Long-term application of organic manures and chemical fertilizers improve the organic carbon and microbiological properties of soil under pearl millet-wheat cropping system in North-Western India.

An on-going long term field experiment started in Rabi 1995 at the Research Farm of the Department of Soil Science, Chaudhary Charan Singh Haryana Agricultural University, Hisar, Haryana (India) under the pearl millet-wheat cropping system was selected to study the effect of long-term application of organic manures and fertilizers on soil organic carbon and microbiological properties. Highest soil organic carbon (SOC: 1.18 %), dissolved OC (DOC: 64.74 mg kg-1) content, microbial biomass C (MBC: 618.40 mg kg-1), dehydrogenase (DHA: 72.83 µg TPF g-1 24 hr-1), alkaline phosphatase (APA: 685.44 µg PNP g-1 soil hr-1) and aryl sulfatase (ASA: 12.56 µg PNP g-1 soil hr-1) activities were observed with the application of 15 Mg FYM+150 kg N+30 kg P2O5 ha-1. Integrated application of chemical fertilizers with pressmud showed superiority in the improvement of microbial biomass nitrogen (MBN: 73.73 mg kg-1) and urease activity (69.54 µg NH4+ g-1 hr-1) than FYM or poultry manure plus NP. Beneficial impacts of the sole application of organic manures on SOC, DOC, MBC content, DHA, APA, and ASA were found in order as: FYM > pressmud > poultry manure. Impacts of nutrient management practices on soil carbon fractions decreased with depth. Poultry manure application, either alone or in combination with NP fertilizers was inferior to FYM and pressmud. The SOC had a positive relationship with MBC (R2 = 0.95) and MBN (R2 = 0.75) and, also showed a highly positive and significant correlation with microbiological properties of soil. This dynamic equilibrium among soil properties indicated that the nutrient management practices that improve SOC could lead to improve soil fertility and accrued microbiological properties in these soils. This study revealed that conjuctive use of organic manures and chemical fertilizers have positive impact on soil fertility and microbiological properties as compared to sole application of organic manures or fertilizers; and among organic manures, FYM was superior to pressmud followed by poultry manure.

Unveiling Diversity for Quality Traits in the Indian Landraces of Horsegram [Macrotyloma uniflorum (Lam.) Verdc.].

Horsegram (Macrotyloma uniflorum [Lam.] Verdc.) is an underutilized pulse crop primarily cultivated in South Asian countries like India, Nepal, and Sri Lanka. It offers various nutraceutical properties and demonstrates remarkable resilience to both biotic and abiotic stresses. As a result, it has emerged as a promising crop for ensuring future food and nutritional security. The purpose of this study was to assess the nutritional profile of 139 horsegram germplasm lines obtained from 16 Indian states that were conserved at the National Gene Bank of India. Standard analytical methods, including those provided by the Association of Official Analytical Chemists (AOAC), were used for this investigation. The study revealed substantial variability in essential nutrients, such as protein (ranging from 21.8 to 26.7 g/100 g), starch (ranging from 26.2 to 33.0 g/100 g), total soluble sugars (TSSs) (ranging from 0.86 to 12.1 g/100 g), phenolics (ranging from 3.38 to 11.3 mg gallic acid equivalents (GAEs)/g), and phytic acid content (ranging from 1.07 to 21.2 mg/g). Noteworthy correlations were observed, including a strong positive correlation between sugars and phenols (r = 0.70) and a moderate negative correlation between protein and starch (r = -0.61) among the studied germplasm lines. Principal component analysis (PCA) highlighted that the first three principal components contributed to 88.32% of the total variability, with TSSs, phytates, and phenols emerging as the most significant contributors. The cluster analysis grouped the accessions into five clusters, with cluster III containing the accessions with the most desirable traits. The differential distribution of the accessions from north India into clusters I and III suggested a potential geographical influence on the adaptation and selection of genes. This study identified a panel of promising accessions exhibiting multiple desirable traits. These specific accessions could significantly aid quality breeding programs or be directly released as cultivars if they perform well agronomically.

Enhanced degradation of Congo-red dye by Cr3+ doped α-Fe2O3 nano-particles under sunlight and industrial wastewater treatment.

