IFIT1 + neutrophil is a causative factor of immunosuppressive features of poorly cohesive carcinoma (PCC).

The importance of the immune microenvironment in poorly cohesive carcinoma (PCC) has been highlighted due to its limited response rate to conventional therapy and emerging treatment resistance. A combination of clinical cohorts, bioinformatics analyses, and functional/molecular experiments revealed that high infiltration of Interferon Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) + tumor-associated neutrophils (TANs) is a distinguishing feature of PCC patients. Upregulation of IFIT1 + TANs promote migration and invasion of gastric cancer (GC) cell lines (MKN45 and MKN74) and stimulates the growth of cell-derived xenograft models. Besides, by promoting macrophage secreted phosphoprotein 1 (SPP1) expression and facilitating cancer-associated fibroblast and endothelial cell recruitment and activation through TANs, IFIT1 promotes a mesenchymal phenotype, which is associated with a poor prognosis. Importantly, compared to non-PCC (NPCC), PCC tumors is more immunosuppressive. Mechanistically, IFIT1 can be stimulated by IFN-γ and contributes to the expression of Programmed Cell Death 1 Ligand (PDL1) in TANs. We demonstrated in mouse models that IFIT1 + PDL1 + TANs can induce acquired resistance to anti-PD-1 immunotherapy, which may be responsible for the difficulty of PCC patients to benefit from immunotherapy. This work highlights the role of IFIT1 + TANs in mediating the remodeling of the tumor immune microenvironment and immunotherapeutic resistance and introduces IFIT1 + TANs as a promising target for precision therapy of PCC.

Spatiotemporal heterogeneity of LMOD1 expression summarizes two modes of cell communication in colorectal cancer.

Cellular communication (CC) influences tumor development by mediating intercellular junctions between cells. However, the role and underlying mechanisms of CC in malignant transformation remain unknown. Here, we investigated the spatiotemporal heterogeneity of CC molecular expression during malignant transformation. It was found that although both tight junctions (TJs) and gap junctions (GJs) were involved in maintaining the tumor microenvironment (TME), they exhibited opposite characteristics. Mechanistically, for epithelial cells (parenchymal component), the expression of TJ molecules consistently decreased during normal-cancer transformation and is a potential oncogenic factor. For fibroblasts (mesenchymal component), the expression of GJs consistently increased during normal-cancer transformation and is a potential oncogenic factor. In addition, the molecular profiles of TJs and GJs were used to stratify colorectal cancer (CRC) patients, where subtypes characterized by high GJ levels and low TJ levels exhibited enhanced mesenchymal signals. Importantly, we propose that leiomodin 1 (LMOD1) is biphasic, with features of both TJs and GJs. LMOD1 not only promotes the activation of cancer-associated fibroblasts (CAFs) but also inhibits the Epithelial-mesenchymal transition (EMT) program in cancer cells. In conclusion, these findings demonstrate the molecular heterogeneity of CC and provide new insights into further understanding of TME heterogeneity.

USP51/ZEB1/ACTA2 axis promotes mesenchymal phenotype in gastric cancer and is associated with low cohesion characteristics.

poorly cohesive (PC) gastric cancer (GC) (PC-GC) is a distinct histological subtype of GC and is defined as a tumor consisting of isolated or small clusters of tumor cells with poorly differentiated and metastatic characteristics. According to multiple studies, PC-GC is intrinsically heterogeneous, with mesenchymal variants being the most aggressive. However, to date, the molecular mechanisms associated with PC-GC are still not fully understood. This study investigated the role of the USP51/ZEB1/ACTA2 axis in promoting GC metastasis. Single-cell sequencing revealed that E-box binding homeobox 1 (ZEB1) expression was significantly increased in a subpopulation of low-adherent cells and was an independent prognostic factor in GC patients. Furthermore, the bulk transcriptome analysis revealed a significant positive correlation between Ubiquitin Specific Peptidase 51 (USP51), ZEB1, and Actin Alpha 2 (ACTA2), and our data further confirmed that all three were highly co-localized in PC-GC tissues. According to the findings of in vitro and in vivo experiments, USP51 was able to maintain ZEB1 expression to promote ACTA2 transcription, thereby activating the mesenchymal phenotype of GC cells and promoting tumor metastasis. Moreover, USP51 could recruit and activate stromal cells, including M2-like macrophages and fibroblasts, through cancer cells. Clinical data suggested that overexpression of USP51 predicts that patients have difficulty benefiting from immunotherapy and is associated with immune-exclusion tumor characteristics. Collectively, the findings of this study shed light on a key mechanism by which elevated USP51 expression induces Epithelial-mesenchymal transition (EMT) in GC cells, hence facilitating GC cell proliferation, survival, and dissemination. In this view, USP51/ZEB1/ACTA2 may serve as a candidate therapeutic target against GC metastasis.

