Nitric oxide: A potential etiological agent for vaso-occlusive crises in sickle cell disease.

Nitric oxide (NO), a vasodilator contributes to the vaso-occlusive crisis associated with the sickle cell disease (SCD). Vascular nitric oxide helps in vasodilation, controlled platelet aggregation, and preventing adhesion of sickled red blood cells to the endothelium. It decreases the expression of pro-inflammatory genes responsible for atherogenesis associated with SCD. Haemolysis and activated endothelium in SCD patients reduce the bioavailability of NO which promotes the severity of sickle cell disease mainly causes vaso-occlusive crises. Additionally, NO depletion can also contribute to the formation of thrombus, which can cause serious complications such as stroke, pulmonary embolism etc. Understanding the multifaceted role of NO provides valuable insights into its therapeutic potential for managing SCD and preventing associated complications. Various clinical trials and studies suggested the importance of artificially induced nitric oxide and its supplements in the reduction of severity. Further research on the mechanisms of NO depletion in SCD is needed to develop more effective treatment strategies and improve the management of this debilitating disease.

A cell line derived from heart of rainbow trout is refractory to Tilapia lake virus.

Cell lines are important in vitro models to answer biological mechanisms with less genetic variations. The present study was attempted to develop a cell line from rainbow trout, where we obtained a cell line from the heart, named "RBT-H." The cell line was authenticated using karyotyping and cytochrome c oxidase subunit I (COI) gene sequencing. The karyotype demonstrated diploid chromosome number (2n) as 62 and the sequence of partial COI gene was 99.84% similar to rainbow trout COI data set, both suggesting the origin of RBT-H from the rainbow trout. The heart cell line was mycoplasma-free and found to be refractory to infection with the Tilapia lake virus. The RBT-H cell line is deposited in the National Repository of Fish Cell Line (NRFC) at ICAR-NBFGR, Lucknow, India, with Accession no. NRFC0075 for maintenance and distribution to researchers on request for R&D.

Interferon inducible guanylate-binding protein 1 modulates the lipopolysaccharide-induced cytokines/chemokines and mitogen-activated protein kinases in macrophages.

Guanylate-binding proteins (GBPs) are a family of interferon (IFN)-inducible GTPases and play a pivotal role in the host immune response to microbial infections. These are upregulated in immune cells after recognizing the lipopolysaccharides (LPS), the major membrane component of Gram-negative bacteria. In the present study, the expression pattern of GBP1-7 was initially mapped in phorbol 12-myristate 13-acetate-differentiated human monocytes THP-1 and mouse macrophages RAW 264.7 cell lines stimulated with LPS. A time-dependent significant expression of GBP1-7 was observed in these cells. Moreover, among the various GBPs, GBP1 has emerged as a central player in regulating innate immunity and inflammation. Therefore, to study the specific role of GBP1 in LPS-induced inflammation, knockdown of the Gbp1 gene was carried out in both cells using small interfering RNA interference. Altered levels of different cytokines (interleukin [IL]-4, IL-10, IL-12ß, IFN-γ, tumor necrosis factor-α), inducible nitric oxide synthase, histocompatibility 2, class II antigen A, protein kinase R, and chemokines (chemokine (C-X-C motif) ligand 9 [CXCL9], CXCL10, and CXCL11) in GBP1 knockdown cells were reported compared to control cells. Interestingly, the extracellular-signal-regulated kinase 1/2 mitogen-activated protein (MAP) kinases and signal transducer and activator of transcription 1 (STAT1) transcription factor levels were considerably induced in knockdown cells compared to the control cells. However, no change in the level of phosphorylated nuclear factor-kB, c-Jun, and p38 transcription factors was observed in GBP1 knockdown cells compared to the control cells. This study concludes that GBP1 may alter the expression of cytokines, chemokines, and effector molecules mediated by MAP kinases and STAT1 transcription factors.

Xylooligosaccharides from lignocellulosic biomass and their applications as nutraceuticals: a review on their production, purification, and characterization.

Xylooligosaccharides (XOS) are considered a potent source of prebiotics for humans. The global prebiotic market is expanding in size, was valued at USD 6.05 billion in 2021, and is expected to grow at a 14.9% compound annual growth rate between 2022 and 2030, indicating a huge demand. These XOS are non-digestible pentose sugar oligomers comprising mainly xylose. Xylose is naturally present in the lignocellulosic biomass (LCB), fruits and vegetables. Apart from the prebiotic effect, these XOS have been reported to reduce blood cholesterol, possess antioxidant effects, increase calcium absorption, reduce colon cancer risk, and benefit diabetic patients. The primary use of XOS is reported in the feed industry followed by health, medical use, food and drinks. LCB mainly contains glucan, xylan and lignin. After glucan, xylan is the second-highest available sugar on the globe composed of xylose. Therefore, the xylan fraction of LCB has great significance in producing food, feed and energy. Glucan has been exploited for the commercial production of ethanol, xylitol, furfural, hydroxymethyl furfural and glucose. As of now, xylan has limited applications. Therefore, xylan can be exploited to convert to XOS. The production of XOS from LCB fraction not only helps to produce these at a very low price, but also helps in the reduction of greenhouse gases. Its use in food and drinks is increasing as it can be derived from the abundantly and cheaply available LCB. The article provides a review on the production, purification and characterization of XOS in view of their use as nutraceuticals. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Exploring the genetic mechanisms: SELP gene's contribution to alleviating vaso-occlusive crisis in sickle cell disease.

