The prognosis of patients with colorectal cancer (CRC) remains poor owing to diagnosis typically occurring at advanced stages of the disease. The understanding of the molecular regulatory signatures of CRC may lead to the identification of biomarkers for the early detection, prevention and clinical intervention of CRC. Epidemiological studies have indicated that cyclooxygenase-1 (COX-1) serves an active function in colon carcinogenesis. However, the molecular mechanism underlying COX-1 regulation in CRC remains unknown. In the present study, COX-1 was identified to be markedly upregulated in colorectal tissues of patients with CRC, and in the CRC cell lines HCT116 and HT29. To determine the function of COX-1 in cancer development, short hairpin RNA knockdown of COX-1 was employed in HCT116 and HT29 CRC cells in the present study. The results demonstrated that silencing of COX-1 depolarized the mitochondrial membrane potential, inhibited adenosine triphosphate production, induced the generation of intracellular reactive oxygen species and triggered caspase-dependent mitochondrial apoptosis. Furthermore, depletion of COX-1 suppressed anti-apoptotic B-cell lymphoma 2 and enhanced pro-apoptotic Bcl-2-associated X protein expression by inhibiting the p65 subunit phosphorylation of nuclear factor κB (NF-κB). Taken together, the results of the present study indicated that COX-1 inhibition significantly triggered cell death by destroying the mitochondrial function that is associated with deactivation of the NF-κB signaling pathway. These results suggest COX-1 as a potential anticancer target in CRC.

As a malignant tumour of the central nervous system, glioma exhibits high incidence and poor prognosis. Although TNIP1 and the TNF‐α/NF‐κB axis play key roles in immune diseases and inflammatory responses, their relationship and role in glioma remain unknown. Here, we revealed high levels of TNIP1 and TNF‐α/NF‐κB in glioma tissue. Glioma cell proliferation was activated with TNF‐α treatment and showed extreme sensitivity to the TNF receptor antagonist. Furthermore, loss of TNIP1 disbanded the A20 complex responsible for IκB degradation and NF‐κB nucleus translocation, and consequently erased TNFα‐induced glioma cell proliferation. Thus, our investigation uncovered a vital function of the TNIP1‐mediated TNF‐α/NF‐κB axis in glioma cell proliferation and provides novel insight into glioma pathology and diagnosis.

Parkinson's disease (PD) is the second most common neurodegenerative disease amongst the middle-aged and elderly populations. Several studies have confirmed that the microbiota-gut-brain axis (MGBA) serves a key role in the pathogenesis of PD. Changes to the gastrointestinal microbiome (GM) cause misfolding and abnormal aggregation of α-synuclein (α-syn) in the intestine. Abnormal α-syn is not eliminated via physiological mechanisms and is transported into the central nervous system (CNS) via the vagus nerve. The abnormal levels of α-syn aggregate in the substantia nigra pars compacta, not only leading to the formation of eosinophilic Lewis Bodies in the cytoplasm and mitochondrial dysfunction in dopaminergic (DA) neurons, but also leading to the stimulation of an inflammatory response in the microglia. These pathological changes result in an increase in oxidative stress (OS), which triggers nerve cell apoptosis, a characteristic of PD. This increase in OS further oxidizes and intensifies abnormal aggregation of α-syn, eventually forming a positive feedback loop. The present review discusses the abnormal accumulation of α-syn in the intestine caused by the GM changes and the increased levels of α-syn transport to the CNS via the MGBA, resulting in the loss of DA neurons and an increase in the inflammatory response of microglial cells in the brain of patients with PD. In addition, relevant clinical therapeutic strategies for improving the GM and reducing α-syn accumulation to relieve the symptoms and progression of PD are described. Contents 1. Introduction 2. An aberrant GM affects α-syn accumulation in the intestine of patients with PD 3. α-syn accumulation contributes to neurodegeneration in the CNS of patients with PD 4. Novel treatments based on the MGBA and α-syn for PD 5. Conclusion

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