ABSTRACT Objective Uniparental disomy of chromosome 6, typically paternal in origin (UPD6pat), results in significant phenotypic variability across different cases. This study integrates transcriptome‐wide profiling of amniotic fluid cell‐free RNA (cfRNA) with molecular diagnostics to elucidate the gene expression landscape and pathway dysregulation in two phenotypically distinct UPD6pat cases. Methods RNA sequencing (RNA‐seq) was performed on amniotic fluid supernatants from two UPD6pat fetuses and two gestational age‐matched controls. Results Differential expression analysis revealed 372 significantly dysregulated genes (242 upregulated and 130 downregulated; p < 0.05, |logFC| ≥ 0.5) enriched in pathways related to glucose metabolism, neurodegenerative diseases, and cellular processes. Gene set enrichment analysis (GSEA) further highlighted UPD6pat‐associated perturbations in type 1 diabetes and glycosylphosphatidylinositol biosynthesis pathways. Phenotype‐specific analysis revealed opposing expression trends in growth restriction genes and clubfoot‐related genes (EP300 and CHD7), with protein–protein interaction (PPI) networks implicating epigenetic modulation and cytoskeletal dynamics as potential drivers of phenotypic divergence. Conclusion Despite limitations in sample size, our findings underscore the utility of amniotic fluid cfRNA analysis as a noninvasive tool for prenatal diagnostics and highlight novel targets for further functional validation.

Objective To characterize the clinical features of a fetus with postaxial polydactyly caused by a de novo PRKACB gene variant and to perform a genetic analysis. Methods A pregnant woman who presented to Zhejiang Provincial People's Hospital on 4 December 2024 was enrolled in this study. Fetal clinical data were collected, and genomic DNA was extracted from the fetus and both parents. Clinical whole-exome sequencing (WES) was performed on the trio (fetus and both parents). Candidate variants were identified and validated by Sanger sequencing, followed by bioinformatics analysis. This study was approved by the Medical Ethics Committee of Zhejiang Provincial People’s Hospital (approval number: QT2025076). Results Prenatal ultrasonography revealed bilateral postaxial polydactyly and several fetal biometric measurements that were inconsistent with gestational age. The clinical diagnoses were intrauterine growth restriction and polydactyly. WES identified a de novo heterozygous variant (c.802G>A; p.Asp268Asn) in exon 8 of the fetal PRKACB gene (NM_182948.4). According to the ACMG variant-classification guidelines, this variant was interpreted as likely pathogenic (PS2_Moderate, PM1, PM2_Supporting and PP3). AlphaFold-based structural prediction indicated that the PRKACB p.Asp268Asn substitution resulted in the loss of two hydrogen bonds, thereby altering the protein's three-dimensional conformation and affecting structural stability. Conclusion: The PRKACB gene c.802G>A (p.Asp268Asn) variant is a potential genetic cause of bilateral postaxial polydactyly in the fetus. Identification of this variant expands the known mutational spectrum of PRKACB gene and provides an important reference for genetic counselling and prenatal diagnosis.

Purpose: Gastric cancer (GC) is among the deadliest malignancies and the third leading cause of cancer-related deaths worldwide. Galectin-1 (Gal-1) is a primary protein secreted by cancer-associated fibroblasts (CAFs); however, its role and mechanisms of action of Gal-1 in GC remain unclear. In this study, we stimulated GC cells with exogenous human recombinant galectin-1 protein (rhGal-1) to investigate its effects on the proliferation, migration, and resistance to cisplatin. Materials and Methods: We used simulated rhGal-1 protein as a paracrine factor produced by CAFs to induce GC cells and investigated its promotional effects and mechanisms in GC progression and cisplatin resistance. Immunohistochemical (IHC) assay confirmed that Gal-1 expression was associated with clinicopathological parameters and correlated with the expression of neuropilin-1 (NRP-1), c-JUN, and Wee1. Results: Our study reveals Gal-1 expression was significantly associated with poor outcomes. Gal-1 boosts the proliferation and metastasis of GC cells by activating the NRP-1/C-JUN/ Wee1 pathway. Gal-1 notably increases GC cell resistance to cisplatin The NRP-1 inhibitor, EG00229, effectively counteracts these effects. Conclusions: These findings revealed a potential mechanism by which Gal-1 promotes GC growth and contributes to chemoresistance, offering new therapeutic targets for the treatment of GC.