Sickle cell disease is a catastrophic inflammatory disorder characterized by microvascular vaso-occlusion, leading to high morbidity and increased mortality. P-selectin, a cell adhesion molecule, plays a crucial role in the pathogenesis and severity of sickle cell disease. Its expression and binding with its ligand PSGL-1 is involved in various mechanisms that contribute to inflammation and immune response, resulting in complications in sickle cell disease. Preclinical data have verified the efficacy of P-Selectin inhibition in mitigating vaso-occlusive events and severity of disease. Currently clinical trials are ongoing to evaluate the safety and efficiency of P-Selectin-targeted therapies and concede the challenges and limitations associated with their use. Despite of its proven role in reducing severity in sickle cell disease, future research should focus on identifying other novel targets within the adhesion cascade and explore combination therapies. Conducting trials and addressing concerns about accessibility are crucial steps towards fully harnessing the potential of P selectin inhibitors as a groundbreaking treatment option. This review focuses on understanding the role of p selectin and its interactions with molecules involved in inflammation providing insights about the molecular etiology, pathophysiology, and potential therapeutic targets in sickle cell disease.

Anion-Relay Double Aza-Michael-Michael Cascades to Enone-Tethered Cyclohexadienones: Access to an Intricate Bridged Ring System.

An anion-relay double aza-Michael-Michael addition strategy has been reported for the synthesis of intricate scaffolds from enone-tethered cyclohexadienones and primary amines. This method discloses the base-catalyzed synthesis of highly valued bridged aza-tricyclic frameworks with a high level of product selectivity and stereoselectivity. Gram scale synthesis and synthetic transformation were shown to afford structurally diverse bridged aza-polycyclic amines. Control experiments and the kinetic profile were studied to determine a plausible reaction mechanism.

Polycyclic Pyrazoles from Alkynyl Cyclohexadienones and Nonstabilized Diazoalkanes via [3 + 2]-Cycloaddition/[1,5]-Sigmatropic Rearrangement/Aza-Michael Reaction Cascade.

An efficient method for the stereoselective synthesis of "all center substituted" polycyclic pyrazoles from alkynyl cyclohexa-2,5-dienones and nonstabilized diazoalkanes via sequential [3 + 2]-cycloaddition/[1,5]-sigmatropic rearrangement and aza-Michael reactions is reported. The developed process is highly regioselective and stereoselective. It employs a wide substrate scope to furnish structurally diverse linear and bridged [4.4.n.0] ring-fused pyrazoles in moderate to good yields. One-pot and gram-scale syntheses and synthetic transformations have also been showcased.

Solvothermally Synthesized Nickel-Doped Marigold-Like SnS2 Microflowers for High-Performance Supercapacitor Electrode Materials.

Two-dimensional transition-metal dichalcogenides (TMDs) have emerged as promising capacitive materials for supercapacitors owing to their layered structure, high specific capacity, and large surface area. Herein, Ni-doped SnS2 microflowers were successfully synthesized via a facile one-step solvothermal approach. The obtained Ni-doped SnS2 microflowers exhibited a high specific capacitances of 459.5 and 77.22 F g-1 at current densities of 2 and 10 A g-1, respectively, in NaClO4 electrolyte, which was found to be higher than that of SnS2-based electrodes in various electrolytes such as KOH, KCl, Na2SO4, NaOH, and NaNO3. Additionally, these microflowers demonstrate a good specific energy density of up to 51.69 Wh kg-1, at a power density of 3204 Wkg-1. Moreover, Ni-doped SnS2 microflowers exhibit a capacity retention of 78.4% even after 5000 cycles. Better electrochemical performance of the prepared electrode may be attributed to some important factors, including the utilization of a highly ionic conductive and less viscous NaClO4 electrolyte, incorporation of Ni as a dopant, and the marigold flower-like morphology of the Ni-doped SnS2. Thus, Ni-doped SnS2 is a promising electrode material in unconventional high-energy storage technologies.

Fish cell line: depositories, web resources and future applications.

