Multiple pulmonary cavernous haemangiomas with concurrent primary pulmonary adenocarcinoma: a case report and literature review.

Background: Cavernous haemangiomas (CHs) commonly occurred in the skin, subcutaneous tissue, muscles, and liver. Pulmonary cavernous haemangiomas (PCHs) are quite rare and usually present with nonspecific clinical symptoms. When lung cancer patients are complicated with pulmonary cavernous haemangiomas, radiologically, these haemangioma lesions can be easily misinterpreted as intrapulmonary metastases, potentially resulting in misdiagnosis, or missed diagnosis. Case presentation: The present study reported the case of a 53-year-old female patient with pulmonary adenocarcinoma coexisting with multiple PCHs. 18F-FDG-Positron emission tomography-computed tomography (PET-CT) showed an elevated glucose metabolism in the apicoposterior segment of the left upper lobe; however, the other nodules were not hypermetabolic. Percutaneous lung biopsy was performed on the nodule in the apicoposterior segment of the left upper lobe, which were diagnosed as primary adenocarcinoma. Some nodules in the upper left lobe underwent wedge resection by video-assisted thoracic surgery (VATS) and intraoperative frozen section identified as PCHs. Finally, the patient underwent lobectomy of the left upper lobe via VATS, cancerous nodule in the apicoposterior segment of the left upper lobe underwent genetic molecular testing of PCR-Sanger sequencing, suggested EGFR mutation, and patient received treatment with Osimertinib. During the 4-months follow-up, contrast-enhanced CT showed no recurrence of either disease. PCHs are rare benign tumours of the lung, which can lead to misdiagnosis due to their non-specific clinical symptoms and radiological features, especially when they coexist with lung cancer. PCHs is easily misunderstood as metastatic lung cancer, in this case, PET-CT can assist in differentiating benign from malignant. For the cases of early lung cancer complicated with PCHs, lung cancer can be surgically resected, and whether PCHs should be removed or not should be determined according to the size and distribution of the lesions.

[Research progress on development and utilization of minor ginsenosides].

Minor ginsenosides are a class of processed saponins with minor natural content, high bioavailability, and outstanding bio-logical activity, which are usually obtained by biological or chemical transformation of prototype saponins directly extracted from Panax plants. In recent years, with the clarification of the biosynthetic pathway of saponins and the development of synthetic biology, it has become possible to use synthetic metabolic engineering methods with microorganisms as hosts to produce saponins. Minor ginsenosides have received widespread attention because of their remarkable biological activities in enhancing the immune function of the body and antitumor property. At present, most of the reviews on minor ginsenosides focus on transformation preparation, process optimization, and pharmacological activity, but there are some deficiencies in industrial analysis. This study summarized structural types, pharmacological activities, sources of acquisition, and transformation pathways of minor ginsenosides based on the relevant literature in China and abroad, proposed problems in the preparation of existing minor ginsenosides, and discussed the future research and utilization prospects, to provide a theoretical basis for improving the basic research of minor ginsenosides and promoting their industrialization.

Overexpression of MTFR1 promotes cancer progression and drug-resistance on cisplatin and is related to the immune microenvironment in lung adenocarcinoma.

OBJECTIVE: The roles of MTFR1 in the drug resistance of lung adenocarcinoma (LAC) to cisplatin remain unexplored. In this study, the expression, clinical values and mechanisms of MTFR1 were explored, and the relationship between MTFR1 expression and immune microenvironment was investigated in LAC using bioinformatics analysis, cell experiments, and meta-analysis. METHODS: MTFR1 expression and clinical values, and the relationship between MTFR1 expression and immunity were explored, through bioinformatics analysis. The effects of MTFR1 on the growth, migration and cisplatin sensitivity of LAC cells were identified using cell counting kit-8, wound healing and Transwell experiments. Additionally, the mechanisms of drug resistance of LAC cells involving MTFR1 were investigated using western blotting. RESULTS: MTFR1 was elevated in LAC tissues. MTFR1 overexpression was associated with sex, age, primary therapy outcome, smoking, T stage, unfavourable prognosis and diagnostic value and considered an independent risk factor for an unfavourable prognosis in patients with LAC. MTFR1 co-expressed genes involved in the cell cycle, oocyte meiosis, DNA replication and others. Moreover, interfering with MTFR1 expression inhibited the proliferation, migration and invasion of A549 and A549/DDP cells and promoted cell sensitivity to cisplatin, which was related to the inhibition of p-AKT, p-P38 and p-ERK protein expression. MTFR1 overexpression was associated with stromal, immune and estimate scores along with natural killer cells, pDC, iDC and others in LAC. CONCLUSIONS: MTFR1 overexpression was related to the unfavourable prognosis, diagnostic value and immunity in LAC. MTFR1 also participated in cell growth and migration and promoted the drug resistance of LAC cells to cisplatin via the p-AKT and p-ERK/P38 signalling pathways.

