Polydatin, a potential NOX5 agonist, synergistically enhances antitumor activity of cisplatin by stimulating oxidative stress in non­small cell lung cancer.

Non­small cell lung cancer (NSCLC) is one of the major causes of cancer­related death worldwide. Cisplatin is a front­line chemotherapeutic agent in NSCLC. Nevertheless, subsequent harsh side effects and drug resistance limit its further clinical application. Polydatin (PD) induces apoptosis in various cancer cells by generating reactive oxygen species (ROS). However, underlying molecular mechanisms of PD and its effects on cisplatin­mediated antitumor activity in NSCLC remains unknown. MTT, colony formation, wound healing analyses and flow cytometry was employed to investigate the cell phenotypic changes and ROS generation. Relative gene and protein expressions were evaluated by reverse transcription­quantitative PCR and western blot analyses. The antitumor effects of PD, cisplatin and their combination were evaluated by mouse xenograft model. In the present study, it was found that PD in combination with cisplatin synergistically enhances the antitumor activity in NSCLC by stimulating ROS­mediated endoplasmic reticulum stress, and the C­Jun­amino­terminal kinase and p38 mitogen­activated protein kinase signaling pathways. PD treatment elevated ROS generation by promoting expression of NADPH oxidase 5 (NOX5), and NOX5 knockdown attenuated ROS­mediated cytotoxicity of PD in NSCLC cells. Mice xenograft model further confirmed the synergistic antitumor efficacy of combined therapy with PD and cisplatin. The present study exhibited a superior therapeutic strategy for some patients with NSCLC by combining PD and cisplatin.

Men's symptom experience throughout androgen deprivation therapy for prostate cancer: A systematic review and meta-aggregation.

BACKGROUND: Androgen deprivation therapy is a common treatment for men with advanced prostate cancer. They have experienced many complex symptoms that affect their quality of life. However, qualitative reviews that synthesize the symptom experience for men with prostate cancer are lacking. OBJECTIVE: To explore the men's symptom experience throughout androgen deprivation therapy for prostate cancer. DESIGN: A qualitative evidence synthesis using meta-aggregation. DATA RESOURCES: Published and unpublished literature between January 2001 and August 2023 were identified from PubMed, Embase (Ovid), Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), The Cochrane Library, ProQuest, Google Scholar, China National Knowledge Infrastructure (CNKI), Wang Fang, and VIP. REVIEW METHODS: Two reviewers independently conducted screening, study selection and data extraction, and quality appraisal was performed using the Joanna Briggs Institutes Critical Appraisal Checklist for Qualitative Research. Data synthesis was conducted using meta-aggregative approach. RESULTS: 24 articles of moderate to high methodological quality were included. A total of 98 findings were extracted with 59 unequivocal or equivocal findings eligible for meta-aggregation, aggregated into nine categories, and developed four synthesized findings: (1) production of symptoms: unrecognized and underestimated, (2) perception of symptoms: varied and complicated, (3) meaning of symptoms: threatened and affected, and (4) response to symptoms: push and pull. CONCLUSIONS: Men throughout androgen deprivation for prostate cancer experience the four crisis-packed stages in their symptomatic journey. Health care provider need to understand the men's thoughts whether in the process of shared decision-making or in the course of the chosen therapy. Future research should develop individual suitable interventions and offer practical strategies for managing symptom. PROSPERO registration: CRD42023449129.

Erratum: Linc-KILH potentiates Notch1 signaling through inhibiting KRT19 phosphorylation and promotes the malignancy of hepatocellular carcinoma: Erratum.

[This corrects the article DOI: 10.7150/ijbs.52279.].

Photodynamic therapy for recalcitrant plantar warts: Case reports and a literature review.

Plantar wart is one of the most recalcitrant types of cutaneous warts with a high recurrence rate. Recalcitrant plantar warts are resistant to traditional treatments such as cryotherapy. Photodynamic therapy (PDT) is a modern, non-invasive method utilized to treat benign and malignant skin disorders. Several previous studies have reported the effective application of PDT treatment for plantar warts. We reported three cases of recalcitrant plantar warts successfully treated with PDT.

Integrated analysis of single-cell RNA-seq and bulk RNA-seq unravels the molecular feature of M2 macrophages of head and neck squamous cell carcinoma.

The connection between head and neck squamous cell carcinoma (HNSC) and M2 tumour-associated macrophages is not yet fully understood. We gathered gene expression profiles and clinical data from HNSC patients in the TCGA database. Using Consensus Clustering, we categorized these patients into M2 macrophage-related clusters. We developed a M2 macrophage-related signature (MRS) through statistical analyses. Additionally, we assessed gene expression in HNSC cells using single-cell sequencing data (GSE139324). We identified three distinct M2 macrophage-related clusters in HNSC, each with different prognostic outcomes and immune characteristics. Patients with different MRS profiles exhibited variations in immune infiltration, genetic mutations and prognosis. FCGR2A may play a role in creating an immunosuppressive tumour microenvironment and could potentially serve as a therapeutic target for HNSC. Our study demonstrated that M2 macrophage-related genes significantly impact the development and progression of HNSC. The M2 macrophage-related model offered a more comprehensive assessment of HNSC patient prognosis, genetic mutations and immune features. FCGR2A was implicated in immunosuppressive microenvironments and may hold promise for the development of novel immunotherapeutic strategies for HNSC.

