The present review is focused on the prebiotic impact of inulin on the management of the gastrointestinal disorder. Prebiotics can be described as "non-digestible food ingredient stimulating the growth of a certain number of bacteria in the colon, which can improve the host health". In 2004 this definition was modernized to include other areas that may benefit from selective targeting of particular microorganisms: "selectively fermented ingredients that alter the configuration and activity in the gastrointestinal microbiota that confer positive effect". The positive impact of prebiotics in experimental colitis and human inflammatory bowel disease (IBD) has already been established. Prebiotics shows a positive effect in the prevention of IBD by modulating the trophic functions of the flora. Inulin enhances the growth of indigenous lactobacilli and/or bifidobacteria by inducing colonic production of short chain fatty acids (SCFA's) and these properties are related to decreased mucosal lesion scores and diminished mucosal inflammation. Inulin shows a positive approach to retain microbial populations and to support epithelial barrier function by their prebiotic effect which helps in the host defense against invasion and pathogens translocation (endogenous and/or exogenous) and in the inhibition of gastrointestinal diseases and this impact should be verified in further clinical studies. In the present review, we discussed the positive effect of prebiotics in rat IBD models and in human subjects along with their potential protective mechanisms. Preclinical and clinical data revealed that the gut mucosal barrier would be improved by the use of prebiotics in IBD.
Curcuma longa L. (CLL) extract has previously been reported to alleviate liver damage. The current study examined the antioxidant activity of CLL by which the extract protects the liver against bleomycin (BLM)-induced hepatotoxicity in mice. The hypothesis was that CLL extract would protect the liver by reducing oxidative stress (induced superoxide dismutase (SOD) and catalase (CAT) activity), inhibiting lipid peroxidation, lowering biochemical parameters, and decreasing ROS production. Hepatic toxicity was induced by intraperitoneal injection of mice once daily with BLM (0.069 U/mL; 0.29 U/kg bw.) for a period of 4 weeks. The CLL was administered once a day for 4 weeks, 2 h prior at dose (40 mg/mL; 0.187 mg/kg/day). CLL extract significantly protected the liver, it decreased plasma bilirubin (BL) and gamma glutamyl transpeptidase (GGT), and it reduced lipid peroxidation levels. BLM intoxication produced oxidative stress, in which the antioxidant system functioned incorrectly and ROS production significantly increased. The CLL extract provided significant hepatic protection against BLM toxicity by improving SOD, CAT (p < 0.05), and MDA levels and decreasing ROS in the group receiving BLM (p < 0.05), leading to reduced membrane lipid peroxidation. Throughout this study, the CLL extract facilitated recovery from BLM-induced hepatic injury by suppressing oxidative stress. Therefore, the CLL extract has the potential to serve as an antioxidant compound to treat chronic hepatotoxicity.
The expression of leucine aminopeptidase 3 (LAP3) is associated with the prognosis for and malignant transformation of many types of tumors. Therefore, a LAP3 inhibitor may represent a new strategy for cancer therapy. Evaluating the suppression of enzyme activity by an LAP3 inhibitor is essential. Right now, leucine aminopeptidases (LAPs) purified from the porcine kidneys are the only enzymes that can be used to evaluate the suppression of enzyme activity by an LAP3 inhibitor. This approach cannot accurately reflect the suppression of human LAP3 by an inhibitor. The current study developed a new method with which to evaluate the suppression of enzyme activity by an LAP3 inhibitor. Total protein from K562 cells seldom catalyzed the LAP3 substrate. A lentivirus was used to induce K562 cells to overexpress LAP3 (K562-LAP3). After puromycin screening, flow cytometry data indicated that 98.8% of cells expressed green fluorescent protein. The expression of LAP3 in K562-LAP3 cells was also assessed using Western blotting. K562-LAP3 cells were lysed with ultrasonication. Total protein was used as an enzyme source and L-leucine p-nitroaniline hydrochloride was used as a substrate to measure enzyme activity. Total protein from K562-LAP3 cells catalyzed the substrate more than that from K562 cells did. The LAP3 inhibitor ubenimex was used as a positive control to evaluate the suppression of LAP3 enzyme activity. Results indicated that ubenimex significantly inhibited the enzyme activity of LAP3. This approach provides a convenient and accurate way to evaluate the suppression of enzyme activity by an LAP3 inhibitor.
