Phellopterin attenuates ovarian cancer proliferation and chemoresistance by inhibiting the PU.1/CLEC5A/PI3K-AKT feedback loop.

Ovarian cancer is known as the second leading cause of gynecologic cancer-associated deaths in women worldwide. Developing new and effective compounds to alleviate chemoresistance is an urgent priority in ovarian cancer. Here, we aimed to reveal the biological function and underlying mechanisms of phellopterin, a naturally sourced ingredient of Angelica dahurica, in ovarian cancer progression as well as evaluate the therapeutic potential of phellopterin in ovarian cancer patients. In this investigation, we found that phellopterin mitigated DNA replication and induced cell cycle arrest, apoptosis, and DNA damage, attenuating cell proliferation and chemoresistance of ovarian cancer. Interestingly, bioinformatics analyses of data from our RNA sequencing and The Cancer Genome Atlas ovarian cancer dataset suggested that phellopterin presented anti-cancer activities in ovarian cancer cells by modulating signals affecting ovarian cancer progression and identified phellopterin as a potential compound in improving ovarian cancer patients' prognosis. In addition, the C-Type Lectin Domain Containing 5A (CLEC5A) was demonstrated as a downstream effector of phellopterin and involved in a positive PU.1/CLEC5A/PI3K-AKT feedback loop. Interestingly, phellopterin might inactivate the positive feedback circuit to suppress ovarian cancer progression. Collectively, our investigation revealed that phellopterin mitigated ovarian cancer proliferation and chemoresistance through suppressing the PU.1/CLEC5A/PI3K-AKT feedback loop, and predicted phellopterin as a new and effective cytotoxic drug and CLEC5A as a potential target for the treatment of ovarian cancer.

Dietary Diversity Changes and Cognitive Frailty in Chinese Older Adults: A Prospective Community-Based Cohort Study.

Evidence for the effects of dietary diversity changes and cognitive frailty (CF) in the older adults is not clear. This study aimed to investigate the relationship between dietary diversity changes and CF in older adults Chinese. A total of 14,382 participants (mean age: 82.3 years) were enrolled. Dietary diversity scores (DDSs) were collected and calculated using a food frequency questionnaire. DDS changes between baseline and first follow-up were categorized into nine patterns. The associations between DDS changes and the incidence of CF were estimated using Cox proportional hazards models. During an 80,860 person-year follow-up, 3023 CF cases were identified. Groups with a decrease in DDS had increased CF risk compared with the high-to-high DDS group, with adjusted hazard ratios (HRs; 95% confidence intervals (Cis)) of 1.30 (1.06, 1.59), 2.04 (1.51, 2.74), and 1.81 (1.47, 2.22) for high-to-medium, high-to-low, and medium-to-low groups, respectively. Lower overall DDS groups were associated with greater CF risks, with HRs (95% CIs) of 1.49 (1.19, 1.86) for the low-to-medium group and 1.96 (1.53, 2.52) for the low-to-low group. Compared with the high-to-high group, significant associations with CF were found in other DDS change groups; HRs ranged from 1.38 to 3.12 for the plant-based DDS group and from 1.24 to 1.32 for the animal-based DDS group. Additionally, extreme and moderate declines in overall DDS increased CF risk compared with stable DDS, with HRs (95% CIs) of 1.67 (1.50, 1.86) and 1.13 (1.03, 1.24), respectively. In conclusion, among older adults, a declining or persistently low DDS and a moderately or extremely declining DDS were linked to higher incident CF. Plant-based DDS changes correlated more strongly with CF than animal-based DDS changes.

Circular RNA CDK6 suppresses cervical cancer proliferation and metastasis by sponging miR-449a.

Cervical cancer is a malignant tumor that severely threatens female health. Recently, more and more studies indicated that circRNA could function as a tumor activator or suppressor in cervical cell development. Therefore, we aimed to study the effect of circRNA CDK6 (circCDK6) on the development and biological behavior of cervical cancer. We used quantitative real-time PCR (qRT-PCR) to examine the circCDK6 expression level in cervical cancer cell lines. RNA-fluorescence in situ hybridization confirmed the location of circCDK6 and miR-449a in HeLa and CaSki cells, respectively. Then, the biological function of silencing circCDK6 in cellular proliferation, metastasis, and Epithelial-Mesenchymal Transition (EMT)-related process was determined. We also performed RNA Binding Protein Immunoprecipitation (RIP) and Dual-luciferase reporter assay to determine the relationship between the circCDK6 and miR-449a. Finally, the results showed that circCDK6 level remarkably increased in several cervical cancer cells, especially in Hela and CaSki cells. The miR-449a was further confirmed to be a potential target of circCDK6, and its expression increased by silencing circCDK6. The circCDK6 participated in tumorigenesis and cancer progression and might serve as a tumor suppressive factor in cervical cell progression via Epithelial-MesenchymalTransition (EMT) process by regulating miR-449a.