Decreased APOC1 expression inhibited cancer progression and was associated with better prognosis and immune microenvironment in esophageal cancer.

Several studies have demonstrated the involvement of apolipoprotein C1 (APOC1) in multiple cancers. However, the role of APOC1 in esophageal cancer (ESCA) has not been elucidated. Hence, we examined the expression of APOC1 in ESCA tissues acquired from The Cancer Genome Atlas (TCGA) database and clinical samples from our hospital. An investigation of the association of APOC1 with the clinicopathological characteristics, prognosis, and diagnosis of ESCA was carried out on the basis of survival, receiver operating characteristics, and correlation analyses. Gene ontology, KEGG analysis, and protein-protein interaction network showed that co-expressed APOC1 genes were involved in the functions, mechanisms, and action network. The effects of APOC1 expression on ESCA cells were explored using CCK-8, migration and invasion assays. The relationship between APOC1 expression and ESCA immune-infiltrating cells and cell markers were examined using correlation analysis. We found that APOC1 was overexpressed in TCGA ESCA tissues and the same was validated in clinical ESCA tissues, with the area under the curve for APOC1 being 0.887. Overexpression of APOC1 was associated with short overall survival, disease-specific survival, progression-free interval, T stage, pathological stage, body mass index, and histological grade. Inhibition of APOC1 expression significantly reduced the proliferation, migration, and invasion of ESCA cells. Furthermore, APOC1 expression positively correlated with the ESTIMATE, immune, and stromal scores in ESCA. Overexpression of APOC1 correlated with the tumor purity, B cells, T helper cells, natural killer cells, cytotoxic cells, and other immune cells. Moreover, APOC1 was involved in ESCA progression via T cell receptor, B cell receptor, and other immune signaling pathways. Thus, APOC1 overexpression is expected to be a biomarker for dismal prognosis and diagnosis of ESCA. Inhibition of APOC1 expression significantly reduced the proliferation, migration, and invasion of ESCA cells. Overexpression of APOC1 was associated with the immune microenvironment in ESCA. Thus, APOC1 may be an efficient biomarker for proper prognosis and diagnosis of ESCA.

After the blades: The late MIS3 flake-based technology at Shuidonggou Locality 2, North China.

Contrasting with the predominance of blade-based assemblages in the Eurasian Upper Paleolithic, the large-scale persistence of a core-and-flake technology remains one of the defining features of Late Pleistocene lithic technology in East Asia. In North China, Shuidonggou is an exceptional site where both technologies are documented, therefore, it is an important archaeological sequence to understand regional technological evolution during the Marine Isotopic Stage 3. Blade technology first occurred at Shuidonggou Locality 1 and 2 around 41 ka cal BP while core-and-flake assemblages were widespread in North China. However, systematic technological studies on assemblages postdating 34 ka cal BP have not been conducted to examine whether the blade technology appeared and disappeared over a short yet abrupt episode, or persists and integrates into other forms in the region. Here, we conducted qualitative and quantitative analyses to reconstruct lithic productions on the assemblages at Shuidonggou Locality 2, dated after 34 ka cal BP. Our results show that there is a total absence of laminar elements in stone artifacts dated to 34-28 ka cal BP at Shuidonggou. Instead, we observe a dominance of an expedient production of flakes in the younger assemblages, illustrating a rapid return to flake-based technology after a relatively brief episode of stone blade production. Combining archaeological, environmental, and genetic evidence, we suggest that this technological 'reversal' from blades back to core and flake technology reflect population dynamics and adaptive strategies at an ecological interface between East Asian winter and summer monsoon.

