- by Rosa, A., Raneri, A., Campolo, M., Esposito, E., Gecchele, E., Butler, J., Ma, J., Sofat, N., Figueira, S., Pivotto, D., Ms Cormick, A., Bartoloni, E., Zampieri, R., AVESANI, L.Nanoparticle-based strategies offer a promising tool for inducing antigen-specific immune tolerance across various autoimmune conditions, by acting as master switch to turn-off the autoimmune response. Building on our previous work demonstrating the therapeutic potential of plant-made nanoparticles in rheumatoid arthritis, we present a systematic evaluation of key parameters, including dosing regimen, route of administration, and immunization schedule, to optimize both efficacy and safety. We developed virus-based nanomaterials expressing Tomato Bushy Stunt Virus (TBSV) nanoparticles engineered to display the immunodominant Liprin-1 […]
- by Lu, M., Chen, D., Liang, X., Feng, L., Liu, X., Hu, X., Hong, W.Atopic dermatitis is a common inflammatory skin disorder characterised by recurrent eczematous lesions and intense itch. Quercetin is a naturally occurring flavonoid, exhibits antioxidant and anti-inflammatory properties. Previous studies have indicated its beneficial role in managing atopic dermatitis (AD); however, the precise underlying mechanism remains unclear. This study aimed to investigate the protective effects of quercetin against AD and to elucidate its potential mechanisms. We demonstrated that quercetin effectively suppressed the overexpression of pro-inflammatory effector factors–including interleukin (IL)-1{beta}, thymic stromal […]
- by Lal, R., Tikoo, O., Soni, N., Bhattacharya, A., Kondepudi, K. K., Chopra, K., Bishnoi, M.Background: Aging impairs thermogenic and metabolic flexibility, increasing metabolic disease risk. We examined six aging male mouse strains for responses to chronic topical menthol, a pharmacological cold mimetic. Material and methods: Male (C57BL/6J, A/J, BALB/c, C3H/hej, DBA/2J, and FVB/NJ) mice were treated with 4g/kg of 10% menthol weight per volume cream once per day or vehicle as control using finger application for 15 days. After last application, core body temperature measurement, BAT thermography, Nesting behaviour, and metabolic tolerance test were […]
- by Lal, R., Soni, N., Agarwal, K., Kondepudi, K. K., Khare, P., Zimmermann, K., Lewinska, M. K., Gesing, A., Aggarwal, V., Chopra, K., Bishnoi, M.Menthol, a TRPM8 agonist and pharmacological cold mimic, activates brown adipose tissue (BAT) to increase adaptive thermogenesis and whole-body energy expenditure. BAT is highly innervated with sensory and sympathetic nerve fibers. There is existing literature that sympathetic nerves have a critical role in regulating menthols (or cold) effect on energy homeostasis, but there is minimal literature about the involvement of somatosensory innervations. Here, we ought to investigate whether short-term topical application (3 days) of menthol elicits sympathetic and sensory nerves. […]
- Improved efficacy and tolerability of antisense oligonucleotide with Guanidine- bridged nucleic acidby Tomita, H., Kawanobe, T., Shrestha, A. R.Guanidine- bridged nucleic acid (GuNA) is a bridged nucleic acid analog with high binding affinity towards complementary strands along with high nuclease resistance. GuNA has been developed to improve pharmacokinetics and safety profiles of phosphorothioate modified gapmers. Here, we evaluated antisense oligonucleotides (ASOs) modified with combination of GuNA and 2-O-methoxyethyl (MOE) could significantly improve KD activity in vitro and in vivo. Long-term efficacy evaluation showed that intracerebroventricularly administered GuNA modified gapmers stayed active for over 24 weeks in mouse brain. […]
- by Calvo-Barreiro, L., Boutitah-Benyaich, I., Eixarch, H., Espejo, C., Gabr, M.BackgroundNeuroinflammation driven by dysregulated adaptive and innate immune responses plays a central role in the pathogenesis of multiple sclerosis and related autoimmune disorders of the central nervous system. While bile acids are increasingly recognized as endogenous immunomodulators, their therapeutic exploitation has been limited by modest potency and incomplete mechanistic understanding. Here, we report the rational engineering of a bile acid-derived scaffold that yields a potent small molecule immunomodulator with therapeutic efficacy in experimental autoimmune encephalomyelitis, a preclinical model of multiple […]
- by Peng, G., Ni, L., Guo, Z., Huang, L., Ma, W., Zheng, F., Zhang, Y., Gao, F., Wang, Z., Cai, W.Doxorubicin (DOX) treatment increases the risk of myocardial dysfunction and heart failure, in which oxidative stress plays a central role. Empagliflozin (EMPA) has been shown to benefit heart failure patients, yet its underlying mechanism remains unclear. In this study, we showed that EMPA treatment improved cardiac function, ameliorated structural remodeling, and increased survival in DOX-treated mice. Furthermore, EMPA reduced DOX-induced reactive oxygen species (ROS) overproduction and myocardial injury. Through functional analysis overlapping DIC- and EMPA-regulated genes, we identified the involvement […]
