- by Gutierrez, A., Taffe, M. A.Adolescent drug exposure has been associated with more severe mental health outcomes related to substance abuse and anxiety disorders. The aim of the present study was to contrast the long-term effects of repeated heroin vapor inhalation during adolescence with similar heroin exposure in adulthood. Groups of female Wistar rats underwent twice daily 30-minute sessions of heroin or propylene glycol (control) vapor inhalation from postnatal days (PND) 36-45 or PND 85-94, respectively. Nociception was assessed after vapor inhalation sessions and forty […]
- by Kubota, K., Katsurabayashi, S., Watanabe, T., Iwasaki, K., Nagamatsu, T., Akaike, N.Increased production of reactive oxygen species (ROS) and oxidative stress are implicated in mitochondrial dysfunction, contributing to the pathogenesis of many neurodegenerative diseases. Research is ongoing into a new treatment approach for neurodegeneration, focusing on reactivating dysfunctional mitochondria. Some 5-deazaflavins, such as 10-ethyl-3-methylpyrimido[4,5-b]quinoline-2,4(3H,10H)-dione (TND1128), and four analogs of 5-deazaflavin, including {beta}-nicotinamide mononucleotide ({beta}-NMN), demonstrate efficient self-redox abilities similar to {beta}-NMN, making them potential activators of mitochondrial energy synthesis. This study examines whether TND1128 and its analogs have protective effects against […]
- by Ito, K., Hosoki, H., Kasai, Y., Sasaki, H., Haraguchi, A., Shibata, S., Nozaki, C.It is widely said that healthy intestinal environment takes essential role for better mental condition. One of the known dietary nutrients which maintains intestinal environment is the dietary fiber. Recent study showed that maintaining intestinal environment by dietary fiber succeeded to alleviate the psychiatric disorder symptoms in animals. However, such effects have only been reported with soluble fiber, which is highly fermentable and promotes short-chain fatty acid (SCFA) production, and not with insoluble fiber. Therefore, we aimed to verify whether […]
- by Distefano Wiltenburg, V., Morales-Lima, G., Sousa Santos, A. V., Echeverry Bermudez, M., Cardoso Cruz, F., de Oliveira Silveira, G., Yonamine, M., Ayako Tiba, P., Rieli Mendes, F.Ayahuasca, a psychoactive brew originally used ritually and therapeutically by various traditional peoples in the Amazon, is receiving special attention for its potential therapeutic effects on addiction. This study investigates the effects of lyophilized ayahuasca in alcohol-induced animal model, examining behavioral, pharmacological, and neurobiological aspects. Phytochemical analysis confirmed the presence of {beta}-carbolines and dimethyltryptamine, with all compound levels within literature ranges. Pharmacological screening revealed dose-dependent behavioral changes, with the highest dose inducing transient effects. Motor coordination deficits were observed at […]
- by Haratipour, Z., Foutch, D., Blind, R.The nuclear receptor Liver Receptor Homolog-1 (LRH-1, NR5A2) is a ligand-regulated transcription factor and validated drug target for several human diseases. LRH-1 activation is regulated by small molecule ligands, which bind to the ligand binding domain (LBD) within the full-length LRH-1. We recently identified 57 compounds that bind LRH-1, and unexpectedly found these compounds regulated either the isolated LBD, or the full-length LRH-1 in cells, with little overlap. Here, we correlated compound binding energy from a single rigid-body scoring function […]
- by Shen, H., Nourmohammadi, S., Zhou, Y., Harata-Lee, Y., Qu, Z., Wang, W., Yool, A. J., Adelson, D. L.Background and PurposeDue to the complexity of traditional Chinese medicine based on complex mixtures of natural products and their multi-target mechanism of action, the discovery and validation of relevant targets have always been challenging. In previous studies, using transcriptomic methods and Compound Kushen Injection (CKI) as a model drug, we identified multiple pathways and target genes through which CKI exerts its pharmacological effects. Therefore, we wished to verify these targets by perturbing those genetic pathways. Experimental ApproachIn this study, we […]
- by Septisetyani, E. P., Harsan, H. S., Kumara, D., Prasetyaningrum, P. W., Paramitasari, K. A., Cahyani, A. D., Anam, K., Kastian, R. F., Santoso, A., Ikawati, M., Meiyanto, E.Orange (Citrus reticulata Blanco) peel contains a flavonoid glycoside hesperidin (HSD) as the primary component. HSD, upon enzymatic hydrolysis, forms hesperetin (HST) aglycone derivate. These two flavonoids have been predicted to have in-silico affinities for ACE2 and SARS-CoV-2 spike, crucial proteins in SARS-CoV-2 infection mechanisms. However, in vitro antiviral testing of orange peel extract, HSD, and HST has not been reported. This study presents for the first time a pseudovirus entry assay approach to test the anti-SARS-CoV-2 effect of HSD, […]