Neural network training method for materials science based on multi-source databases.

The fourth paradigm of science has achieved great success in material discovery and it highlights the sharing and interoperability of data. However, most material data are scattered among various research institutions, and a big data transmission will consume significant bandwidth and tremendous time. At the meanwhile, some data owners prefer to protect the data and keep their initiative in the cooperation. This dilemma gradually leads to the "data island" problem, especially in material science. To attack the problem and make full use of the material data, we propose a new strategy of neural network training based on multi-source databases. In the whole training process, only model parameters are exchanged and no any external access or connection to the local databases. We demonstrate its validity by training a model characterizing material structure and its corresponding formation energy, based on two and four local databases, respectively. The results show that the obtained model accuracy trained by this method is almost the same to that obtained from a single database combining all the local ones. Moreover, different communication frequencies between the client and server are also studied to improve the model training efficiency, and an optimal frequency is recommended.

The Risk Model Based on the Three Oxidative Stress-Related Genes Evaluates the Prognosis of LAC Patients.

Background: Oxidative stress plays a role in carcinogenesis. This study explores the roles of oxidative stress-related genes (OSRGs) in lung adenocarcinoma (LAC). Besides, we construct a risk score model of OSRGs that evaluates the prognosis of LAC patients. Methods: OSRGs were downloaded from the Gene Set Enrichment Analysis (GSEA) website. The expression levels of OSRGs were confirmed in LAC tissues of the TCGA database. GO and KEGG analyses were used to evaluate the roles and mechanisms of oxidative stress-related differentially expressed genes (DEGs). Survival, ROC, Cox analysis, and AIC method were used to screen the prognostic DEGs in LAC patients. Subsequently, we constructed a risk score model of OSRGs and a nomogram. Further, this work investigated the values of the risk score model in LAC progression and the relationship between the risk score model and immune infiltration. Results: We discovered 163 oxidative stress-related DEGs in LAC, involving cellular response to oxidative stress and reactive oxygen species. Besides, the areas under the curve of CCNA2, CDC25C, ERO1A, CDK1, PLK1, ITGB4, and GJB2 were 0.970, 0.984, 0.984, 0.945, 0.984, 0.771, and 0.959, respectively. This indicates that these OSRGs have diagnosis values of LAC and are significantly related to the overall survival of LAC patients. ERO1A, CDC25C, and ITGB4 overexpressions were independent risk factors for the poor prognosis of LAC patients and were associated with risk scores in the risk model. High-risk score levels affected the poor prognosis of LAC patients. Notably, a high-risk score may be implicated in LAC progression via cell cycle, DNA replication, mismatch repair, and other mechanisms. Further, ERO1A, CDC25C, and ITGB4 expression levels were related to the immune infiltrating cells of LAC, including mast cells, NK cells, and CD8 T cells. Conclusion: In summary, ERO1A, CDC25C, and ITGB4 of OSRGs are associated with poor prognosis of LAC patients. We confirmed that the risk model based on the ERO1A, CDC25C, and ITGB4 is expected to assess the prognosis of LAC patients.

SPDL1 Overexpression Is Associated With the 18F-FDG PET/CT Metabolic Parameters, Prognosis, and Progression of Esophageal Cancer.

Esophageal cancer (ESCA) is one of the common malignant tumors. The roles and signaling mechanisms of spindle apparatus coiled-coil protein 1 (SPDL1) in ESCA progression have not been reported previously. Therefore, the expression levels and potential clinical roles of SPDL1 were investigated using data from multiple databases and tissue samples of 53 ESCA patients who underwent 18F-FDG positron emission tomography (PET)/computed tomography (CT) before therapy. The signaling mechanisms of SPDL1 involved in ESCA progression were investigated via bioinformatics analysis. The effects of SPDL1 on the growth and migration of ESCA cells were investigated using CCK-8, Edu, and transwell assays. SPDL1 was upregulated in ESCA tissues. Increased SPDL1 expression was associated with age, grade, drinking history, cancer stage, lymph node metastasis, TP53 mutation, and poor prognosis in patients with ESCA. SPDL1 overexpression was significantly correlated with SUVmax, SUVmean, and TLG of PET/CT. SPDL1 silencing inhibited cell proliferation, migration, and invasion. SPDL1 was significantly enriched in cell cycle, spliceosome, DNA replication, and other processes. The hub genes of a constructed protein-protein interaction network included CDK1, BUB1, CCNB1, BUB1B, CCNA2, CDC20, MAD2L1, AURKB, NDC80, and PLK1, which were related to SPDL1 expression. The findings of this study suggest that SPDL1 may serve as a biomarker of ESCA prognosis.

