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The study was performed to understand the detailed mechanism of diabetic wound healing by bilirubin-deferoxamine (DFO) combination on topical application.There were two study groups, control, and treatment. The granulation tissues collected on different days (3, 7, 14, and 19) were studied in detail for inflammatory mediators, angiogenesis markers, epithelialization, and oxidative stress parameters.A significant increase in wound contraction percentage was observed from day 7 in the bilirubin-DFO treatment group. The combinatorial treatment significantly reduced tumour necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), and enhanced IL-10 levels. Upregulated mRNAs of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 alpha (HIF-1 α) along with CD31 immunohistochemistry showed the pro-angiogenesis potential of the combination. Hematoxylin and Eosin (H and E) staining and Masson's trichrome staining showed reduced inflammatory cell infiltration, enhanced fibroblast proliferation, well-organized collagen fibers, and the development of new blood vessels. Collagen deposition is further supported by immunohistochemistry studies and Masson's trichrome staining. Bilirubin-DFO combination also reduced lipid peroxidation and elevated antioxidative enzymes.Topical application of bilirubin-DFO showed immense potential in augmenting skin wound regeneration in diabetes by upregulating the antioxidant status as well as increasing angiogenesis, collagen deposition, and modulating cytokines.

Aflatoxins, particularly Aflatoxin B1 (AFB1), are the most common feed contaminants worldwide, causing significant economic losses to the livestock sector. The current paper describes an outbreak of aflatoxicosis in a herd of 160 male young goat kids (3–4 months), of which 68 young kids succumbed over a period of 25 days after showing neurological signs of abnormal gait, progressive paralysis and head pressing. The haematobiochemical investigation showed reduced haemoglobin, leucocyte count, PCV level, increased levels of AST, ALT, glucose, BUN, creatinine and reduced level of total protein. Grossly, kids had pale mucous membranes, pale and swollen liver; right apical lobe consolidation, and petechiation of the synovial membrane of the hock joints. The microscopic changes were characterized by multifocal hemorrhages, status spongiosus/ vacuolation, vasculitis, focal to diffuse gliosis, satellitosis, and ischemic apoptotic neurons in different parts of the brain and spinal cord. These changes corresponded well with strong immunoreactivity for AFB1 in neurons, glia cells (oligodendrocytes, astrocytes, and ependymal cells) in various anatomical sites of the brain. The higher values of LPO and reduced levels of antioxidant enzymes (Catalase, SOD, GSH) with strong immunoreactivity of 8-OHdG in the brain indicating high level of oxidative stress. Further, the higher immunosignalling of caspase-3 and caspase-9 in the brain points towards the association with intrinsic pathway of apoptosis. The toxicological analysis of feed samples detected high amounts of AFB1 (0.38ppm). These findings suggest that AFB1 in younger goat kids has more of neurotoxic effect mediated through caspase dependent intrinsic pathway, than hepatic toxicity.

Anthropogenic activities like contemporary agricultural methods, and the effects of industrialization on our environment are long-term and harmful. As a result of all of these variables, heavy metal levels in soil, water and air rise. Metals have the potential to be hazardous to plants only when, they are found in bioavailable forms in large quantities. Cadmium, zinc, mercury, lead, chromium, copper, cobalt, nickel, manganese, arsenic and iron are among the elements. Hence, plants have also evolved some of the detoxifying mechanisms to mitigate the harmful effects of heavy metal exposure, its build-up and the studies regarding these have been covered in this overview.

The contemporary trend of unceasing release of rice and wheat varieties from Central and State Varietal Release Committee has defensible to develop suitable techniques for varietal identification at the laboratory level particularly when the seeds have been submitted for seed purity analysis. Maintenance of genetic purity of varieties is of primary importance for preventing varietal deterioration during succeeding regeneration cycles and for guaranteeing varietal performance at an expected level. There is a snowballing need for development of laboratory identification procedures for purposes of plant variety protection, seed certification, quality control and consumer protection. In the past there were fewer commercial varieties and field-testing methods based on morphological differences were used satisfactorily. These tests require several months to complete and are subsequently of limited practical use. With the large number of current varieties, visual differences are much smaller and the task of identification is increasingly difficult. The chemical test discloses differences among the seeds and seedlings of different varieties. These tests require little technical expertise or training and that can be gained in a shorter time. The results of these tests are usually distinct, easily interpreted and help in grouping the genotypes.

Altered lipid metabolism in obesity causes pregnancy complications in humans and animals. Leptin levels increase in pregnancy, as well as obesity. However, the effect of obesity on uterine leptin receptors and its distal signaling is not clear. The present study aimed to understand the effect of increased fat on leptin signaling in rat uterus. Wistar female rats were fed with an HF diet (40% Fat, 17% Sucrose, 1.25% Cholesterol, 0.75% Cholic acid) for 6 weeks before the mating and during pregnancy. HF diet significantly increased the fat depots, liver weight, serum, and tissue cholesterol levels. It produced fatty degeneration in the liver and caused infiltration of inflammatory cells, cystic endometrial glands, and sub endometrial fibrosis of the uterus. In isometric tension experiments, leptin caused a significant increase in uterine contractions in high fat-fed animals compared to control animals. Analysis of receptor expressions revealed no significant difference between the groups. However, a significant decrease in the JAK2 and BKCaα mRNA expression was observed in the uterus of high fat-fed rats. No change in the BKCaβ, eNOS, iNOS, MLCP, and MLCK mRNA expressions was noticed in the HF group compared to the control. The findings of the present study suggest that the contractile response to leptin in the uterus of high fat-fed rats may be attributed to reduced signaling through JAK2 and, lowered expressions of BKCa channel α subunits.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - a novel coronavirus has rapid spread, and caused community infection around the globe. During the absence of a vaccine, people focused more on an immunity-boosting diet and needed clear knowledge about immunity-boosting foods. However, after the vaccination drive, the importance of food as a natural source of immunomodulation cannot be neglected. So, the purpose of this review was to describe the role of vital nutrient in boosting immune system of body apart from other factors like adequate sleep, exercise, and low stress levels. Macrophages, neutrophils, natural killer cells, dendritic cells, B-cells, and T-cells are the important components having important role in maintaining immunity of the human body. The first four-act as the initial mediators of innate host defense, and the latter two produce antibodies for pathogen destruction. The review investigated vital nutrients like vitamin-C, A, E and D, iron, zinc, folic acid, probiotics, and prebiotics affecting these immune components in some extent. Fruits, vegetables, spices, herbs, seeds, nuts, cereals, millets, and superfoods like chlorella and spirulina are good sources of these nutrients. However, fortified foods, functional foods, encapsulated foods with bioactive compounds and plant-based foods have shown immense potential in boosting immunity against viral infections like COVID-19. Some clinical trials and retrospective cohort studies have shown reduction in the severity of COVID-19 patients with relation to plant-based diet, vitamin D and C doses, probiotic, and zinc salts application.

The present study was undertaken to investigate the safety of kaempferol (KEM) and biochanin-A (BCA) following subacute exposure in mice. KEM and BCA were administered in three different doses by oral administration for 28 days. Evaluation of general toxicity parameters by examining the clinical signs, body weight, organ weights, haematological, biochemical, oxidative stress parameters, and histopathology was done. Administration of KEM and BCA for 28 days did not show any clinical signs of toxicity, nor any treatment-related changes in body weight and organ weights in comparison to control. The haematological parameters such as red blood cell, white blood cell, platelets count, haemoglobin (Hb) level, haematocrit, mean corpuscular haemoglobin concentration, red cell distribution width, and platelet distribution width did not show any change in the treated groups and control. Furthermore, different biochemical parameters like markers of the liver (alanine aminotransferase and aspartate aminotransferase), kidney (creatinine and urea), and heart (creatinine kinase-myocardial band and lactate dehydrogenase) injury along with other biochemical parameters showed nonsignificant differences between treated groups and control. Results of oxidative stress parameters in treated groups showed insignificant variations with control. The level of antioxidant enzymes such as superoxide dismutase and catalase were markedly increased in the treated groups; however, these were nonsignificant in comparison to control. In histopathology, evaluation of all vital organs, such as liver, kidney, heart, and lungs, did not show any morphological abnormalities and lesions in treated groups and control. The present study suggests that KEM and BCA have no adverse effects on the general physiology in mice.

Luteolin, a naturally occurring flavonoid, is thought to have health-promoting properties as a part of human diet and has been reported to possess a wide range of pharmacological activities. Therefore, the present study was undertaken to evaluate the effect of luteolin pre-treatment on vascular dysfunctions in sepsis induced by caecal ligation and puncture (CLP) in the mouse model.Mice were divided into four groups: sham, luteolin plus sham, CLP, and luteolin plus CLP. Luteolin was administered (0.2 mg/kg body weight) intraperitoneally one hour (h) before CLP surgery in mice. 20 ± 2 h post CLP surgery, the isolated thoracic aorta of mice was assessed for its vascular reactivity to noradrenaline (NA) and acetylcholine (ACh). To explore the underlying mechanism, aortic mRNA expressions of αIn mice with CLP-induced sepsis luteolin pre-treatment markedly increased the survival time and attenuated serum lactate level. The CLP group manifested the reduced vascular reactivity to NA and this deficit was restored by luteolin pre-treatment. However, luteolin pre-treatment did not improve αThe present study suggests that the vasoplegic state to NA in aorta was restored through the iNOS pathway and endothelial dysfunction was reversed via eNOS and NO production pathway.

Rabies is a zoonotic viral disease with inevitably fatal outcome. Toll-like receptor 3 (TLR3) could sense dsRNA viral infections, and implicated in pathogenesis of rabies and Negri bodies (NBs) formation. Present study was undertaken to elucidate the role of TLR3 in pathogenesis, NBs formation, and therapeutic potential of blocking TLR3/dsRNA interaction in rabies infection. Young Swiss albino mice were infected with 100 LD

Porcine circovirus type 2 (PCV-2) is of great economic significance to porcine industry worldwide. PCV-2 variants and genotypes, alternating world over, are the etiological agent of several clinical syndromes such as porcine dermatitis and nephropathy syndrome (PDNS), post-weaning multi-systemic wasting syndrome (PMWS) and others in pigs. This study is reporting an atypical manifestation of PDNS in twelve grower pigs, 3- to - 4.5 months age and either sex, died of the disease, with predominant lesions of nephropathy and no obvious clinical lesions in skin. Necropsy examination of pigs showed lesions of petechial -to- ecchymotic hemorrhages in the kidneys and in the right auricular musculature of the hearts. Microscopic lesions in HE sections of the kidneys showed acute glomerulonephritis, interstitial nephritis, and vasculitis, but the skin morphology and architecture remained unaltered in contrast to the pathognomonic lesions of PDNS described in the literature. Other syndromic associations of PDNS in these cases included-perimyocarditis, interstitial pneumonia, depleted lymphoid tissues, tonsillitis, enteritis, and meningo-encephalitis. The lesional sites in duplicate paraffin tissue sections of kidneys, heart, lungs, spleen, lymph nodes, intestine, and brain demonstrated PCV-2 antigen in the cytoplasm of cells as highlighted by the intense immunolabeling on IHC staining. The PCV-2 positive organs reconfirmed by PCR, targeting ORF2 gene, which yielded 481bp size of products. The sequencing results of 481bp products on phylogenetic analysis showed 94% similarity with that of PCV-2 sequences in the database that grouped into PCV2d-2 genotype. The present report confirms, probably for the first time, the atypical PDNS cases due to PCV2d-2 genotype in naturally affected grower pigs of India.

Foot-and-mouth disease (FMD) is an extremely contagious and economically devastating viral disease of cloven-hoofed domestic and wildlife animals. The disease is endemic in India and other developing countries of the world. The disease is mainly characterized by the presence of vesicular lesions and "tigroid heart" in calves. The current report describes the novel pathologic findings along with the distribution of FMDV antigens in brain of young calves naturally infected with FMDV. The carcasses of 37 calves suspected to have died from FMD were presented for postmortem investigation. Out of 37 dead calves, 10 calves showed the clinical signs of neurological abnormalities like opisthotonos, muscle twitching and tremor in hind limbs, stiffening of the neck followed by death. Microscopically, the meninges were congested, hemorrhagic, and infiltrated with mononuclear cells. The various sub anatomical sites of the brain showed the varying degrees of vascular changes, perivascular cuffing, focal to diffuse gliosis as well as degeneration and neuronal necrosis, indicating the nonsuppurative encephalitis. The immunolabeling of FMDV antigen was demonstrated in the neurons, inflammatory cells, and microglial cells besides its typical locations. The neurons of the brain also showed strong immunopositivity for caspase-3, caspase-9 and p53 and negative for Bcl-2 and apoptosis-inducing factor (AIF) by both immunohistochemistry and western blotting indicating the role of caspase mediated intrinsic, and p53 dependent apoptotic pathway. Further, the TUNEL assay also confirmed the apoptosis in the neurons and glial cells of the brain of naturally infected calves. This study in calves establishes a basis for resemblance to other members of Picornaviruses, such as Enterovirus 71 and Coxsackievirus of humans and showing the neuropathological alterations along with the distribution of FMDV antigens associated with apoptosis in younger calves.

Acute Myeloid Leukemia (AML), the most common form of leukemia in adults. Despite intensive chemotherapy regimen, approximately 60% of patients subsequently relapse. Inflammatory cells and mesenchymal stem cells (MSC) which are part of bone marrow (BM) microenvironment, play a critical role in cancer progression. Current strategies are focused on understanding cell-cell contact dependent/independent communication within the leukemic stem cell niche. NLRP3 is a part of innate immune mechanisms, resulting in the release of IL-1β and IL-18 immunomodulatory cytokines. Current study was aimed at analyzing NLRP3 pathway regulation at phenotypic and genotypic level in AML BM-MSC compared to healthy BM-MSC and their cross-talk with immune function in AML stem cell niche. MSC were isolated and cultured from AML BM that exhibited heterogenous fibroblastoid shape. Multi-color flow cytometry of AML BM-MSC revealed characteristic high expression of CD90 and minimal expression of CD45. They also expressed immune checkpoint markers TIM3, PDL-1, adenosine receptors A1R/A2BR, vimentin and NLRP3. Cultured AML BM MSC and fresh leukemic blasts demonstrated tunneling nanotubules, increased vesicles and increase in mitochondria which were of irregular shapes and sizes as seen by transmission electron microscopy. Microarray data revealed genes of NLRP3 damage-associated molecular patterns (DAMP) pathway viz. Nlrp3, NME8, Pycard and IL-18 were distinctly upregulated in AML BM-MSC compared to uninvolved BM-MSC. AML peripheral blood (PB) plasma showed immunosuppressive effect on healthy peripheral blood mononuclear cells. NK cell cytotoxicity was found to be significantly reduced in presence of culture supernatant of AML cell line and further reduced with supernatant of cells activated for NLRP3 pathway. Immunofluorescence demonstrated NLRP3 expression in AML BM-MSC and also in vesicles released from MSC. NLRP3 pathway activation was observed in AML cell line which was significantly abrogated upon treatment with NLRP3 inhibitor. NLRP3 pathway is stimulated using basic DAMP agent LPS and secondary activators ATP or Nigericin. Activation was visualized by colocalization of NLRP3 and caspase-1, in the presence/absence of NLRP3 inhibitor. Expression of IL-1β was observed using immunofluorescence and its release in culture supernatants was measured by ELISA. Inhibition of NLRP3 corroborated with decreased secretion of IL-1β in AML cell line. Thus, a positive correlation of IL-1β release was observed with expression of NLRP3. Paraffin sections of AML BM are being evaluated for NLRP3 pathway markers by immunohistochemistry. Understanding remodelling of BM-MSC, leukemia target and immune cell dynamics through NLRP3 pathway regulation in stroma microenvironment may provide crucial leads in therapeutic modulation of the immune response within the stem cell niche. Citation Format: Monalisa Sahoo, Manasi Nagare, Naythan Dcunha, Meena Patkar, Manju Sengar, Navin Khattry, Anant Gokarn, Sachin Punatar, Sridhar Epari, Tanuja Shet, Jyoti Kode. Deciphering role of NLRP3 inflammasome in acute myeloid leukemia microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5608.

Bacterial septicemia causes huge economic losses in the poultry industry and there is no systematic research available in India on the connection of various pathogens associated with septicemia. The present molecular epidemiological study was conducted to investigate the association of different bacterial and immunosuppressive viral pathogens in septicemia suspected chickens. A total of 443 chicken carcasses with septicemic conditions from 71 different flocks were included in this study. Heart blood swabs were subjected to bacterial culture for Salmonella spp., Pasteurella multocida, Escherichia coli, and Gallibacterium anatis. Of these 51 flocks tested for E. coli, 49 (96.1%) flocks were found positive. Among flocks tested for Salmonella spp., 2 flocks were found positive. All tested flocks were found negative for G. anatis and P. multocida as well as air sac swabs tested negative for Mycoplasma spp. Bacterial cultural examination revealed that majority of septicemic chickens were found to be infected with E. coli and these E. coli isolates showed the highest resistance to vancomycin (60%), followed by erythromycin (50%) and cefotaxime (38%) and maximum sensitivity to cefotaxime and clavulanic acid combinations (81.5%), followed by chloramphenicol (69.6%) and ertapenem (67.2%). Among the 5 avian pathogenic E. coli (APEC) virulence genes were detected in 36 flocks and highest frequency of iss (100%), followed by ompT or iutA (97.2%), hly (61.1%) and iroN (47.2%) genes. On polymerase chain reaction (PCR) screening, 10.5, 4.5, 52.2, 19.4, 9.0, 4.5, 20.1 and 19.4% of the flocks were positive for G. anatis, Ornithobacterium rhinotracheale, APEC, Salmonella spp., Mycoplasma gallisepticum, Mycoplasma synoviae, chicken infectious anemia virus and Marek's disease virus, respectively. To our knowledge, the present study is first on the etiology of septicemia in chicken flocks in India. The present study infers that the majority of septicemic deaths in broiler chickens less than 8 weeks have been connected with APEC and majority of E. coli isolates are multidrug resistance, suggesting the need for surveillance and intervention to curb the inadvertent use of antibiotics. Although, incidence of G. anatis association with septicemia was reported, still requires a rigorous epidemiological study to determine the actual prevalence. However, more detailed studies encompassing vast geographical area with large sample size and long duration of the studies are necessary to provide a clear picture of the interaction of different pathogens causing septicemia in chicken.