Serum kallistatin as a marker of severity of liver fibrosis in cirrhosis: A cross-sectional observational study.

Background: Liver cirrhosis is among the leading causes of morbidity and mortality worldwide. Although liver biopsy is the gold standard for the assessment of liver fibrosis in cirrhosis, it has its own limitations. Therefore, noninvasive methods to detect liver fibrosis are widely preferred. However, they also have their own limitations. Thus, there is always a need to extend the battery of serum-based assays. Kallistatin is a protein synthesized primarily in the liver. As it is a negative acute-phase protein, its blood level decreases with a decline in liver function. In our study, we explored the relationship between serum kallistatin and radiological evidence of liver fibrosis by transient elastography to determine if kallistatin levels can be used as a diagnostic marker of liver fibrosis. Materials and Methods: A cross-sectional study of 1-year duration was conducted at a leading tertiary care hospital in northern India. Patients between 15 and 75 years of age having evidence of chronic liver disease were enrolled. All enrolled patients were evaluated by detailed history, physical examination, and relevant investigations. Serum kallistatin levels were quantified using the ELISA method. Grading of liver fibrosis was done using transient elastography. A FibroScan scoring card was used to convert FibroScan results measured in kPa into the Metavir scale F1-F4. Results: A total of 128 subjects, including 64 patients with cirrhosis and 64 healthy controls, were enrolled. Our study suggested that FibroScan values were significantly higher in cases as compared to controls. The kallistatin level of cases was significantly lower than that of controls. An inverse correlation was found between FibroScan value and kallistatin level among cases. Conclusion: We conclude that serum kallistatin levels are low in patients with liver fibrosis and can be used as a potential marker of liver fibrosis.

Biodegradation of phenol in batch culture by pure and mixed strains of Paenibacillus sp. and Bacillus cereus.

The bacterial strains, Paenibacillus sp. (AY952466) and Bacillus cereus (DQ002384), have proven capacity to degrade lignin and pentachlorophenol. In the present study, both strains were screened at different concentrations of phenol on mineral salt agar medium in the presence of glucose. At optimized condition (pH 7.5 +/- 0.2, 37 +/- 1 degrees C, 120 rpm, 1% glucose w/v), it was observed that both Paenibacillus sp., B. cereus and its mixed culture degraded phenol (500 mg/l) up to 53.86%, 91.63% and 67.76% within 168 h of incubation, respectively. Phenol degradation was routinely monitored spectrophotometrically and further confirmed by HPLC. Catechol and 2-hydroxy muconic semialdehyde were identified as intermediate products from degraded samples using GC-MS. It was also observed that, in the absence of glucose, bacterial strains were unable to utilize phenol indicating the phenomenon of co-metabolism.

A case control study of clinical and biochemical parameters of metabolic syndrome with special attention among young and middle aged population.

BACKGROUND: Metabolic syndrome (MS) increases the risk of heart disease, stroke, and other complications. AIM: The aim of this study was to assess the clinical and biochemical parameters of MS and its complications (cerebrovascular accidents, cardiovascular accidents, DN or chronic kidney disease (CKD) compared with healthy controls especially among the younger population in Northern India. MATERIAL AND METHODS: A total of 245 (healthy, MS and it's complicated) aged 18-70 years participated in the Open-Label, Single Centered; hospital-based random selection case-control comparative study. All anthropometric and biochemical assessment was done after proper consent. The metabolic syndrome was determined by IDF criteria. RESULTS: The key risk parameters in three groups i.e. Control, Metabolic syndrome, and Complicated was TG (96.5 ±â€¯46.9, 194.1 ±â€¯87.8, 148.0 ±â€¯102.2). LDL (91.2 ±â€¯27.2, 114.0 ±â€¯31.8, 69.1 ±â€¯42.5, BP (120.1 ±â€¯9.9, 139.3 ±â€¯13.3, 132.1 ±â€¯15.0) and high fasting glucose (81.1 ±â€¯13.7, 164.5 ±â€¯84.3, 138.0 ±â€¯74.5). The hs-CRP is also significantly increased in the complicated group. The subanalysis of data also indicates that younger middle age (36-55 years) group both male and female is obese, hypertensive, diabetic with lipid abnormality according to IDF criteria. CONCLUSION: The risk factors like high TG, low HDL, high BP, and high fasting glucose were found higher particularly in younger population which may lead to diagnosis & complications of diabetes, hypertension and lipid abnormality. Due to changing physiology in young and middle age population these individuals are moving towards metabolic syndrome easily and needs frequent monitoring, preventive checkups, and lifestyle changes to prevent complications.

