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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 (

Pseudomonas aeruginosa, 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.

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. Keywords: nanoparticles, guar gum, celecoxib, colorectal cancer, release kinetics, cytotoxicity

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.

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.

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.

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 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.

The antimicrobial activity of silver nanoparticles (AgNPs) prepared using root extracts of Berginea ligulata (Paashaanbhed), Rheum australe (Himalayan rhubarb) and Selinum vaginatum (Bhutakeshi) plants was compared with the antimicrobial activity of chemically synthesized AgNPs using Gelatin, Polyvinyl Alcohol (PVA) and Polyvinylpyrrolidone (PVP) against bacterial strains Salmonella enteric typhi, Bacillus cerus, and Pseudomonas aeruginosa. The physico-chemical characterization was carried out by employing UV–vis spectrometry, Transmission electron microscopy (TEM), Fourier transforms infrared spectrometry (FTIR) and Zeta potential analyzer. The AgNPs synthesized using green pathway showed higher efficacy in comparison to those synthesized using chemical pathway. The overall antimicrobial activity order was found to be S. vaginatum > R. australe > B. ligulata > gelatin > PVP > PVA stabilized AgNPS respectively. This is the first study dealing with the comparative efficacy of green and chemically synthesized AgNPs against the strains Salmonella enteric typhi and Pseudomonas aeruginosa.

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.

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

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.

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

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.

Acinetobacter baumannii is an emerging multi-drug resistant pathogen causing significant mortality in hospitalized ICU patients which demands developing new methods for prevention and treatment. A. baumannii 19606 proteome was analysed in silico through the online tool Vaxign for finding potential vaccine candidates. The selected nuclease (NucAb) was predicted to possess all the attributes of a promising vaccine candidate like outer membrane localization, high adhesin probability (0.53), one transmembrane helix only, non-homology to human proteins and presence of B-cell and T-cell epitopes binding with high affinity (percentile rank≤1) to HLA alleles prevalent at high frequency in North Indian populations. nucAb gene was highly prevalent (100%) among the clinical isolates (40/40) and conserved (>98%) among NCBI sequenced Acinetobacter strains. It was cloned in pET28a, purified and its immunoprotective potential was validated in murine pneumonia model. Immunization of BALB/c mice with recombinant NucAb (25μg) elicited high antibody titre (1-5×10(5)) which reduced bacterial load by 5 log cycles in lungs of mice challenged with optimized lethal dose (10(8)CFU). Lung histopathology revealed marked suppression of inflammation. Pro-inflammatory cytokines (TNF-α and IL-6) levels were reduced significantly and anti-inflammatory (IL-10) cytokine increased in lungs and serum leading to decreased severity and slow progression of disease. Though active immunization showed low survival rate (20%), passive immunization improved the survival (40%). This is the first study reporting an outer membrane nuclease as a vaccine candidate in Gram negative bacterium, A. baumannii through reverse vaccinology approach.

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.

A plethora of evidences support the health benefits of a sulfur containing compound called Benzyl Isothiocyanate. However, its therapeutic application is limited due to its low solubility, poor stability and inadequate bioavailability. The problem has been worked upon and resolved by the synthesis of biodegradable nanoparticles using chitosan as the controlled delivery nanowagon. The prepared nanoparticles have been characterized using UV-visible absorption spectroscopy, IR spectroscopy, XRD, TGA, TEM and FE-SEM. Results reveal that loading of benzyl isothiocyanate into chitosan nanoparticles increases its solubility and stability. The maximum encapsulation efficiency was obtained to be 64.68±4.7% with slow and sustained release of 77.78% in 144h at pH5.5. Clear enhancement in the stability of benzyl isothiocyanate that is sensitive to ultraviolet light has been showcased after its encompassment in the cationic polymer. Further the biosafety of the fabricated system has been demonstrated by haemolysis and its interaction with biomolecules. The antimicrobial activity connotes that the prepared nanoparticles can act as a useful and safe carrier for the loading of benzyl isothiocyanate making it a promising formulation for biological applications in future.