NLRP12 reduces proliferation and inflammation of rheumatoid arthritis fibroblast-like synoviocytes by regulating the NF-κB and MAPK pathways.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by abnormal synovial hyperplasia and the release of inflammatory cytokines. NLRP12 is a member of the family nod-like receptor (NLR) families that are activators of inflammation. However, the role of NLRP12 in fibroblast-like synoviocytes (FLSs) is still unclear. In the present study, we have investigated the role of NLRP12 in fibroblast-like synoviocytes (FLSs). The results demonstrated that NLRP12 overexpression inhibited proliferation and promoted cell apoptosis in RA-FLSs. Moreover, NLRP12 overexpression repressed inflammation by downregulation of IL-1ß, TNF-α, IL-6, IFN-γ and MCP-1 production and upregulation of IL-10 levels with knockdown of NLRP12 expression showing opposite effects. In addition, NLRP12 overexpression suppressed phosphorylation of JNK, ERK, p38 and NF-κB in RA-FLSs, whereas NLRP12 knockdown promoted phosphorylation of these proteins. In conclusion, these findings demonstrate that NLRP12 inhibits proliferation and inflammation of RA-FLSs via the regulation of the NF-κB and MAPK signaling pathways, suggesting that NLRP12 might be a potential target for RA treatment.

Evaluation of the roles and regulatory mechanisms of PD-1 target molecules in NSCLC progression.

BACKGROUND: Targeted programmed cell death protein 1 (PD-1) therapy could effectively improve the long-term prognosis of patients with non-small cell lung cancer (NSCLC). The role of PD-1 targets in the progression of NSCLC has not been fully revealed. METHODS: The differentially expressed genes (DEGs) in patients' blood after NSCLC treatment with PD-1 blocker nivolumab in the GSE141479 dataset were analyzed by GEO2R and identified in the TCGA database. The mechanism of action involved in the PD-1 target molecules via the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The protein-protein interaction (PPI) network shows the relationship between PD-1 target molecules. The factors affecting the prognosis of NSCLC patients were identified via the COX regression analysis and survival analysis to build the risk model and nomogram. RESULTS: There were 64 DEGs in patients' blood after nivolumab treatment and 48 DEGs in NSCLC tissues. The PD-1 target molecules involved cell proliferation, DNA replication, cell cycle, lung cancer, and other cellular processes. The prognostic factors CCNA2, CHEK1, DLGAP5, E2F8, FOXM1, HIST1H2BH, HJURP, MKI67, PLK1, TPX2, and TYMS, and the independent factors HIST1H2BH and PLK1, influenced the prognosis of NSCLC patients. HIST1H2BH and PLK1 were overexpressed in LUAD and LUSC tissues. The elevated expression levels of HIST1H2BH and PLK1 were related to the overall survival (OS) and the progression-free survival of NSCLC patients. High-risk NSCLC patients had a poor prognosis and were an independent factor influencing the poor prognosis of NSCLC patients. The high-risk model group was enriched with signaling mechanisms such as cell cycle, DNA replication, and homologous recombination. CONCLUSIONS: The risk model based on PD-1 target molecules was helpful to assess the prognosis of NSCLC patients. HIST1H2BH and PLK1 might become prognostic biomarkers of NSCLC patients.

[Retracted] miR­152 inhibits rheumatoid arthritis synovial fibroblast proliferation and induces apoptosis by targeting ADAM10.

Following the publication of this paper, the authors alerted the Editorial Office to the fact that a reader had informed them that miR­152 overexpression did not affect cell apoptosis and cell cycle. The authors subsequently confirmed that they were unable to obtain consistent results from these experiments.Furthermore, an independent investigation of this paper revealed that the cell apoptotic data shown in Fig. 2D were strikingly similar to those that had appeared in an article published previously with different authors, although one of the institutions was held in common. The authors have requested that the above article be retracted from the publication, and the Editor agrees with this course of action. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 42: 643­650, 2018; DOI: 10.3892/ijmm.2018.3636].