- by Lu, C., Nelson, S., Coy, G., Neumann, C. A., Parkinson, E. I., Rice, C. A.Balamuthia mandrillaris is a pathogenic free-living amoeba that causes infection of central nervous system, called Balamuthia amoebic encephalitis (BAE), as well as cutaneous and systemic diseases. Patients infected with B. mandrillaris have a high mortality rate due to the lack of effective treatments. A combination of non-optimized antimicrobial drug regimen is typically recommended; however, they have poor parasite activity and can cause various severe side effects. Cyclic peptides exhibit a broad spectrum of antimicrobial activities and lower cytotoxicity. In this […]
- by Alahmadi, H., Martinez, S., Farrell, R., Bikienga, R., Arinzeh, N., Potts, C., Li, Z., Warner, G. R.Phthalates are a class of known endocrine disrupting chemicals that are found in common everyday products. Several studies associate phthalate exposure with detrimental effects on ovarian functions, including growth and development of the follicle and production of steroid hormones. We hypothesized that dysregulation of the ovary by phthalates may be mediated by phthalate toxicity towards granulosa cells, a major cell type in ovarian follicles responsible for key steps of hormone production and nourishing the developing oocyte. To test the hypothesis […]
- by Alberich, M., Garcia, M., Petermann, J., Blancfuney, C., Jouffroy, S., Jacquiet, P., Lespine, A.Grazing ruminants suffer from various helminth infections particularly those caused by gastrointestinal nematode (GIN) parasites, which have a considerable impact on their welfare and productivity. Treatment predominantly relies on macrocyclic lactone (ML) anthelmintics, but their widespread application has led to the emergence of drug-resistant parasite populations worldwide. The standard method for detecting resistance, the Faecal Egg Count Reduction Test (FECRT), is susceptible to misinterpretation, leading to flawed management decisions that undermine parasite control efforts. Thus, there is a pressing need […]
- by Kotova, P. D., Dymova, E. A., Rogachevskaja, O. A., Kolesnikov, S. S.The phosphoinositide 3-kinase (PI3K) is involved in regulation of multiple intracellular processes. Although the inhibitory analysis is generally employed for validating a physiological role of PI3K, increasing body of evidence suggests that PI3K inhibitors can exhibit PI3K-unrelated activity as well. Here we studied effects of PI3K inhibitor LY294002 and its inactive analogue LY303511 on Ca2+ and cAMP signals initiated by serotonin. In the present study several monoclonal HEK293 cell lines were used, in particular, monitoring of Ca2+ signals were carried […]
- by Lavigna, G., Grasso, A., Pasini, C., Grande, V., Mignogna, L., Restelli, E., Masone, A., Fracasso, C., Lucchetti, J., Gobbi, M., Chiesa, R.There is no cure for Marinesco-Sjogren syndrome (MSS), a genetic multisystem disease linked to loss-of-function mutations in the SIL1 gene, encoding a BiP co-chaperone. We previously found that the PERK kinase inhibitor GSK2606414 delayed cerebellar Purkinje cell (PC) degeneration and the onset of ataxia in the woozy mouse model of MSS. However, GSK2606414 is toxic to the pancreas and does not completely rescue the woozy phenotype. The present study tested trazodone and dibenzoylmethane (DBM), which partially inhibit PERK signaling with […]
- by Inostroza, P. A., Soriano, Y., Carmona, E., Krauss, M., Brack, W., Backhaus, T., Quinones, R. A.Synthetic organic chemicals, including pesticides, pharmaceuticals, and industrial compounds, pose a growing threat to marine ecosystems as they enter through a variety of pathways, including direct discharges of wastewater (untreated or treated) from industrial, agricultural, and urban sources. Additionally, runoff from residential and agricultural land, as well as inland waterways, transport these chemicals to coastal zones. Despite their potential impact, data on the co-occurrence of these contaminants in the marine environment remains limited. Such information is critical for assessing coastal […]
- by Tapaswi, A., Cemalovic, N., Polemi, K. M., Sexton, J. Z., Colacino, J.There are a substantial number of chemicals to which individuals in the general population are exposed which have putative, but still poorly understood, links to breast cancer. Cell Painting is a high-content imaging-based in vitro assay that allows for rapid and unbiased measurements of the concentration-dependent effects of chemical exposures on cellular morphology. We optimized the Cell Painting assay and measured the effect of exposure to 16 human exposure relevant chemicals, along with 21 small molecules with known mechanisms of […]