Investigation of the biotransformation of pentachlorophenol and pulp paper mill effluent decolorisation by the bacterial strains in a mixed culture.

Mixed culture of two bacterial strains Bacillus sp. and Serratia marcescens showed potential pentachlorophenol (PCP) degradation and decolorisation of pulp paper mill effluent. The physico-chemical quality of pulp paper mill effluent has been analyzed after 168 h incubation period degraded by mixed culture. The study revealed that it has decreased high load of BOD, COD, TS, TDS, TSS, sulphate, phosphate, total nitrogen, total phenols, metals and different salts (i.e. chloride, sodium, nitrate, potassium) at 168 h incubation period. PCP degradation in pulp paper mill effluent was confirmed by HPLC analysis. Mixed culture was found to degrade PCP up to (94%) present in pulp paper mill effluent with 1% glucose and 0.5% peptone (w/v) at 30+/-1 degrees C, pH 8.0+/-0.2 at 120 rpm in 168 h incubation period. The simultaneous release of chloride ion up to 1,200 mg/l at 168 h emphasized the bacterial dechlorination in the medium. The pulp paper mill effluent degradation was also supported by decline in pH, AOX (absorbable organic halides), color, D.O., BOD, COD and PCP. The analysis of pulp paper mill effluent degradation products by GC-MS analysis revealed the formation of low molecular weight compound like 2-chlorophenol (RT=3.8 min) and tetrachlorohydroquinone (RT=11.86 min) from PCP extracted degraded sample. Further, mixed culture may be used for bioremediation of PCP containing pulp paper mill waste in the environment.

Isolation and characterization of bacterial strains Paenibacillus sp. and Bacillus sp. for kraft lignin decolorization from pulp paper mill waste.

Eight aerobic bacterial strains were isolated from pulp paper mill waste and screened for tolerance of kraft lignin (KL) using the nutrient enrichment technique in mineral salt media (MSM) agar plate (15 g/L) amended with different concentrations of KL (100, 200, 300, 400, 500, 600 ppm) along with 1% glucose and 0.5% peptone (w/v) as additional carbon and nitrogen sources. The strains ITRC S6 and ITRC S8 were found to have the most potential for tolerance of the highest concentration of KL. These organisms were characterized by biochemical tests and further 16S rRNA gene (rDNA) sequencing, which showed 96.5% and 95% sequence similarity of ITRC S(6) and ITRC S(8) and confirmed them as Paenibacillus sp. and Bacillus sp., respectively. KL decolorization was routinely monitored with a spectrophotometer and further confirmed by HPLC analysis. Among eight strains, ITRC S(6) and ITRC S(8) were found to degrade 500 mg/L of KL up to 47.97% and 65.58%, respectively, within 144 h of incubation in the presence of 1% glucose and 0.5% (w/v) peptone as a supplementary source of carbon and nitrogen. In the absence of glucose and peptone, these bacteria were unable to utilize KL. The analysis of lignin degradation products by GC-MS analysis revealed the formation of various acids as lignin monomers which resulted in a decrease in pH and a major change in the chromatographic profile of the bacterial degraded sample as compared to the control clear indications of biochemical modification of KL due to the bacterial ligninolytic system by ITRC S(6), namely, acetic acid, propanoic acid, butanoic acid, guaiacol, hexanoic acid, and ITRC S(8), namely acetic acid, propanoic acid, ethanedioic acid, furan carboxylic acid, 2-propanoic acid, butanoic acid, 3-acetoxybutyric acid, propanedioic acid, acetoguiacone, 1,2,3-thiadiazole, 5-carboxaldixime, 4-hydroxy-3,5-dimethoxyphenol, and dibutyl phthalate, indicating the bacterium characteristic to degrade G and S units of lignin polymer.

Mucosal HPV E6/E7 Peptide Vaccination in Combination with Immune Checkpoint Modulation Induces Regression of HPV+ Oral Cancers.