Upregulated expression of MTFR2 as a novel biomarker predicts poor prognosis in hepatocellular carcinoma by bioinformatics analysis.

Aim: The authors investigated the clinical role of MTFR2 in hepatocellular carcinoma (HCC) progression. Results: MTFR2 expression and methylation were abnormal in HCC tissues, and HCC patients with increased MTFR2 expression or methylation had poor or better overall survival, respectively. In addition, increased MTFR2 expression was correlated with age, grade, cancer stage and T stage. MTFR2 was an independent predictor of dismal prognosis in HCC patients. MTFR2 was involved in HCC progression by modulating the cell cycle, homologous recombination, DNA replication, p53 signaling pathway, etc. The ten hub genes were overexpressed in HCC tissues and were linked to cancer stage and dismal prognosis in HCC patients. Conclusion: MTFR2 could be a prospective biomarker of poor prognosis in individuals with HCC.

Lay abstract In this study, MTFR2 expression and methylation were found to be abnormal in hepatocellular carcinoma (HCC) tissues. HCC patients with increased MTFR2 expression or methylation had poor or better overall survival, respectively, via Kaplan­Meier survival analysis. Elevated expression of MTFR2 was linked to the age, grade, cancer stage and T stage of HCC patients. The results of Cox regression revealed MTFR2 to be an independent predictor of dismal prognosis in HCC patients. The authors found that MTFR2 was involved in HCC progression by modulating the cell cycle, p53 signaling pathway, DNA replication, etc. High expression of CDK1, AURKB, CDC20, BUB1B, CCNB1, PLK1, CCNB2, CCNA2, BUB1 and CDCA8 was associated with unfavorable stage and prognosis in individuals with HCC.

Prognostic Nomogram for Postoperative Patients With Gastroesophageal Junction Cancer of No Distant Metastasis.

BACKGROUND: Gastroesophageal junction (GEJ) was one of the most common malignant tumors. However, the value of clinicopathological features in predicting the prognosis of postoperative patients with GEJ cancer and without distant metastasis was still unclear. METHODS: The 3425 GEJ patients diagnosed and underwent surgical resection without distant metastasis in the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2015 were enrolled,and they were randomly divided into training and validation cohorts with 7:3 ratio. Univariate and multivariate Cox regression analysis were used to determine the predictive factors that constituted the nomogram. The predictive accuracy and discriminability of Nomogram were determined by the area under the curve (AUC), C index, and calibration curve, and the influence of various factors on prognosis was explored. RESULTS: 2,400 patients were designed as training cohort and 1025 patients were designed as validation cohort. The percentages of the distribution of demographic and clinicopathological characteristics in the training and validation cohorts tended to be the same. In the training cohort, multivariate Cox regression analysis revealed that the age, tumor grade, T stage and N stage were independent prognostic risk factors for patients with GEJ cancer without distant metastasis. The C index of nomogram model was 0.667. The AUC of the receiver operating characteristic (ROC) analysis for 3- and 5-year overall survival (OS) were 0.704 and 0.71, respectively. The calibration curve of 3- and 5-year OS after operation showed that there was the best consistency between nomogram prediction and actual observation. In the validation cohort, the C index of nomogram model, the AUC of 3- and 5-year OS, and the calibration curve were similar to the training cohort. CONCLUSIONS: Nomogram could evaluate the prognosis of patients with GEJ cancer who underwent surgical resection without distant metastasis.

KDM4B Overexpression Promotes the Growth, Migration, and Invasion of Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Activating STAT3 Pathway.