This study was done with aim to assess the serum sclerostin and dickkopf-1 (DKK-1) level in patients of rheumatoid arthritis (RA) and to correlate their level with disease activity and bone mineral density. Fifty patients of RA and equal age and sex matched healthy controls were included in the study. Patients were evaluated clinically and investigated with routine blood tests along with rheumatoid factor (RF), anti-citrullinated protein antibody (anti-CCP2), radiographs and bone mineral density (BMD). Serum sclerostin and DKK-1 levels of both cases and controls was assayed by using enzyme-linked immunosorbent assay (ELISA) assay [RayBio®, Georgia, USA with coefficient of variation percent (CV %), < 10%] and compared with disease activity and bone mineral density. Disease activity was measured by Disease Activity Score 28 (DAS28) along with Modified Health Assessment Questionnaire (MHAQ) score. Mean serum sclerostin and DKK-1 was significantly higher in study group as compared to control group. Serum sclerostin showed significant correlation with disease activity scores (DAS score and MHAQ score), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level. Serum sclerostin at level of 394 pg/mL was found to have diagnostic significance with sensitivity of 100% and specificity of 90%. DKK-1 level shows significantly positive correlation with larson score which denotes radiological progression (r value 0.468; p value 0.001). More studies with larger sample size of RA patients are needed for better determination of the role of sclerostin and DKK-1 in RA. Also, the correlation of these and other bone turn over markers will help decipher their role with disease progression in RA patients.
Candida albicans is a commensal fungus in human mucosal surfaces, including the oral cavity. Lactoferrin (LF) and the lactoperoxidase (LPO) system, which are host protection components in exocrine secretions, each exhibit weak anti-candida activity. We herein examined the effects of the combination of LF and the LPO system on C. albicans. Morphological observations indicated that the combination of LF and the LPO system reduced the mycelial volume of C. albicans and changed the size and shape of cells more than each agent alone. The combination of LF and the LPO system also exerted strong inhibitory effects on the cellular metabolic activity and adhesive hyphal form of C. albicans. A checkerboard analysis revealed that the anti-candida activity of LF and the LPO system was synergistic. These results suggest that the combination of LF and the LPO system is useful for preventing candidiasis.
Early detection and prediction of preeclampsia (PE) may avert serious materno-fetal complications. This prospective nested study was conducted to evaluate the role of serum beta human chorionic gonadotropin (hCG) and the neutrophil-lymphocyte ratio (NLR) in predicting the development and severity of PE. Four hundred and forty primigravidas, between 16 to 18 weeks of gestation, were recruited in the study. Serum beta-hCG and NLR were measured at the time of recruitment and they were followed and monitored for the development of PE and severe PE. Out of these 440 women, 64 (14%) developed PE; of which 25 (39%) developed severe PE. The mean values of NLR and serum beta hCG were significantly higher in patients developing PE and severe PE. NLR, with a cutoff value of 5.6, predicted the development of PE with 73.4% sensitivity and 88.6% specificity and severe PE with sensitivity 93.3% and specificity 86.6% respectively. The sensitivity and specificity of serum beta hCG in predicting the development of PE was 75% each for a cutoff value of 25,415 IU/mL whereas these values were 86.7%, and 79.1% respectively, for a cut-off value of 29,654 IU/mL for predicting the development of severe PE. These findings suggest that NLR and serum beta hCG can be used as excellent biomarkers in predicting both the development of PE and its severity. Multicentric studies involving subjects of multiple ethnicities should be done for establishing its utility as a routine screening test.
