Sublethal dosages of imidacloprid cause long-term destructive effects on honey bees at the individual and colony levels. In this review, the molecular effects of sublethal imidacloprid were integrated and reported. Several general effects have been observed among different reports using different approaches. Quantitative PCR approaches revealed that imidacloprid treatments during the adult stage are expressed as changes in immuneresponse, detoxification, and oxidation-reduction response in both workers and queens. In addition, transcriptomic approaches suggested that phototransduction, behavior, and somatic muscle development also were affected. Although worker larvae show a higher tolerance to imidacloprid than adults, molecular evidence reveals its potential impacts. Sublethal imidacloprid treatment during the larval stage causes gene expression changes in larvae, pupae, and adults. Transcriptome profiles suggest that the population and functions of affected differentially expressed genes, DEGs, vary among different worker ages. Furthermore, an early transcriptomic switch from nurse bees to foragers was observed, suggesting that precocious foraging activity may occur. This report comprehensively describes the molecular effects of sublethal dosages of imidacloprid on the honey bee Apis mellifera. The corresponding molecular pathways for physiological and neurological responses in imidacloprid-exposed honey bees were validated. Transcriptomic evidence suggests a global and sustained sublethal impact of imidacloprid on honey bee development.

Radiotherapy is one of the most common treatment options for local or regional advanced prostate cancer (PCa). Importantly, PCa is prone to radioresistance and often develops into malignancies after long-term radiotherapy. Antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, possesses pharmacological efficacy against various cancer types; however, its therapeutic potential requires comprehensive exploration, particularly in radioresistant PCa cells. In this study, we emphasized the effects of antrocin on radioresistant PCa cells and addressed the molecular mechanism underlying the radiosensitization induced by antrocin. Our results showed that a combination treatment with antrocin and ionizing radiation (IR) synergistically inhibited cell proliferation and induced apoptosis in radioresistant PCa cells. We further demonstrated that antrocin downregulated PI3K/AKT and MAPK signaling pathways as well as suppressed type 1 insulin-like growth factor 1 receptor (IGF-1R)-mediated induction of β-catenin to regulate cell cycle and apoptosis. Using xenograft mouse models, we showed that antrocin effectively enhanced radiotherapy in PCa. Our study demonstrates that antrocin sensitizes PCa to radiation through constitutive suppression of IGF-1R downstream signaling, revealing that it can be developed as a potent therapeutic agent to overcome radioresistant PCa.

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality in both sexes globally. This is not unconnected with the heterogeneity and plasticity of CRC stem cells (CRC-SCs) which stealthily exploit the niche-related and (epi)genetic factors to facilitate metastasis, chemoresistance, tumor recurrence, and disease progression. Despite the accumulating evidence of the role of dysregulated microRNAs in malignancies, the therapeutic efficacy of pharmacological-targeting of CRC-SC-associated microRNAs is relatively under-explored. Experimental approach: In this present study, we employed relatively new bioinformatics approaches, analyses of microarray data, Western blot, real-time polymerase chain reaction (RT-PCR), and functional assays to show that hsa-miR-324-5p expression is significantly suppressed in CRC cells, and inversely correlates with the aberrant expression of SOD2. Results: This converse hsa-miR-324-5p/SOD2 relationship is associated with enhanced oncogenicity, which is effectively inhibited by 4-acetylantroquinonol B (4-AAQB), as evidenced by inhibited cell viability and proliferation, as well as attenuated migration, invasion, and clonogenicity in 4-AAQB-treated DLD1 and HCT116 cells. Interestingly, 4-AAQB did not affect the viability and proliferation of normal colon cells. We also showed that 4-AAQB-induced re-expression of hsa-miR-324-5p, akin to short-interfering RNA, reduced SOD2 expression, correlates with the concurrent down-regulation of SOD2, N-cadherin, vimentin, c-Myc, and BcL-xL2, with concomitant up-regulation of E-cadherin and BAX2 proteins. Enhanced expression of hsa-miR-324-5p in the CRC cells suppressed their tumorigenicity in vitro and in vivo. Additionally, 4-AAQB synergistically potentiates the FOLFOX (folinate (leucovorin), fluorouracil (5FU), and oxaliplatin) anticancer effect by eliciting the re-expression of SOD2-suppressed hsa-miR-324, and inhibiting SOD2-mediated tumorigenicity. Conclusion: Our findings highlight the pre-clinical anti-CSC efficacy of 4-AAQB, with or without FOLFOX in CRC, and suggest a potential novel therapeutic strategy for CRC patients.

