Fangchinoline (Fan) is a bioactive compound isolated from the Chinese herb S. Moore (Fen Fang Ji). The aim of the present study was to investigate the effect of Fan on the proliferation of SPC-A-1 lung cancer cells, and to define the associated molecular mechanisms. Following treatment with Fan, Cell Counting Kit-8, phase contrast imaging and Giemsa staining assays were used to detect cell viability; flow cytometry was performed to analyze the cell cycle distribution; and reverse transcription-quantitative polymerase chain reaction and western blot assays were used to investigate changes in the expression levels of cell cycle-associated genes and proteins. In the present study, treatment with Fan markedly inhibited the proliferation of SPC-A-1 lung cancer cells and significantly increased the percentage of cells in the G/G phase of the cell cycle in a dose-dependent manner (P<0.05 for 2.5-5 µm; P<0.01 for 10 µm), whereas the percentage of cells in the S and G/M phases were significantly reduced following treatment (P<0.05 for 5 µm; P<0.01 for 10 µm). Mechanistically, Fan significantly reduced the mRNA expression levels of cyclin D1, cyclin-dependent kinase 4 (CDK4) and CDK6 (P<0.05 for 2.5-5 µm; P<0.01 for 10 µm), which are key genes in the regulation of the G/G phase of the cell cycle. Furthermore, treatment with Fan also decreased the expression of phosphorylated retinoblastoma (Rb) and E2F transcription factor-1 (E2F-1) proteins (P<0.05 for 5 µm; P<0.01 for 10 µm). In summary, the present study demonstrated that Fan inhibited the proliferation of SPC-A-1 lung cancer cells and induced cell cycle arrest at the G/G phase. These effects may be mediated by the downregulation of cellular CDK4, CDK6 and cyclin D1 levels, thus leading to hypophosphorylation of Rb and subsequent suppression of E2F-1 activity. Therefore, the present results suggest that Fan may be a potential drug candidate for the prevention of lung cancer.

Titanium (Ti) and Ti‐based alloys are widely used in the manufacture of dental and orthopedic implants. However, how to improve their osteogenic differentiation ability is still a key issue to be resolved. In this study, gradient nanostructured surface (GNS) samples were prepared by surface mechanical grinding treatment, and coarse‐grained (CG) samples were obtained by recrystallization annealing, making sure that the two kinds of specimens had similar roughness. Then, human amniotic mesenchymal stem cells (hAMSCs) were cocultured with the two kinds of Ti to investigate the material effects on the cellular functions. The results demonstrated that the grains with size ~56 nm were formed on the surface of the GNS Ti, and the grain size gradually increases from the sample surface to interior. Compared to the CG samples, the GNS ones could make the adhesion effect of the hAMSCs better, and promote the cell proliferation and osteogenic differentiation more significantly, the preliminary mechanism of which might be due to their specific nanostructure, the thicker oxide layer formed on their surface and the enhanced hardness. Our results indicated that the gradient nanostructured Ti materials could enhance both osteogenic differentiation and mechanical properties, which may possess broader applications in bone tissue engineering and clinical implanting.

Exercise-induced autophagy is associated with physiological left ventricular hypertrophy (LVH), and a growing body of evidence suggests that microRNAs (miRNAs) can regulate autophagy-related genes. However, the precise role of miRNAs in exercise induced autophagy in physiological LVH has not been fully defined. In this study, we investigated the microRNA-autophagy axis in physiological LVH and deciphered the underlying mechanism using a rat swimming exercise model. Rats were assigned to sedentary control (CON) and swimming exercise (EX) groups; those in the latter group completed a 10-week swimming exercise without any load. For in vitro studies, H9C2 cardiomyocyte cell line was stimulated with IGF-1 for hypertrophy. We found a significant increase in autophagy activity in the hearts of rats with exercise-induced physiological hypertrophy, and miRNAs showed a high score in the pathway enriched in autophagy. Moreover, the expression levels of miR-26b-5p, miR-204-5p, and miR-497-3p showed an obvious increase in rat hearts. Adenovirus-mediated overexpression of miR-26b-5p, miR-204-5p, and miR-497-3p markedly attenuated IGF-1-induced hypertrophy in H9C2 cells by suppressing autophagy. Furthermore, attenuated autophagy in H9C2 cells through targeting ULK1, LC3B, and Beclin 1, respectively. Taken together, our results demonstrate that swimming exercise induced physiological LVH, at least in part, by modulating the microRNA-autophagy axis, and that miR-26b-5p, miR-204-5p, and miR-497-3p may help distinguish physiological and pathological LVH.