Lens epithelium cell ferroptosis mediated by m6A-lncRNA and GPX4 expression in lens tissue of age-related cataract.

BACKGROUND: In the present study, we explored the role of N6-methyladenosine (m6A) modification of long non-coding RNAs (lncRNAs) and its association with ferroptosis in lens epithelium cells (LECs) of age-related cataract (ARC). METHODS: Through m6A RNA immunoprecipitation sequencing (m6A-RIP-seq) and RNA sequencing (RNA-seq), we identified m6A mediated and differentially expressed lncRNAs (dme-lncRNAs) in ARC patients. Based on bioinformatics analysis, we selected critical dme-lncRNAs and pathways associated with ARC formation to reveal their potential molecular mechanisms. The downregulation of glutathione peroxidase 4 (GPX4), a key component of ferroptosis, was confirmed by real-time RT-PCR (RT-qPCR) and Western blotting in age-related cortical cataract (ARCC) samples. Transmission electron microscopy was used to assess the change in mitochondrial in LECs. RESULTS: The analysis revealed a total of 11,193 m6A peaks within lncRNAs, among which 7043 were enriched and 4150 were depleted. Among those, lncRNA ENST00000586817(upstream of the GPX4 gene) was not only significantly upregulated in the LECs of ARCC but also potentially augmented the expression of GPX4 through a cis mechanism. The expression of m6A-modified lncRNA (ENST00000586817) was correlated with that of GPX4 and was downregulated in ARC patients. The TEM results indicated significant mitochondrial changes in ARCC samples. GPX4 downregulation enhanced LEC ferroptosis and decreased viability via RSL3 in SRA01/04 cells. CONCLUSIONS: Our results provide insight into the potential function of m6A-modified lncRNAs. M6A-modified lncRNA ENST00000586817 might regulate the expression of GPX4 by a cis mechanism and be implicated in ferroptosis in ARCs.

Ir-Catalyzed Enantioselective Synthesis of gem-Diborylalkenes Enabled by 1,2-Boron Shift.

Asymmetric cross-couplings based on 1,2-carbon migration from B-ate complexes have been developed efficiently to access valuable organoboronates. However, enantioselective reactions triggered by 1,2-boron shift have remained to be unaddressed synthetic challenge. Here, Ir-catalyzed asymmetric allylic alkylation enabled by 1,2-boron shift was developed. In this reaction, we disclosed that excellent enantioselectivities were achieved through an interesting dynamic kinetic resolution (DKR) process of allylic carbonates at the elevated temperature. Notably, the highly valuable (bis-boryl)alkenes have enabled an array of diversifications to access versatile molecules. Extensive experimental and computational studies were conducted to elucidate the reaction mechanism of DKR process and clarify the origin of excellent enantioselectivities.

MoIug4 is a novel secreted effector promoting rice blast by counteracting host OsAHL1-regulated ethylene gene transcription.

Magnaporthe oryzae secretes several effectors that modulate and hijack rice processes to colonize host cells, but the underlying mechanisms remain unclear. We report on a novel cytoplasmic effector MoIug4 that targets the rice ethylene pathway as a transcription repressor to subvert host immunity. We found that MoIug4 binds to the promoter of the host OsEIN2 gene that encodes a central signal transducer in the ethylene-signaling pathway. We also identified a MoIug4 interacting protein, OsAHL1, which acts as an AT-hook motif-containing protein binding to the A/T-rich promoter regions. Our knockout and overexpression studies showed that OsAHL1 positively regulates plant immunity in response to M. oryzae infection. OsAHL1 exhibits transcriptional regulatory activities by binding the OsEIN2 promoter region, similar to MoIug4. Intriguingly, we found that MoIug4 exhibits a higher binding affinity than OsAHL1 to the OsEIN2 promoter, suggesting differential regulatory specificities. These results revealed a counter-defense strategy by which the pathogen effector suppresses the activation of host defense genes by interfering with host transcription activator functions.

Identification of COX4I2 as a hypoxia-associated gene acting through FGF1 to promote EMT and angiogenesis in CRC.