This study presents a case of a female infertile patient suffering from embryonic arrest and recurrent implantation failure. The primary objective was to assess the copy number variations (CNVs) and DNA methylation of her embryos. Genetic diagnosis was conducted by whole-exome sequencing and validated through Sanger sequencing. CNV evaluation of two cleavage stage embryos was performed using whole-genome sequencing, while DNA methylation and CNV assessment of two blastocysts were carried out using whole-genome bisulfite sequencing. We identified two novel pathogenic frameshift variants in the MEI1 gene (NM_152513.3, c.3002delC, c.2264_2268 + 11delGTGAGGTATGGACCAC) in the proband. These two variants were inherited from her heterozygous parents, consistent with autosomal recessive genetic transmission. Notably, two Day 3 embryos and two Day 6 blastocysts were all aneuploid, with numerous monosomy and trisomy events. Moreover, global methylation levels greatly deviated from the optimized window of 0.25–0.27, measuring 0.344 and 0.168 for the respective blastocysts. This study expands the mutational spectrum of MEI1 and is the first to document both aneuploidy and abnormal methylation levels in embryos from a MEI1-affected female patient presenting with embryonic arrest. Given that females affected by MEI1 mutations might experience either embryonic arrest or monospermic androgenetic hydatidiform moles due to the extrusion of all maternal chromosomes, the genetic makeup of the arrested embryos of MEI1 patients provides important clues for understanding the different disease mechanisms of the two phenotypes.

Abstract Background Due to its rarity, duodenal papillary carcinoma (DPC) is seldom studied as a unique disease and no specific molecular features or treatment guidelines are provided. Methods Whole‐exome sequencing was performed to gain new insights into the DPC mutation landscape and to identify potential signalling pathways and therapeutic targets. Mechanistically, immunohistochemistry (IHC), immunofluorescence, RNA‐seq, ATAC‐seq and in vitro cell function experiments were performed to confirm the underlying mechanisms. Results We described the mutational landscape of DPC for the first time as a group of rare tumours with a high frequency of dysregulation in the chromatin remodelling pathway, particularly PBRM1‐inactivating mutations that are significantly higher than duodenal adenocarcinomas and ampullary adenocarcinoma (27% vs. 0% vs. 7%, p < .01). In vitro cell experiments showed that downregulation of PBRM1 expression could significantly promote the cancer progression and epithelial‐to‐mesenchymal transition via the PBRM1‐c‐JUN‐VIM axis. The IHC data indicated that PBRM1 deficiency (p = .047) and c‐JUN expression (p < .001) were significantly associated with poor prognosis. Meanwhile, the downregulation of PBRM1 expression in HUTU‐80 cells was sensitive to radiation, which may be due to the suppression of c‐JUN by irradiation. Conclusions Our findings define a novel molecular subgroup of PBRM1‐inactivating mutations in DPC. PBRM1 play an important role in DPC progression and may serve as a potential therapeutic target and prognostic indicator.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/1471-2407-14-218.