Low-grade fetal lung adenocarcinoma (L-FLAC) is an exceptionally rare pulmonary tumor, presenting with unclear histological and molecular features. In particular, the potential driver genes of L-FLAC remain elusive. To date, only five reports have documented genetic aberrations in L-FLAC. In the current study, we describe an unusual case of L-FLAC coexisting with adenocarcinoma in situ (AIS) of the lung, harboring different genetic mutations. A 39-year-old non-smoker female patient was referred to our hospital with the chief complaint of dyspnea for 20 days. Chest computed tomography (CT) revealed a-2.5×1.5×1.5 cm nodule in the right middle lobe, with no mediastinal lymph node enlargement or distant metastases. Thoracoscopic surgery was performed to remove the nodules. Histopathological analysis of the tissue sections, based on findings from immunohistochemical staining, confirmed a diagnosis of L-FLAC coexisting with AIS of the lung. Nextgeneration sequencing revealed L-FLAC-based mutations in DICER1 and CTNNB1, and AIS harboring KRAS mutations. Currently, the patient remains recurrence-free 17 months after the initial diagnosis. This report presents the first case demonstrating the coexistence of L-FLAC and AIS in the same pulmonary nodule, harboring different genetic mutations. Based on the literature review, this is the second reported case of L-FLAC bearing DICER1 mutations.

Nonpharmaceutical therapies such as exercise training and diet intervention are widely used for the treatment of insulin resistance (IR). Although the skeletal muscle is the major peripheral tissue of glucose metabolism under insulin stimulation, the mechanism underlying muscle IR is poorly understood. Using a high-fat diet-induced IR mouse model, we here show that NADPH oxidase 4 (Nox4) upregulation mediates the production of reactive oxygen species (ROS) that causes metabolic syndrome featuring IR. The Nox4 expression level was markedly elevated in IR mice, and Nox4 overexpression was sufficient to trigger IR. Conversely, downregulation of Nox4 expression through exercise training prevented diet-induced IR by reducing the production of ROS and enhancing the AKT signaling pathway. Thus, this study indicates that exercise might improve IR through a reduction of Nox4-induced ROS in the skeletal muscle and enhancement of AKT signal transduction.

Respiratory diseases, including pulmonary fibrosis, silicosis, and allergic pneumonia, can be caused by long-term exposure to dental prosthesis grinding dust. The extent of the toxicity and pathogenicity of exposure to PMMA dust, Vitallium dust, and dentin porcelain dust differs. The dust from grinding dental prosthesis made of these three materials was characterized in terms of morphology, particle size, and elemental composition. The adverse effects of different concentrations of grinding dust (50, 150, 300, 450, and 600 μg ml −l) on RAW264.7 macrophages were evaluated, including changes in cell morphology and the production of lactate dehydrogenase (LDH) and reactive oxygen species (ROS). The dust particles released by grinding dental prosthesis made of these materials had different morphologies, particle sizes, and elemental compositions. They also induced varying degrees of cytotoxicity in RAW264.7 macrophages. A possible cytotoxicity mechanism is the induction of lipid peroxidation and plasma membrane damage as the dust particles penetrate cells. Therefore, clinicians who regularly work with these materials should wear the appropriate personal protection equipment to minimize exposure and reduce the health risks caused by these particulates. Dental prostheses are made and tested, a variety of dust particles are emitted from the grinding performed to correct defects 1-4. Commonly used prosthetic materials include PMMA, Vitallium, and porcelain, and the dust created from grinding them may pose various health hazards to oral care workers, such as pulmonary fibrosis, silicosis, allergic pneumonia, lung granuloma, asthma, and lung cancer 5-8. Epidemiological investigations indicated that the effects of dental prosthesis grinding dust on the respiratory system of oral care workers may be correlated with dust exposure time and the type of dust. In addition, many studies have reported that the type of abrasive dust is closely related to specific respiratory diseases of oral care workers 9-13. Zhang et al. reported that animals were subjected to mixed dust types generated from grinding dental prostheses (PMMA, Vitallium and porcelain dust, etc.), and then, the histopathology of their lung tissue was examined. It was proposed that grinding dust induced fibrosis in rat lung tissue 14. Upadhyay et al. found that rats exposed to three different quality levels of fine dust (including 250, 500 and 1,000 μg ml −l) presented with increases in the total number of inflammatory cells and levels of interleukin-6 15. RAW264.7 cells are mouse mononuclear macrophage leukaemia cells that play key roles in inflammation, immunity and phagocytosis. They are readily available and their use raises fewer ethical issues than using human macrophages. The macrophage pneumoconiosis model is a currently established model 16. Various particles produce similar results. When calcium carbonate, silica dust, etc., are applied to cells, reactive oxygen species (ROS) and lactate dehydrogenase (LDH) are commonly measured as indicators of cytotoxicity...

