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Abstract Nasopharyngeal carcinoma (NPC) is the most common cancer originating in nasopharynx. Metabolic reprogramming plays a critical role in tumor progression. Exploring mechanisms underlying metabolic reprogramming contributes to deeper understanding of NPC pathogenesis. Here, we found downregulation of RORA and SPLUNC1 in NPC, and RORA downregulation indicates poor prognosis. RORA binds to SPLUNC1 promoter to induce its transcription, and RORA overexpression inhibits cell proliferation and glycolysis by directly upregulating SPLUNC1. UBR5 inhibits RORA via promoting RORA ubiquitination and degradation, and UBR5 silencing represses proliferation and glycolysis in NPC. Additionally, METTL14, which is highly expressed in NPC, facilitates UBR5 mRNA stability by promoting its m6A modification through IGF2BP2. UBR5/RORA/SPLUNC1 axis facilitates M2 polarization by activating the GPR132 signaling. UBR5 silencing inhibits tumor growth, glycolysis and M2 polarization through RORA/SPLUNC1 signaling in mice. In conclusion, UBR5 promotes proliferation, glycolysis and M2 polarization by metabolically reprograming NPC cells through suppression of the RORA/SPLUNC1 signaling.

Abstract The incidence of nasopharyngeal carcinoma (NPC) exhibits significant variations across different ethnic groups and geographical regions, with Southeast Asia and North Africa being endemic areas. Of note, Epstein-Barr virus (EBV) infection is closely associated with almost all of the undifferentiated NPC cases. Over the past three decades, radiation therapy and chemotherapy have formed the cornerstone of NPC treatment. However, recent advancements in immunotherapy have introduced a range of promising approaches for managing NPC. In light of these developments, it has become evident that a deeper understanding of the tumor microenvironment (TME) is crucial. The TME serves a dual function, acting as a promoter of tumorigenesis while also orchestrating immunosuppression, thereby facilitating cancer progression and enabling immune evasion. Consequently, a comprehensive comprehension of the TME and its intricate involvement in the initiation, progression, and metastasis of NPC is imperative for the development of effective anticancer drugs. Moreover, given the complexity of TME and the inter-patient heterogeneity, personalized treatment should be designed to maximize therapeutic efficacy and circumvent drug resistance. This review aims to provide an in-depth exploration of the TME within the context of EBV-induced NPC, with a particular emphasis on its pivotal role in regulating intercellular communication and shaping treatment responses. Additionally, the review offers a concise summary of drug resistance mechanisms and potential strategies for their reversal, specifically in relation to chemoradiation therapy, targeted therapy, and immunotherapy. Furthermore, recent advances in clinical trials pertaining to NPC are also discussed.

Background: Nursing home is critical for the elderly. Methods: To investigate the effects of decision-making process in terms of choosing room type and roommates on cognitive and psychosocial conditions of the elderly, 174 eligible participants were randomly assigned into three groups. In the first two groups, participants were randomly assigned to single-person rooms (Group SPR, n = 58) and multi-person rooms (2–4 persons per room, Group MPR, n = 58), and the third group of participants were allowed to voluntarily choose to live in single-person room or with preferred roommates (Group VPR, n = 58). Results: Participants who voluntarily choose room type and roommates (Group VPR) showed the least deterioration of cognitive function, psychosocial, and physical health, with Group MPR showing less deterioration than Group SPR. Allowing elderly people to voluntarily choose room type and roommate is better for preserving their cognitive, psychological, and physical health. Conclusions: Voluntary choice of room type and roommates is beneficial to the cognitive, psychological, and physical health of elderly people.

Background: Mindfulness training exhibits favorable effects on both psychological and physiological outcomes. We aimed at assessing its effects on post-percutaneous coronary intervention (PCI) patients. Methods: We recruited 357 patients arranged with PCI and randomized them in a ratio of 1:1 (n = 178 versus n = 179) into a 3-month mindfulness training class in addition to usual care. The primary outcomes were the physiological and health-related quality of life outcomes of patients post-PCI. The secondary outcomes were the psychological outcomes of the patients. Results: Compared to the control group, the 3-month mindfulness training improved the physiological outcomes including systolic blood pressure, body mass index, total cholesterol level, low-density lipoprotein-cholesterol, and triglyceride levels of patients post-PCI. The psychological outcomes including depression, anxiety, self-efficacy, and stress of these patients were also improved statistically. Conclusion: Mindfulness training exhibited benefits on both physiological and psychological outcomes of patients post-PCI.