In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) present a unique aggressive phenotype and have a passive response to the inflammatory microenvironment, which are critical for the disease's progression. KDM4B, as a histone demethylase, functions as an oncogenic factor in many cancers and is implicated in osteoclastogenesis as well as pro-inflammatory cytokine release in inflammatory diseases. However, the effects of KDM4B on RA FLS have not been reported. To investigate this issue, our study determined the expression of KDM4B in RA FLS using RT-qPCR and western blot. The effects of KDM4B on RA FLS viability, apoptosis, migration, and invasion were detected by MTT, flow cytometry, transwell migration, and invasion assays. Furthermore, the interaction of KDM4B with STAT3 signaling was studied by western blot, MTT, flow cytometry, transwell migration, and invasion assays. The experimental results showed that KDM4B expression was upregulated in RA synovial tissues and FLS as compared to healthy control tissues and normal FLS. Knockdown of KDM4B obviously suppressed RA FLS viability, migration and invasion, and induced apoptosis. In addition, knockdown of KDM4B in RA FLS decreased the expression of p-STAT3 and MMP-9 but increased cleaved caspase-3 expression compared with the control group. Moreover, KDM4B overexpression could promote cell growth, migration and invasion, and suppress apoptosis in RA FLS by activating STAT3 signaling. Therefore, these findings provide new insight for understanding the pathogenesis of RA and indicate that KDM4B may have a potential to be an effective therapeutic target for RA.

The roles of risk model based on the 3-XRCC genes in lung adenocarcinoma progression.

BACKGROUND: The abnormal expression of deoxyribonucleic acid (DNA) repair genes might be the cause of tumor development and resistance of malignant cells to chemotherapeutic drugs. A risk model based on the X-ray repair of cross-complementary (XRCC) genes was constructed to improve the diagnosis and treatment of lung adenocarcinoma (LUAD) patients. METHODS: The expression levels, diagnostic values, and prognostic values of XRCC genes were identified, and the roles and regulatory mechanisms of the risk model based on the XRCC4/5/6 in LUAD progression was explored via The Cancer Genome Atlas (TCGA) and Oncomine databases. RESULTS: XRCC1/2/3/4/5/6, XRCC7 (PRKDC), and XRCC9 (FANCG) were overexpressed, and had diagnostic value for LUAD. The XRCC genes were involved in DNA repair, and participated in the regulation of non-homologous end-joining, homologous recombination, etc. The overall survival (OS), tumor (T) stage, and survival status of patients were significantly different between the Cluster1 and Cluster2 groups. XRCC4/5/6 were independent risk factors affecting the prognosis of LUAD patients. The risk score was related to the prognosis, sex, clinical stage, T, lymph node (N), and metastasis (M) stage, as well as the survival status of LUAD patients. The clinical stage and risk score were independent risk factors for poor prognosis in LUAD patients. The risk model was involved in RNA degradation, cell cycle, basal transcription factors, DNA replication etc. The risk scores were significantly correlated with the expression levels of TGFBR1, CD160, TNFSF4, TNFRSF14, IL6R, CXCL16, TNFRSF25, TAPBP, CCL16, and CCL14. CONCLUSIONS: The risk model based on the XRCC4/5/6 genes could predict the progression of LUAD patients.

Role of the NLRP3 inflammasome in autoimmune diseases.

NOD-like receptor family pyrin domain containing 3 (NLRP3) is an intracellular receptor that senses foreign pathogens and endogenous danger signals. It assembles with apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 to form a multimeric protein called the NLRP3 inflammasome. Among its various functions, the NLRP3 inflammasome can induce the release of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-18 while also promoting gasdermin D (GSDMD)-mediated pyroptosis. Previous studies have established a vital role for the NLRP3 inflammasome in innate and adaptive immune system as well as its contribution to several autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), systemic sclerosis (SSc), and ankylosing spondylitis (AS). In this review, we briefly introduce the biological features of the NLRP3 inflammasome and present the mechanisms underlying its activation and regulation. We also summarize recent studies that have reported on the roles of NLRP3 inflammasome in the immune system and several autoimmune diseases, with a focus on therapeutic and clinical applications.

Periplocin induces apoptosis and inhibits inflammation in rheumatoid arthritis fibroblast-like synoviocytes via nuclear factor kappa B pathway.