e14536 Background: Polybromo 1 ( PBRM1), which is required for the stability of the SWI/SNF chromatin remodeling complex, is often deleted or mutated in clear cell renal cell carcinoma (ccRCC). However, the prognostic value of PBRM1 in ccRCC with immunotherapy was controversial and less explored in other cancer types. Methods: The sequencing data and clinical information of patients were obtained from The Cancer Genome Atlas (TCGA) cohort (n = 10967) and the immunotherapy MSKCC cohort (n = 387). In TCGA cohort, the expression levels of PD1 were defined as high or low using a 75% cut-off. The association of PBRM1 mutation and related immune biomarkers such as PD1, TMB and immune infiltrates CD4+ and CD8+ T cells was analyzed. Results: Loss-of-function (LOF) of PBRM1 mutation ( PBRM1 LOF ), including frameshift, nonsense and splice, accounted for 61.4% of all somatic mutations, with a frequency of 2.2% across all cancer types. It is most common in renal clear cell carcinoma (KIRC; 23.2%, 119/512), followed by stomach adenocarcinoma (STAD; 4.1%, 18/440), uterine corpus endometrial carcinoma (UCEC; 3.8%, 20/529), and colon adenocarcinoma (COAD; 2.5%, 11/439) in TCGA cohort. In KIRC, no differences of PD1 expression (P = 0.307) and TMB (P = 0.389) were observed between patients with PBRM1 LOF and non- PBRM1 LOF mutations, while in STAD, UCEC and COAD, patients with PBRM1 LOF mutations had significantly higher levels of PD1 (P = 0.002 in COAD, P < 0.001 in STAD and UCEC) and TMB (all P < 0.001). As for immune infiltrates, expression levels of CD4+ (P = 0.34) and CD8+ (P = 0.18) were found no difference between patients with PBRM1 LOF and non- PBRM1 LOF in KIRC. However, significantly higher expression levels of CD4+ (P = 0.0014) and CD8+ (P = 0.0016) in UCEC, and CD8+ in COAD (P = 0.04) were found in patients with PBRM1 LOF compared with non- PBRM1 LOF mutations. Further, in MSKCC cohort, a cohort of patients who had undergone immunotherapy, PBRM1 LOF was shown no significant effect on patient outcome in KIRC (P = 0.42), while in other cancer types (COAD+STAD), PBRM1 LOF trended towards a promising biomarker for better survival even though the difference was not statistically significant in this small cohort (P = 0.51). Conclusions: PBRM1 LOF may play different prognostic roles on immunotherapy in different cancer types. In KIRC, PBRM1 LOF was not associated with immune-related biomarkers as well as prognosis of immunotherapy. In COAD, STAD and UCEC, PBRM1 LOF was positively associated with immune-related biomarkers and might be a promising biomarker for immunotherapy. This result needs further validation in a lager cohort.

目的 应用转录组学技术分析伴与不伴糖尿病视网膜病变(DR)和糖尿病肾病(DN)的T2DM患者的差异表达基因,寻找DR伴DN相关基因.方法 入组T2DM患者14例,其中8例伴DR和DN纳入DNDR组、6例不伴DN和DR纳入DM组.采集患者外周血,分离白细胞,抽提总RNA,反转录为cDNA,构建转录组文库,Illumina?HiSeqTM2000系统测序,取得每份样本转录组数据.以两组间差异基因表达量均数和中位数差异倍数上下调均≥2.0倍为标准,筛选差异表达基因.并行基因本体(GO)显著性富集分析、生化代谢与信号转导通路(Pathway)显著性富集分析、基因关系网络分析.实时荧光定量PCR(RT-qPCR)检测外周血白细胞蛋白激酶C?delta结合蛋白(PRKCDBP)基因、CD177抗原(CD177)基因的mRNA水平,验证转录组测序结果.结果 与DM组比较,DNDR组筛选出差异表达基因98个,其中上调42个,下调56个.GO富集分析显示,差异基因在分子功能、细胞组分、生物学过程中富集最多的条目分别为结合功能、细胞和细胞成分、单一生物过程.Pathway显著性富集分析显示差异基因参与85个Pathway,抗原处理和递呈为富集最显著的Pathway之一,下调最显著的杀伤细胞免疫球蛋白样受体2DS1(KIR2DS1)参与其中.基因相互作用网络分析示差异表达基因中淋巴因子激活的杀伤T细胞来源蛋白激酶(PBK)与PRKCDBP、Ras关联域家族成员6(RASSF6)之间存在相互作用.杀伤细胞免疫球蛋白样受体2DL1(KIR2DL1)与KIR2DS1有相互作用关系.RT-qPCR示DNDR组PRKCDBPmRNA表达量低于DM组、CD177mRNA表达量高于DM组.结论 两组外周血白细胞中有多种差异表达基因,下调基因中的KIR2DL1、KIR2DS1、SPINK4、PRKCDBP,上调基因中的ABHD11-AS1、WNT3、CD177是否与DNDR的发病和进展有关,有待于进一步验证.

