The pathochemical role of endothelins in kidney diseases

Introduction. Endothelin-1(ET-1) is an important regulator of kidney function in health and disease. ET-1, largely through activation of endothelin A receptors, has been strongly implicated in renal cell injury, proteinuria, inflammation and fibrosis leading to chronic kidney disease (CKD). Objective of the study. To study the pathochemical role and biochemical mechanisms of endothelins in the kidney diseases and to develop an effective treatment in those diseases. Material and Methods. To achieve the proposed goal, it has been made a synthesis of the literature published since 2011 until 2022, using 5 bibliographic sources, including electronic libraries like PubMed, Medscape, Hinari. Results. The study revealed the role of ET in CKD pathogenesis and discusses the potential therapeutic benefit of targeting the ET system in CKD, with attention to the risks and benefits of such an approach. Endothelin receptor antagonists (ERAs) have been demonstrated to ameliorate or even reverse renal injury and/or fibrosis in experimental models of CKD, while clinical trials indicate a substantial antiproteinuric effect of ERAs in diabetic and non-diabetic CKD patients even on top of maximal renin angiotensin system blockade. Abnormal activation of the renal endothelin system can promote CKD progression, inhibition of primarily ETA receptors has been shown to ameliorate renal injury and fibrosis at multiple levels. Conclusion. Preclinical evidence and early phase clinical trials suggest that ERAs have potential therapeutic benefit as antiproteinuric and nephroprotective drugs for diabetic nephropathy, hypertensive nephropathy, focal segmental glomerulosclerosis (FSGS) and possibly other forms of CKD

Finite Element Study on the Effect of Geometrical Parameters on the Mechanical Behavior of 3D Reentrant Auxetic Honeycombs.

Abstract Auxetic materials are a special case of cellular materials, which exhibit a negative Poisson’s ratio. This in fact is the reason behind their peculiar behavior i.e. lateral shrinkage under longitudinal compression and vice versa. Since these materials do not obey the laws of “normal” materials and go beyond common sense, they are still an emerging class which can be put to use for various purposes like self-locking reinforcing fibers in composites, controlled release media, self-healing films, piezoelectric sensors, and also be used in biomedical engineering. Their stress-strain behavior, Poisson’s ratio and impact energy absorption are controlled by bulk material as well as the unit cell geometry. Among many forms of auxetic structures available, we have chosen a three-dimensional reentrant auxetic honeycomb unit cell. The unit cell geometrical parameters were taken from literature. In this study, we try to understand the effects of strut angle through finite element simulations while keeping the bulk material, unit cell size, strut thickness and number of repetitions constant. A total of three different angles were tested, based on which we conclude that as angle increases, the Poisson’s ratio increases and Energy absorption is maximum at 30 deg

Death sentence on taxonomy in India

The Biological Diversity Act, 2002 seriously curtails the scientific freedom of individual taxonomists by putting draconian regulations on the free exchange of specimens for taxonomic research and threatens to strangulate biodiversity research in India with legal as well as bureaucratic control 1. Rules and guidelines framed to implement the Biological Diversity Act, which itself is flawed and based on wrong premises, reveal the appalling ignorance on the part of the implementing agencies. Guidelines accepted by the Ministry of Environment and Forests, Government of India and the National Biodiversity Authority for international collaboration in biodiversity research are testimony to this. Draft guidelines accepted by the National Biodiversity Authority stipulate that ‘Exchange and transfer of dead specimens and/or herbariums (of no commercial value) on loan for taxonomic studies and return by bona fide scientists/professors of recognized universities and Government Institutions of India who are engaged in pure classical taxonomic studies shall be done through the concerned departments/Ministries of the Government of India 2.’ Similarly, a recent notification of the Ministry of Environment and Forests,based on the above guidelines,states that ‘In case the collaborative research projects involve exchange and transfer of dead or preserved specimen(s) and/or herbarium(s) of India on loan or on any other terms for taxonomic studies as required by bona fide scientists/ professors of recognized universities and Government Institutions of India who are engaged in pure classical taxonomic studies, this shall be done with the approval of concerned Departments/Ministries of the Government of India3.’ These guidelines on implementation would achieve the ultimate bureaucratic control in the history of science in India! Proponents of these guidelines have already revealed their mettle through some ludicrous suggestions to entomologists to send pictures, not (dead) specimens, for identification 4. Being paranoid about biopiracy(!), they may even suggest that microbiologists send digital images of microbes abroad for identification, as live cultures are required for identification and they can be easily multiplied and patented

Osteological morphometric analysis of instrumentation safe zones of C1 and C2 vertebra in North Indian population: a multicentric study

Background: The complex anatomy and critical functional role of the C1 and C2 vertebrae necessitate precise understanding of safe zones for instrumentation to mitigate risks during surgical interventions. This study aimed to conduct a comprehensive morphometric analysis to identify and characterize safe zones for instrumentation within C1 and C2 vertebrae. Though there are multiple radiological based studies, actual osteological measurements are not available for North Indian population. Methods: 200 atlas and axis vertebrae were measured within an accuracy of 0.01 mm to ascertain various dimensions, distances and angles to guide safe exposure and instrumentation. To the best of our knowledge this observational morphometric study is first to provide actual osteological measurements in large number of C1 and C2 vertebrae in North Indian population. Results: The morphometric analysis revealed precise measurements of pedicle dimensions, transverse foramen parameters, and distances from key anatomical landmarks within C1 and C2 vertebrae. Safe zones for instrumentation were identified based on these measurements, considering the optimal implant size and trajectory to minimize the risk of neural or vascular damage. Differences between the morphology of North Indian, South Indian and Turkish C1 and C2 morphology was also identified. Conclusions: This study provides critical insights into the morphometric parameters which can be used to identify safe zones for instrumentation within the C1 and C2 vertebrae. The identified safe zones and associated measurements are essential for optimizing surgical strategies, enhancing instrumentation accuracy, and ultimately improving patient outcomes during craniovertebral surgical procedures. Spine Surgeons can utilize this data to tailor surgical approaches and implant placements, promoting safer and more effective interventions in the challenging anatomical region of the craniovertebral junction