BACKGROUND: Current evidence suggests that the hypoxic tumor microenvironment further aggravates tumor progression, leading to poor therapeutic outcomes. There is as yet no biomarker capable of evaluating the hypoxic state of the tumor. The cytochrome c oxidase (COX) subunit is crucial to the mitochondrial respiratory chain. METHODS: We investigated the potential oncogenic role of COX subunit 4 isoform 2 gene (COX4I2) in colorectal cancer (CRC) by least absolute shrinkage and selection operator (LASSO) and COX regression analysis to examine whether COX4I2 overexpression can predict colorectal cancer (CRC) prognosis. The association of COX4I2 levels with clinical features and its biological actions were evaluated both in vitro and in vivo. RESULTS: Our analysis showed that elevated COX4I2 levels were correlated with poor clinical outcomes. We also observed that that COX4I2 may be involved in epithelial-mesenchymal transition, activation of cancer-related fibroblasts and angiogenesis in relation to fibroblast growth factor 1. CONCLUSIONS: The COX4I2 level may be a predictor of outcome in CRC and may represent a novel target for treatment development.

Risk factors and prevention of postoperative pancreatic fistula after insulinoma enucleation:a retrospective study from a high-volume center.

BACKGROUND/OBJECTIVES: Enucleation is an effective surgical method to treat pancreatic insulinoma, however, the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) is high. We aim to investigate the risk factors for CR-POPF which have not been well characterized and develop effective methods to prevent CR-POPF after enucleation. METHODS: This retrospective cohort study included 161 patients diagnosed with insulinoma from June 2016 to July 2020 in Peking Union Medical College Hospital. The risk factors for CR-POPF were evaluated and the role of prophylactic pre-operative pancreatic stent to prevent the occurrence of CR-POPF after enucleation of pancreatic insulinoma were explored. RESULTS: A cohort of 161 insulinoma cases were reviewed. The CT or MRI imaging reports could be tracked in 108 cases. A total of 96 patients underwent surgery, while 81 experienced pancreatic enucleation. Univariate and multivariate analyses showed that the distance from insulinoma to the main pancreatic duct (MPD) ≤2 mm was an independent risk factor for CR-POPF (p = 0.003, OR = 6.011, 95% Cl 1.852-19.512). The pre-operative pancreatic stent substantially reduced the incidence of CR-POPF in patients with tumor located in proximity to (distance ≤2 mm) the MPD (CR-POPF of the stented group vs the non-stented group: 37.5% vs 71.4%, p = 0.028). CONCLUSIONS: The distance from insulinoma to MPD ≤2 mm is a predictive factor for CR-POPF after enucleation. Pancreatic duct stenting may benefit patients with insulinoma in proximity to the MPD by enabling a lower CR-POPF rate, so it should be considered before the enucleation of the insulinoma in proximity to the MPD (distance ≤2 mm).

Microplastics contamination in the surface water of the Yangtze River from upstream to estuary based on different sampling methods.

In this study, we investigated microplastic contamination of the Yangtze River from the upper reaches to the estuary using different sampling methods to understand extensive information on microplastic pollution. The microplastic samples were collected at 10 sites using two conventional methods: trawling and filtering water. The results showed that the average abundance of microplastics ranged from 1.62±0.61 × 105 to 4.25±3.87 × 106 items/km2 (trawling samples) and 800.0±300.0 to 3088.9±330.6 items/m3 (filtering water samples). The average abundance (by trawling) in the Three Gorges Reservoir (2.80±1.86 × 106 items/km2) was one order of magnitude higher than that of other sections, which affirmed the barrier effect of dams on microplastic distribution. The barrier effect was more obvious on larger size particles by comparing the results of two methods. The abundances near the left, right banks, and in the midstream showed no significant difference by both two methods, illustrating that sampling at each bank along the Yangtze River was also representative in one section. Characteristics analysis demonstrated that fragments (47.9%) dominated in trawling samples and fiber (63.4%) dominated in filtering water samples. Microplastics of small sizes (<1 mm) and transparent were dominant in samples collected by the two methods. Polyethylene (PP) and polypropylene (PE) were the dominant polymer types in the detected microplastics. In this study, we provided detailed information on microplastic pollution of the Yangtze River from the upstream to the estuary, which is useful for microplastic management and control in this area.

MoYvh1 subverts rice defense through functions of ribosomal protein MoMrt4 in Magnaporthe oryzae.