Background: Apigenin has been reported to exhibit anti-inflammatory and anti-oxidative activities. This study aimed to investigate the protective role of Apigenin on chemotherapy-induced peripheral neuropathy (CIPN). Methods: CIPN mouse model was established using Paclitaxel treatment. Hot plate and tail prick latency tests were performed to examine the allodynia and hyperalgesia behaviors. Anti-inflammatory and anti-oxidative effects of Apigenin on CIPN were determined by enzyme-linked immunosorbent (ELISA) assay, Western blot, and qRT-PCR. Nuclear recruitment of nuclear factor erythroid 2-related factor 2 (NRF2) was analyzed to evaluate the underlying mechanisms of the protective effects of Apigenin. Results: Apigenin significantly alleviated CIPN-induced nociceptive behaviors of CIPN mice. It also decreased the TNF-α and IL-1β levels, suppressed oxidative stress and inflammation in the surgical spinal cord tissues. Mechanistically, Apigenin altered the pro-inflammatory and anti-inflammatory phenotypes ratio of microglia through promoting the nuclear recruitment of NRF2 and activating the NRF2/Antioxidant Response Element (ARE) signaling pathway. Conclusions: In summary, Apigenin relieves CIPN by regulating microglia activation and polarization, which provides a potential therapeutic strategy for CIPN treatment.

Sevoflurane is an inhalation anaesthetic agent widely used in clinical settings. Despite good surgical outcomes using sevoflurane, patients frequently develop postoperative cognitive dysfunction (POCD). An enriched environment (EE), as a rehabilitation technique, could provide objects and tools to facilitate neuromotor and visual stimuli and brain activity, and is reported to improve cognitive functions. We aim to investigate the impairments of sevoflurane inhalation on cognitive function in mice and determine the benefits of EE in ameliorating POCD. Eighteen-month-old mice were exposed to sevoflurane inhalation for 2 h and then placed in standard environment (SE) or EE cages. The mice without sevoflurane exposure in standard or EE cages were used as controls. The behavioural tests include Morris water maze, Y maze and novel object recognition. Magnetic resonance imaging (MRI) was used to determine the blood circulation in the brains. The proangiogenic factors (CD31, angiopoietin-1, vascular endothelial growth factor, and N-cadherin) and neurotrophic (brain-derived neurotrophic factor, post-synaptic density protein 95) expression in hippocampus of aged mice were evaluated by Western blotting and RT-PCR analysis. Sevoflurane-exposed mice demonstrated reduced performance in learning, memory and spatial memory tests. Enriched environment improved the behavioural performance of sevoflurane-exposed animals. Sevoflurane exposure reduced the blood flow in the brains, and these effects were ameliorated by EE habitation. The EE also promoted the expression of angiogenic and neurotropic factors in sevoflurane-exposed animals. In summary, EE is effective in ameliorating the side-effects of sevoflurane exposure in aged mice. [ABSTRACT FROM AUTHOR]

To examine the effect and mechanism of dexmedetomidine pretreatment mediated adenylate adenosine monophosphate-activated protein kinase pathway on hypoxic reoxygenation injured rat cardiomyocytes. A total of sixty Sprague-Dawley rats were allocated into three groups, namely the sham surgery group, model group, and dexmedetomidine intervention group, utilizing a random number table. Each group consisted of twenty rats. The model group and the intervention group of dexmedetomidine were used to prepare a rat myocardial hypoxia reoxygenation injury model using an improved thread occlusion method. The sham surgery group only underwent thoracotomy without ligation, and the intervention group of dexmedetomidine was pretreated with dexmedetomidine before establishing the model. Western blot was used to detect adenosine monophosphate-activated protein kinase, uncoupling protein 2, and Kruppel-like factor 2 proteins; using flow cytometry to detect the average fluorescence intensity of reactive oxygen species; detection of cell apoptosis rate using terminal deoxynucleotidyl transferase dUTP nick end labeling method; using the enzyme-linked immunosorbent assay detection kit manual to detect serum interleukin-6 and tumor necrosis factor-alpha, interleukin-1 beta and the levels of various indicators such as superoxide dismutase and malondialdehyde. Adenosine monophosphate-activated protein kinase, Kruppel-like factor 2, and uncoupling protein 2 proteins in the myocardium of the model group rats were markedly lower than those of the sham operation group; adenosine monophosphate-activated protein kinase, Kruppel-like factor 2, and uncoupling protein 2 in the myocardium of rats in the dexmedetomidine intervention group were markedly higher than the model group. The superoxide dismutase level of the model group rats was markedly reduced than the sham operation group, with malondialdehyde, interleukin-6 and tumor necrosis factor-alpha, interleukin-1 beta was markedly higher than that of the sham surgery group; superoxide dismutase, malondialdehyde, interleukin-6 and tumor necrosis factor-alpha in the intervention group of dexmedetomidine were markedly higher than the model group, tumor necrosis factor-alpha, interleukin-1 beta was markedly reduced than that of the model group. Dexmedetomidine can activate adenosine monophosphate-activated protein kinase pathway, upregulation of uncoupling protein 2 expressions and the inhibition of mitochondrial reactive oxygen species production are observed, thereby restraining the oxidative irritability of myocardial tissue under hypoxia/reoxygenation conditions and playing a role in myocardial cytoprotection. [ABSTRACT FROM AUTHOR]