed that there was down regulation of anti-apoptotic protein Bcl-2 and up regulation of pro-apoptotic protein Bax in infected placenta, suggesting the involvement of mitochondrial pathway of apoptosis which was further confirmed by activation of caspase 9. However, no change in the expression of Fas gene and caspase 8 activity, indicated the absence of death receptor pathway. Thus, it can be concluded that the placental pathology during malarial infection is mediated by mitochondrial pathway of apoptosis occurring due to augmented lipid peroxidation which may in turn jeopardise the materno-fetal relationship. [ABSTRACT FROM AUTHOR]

Background: Amoebiasis is a major public health problem in tropical and subtropical countries. Currently, metronidazole is the gold choice medication for the treatment of this disease. However, reports have indicated towards the possibility of development of metronidazole-resistance in Entamoeba strains in near future. In view of the emergence of this possibility, in addition to the associated side effects and mutagenic ability of the currently available anti-amoebic drugs, there is a need to explore newer therapeutics against this disease. In this context, the present study evaluated the amoebicidal potential of cryptdin-2 against E. histolytica. Methods/Principal Findings: In the present study, cryptdin-2 exhibited potent in-vitro amoebicidal activity against E. histolytica in a concentration dependent manner at a minimum amoebicidal concentration (MAC) of 4 mg/L. Scanning electron microscopy as well as phase contrast microscopic investigations of cryptdin-2 treated trophozoites revealed that the peptide was able to induce significant morphological alterations in terms of membrane wrinkling, leakage of the cytoplasmic contents and damaged plasma membrane suggesting a possible membrane dependent amoebicidal activity. N-phenyl napthylamine (NPN) uptake assay in presence of sulethal, lethal as well as twice the lethal concentrations further confirmed the membrane-dependent mode of action of cryptdin-2 and suggested that the peptide could permeabilize the plasma membrane of E. histolytica. It was also found that cryptdin-2 interfered with DNA, RNA as well as protein synthesis of E. histolytica exerting the highest effect against DNA synthesis. Thus, the macromolecular synthesis studies correlated well with the observations of membrane permeabilization studies. Significance/Conclusions: The amoebicidal efficacy of cryptdin-2 suggests that it may be exploited as a promising option to combat amoebiasis or, at least, may act as an adjunct to metronidazole and/or other available anti-amoebic drugs. Author Summary: Intestinal amoebiasis, caused by Enatmoeba histolytica continues to be a major public health problem in tropical and subtropical countries and is considered to be the third principal parasitic disease responsible for mortality in the world. In addition to the mutagenic ability and known toxicity of conventional anti-amoebic drugs, there are reports indicating the emergence of treatment failures to these drugs. Therefore, there has been a considerable interest in exploring the potential of various antimicrobial peptides having higher efficacy and lower toxicity to combat such parasitic infections. Herein, we present the amoebicidal efficacy of cryptdin-2, a Paneth cell alpha-defensin against E. histolytica. Cryptdin-2 was found to decrease the number of trophozoites of E. histolytica in a concentration dependent manner. By and large, cryptdin-2 could retain its amoebicidal activity in the presence of cations, bile salts and at various pH values. Microscopic analysis and N-phenyl napthylamine (NPN) uptake assay revealed membrane dependent amoebicidal action of the peptide. It was also demonstrated that cryptdin-2 has the potential to target the intracellular macromolecular synthesis machinery of Entamoeba. Based on these results, cryptdin-2 seems to be a promising agent for the development of novel therapeutics against amoebiasis or at least may act as an adjunct to conventional antibiotics against E. histolytica. [ABSTRACT FROM AUTHOR]

The present study was designed to delineate the effect of Giardia duodenalis in malnourished and renourished BALB/c mice. Control and renourished mice were fed with a standard pellet diet while malnourished mice were fed with a low protein (4.3 %) diet both before and after being challenged orally with actively growing G. duodenalis trophozoites. It was observed that malnourished mice had a greater severity and longer duration of Giardia infection compared with renourished mice. These malnourished mice also had less body mass but higher cyst and trophozoite counts. Malnourished mice infected with Giardia had significantly decreased level of total serum proteins, albumin, globulins, hemoglobin, leukocyte, and differential leukocyte counts compared with renourished mice. From the data it is concluded that protein malnutrition profoundly affects the anthropometric and physiological parameters of the body indicating greater susceptibility and severity of the disease. [ABSTRACT FROM AUTHOR]