The accumulation of the reactive oxygen species (ROS) in rice is important in its interaction with the rice blast fungus Magnaporthe oryzae during which the pathogen scavenges ROS through the production of extracellular enzymes that promote blast. We previously characterized the MoYvh1 protein phosphatase from M. oryzae that plays a role in scavenging of ROS. To understand the underlying mechanism, we found that MoYvh1 is translocated into the nucleus following oxidative stress and that this translocation is dependent on MoSsb1 and MoSsz1 that are homologous to heat-shock protein 70 (Hsp70) proteins. In addition, we established a link between MoYvh1 and MoMrt4, a ribosome maturation factor homolog whose function also involves shuttling between the cytoplasm and the nucleus. Moreover, we found that MoYvh1 regulates the production of extracellular proteins that modulate rice-immunity. Taking together, our evidence suggests that functions of MoYvh1 in regulating ROS scavenging require its nucleocytoplasmic shuttling and the partner proteins MoSsb1 and MoSsz1, as well as MoMrt4. Our findings provide novel insights into the mechanism by which M. oryzae responds to and subverts host immunity through the regulation of ribosome biogenesis and protein biosynthesis.

A variant in a microRNA binding site in NEIL2 3'UTR confers susceptibility to age-related cataracts.

DNA damage in lens cells is considered a critical trigger for the onset of age-related cataracts (ARCs). Among DNA repair pathways, the base excision repair (BER) pathway is responsible for mending single-strand breaks in DNA. In this case-control study with 993 ARC cases and 993 healthy controls, we genotyped 9 single-nucleotide polymorphisms (SNPs) within microRNA (miRNA) regions of 6 BER pathway genes and examined their associations with ARC susceptibility. We identified rs4639:T > C in the Nei-like DNA glycosylase 2 (NEIL2) gene as significantly associated with ARCs. Individuals carrying different rs4639 alleles had distinct NEIL2 expression in lens capsule tissues from ARC cases and controls. Bioinformatics predicts that the rs4639 T allele could disrupt hsa-miR-3912-5p binding. The results of the luciferase reporter assay were in concordance with this prediction. This study has added more evidence that SNP-modified posttranscriptional gene regulation by miRNA might be a potential pathogenic mechanism of ARCs. SNPs potentially affecting miRNA binding to the 3'UTR of BER pathway genes could contribute to discrepant disease susceptibility. NEIL2-rs4639T was strongly associated with a protective role in ARCs. This protective role might be fulfilled by maintaining normal expression of NEIL2 in the mediation of disrupted binding of rs4639T with hsa-miR-3912-5p. A further study to generate model systems (cell lines or animal models) with NEIL2 variants is warranted. The results provide 2 molecular targets (e.g., NEIL2 and hsa-miR-3912-5p) for intervention strategies of ARC in the future.-Kang, L., Zou, X., Zhang, G., Xiang, J., Wang, Y., Yang, M., Chen, X., Wu, J., Guan, H. A variant in a microRNA binding site in NEIL2 3'UTR confers susceptibility to age-related cataract.

Modified Bu-zhong-yi-qi decoction synergies with 5 fluorouracile to inhibits gastric cancer progress via PD-1/PD- L1-dependent T cell immunization.

Gastric cancer remains the second most common tumor in China. Modified-Bu-zhong-yi-qi decoction (mBYD) as an adjuvant therapy for gastric cancer patients after chemotherapy could significantly prolong the survival time of patients. However, the potential anticancer mechanism for mBYD has not been well characterized. Here, we conducted a comprehensive study of mBYD on a gastric cancer xenograft model with MFC cells in 615 mice and patients. Our results showed that the survival times of the 5-FU + mBYD and mBYD groups were significantly longer than that of the control group. Moreover, the 5-FU + mBYD group had a longer survival time than the 5-FU group. Flow cytometry revealed that the value of CD4+/CD8+ in the mBYD group increased and that the proportions of CD8+PD-1+ T cells and PD-1+Treg cells were decreased when compared to the control group. Compared with the 5-FU group, CD8+PD-1+ T cells and Treg cells were both decreased when 5-FU was combined with mBYD. Further analysis showed that mBYD inhibited PD-L1 expression by the PI3K/AKT pathway in gastric cancer. An in vitro study also showed that mBYD directly promoted the proliferation, activation and cytotoxicity of T lymphocytes. Meanwhile, mBYD reduced the upregulation of CD8+PD-1+ T cells induced by chemotherapy in patients with gastric cancer. In conclusion, mBYD could modulate peripheral immunity and suppress the immune escape of tumors, which may be a promising therapy for gastric cancer.