Comparison of Prognosis Between Juvenile and Adult Nasopharyngeal Carcinoma: A Propensity Score-Matched Analysis.

PURPOSE: To investigate whether juvenile patients with nasopharyngeal carcinoma (NPC) in China have better prognosis than their adult counterparts in the intensity-modulated radiation therapy (IMRT) era, after controlling for potential confounding variables. METHODS: Data pertaining to 1139 patients with newly diagnosed NPC without metastasis, who were treated with IMRT at our hospital, were retrospectively analyzed. Of these, 60 patients were juvenile (age ≤18 years) diagnosed between January 2003 and December 2018, while 1079 patients were adults (≤65 years) diagnosed between January 2013 and December 2014. To minimize the influence of selection and confounding bias, 1:2 propensity score matching (PSM) was used. Overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated using the Kaplan-Meier method and between-group differences assessed using the Log rank test. The long-term toxicity of the juvenile patients was evaluated according to the criteria of the Radiation Therapy Oncology Group (RTOG) and the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: Five-year OS of juvenile and adult patients were 88.07% and 85.08%, respectively. Before PSM, OS, PFS, DMFS, or LRFS were comparable in the two groups (all P > 0.05). After PSM, OS, DFS, and LRFS in the juvenile group were markedly longer than that in adults (P = 0.005, P = 0.027, and P = 0.024, respectively). With respect to long-term toxicity, the most common adverse effects in juvenile patients were cervix fibrosis, ototoxicity, and xerostomia. However, except for two patients who developed grade 3 ototoxicity, all adverse effects were within grade 2. CONCLUSION: In the IMRT era, juvenile Chinese patients with NPC had better 5-year OS, DFS, and LRFS than their adult counterparts. The adverse events in the juvenile cohort were relatively mild; however, the risk of severe ototoxicity should not be neglected.

Unidimensional measurement may be superior to assess primary tumor response after neoadjuvant chemotherapy for nasopharyngeal carcinoma.

Application of current response evaluation criteria in solid tumors (RECIST 1.1) for assessment of irregularly shaped nasopharyngeal carcinoma (NPC) is a gray area with much ambiguity. Our aim was to compare unidimensional measurements (UDM) and bidimensional measurements (BDM) on magnetic resonance images in alternative planes for measurement of tumor response after neoadjuvant chemotherapy (NACT) in patients with locally advanced NPC. 59 patients with untreated non-metastatic NPC were prospectively enrolled. The size or change in size of the primary tumor and retropharyngeal nodes was assessed by UDM and BDM on axial and coronal planes before and after 2 cycles of NACT. Tumor volume was considered as the reference standard. Correlation between volume and diameter was analyzed using a general linear model. The degree of agreement and discordance of response classification based on different measures were evaluated with κ statistic and McNemar's test, respectively. Both axial UDM (RECIST 1.1) and axial BDM (WHO) showed a significant association with volumetric standard. However, the agreement of axial UDM with VM was better than that of axial BDM (κ value: 0.514 to 0.372). In addition, when increasing coronal planes to evaluate tumor response with UDM and BDM, an inferior agreement between coronal BDM and VM was still observed. Notably, coronal UDM showed the best consistency with volume (κ = 0.585). Hence, axial UDM showed better correlation with volumetric measurements than axial BDM. Since coronal UDM showed high correlation to VM, we suggest further research to assess its use for response assessment of NPC after NACT.

Effects of the lifting manipulation of scalp acupuncture for raising myodynamia of the affected limbs in hemiplegic patients due to cerebral thrombosis.

OBJECTIVE: To provide a new therapy with definite quality controllable therapeutic effects for functional restoration of the affected limbs in hemiplegic patients due to cerebral thrombosis. METHOD: 180 patients with hemiplegia due to cerebral thrombosis were randomly divided into 2 groups: the treatment group (treated with scalp acupuncture by using the lifting manipulation) and the control group (treated with scalp acupuncture by using the twirling manipulation). Evaluations were given for the two groups based on the improvement of myodynamia and comprehensive functions after the treatment. RESULTS: Both groups showed increased myodynamia, but with different cured and much relieved rates (86.67% in the treatment group and 5% in the control group, P<0.01). CONCLUSION: Scalp acupuncture with the lifting manipulation can dramatically increase myodynamia of the affected limbs in hemiplegic patients due to cerebral thrombosis.