Radiotherapy-induced Immune Response Enhanced by Selective HDAC6 Inhibition.

Radiotherapy is a curative cancer treatment modality that imparts damage to cellular DNA, induces immunogenic cell death, and activates antitumor immunity. Despite the radiotherapy-induced direct antitumor effect seen within the treated volume, accumulating evidence indicates activation of innate antitumor immunity. Acute proinflammatory responses mediated by anticancer M1 macrophages are observed in the immediate aftermath following radiotherapy. However, after a few days, these M1 macrophages are converted to anti-inflammatory and pro-cancer M2 phenotype, leading to cancer resistance and underlying potential tumor relapse. Histone deacetylase 6 (HDAC6) plays a crucial role in regulating macrophage polarization and innate immune responses. Here, we report targeting HDAC6 function with a novel selective inhibitor (SP-2-225) as a potential therapeutic candidate for combination therapy with radiotherapy. This resulted in decreased tumor growth and enhanced M1/M2 ratio of infiltrating macrophages within tumors. These observations support the use of selective HDAC6 inhibitors to improve antitumor immune responses and prevent tumor relapse after radiotherapy.

Dermal Drivers of Injury-Induced Inflammation: Contribution of Adipocytes and Fibroblasts.

Irregular inflammatory responses are a major contributor to tissue dysfunction and inefficient repair. Skin has proven to be a powerful model to study mechanisms that regulate inflammation. In particular, skin wound healing is dependent on a rapid, robust immune response and subsequent dampening of inflammatory signaling. While injury-induced inflammation has historically been attributed to keratinocytes and immune cells, a vast body of evidence supports the ability of non-immune cells to coordinate inflammation in numerous tissues and diseases. In this review, we concentrate on the active participation of tissue-resident adipocytes and fibroblasts in pro-inflammatory signaling after injury, and how altered cellular communication from these cells can contribute to irregular inflammation associated with aberrant wound healing. Furthering our understanding of how tissue-resident mesenchymal cells contribute to inflammation will likely reveal new targets that can be manipulated to regulate inflammation and repair.

Carbon: Nitrogen (C:N) ratio level variation influences microbial community of the system and growth as well as immunity of shrimp (Litopenaeus vannamei) in biofloc based culture system.

Biofloc technology (BFT) is a novel modern aquaculture farming technique used to reduce toxic nitrogen concentration, act as in situ food source and eradicate pollutants using carbon and therefore to control C:N ratio in an aquaculture system. In this study, effect of different C:N ratios of a biofloc based system on water quality such as the level of Total ammonia nitrogen (TAN) nitrite-nitrogen (NO2--N) and nitrate nitrogen (NO3--N) were explored. Further, the growth and immunity status of shrimp L. vannamei under the influence of different C:N ratios were evaluated. Two of the C:N ratios (15 and 20) could significantly (P < 0.05) reduce TAN, NO2-N and NO3-N levels (0.456 ±â€¯0.01, 0.145 ±â€¯0.09, and 0.102 ±â€¯0.02 ppm) compared to control (1.45 ±â€¯0.1, 0.749 ±â€¯0.14 and 0.675 ±â€¯0.16 ppm). Large variations in the frequency distribution of operational taxonomic units (OTUs) for the bacterial community in water with different C:N ration (BFT) and control were observed. Vibrios often considered as opportunistic pathogens, where the most dominant bacterial flora of water in control (79%) and C:N5 (37%) group. In C:N10, Thauera (62%) was most represented genus. Similarly, Attheyaceae (56%), followed by Peridiniaceae (30%) were the most dominant groups in C:N15 treatment. The diversity of bacterial flora was more spread in C:N20 treatments with Psychrobacter (26%), Proteobacteria (25%) and Peridiniaceae (20%) as the major groups. The trend of Vibrio dominance decreased with the increase in C:N ratios and thus confirming the dominance of heterotrophic bacteria in high C:N ratio groups. Upon challenge with pathogens, shrimps from C:N10, C:N15 and C:N20 groups showed significantly higher survival (P < 0.05) compared to the C:N5 and control group. Similarly, better growth rate was also observed in BFT tanks compared to control both during the culture and at harvest. Comparatively higher expression of four immune-related genes (ras-related nuclear gene (RAN), serine proteinase gene (SP), prophenoloxidase activating enzyme (PPAE), and crustin were observed in different C:N ratio ponds than control and these were in increasing trend with the C:N ratio. Gene expression analysis showed that the transcripts of those immune genes were significantly increased among all C:N treatments than that of control. Overall, these findings demonstrated that with optimum C:N ratio, BFT can be used to optimize the bacterial community composition for both optimal water quality and optimal shrimp health. This study thus indicates the possibility of obtaining better performance of L. vannamei culture with proper adjustment of C:N ratio in a biofloc based system.