Apoptotic resistance and excessive proliferation of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) stimulated by inflammation could lead to distal joint destruction and bone damage. Periplocin could promote apoptosis, resist proliferation, and reduce inflammation. However, the effect and mechanism toward periplocin in proliferation and inflammation of RA-FLSs remain unclear. The role of tumor necrosis factor (TNF)-α induced proliferation and expression of inflammatory cytokines in RA-FLSs was established. Our studies noted that cell viability of TNF-α-induced RA-FLSs was inhibited in periplocin treatment via dose-response, whereas cell apoptosis of RA-FLSs was triggered by dose-dependent effect of periplocin. Bcl-2 protein, one of the apoptotic regulators, was downregulated, while other regulators of apoptosis, including BAX, cleaved caspase-3, and cleaved caspase-9, were upregulated in RA-FLSs under periplocin treatment. In addition, periplocin decreased the TNF-α-induced mRNA and protein expression levels of interleukin (IL)-1ß and IL-6 in RA-FLSs in a dose-dependent way. Finally, the increased levels of phospho (p)-inhibitor of kappa B (IκBα)/IκBα and p-NF (nuclear factor)-κB/nuclear factor kappa B (NF-κB) ratio of RA-FLSs stimulated by TNF-α were decreased by periplocin treatment. Taken together, periplocin treatment decreased cell viability and cytokines expression and promoted cell apoptosis of TNF-α-induced RA-FLSs through inhibition of NF-κB signaling pathway, providing a potential therapeutic approach for RA.

Inhibiting role of long non-coding RNA LINC01197 in inflammation in rheumatoid arthritis through the microRNA-150/THBS2 axis.

PURPOSE: Rheumatoid arthritis (RA) is a commonly diagnosed systemic autoimmune disease. Aberrant expression of long non-coding RNAs (lncRNAs) is closely linked to the development of RA. This study was conducted to explore the functions of the lncRNA LINC01197 in RA progression. METHODS: Differentially expressed lncRNAs/microRNAs/mRNAs in patients with RA were analyzed using RNA microarrays. A mouse model with RA was established and RA-fibroblast-like synoviocytes (RA-FLS) were acquired for in vitro experiments. The function of LINC01197 in inflammation and RA progression in mice and its role in the viability of RA-FLS were determined by experiments involving its overexpression or suppression. The sub-cellular localization of LINC01197 was determined and the downstream molecules involved in LINC01197-mediated events were identified. RESULTS: LINC01197 was poorly expressed in the synovial tissues in the RA model mice. Overexpression of LINC01197 reduced RA severity in mice and inhibited proliferation and inflammatory responses as well as promoted apoptosis in RA-FLS. Online predictions and dual luciferase reporter gene assays suggested that LINC01197 could bind to miR-150 and further regulate THBS2 expression. LINC01197 promoted THBS2 expression through miR-150 sponging and inactivated the TLR4/NF-κB signaling pathway, thus alleviating RA inflammation. CONCLUSION: The current study suggested that LINC01197 sponged miR-150 to promote THBS2 expression, leading to TLR4/NF-κB inactivation, and ameliorated RA inflammation. These findings may offer new insights into RA treatment.

A chronological model for the Late Paleolithic at Shuidonggou Locality 2, North China.

The site of Shuidonggou Locality 2 offers important evidence for the Late Paleolithic sequence of north China. The site not only contains one of the earliest instances of ornamental freshwater shell and ostrich eggshell beads in the region, but also stone artifacts with features arguably resembling the Initial Upper Paleolithic (IUP) blade technology found farther north. The appearance of these innovative archaeological forms have been attributed to the arrival of hominin populations, possibly modern humans, into the region during Marine Isotope Stage 3. Yet, the chronology of the site remains debated due to ambiguities in the existing dates. In this study, we conduct a systematical radiocarbon analysis of charcoal and ostrich eggshell samples obtained throughout the site sequence. Both acid-base-acid and the more stringent acid-base-oxidation pretreatment methods were applied to the charcoal samples. The resulting ages follow an age-depth relationship that is consistent with the stratigraphic profile. In line with previous stratigraphic assessments, Bayesian age modeling suggests that site formation history can be split into two phases: an early phase 43-35 cal kBP associated with a lacustrine depositional environment, and a later phase 35-28 cal kBP associated with rapid terrestrial silt accumulation. The chronology of the archaeological layers containing IUP-like artifacts are placed at 43-39 cal kBP and 35-34 cal kBP respectively. This finding supports the interpretation that an IUP-like blade technology appeared in the SDG region by at least ~41 ka.