Notes

Effective adsorptive removal of atrazine herbicide within lake marine environments with a book hydrochar based on Prunus serrulata bark.
Moreover, circumdatin D interfered with inflammatory response by inhibiting the secretion of pro-inflammatory cytokines in LPS-induced BV-2 and primary microglia cells. Mechanistically, circumdatin D modulated Toll-like receptor 4 (TLR4)-mediated NF-κB, MAPKs and JAK/STAT inflammatory pathways in LPS-stimulated BV-2 cells, and protected primary neurons cells from LPS-induced neurotoxicity. Thus, circumdatin D is a potential agent for neuroprotective effects by the multi-target strategy.Since incurable castration-resistant prostate cancer (CRPC) inevitably develops following treatment with androgen deprivation therapy, there is an urgent need to devise new therapeutic strategies to treat this cancer. Pyrimethamine, an FDA-approved antimalarial drug, is known to exert an antitumor activity in various types of human cancer cells. However, whether pyrimethamine can inhibit prostate cancer is not well established. Hence, the present study aimed to characterize the mechanism of action of pyrimethamine on prostate cancer. We investigated the potential effect of pyrimethamine on cell proliferation, cell cycle, and apoptosis in metastatic DU145 and PC3 prostate cancer cells. We found that pyrimethamine inhibited cell proliferation, induced cell cycle arrest in the S phase, and promoted cell apoptosis of prostate cells in vitro; it also suppressed tumor growth in xenograft models. selleck inhibitor In addition, we observed that pyrimethamine suppressed prostate cancer growth by inhibiting the p38-NF-κB axis in vitro and in vivo. Thus, this study demonstrates that pyrimethamine is a novel p38 inhibitor that can exert antiproliferative and proapoptotic effects in prostate cancer by affecting cell cycle and intrinsic apoptotic signaling, thereby providing a novel strategy for using pyrimethamine in CRPC treatment.Leishmania is a parasitic protozoon responsible for the neglected tropical disease Leishmaniasis. Approximately, 350 million people are susceptible and close to 70,000 death cases globally are reported annually. The lack of effective leishmanicides, the emergence of drug resistance and toxicity concerns necessitate the pursuit for effective antileishmanial drugs. Natural compounds serve as reservoirs for discovering new drugs due to their chemical diversity. Hardwickiic acid (HA) isolated from the stembark of Croton sylvaticus was evaluated for its leishmanicidal potential against Leishmania donovani and L. major promastigotes. The susceptibility of the promastigotes to HA was determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide/phenazine methosulfate colorimetric assay with Amphotericin B serving as positive control. HA showed a significant antileishmanial activity on L. donovani promastigotes with an IC50 value of 31.57± 0.06 µM with respect to the control drug, amphotericin B wting the experimental activity. Therefore, HA is a promising antileishmanial molecule worthy of further development as a biotherapeutic agent.As chemical analysis for quality control (QC) of traditional Chinese medicine (TCM) formula is difficult to guarantee the effectiveness, a bioassay method that combines QC with evaluation of therapeutic effects has been developed to assess the TCM quality. Here, we chose a thirteen-component TCM formula, Lianhua Qingwen capsule (LHQW), as a representative sample, to explore the pivotal biomarkers for a bioassay and to investigate close association between QC and pharmacological actions. Initially, our results showed that chemical fingerprinting could not effectively distinguish batches of LHQW. Pharmacological experiments indicated that LHQW could treat influenza A virus (H1N1) infection in the H1N1 mouse model, as claimed in clinical trials, by improving pathologic alterations and bodyweight loss, and decreasing virus replication, lung lesions and inflammation. Furthermore, by using serum metabolomics analysis, we identified two important metabolites, prostaglandin F2α and arachidonic acid, and their metabolic pathway, arachidonic acid metabolism, as vital indicators of LHQW in treatment of influenza. Subsequently, macrophages transcriptomics highlighted the prominent role of cyclooxygenase-2 (COX-2) as the major rate-limiting enzyme in the arachidonic acid metabolism pathway. Finally, COX-2 was validated by in vivo gene expression and in vitro enzymatic activity with 43 batches of LHQW as a viable pharmacological biomarker for the establishment of bioassay-based QC. Our study provides systematic methodology in the pharmacological biomarker exploration for establishing the bioassay-based QC of LHQW or other TCM formulas relating to their pharmacological activities and mechanism.Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly afflicts the elderly population. Soluble oligomers (AβOs) has been implicated in AD pathogenesis however, the molecular events underlying a role for Aβ are not well understood. We studied the effects of AβOs on mitochondrial function and on key proteins that regulate mitochondrial dynamics and biogenesis in hippocampal neurons and PC-12 cells. We find that AβOs treatment caused a reduction in total Mfn1 after a 2 h exposure (42 ± 11%); while DRP1 increased at 1 and 2 h (205 ± 22% and 198 ± 27%, respectively), correlating to changes in mitochondrial morphology. We also observed that SIRT1 levels were reduced after acute and chronic AβOs treatment (68 ± 7% and 77 ± 6%, respectively); while PGC-1α levels were reduced with the same time treatments (68 ± 8% and 67 ± 7%, respectively). Interestingly, we found that chronic treatment with AβOs increased the levels of pSIRT1 (24 h 157 ± 18%), and we observed changes in the PGC-1α and p-SIRT1 nucleus/cytosol ratio and SIRT1-PGC-1α interaction pattern after chronic exposure to AβOs. Our data suggest that AβOs induce important changes in the level and localization of mitochondrial proteins related with the loss of mitochondrial function that are mediated by a fast and sustained SIRT1/PGC-1α complex disruption promoting a "non-return point" to an irreversible synaptic failure and neuronal network disconnection.
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