Extracellular vesicles: Novel communicators in lung diseases

This work is licensed under a Creative Commons Attribution 4.0 International License.The lung is the organ with the highest vascular density in the human body. It is therefore perceivable that the endothelium of the lung contributes significantly to the circulation of extracellular vesicles (EVs), which include exosomes, microvesicles, and apoptotic bodies. In addition to the endothelium, EVs may arise from alveolar macrophages, fibroblasts and epithelial cells. Because EVs harbor cargo molecules, such as miRNA, mRNA, and proteins, these intercellular communicators provide important insight into the health and disease condition of donor cells and may serve as useful biomarkers of lung disease processes. This comprehensive review focuses on what is currently known about the role of EVs as markers and mediators of lung pathologies including COPD, pulmonary hypertension, asthma, lung cancer and ALI/ARDS. We also explore the role EVs can potentially serve as therapeutics for these lung diseases when released from healthy progenitor cells, such as mesenchymal stem cells.NiH R01DA042715NIH R01HL129875NIH P20 GM10363

Antistaphylococcal activity of bacteriophage derived chimeric protein P128

<p>Abstract</p> <p>Background</p> <p>Bacterial drug resistance is one of the most significant challenges to human health today. In particular, effective antibacterial agents against methicillin-resistant <it>Staphylococcus aureus </it>(MRSA) are urgently needed. A causal relationship between nasal commensal <it>S. aureus </it>and infection has been reported. Accordingly, elimination of nasal <it>S. aureus </it>reduces the risk of infection. Enzymes that degrade bacterial cell walls show promise as antibacterial agents. Bacteriophage-encoded bacterial cell wall-degrading enzymes exhibit intrinsic bactericidal activity. P128 is a chimeric protein that combines the lethal activity of the phage tail-associated muralytic enzyme of Phage K and the staphylococcal cell wall targeting-domain (SH3b) of lysostaphin.</p> <p>Here we report results of in vitro studies evaluating the susceptibility of staphylococcal strains to this novel protein.</p> <p>Results</p> <p>Using the broth microdilution method adapted for lysostaphin, we found that P128 is effective against <it>S. aureus </it>clinical strains including MRSA, methicillin-sensitive <it>S. aureus </it>(MSSA), and a mupirocin-resistant <it>S. aureus</it>. Minimum bactericidal concentrations and minimum inhibitory concentrations of P128 (1-64 μg/mL) were similar across the 32 <it>S. aureus </it>strains tested, demonstrating its bactericidal nature.</p> <p>In time-kill assays, P128 reduced colony-forming units by 99.99% within 1 h and inhibited growth up to 24 h.</p> <p>In an assay simulating topical application of P128 to skin or other biological surfaces, P128 hydrogel was efficacious when layered on cells seeded on solid media. P128 hydrogel was lethal to Staphylococci recovered from nares of healthy people and treated without any processing or culturing steps, indicating its in situ efficacy. This methodology used for in vitro assessment of P128 as an agent for eradicating nasal carriage is unique.</p> <p>Conclusions</p> <p>The novel chimeric protein P128 is a staphylococcal cell wall-degrading enzyme under development for clearance of <it>S. aureus </it>nasal colonization and MRSA infection. The protein is active against globally prevalent antibiotic-resistant clinical isolates and other clinically significant staphylococcal species including <it>S. epidermidis</it>. The P128 hydrogel formulation was bactericidal against Staphylococci including <it>S. aureus </it>recovered from the nares of 31 healthy people, demonstrating its in situ efficacy.</p

Urinary Exosomal microRNA-451-5p Is a Potential Early Biomarker of Diabetic Nephropathy in Rats