Tumor cells develop a series of metabolic reprogramming mechanisms to meet the metabolic needs for tumor progression. As metabolic hubs in cells, mitochondria play a significant role in this process, including energy production, biosynthesis, and redox hemostasis. In this study, we show that 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL), a previously uncharacterized protein, is positively associated with the development of pancreatic ductal adenocarcinoma (PDAC) and disease prognosis. We found that overexpression of HPDL in PDAC cells promotes tumorigenesis in vitro, whereas knockdown of HPDL inhibits cell proliferation and colony formation. Mechanistically, we found that HPDL is a mitochondrial intermembrane space localized protein that positively regulates mitochondrial bioenergetic processes and adenosine triphosphate (ATP) generation in a glutamine dependent manner. Our results further reveal that HPDL protects cells from oxidative stress by reprogramming the metabolic profile of PDAC cells toward glutamine metabolism. In short, we conclude that HPDL promotes PDAC likely through its effects on glutamine metabolism and redox balance.

BACKGROUND Bifidobacteria are among the probiotics used in treating intestinal diseases and are rarely used for allergic asthma treatment. The present study investigated the mechanism of B. infantis in treating allergic asthma in mice. MATERIAL AND METHODS A total of 40 male Balb/c mice were randomized into control, ovalbumin (OVA), montelukast (Mon), and B. infantis (B10) groups, and allergic asthma was induced in the OVA, Mon, and B10 groups. Airway reactivity was measured on day 29 by methacholine at various doses. The numbers of total cells and inflammatory cells in bronchoalveolar lavage fluid (BALF) were counted by blood cell counter and Diff-Quik staining. Hematoxylin-eosin (HE) staining was performed to observe inflammatory cell infiltration in lung tissues. Total IgE and OVA-specific IgE in serum were measured by ELISA. Mucin 5AC expression was detected by Western blot to evaluate airway obstruction. The levels of Th1 (IFN-γ, IL-2) and Th2 (IL-4, IL-5, IL-13) cytokines in BALF and tissues were detected by ELISA and qRT-PCR, respectively. RESULTS The mice in the OVA group had airway hyperreactivity, while the symptoms in the B10 group and Mon group were effectively relieved. B10 reduced the number of inflammatory cells in BALF as well as inflammatory cell infiltration in tissues. Moreover, the levels of total serum IgE, OVA-specific IgE, and Mucin 5AC were increased in the OVA group, but were reduced in the Mon group and B10 group. B. infantis increased the levels of Th1 cytokines and decreased those of Th2 cytokines. CONCLUSIONS B. infantis can reduce the infiltration of inflammatory cells induced by OVA-specific antibodies in mice. B. infantis has therapeutic effects on allergic asthma by promoting Th1 and inhibiting Th2 immune responses.

BACKGROUND:Colon cancer (CRC) is a common type of tumour, and IQGAP family proteins play an important role in many tumours. However, their roles in CRC remain unclear. METHODS:First, we searched many public databases to comprehensively analyze expression of IQGAPs in CRC. Next, real-time PCR, immunohistochemical (IHC), transwell, siRNA transfection and Western blot assays were used to evaluate relationships among IQGAP3 expression, clinical pathological parameters and CRC prognosis, and the underlying molecular mechanism was investigated. RESULTS:IQGAP3 was elevated in CRC tissues, whereas there was no significant change in expression of IQGAP1 or IQGAP2. Additionally, IQGAP3 expression in CRC tissues was associated with tumour progression, invasion and poor prognosis. In mechanistic studies, we found that IQGAP3 was positively coexpressed with PIK3C2B. In an in vitro assay, the PIK3C2B expression level was increased after exogenous overexpression of IQGAP3, resulting in the promotion of cell invasion, which was blocked by pretransfecting cells with PIK3C2B siRNA. Furthermore, we found that high expression of IQGAP3 and PIK3C2B correlated with tumour stage and vessel invasion in human CRC, whereby patients with high expression of both in tumours had a worse prognosis compared with patients with single-positive or double-negative tumours. CONCLUSION:The results of our current study and corresponding previous studies provide evidence that IQGAP3 is elevated in CRC and promotes colon cancer growth and metastasis by regulating PIK3C2B activation.