A study of predictors for identification of risk of complications in patients with liver abscess.

BACKGROUND/AIMS: Liver abscess is a significant health problem in developing countries and the complications associated with it are frequently fatal. Hence identification of these complications and anticipating the same will lead to reduction in the mortality and morbidity rate. Such a work will facilitate in identifying patients with risk of complications and will allow for planning of an early intervention. The aim of this study was to identify the predictors of risk of complications in patients with liver abscess. MATERIALS AND METHODS: The data for this retrospective study was obtained from hospital records and included 100 patients diagnosed to have solitary or multiple liver abscess. Complications were defined and history, lab and radiological findings and course of treatment were observed and analyzed in correlation with occurrence of complications. A predictive scoring system was designed for 15 points by giving two points to the factors with 100% correlation and one point to other factors with strong correlation. The score was applied to a validation cohort of 114 different patients and results were noted. RESULTS: Out of the 100 cases studied 24 cases had complications of and the predictive factors included history of alcoholism (> 10 yrs), INR > 1.7 , TLC > 20000/cc and pleural effusion, while other factors had a varying degree of correlation with complication occurrence. It was observed that the new scoring system was successful in identifying patients at risk of developing complications with 100% sensitivity and 93.75% specificity. CONCLUSION: Management of liver abscess can be clearly defined by dividing patients into categories depending upon a new scoring system described in the study and intervention can be planned.

Probiotics and its functionally valuable products-a review.

During the past two decades probiotic bacteria have been increasingly proposed as health promoting bacteria in variety of food system, because of its safety, functional, and technological characteristics. Commonly, Lactobacillus spp., Bifidobacterium spp., Saccharomyces boulardii, and some other microorganisms have been considered as probiotic strains. Possibly these bacterial strains exerted several beneficial effects into gastrointestinal tract of host while administered with variety of food system. Lactic acid bacteria (LAB) usually produce antimicrobial substances like bacteriocin which have broad spectrum of antagonist effect against closely related Gram positive and Gram negative pathogens. LAB strains often produce polymeric substances such as exopolysaccharides (EPS) which increase the colonization of probiotic bacteria by cell-cell interactions in gastrointestinal tract. LAB also produces biosurfactant which showed that the wide range of antimicrobial activity against bacterial pathogen as well as its antiadhesive properties reduces the adhesion of pathogens into gastric wall membrane. Furthermore, LAB strains have also been reported for production of antioxidants which are ability to scavenge the free radicals such as superoxide anions and hydroxyl radicals. For this sense, this review article is mainly focused on the ecology, biosynthesis, genetics, target sites, and applications of bacteriocins and EPS from LAB strains. Moreover, this review discusses about the production and functions of nutritive essential element folate and iron chelating agent such as siderophores from LAB.

Traditional Indian fermented foods: a rich source of lactic acid bacteria.

This review describes the diversity of Indian fermented food and its significance as a potential source of lactic acid bacteria (LAB). Fermented foods consumed in India are categorized based upon their base material. Fermented foods such as dahi, gundruk, sinki, iniziangsang, iromba, fermented rai, kanjika and handua were reported to have significant medicinal properties. Some fermented products such as koozh, dahi and kanjika are consumed unknowingly as, probiotic drinks, by local people. There are very few reports regarding isolation of LAB from Indian fermented foods available in the past; however, due to growing consciousness about potential health benefits of LAB, we now have scores of reports in this field. There is an abundant opportunity available for food microbiologists to explore the Indian fermented foods for the isolation of new LAB strains for their potential role in probiotic research.