The inexorable increase in the incidence of colorectal cancer has led to growing interest in its prevention by natural interventions. Thus, the present study was designed with the aim of delineating the antioxidative and antitumorigenic effects of synbiotics in experimental colon carcinogenesis. It was observed that administration of a synbiotic, before 1,2 dimethylhydrazine dihydrochloride (DMH)-induced colon carcinogenesis in Sprague-Dawley rats, led to increased body weight and growth rate, and decreased tumor incidence compared with the DMH-only-treated group of animals. Most notably, the level of malondialdehyde, a measure of lipid peroxidation, decreased, and levels of the antioxidants, glutathione reductase, superoxide dismutase, and glutathione peroxidase increased in animals in the Lactobacillus acidophilus+DMH, inulin+DMH, and synbiotic+DMH groups compared with DMH-only-treated animals. Histopathological observations of the colon also documented fewer dysplastic changes and increased the number of goblet cells in the probiotic-treated, prebiotic-treated, and synbiotic-treated animals compared with DMH-only-treated animals. Taken together, the present study shows that the use of synbiotics is a better prophylactic strategy than the use of probiotic and prebiotic alone because of the greater increase in antioxidants associated with the higher degree of attenuation of DMH-induced tumorigenesis.

Malaria infection during pregnancy is a risk factor for foetus survival and is associated with abortion, premature delivery and low birth weight of infants in malaria endemic regions. In these regions, prophylactic measures and treatment mainly rely on chloroquine and sulphadoxine pyrimethamine, but their efficacy in reducing the placental pathology has not been studied. Therefore, the present study was designed to assess the effectiveness of chloroquine and sulphadoxine pyrimethamine treatment in reducing the placental pathology of Plasmodium berghei infected BALB/c mice. It was observed that pregnant-infected mice, treated either with chloroquine or sulphadoxine pyrimethamine had significantly lower percent parasitaemia, 100% survival and delivered normally compared with untreated pregnant-infected mice. Interestingly, antimalarial treatment significantly reduced malondialdehyde (MDA) levels, measure of lipid peroxidation and number of apoptotic cells in the placentae of pregnant-infected treated mice. Histologically also no morphological and cellular alterations were observed in the placentae of pregnant-infected treated mice. Taken together, the study shows the effectiveness of chloroquine and sulphadoxine pyrimethamine treatment, when administered in second trimester in abrogating malaria induced oxidative stress, apoptosis and histopathological alterations in the placenta, leading to normal foetal development.

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.

Prebiotics are substances that promote the growth of beneficial microorganisms thus, having health benefits as functional food. In the present study, comparative effect of prebiotics inulin and lactulose on 1,2-dimethylhydrazine dihydrochloride (DMH) induced procarcinogenic biomarkers in early colon carcinogenesis is described. It was found that aberrant crypt foci counts were significantly (p

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.

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 × 10(9) lactobacilli daily for 1 week, and then a weekly injection of DMH was given intraperitoneally for 6 wks with daily administration of probiotic. Lactobacillus GG and L.acidophilus + DMH-treated animals had maximum percent reduction in ACF counts. A significant decrease (P < 0.05) in fecal nitroreductase activity was observed in L.casei + DMH and L.plantarum + DMH-treated rats whereas β-glucuronidase activity decreased in L.GG + DMH and L.acidophilus + DMH-treated rats. Animals treated with Bifidobacterium 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, and L.acidophilus can be used as the better prophylactic agents for experimental colon carcinogenesis.

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.

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 situ single 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-a-vis the pure drug. In vivo pharmacodynamic studies in Plasmodium berghi infected 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-a-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.

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 (10(8) 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-1β 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.