目的 利用转录组学技术研究有无糖尿病视网膜病变(DR)患者差异表达基因,寻找DR相关基因.设计 前瞻性比较性病例系列.研究对象 14例2型糖尿病(T2DM)患者,其中8例合并中度以上非增生性DR(NPDR)或增生性DR(PDR)的T2DM患者纳入DR组,6例不合并DR的T2DM患者纳入DM组.方法 采集每例患者外周血,分离白细胞,抽提总RNA,反转录为cDNA,构建转录组文库,Illumina HiSeqTM2000系统测序,对测序结果进行生物信息学分析.RT-qPCR检测外周血白细胞钙调蛋白1(CNN1)、溶血磷脂酸受体3(LPAR3)mRNA水平,验证转录组测序结果.以两组间差异基因表达量均数和中位数差异倍数上下调均≥2.0倍为标准筛选差异表达基因.主要指标 两组间差异表达基因,差异基因本体(GO)注释和富集、生化代谢与信号转导通路(Pathway)注释和富集、差异基因相互作用网络.两组间外周血白细胞CNN1、LPAR3的mRNA水平差异.结果 与DM组相比,DR组筛选出差异表达基因103个,其中上调41个,下调62个.下调最明显的为杀伤细胞免疫球蛋白样受体2DS1(KIR2DS1),上调最明显的为U105B小核仁RNA基因(RNU105B).GO富集分析显示在生物学过程(GO-P)、分子功能(GO-F)中显著富集的GO条目为细胞过程、单一生物过程、结合功能.谷胱甘肽S转移酶mu1(GSTM1)、早期生长应答1(EGR-1)、LPAR3、CNN1在以上条目均有富集.Pathway显著性富集分析显示,差异基因富集最多的为抗原处理和呈现、自然杀伤细胞介导的细胞毒性通路,KIR2S1均参与其中.差异基因相互作用网络分析示,差异表达基因中GAS1与多个基因之间存在相互作用.RT-qPCR结果显示,与DM组比较,DR组中的CNN1和LPAR3的mRNA含量均升高(P均＜0.05).结论 采用转录组学技术发现,DR组患者外周血白细胞存在多种差异表达基因,下调的基因中KIR2DS1、GSTM1、EGR-1、GAS1,上调的基因中RNUI05B、LPAR3、CNN1是否与DR的发生发展有关有待于进一步验证.

PURPOSE:miR-205 is a tumor suppressor and plays an important role in tumor invasiveness. However, the role of miR-205 in human gastric cancer (GC) epithelial-mesenchymal transition (EMT) remains unclear. The aim of this study was to investigate the molecular mechanism of miR-205 in the regulation of EMT in GC invasion.MATERIALS AND METHODS:Quantitative polymerase chain reaction (qPCR) was used to detect the expression of miR-205 in GC. Further, the correlation between the pathological parameters and prognosis of GC was statistically analyzed. A transwell model was used to evaluate the effect of miR-205-3p on the invasion and migration of GC cells. qPCR, western blotting, and luciferase assay were performed to analyze the relationship and target effects between miR-205-3p and the expression of zinc finger electron box binding homologous box 1 (ZEB1) and 2 (ZEB2).RESULTS:We found that the levels of miR-205-3p were significantly lower (P<0.05) in GC tissues than in matched normal tissues. Additionally, the expression of miR-205-3p was related to the tumor invasion depth, lymph node metastasis, lymph node invasion, and tumor, node, metastasis stage. Patients with lower miR-205-3p expression levels in the tumors had a poorer prognosis. The in vitro assays indicated that miR-205-3p could affect the invasion ability and EMT of GC cells by targeting the expression of both ZEB1 and ZEB2.CONCLUSIONS:miR-205-3p promotes GC progression and affects the prognosis of patients by targeting both ZEB1 and ZEB2 to directly influence EMT.