A neo-clerodane diterpene from Teucrium tomentosum. Corrigendum

Corrigendum to Acta Cryst. (2004), E60, o117–o119

Biological Diversity Act, 2002: Shadow of permit-raj over research

It is too late in history of the world to think that there is time to produce ordered classifications of all plants, animals, fungi and micro-organisms, and then to employ these classifications to seek new kinds of generalities while these organisms are still extant. –Peter Rave

Harnessing the probiotic properties and immunomodulatory effects of fermented food-derived Limosilactobacillus fermentum strains: implications for environmental enteropathy

IntroductionEnvironmental enteropathy (EE), a chronic small intestine disease characterized by gut inflammation, is widely prevalent in low-income countries and is hypothesized to be caused by continuous exposure to fecal contamination. Targeted nutritional interventions using potential probiotic strains from fermented foods can be an effective strategy to inhibit enteric pathogens and prevent chronic gut inflammation.MethodsWe isolated potential strains from fermented rice water and lemon pickle and investigated their cell surface properties, antagonistic properties, adhesion to HT-29 cells, and inhibition of pathogen adherence to HT-29 cells. Bacteriocin-like inhibitory substances (BLIS) were purified, and in vivo, survival studies in Caenorhabditis elegans infected with Salmonella enterica MW116733 were performed. We further checked the expression pattern of pro and anti-inflammatory cytokines (IL-6, IL8, and IL-10) in HT-29 cells supplemented with strains.ResultsThe strains isolated from rice water (RS) and lemon pickle (T1) were identified as Limosilactobacillus fermentum MN410703 and MN410702, respectively. Strains showed probiotic properties like tolerance to low pH (pH 3.0), bile salts up to 0.5%, simulated gastric juice at low pH, and binding to extracellular matrix molecules. Auto-aggregation of T1 was in the range of 85% and significantly co-aggregated with Klebsiella pneumoniae, S. enterica, and Escherichia coli at 48, 79, and 65%, respectively. Both strains had a higher binding affinity to gelatin and heparin compared to Bacillus clausii. Susceptibility to most aminoglycoside, cephalosporin, and macrolide classes of antibiotics was also observed. RS showed BLIS activity against K. pneumoniae, S. aureus, and S. enterica at 60, 48, and 30%, respectively, and the protective effects of BLIS from RS in the C. elegans infection model demonstrated a 70% survival rate of the worms infected with S. enterica. RS and T1 demonstrated binding efficiency to HT-29 cell lines in the 38–46% range, and both strains inhibited the adhesion of E. coli MDR and S. enterica. Upregulation of IL-6 and IL-10 and the downregulation of IL-8 were observed when HT-29 cells were treated with RS, indicating the immunomodulatory effects of the strain.DiscussionThe potential strains identified could effectively inhibit enteric pathogens and prevent environmental enteropathy

Insight into the Transmission Biology and Species-Specific Functional Capabilities of Tsetse (Diptera: Glossinidae) Obligate Symbiont Wigglesworthia

Ancient endosymbionts have been associated with extreme genome structural stability with little differentiation in gene inventory between sister species. Tsetse flies (Diptera: Glossinidae) harbor an obligate endosymbiont, Wigglesworthia, which has coevolved with the Glossina radiation. We report on the ~720-kb Wigglesworthia genome and its associated plasmid from Glossina morsitans morsitans and compare them to those of the symbiont from Glossina brevipalpis. While there was overall high synteny between the two genomes, a large inversion was noted. Furthermore, symbiont transcriptional analyses demonstrated host tissue and development-specific gene expression supporting robust transcriptional regulation in Wigglesworthia, an unprecedented observation in other obligate mutualist endosymbionts. Expression and immunohistochemistry confirmed the role of flagella during the vertical transmission process from mother to intrauterine progeny. The expression of nutrient provisioning genes (thiC and hemH) suggests that Wigglesworthia may function in dietary supplementation tailored toward host development. Furthermore, despite extensive conservation, unique genes were identified within both symbiont genomes that may result in distinct metabolomes impacting host physiology. One of these differences involves the chorismate, phenylalanine, and folate biosynthetic pathways, which are uniquely present in Wigglesworthia morsitans. Interestingly, African trypanosomes are auxotrophs for phenylalanine and folate and salvage both exogenously. It is possible that W. morsitans contributes to the higher parasite susceptibility of its host species

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019 : a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. Methods For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dosespecific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in countryreported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. Findings By 2019, global coverage of third-dose DTP (DTP3; 81.6% [95% uncertainty interval 80.4-82 .7]) more than doubled from levels estimated in 1980 (39.9% [37.5-42.1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38.5% [35.4-41.3] in 1980 to 83.6% [82.3-84.8] in 2019). Third- dose polio vaccine (Pol3) coverage also increased, from 42.6% (41.4-44.1) in 1980 to 79.8% (78.4-81.1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56.8 million (52.6-60. 9) to 14.5 million (13.4-15.9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. Interpretation After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe