Recent and advanced animal models used in the Screening of analgesics and anti-inflammatory activity

Non-Steroidal anti-inflammatory drugs (NSAIDs) are consisting of three major anti-pyretic, anti-inflammatory and anti-analgesics properties. They have reduced the sensation of pain, body temperature, and inflammation. It is also used for the treatment of the long-term health problems like arthritis (rheumatoid arthritis, osteoarthritis, and lupus). NSAIDs highly protect the lining of the stomach and intestines from the damaging effects of acid promote blood clotting by activating blood platelets, and promote normal function of the kidney. Incompatible with the action of NSAIDs many different types of drugs and plant use for the treatment of the analgesic, inflammation and pyretic activity. Diclofenac inhibit the cyclooxygenase (COX-2) enzyme with the greater potency that it (COX-1). NSAIDs are generally used in the management of pain because of the integrated role of the COX pathway that is recognition of pyretic, inflammation and analgesic. Introduction to painful procedures and/or stressors during the early neonatal period can reprogram the underlying neurocircuitry involved in nociception and neuropathic pain perception. The reprogramming of these systems can result in an enduring elevation in sympathy towards mechanical and thermal stimuli. During adolescence, hind paw mechanical removal thresholds were evaluated using an electronic von Frey Anesthesiometer. Animals challenged neonatally with LPS (nLPS) had increased pain sensitivity on this measure which was related with decreased Oprm1 expression in the prefrontal cortex (PFC) and periaqueductal gray (PAG) of both male and female rats. There was no effect of inflammatory treatment on either anxiety or depressive-like behavior suggesting that affective functioning did not account for differences in mechanical pain sensitivity

Detection and Classification of Glioblastoma Brain Tumor

Glioblastoma brain tumors are highly malignant and often require early detection and accurate segmentation for effective treatment. We are proposing two deep learning models in this paper, namely UNet and Deeplabv3, for the detection and segmentation of glioblastoma brain tumors using preprocessed brain MRI images. The performance evaluation is done for these models in terms of accuracy and computational efficiency. Our experimental results demonstrate that both UNet and Deeplabv3 models achieve accurate detection and segmentation of glioblastoma brain tumors. However, Deeplabv3 outperforms UNet in terms of accuracy, albeit at the cost of requiring more computational resources. Our proposed models offer a promising approach for the early detection and segmentation of glioblastoma brain tumors, which can aid in effective treatment strategies. Further research can focus on optimizing the computational efficiency of the Deeplabv3 model while maintaining its high accuracy for real-world clinical applications. Overall, our approach works and contributes to the field of medical image analysis and deep learning-based approaches for brain tumor detection and segmentation. Our suggested models can have a major influence on the prognosis and treatment of people with glioblastoma, a fatal form of brain cancer. It is necessary to conduct more research to examine the practical use of these models in real-life healthcare settings.Comment: 12 pages, 8 figure

Splenic accumulation of IL-10 mRNA in T cells distinct from CD4+CD25+ (Foxp3) regulatory T cells in human visceral leishmaniasis

Visceral leishmaniasis (VL) is a life-threatening disease characterized by uncontrolled parasitization of the spleen, liver, and bone marrow. Interleukin (IL)-10 has been implicated in the suppression of host immunity in human VL based on the elevated levels of IL-10 observed in plasma and lesional tissue, and its role in preventing clearance of Leishmania donovani in murine models of VL. The aim of this study was to identify the cellular source of IL-10 in human VL and determine if CD4+CD25+ (Foxp3high) regulatory T (T reg) cells are associated with active disease. We analyzed surface marker and gene expression in peripheral blood mononuclear cells and splenic aspirates from Indian VL patients before and 3–4 wk after treatment with Amphotericin B. The results did not point to an important role for natural CD4+CD25+ (Foxp3high) T reg cells in human VL. They did not accumulate in and were not a major source of IL-10 in the spleen, and their removal did not rescue antigen-specific interferon γ responses. In contrast, splenic T cells depleted of CD25+ cells expressed the highest levels of IL-10 mRNA and were the predominant lymphocyte population in the VL spleen. The elevated levels of IL-10 in VL plasma significantly enhanced the growth of L. donovani amastigotes in human macrophages. The data implicate IL-10–producing CD25−Foxp3− T cells in the pathogenesis of human VL

Caerulomycin A inhibits Th2 cell activity: a possible role in the management of asthma