Background: Amoebiasis is a major public health problem in tropical and subtropical countries. Currently, metronidazole is the gold choice medication for the treatment of this disease. However, reports have indicated towards the possibility of development of metronidazole-resistance in Entamoeba strains in near future. In view of the emergence of this possibility, in addition to the associated side effects and mutagenic ability of the currently available anti-amoebic drugs, there is a need to explore newer therapeutics against this disease. In this context, the present study evaluated the amoebicidal potential of cryptdin-2 against E. histolytica. Methods/Principal Findings: In the present study, cryptdin-2 exhibited potent in-vitro amoebicidal activity against E. histolytica in a concentration dependent manner at a minimum amoebicidal concentration (MAC) of 4 mg/L. Scanning electron microscopy as well as phase contrast microscopic investigations of cryptdin-2 treated trophozoites revealed that the peptide was able to induce significant morphological alterations in terms of membrane wrinkling, leakage of the cytoplasmic contents and damaged plasma membrane suggesting a possible membrane dependent amoebicidal activity. N-phenyl napthylamine (NPN) uptake assay in presence of sulethal, lethal as well as twice the lethal concentrations further confirmed the membrane-dependent mode of action of cryptdin-2 and suggested that the peptide could permeabilize the plasma membrane of E. histolytica. It was also found that cryptdin-2 interfered with DNA, RNA as well as protein synthesis of E. histolytica exerting the highest effect against DNA synthesis. Thus, the macromolecular synthesis studies correlated well with the observations of membrane permeabilization studies. Significance/Conclusions: The amoebicidal efficacy of cryptdin-2 suggests that it may be exploited as a promising option to combat amoebiasis or, at least, may act as an adjunct to metronidazole and/or other available anti-amoebic drugs. [ABSTRACT FROM AUTHOR]

The study describes the in vivo activity of Lactobacillus casei in malnourished Giardia lamblia-infected BALB/c mice. By experimentation, it was found that daily administration of the probiotic 7 days before inoculation with Giardia trophozoites in malnourished mice efficiently reduced both the severity and duration of giardiasis. More specifically, excretion of Giardia cysts and trophozoites counts were reduced, while faecal lactobacilli counts increased significantly in probiotic-fed malnourished mice, compared with control mice. Interestingly, it was also observed that oral feeding of the probiotic to malnourished mice abrogated all the anthropometric and biochemical anomalies. Histologically, morphological and cellular alteration of microvillus membrane integrity revealed that probiotic administration ameliorated the mucosal damage in malnourished, probiotic-inoculated, Giardia-infected mice compared with the severe microvillus atrophy, œdematous and vacuolated epithelial cells, and ileitis in malnourished Giardia-infected mice. The results clearly show the antigiardial effect of the probiotic in vivo by modulating the gut cells to inhibit the colonization and multiplication of Giardia trophozoites, thus reducing the severity and duration of murine giardiasis. Cette étude décrit l'activité de Lactobacillus casei in vivo chez des souris BALB/c malnutries et infectées par Giardia lamblia. Expérimentalement, l'administration quotidienne de probiotiques 7 jours avant l'inoculation de trophozoïtes de Giardia aux souris malnutries des réduisait efficacement tant la sévérité que la durée de la lambliase. Plus spécifiquement, l'excrétion de kystes de Giardia et la numération de trophozoïtes étaient réduites alors que les comptes de lactobacilles fécales augmentaient significativement chez les souris malnutries ayant reçu des probiotiques, comparativement aux souris contrôles. Fait intéressant, l'administration orale de probiotiques chez les souris malnutries annulait toutes les anomalies morphologiques et biochimiques. Histologiquement, la modification morphologique et cellulaire de l'intégrité de la membrane des microvillosités a révélé que l'administration de probiotiques atténuait les dommages causées par Giardia aux muqueuses des souris malnutries, alors que les souris malnutries et infectées n'ayant pas reçu de probiotiques présentaient une atrophie sévère des microvillosités, des cellules épithéliales oedémateuses et vaculolées ainsi que des signes d'iléite. Ces résultats démontrent clairement l'effet anti-lambliase des probiotiques in vivo, par la modulation de la capacité des cellules de l'intestin à inhiber la colonisation et la multiplication des trophozoïtes de Giardia, réduisant ainsi la sévérité et la durée de la lambliase chez la souris. [ABSTRACT FROM AUTHOR]