Despite the significant advancement in therapeutic strategies, breast, colorectal, gastric, lung, liver, and prostate cancers remain the most prevalent cancers in terms of incidence and mortality worldwide. The major causes ascribed to these burdens are lack of early diagnosis, high metastatic tendency, and drug resistance. Therefore, exploring reliable early diagnostic and prognostic biomarkers universal to most cancer types is a clinical emergency. Consequently, in the present study, the differentially expressed genes (DEGs) from the publicly available microarray datasets of six cancer types (liver, lung colorectal, gastric, prostate, and breast cancers), termed hub cancers, were analyzed to identify the universal DEGs, termed hub genes. Gene set enrichment analysis (GSEA) and KEGG mapping of the hub genes suggested their crucial involvement in the tumorigenic properties, including distant metastases, treatment failure, and survival prognosis. Notably, our results suggested high frequencies of genetic and epigenetic alterations of the DEGs in association with tumor staging, immune evasion, poor prognosis, and therapy resistance. Translationally, we intended to identify a drug candidate with the potential for targeting the hub genes. Using a molecular docking platform, we estimated that ovatodiolide, a bioactive anti-cancer phytochemical, has high binding affinities to the binding pockets of the hub genes. Collectively, our results suggested that the hub genes were associated with establishing an immune-suppressive tumor microenvironment favorable for disease progression and promising biomarkers for the early diagnosis and prognosis in multiple cancer types and could serve as potential druggable targets for ovatodiolide.

Alzheimer’s disease (AD) is the most frequent cause of neurodegenerative dementia and affects nearly 50 million people worldwide. Early stage diagnosis of AD is challenging, and there is presently no effective treatment for AD. The specific genetic alterations and pathological mechanisms of the development and progression of dementia remain poorly understood. Therefore, identifying essential genes and molecular pathways that are associated with this disease’s pathogenesis will help uncover potential treatments. In an attempt to achieve a more comprehensive understanding of the molecular pathogenesis of AD, we integrated the differentially expressed genes (DEGs) from six microarray datasets of AD patients and controls. We identified ATPase H+ transporting V1 subunit A (ATP6V1A), BCL2 interacting protein 3 (BNIP3), calmodulin-dependent protein kinase IV (CAMK4), TOR signaling pathway regulator-like (TIPRL), and the translocase of outer mitochondrial membrane 70 (TOMM70) as upregulated DEGs common to the five datasets. Our analyses revealed that these genes exhibited brain-specific gene co-expression clustering with OPA1, ITFG1, OXCT1, ATP2A2, MAPK1, CDK14, MAP2K4, YWHAB, PARK2, CMAS, HSPA12A, and RGS17. Taking the mean relative expression levels of this geneset in different brain regions into account, we found that the frontal cortex (BA9) exhibited significantly (p < 0.05) higher expression levels of these DEGs, while the hippocampus exhibited the lowest levels. These DEGs are associated with mitochondrial dysfunction, inflammation processes, and various pathways involved in the pathogenesis of AD. Finally, our blood–brain barrier (BBB) predictions using the support vector machine (SVM) and LiCABEDS algorithm and molecular docking analysis suggested that antrocin is permeable to the BBB and exhibits robust ligand–receptor interactions with high binding affinities to CAMK4, TOMM70, and T1PRL. Our results also revealed good predictions for ADMET properties, drug-likeness, adherence to Lipinskís rules, and no alerts for pan-assay interference compounds (PAINS) Conclusions: These results suggest a new molecular signature for AD parthenogenesis and antrocin as a potential therapeutic agent. Further investigation is warranted.