Nm23-H1 inhibits hypoxia induced epithelial-mesenchymal transition and stemness in non-small cell lung cancer cells.

The Nm23 gene has been acknowledged to play a crucial role in lung cancer metastasis inhibitory cascades controlled by multiple factors. Low expression or allelic deletion of nm23-H1 is strongly linked to widespread metastasis and poor differentiation of non-small cell lung cancer (NSCLC). In this study, nm23-H1 was down regulated in epithelial-mesenchymal transition (EMT) and stemness enhancement under cobalt chloride (CoCl2)-induced hypoxia in NSCLC cells. Moreover, knocking down of nm23-H1 by shRNA apparently promoted hypoxia induced EMT and stemness, which was entirely suppressed via over expression of nm23-H1. Mechanistically, the Wnt/ß-catenin signaling pathway was found to participate in the nm23-H1-mediated process. Besides, XAV939 prohibited cell EMT and stemness which could be impaired by knocking down of nm23-H1, while stable transfection of nm23-H1 attenuated hypoxia phonotype induced by lithium chloride (LiCl). Generally, our experiment provided evidence that nm23-H1 can reverse hypoxia induced EMT and stemness through the inhibition of the Wnt/ß-catenin pathway, which may furnish a deeper perspective into the better treatment or prognosis for NSCLC.

Solasodine inhibits human colorectal cancer cells through suppression of the AKT/glycogen synthase kinase-3ß/ß-catenin pathway.

Solasodine is a main active component isolated from Solanum incanum L. that performs a wide range of functions containing anti-oxidant, anti-infection, and neurogenesis promotion. In this study, we explored the influence of solasodine on three types of human colorectal cancer (CRC) cell lines. The results show that solasodine prohibited CRC cell proliferation dose- and time-dependently and impeded CRC cell motility by downregulating MMPs. Solasodine was also found to fuel caspase-cascade reaction and increase the ratio between Bax and Bcl-2 so as to induce CRC cell apoptosis. When cells were pretreated with AKT activator (insulin-like growth factor-1) followed by solasodine, the solasodine-induced apoptosis was partially abrogated by insulin-like growth factor-1. Moreover, solasodine hindered tumor development and stimulated similar mechanisms in vivo. In general, our study provides the first evidence that solasodine has a suppressive effect on CRC cells and that this agent may be a novel therapeutic drug for CRC treatment.

[Effects of ß-asarone on Epithelial-Mesenchymal Transition of Gastric Cancer in Nude Mice].

Objective To observe the effects of ß-asarone on epithelial-mesenchymal transition (EMT) of human gastric cancer MGC-803 cells in BALB/c nude mice,and to study its possible molecular mechanism. Methods Gastric cancer MGC-803 cells were subcutaneously inoculated to nude mice for preparing transplanted tumor model. Totally 24 nude mice were then divided into the negative control group (model) , the positive control group (5-FU,25 mg/kg) , the high dose ß-asarone group (100 mg/ kg) , the low dose ß-asarone group (50 mg/kg) , 8 in each group. Corresponding medicines were adminis- tered to rats in respective group by gastrogavage, once per day for 10 successive days. The mice were sacrificed at the end of the intervention, and the tumor inhibition rate was calculated. The expressions of E-cadherin, N-cadherin, Snail, phosphatidylinositol 3-kinase (PI3K), phosphorylation of phosphatidylinositol 3-kinase ( p-PI3K ) , serine/threonine kinase ( AKT) , phosphorylation of serine/threonine kinase (p-AKT) were detected by Real-time PCR and Western Blot. Results Compared with the model group, the volume of transplanted tumor was obviously reduced in 5-FU group and ß-asarone groups from day7 to day 11 (P <0.05). Protein and mRNA expressions of N-cadherin, Snail, p-PI3K, p-AKT decreased, and protein and mRNA expressions of E-cadherin increased in 5-FU group and ß-asarone groups (P < 0. 05). Conclusions ß-asarone could inhibit proliferation ability of gastric cancer cells, and its mecha- nism might be associated with down-regulating P13K/AKT signal pathway of gastric cancer cells and re- straining EMT of gastric cancer cells.