- by Chu, Z.-Y., Zi, X.-J.Pancreatic cancer is a highly lethal cancer with limited treatment options. The number of pancreatic cancer patients is increasing rapidly worldwide. Many natural products have been shown to have anticancer activity in a range of studies. Sotetsuflavone is derived from Cycas revoluta Thunb. and exhibits anticancer activity. The present study incorporates network pharmacology, single gene survival analysis, gene expression analysis and molecular docking to reveal the mechanism of Sotetsuflavone in the treatment of pancreatic cancer. Initially, it was evaluated through […]
- by Wiprich, M. T., Vasques, R. d. R., Zaluski, A. B., Bertoncello, K., Altenhofen, S., Gusso, D., Rodrigues, G., Sachett, A., Piato, A., Maito, F. L. D. M., Vianna, M. R. M., Bonan, C. D.Huntingtons disease (HD) is a neurodegenerative disease marked by progressive motor and non-motor symptoms such as neuropsychiatric disruption and cognitive dysfunction. It has been reported that some pathogenic mechanisms resulting in neuronal cell death in this disease involve neurodegeneration and oxidative stress. 3-Nitropropionic acid (3-NPA), a natural toxin that promotes the irreversible suppression of mitochondrial complex II, has been used to understand the HD pathogenesis. This neurotoxin mimics the biochemical, central neurodegeneration, peripheral and behavioral phenotype alterations observed in HD. […]
- by Eya ane Meva, F., Pereira, R., Ngnihamye, S. E., Armel Florian, T. N., Ntoumba, A. A., Hzounda Fokou, j. B., Beglau, T. H. Y., Fetzer, M. N., Kaul, M., Schlierf, B., Mintang Fongang, U. A., Belle Ebanda Kedi, P., Fannang, S. V., Herrmann, M., Janiak, C.Multiple metallic nanoparticles are able to promote cellular and tissue health, but these nanoparticles can be difficult to synthesize and can also cause unintended side-effects. Here, we study the effects on wounds healing and bone reparation of Mg(OH)2 from Anthocleista schweinfurthii Gilg (Loganiaceae) leaves (AS), which are local to the Africa region and have been used in traditional medicine to treat injuries. Mg(OH)2 nanoneedles were synthesized from aqueous extracts of Anthocleista schweinfurthii Gilg (Loganiaceae) leaves (AS) and magnesium nitrate. The […]
- by Ibrahima, N. A., Buabeid, M. A., Arafa, E.-S. A., Ghulam, M.Obesity and fatty liver are relatively benign states but continued inflammatory stress and its metabolic implications turn them into one of the most devastating diseases of humankind. Generally, obesity and fatty liver precede diabetes mellitus, cardiovascular problems and malignant growths. The present research aimed to explore the efficacy of methanolic extract of Moringa Olifera (Me.MO) for the management of obesity and fatty liver and related inflammatory state that prime the body for devastating effects. A series of in-vitro and in-vivo […]
- by Bjorn-Yoshimoto, W. E., Ramiro, I. B. L., Koch, T. L., Engholm, E., Yeung, H. Y., Sorensen, K. K., Goddard, C. M., Jensen, K. L., Smith, N. A. A., Martin, L. F., Smith, B. J., Madsen, K. L., Jensen, K. J., Patwardhan, A., Safavi-Hemami, H.Persistent pain affects one in five people worldwide, often with severely debilitating consequences. Current treatment options, which can be effective for mild or acute pain, are ill-suited for moderate-to-severe persistent pain, resulting in an urgent need for new therapeutics. In recent years, the somatostatin receptor 4 (SSTR4), which is expressed in sensory neurons of the peripheral nervous system, has emerged as a promising target for pain relief. However, the presence of several closely related receptors with similar ligand-binding surfaces complicates […]
- by Huang, R., Xia, H., Lin, W., Wang, Z., Li, L., Deng, J., Ye, T., Li, Z., Yang, Y., Huang, Y.Cancer treatments, including cytotoxic therapy, often result in male infertility, necessitating the development of safe and effective strategies to preserve male reproductive potential during chemotherapy. Notably, our study uncovers the potential of repurposing riluzole, an FDA-approved drug for amyotrophic lateral sclerosis (ALS), in enhancing spermatogenesis. Hence, this research aims to explore the feasibility of utilizing riluzole to alleviate male infertility induced by busulfan (BSF), a commonly used chemotherapy drug. We established a BSF-induced oligospermia model in 4-week-old male mice and […]
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