- by Tokmakjian, L., Han, D., Sihuta, K., Aggarwal, A., Pirhadi, S., Wang, Y., Burns, A. R., Cooke, B., Ren, S., Cummins, C., Nodwell, J. R., Koes, D. R., Roy, P.Cationic Amphiphilic Drugs (CADs) severely disrupt lysosomal function, which leads to a cellular pathology characterized by excess phospholipids called phospholipidosis. Through a forward genetic screen and mining of published datasets, we discovered that CADs induce the expression of the CYP-35B family of cytochrome P450s and the PGP-13 p-glycoprotein pump via the nuclear receptors NHR-70 and NHR-107 in the nematode C. elegans. A pgp-13 fluorescent reporter revealed hundreds of human drugs that upregulate the CAD defense system in vivo. Chemoinformatic analyses […]
- by Jesudason, C. D., Rangel-Barajas, C., Beach, C. J., Beck, D. E., Caballero-Floran, I. H., Clayton, W. B., Da Silva, L., David, J. C., Doolen, S., Faulkner, A. N., Hamdani, A. K., Huhe, H., Huynh, K., Imhoff, R. D., Javens-Wolfe, J., Mason, E. R., Moussaif, M., Singhal, K., Soni, D. M., Van Buuren-Milne, M., Williams, S.-P., Angus, S. P., Chu, S., Dage, J. L., Hipskind, P. A., Johnson, T. S., Kadurah-Dauok, R. F., Lamb, B. T., Meikle, P. J., Mesecar, A. D., Palkowitz, A. D., Quinney, S. K., Sukoff Rizzo, S. J., Oblak, A. L., Richardson, T. I.Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1), encoded by the gene INPP5D, is a lipid phosphatase that negatively regulates immune receptor signaling in hematopoietic cells and microglia. Here, we describe a pyridyl-pyrazole-piperidine scaffold and the lead compound 3-((2-chlorobenzyl)oxy)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridine (32), which demonstrates SHIP1 target engagement, brain exposure, and evidence of a central pharmacodynamic response in vivo. Structure-activity relationship studies, guided by biochemical and cellular assays using multiple human and murine protein constructs and cells, identified SHIP1-active ligands. A thermal shift […]
- Hair promotion effect of Beta vulgaris L. fruit extracts; physicochemical, and analytical evaluationby Hasan, F., Khan, S., Tariq, A., Islam, M.Natural products are used frequently for medicinal purposes due to their lower toxicity effect and greater safety than synthetic products. Alopecia is becoming common due to inheritance, hormonal change and environmental factors. The current study evaluates the physicochemical, analytical and hair growth promotion activity of extracts of Beta vulgaris L. Extraction was done by using hexane, chloroform, methanol, ethanol and water in increasing order of their polarity. For the hair growth activity, five groups (positive, negative, untreated, test-group 1 and […]
- by Hansen, B. C., Hatem, S. A., Huang, L., Amory, J. K., Faustman, E. M., Kelly, E. J.Spermatogonial differentiation is controlled by distinct spatial and temporal activities of metabolizing enzymes and signaling molecule formation. In vitro models are reductionist ways to examine the interactions between Sertoli cells and spermatogonial stem cells, which may be therapeutic targets for infertility that cause non-obstructive azoospermia, due to either Sertoli-cell only syndrome, hypospermatogenesis or maturation arrest. Here, we find that nanomolar doses of isotretinoin are sufficient to drive Stra8 expression in vitro, an interaction that is both dose-dependent and inhibitable. We […]
- by Wijerathne, S. K., Oshadi, E. A., Gunawardana, S. D. V., Kothalawala, A., Dissanayake, T. L., Ranaweera, G., Murugananthan, A., Galhena, P., Senathilake, K., Samarakoon, S. R.Vernolac is a commercially available polyherbal formulation comprising Vernonia zeylanica aerial parts, Nigella sativa seeds, Hemidesmus indica roots, Smilax glabra rhizome, and Leucas zeylanica aerial parts. Although previous in vitro studies have demonstrated anticancer potential of Vernolac and its active ingredients, safety data are available only for some of the plant ingredients of Vernolac. In the present study, acute and 28-day repeat-dose toxicity of Vernolac were evaluated in Wistar rats following OECD guidelines 420 and 407, respectively. Acute toxic effect […]
- by Jiang, F., Ma, Y., Zhang, Y., Shang, D., Dong, W.Tryptophan (Trp)-substitution antimicrobial peptides (AMPs) exhibit enhanced interactions with bacterial cell membranes, potentially improving their antimicrobial efficacy. K. pneumoniae (20.59% of 2054 ICU isolates) is resistant to multiple clinically used antibiotics and presents significant treatment challenges. In the present study, three Trp-modified peptides (I4W, L12W, and I1WL5W) were generated by substituting Ile or Leu residues in temporin-1CEb, a peptide derived from frog skin, with Trp at various sites to assess their antibacterial effects and mechanisms against K. pneumoniae. Compared with […]
