EXCLI Journal最新文献

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).

Adolescence is a developmental phase largely characterized by rapid biological and non-biological transformations, with a heightened susceptibility to social and environmental influences. Hence, adolescents are particularly vulnerable to external stressors, underscoring the need to safeguard their well-being and prioritize mental health interventions. The coronavirus disease (COVID-19) pandemic caused a global crisis with profound societal disruptions, and led to lasting impact on global public health, disproportionately affecting vulnerable populations, including adolescents. In view of the unique developmental challenges faced by adolescents, it is imperative to assess the growing burden of mental health issues exacerbated by the pandemic. This review synthesizes existing evidence on the emerging mental health challenges faced by adolescents in the United Kingdom (UK) as exacerbated by the COVID-19 pandemic. A systematic literature search was conducted using PubMed, ScienceDirect, MEDLINE, and SpringerNature databases, resulting in the selection of ten high-quality studies. A thematic analysis of the collected data revealed that depression and anxiety were the most frequently reported mental health conditions among adolescents. These conditions were particularly prevalent among adolescents who were from low-income households, those with pre-existing mental health disorders, adolescents experiencing household conflicts, females, and those who provided self-reported data. Several key risk factors were identified, including family and peer relationships, academic pressures such as examinations and grades, financial constraints within households, and the corruptive influence of social media. The findings underscore the urgency of targeted mental health interventions tailored to the specific needs of adolescents in the U.K. By addressing the identified risk factors, mental health professionals, policymakers, and educators can develop more effective strategies to mitigate the psychological impact of the pandemic on this vulnerable population. This study contributes to the evolving body of literature and emphasizes the need for evidence-based policies to foster overall well-being and resilience in adolescents navigating post-pandemic challenges.

Ischemic heart disease (IHD) is a leading cause of morbidity and mortality worldwide, presenting with acute and chronic coronary syndromes. Although coronary atherosclerosis is a major cause of IHD, many patients with angina or myocardial ischemia do not have obstructive coronary heart disease and impairment of the coronary microcirculation has been increasingly implicated as a relevant cause of IHD. Therefore, coronary microvascular dysfunction (CMD) refers to a term covering a wide spectrum of structural and functional alterations which affect the coronary microcirculation leading to myocardial ischemia and angina. The advent of non-invasive and invasive functional tests has exponentially broadened the ability to recognize CMD and delineate related clinical and biochemical features. Despite major advances in diagnosing and stratifying this condition, therapeutic strategies remain limited and poorly defined. In this review, we will provide an overview of the pathophysiology and the diagnostic evaluation of CMD across the spectrum of cardiovascular diseases. Furthermore, we will discuss the novel therapeutic strategies available for these patients in the perspective of a personalized medicine approach.

[This corrects the article on p. 968 in vol. 20, PMID: 34267609.].

Glioblastoma multiforme (GBM) is an aggressive brain tumor with a poor prognosis, worsened by resistance to temozolomide (TMZ). TMZ-induced DNA damage is counteracted by the repair enzyme O-6-methylguanine-DNA methyltransferase (MGMT), promoting tumor recurrence. Targeting oxidative phosphorylation (OXPHOS), essential for cellular energy production, offers a potential therapeutic strategy to overcome TMZ resistance and improve GBM treatment outcomes. Gboxin, a small-molecule drug, selectively inhibits OXPHOS by targeting complex V, with minimal toxicity to normal cells. It accumulates in the mitochondria of GBM cells, exploiting their high membrane potential and pH, thereby inhibiting cell proliferation. This study evaluates Gboxin's efficacy in TMZ-resistant (TMZ-R) GBM. Results show that Gboxin suppresses the growth of both TMZ-sensitive and TMZ-R GBM cells by inhibiting proliferation, inducing apoptosis, and reducing OXPHOS activity. These findings were confirmed in an in vivo model, highlighting Gboxin as a promising therapeutic for both TMZ-sensitive and TMZ-R GBM. See also the graphical abstract(Fig. 1).