EXCLI Journal最新文献

Baccharis articulata (Lam) Pers. is an herb native to southern Brazil and is widely used in local traditional medicine for weight loss and for the treatment of digestive and liver diseases. However, only a few studies have been conducted to scientifically validate the folk use of this plant. This study assessed the in vitro therapeutic effects of an aqueous extract of B. articulata and chlorogenic acid on liver fibrosis in murine hepatic stellate cells (HSC; GRX cell line). The decrease in cell proliferation and cytotoxicity, as well as phenotypic reversion by the presence of lipid droplets and reduction in collagen content after seven days of treatment, were evaluated. The mechanisms responsible for the antifibrotic effects of the extract, including the plasminogen activation system, were assessed. from high-performance liquid chromatography coupled with diode array detector and tandem mass spectrometry (HPLC-DAD-MS/MS) data. Twenty-six metabolites were identified in the extract, including flavonoids, phenylpropanoid derivatives, and diterpenes. Treatment with the extract significantly induced the accumulation of lipids in the cytoplasm of cells, indicating that it could revert the HSC phenotype to a quiescent state with no cytotoxic or antiproliferative effects. These findings may be related to the inhibition of the TGF-β1 pathway, a biomarker of liver fibrosis, upregulation of the plasminogen system, and dose-dependent inhibition of plasmin activity. The presence of caffeoylquinic acids seems to be partially related to the extract effect, as chlorogenic acid displayed antiproliferative activity and reduced collagen content in hepatic stellate cells. Considering the unmet need for antifibrotic therapies, the use of medicinal plants to inhibit the proliferation of activated HSC is promising, and this study indicated that the aqueous extract of B. articulata has potential therapeutic activity against hepatic fibrosis (see also Figure 1(Fig. 1) graphical abstract).

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder lacking effective treatments. This systematic review and meta-analysis assesses the efficacy and safety of sulforaphane (SFN) for ASD. Eight databases were searched from inception to September 2024, identifying six randomized controlled trials for inclusion. Efficacy outcomes included ASD symptoms measured by the mean difference (MD) or standardized mean difference (SMD), while safety outcomes included adverse events measured by relative risk. Risk of bias was assessed using the Cochrane tool, and evidence certainty was evaluated via the Grade of Recommendations Assessment Development and Evaluation (GRADE). Results showed that SFN significantly improved total symptoms (SMD = -0.27, 95 % confidence interval (CI), -0.42, -0.12), aberrant behavior (SMD = -0.43, 95 % CI, -0.66, -0.19), hyperactivity (SMD = -0.58, 95 % CI, -1.03, -0.13), social interaction (SMD = -0.43, 95 % CI, -0.59, -0.27), social communication (SMD = -0.24, 95 % CI, -0.35, - 0.12), and restricted and repetitive behaviors (RRB) (SMD = -0.16, 95 % CI, -0.31, -0.00). Effects on irritability, anxiety, sensory sensitivity, total social skills, social awareness, social cognition, and social motivation were not statistically significant. Adverse events were similar between intervention and control groups. In conclusion, SFN shows potential in improving ASD symptoms without significant adverse effects. However, results should be interpreted cautiously due to potential influences from assessment tools, outcome assessors, and treatment duration. Further research is needed to confirm the long-term efficacy and safety of SFN for ASD.

Antimicrobial resistance is a growing public health threat worldwide, and the current drug development pipeline has thus far been inadequate in addressing this impending crisis. Further research into antibiotic agents, both existing and novel, is therefore paramount for identifying suitable candidates to combat antibiotic-resistant pathogens. Sulfonamides, the first class of synthetic antibiotics, target dihydropteroate synthase (DHPS), a key bacterial enzyme. While this class of antibiotics has historically demonstrated great utility, their use has diminished due to resistance and undesired side effects. In the present study, we synthesized a selection of four sulfonamide analogues (FQ5, FQ6, FQ7 and FQ12), validated their structures through NMR spectroscopy, and evaluated their inhibitory potential through computational docking and MIC assays against four bacterial strains: Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 35401 and Bacillus subtilis ATCC 6633. Each compound exhibited antibacterial activity; FQ5 demonstrated the most potent activity, with an MIC of 32, 16, 16, and 16 µg/mL against aforementioned strains, respectively. FQ6, FQ7 and FQ12, on the other hand, exhibited moderate activity against P. aeruginosa and E. coli (MIC = 128 µg/mL each) and low activity against S. aureus and B. subtilis (MIC = 256 µg/mL each). Molecular docking studies indicated that FQ5 captures multiple hydrogen bonding, ionic, and π-π interactions with key binding pocket residues of DHPS, and FQ5 also demonstrated superior predicted drug-likeness in in silico ADMET studies compared to other compounds. FQ5 is therefore a favorable starting point for further optimization.

Ethylbenzene (EB) was placed on List 2 for Tier 1 endocrine screening in the U.S. EPA's two-tiered Endocrine Disruptor Screening Program (EDSP) and was scheduled for evaluation under TSCA. Results of toxicology studies on EB were used to evaluate estrogen, androgen, thyroid, and steroidogenic (EATS) endpoints by a Weight of Evidence (WoE) methodology, as required by U.S. EPA and OECD guidelines for evaluating a chemical's endocrine disruptive potential. The WoE method involved problem formulation, systematic literature search and selection, data quality evaluation, relevance weighting of endpoint data, and application of specific interpretive criteria. Data on EB were sufficient to assess its effects on endpoints that would be expected to respond to chemicals that operate via EATS modes of action (MoAs) in various screening assays (Tier 1) and toxicity tests (Tier 2) that evaluate reproduction, development, and sub-chronic and chronic toxicity. In those studies, EB produced a pattern of responses inconsistent with the responses that would be expected for hormones and chemicals known to operate via EATS MoAs. Endocrine-sensitive endpoints that respond to EB administration generally do so only at dose levels above its kinetic maximum dose, indicating a lack of relevance to potential effects at lower dose levels in either the test species or humans. This comprehensive WoE evaluation demonstrates that EB lacks the potential to exhibit endocrine disruptive properties and cannot be deemed an endocrine disruptor or potential endocrine disruptor. Because this WoE evaluation was based largely on Tier 2-level studies of the type considered by the U.S. EPA and OECD to be more definitive than results of Tier 1 EDSP screening results, no additional useful information would be obtained by subjecting EB to further endocrine screening. As such, further endocrine screening of EB would be unjustified from animal welfare perspectives. This analysis supports a regulatory decision to halt further testing of EB for endocrine disruption unless unique and compelling data to the contrary arise. See also the graphical abstract(Fig. 1).