Microbial decolorization of synthetic dyes and reactive dyes of industrial effluents by using a novel fungus Aspergillus proliferans.

A decolorizing fungal strain was isolated and identified by the morphology and genotypic characterization as Aspergillus proliferans. The effect of A. proliferans on decolorization of synthetic dyes (70 mg ml(-1)) and colored effluent was evaluated in liquid culture medium. A. proliferans expressed their effective decolorization activity in effectual decolorization of synthetic dyes and industrial effluent. Synthetic dyes were decolorized by 76 to 89% within 6 days of treatment and 73.5% of color was removed in industrial effluent within 8 days. The addition of optimum carbon and nitrogen sources were effectively stimulated the decolorization activity. The high concentration of glucose repressed the decolorization activity and supplementation of yeast extract has significantly enhanced the effluent decolorization at p < 0.05. Laccase enzyme was isolated from liquid state fermentation, which showed significant enzyme activity (10,200 Uml(-1)) at p < 0.005. The crude enzyme decolorizes the dyes aniline blue and congo red in 14 hours (40.9 to 70%) and the effluent in 14 hours (88.6%). Moreover, the culture free supernatant without the fungal biomass has also effectively decolorized the effluent and synthetic dyes. The fungi Aspergillus proliferans was used not only for decolorization but also for better bioremediation of industrial effluent.

Purification and characterization of enterocin MC13 produced by a potential aquaculture probiont Enterococcus faecium MC13 isolated from the gut of Mugil cephalus.

A bacteriocin producer strain MC13 was isolated from the gut of Mugil cephalus (grey mullet) and identified as Enterococcus faecium. The bacteriocin of E. faecium MC13 was purified to homogeneity, as confirmed by Tricine sodium dodecyl sulphate - polyacrylamide gel electrophoresis (SDS-PAGE). Reverse-phase high-performance liquid chromatography (HPLC) analysis showed a single active fraction eluted at 26 min, and matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry analysis showed the molecular mass to be 2.148 kDa. The clear zone in native PAGE corresponding to enterocin MC13 band further substantiated its molecular mass. A dialyzed sample (semicrude preparation) of enterocin MC13 was broad spectrum in its action and inhibited important seafood-borne pathogens: Listeria monocytogenes , Vibrio parahaemolyticus, and Vibrio vulnificus. This antibacterial substance was sensitive to proteolytic enzymes: trypsin, protease, and chymotrypsin but insensitive to catalase and lipase, confirming that inhibition was due to the proteinaceous molecule, i.e., bacteriocin, and not due to hydrogen peroxide. Enterocin MC13 tolerated heat treatment (up to 90 °C for 20 min). Enterococcus faecium MC13 was effective in bile salt tolerance, acid tolerance, and adhesion to the HT-29 cell line. These properties reveal the potential of E. faecium MC13 to be a probiotic bacterium. Enterococcus faecium MC13 could be used as potential fish probiotic against pathogens such as V. parahaemolyticus, Vibrio harveyi, and Aeromonas hydrophila in fisheries. Also, this could be a valuable seafood biopreservative against L. monocytogenes.

Lactobacillus plantarum AS1 binds to cultured human intestinal cell line HT-29 and inhibits cell attachment by enterovirulent bacterium Vibrio parahaemolyticus.

AIM: Lactobacillus plantarum AS1 was incubated with HT-29 adenocarcinoma cell line to assess its adhesion potency and examined for its inhibitory effect on the cell attachment by an enterovirulent bacterium Vibrio parahaemolyticus. METHODS AND RESULTS: Lactobacillus plantarum AS1 attached efficiently to HT-29 cells as revealed by scanning electron microscopy and bacterial adhesion assay. Lactobacillus plantarum AS1 significantly reduced V. parahaemolyticus attached to HT-29 cells by competition, exclusion and displacement mode. Lactobacillus plantarum AS1 seems to adhere to human intestinal cells via mechanisms that involve different combinations of carbohydrate and protein factors on the bacteria and eukaryotic cell surface. CONCLUSION: Strain Lact. plantarum AS1 inhibits the cell attachment of a pathogen V. parahaemolyticus by steric hindrance mechanism. Also, antibacterial factors such as bacteriocins, lactic acid and exopolysaccharides could be involved. SIGNIFICANCE AND IMPACT OF THE STUDY: The ability to inhibit the adhesion of V. parahaemolyticus to intestinal cell line warrants further investigation to explore the use of probiotic strain Lact. plantarum AS1 in the management of gastroenteritis caused by V. parahaemolyticus.