High-risk human papillomavirus (HPV)-associated squamous cell carcinomas of the oropharynx (SCCOP) are among the fastest growing cancers. After standard-of-care treatment, however, patients with HPV+ SCCOP have better overall and disease-specific survival than patients with HPV- SCCOP, suggesting the importance of HPV-specific immunity. We reasoned that therapeutic vaccination targeting the HPV-16 E6 and E7 oncogenes could elicit high-affinity, high-frequency tumor antigen-specific T-cell responses, which could then be augmented and shielded from suppression in the tumor microenvironment by immune checkpoint modulation. In this study, we used a preclinical syngeneic mouse model of oral cancer comprised of mouse tonsil-derived epithelial cells stably expressing HPV-16 E6 and E7 genes along with H-ras oncogene (mEER) to identify combinations of vaccination and checkpoint antibodies capable of promoting tumor regression. Intranasal HPV E6/E7 peptide vaccination and single checkpoint antibodies failed to elicit responses in more than half of animals; however, 4-1BB agonist antibody along with either CD40 agonist antibody or CTLA-4 blockade eliminated the majority of established mEER tumors. The combination of intranasal HPV peptide vaccine and α4-1BB and αCTLA-4 antibodies produced curative efficacy and a better safety profile against orally implanted mEER tumors. Correlates of protective immunity included enhanced intratumoral levels of CD8 T cells relative to immunosuppressive regulatory T cells and myeloid-derived suppressor cells. Overall, our results demonstrate combination vaccine-immunotherapy modalities as novel treatment options for HPV+ SCCOP.Significance: Combinations of vaccine and checkpoint modulation are effective and safe treatment options for HPV+ oral cancers. Cancer Res; 78(18); 5327-39. ©2018 AACR.

Isolation and characterization of novel Serratia marcescens (AY927692) for pentachlorophenol degradation from pulp and paper mill waste.

Seven aerobic bacterial strains were isolated from pulp paper mill waste and screened for pentachlorophenol (PCP) tolerance on PCP containing mineral salt agar medium (MSM). The organism was characterized by 16S rDNA sequencing which showed 99.7% sequence similarity with Serratia marcescens. PCP degradation was routinely monitored with spectrophotometric analysis and further confirmed by HPLC analysis. Among seven strains, ITRC S7 was found to degrade up to 90.33% of 1.127 mM (300 mg/l) of PCP and simultaneous release of chloride ion (2.435 mM) emphasized the bacterial dechlorination in the medium in presence of glucose as an additional carbon and energy source under optimized condition within 168 h incubation. In absence of glucose bacterium was unable to utilize PCP indicating the phenomenon of co-metabolism. Bacterium was identified as S. marcescens (AY927692), was a novel and potential aerobic bacterial strain capable of degrading PCP in axenic condition. Further, this strain may be used for bioremediation of PCP containing pulp paper mill waste in the environment.

Seasonal bacteriological analysis of Gola river water contaminated with pulp paper mill waste in Uttaranchal, India.

The seasonal physico-chemical and microbial quality of Gola river water has been analyzed after confluence of pulp paper mill waste. The study revealed that it has enhanced 20-30 times pollution load of BOD, COD, TDS, TSS, sulphate, chloride, sodium, nitrate, potassium, lignin and phenol after mixing of pulp paper mill waste with river water in all season. Further, it induced the bacterial growth by increasing most probable number value of E. coli was 1.57 x 10(4), 1.6 x 10(4), 1.37 x 10(4) and SPC count was 1.68 x 10(4), 1.64 x 10(4), 1.67 x 10(4)/100 ml during summer, monsoon, winter respectively. While the most probable number value in river water before mixing of pulp paper mill waste was 1.4 x 10(2), 1.82 x 10(2), 1.5 x 10(2) and SPC count was 2.8 x 10(3), 2.89 x 10(3), 2.78 x 10(3)/100 ml during summer, monsoon and winter respectively. This indicated from 88-114 fold increase in most probable number value of E. coli and 56.55-60.0 times increase in SPC count of river water after mixing of effluent in summer, monsoon and winter. Moreover, the most probable number value in effluent itself before mixing was 3.4 x 10(2), 3.3 x 10(2), 2.8 x 10(2) and SPC count was 6 x 10(4), 6.5 x 10(4), 6 x 10(4)/100 ml during summer, monsoon, winter, respectively. Furthermore, it was revealed that the seasonal variation also regulated the bacterial population dynamics as per the physico-chemical quality, in which E. coli was found highest at the rate of (5.9 x 10(4)), E. aerogenes (5.3 x 10(4)), P. aeruginosa (1.3 x 10(4)), S. aureus (3.2 x 10(3)), K. pneumoniae (2.6 x 10(4)), Enteritidis (1.1 x 10(4)) on monsoon season and V. cholerae (7.4 x 10(2)), V. vulnificus (9.2 x 10(2))/100 ml in river water when contaminated with pulp paper mill waste in monsoon season. Thus, the monsoon season showed presence of FC and TC indicated the thermo-tolerant and disease causing group of bacterial population in effluent and its sequence was observed as monsoon>summer>winter. This indicated the growth of many pathogenic and non-pathogenic bacteria for health hazards with contamination of pulp paper waste in aquatic ecosystem within the vicinity of pulp paper mill industry.