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Three new aaptamines (1–3) together with two known derivatives (4–5) were isolated from the South China Sea sponge Aaptos suberitoides. The structures of all compounds were unambiguously elucidated by spectroscopic analyses as well as the comparison with literature data. All the compounds were evaluated for their cytotoxic activities against five human cancer cell lines including H1299, H520, SCG7901, CNE-2 and SW680 cells. As a result, compounds 3–5 showed moderate cytotoxicities against H1299 and H520 cells with IC50 values ranging from 12.9 to 20.6 μg/mL. Besides, compounds 3–5 also showed potent inhibitory activities toward cyclin-dependent kinase-2 (CDK2) with IC50 values of 14.3, 3.0 and 6.0 μg/mL, respectively. In addition, compounds 3–5 significantly induced G1 arrests of H1299 cells at low concentrations. Drug affinity responsive target stability (DARTS) experiments were carried out and further demonstrated that compound 3 could effectively bind with CDK2 protein and protect it from the degradation by pronase.

Background GALAD score, comprising five clinical parameters, is a predictive model developed for hepatocellular carcinoma (HCC) detection. Since its emergence, its diagnostic ability has been validated in different populations with a wide variation. Therefore, we conducted a meta-analysis to investigate its overall diagnostic performance in differentiating HCC in chronic liver diseases. Methods Eligible studies were searched in the Web of Science, PubMed, Scopus, Ovid, Cochrane Library, and Embase databases by 29 May 2022. Pooled sensitivity, pooled specificity, and area under the receiver operating characteristic curve (AUC) with the corresponding 95% confidence intervals (CI) were estimated. Results Fifteen original studies (comprising 19,021 patients) were included. For detecting any-stage HCC, GALAD score yielded an excellent ability, with pooled sensitivity, specificity, and AUC of 0.82 (95%CI: 0.78–0.85), 0.89 (95%CI: 0.85–0.91), and 0.92 (95%CI: 0.89–0.94), respectively. Notably, further analyses demonstrated a good diagnostic accuracy of GALAD score for identifying Barcelona Clinic Liver Cancer staging (BCLC) 0/A HCC, with a moderate sensitivity (0.73 (95%CI: 0.66–0.79)) and a high specificity (0.87 (95%CI: 0.81–0.91)); by contrast, only 38% of early-stage patients can be identified by alpha-fetoprotein, with an AUC value of 0.70 (95%CI: 0.66–0.74). Following subgroup analyses based on different HCC etiologies, higher sensitivities and AUC values were observed in subgroups with hepatitis C or non-viral liver diseases. For detecting BCLC 0/A HCC in the cirrhotic population, GALAD score had a pooled sensitivity, specificity, and AUC of 0.78 (95%CI: 0.66–0.87), 0.80 (95%CI: 0.72–0.87), and 0.86 (95%CI: 0.83–0.89). Conclusions We highlighted the superior diagnostic accuracy of GALAD score for detecting any-stage HCC with a high sensitivity and specificity, especially for early-stage HCC, with a relatively stable diagnostic performance. The addition of GALAD score into ultrasound surveillance may identify more HCC patients. Our findings imply the robust power of the GALAD score as a HCC screening or diagnostic tool, and it should be further validated by more studies with high quality.

Cigarette smoking aggravates the symptoms of asthma, leading to the rapid decline of lung function. Dendritic cells (DCs) and lymphocytes are considered initiating and promoting factors for the airway inflammation reactions of asthma. In addition, activation of CC chemokine receptor 7 (CCR7) by chemokine (C-C motif) ligand (CCL) 19 and 21 promotes DCs and T cells migration to lymphoid tissues during inflammation. We aimed to examine how cigarette smoke affects the expression of CCR7 in the lungs of asthmatic rats and explore the signaling mechanism linking CCR7 expression to exacerbation of symptoms.Forty Wistar rats were randomized to four groups: control, asthma, smoke exposure, and asthma with smoke exposure groups. A rat asthma model was established by intraperitoneal ovalbumin injection. CCR7 expression was examined with immunohistochemistry and western blotting. The number of airway DCs was determined by OX62 immunohistochemistry. Interferon (INF)-γ, interleukin (IL)-4, CCL19, and CCL21 expression levels in blood and bronchioalveolar lavage fluid (BALF) were determined by enzyme-linked immunosorbent assays (ELISAs).Tissue CCR7 expression, peripheral blood and BALF CCL19 and CCL21 concentrations, and the number of airway DCs were significantly higher in the asthma with smoke exposure group than the asthma group (P0.01). In addition, INF-γ expression was decreased and IL-4 increased in the asthma and asthma with smoke exposure groups compared with the control group (P0.01), and in the asthma with smoke exposure group compared with the asthma group (P0.01). Expression of CCR7 correlated negatively with INF-γ expression in peripheral blood and BALF (P0.01), and positively with the airway DCs and IL-4 expression in the peripheral blood and BALF (P0.01).Cigarette smoking may aggravate asthma symptoms by attenuating immunity, possibly through CCR7-mediated DCs aggregation in lung tissue.

Objective The aims of this study were to estimate the prevalence of radiographic osteoarthritis (OA) and to assess the association between smoking patterns and OA prevalence in adults aged 50 years or older belonging to the Shanxi province of China. Methods A cross-sectional study in the rural regions of the Shanxi province was conducted among 2638 Chinese adults (aged ≥50 years). Demographic characteristics and behavioral information were collected through epidemiological surveys. All participants with joint pain underwent plain radiographic examination and were diagnosed by a professional orthopedist. Associations between smoking patterns and the prevalence of OA were assessed using binary logistic regression modeling. Results Among 2638 individuals (men, 50.3% and women, 49.7%; mean age, 61.5 years) included in the analysis, 49.8% had radiographic OA and 27.5% had knee OA. The prevalence of radiographic OA was higher in women than in men (P Conclusions This study showed that smoking may not be an independent risk factor for OA; however, there was a positive correlation between active and passive smoking and OA.

Objective: To explore the expression of p16 in human colorectal cancer and its clinical significance. Methods: Neoplastic tissues and autologous non-neoplastic tissues were taken from 30 patients with colorectal cancer immediately after the operation. The expression of p16 in these tissues was detected using immunohistochemistry, and then was confirmed with HT-29 cell line by Western-blot assay. Results: The positive rate of p16 expression in neoplastic tissues was 23.3%, significantly lower than that in non-neoplastic tissues (P

Pure and Ni-doped manganese dioxides were prepared by liquid-phase reaction method. The morphology of the samples was characterized by SEM and the electrochemical capacitance behaviors of pure MnO2 and Ni-doped MnO2 electrode were investigated by cyclic voltammetry, galvanostatic charge/discharge and electrochemical impedance spectroscopy tests. The results show that nickel doping can enhance the specific capacitance of MnO2. The 1 % Ni-doped MnO2 electrode shows a relative high specific capacitance of 451 F g-1at a scan rate of 5 mV s-1 and 267.3 F g-1 at a current density of 0.3 A g-1 in 1 M Na2SO4 electrolyte.