Considering the increasing amount of water pollution, nanocomposite advances for the effective elimination of hazardous pollutants are still needed. α-Fe2O3, Cr0·5Fe1·5O3 and CrFeO3 nanoparticles were synthesized via an eco-friendly material synthesis i. e hydrothermal route without using any precipitating agent and were studied to remove congo-red dye using photocatalytic properties. X-ray diffraction (XRD), Transmission electron microscopy (TEM), Field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy (FESEM), Brunauer-Emmett-Teller (BET), X-ray photoelectron spectroscopy (XPS) characterizations have been performed to know about the material structure and properties of synthesized samples. High efficiency (95.2%) of degradation was achieved under sunlight using a very low amount of CrFeO3 catalyst (0.2 g/L) at a 6-pH level of dye and was confirmed using UV spectroscopy, TOC (84%), LC-HRMS. Also, the potential to degrade the CR dye was concluded from the high rate of BOD5/COD. The results showed a significant enhancement in the degradation of α-Fe2O3 from 52.3% to 95.2% in a short duration of 15 min by introducing chromium as a dopant. The doping of chromium influenced the major factors responsible for the photocatalytic activity such as the increase in range of absorbance, increased e--h+ pair separation, improvement in the charge transfer process and active site formation which significantly enhanced the process of degradation. We found that the Cr-doped α-Fe2O3 nanomaterial could effectively remove dyes, such as congo-red, from industrial water-waste.

Comparative evaluation of canal transportation and centering ability of rotary and reciprocating file systems using cone-beam computed tomography: An in vitro study.

Aim: The aim of the study was to evaluate the canal transportation and centering ability of rotary and reciprocating file systems using cone-beam computed tomography. Materials and Methods: Mesiobuccal canals of sixty mandibular molars were selected for the study. Canals of length 19 mm, curvature of 10°-12°, and uncalcified with fully formed apex were selected. Canals were randomly divided into three groups of 20 teeth, and canal preparation with the WaveOne Gold, TruNatomy, and One Curve systems was performed according to the manufacturers' instructions. Cone-beam computed tomographic images were taken before and after instrumentation in the same position for comparative analysis. Statistical Analysis Used: Apical transportation was calculated at the distances of 2, 3, and 4 mm from the apex. Tukey's post hoc test and unpaired "t"-tests were used to statistically analyze the data. Results: WaveOne Gold caused less canal transportation and better-centering ability than TruNatomy and One Curve at all the three levels; there was a significant difference in canal transportation and centering ability among all the groups as well as all the three levels, i.e., 2, 3, and 4 mm from the apex. Conclusion: WaveOne Gold (Reciprocating) reported less canal transportation and better-centering ability than rotary instruments TruNatomy and One Curve (Rotary) at all the three levels.

Rare fatal effect of combined use of sildenafil and alcohol leading to Cerebrovascular Accident.

Sildenafil is the first internationally approved drug for erectile dysfunction. Unsupervised and non-prescribed use of sildenafil among young Indian population has increased in last few years. Sildenafil helps in erection of penis by inhibiting the action of Phosphodiesterase-5 (PDE-5) enzyme, present in the vasculature of corpus cavernosum muscle and lengthens the duration of erection. Documented adverse effects of sildenafil are headache, flushing, nasal congestion, dyspepsia, and slight decrease in systolic and diastolic blood pressure. We present a rare case of sudden death due to cerebrovascular hemorrhage after sildenafil use and concomitant alcohol intake. The history is that a 41-year-old male with no significant past medical and surgical history was staying at a hotel room with a female friend; he had consumed 2 tablets of sildenafil (50 mg each) and alcohol at night. Next morning, he developed uneasiness following which he was taken to the Hospital where he was declared dead on arrival. The important autopsy findings include edematous brain with about 300 g of clotted blood in the right basal ganglia extending to bilateral ventricles, and in pons region. Other significant findings on microscopic examination were hypertrophic ventricular wall of heart, fatty changes in liver and acute tubular necrosis and hypertensive changes in the kidney. The findings are discussed in the light of the literature about the lethal complications of combined use of sildenafil and alcohol including cerebrovascular accidents. As a forensic pathologist it is the duty of the doctor to execute meticulous autopsy along with ancillary investigations including toxicological analysis and to correlate all these findings to determine the possible effects of drugs when present, so as to gather knowledge about potentially fatal drugs and further create public awareness regarding the same.