Malarial infection during pregnancy has been associated with maternal anemia and death, abortion, still-birth and is a major cause of low birth weight, an important risk factor for infant morbidity and mortality in endemic areas. The present study was designed to delineate the oxidative stress in various organs (liver, spleen, kidney, brain and placenta) of pregnant Plasmodium berghei infected BALB/c mice. It was observed that pregnant-infected mice had higher parasitaemia than nonpregnant-infected mice. Most notably, levels of malondialdehyde (MDA), a measure of lipid peroxidation, reduced glutathione (GSH) and superoxide dismutase (SOD) levels were significantly higher in the liver, spleen, kidney and brain of pregnant-infected mice compared with pregnant mice. Although MDA levels were significantly higher, GSH and SOD levels remained unaltered in the placenta of pregnant-infected mice compared with pregnant mice. Furthermore, catalase activity was significantly lower in all the organs of pregnant-infected mice compared with pregnant mice. Histopathological observations in the organs clearly show the cellular and morphological alterations that may be occurring due to increased lipid peroxidation. Taken together, the data suggest that the increased severity of malarial infection during pregnancy may be due to accentuated oxidative stress.

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.

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.

The study reports the characterization and pharmacological activity of sulphadoxine which is encaged by β-CD and its hydroxypropyl and methyl derivatives. Phase solubility studies depict AL type of curves suggesting 1:1 complexation. Inclusion of drug in solid state was evidenced by Differential scanning calorimeter (DSC), Powder X-ray diffractometery (PXRD), Fourier transform infrared spectroscopy (FTIR) and in solution phase by NMR and solution calorimetry. In the proton NMR chemical shifts of aniline ring and methoxy group of pyrmidine ring moved downfield upon inclusion indicating the potentiality of both sides of the drug to interact with the cavity. Insertion of whole of the drug molecule inside the cavity is ruled out because of its three dimensional (3D) structure. Thus, co-existence of two 1:1 complexes is proposed in the present study. The calorimetric data are fitted into two class binding model to evaluate the values of stability constants (K 1 and K 2) along with enthalpy of binding (∆H 1 and ∆H 2). Efficiency of the encaged drug was evaluated by in vitro drug release studies and provided useful information for the selection of appropriate form for further studies. The best performance in terms of dissolution rate enhancement was displayed by the Sulpha-M-β-CD lyophilized product. This was further evaluated on the basis of its pharmacological activity using Balb/C mice and showed significantly higher survival rate (83.3%) after 30 days as to the uncomplexed drug which showed (33%) survival.

The purpose of the present work is to improve the antimalarial activity of arteether through enhancing its solubility subsequently bioavailability by incorporating the drug into the cyclodextrins cavity. The effect of hydrophilic polyvinyl propylene (PVP) polymer on the complexation and solubilizing efficiencies of cyclodextrins (CDs) is also elucidated. Inclusion of arteether molecule in solid state was evidenced by Differential scanning calorimeter (DSC), Powder X-ray diffractometery (PXRD), and in solution state by NMR and solution calorimetry. A 1:1 stoichiometry was proposed by the phase solubility studies both in presence and absence of PVP. The most plausibe mode of inclusion of arteether into the CD cavity is revealed by molecular modeling studies utalizing Fast Rigid Exhaustive Docking acronym. Solution calorimetry was used further to confirm 1:1 stiochiometry in presence or absence of PVP by determining the enthalpy of interaction between the drug and cyclodextrins. The inclusion of drug was found to be exothermic process accompanied by small positive value of entropy (ΔSo). The methylated-β-CD showed the best ability to solublize arteether which is approximately at par with β-CD in the presence of PVP. Better complexation efficiency of β-CD in presence of PVP is also reflected by the higher numerical values of stability constant (K). Compelete eradication of the parasite from the blood and highest anti-malarial pharmacological activity was observed in the complexes of arteether with M-?-CD while 83.7% was observed for ternary complexes of β-CD in presence of PVP.

Objective To assess the role of heat shock proteins (hsps) in the placental pathology of Plasmodium berghei infected mice. Methods Female BALB/c mice were infected with Plasmodium berghei infected RBC intraperitoneally on 10th gestational day. The expression of hsps in the placenta were monitored by reverse transcriptase real time PCR. Results There was increased expression of hsps 90, 70, 60 and 25 genes on day 2, 4 and 6 post infection in the infected placenta. However, the expression of hsps 70, 60 and 25 genes decreased with the progression of malaria infection. Conclusions Decreased expression of hsps 70, 60 and 25 genes in the malaria infected placenta might be one of the many other factors responsible for apoptosis in the placenta and may be responsible for associated altered placental pathology and fetal abnormalities.