Non-invasive renal signatures can help in serial monitoring of diabetic patients. We tested whether urinary exosomal (UE) microRNA (miR) analysis could non-invasively predict renal pathology in diabetic rats during the course of diabetes. Diabetes mellitus (DM) was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg body weight). Non-diabetic control (CTRL) rats were injected with vehicle. Insulin (INS) treatment (5U/d, s.c.) was provided to 50% of the DM rats. Urine samples were collected at weeks 3, 6, and 9 following injections and UE prepared. An increase in miR-451-5p and miR-16, observed by pilot small RNA sequencing of UE RNA, was confirmed by quantitative real-time polymerase chain reaction (qPCR) and selected for further study. Subsets of rats were euthanized after 3, 6, and 9 weeks of diabetes for renal pathology analysis, including determination of the tubulointerstitial fibrotic index (TFI) and glomerulosclerotic index (GI) scores. qPCR showed a substantial rise in miR-451-5p in UE from DM rats during thecourse of diabetes, with a significant rise (median fold change >1000) between 3 and 6 weeks. Moreover, UE miR-451-5p at 6 weeks predicted urine albumin at 9 weeks (r = 0.76). A delayed but significant rise was also observed for miR-16. In contrast, mean urine albumin only increased 21% between 3 and 6 weeks (non-significant rise), and renal TFI and GI were unchanged till 9 weeks. Renal expression of miR-451-5p and miR-16 (at 10 weeks) did not correlate with urine levels, and moreover, was negatively associated with indices of renal pathology (r�-0.70, p = 0.005 for TFI and r�-0.6, p�0.02 for GI). Overall, a relative elevation in renal miR-451-5p and miR-16 in diabetes appeared protective against diabetes- induced kidney fibrosis; while UE miR-451-5p may hold prognostic value as an earlyand sensitive non-invasive indicator of renal diseas

Conservation Management of the Endangered Asiatic Lions in Gujarat, India, Using GPS Satellite Telemetry

Endangered Asiatic lions (Panthera leo persica) are found in the Asiatic Lion Landscape, Gujarat, which includes protected areas and a multi-use land matrix. Therefore, monitoring lions’ space-use and spatio-temporal location is vital for managing various facets of human−lion interaction. Our study demonstrates how this was achieved by tracking lions using GPS radio-collars, triggering prompt action via an efficient communication network across political and forest administrative boundaries. We monitored the movement of 19 individual lions for 436.5 ± 32 days and also derived the mean daily activity from three-axis accelerometer-based activity-sensing feature of a radio-collar. We also monitored geofence breaches. We proposed that immobility and movement are two aspects that generate management action on the ground. While the movement is related to ranging and dispersal, immobility is a situation related to either the animal’s feeding or its health status. From a management standpoint, we discussed the efficacy of the virtual geofence in preventing accidents when lions moved and also presented the advantages of being able to track dispersal through a case study of sub-adult lions. To strengthen our response to lion immobility, we developed a predictive model that specifically highlights an individual lion’s health status and makes the alert response more precise. In conclusion, we critically reviewed the capabilities provided by GPS telemetry and provide protocols that help in the conservation management of lions and that will also have a wider application

Opium alkaloids, biosynthesis, pharmacology and association with cancer occurrence

Papaver somniferum L. (Family: Papaveraceae) is a species well known for its diverse alkaloids (100 different benzylisoquinoline alkaloids (BIAs)). L-tyrosine serves as a precursor of several specific metabolites like BIAs. It has been used as an antitussive and potent analgesic to alleviate mild to extreme pain since ancient times. The extraction of pharmaceutically important alkaloids like morphine and codeine from poppy plant reflects the need for the most suitable and standard methods. Several analytical and extraction techniques have been reported in open literature for morphine, codeine and other important alkaloids which play a vital function in drug development and drug discovery. Many studies suggest that opioids are also responsible for adverse effects or secondary complications like dependence and withdrawal. In recent years, opium consumption and addiction are the most important risk factors. Many evidence-based reviews suggest that opium consumption is directly linked or acts as a risk factor for different cancers. In this review, we highlight significant efforts related to research which have been done over the past 5 decades and the complete information on Papaver somniferum including its phytochemistry, pharmacological actions, biosynthetic pathways and analytical techniques of opium alkaloid extraction and the link between opium consumption and cancer-related updates

Home Range, Movement and Activity Patterns of Six vulture Species Using Satellite Telemetry in Saurashtra landscape, Gujarat, India