Cell lines are important bioresources to study the key biological processes in the areas like virology, pathology, immunology, toxicology, biotechnology, endocrinology and developmental biology. Cell lines developed from fish organs are utilized as a model in vitro system in disease surveillance programs, pharmacology, drug screening and resolving cases of metabolic abnormalities. During last decade, there were consistent efforts made globally to develop new fish cell lines from different organs like brain, eye muscles, fin, gill, heart, kidney, liver, skin, spleen, swim bladder, testes, vertebra etc. This increased use and development of cell lines necessitated the establishment of cell line depositories to store/preserve them and assure their availability to the researchers. These depositories are a source of authenticated and characterized cell lines with set protocols for material transfer agreements, maintenance and shipping as well as logistics enabling cellular research. Hence, it is important to cryopreserve and maintain cell lines in depositories and make them available to the research community. The present article reviews the current status of the fish cell lines available in different depositories across the world, along with the prominent role of cell lines in conservation of life on land or below water. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-023-00601-2.

Renal Adverse Effects of Tenofovir Containing Regimens in HIV-Infected Children and Adolescents in North India.

OBJECTIVE: To study the prevalence of abnormal renal functions among children living with HIV (CLHIV) receiving tenofovir disoproxil fumarate (TDF) containing antiretroviral therapy (ART). METHODS: A prospective, observational study was conducted among CLHIV aged 10 years to 21 years attending the pediatric HIV clinic. We included CLHIV weighing ≥ 30 kg who had been receiving TDF-containing regimens for at least 6 months, with estimated glomerular filtration rate (eGFR) > 60 ml/min/m2 at enrolment and for whom baseline laboratory parameters were available before starting ART. Clinical and laboratory parameters like serum creatinine, serum phosphate, urinary protein and glucose estimation, CD4 count and viral load were noted from records. The mean change in serum creatinine, estimated glomerular filtration rate (eGFR), creatinine clearance, serum phosphate, and presence of urinary glucose and protein by dipstick were assessed at 3- and 12-months follow-up. RESULTS: We enrolled 70 patients with mean (SD) age 14.99 (2.45) years who had been receiving TDF-based ART for a mean (SD) duration of 14.60 (12.80) months. At 3-months and 12-months follow-up, 32.85% and 41.42% patients, respectively, had eGFR below 90 mL/min/1.73m2, while 4.2% and 2.8% patients, respectively, had eGFR between 50-60 mL/min/1.73m2. One patient had creatinine clearance below 50 mL/min/1.73m2. Four patients had hypophosphatemia at the first and last follow-up respectively, and five patients had proteinuria. There was no statistically significant change in CD4 counts, serum potassium, or serum uric acid during study duration. CONCLUSION: TDF-containing ART regimen is associated with decreased eGFR, creatinine clearance and proteinuria.

Antidiabetic Evaluation of Kigelia pinnata Root Bark Extract in Streptozotocin-Induced Type-2 Diabetes Model of Rats.

Diabetes mellitus (DM) is the most common endocrine disorder characterized by increased blood glucose levels resulting from defective insulin secretion, resistance to insulin action, or both. DM is often associated with severe complications, and there is an increasing appreciation that cognitive function declines in DM. The aim of this research work was to evaluate Kigelia pinnata root bark extract in Streptozotocin (STZ)-induced type-2 diabetes. Experimental diabetes was induced by a single administration of STZ (60 mg/kg, intraperitoneal [i.p.]), immediately after the STZ administration, and all animals were fed with normal food and water. Nicotinamide was administered (120 mg/kg, i.p.) 15 min before STZ. The development of hyperglycemia was confirmed by the elevated blood glucose levels determined at fixed intervals, which was confirmed by measuring fasting blood glucose levels in rats' blood taken from the tail vein. Supplementation with ethanolic extract of K. pinnata root bark (EEKP) significantly reduced the elevated blood glucose in STZ-induced hyperglycemia in rats. EEKP significantly restored the biochemical and antioxidant defense system. On the final day of the protocol, the extract also reduced inflammatory cytokines in the blood serum.

Design, synthesis and biological evaluation of novel pyrimidine derivatives as bone anabolic agents promoting osteogenesis via the BMP2/SMAD1 signaling pathway.

Anti-resorptive inhibitors such as bisphosphonates are widely used but they have limited efficacy and serious side effects. Though subcutaneous injection of teriparatide [PTH (1-34)] is an effective anabolic therapy, long-term repeated subcutaneous administration is not recommended. Henceforth, orally bio-available small-molecule-based novel therapeutics are unmet medical needs to improve the treatment. In this study, we designed, synthesized, and carried out a biological evaluation of 31 pyrimidine derivatives as potent bone anabolic agents. A series of in vitro experiments confirmed N-(5-bromo-4-(4-bromophenyl)-6-(2,4,5-trimethoxyphenyl)pyrimidin-2-yl)hexanamide (18a) as the most efficacious anabolic agent at 1 pM. It promoted osteogenesis by upregulating the expression of osteogenic genes (RUNX2 and type 1 col) via activation of the BMP2/SMAD1 signaling pathway. In vitro osteogenic potential was further validated using an in vivo fracture defect model where compound 18a promoted the bone formation rate at 5 mg kg-1. We also established the structure-activity relationship and pharmacokinetic studies of 18a.