Titanium (Ti) is widely used in oral implants. However, there is still a challenge to promote the osseointegration of bone tissue on the surface of Ti. To solve this problem, we prepared novel gradient nanostructured (GNS) Ti and studied the effect of GNS on the adhesion, proliferation, and apoptosis of MG63 cells in vitro. The results demonstrated that the GNS Ti promoted the adhesion effect and proliferation of MG63 cells better than the annealed Ti, while the ability of GNS Ti to inhibit cell apoptosis was better than that of the annealed Ti, the preliminary mechanism of which indicated by this study might be the enhanced mineralization capacity, protein adsorption ability, and hydrophilicity of the GNS Ti due to its specific nanostructure which improved the cell behaviours. The results in this study provide the theoretical and experimental foundations for the applications of GNS Ti in dental implants and joint replacements.

Background: Seizure-related 6 homolog (mouse)-like 2 (SEZ6L2) is a type 1 transmembrane protein that is primarily expressed in the brain . In recent reports, SEZ6L2 has been found to be overexpressed in some cancers and can drive the progression of tumors. However, its function and mechanism in thyroid cancer remain unclear. Methods:In this article ,we searched for the SEZ6L2 expressions in Pan-cancer on TCGA (The Cancer Genome Atlas) and evaluated these data using the TIMER2 method. Then, the immunohistochemical score (IHC score) of SEZ6L2 in cancer tissue was collected in human protein mapping (HPA) data. And we used CIBERSORT to assess the association between the levels of SEZ6L2 expression and the number of various immune cells in papillary thyroid carcinoma (PTC) tissue. Finally, Gene Expression Omnibus (GEO) analyses, real-time quantitative polymerase chain reaction (qRT-PCR) of tissues, and immunohistochemical staining were used to detect the result. Results:The article illustrated that a large number of cancers had a higher expression of SEZ6L2 compared to the control tissues. And the immunohistochemical score (IHC score) of SEZ6L2 in cancer tissue was considerably elevated compared to that in normal tissues SEZ6L2 was elevated in thyroid carcinoma (THCA) tissue, besides, GEO analyses, qRT-PCR of tissues, and immunohistochemical staining were conducted to test the results. Finally, the Kaplan-Meier survival analysis illustrated that the increased expression of SEZ6L2 was correlated with a dismal prognosis-higher SEZ6L2 is associated with shorter survival. And the univariate analysis illustrated that T stage, SEZ6L2 and Pathologic stage were related to the overall survival (OS), multivariate analysis stated that elevated expression of SEZ6L2 was an independent risk factor that affected progression-free interval (PFI) (P<0.05). Consequently, we found that the expression of SEZ6L2 was correlated with tumor-infiltrating immune cells by TIMER.Conclusions: SEZ6L2 was upregulated in patients with THCA and that increased expression of SEZ6L2 was related with clinical progression and was regarded as an independent risk factor for PFI. In THCA patients, the expression of SEZ6L2 could be a significant prognostic factor, which is expected to be a prospective biomarker for THCA in the future.