We have recently demonstrated that Caerulomycin A induces regulatory T cells differentiation by suppressing Th1 cells activity. The role of regulatory T cells is well established in suppressing the function of Th2 cells. Th2 cells are known to inflict the induction of the activation of asthma. Consequently, in the present study, we monitored the influence of Caerulomycin A in inhibiting the activity of Th2 cells and its impact in recuperating asthma symptoms. Interestingly, we observed that Caerulomycin A significantly suppressed the differentiation of Th2 cells, as evidenced by downregulation in the GATA-3 expression. Further, decline in the levels of IL-4, IL-5 and IL-13 cytokines and IgE was noted in the animals suffering from asthma. Furthermore, we noticed substantial suppression in the inflammatory response and number of eosinophils in the lungs. In essence, this study signifies an important therapeutic role of Caerulomycin A in asthma

Analyses of intra-annual density fluctuation signals in Himalayan cedar trees from Himachal Pradesh, western Himalaya, India, and its relationship with apple production

Intra-annual density fluctuation (IADF) refers to anatomical changes in the tree ring caused by a sudden change in wood density triggered by a combination of climate variations and various biotic and abiotic influences. To reveal the occurrence of IADFs, we analyze the growth rings of Himalayan cedar (Cedrus deodara) growing over the Kullu region, Himachal Pradesh, western Himalaya. Using 30 increment cores, we precisely dated and developed a 214-year-long tree-ring chronology extending back to AD 1808. The tree–growth–climate relationship using ring-width chronology and observed climate data revealed that cool and moist condition provides favorable condition for Himalayan cedar tree growth. Delving deeper into wood anatomy of growth rings, we revealed the frequent occurrences of IADFs in both earlywood (IADFe) and latewood (IADFl). The formation of IADFs in earlywood (IADFe) is related to the reduced precipitation from April to July, causing moisture stress in the soil and surrounding climate. However, wetter conditions in the late growing season, mainly August–October, activated the formation of IADFs in latewood (IADFl). The study revealed several IADF years in earlywood and latewood, such as 1901, 1902, 1903, 1914, 1915, 1919, 1920, 1923, 1925, 1943, 1958, 1959 and 1937, 1955, 1956, 1988, respectively. These IADF years corresponded with unusual climatic fluctuations that severely affected apple production, the major cash crop in the region. The analyses demonstrated that the IADF chronology of Himalayan cedar would be a valuable proxy to understand abrupt and unusual climatic fluctuations from a long-term perspective for the data-scarce western Himalayan region

DENDRIMERS IN DRUG DELIVERY, DIAGNOSIS AND THERAPY: BASICS AND POTENTIAL APPLICATIONS

This review gives concise information about the dendrimers, properties, synthesis and application in drug delivery, diagnosis and therapy. Due to their unique architecture these have improved physical and chemical properties. They show high solubility, miscibility and reactivity due to their terminal groups. Dendrimers have well defined size, shape, molecular weight and monodispersity. These properties make the dendrimers a suitable carrier in drug delivery application. Dendrimers are unimolecular miceller in nature and due to this enhances the solubility of poorly soluble drugs. Their compatibility with DNA, heparin and polyanions make them more versatile. Dendrimers, also referred as modern day polymers, they offer much more good properties than the conventional polymers. Due to their multivalent and mono disperse character dendrimers have stimulated wide interest in the field of chemistry biology, especially in applications like drug delivery, gene therapy and chemotherapy. Self assembly produces a faster means of generating nanoscopic functional and structural systems. But their actual utility in drug delivery can be assessed only after deep understanding of factors affecting their properties and their behavior in vivo. Key words: Dendrimers, PAMAM, monodispersity, Divergent-Convergent synthesis, carrier for drug deliveryÂ

POTENTIAL APPLICATION OF DENDRIMERS IN DRUG DELIVERY: A CONCISE REVIEW AND UPDATE

This review gives concise information about the application of dendrimers in the field of drug delivery. Due to their unique architecture these have improved physical and chemical properties. Due to their terminal groups these show high solubility, miscibility and reactivity. Dendrimers have well defined size, shape, molecular weight and monodispersity. These properties make the dendrimers a suitable carrier in drug delivery application. Dendrimers are unimolecular miceller in nature and due to this enhances the solubility of poorly soluble drugs. Their compatibility with DNA, heparin and polyanions make them more versatile. Dendrimers, also referred as modern day polymers, they offer much more good properties than the conventional polymers. Due to their multivalent and mono disperse character dendrimers have stimulated wide interest in the field of chemistry biology, especially in applications like drug delivery, gene therapy and chemotherapy. Self assembly produces a faster means of generating nanoscopic functional and structural systems. But their actual utility in drug delivery can be assessed only after deep understanding of factors affecting their properties and their behavior in vivo. Key words: Dendrimers, Drug targeting, nanoscale carriers