[Effect of tumor volume on pulmonary dose-volume parameter by intensity-modulated radiation therapy in non-small cell lung cancer].

OBJECTIVE: To explore the effectof tumor volume on pulmonary dose-volume parameters by intensity-modulated radiation therapy (IMRT) in non-small cell lung cancer (NSCLC), and to provide a basis for pulmonary dose parameters in IMRT treatment.
 Methods: A total of 204 patients with NSCLC received IMRT were retrospectively analyzed from June, 2009 to October, 2013. The prescribed dose of planning target volume (PTV) for primary tumor was 60-66Gy (2.00-2.25 Gy, 27-33 times in all). The fractional volume percent of the lung received a dose >5 or 20 Gy (V5, V20), and absolute volume of lung received a dose <5 Gy (AVS5).The mean lung dose (MLD) in normal tissues were analyzed. Regression model curve was used to analyze them along with the change of primary tumor volume.
 Results: With the increase in lung tumor volume, the V5, V20 and MLD presented quadratic equation curve, and AVS5 presented logarithmic equation. When the tumor volume, less than a certain value (294.6, 283.2, 304.9 cm3, respectively), the V5, V20 and MLD increased with tumor size and presented an increased quadratic curve; when the tumor volume was higher than a certain value (294.6, 283.2, 304.9 cm3 respectively), the V5, V20 and MLD was declined. The AVS5 was declined in a logarithmic curve along with the increase of tumor volume.
 Conclusion: With the increase in lung tumor volume, the change in rule of V5, V20, MLD and AVS5 is not completely equivalent. When the tumor volume exceeds a certain boundary value (about 300 cubic centimeter), the corresponding tumor diameter is about 7-8 cm. In addition to the focus on pulmonary V5, V20 and MLD, we should also pay more attention to AVS5 restrictions in establishment of IMRT in NSCLC.

Dioscin inhibits gastric tumor growth through regulating the expression level of lncRNA HOTAIR.

BACKGROUND: As a member of non-coding RNAs family, long non-coding RNAs' functions in cancer needs to be further investigated. It has been indicated that the functions of Hox transcript antisense intergenic RNA (lncRNA: HOTAIR) include reprogramming chromatin organization and promoting tumor metastasis such as breast and colorectal tumor. The aim of this study is to investigate the functions of Hox in gastric cancer. METHODS: In the present study, the expression level of HOTAIR was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR), 20 gastric cancer tissues and 20 normal tissues was included. All clinical data were analyzed retrospectively. The CCK-8 and colony formation assay was used to identify if the knockdown of HOTAIR have an influence on gastric cancer cell lines. RESULTS: Compared with normal tissues, higher expression level of HOTAIR was found in gastric cancer tissues. Dioscin inhibits proliferation of the three gastric cancer cell lines and decrease HOTAIR expression. CONCLUSIONS: The expression of HOTAIR is up regulated in gastric cancer and gastric cancer cell lines, dioscin inhibits the proliferation of three gastric cancer cell lines and the anti-tumor effect of dioscin may partly depend on the down regulation of HOTAIR.

[Effect of Jianpi Yangzheng Xiaozheng Recipe on Apoptosis and Autophagy of Subcutaneous Transplanted Tumor in Nude Mice: an Experimental Study on Mechanism].