The gut microflora is an important constituent in the intestinal mucosal barrier and has been introduced as the concept of probiotic therapy that beneficially affects the host by improving its intestinal microbial balance. Therefore, the main objective of the study was to explore the protective potential of various lactobacilli strains for murine giardiasis. By experimentation, it was found that the probiotic supplementation of either Lactobacillus casei, L. acidophilus, L. plantarum, or L. rhamnosus GG, 7 days prior to inoculation with G. lamblia trophozoites, reduced the rate of cyst excretion compared with Giardia-infected mice. Interestingly, L. GG was found to be the most effective probiotic in reducing the duration of giardia cycle and acts as an effective prophylactic probiotic for murine giardiasis but needs to be clinically correlated due to entirely different human microflora. [ABSTRACT FROM AUTHOR]

This study describes the in vivo activity of Lactobacillus acidophilus in Giardia lamblia infected BALB/c mice. Experimentally, it was observed that daily administration of lactobacilli 7 days before or in simultaneous inoculation with Giardia trophozoites efficiently reduced G. lamblia infection in mice. More specifically, excretion of Giardia cysts were reduced significantly in probiotic-treated groups, and resolution of infection was observed by day 21 post-inoculation. It was also observed that the lactobacillus count increased tremendously and continuously in faeces of all probiotic-fed mice, and was significantly higher as compared with that in control mice. Histological analysis of microvilli membrane integrity revealed that probiotic administration also protected mice against parasite-induced mucosal damage, whereas Giardia-infected mice had severe villous atrophy, oedema, vacuolation and ileitis. Immunologically, the anti- Giardia serum IgG level was not stimulated significantly by probiotic treatment administered both prior to and simultaneous with Giardia infection, but remained high after the infection peak. Taken together, the data demonstrates the anti-giardial effect of the probiotic in vivo by modulation of the intestinal epithelial cells, inhibiting the colonization of Giardia trophozoites and thereby reducing the severity of Giardia infection. [ABSTRACT FROM AUTHOR]

The present study aimed to improve solubility, dissolution and ultimate bioavailability of poorly soluble artemether, an antimalarial drug, by encapsulating it in β-cyclodextrin (β-CD) and its methyl and hydroxylpropyl derivatives. The effect of these complexes was confirmed by in vivo studies. Phase solubility studies indicated 1:1 stoichiometry and were supported by mass spectrometry and proton nuclear magnetic resonance (¹H-NMR) spectroscopy. True inclusion of artemether into the cyclodextrin cavity was observed in lyophilized complexes by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR) studies. The mode of inclusion was supported by two-dimensional (2D) NMR. Solution calorimetry was used to confirm 1:1 stiochiometry by determining the enthalpy of interaction between the drug and cyclodextrins. The stability constant (K) of inclusion and other thermodynamic parameters such as enthalpy (ΔH) as well as entropy (ΔS) of binding accompanying the encapsulation were determined. The calculated value of K indicated that M-β-CD has maximum complexing efficiency. Dissolution studies indicated that the highest release rate was observed for lyophilized complexes. In vivo studies of lyophilized complexes of M-β-CD showed a 3-fold increase in antimalarial activity compared to artemether and resulted in 100% eradication of parasite. However, 83% and 50% survival rates were achieved in 40 days using HP-β-CD and β-CD complexes respectively. The study concludes that encapsulation of artemether by cyclodextrins is a good alternative to enhance the bioavailability of the drug. [ABSTRACT FROM AUTHOR]

The present study was designed to evaluate the effect of Plasmodium and Salmonella co-infection in LACA mice. The parasitaemic level, bacterial load, histological alterations and levels of oxidants/antioxidant activity were measured. Co-infected mice had a high parasitaemic level, increased bacterial load, and died earlier than Plasmodium-infected mice. Histologically, co-infected mice had more architectural damage in the liver, spleen, kidney, and brain than the control groups. The level of lipid peroxidation was significantly increased and the activities of antioxidative enzymes (superoxide dismutase and catalase) were decreased in all organs of co-infected mice compared to the control groups, indicating depression of the antioxidant defense system. The present study demonstrates more severe histological and biochemical alterations in co-infected mice, highlighting the importance of early diagnosis for selection of appropriate treatments and reducing the likelihood of further complications. [ABSTRACT FROM AUTHOR]

