Shun-Hua Chen

Aim: Chemoresistance in cancer challenges the classical therapeutic strategy of 'one molecule-one target'. To combat this, multi-target therapies that inhibit various cancer-relevant targets simultaneously are proposed. Methods & results: We introduce 5-hydroxybenzothiophene derivatives as effective multi-target kinase inhibitors, showing notable growth inhibitory activity across different cancer cell lines. Specifically, compound 16b, featuring a 5-hydroxybenzothiophene hydrazide scaffold, emerged as a potent inhibitor, displaying low IC₅₀ values against key kinases and demonstrating significant anti-cancer effects, particularly against U87MG glioblastoma cells. It induced G2/M cell cycle arrest, apoptosis and inhibited cell migration by modulating apoptotic markers. Conclusion: 16b represents a promising lead for developing new anti-cancer agents targeting multiple kinases with affinity to the hydroxybenzothiophene core.

For many inflammatory diseases, new effective drugs with fewer side effects are needed. While it appears promising to target the activation of the central pro-inflammatory transcription factor NF-κB, many previously discovered agents suffered from cytotoxicity. In this study, new alkylthiourea quinazoline derivatives were developed that selectively inhibit the activation of NF-κB in macrophage-like THP−1 cells while showing low general cytotoxicity. One of the best compounds, 19, strongly inhibited the production of IL-6 (IC₅₀ = 0.84 µM) and, less potently, of TNFα (IC₅₀ = 4.0 µM); in comparison, the reference compound, caffeic acid phenethyl ester (CAPE), showed IC₅₀s of 1.1 and 11.4 µM, respectively. Interestingly, 19 was found to block the translocation of the NF-κB dimer to the nucleus, although its release from the IκB complex was unaffected. Furthermore, 19 suppressed the phosphorylation of NF-κB-p65 at Ser468 but not at Ser536; however, 19 did not inhibit any kinase involved in NF-κB activation. The only partial suppression of p65 phosphorylation might be associated with fewer side effects. Since several compounds selectively induced cell death in activated macrophage-like THP−1 cells, they might be particularly effective in various inflammatory diseases that are exacerbated by excess activated macrophages, such as arteriosclerosis and autoimmune diseases.

The novel 2019 coronavirus disease (COVID-19) is still not under control globally. The pandemic has caused mental health issues among many different cohorts and suicidal ideation in relation to COVID-19 has been reported in a number of recent studies. Therefore, the present study proposed a model to explain the associations between generalized trust, fear of COVID-19, insomnia, and suicidal ideation during the COVID-19 pandemic among a large-scale Iranian sample. Utilizing cluster sampling with multistage stratification, residents from Qazvin province in Iran were invited to participate in the present study. Adults aged over 18 years (n = 10,843; 6751 [62.3%] females) completed ‘paper–and-pencil’ questionnaires with the assistance of a trained research assistant. Structural equation modeling (SEM) was applied to understand the associations between generalized trust, fear of COVID-19, insomnia, and suicidal ideation. Slightly over one-fifth of the participants (n = 2252; 20.8%) reported suicidal ideation. Moreover, the SEM results indicated that generalized trust was indirectly associated with suicidal ideation via fear of COVID-19 and insomnia. Furthermore, generalized trust was not directly associated with suicidal ideation. The proposed model was invariant across gender groups, age groups, and participants residing in different areas (i.e., urban vs. rural). Generalized trust might reduce individuals’ suicidal ideation during the COVID-19 pandemic period via reduced levels of fear of COVID-19 and insomnia. Healthcare providers and policymakers may want to assist individuals in developing their generalized trust, reducing fear of COVID-19, and improving insomnia problems to avoid possible suicidal behaviors.

Strengthening pro-environmental behaviors such as green purchasing behavior is important for environmental sustainability. An integrated social cognition model which incorporates constructs from habit theory, health action process approach (HAPA), and theory of planned behavior (TPB) is adopted to understand Iranian adolescents’ green purchasing behavior. Using a correlational-prospective design, the study recruited Iranian adolescents aged between 14 and 19 years (N = 2374, n = 1362 (57.4%) females, n = 1012 (42.6%) males; Mean (SD) age = 15.56 (1.22)). At baseline (T1), participants self-reported on the following constructs: past behavior; habit strength (from habit theory); action planning and coping planning (from HAPA); and intention, perceived behavioral control, subjective norm, and attitude (from TPB) with respect to green purchasing behavior. Six months later (T2), participants self-reported on their actions in terms of purchasing green goods. Our findings reported direct effects of perceived behavioral control, subjective norms, attitude, and past behavior on intention; intention and perceived behavioral control on green purchase behavior; intention on two types of planning (i.e., action and coping planning); both types of planning on green purchase behavior; and past green purchase behavior and habits on prospectively measured green purchase behavior. These results indicate that adolescent green purchasing behavior is underpinned by constructs representing motivational, volitional, and automatic processes. This knowledge can help inform the development of theory-based behavior change interventions to improve green purchasing in adolescents, a key developmental period where climate change issues are salient and increased independence and demands in making self-guided decisions are needed.