Prevalence of C-shaped canal and related variations in maxillary and mandibular second molars in the Indian Subpopulation: A cone-beam computed tomography analysis.

Aim: The aim of this study was to evaluate the prevalence and anatomical configuration of the C-shaped canal in permanent maxillary and mandibular second molars in the Greater Noida population by compiling the results of data that used cone-beam computed tomography (CBCT) analysis. Subjects and Methods: CBCT images were taken from the archive in the department of oral medicine and radiology taken for diagnostic purposes referred by other departments in the dental college. Five hundred CBCT records of patients, between the age group of 15-40 years, containing maxillary second molars and mandibular second molars were selected and reviewed. Statistical Analysis: Statistical analysis was done using the Chi-square test to find out the most common configuration of the C-shaped canal between maxillary and mandibular second molars. Results: Hundred and ten out of 500 patients had C-shaped canals (22%). Among them, 58 teeth (52.7%) were continuous C-shaped canals, 41 teeth (37.3%) were semicolon-shaped canals and 11 teeth (10%) had separated canals. (Chi-square test value = 8.26, P = 0.024). Statistically significant difference was found in configuration types. Among the jaw type, 62 maxillary second molar presented with C-shaped canal (25.1%) and 48 mandibular second molar presented with C-shaped canal (18.9%) (Chi-square test value = 3.87, P = 0.276). However, the difference was statistically insignificant in relation to the jaw type. Conclusions: Within the limitation of the study, we can conclude that the overall prevalence of C-shaped canals was 22% and the most common C-shaped canal configuration type was continuous (52.7%). However, no statistically significant difference was found in relation to jaw type.

Plant probiotics - Endophytes pivotal to plant health.

Endophytes as a ubiquitous associate of the plant are considered as a promising candidate for sustainable agriculture. These organisms play a pivotal role in the regulation of the primary and secondary metabolism of their host plant. The direct and long-lasting interaction of endophytes with the host enables them to escape from harsh environmental conditions. Especially, their endophytic nature makes them better candidates over epiphytes and rhizospheric microbes in interaction with plants. Current research findings revealed that the endophytes help plants in making nutrient acquisition from the soil, nitrogen fixation, phosphate availability, phytohormone and antimicrobial production. There is a huge potential for developing novel products like endophytes-based microbial formulations and elicitors to improve plant health, ameliorating stress tolerance in plants and source of therapeutically important secondary metabolites. The present review specifically dealt with attributes such as host-tissue specificity of endophytes, the importance of seed-associated endophytes, endophyte-parasite plant-host plant interaction as well as their applications in plant in-vitro systems and as microbial consortium. In addition, the conserved endophytic microbial communities in different plants are also looked upon possibly to understand the plant-endophytic microbiome on similar lines of the animal-gut microbiome. Primarily, the purpose of this review is to implicate the endophytic flora as probiotics influencing overall plant health and their survival under extreme environmental conditions.

Role of Endothelial Cell Lipoprotein Lipase for Brown Adipose Tissue Lipid and Glucose Handling.

Cold-induced activation of brown adipose tissue (BAT) has an important impact on systemic lipoprotein metabolism by accelerating the processing of circulating triglyceride-rich lipoproteins (TRL). Lipoprotein lipase (LPL) expressed by adipocytes is translocated via endothelial to the capillary lumen, where LPL acts as the central enzyme for the vascular lipoprotein processing. Based on preliminary data showing that LPL is not only expressed in adipocytes but also in endothelial cells of cold-activated BAT, we aimed to dissect the relevance of endothelial versus adipocyte LPL for lipid and energy metabolism in the context of adaptive thermogenesis. By metabolic studies we found that cold-induced triglyceride uptake into BAT, lipoprotein disposal, glucose uptake and adaptive thermogenesis were not impaired in mice lacking Lpl exclusively in endothelial cells. This finding may be explained by a compensatory upregulation in the expression of adipocyte-derived Lpl and endothelial lipase (Lipg).