MicroRNA-301a (miRNA/miR-301a) and nuclear factor (NF)-κB signaling play important roles in tumor invasion, migration and progression. However, the role of miRNA-301a-3p in human gastric cancer (GC), and specifically in the activation of NF-κB signaling, remains unclear. The aim of the present study was to investigate miRNA-301a-3p expression in GC progression and the molecular mechanisms as regards the regulation of NF-κB signaling. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect miRNA-301a-3p expression in GC and paired normal tissues. The association between the expression of miRNA-301a-3p and patient pathological parameters and the prognosis of GC was statistically analyzed using an in situ hybridization (ISH) assay. An MTS assay and a Transwell assay were performed to evaluate the effects of miRNA-301a-3p on the proliferation, invasion and migration of GC cells. RT-qPCR and western blot analysis were used to analyze the association between miRNA-301a-3p and nuclear factor-κB repressing factor (NKRF) expression and the corresponding downstream NF-κB signaling molecules. A luciferase assay was used to verify the target effect of miRNA-301a-3p and NKRF. It was found that miRNA-301a-3p expression was significantly higher in 30 cases of primary GC compared with matched normal tissues. Additionally, the ISH assay indicated that the high expression of miRNA-301a-3p in GC was associated with tumor invasion depth, lymph node metastasis, lymph node invasion and tumor metastasis stage. Patients whose tumors had a higher miRNA-301a-3p expression level exhibited a poorer prognosis. The in vitro assay indicated that miRNA-301a-3p affected the proliferative and invasive ability of GC cells by targeting the expression of NKRF, which then affected NF-κB signaling. Therefore, it was hypothesize that miRNA-301a-3p promotes GC progression and affects the prognosis of patients with GC by targeting NKRF, which in turn, directly influences NF-κB activation.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer type with poor prognosis due to its high metastatic potential, however, the role of metabolic reprogramming in the metastasis of PDAC cell is not known. Here, we report that COX6B2 drive metastasis but not cancer cell proliferation in PDAC by enhancing oxidative phosphorylation function (OXPHOS). Transcriptome and clinical analyses revealed that cytochrome c oxidase subunit 6B2 (COX6B2) positively associated with metastasis of PDAC cells. Knockdown of COX6B2 in PDAC cells tuned down the assembly of complex IV and downregulated the function of OXPHOS, whereas re-expression of COX6B2 restored the function of OXPHOS and metastatic potential. Mechanistically, COX6B2 upregulated OXPHOS function to active purinergic receptor pathway for the metastasis of PDAC cells. Notably, the metastatic potential in PDAC could be reversely regulated by metformin, a drug was found accelerating the degradation of COX6B2 mRNA in this study. Collectively, our findings indicated that a complex metabolic control mechanism might be involved in achieving the balance of metabolic requirements for both growth and metastasis in PDAC, and regulation of the expression of COX6B2 could potentially encompass one of the targets.