Enhancement of thermoelectric figure of merit in Bi2Se3 crystals through a necking process

The growth of good quality bulk single crystals of bismuth selenide by employing a high-temperature vertical Bridgman technique with a specially designed ampoule having a provision for a necking process is reported. Several growth experiments were performed and reproducible results were obtained. The crystal structure and lattice dimensions were confirmed by powder X-ray diffraction (PXRD), the bulk crystalline perfection was assessed using high-resolution X-ray diffractometry and the good bulk crystalline perfection with an indication of layered structure was confirmed. Transmission electron microscopy (TEM) was carried out for the grown single crystal and confirmed the layered structure. High-resolution TEM (HRTEM) was also used to further assess the crystalline perfection. The direct measurement of d spacing obtained from HRTEM imaging was found to be in good agreement with the data obtained from PXRD. The thermal behavior was examined by differential scanning calorimetry and a sharp melting was found at 983K, which revealed the purity of the bismuth selenide. The Seebeck coefficient and electrical and thermal conductivities were measured, and a thermoelectric figure of merit was calculated in order to assess the suitability of the crystal for thermoelectric applications such as refrigeration and portable power generation. Nanoindentation analysis was also performed for the first time

Increasing complexity and interactions of oxidative stress in chronic respiratory diseases: An emerging need for novel drug delivery systems

© 2018 Elsevier B.V. Oxidative stress is intensely involved in enhancing the severity of various chronic respiratory diseases (CRDs) including asthma, chronic obstructive pulmonary disease (COPD), infections and lung cancer. Even though there are various existing anti-inflammatory therapies, which are not enough to control the inflammation caused due to various contributing factors such as anti-inflammatory genes and antioxidant enzymes. This leads to an urgent need of novel drug delivery systems to combat the oxidative stress. This review gives a brief insight into the biological factors involved in causing oxidative stress, one of the emerging hallmark feature in CRDs and particularly, highlighting recent trends in various novel drug delivery carriers including microparticles, microemulsions, microspheres, nanoparticles, liposomes, dendrimers, solid lipid nanocarriers etc which can help in combating the oxidative stress in CRDs and ultimately reducing the disease burden and improving the quality of life with CRDs patients. These carriers improve the pharmacokinetics and bioavailability to the target site. However, there is an urgent need for translational studies to validate the drug delivery carriers for clinical administration in the pulmonary clinic

Metabolomics-Driven Mining of Metabolite Resources:Applications and Prospects for Improving Vegetable Crops

Vegetable crops possess a prominent nutri-metabolite pool that not only contributes to the crop performance in the fields, but also offers nutritional security for humans. In the pursuit of identifying, quantifying and functionally characterizing the cellular metabolome pool, biomolecule separation technologies, data acquisition platforms, chemical libraries, bioinformatics tools, databases and visualization techniques have come to play significant role. High-throughput metabolomics unravels structurally diverse nutrition-rich metabolites and their entangled interactions in vegetable plants. It has helped to link identified phytometabolites with unique phenotypic traits, nutri-functional characters, defense mechanisms and crop productivity. In this study, we explore mining diverse metabolites, localizing cellular metabolic pathways, classifying functional biomolecules and establishing linkages between metabolic fluxes and genomic regulations, using comprehensive metabolomics deciphers of the plant’s performance in the environment. We discuss exemplary reports covering the implications of metabolomics, addressing metabolic changes in vegetable plants during crop domestication, stage-dependent growth, fruit development, nutri-metabolic capabilities, climatic impacts, plant-microbe-pest interactions and anthropogenic activities. Efforts leading to identify biomarker metabolites, candidate proteins and the genes responsible for plant health, defense mechanisms and nutri-rich crop produce are documented. With the insights on metabolite-QTL (mQTL) driven genetic architecture, molecular breeding in vegetable crops can be revolutionized for developing better nutritional capabilities, improved tolerance against diseases/pests and enhanced climate resilience in plants