Hepatic IRF3 fuels dysglycemia in obesity through direct regulation of Ppp2r1b.

Inflammation has profound but poorly understood effects on metabolism, especially in the context of obesity and nonalcoholic fatty liver disease (NAFLD). Here, we report that hepatic interferon regulatory factor 3 (IRF3) is a direct transcriptional regulator of glucose homeostasis through induction of Ppp2r1b, a component of serine/threonine phosphatase PP2A, and subsequent suppression of glucose production. Global ablation of IRF3 in mice on a high-fat diet protected against both steatosis and dysglycemia, whereas hepatocyte-specific loss of IRF3 affects only dysglycemia. Integration of the IRF3-dependent transcriptome and cistrome in mouse hepatocytes identifies Ppp2r1b as a direct IRF3 target responsible for mediating its metabolic actions on glucose homeostasis. IRF3-mediated induction of Ppp2r1b amplified PP2A activity, with subsequent dephosphorylation of AMPKα and AKT. Furthermore, suppression of hepatic Irf3 expression with antisense oligonucleotides reversed obesity-induced insulin resistance and restored glucose homeostasis in obese mice. Obese humans with NAFLD displayed enhanced activation of liver IRF3, with reversion after bariatric surgery. Hepatic PPP2R1B expression correlated with HgbA1C and was elevated in obese humans with impaired fasting glucose. We therefore identify the hepatic IRF3-PPP2R1B axis as a causal link between obesity-induced inflammation and dysglycemia and suggest an approach for limiting the metabolic dysfunction accompanying obesity-associated NAFLD.

Exosomes Secreted by Umbilical Cord Blood-Derived Mesenchymal Stem Cell Attenuate Diabetes in Mice.

Mesenchymal stem cell (MSC) therapy is an innovative approach in diabetes due to its capacity to modulate tissue microenvironment and regeneration of glucose-responsive insulin-producing cells. In this study, we investigated the role of MSC-derived exosomes in pancreatic regeneration and insulin secretion in mice with streptozotocin-induced diabetes. Mesenchymal stem cells (MSCs) were isolated and characterized from umbilical cord blood (UCB). Exosomes were isolated and characterized from these MSCs. Diabetes was induced in male C57Bl/6 mice by streptozotocin (STZ; 40 mg/kg body weight, i.p.) for five consecutive days. The diabetic mice were administered (i.v.) with MSC (1 × 105 umbilical cord blood MSC cells/mice/day), their derived exosomes (the MSC-Exo group that received exosomes derived from 1 × 105 MSC cells/mice/day), or the same volume of PBS. Before administration, the potency of MSCs and their exosomes was evaluated in vitro by T cell activation experiments. After day 7 of the treatments, blood samples and pancreatic tissues were collected. Histochemistry was performed to check cellular architecture and ß cell regeneration. In body weight, blood glucose level, and insulin level, cell proliferation assay was done to confirm regeneration of cells after MSC and MSC-Exo treatments. Hyperglycemia was also attenuated in these mice with a concomitant increase in insulin production and an improved histological structure compared to mice in the PBS-treated group. We found increased expression of genes associated with tissue regeneration pathways, including Reg2, Reg3, and Amy2b in the pancreatic tissue of mice treated with MSC or MSC-Exo relative to PBS-treated mice. MicroRNA profiling of MSC-derived exosomes showed the presence of miRs that may facilitate pancreatic regeneration by regulating the Extl3-Reg-cyclinD1 pathway. These results demonstrate a potential therapeutic role of umbilical cord blood MSC-derived exosomes in attenuating insulin deficiency by activating pancreatic islets' regenerative abilities.

Electrical, electrochemical and structural studies of a chlorine-derived ionic liquid-based polymer gel electrolyte.