OBJECTIVE: To observe the effect of Jianpi Yangzheng Xiaozheng Recipe (JYXR) on the tumor inhibition rate of subcutaneous transplanted tumor gastric cancer cell line MGC-803 in BALB/c nude mice, and to study its molecular mechanism of apoptosis and autophagy. METHODS: Gastric cancer cell line MGC-803 was subcutaneously inoculated to nude mice for preparing transplanted gastric cancer models. Totally 32 BALB/c nude mice were randomly divided into 4 groups according to random digit table, i.e., the negative control group, the positive control group, the high dose JYXR group, the low dose JYXR group, 8 in each group. Normal saline was administered to mice in the negative control group by gastrogavage. 5-fluorouracil (5-Fu) at 2. 5 mg/kg was administered to mice in the positive control group by gastrogavage. JYXR at 85 and 43 g/kg was administered to mice in the high dose JYXR group and the low dose JYXR group by gastrogavage, once per day for 10 successive days. The effect of JYXR on the tumor inhibition rate of subcutaneous transplanted tumor was observed. Effects of JYXR on gene expression levels of Bax, Bcl-2, Fas, Cyclin D1, Cyclin D2, and Cyclin D3 in transplanted tumor were observed by real-time PCR. Effects of JYXR on protein expression levels of Procaspase-3, Procaspase-8, Procaspase-9, cleaved-PARP, Beclin-1, and LC3B were detected using Western blot. RESULTS: (1) Compared with the negative control group, the tumor weight was obviously reduced in the rest three groups (P <0. 05). The tumor weight was higher in the high dose JYXR group and the low dose JYXR group than in the positive control group (P <0. 05). (2) Results of RT-PCR indicated that, compared with the negative control group, expression levels of Bax were up-regulated, but expression levels of Bcl-2, Cyclin D1, Cyclin D2, and Cyclin D3 were down-regulated in the positive control group and JYXR groups (P <0. 05). The expression level of Fas was up-regulated in the positive control group and the high dose JYXR group (P <0. 05). Compared with the positive control group, expression levels of Fas, and Bax were all down-regulated, but expression levels of Bcl-2, Cyclin D2, and Cyclin D3 were all up-regulated in the high dose JYXR group and the low dose JYXR group (all P <0. 05). The expression level of Cyclin D1 was down-regulated in the high dose JYXR group, but it was up-regulated in the low dose JYXR group ( both P <0. 05). (3) Results of Western blot showed, compared with the negative control group, expression levels of Procaspase-3, Procaspase-8, and Procaspase-9 were down-regulated, but expression levels of cleaved-PARP, Beclin-1, and LC3B II were up-regulated in the high dose JYXR group and the low dose JYXR group (all P <0.05). Compared with the negative control group, expression levels of Procaspase-3, Procaspase-8, Procaspase-9, and LC3B II were down-regulated, but expression levels of cleaved-PARP, Beclin-1, and LC3B I were up-regulated in the positive control group (all P <0. 05). CONCLUSIONS: JYXR showed significant inhibition on subcutaneous transplanted tumor gastric cancer cell line MGC-803 in BALB/c nude mice. Its mechanism might be associated with activating apoptosis and autophagy correlated factors.

No association between Y chromosomal haplogroups and severe acne in the Han Chinese population.

Severe acne presents sexual dimorphism in its incidence in Chinese population. It is more prevalent in males. To assess the possible Y chromosomal contribution to severe acne risk in Han Chinese males, we analyzed 2041 Y chromosomal SNPs (Y-SNPs) in 725 severe acne cases and 651 controls retrieved from our recent genome-wide association study data. After data filtering, we assigned 585 cases and 494 controls into 12 Y chromosomal haplogroups based on 307 high-confidence Y-SNPs. No statistically significant difference in the distribution of Y chromosomal haplogroup frequencies was observed between the case and control groups. Our results showed a lack of association between the incidence of severe acne and the different Y chromosomal haplogroup in the Han Chinese population.

The role of miR-200a in vasculogenic mimicry and its clinical significance in ovarian cancer.

OBJECTIVE: Vasculogenic mimicry (VM) indicates that aggressive cancer cells can form de novo vascular networks and provide a perfusion pathway for rapidly growing tumors. MiR-200a has been reported significantly deregulated in ovarian cancer. However, miR-200a regulation of VM and its clinical significance in ovarian cancer remain not elucidated. METHODS: In this study, we identified the VM structure by CD34-PAS staining in ovarian cancer tissue. MiR-200a and protein expression was tested by quantitative RT-PCR and western blot. Bioinformatics prediction, luciferase assay and intervention experiments were employed to identify the target of miR-200a. RESULTS: We certified the VM structure in ovarian cancer, and found that the VM positive rate was significantly associated with tumor grade, stage and metastasis. Further study showed that miR-200a expression levels were significantly lower in VM positive ovarian cancer. In addition, our results suggested that miR-200a inhibited VM by negatively regulated EphA2 expression. Consistently, the inverse correlation of miR-200a and EphA2 has also been found in ovarian cancer patients. Moreover, the expression of miR-200a/EphA2 was significantly associated with patient's clinicopathological parameter, such as tumor stage and metastases. Kaplan-Meier curves confirmed that the patients with low miR-200a expression and/or VM positive had a significantly shorter overall survival. CONCLUSIONS: Our research demonstrates that VM, miR-200a and EphA2 play key roles in the progression and prognosis of ovarian cancer, and for the first time suggests that miR-200a inhibits VM by directly regulating EphA2. Therefore, we might have identified a genetic mechanism underlying the involvement of miR-200a in ovarian cancer VM.