Heart failure with preserved ejection fraction (HFpEF) is a leading cause of morbidity and mortality without an established treatment. Diastolic dysfunction, the hallmark of HFpEF, is associated with altered myocardial bioenergetics. No previous study has examined the effects of coenzyme Q10 (CoQ10) on left ventricle (LV) diastolic function in patients with HFpEF. We investigated whether CoQ10 could improve LV diastolic function in patients with HFpEF. We performed a randomized controlled trial (RCT) using pretest and posttest control groups of 30 patients with HFpEF. The patients received either CoQ10 100 mg three times a day or no CoQ10 in addition to routine treatment for 30 days. Echocardiographic study was performed at baseline and follow-up. LV diastolic function was evaluated by two dimensional and Doppler echocardiography as follows; average E/e׳, septal and lateral e׳velocity, and left atrium volume index (LAVI). A total of 28 patients completed the study. A statistically significant improvement was observed in the CoQ10 treatment group in terms between groups (∆E/e׳ ‒ 3.6 vs. ‒ 2.4; p = 0.28) and (∆LAVI ‒ 5.4 vs. ‒ 4.4; p = 0.83). Short term CoQ10 supplementation provided no additional benefits in improving LV diastolic function in patients with HFpEF.
End-of-life (EOL) care conferences have an important role in promoting EOL care in nursing homes. However, the details of the conferences remain poorly understood. A Japanese prefecture-wide survey was conducted to investigate the factors involved in such conferences that contribute to an increase in the amount of EOL care. One hundred fifty-three nursing homes performed the conferences. The outcome was the amount of EOL care provided in nursing homes after adjusting for the facility beds in 2014. We investigated the factors of staff experience with EOL care, frequency of the conferences, years the conferences were conducted, review conferences after EOL care, and professional participants in the conferences. The multivariate analysis revealed significant associations between EOL care in nursing homes and nurses' experience with EOL care (adjusted β coefficient 2.9, 95% confidence interval (CI) 0.52 ~ 5.22, p = 0.017), more than 5 years of continuous conferences (adjusted β coefficient 3.8, 95% CI 0.46 ~ 7.05, p = 0.026), and family participation (adjusted βcoefficient ‒4.0, 95% CI ‒7.5 ~ ‒0.48, p = 0.026). In conclusion, the continuation of conferences and enrollment of the nurse with experience in EOL care may promote EOL care in nursing homes, while family enrollment in conferences may decrease EOL care in nursing homes. EOL care conferences in nursing homes should be continuously performed by staff, with an experienced nurse undertaking the task of information sharing before discussing EOL care with the patients' families.
Periplasmic binding proteins (PBPs) of Gram-negative bacteria sense essential nutrients and mediate their uptake by ATP-binding cassette (ABC) transporters. The gene for a PBP of H. pylori SS1, annotated as GlnH, is located within the glnPQH operon encoding an ABC importer system. In this study, GlnH has been expressed in E. coli and purified to > 98% homogeneity. The recombinant protein was folded according to the circular dichroism (CD) analysis and behaved as a monomer in solution. Crystals of GlnH have been grown by the hanging-drop vapour-diffusion method using polyethylene glycol (PEG) 4000 as a precipitating agent. The crystals belonged to the primitive monoclinic space group P21 with unit cell parameters a = 38.67, b = 93.36, c = 64.13 Å, β = 93.72°. A complete X-ray diffraction data set was collected to 1.3 Å resolution from a single crystal using synchrotron radiation. Molecular replacement using this data revealed that the asymmetric unit contains a single molecule. This is a key step towards elucidation of the structural basis of the GlnH function.
Familial hypercholesterolemia (FH) is a form of primary hyperlipoproteinemia characterized by the presence of high concentrations of serum low density lipoprotein (LDL) cholesterol, increased tendency to form xanthomas and early onset of coronary artery disease. This disease is an autosomal dominant disorder caused by defects in the gene that encode for the LDL receptor. Homozygous familial hypercholesterolemia is a rare occurrence and here we report a case of an 18-year-old girl with familial hypercholesterolemia treated with anti-lipidemic drugs and controlled only with LDL apheresis. The patient expired after 3 months highlighting the difficulties in management due to economic constraints in a resource limited setting in spite of availability of effective therapy.