In the present article, an ionic liquid-based polymer gel electrolyte was synthesized by using poly(vinylidene fluoride-co-hexafluoropropylene) (PVdF-HFP) as a host polymer. The electrolyte films were synthesized by using the solution casting technique. The as-prepared films were free-standing and transparent with good dimensional stability. Optimized electrolyte films exhibit a maximum room-temperature ionic conductivity of σ = 8.9 × 10-3 S·cm-1. The temperature dependence of the prepared polymer gel electrolytes follows the thermally activated behavior of the Vogel-Tammann-Fulcher equation. The total ionic transference number was ≈0.91 with a wider electrochemical potential window of 4.0 V for the prepared electrolyte film which contains 30 wt % of the ionic liquid. The optimized films have good potential to be used as electrolyte materials for energy storage applications.

Performance comparison between Chaos and quantum-chaos based image encryption techniques.

Today's digital era has undertaken most of the responsibilities of public and private sectors, not only the industries or big organizations dependent on the internet but individual's household needs also lying on it. To make the data transmission/reception confidential and secure for both internet users and internet service providers, a large number of researches have been done in this field. It has proved that cryptography is the best solution for solving this purpose. Mostly, digital images are continuously transferring on the network rather than texts. Enciphering a digital image is a much bulkier and a complex task. It has been evident from many types of research that chaotic logistic map-based equations provide a great level of randomness. Hence Chaotic logistic maps-based image encryption techniques (also called chaos techniques) were implemented to obtain highly random cipher images. On the other hand, time consumption must be as low as it can be possible to sustain real-time communication. Presently, the advanced encryption schemes based on quantum technology have enhanced efficiency and security because of having a large key-space and less time complexity along with randomness. The quantum-chaos based encryption is done by utilizing uncertainty principles of quantum mechanics on logistic maps. This paper is an effort to compare chaos and quantum chaos-based image encryption schemes. MATLAB 2016a software is used for the execution and the comparison is made based on various security attack analyses. Based on the study and experimental results, the quantum chaos techniques used for bit plane scrambling provides better results in terms of effectiveness, efficiency, and trustworthy that can be adopted for highly secured image encryption.

IRF3 reduces adipose thermogenesis via ISG15-mediated reprogramming of glycolysis.

Adipose thermogenesis is repressed in obesity, reducing the homeostatic capacity to compensate for chronic overnutrition. Inflammation inhibits adipose thermogenesis, but little is known about how this occurs. Here we showed that the innate immune transcription factor IRF3 is a strong repressor of thermogenic gene expression and oxygen consumption in adipocytes. IRF3 achieved this by driving expression of the ubiquitin-like modifier ISG15, which became covalently attached to glycolytic enzymes, thus reducing their function and decreasing lactate production. Lactate repletion was able to restore thermogenic gene expression, even when the IRF3/ISG15 axis was activated. Mice lacking ISG15 phenocopied mice lacking IRF3 in adipocytes, as both had elevated energy expenditure and were resistant to diet-induced obesity. These studies provide a deep mechanistic understanding of how the chronic inflammatory milieu of adipose tissue in obesity prevents thermogenic compensation for overnutrition.

The P2X7 ion channel is dispensable for energy and metabolic homeostasis of white and brown adipose tissues.

Several studies suggest a role of extracellular adenine nucleotides in regulating adipose tissue functions via the purinergic signaling network. Metabolic studies in mice with global deletion of the purinergic receptor P2X7 on the C57BL/6 background indicate that this receptor has only a minor role in adipose tissue for diet-induced inflammation or cold-triggered thermogenesis. However, recent data show that a polymorphism (P451L) present in C57BL/6 mice attenuates P2X7 receptor function, whereas BALB/c mice express the fully functional P451 allele. To determine the potential role of P2rx7 under metabolic and thermogenic stress conditions, we performed comparative studies using male P2rx7 knockout (KO) and respective wild-type controls on both BALB/c and C57BL/6 backgrounds. Our data show that adipose P2rx7 mRNA levels are increased in obese mice. Moreover, P2rx7 deficiency results in reduced levels of circulating CCL2 and IL6 with a moderate effect on gene expression of pro-inflammatory markers in white adipose tissue and liver of BALB/c and C57BL/6 mice. However, P2X7 expression does not alter body weight, insulin resistance, and hyperglycemia associated with high-fat diet feeding on both genetic backgrounds. Furthermore, deficiency of P2rx7 is dispensable for energy expenditure at thermoneutral and acute cold exposure conditions. In summary, these data show that-apart from a moderate effect on inflammatory cytokines-P2X7 plays only a minor role in inflammatory and thermogenic effects of white and brown adipose tissue even on the BALB/c background.