OBJECTIVE:To study the expression of tumor associated vascular insulin receptor (TVIR) in colorectal cancer with or without metabolic syndrome (MS) and its relationship with the pathological features of colorectal cancer.METHODS:The expression of TVIR in 220 colorectal cancer specimens was detected by tissue microarray and immunohistochemistry. The relationships between the expression of TVIR and the pathological features (pathological subtypes, histological grade, invasion depth, lymph node metastasis and TNM stage) of colorectal cancer with/without MS were analyzed.RESULTS:The insulin receptor expression was observed in colorectal cancer tissue or border area between cancer and normal tissue, but not in normal intestinal tissue. The high-expression rates of TVIR in MS group was remarkably lower than that of non-MS group (21.6%vs. 41.0%, P< 0.05). TVIR high expression was significantly associated with tumor deep invasion, lymph node metastasis and high TNM stage (P<0.05 or P<0.01). Univariate logistic regression analysis showed high-expression of TVIR to be significantly associated with risk of deep invasion (OR=2.21, 95% CI: 1.10-4.44, P<0.05), lymph node metastasis (OR=2.21, 95% CI: 1.26-3.86, P<0.01) and high TNM stage (OR=2.08, 95% CI: 1.19-3.63, P<0.05). Such associations can be observed in patients without MS, but not in patients with MS.CONCLUSIONS:s: High-expression of TVIR is associated with aggressive pathological features such as invasion, lymph node metastasis and high TNM stage of colorectal cancer, especially for those patients without MS. TVIR could be a useful biological marker for prognosis of colorectal cancer.

Tumor angiogenesis is required for tumor growth and metastasis. Interleukin‐35 (IL35), a member of the IL12 family, is a dimer composed of IL12A and EBV‐induced gene 3（EBI3）. Elevated plasma IL35 levels have been reported to be associated with the occurrence and development of tumors. However, the role of IL35 in the angiogenesis of gastric cancer (GC) is still unclear. Here, we report that expression of IL35 is correlated with higher microvessel density, distant metastasis and poor prognosis in GC. Moreover, in vitro tube formation assays were performed to show that IL35 may contribute to the tube formation abilities of human umbilical vein endothelial cells. IL12A was observed to be the dominant subunit in promotion of tube formation. IL12A also inhibited expression of tissue inhibitor of metalloproteinase 1 and enhanced expression of plasminogen activator inhibitor 1 and insulin‐like growth factor‐binding protein 1 in a GC cell line. In conclusion, our data suggest that IL35 is involved in angiogenesis and is associated with poor prognosis for GC.

OBJECTIVE To verify the feasibility of treating pressure ulcers (PUs) with autologous platelet-rich fibrin-based (PRF) bioactive membrane, both in vitro and in vivo. METHOD An animal model using adult male Sprague-Dawley rats was used. Pressure was periodically exerted on the skin to induce localised ischaemia by using an external magnet and transplanted metal disc. After a PU developed, the rats were divided into two groups: a treatment group and a control group. Rats in the treatment group were then treated with PRF bioactive membrane every three days. RESULTS A total of 20 rats were used in this study. At days three and seven, the PU area in the PRF bioactive membrane-treated group was significantly smaller than that in the control group, and after 14 days of treatment, the PUs in the PRF bioactive membrane treatment group had healed. Haemotoxylin and eosin staining, immunohistochemistry and Western blot results indicated that PRF bioactive membrane induced wound healing by increasing the thickness of the regenerated epidermis and by upregulating vascular endothelial growth factor expression. Further, we found that different concentrations of rat autologous PRF soluble factors extraction components could significantly promote rat aortic endothelial cell proliferation, wound healing and migration ability in vitro. CONCLUSION Overall, results indicate that PRF bioactive membrane promotes PU healing in rats. Thus, it may represent a natural and effective wound-healing tool for use in the treatment of clinical skin PUs in humans in the future.

Pancreatic cancer is always diagnosed at an advanced stage. Hence, chemotherapy becomes the best choice for patients. Therefore, new anticancer drugs for pancreatic cancer are needed. Riluzole (RIL) is mainly used to treat amyotrophic lateral sclerosis clinically, but many previous studies have shown that RIL could inhibit tumors. However, no report has explored the association between RIL and pancreatic cancer. To validate this association, we performed this study. Our data showed that RIL could induce cytotoxicity, block the cell cycle, and inhibit clone formation, apoptosis, and migration in pancreatic cancer cells. Moreover, we demonstrated that RIL could suppress autophagy. However, more experiments will be needed to validate the reliability of our conclusions. In summary, our data suggest that RIL might provide clues for the development of a treatment for human pancreatic cancer in the future.