- by Chacin Ruiz, E. A., Swindle-Reilly, K. E., Ford Versypt, A. N.Chronic diseases often require repeated oral or local administration, which can compromise patient compliance. In wet age-related macular degeneration (AMD), current therapies rely on intravitreal injections of anti-vascular endothelial growth factor agents every four to six weeks to maintain therapeutic drug levels. Controlled-release drug delivery systems offer a promising alternative by reducing injection frequency and extending drug release. In this study, we developed a continuum diffusion model to describe drug transport through porous polymeric microcapsules, implemented using the finite element […]
- by Pu, Y., Guang, A., Qi, X., Bahudodda, S., Stermer, A. R., Spade, D. J.Ethylene glycol monomethyl ether (EGME) is a testicular germ cell toxicant that selectively targets spermatocytes. In rats, male-only EGME exposure reduces mating success and can lead to an increase in resorbed fetuses. In a previous study, five-day exposure to 50, 60, or 75 mg/kg/d EGME in male rats led to a decrease in sperm motility and increase in retained spermatid heads with a LOAEL of 75 mg/kg/d. At 60 mg/kg/d, EGME exposure altered the proportion of sperm small RNA reads […]
- by He, R., Ding, W., Cao, J., Guo, C., Li, X., Xiao, G.PurposeTo evaluate L-Ergothioneine (EGT), a naturally occurring amino acid and endogenous antioxidant, as a novel therapeutic agent for oxidative stress-related ocular diseases. This evaluation specifically aimed to address the challenge of targeted ocular delivery by assessing EGT s antioxidant potency, stability, ocular tolerance, and crucially, its ability to reach the posterior segment (fundus) via topical administration. MethodsThis study evaluated EGT as a novel ocular antioxidant by examining its radical scavenging capacity (DPPH assay compared to glutathione, astaxanthin, and coenzyme Q10), […]
- by Bonilla, A. M., Garrido, G., Consolini, A. E., Ragone, M. I.Gomphrena perennis L. possesses a rich phenolic profile and has demonstrated cardiovascular and anti-inflammatory activities; however, its neuropharmacological properties re-main unexplored. The behavioral effects, underlying mechanisms, and acute toxicity of Gomphrena perennis tincture (GphT) were investigated in mice. GphT showed no signs of acute toxicity. Furthermore, it did not alter the number of cross lines in the open field test (OFT), but it induced anxiogenic responses in the elevated plus-maze test (EPM) and the novelty-suppressed feeding test (NSFT), which were […]
- by Bueno, C. S., Vieira, G. B., Sciani, J. M., Rocha e Silva, T. A. A.BackgroundChronic myeloid leukemia and acute lymphoblastic leukemia are significant malignancies requiring novel therapeutic agents. This study aimed to identify cytotoxic components of the venom of the spider Enoploctenus cyclothorax against K562 and NALM-6 cell lines. MethodsVenom was extracted, lyophilizated and incubated with cultured K562 and NALM-6 cells at concentrations ranging from 0.1 to 100 {micro}g/mL for 24 and 48 hours. MTT assay for cell viability was assessed to measure cytotoxicity. Venom fractionation started with centrifugation on AMICON(R) filters in a […]
- by Daniyal, M., Rajaiah, R., Golla, U., Pandiyan Shanmugam, M., Duke, K., Mercer, K., Uzun, Y., Valensi, H., Hengst, J., Dovat, S., Qiu, Y., Huang, S., Behura, C. G.Acute myeloid leukemia (AML), the most common hematologic malignancy, generally has a poor prognosis. Despite initial favorable responses to the BCL2 inhibitor venetoclax (VEN), remission is transient, and AML is eventually fatal. Resistance to VEN is primarily due to the overexpression of anti-apoptotic proteins, including MCL-1, BCL2L1 (BCL-XL), and BCL2A1. Casein kinase II (CK2) is a serine-threonine kinase and a known suppressor of apoptosis. We and others have reported that protein kinase CK2 activity is high in leukemic stem cells […]
- by Mach, J., Winardi, K., Hilmer, S. N.Management of older people with frailty commonly includes polypharmacy and deprescribing. The impacts of frailty on the outcomes of medication use and deprescribing are poorly understood; as are the effects of medication use and deprescribing on frailty and function. Here, using aged C57BL/6J (B6) male mice, we explore the effects of different chronic drug regimens (polypharmacy and monotherapy) and deprescribing on daily activities using an automated behavioral recognition cage, and explore the relationship with frailty and trajectories. At 12 months, […]
Mass spectrometry websites, social media, journal feeds, and other links and items of interest to the mass spectrometry community.