The E3 ubiquitin ligase HectD3 attenuates cardiac hypertrophy and inflammation in mice.

Myocardial inflammation has recently been recognized as a distinct feature of cardiac hypertrophy and heart failure. HectD3, a HECT domain containing E3 ubiquitin ligase has previously been investigated in the host defense against infections as well as neuroinflammation; its cardiac function however is still unknown. Here we show that HectD3 simultaneously attenuates Calcineurin-NFAT driven cardiomyocyte hypertrophy and the pro-inflammatory actions of LPS/interferon-γ via its cardiac substrates SUMO2 and Stat1, respectively. AAV9-mediated overexpression of HectD3 in mice in vivo not only reduced cardiac SUMO2/Stat1 levels and pathological hypertrophy but also largely abolished macrophage infiltration and fibrosis induced by pressure overload. Taken together, we describe a novel cardioprotective mechanism involving the ubiquitin ligase HectD3, which links anti-hypertrophic and anti-inflammatory effects via dual regulation of SUMO2 and Stat1. In a broader perspective, these findings support the notion that cardiomyocyte growth and inflammation are more intertwined than previously anticipated.

Adipocytes fail to maintain cellular identity during obesity due to reduced PPARγ activity and elevated TGFß-SMAD signaling.

OBJECTIVE: Obesity due to overnutrition causes adipose tissue dysfunction, which is a critical pathological step on the road to type 2 diabetes (T2D) and other metabolic disorders. In this study, we conducted an unbiased investigation into the fundamental molecular mechanisms by which adipocytes transition to an unhealthy state during obesity. METHODS: We used nuclear tagging and translating ribosome affinity purification (NuTRAP) reporter mice crossed with Adipoq-Cre mice to determine adipocyte-specific 1) transcriptional profiles (RNA-seq), 2) promoter and enhancer activity (H3K27ac ChIP-seq), 3) and PPARγ cistrome (ChIP-seq) profiles in mice fed chow or a high-fat diet (HFD) for 10 weeks. We also assessed the impact of the PPARγ agonist rosiglitazone (Rosi) on gene expression and cellular state of adipocytes from the HFD-fed mice. We integrated these data to determine the transcription factors underlying adipocyte responses to HFD and conducted functional studies using shRNA-mediated loss-of-function approaches in 3T3-L1 adipocytes. RESULTS: Adipocytes from the HFD-fed mice exhibited reduced expression of adipocyte markers and metabolic genes and enhanced expression of myofibroblast marker genes involved in cytoskeletal organization, accompanied by the formation of actin filament structures within the cell. PPARγ binding was globally reduced in adipocytes after HFD feeding, and Rosi restored the molecular and cellular phenotypes of adipocytes associated with HFD feeding. We identified the TGFß1 effector protein SMAD to be enriched at HFD-induced promoters and enhancers and associated with myofibroblast signature genes. TGFß1 treatment of mature 3T3-L1 adipocytes induced gene expression and cellular changes similar to those seen after HFD in vivo, and knockdown of Smad3 blunted the effects of TGFß1. CONCLUSIONS: Our data demonstrate that adipocytes fail to maintain cellular identity after HFD feeding, acquiring characteristics of a myofibroblast-like cell type through reduced PPARγ activity and elevated TGFß-SMAD signaling. This cellular identity crisis may be a fundamental mechanism that drives functional decline of adipose tissues during obesity.

Corrigendum: miR-451 Loaded Exosomes Are Released by the Renal Cells in Response to Injury and Associated With Reduced Kidney Function in Human.

[This corrects the article DOI: 10.3389/fphys.2020.00234.].