In view of the increasing interest in the bioecological and nutritional control of diseases, use of probiotics alone or in combination with prebiotics (synbiotics) appears as a therapeutic option for various diseases. In this study, an attempt was made to explore the protective potential of Lactobacillus acidophilus as a probiotic, inulin as a prebiotic and both L. acidophilus and inulin as synbiotic against Salmonella-induced liver damage in a murine model. The probiotic, prebiotic and synbiotic supplementation resulted in decreased bacterial translocation in the liver of mice challenged with Salmonella typhimurium and decreased levels of serum aminotransferases, suggesting their protective role against Salmonella infection. Mice supplemented with these preparations before Salmonella challenge also revealed decreased levels of lipid peroxidation, increased levels of superoxide dismutase and glutathione, along with reduced levels of nitric oxide. Thus, bacteriological and biochemical alterations correlated well with the histological evidence. Protection afforded by supplementation with the probiotic alone was found to be more effective. None of the observations was suggestive of the synergistic effect in the synbiotic-supplemented animals. Thus, it is indicated that the probiotic and the prebiotic used in the present study may act by different mechanisms involved in affording protection against Salmonella-induced liver damage. [ABSTRACT FROM AUTHOR]

Zinc (Zn) has been reported to influence the susceptibility of the host to a diverse range of infectious pathogens, including viruses, bacteria, fungi and protozoa. We report here an evaluation of the effects of Zn supplementation on Salmonella enterica serovar Typhimurium (S. typhimurium)-induced hepatic injury in the murine model. Zinc levels in the plasma and liver tissues were measured by atomic absorption spectroscopy. The effect of Zn supplementation was evaluated by assessing the bacterial load and levels of lipid peroxidation (LPO), antioxidants and monokines present in the hepatic tissue as well as by histopathological studies. Zinc supplementation reduced the bacterial load in the liver and reversed hepatic microscopic abnormalities. It also decreased the levels of LPO but increased the levels of reduced glutathione (GSH) as well as the activities of superoxide-dismutase (SOD) and catalase in the livers of infected mice supplemented with Zn compared to the livers of infected mice not supplemented with Zn. Zinc supplementation was also able to modulate the levels of monokines such as tumour necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6). Our results indicate a role for Zn in downregulating oxidative stress and upregulating antioxidant defense enzymes through the action of monokines, suggesting that supplementation with Zn has a protective function in Salmonella-induced liver injury. [ABSTRACT FROM AUTHOR]

Colorectal cancer, the third most commonly diagnosed cancer, is a lifestyle disease where diet and gut microbiome contribute intricately in its initiation and progression. Prophylactic bio-interventions mainly probiotics offer an alternate approach towards reducing or delaying its progression. Therefore, the present study was designed wherein a robust protocol for the isolation, characterization, and identification of indigenous probiotics having antigenotoxic and anticancerous activity was followed along with their prophylactic potential assessment in early experimental colorectal carcinogenesis. Among forty-six isolated lactic acid bacterial strains, only three were selected on the basis of antigenotoxicity against N,N-Dimethyl dihydrazine dihydrochloride and 4-Nitroquinoline 1-oxide and probiotic attributes. All three selected probiotic strains exhibited anticancerous potential as is evident by the reduced Aberrant Crypt Foci, reduced fecal pH, enhanced fecal lactic acid bacteria and altered fecal enzymes (β-glucuronidase, nitroreductase, β-glucosidase) that modulated gut microbiota and microenvironment resulting into restored histoarchitecture of the colon. The results are a clear indicator of the prophylactic potential of selected indigenous probiotics which may be used as an alternative prophylactic biological therapy against colon carcinogenesis particularly in highly susceptible individuals. [ABSTRACT FROM AUTHOR]

Hepcidin, a peptide hormone, is a key regulator in mammalian iron homeostasis. Increased level of hepcidin due to inflammatory conditions stimulates the ferroportin (FPN) transporter internalization, impairing the iron absorption; clinically manifested as anemia of inflammation (AI). Inhibiting hepcidin-mediated FPN degradation is proposed as an important strategy to combat AI. A systematic approach involving in silico, in vitro, ex vivo and in vivo studies is employed to identify hepcidin-binding agents. The virtual screening of 68,752 natural compounds via molecular docking resulted into identification of guanosine 5′-diphosphate (GDP) as a promising hepcidin-binding agent. The molecular dynamics simulations helped to identify the important hepcidin residues involved in stabilization of hepcidin-GDP complex. The results gave a preliminary indication that GDP may possibly inhibit the hepcidin-FPN interactions. The in vitro studies revealed that GDP caused FPN stabilization (FPN-GFP cell lines) and increased the FPN-mediated cellular iron efflux (HepG2 and Caco-2 cells). Interestingly, the co-administration of GDP and ferrous sulphate (FeSO4) ameliorated the turpentine-induced AI in mice (indicated by increased haemoglobin level, serum iron, FPN expression and decreased ferritin level). These results suggest that GDP a promising natural small-molecule inhibitor that targets Hepcidin-FPN complex may be incorporated with iron supplement regimens to ameliorate AI. [ABSTRACT FROM AUTHOR]