The information on the ranging behaviour and migration pattern of vultures is of critical conservation importance. Vultures&rsquo; range over vast areas in human-dominated landscapes where anthropogenic activities may influence their long-term survival. This paper uses the satellite telemetry of 11 individuals of six vulture species to assess their home ranges and seasonal movement patterns. The study aimed to find daily and monthly distances covered by vultures, their home range size, and the influence of breeding season on resource utilisation and activity rates. A total of 114,820 locations were collected between October 2020 and November 2021. The results indicate that the size of the core area is smaller during the breeding season of the resident species, such as the Indian vulture (Gyps indicus), white-rumped vulture (Gyps bengalensis), and red-headed vulture (Sarcogyps calvus) than the non-breeding season. vulture&rsquo;s daily and monthly movement (mean) also decreased in the breeding season. The annual home range and core areas, calculated as 95% and 50%Utilisation Distribution differed between breeding and non-breeding seasons. The migratory vultures moved significantly longer distances across days and months than the resident species. Their annual migration patterns also differed with respect to time and migration routes

Wilm's tumor-1 protein levels in urinary exosomes from diabetic patients with or without proteinuria.

BACKGROUND: Podocyte injury is an early feature of diabetic nephropathy (DN). Recently, urinary exosomal Wilm's tumor-1 protein (WT1), shed by renal epithelial cells, has been proposed as a novel biomarker for podocyte injury. However, its usefulness as biomarker for early diabetic nephropathy has not been verified yet. We investigated urinary exosomal WT1 in type-1 diabetic patients to confirm its role as a non-invasive biomarker for predicting early renal function decline. METHODS: The expression of WT1 protein in urinary exosomes from spot urine samples of type-1 diabetes mellitus patients (n = 48) and healthy controls (n = 25) were analyzed. Patients were divided based on their urinary albumin excretion, ACR (mg/g creatinine) into non- proteinuria group (ACR<30 mg/g, n = 30) and proteinuria group (ACR>30 mg/g, n = 18). Regression analysis was used to assess the association between urinary exosomal levels of WT1 with parameters for renal function. Receiver Operating Characteristic (ROC) curve analysis was used to determine the diagnostic performance of exosomal WT-1. RESULTS: WT1 protein was detected in 33 out of 48 diabetic patients and in only 1 healthy control. The levels of urinary exosomal WT1 protein is significantly higher (p = 0.001) in patients with proteinuria than in those without proteinuria. In addition, all the patients with proteinuria but only half of the patients without proteinuria were positive for exosomal WT1. We found that the level of exosomal WT1 were associated with a significant increase in urine protein-to-creatinine ratio, albumin-to-creatinine ratio, and serum creatinine as well as a decline in eGFR. Furthermore, patients exhibiting WT1-positive urinary exosomes had decreased renal function compared to WT1-negative patients. ROC analysis shows that WT-1 effectively predict GFR<60 ml. min-1/1.73 m(2). CONCLUSION: The predominant presence of WT1 protein in urinary exosomes of diabetic patients and increase in its expression level with decline in renal function suggest that it could be useful as early non-invasive marker for diabetic nephropathy

Home Ranges and Migration Routes of Four Threatened Raptors in Central Asia: Preliminary Results

Understanding the migratory route of raptors in their breeding and wintering grounds is crucial for ensuring their effective conservation. This study presents the preliminary findings through satellite telemetry to describe the summer and winter home ranges, movement ecology, activity, and migration routes of single individuals of Greater Spotted Eagle (Clanga clanga), Indian Spotted Eagle (Clanga hastata), Tawny Eagle (Aquila rapax), and Pallid Harrier (Circus macrourus). We calculated the home ranges as the minimum convex polygons (MCPs) and kernel utilisation distributions (KUD). Pallid Harrier had the smallest home range size of 4.29 km2 (95% MCP) and 3.98 km2 (95% KUD) in its breeding ground located in Russia, while the Greater Spotted Eagle had the largest home range size of 9331.71 km2 (95% MCP) and 5991.15 km2 (95% KUD) in Kazakhstan. The monthly and daily distances covered by tagged birds were significantly higher during migration. Our study also reports the first record of the winter and summer home range of the Indian Spotted Eagle in Pakistan. The tagged raptor used low elevation flyways than the straighter northern flyways over the Himalayan Mountain range, as found in another earlier study. Our study is the foremost satellite telemetry attempt from the region, highlighting important aspects of the migration route of migratory raptors to India

Details of phases, study sites, time duration and transects laid in different study sites in Asiatic Lion Landscape, Gujarat, India.

Details of phases, study sites, time duration and transects laid in different study sites in Asiatic Lion Landscape, Gujarat, India.</p