Systemic inhibition of miR-451 increases fibrotic signaling and diminishes autophagic response to exacerbate renal damage in Tallyho/Jng mice.

miRNAs provide fine tuning of gene expression via inhibition of translation. miR-451 has a modulatory role in cell cycling via downregulation of mechanistic target of rapamycin. We aimed to test whether chronic systemic inhibition of miR-451 would enhance renal fibrosis (associated with deranged autophagy). Adult TallyHo/Jng mice (obese insulin resistant) were randomized to two treatment groups to receive either miR-451 inhibition [via a locked nucleic acid construct] or a similar scrambled locked nucleic acid control for 8 wk. All mice were fed a high-fat diet (60% kcal from fat) ad libitum and humanely euthanized after 12 wk. Kidneys and blood were collected for analysis. Renal expression of miR-451 was sixfold lower in inhibitor-treated mice compared with control mice. miR-451 inhibition increased kidney weight and collagen and glycogen deposition. Blood chemistry revealed significantly higher Na+ and anion gap (relative metabolic acidosis) in inhibitor-treated mice. Western blot analysis and immunohistochemistry of the kidney revealed that the inhibitor increased markers of renal injury and fibrosis, e.g., kidney injury molecule 1, neutrophil gelatinase-associated lipocalin, transforming growth factor-ß, 14-3-3 protein-ζ, mechanistic target of rapamycin, AMP-activated protein kinase-α, calcium-binding protein 39, matrix metallopeptidase-9, and the autophagy receptor sequestosome 1. In contrast, the inhibitor reduced the epithelial cell integrity marker collagen type IV and the autophagy markers microtubule-associated protein 1A/1B light chain 3B and beclin-1. Taken together, these results support a protective role for miR-451 in reducing renal fibrosis by enhancing autophagy in obese mice.

miR-451 Loaded Exosomes Are Released by the Renal Cells in Response to Injury and Associated With Reduced Kidney Function in Human.

Micro-RNAs (miRs) encapsulated inside urinary exosomes (uEs) have the potential as early biomarkers. Previously, we reported that a rise in uE miR-451 predicted albuminuria in diabetic rats; however, whether the rise was protective or detrimental, and occurred in response to injury or general hyperglycemia, was unknown. To address this, we studied both human and rat models of renal disease. In humans, uE miR-451 was approximately twofold higher in subjects with early-stage chronic kidney disease (CKD; serum creatinine < 2.0 mg/dl; n = 28), as compared to age-matched healthy controls (n = 23), and had a significant negative correlation with estimated glomerular filtration rate (eGFR) (r 2 = -0.10, p = 0.01). Subgroup analysis of CKD subjects showed that those without diabetes had slightly (∼30%) but significantly higher uE miR-451 as compared to those with diabetes, with no differences in albumin excretion, eGFR, serum sodium, and potassium. Using human proximal tubule (hPT) cells, we found that locked nucleic acid (LNA) inhibition of miR-451 resulted in a significant increase in the messenger RNA (mRNA) expression of kidney-injury-associated miR-451 targets, e.g., CAB39, TBX1, and YWHAZ, as compared to treatment with a control LNA. Moreover, hPT cells and their secreted exosomes showed an increase in miR-451 in response to mechanical injury but not high glucose (20 versus 5 mM). For further proof of concept, in diabetic rats, we showed that atorvastatin (AT), a treatment proven to attenuate renal injury without affecting systemic glucose levels, reduced uE miR-451 with the concomitant restoration of renal miR-451. These data elucidate the stimuli for renal miR-451 expression and exosomal release and support its role as a therapeutic target and early biomarker for renal injury in humans.

Malignant melanoma in a child with giant congenital melanocytic nevus and satellite flekers: A rare entity.

Malignant melanomas in the pediatric age are remarkably rare representing 0.9% of various pediatric malignancies. Congenital nevi occur in 1 in 100 newborns, whereas giant congenital melanocytic nevus (GCMN) measuring more than 20 cm is seen in 1 in 20 000 cases. Very few cases of malignant melanoma arising from GCMN have been described in English literature. The risk of developing malignant melanoma from GCMN is believed to be directly proportional to the size of the nevus and varies from 2.6% to 20% depending on the size of nevus. We present a case of malignant melanoma in a 12-year-old female child who had a congenital giant nevus and multiple satellite flekers all over the body.