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BackgroundObesity is a raising risk factor for many diseases including Cardiovascular risks and Cancer. The present limitations and inaccuracy of anthropometric measures as well as treatment options demand research of integrative management strategies and identification of specific biomarkers of obesity. This study identifies the urine exosome biomarkers and its differential expression profile between 3-timepoints from female obese participants who underwent Ayurveda treatment.MethodologyUrine exosomes were isolated using PEG methods of isolation. The major proteins obtained were identified using label-free quantification in LC-MS/MS. The genes involved in pathway enrichment, functional annotation and disease manifestation were identified and shortlisted based on protein interaction network. The hub genes representing obesity are identified.ResultsThe exosomes isolated were validated using LC-MS/MS. Using UniProt as reference, a total of 210 exosome proteins were identified. 73 genes were overexpressed in pathway enrichment analysis. Further, GO functional annotation identified 15 common genes involved. Finally, the 8 genes common in obesity were identified and its differential expression profile was seen to have corrected at timepoints during treatment.ConclusionThis is the first study to isolate and identify urine exosomes profiles from female obese participants of India. The study results indicate the correction in the differential expression profile of 8 hub genes involved in obesity post treatment. The biomarker signature of the pilot study indicates the specificity of urine exosomes as diagnostic markers. The study also promotes the potential of integrative and complementary treatment approaches like Ayurveda in effective management of many metabolic diseases.

Urinary tract infection (UTI) is a prominent global health care burden. Although UTI is readily treated with antibiotics in healthy adults, complicated cases in immune-compromised individuals and the emerging antibiotic resistance of several uropathogens have accelerated the need for new treatment strategies. Here, we surveyed the composition of urinary exosomes in a mouse model of uropathgenic Escherichia coli (UPEC) UTI to identify specific urinary tract defense constituents for therapeutic development. We found an enrichment of the iron-binding glycoprotein lactoferrin in the urinary exosomes of infected mice. In subsequent in vitro studies, we identified human bladder epithelial cells as a source of lactoferrin during UPEC infection. We further established that exogenous treatment with human lactoferrin (hLf) reduces UPEC epithelial adherence and enhances neutrophil antimicrobial functions including bacterial killing and extracellular trap production. Notably, a single intravesicular dose of hLf drastically reduced bladder bacterial burden and neutrophil infiltration in our murine UTI model. We propose that lactoferrin is an important modulator of innate immune responses in the urinary tract and has potential application in novel therapeutic design for UTI.

Background: To define urine or serum biomarkers in predicting renal function recovery after liver transplantation (LT). Methods: Adults listed for LT (February 2011-July 2014) and with modified diet for renal disease-6 (MDRD-6) Results: Of 271 LT listed patients (mean age 57 years, 63% males, median listing MELD 17.5), 1 year acute kidney injury (AKI) probability was 49%, with odds of 1.3-, 3.0-, 4.6-, and 8.5-fold times for listing MELD 16-20, 21-25, 26-30, and >30, compared to MELD p = 0.003). Differences between acute tubular necrosis (ATN) and hepatorenal syndrome could not be ascertained for a small sample of 3 patients with ATN. Analyzing 15 of 43 receiving LT and MDRD-6 50 mL/min) at 6 months vs. 10 without recovery. Conclusions: AKI is common among LT listed patients, with a negative impact on transplant-free survival. Serum and urine biomarkers are not associated with the recovery of renal function after LT. Multicenter studies are suggested to (a) develop strategies to reduce the development of AKI and (b) derive novel biomarkers for use in accurately predicting renal recovery after LT.

Urinary tract infection (UTI) is a prominent global health care burden. Although UTI is readily treated with antibiotics in healthy adults, complicated cases in immune-compromised individuals and the emerging antibiotic resistance of several uropathogens have accelerated the need for new treatment strategies. Here, we surveyed the composition of urinary exosomes in a mouse model of uropathgenic Escherichia coli (UPEC) UTI to identify specific urinary tract defense constituents for therapeutic development. We found an enrichment of the iron-binding glycoprotein lactoferrin in the urinary exosomes of infected mice. In subsequent in vitro studies, we identified human bladder epithelial cells as a source of lactoferrin during UPEC infection. We further established that exogenous treatment with human lactoferrin (hLf) reduces UPEC epithelial adherence and enhances neutrophil antimicrobial functions including bacterial killing and extracellular trap production. Notably, a single intravesicular dose of hLf drastically reduced bladder bacterial burden and neutrophil infiltration in our murine UTI model. We propose that lactoferrin is an important modulator of innate immune responses in the urinary tract and has potential application in novel therapeutic design for UTI.

Introduction Nephrotoxicity from drugs accounts for 18% to 27% of cases of acute kidney injury. Determining a genetic predisposition may potentially be important in minimizing risk. The aims of this study are as follows: to determine whether a genetic predisposition exists for the development of drug-induced kidney disease (DIKD), using genome-wide association and whole-genome sequencing studies; to describe the frequency, course, risk factors, resolution and outcomes of DIKD cases; to investigate the role of ethnic/racial variability in the genetics of DIKD; and to explore the use of different tools establishing causality of DIKD. Methods A total of 800 patients will be enrolled worldwide and blood samples for DNA collected. Data on the patient risk factors, vital signs, laboratory parameters, drug exposure, and DIKD course will be recorded. A panel of nephrologists will adjudicate all cases. Genome-wide association studies will be conducted using population controls matched on biogeographic ancestry to determine whether there is a genetic predisposition to DIKD. The primary endpoint is the identification of specific drug-related polymorphisms associated with DIKD. Secondary endpoints include the following: frequency of DIKD by causal drug and drug combinations; DIKD genetic variability; exploration of causality assessment tools; risk factor identification; description of the course of DIKD, including mortality and dialysis dependency at hospital discharge and 28 and 90 days post-event. Results Data are currently being analyzed. Results are pending. Discussion The Genetic Contribution to Drug Induced Renal Injury (DIRECT) study will be the first observational cohort study to investigate the genetic determinants of DIKD. If the trial is positive, its findings will potentially translate into safer patient outcomes, by genotypic individualization of therapy and minimization of harm.

In order that malaria be successfully contained, it is important that one has a clear understanding of the normal physiology and biochemistry of the parasite essential to its survival in its human host. Until very recently, the conventional approaches to antimalarial chemotherapy have consistently been plagued with the uncanny ability of the parasite to evolve resistance to drugs. The recently discovered plasmodial fatty acid biosynthetic pathway as well as its inhibition by triclosan that classifies it as belonging to type II, provide with a very crucial breakthrough to the crusade against malaria. How triclosan could tilt the balance in favor of the human hosts of the malarial parasite in a malarial condition is discussed.

In order that malaria be successfully contained, it is important that one has a clear understanding of the normal physiology and biochemistry of the parasite essential to its survival in its human host. Until very recently, the conventional approaches to antimalarial chemotherapy have consistently been plagued with the uncanny ability of the parasite to evolve resistance to drugs. The recently discovered plasmodial fatty acid biosynthetic pathway as well as its inhibition by triclosan that classifies it as belonging to type II, provide with a very crucial breakthrough to the crusade against malaria. How triclosan could tilt the balance in favor of the human hosts of the malarial parasite in a malarial condition is discussed.