Optimization of media components for enhanced production of streptococcus phocae pi80 and its bacteriocin using response surface methodology

The standard MRS components were optimized using response surface methodology for increasing yield of Streptococcus phocae PI80 viable cells and its bacteriocin. The highest amounts of bacteriocin activity and viable cells were recorded from prediction point of optimized MRS medium and achieved two fold higher (33049.8 AU.mL-1 and 14.05 LogCFU.mL-1) than un-optimized counterpart.

Production and purification of a novel exopolysaccharide from lactic acid bacterium Streptococcus phocae PI80 and its functional characteristics activity in vitro.

Optimum culture conditions which ease the synthesis of a novel exopolysaccharide (EPS) from a potent marine strain Streptococcus phocae was proposed in this study. The strain grows well at 35 °C, pH 7.0 and NaCl (2%) with lactose and yeast extract as best carbon and nitrogen sources. The maximum yield of EPS (11.75 and 12.14 g/L) was obtained in the presence of lactose and yeast extract at a concentration of 20 g/L respectively. EPS was refined by gel filtration chromatography using phenyl Sepharose column which revealed the presence of arabinose, fructose and galactose sugar units with molecular mass about 2.8 × 10(5) Da. Emulsifying and flocculating stability of EPS compared with three commercial hydrocolloids. EPS exhibited better activities which are similar to that of commercial hydrocolloids. Both crude and purified EPS exhibited strong antioxidant potential by quenching hydroxyl and superoxide anion radicals. Antibiofilm activity by inhibition of Gram positive and Gram negative biofilm forming bacteria was evident in our studies. Potential antioxidant activity and biofilm inhibiting property of EPS may lead to the development of novel food grade adjuncts.

Optimization of media components for enhanced production of streptococcus phocae pi80 and its bacteriocin using response surface methodology.

The standard MRS components were optimized using response surface methodology for increasing yield of Streptococcus phocae PI80 viable cells and its bacteriocin. The highest amounts of bacteriocin activity and viable cells were recorded from prediction point of optimized MRS medium and achieved two fold higher (33049.8 AU.mL(-1) and 14.05 LogCFU.mL(-1)) than un-optimized counterpart.

Isolation, Characterization and Identification of a Potential Probiont from South Indian Fermented Foods (Kallappam, Koozh and Mor Kuzhambu) and Its Use as Biopreservative.

Twenty-five strains of lactic acid bacteria (LAB) isolated from South Indian traditional fermented foods Kallappam batter, Koozh and Mor Kuzhambu. Further 6 strains were selected based on their antimicrobial activity. They were identified according to morphological, biochemical and physiological criteria. Identification by 16S rDNA sequence homology of the isolates revealed the presence of Weissella paramesenteroides, Lactobacillus plantarum and Lactobacillus fermentum. Lactobacillus plantarum AS1 showed maximum antimicrobial activity among 6 strains and this strain was chosen for biopreservation. When male Albino Wistar rats were fed with L. plantarum AS1 (approx. 10(9) cells/mL for a month), there was no sign of any illness and they were on par with control rats in terms of weight gain/week. In the L. plantarum AS1-treated group, there was reduction in the populations of indigenous microflora of coliforms, yeast and molds; however, the lactobacilli population increased comparatively. L. plantarum AS1 was able to retain its normal growth in the presence of increasing concentration of bile salt in the MRS and it also tolerated the artificial gastric juice simulating the condition inside the stomach where it was viable for 24 h with bacterial count of 6.079 logCFU/mL. L. plantarum AS1 reduced the cholesterol in the MRS broth by 57.3%. Hence, all these properties established it as an effective probiont. L. plantarum AS1 found to be an effective biopreservative in cheese, where it decreased the population of Salmonella typhi by 2.95 log cycles.