Accelerated Aging and Microsatellite Instability in Recessive Dystrophic Epidermolysis Bullosa-Associated Cutaneous Squamous Cell Carcinoma.

Recessive dystrophic epidermolysis bullosa (RDEB) is a severely debilitating disorder caused by pathogenic variants in COL7A1 and is characterized by extreme skin fragility, chronic inflammation, and fibrosis. A majority of patients with RDEB develop squamous cell carcinoma, a highly aggressive skin cancer with limited treatment options currently available. In this study, we utilized an approach leveraging whole-genome sequencing and RNA sequencing across 3 different tissues in a single patient with RDEB to gain insight into possible mechanisms of RDEB-associated squamous cell carcinoma progression and to identify potential therapeutic options. As a result, we identified PLK-1 as a possible candidate for targeted therapy and discovered microsatellite instability and accelerated aging as factors potentially contributing to the aggressive nature and early onset of RDEB squamous cell carcinoma. By integrating multitissue genomic and transcriptomic analyses in a single patient, we demonstrate the promise of bridging the gap between genomic research and clinical applications for developing tailored therapies for patients with rare genetic disorders such as RDEB.

Density Functional Theory Investigation of the Sulfur-Iron Compound Formation Mechanism in Petrochemical Facilities.

In order to investigate the formation mechanism of hydrogen sulfide corrosion products in petroleum and petrochemical facilities, the interaction mechanism between iron oxides and H2S was studied by density functional theory (DFT). First, the adsorption of H2S on Fe2O3 clusters and Fe3O4 clusters was studied. The results indicated that H2S was more inclined to adsorb on the Fe site. After adsorption, the S-H bond changed from 1.356 to 1.360 Å in the gas phase, which was the main reason for the decomposition of H2S. On this basis, the reaction paths of Fe2O3 clusters and Fe3O4 clusters with H2S and the rate-determining steps of different reaction paths were calculated. The thermodynamic parameters and kinetic parameters of the rate-determining step of each path are analyzed. The results indicated that reaction path 1 of H2S and Fe2O3 clusters is the best reaction channel. The reaction will gradually form products such as S, H2O, and Fe2S2, which can release a total of 622.23 kJ/mol heat. The reaction path 2 of H2S and Fe3O4 clusters is the best reaction channel. The reaction will gradually form products such as S, H2O, and Fe3S2, which can release a total of 260.40 kJ/mol heat. Finally, the reaction paths of Fe2S2, Fe3S2, and S2 were further calculated, and it was observed that the products formed by hydrogen sulfide corrosion were easy to react with S2 to form sulfur-iron compounds with different iron-sulfur ratios. This is consistent with the corrosion products including FeS, FeS2, and Fe3S4 observed in the experiment. It lays a theoretical foundation for the subsequent study of the effect of associated elemental sulfur on the spontaneous combustion of sulfur-iron compounds.

Effects of Roasting Conditions on Antibacterial Properties of Vietnamese Turmeric (Curcuma longa) Rhizomes.

Processing with heat treatment has been reported to alter several therapeutic effects of turmeric. In Vietnamese traditional medicine, turmeric has been long used for bacterial infections, and roasting techniques are sometimes applied with this material. However, there have been no studies investigating the effects of these thermal processes on the plant's antibacterial properties. Our study was therefore performed to examine the changes that roasting produced on this material. Slices of dried turmeric were further subjected to light-roasting (80 °C in 20 min) or dark-roasting (160 °C in 20 min) processes. Broth dilution and agar-well diffusion methods were applied to examine and compare the effects of ethanol extracts obtained from non-roasted, light-roasted and dark-roasted samples, on a set of 6 gram-positive and gram-negative bacteria. In both investigations, dark-roasted turmeric was significantly less antibacterial than non-roasted and light-roasted materials, as evident by the higher values of minimum inhibitory concentrations and the smaller diameters of induced inhibitory zones. In addition, dark-roasting was also found to clearly reduce curcumin contents, total polyphenol values and antioxidant activities of the extracts. These results suggest that non-roasting or light-roasting might be more suitable for the processing of turmeric materials that are aimed to be applied for bacterial infections.

Circ-ILF2 in oral squamous cell carcinoma promotes cisplatin resistance and induces M2 polarization of macrophages.

Cisplatin (CDDP) chemoresistance is one of the predominant factors in oral squamous cell carcinoma (OSCC) treatment failure. Uncovering the mechanisms underlying CDDP resistance is of great importance in OSCC therapy. Circular RNAs (circRNAs) are a newly discovered class of noncoding RNAs, which are reported to participate in the progression of various diseases, including cancer. However, the function of circRNAs in CDDP resistance in OSCC remains unclear. Quantitative reverse transcription PCR was used to search for different circRNAs between OSCC cell lines and CDDP-resistant cell lines. The results showed that circ-ILF2 expression was higher in CDDP-resistant OSCC cell lines. The stability of circ-ILF2 was also confirmed using RNase R and actinomycin D assays. Functional experiments, including cytotoxicity, apoptosis and growth rate assays, showed that upregulation of circ-ILF2 contributes to CDDP resistance. Luciferase reporter-gene, RNA pull-down and quantitative real-time PCR (RT-qPCR) assays showed that circ-ILF2 functions as a microRNA sponge for miR-1252. Luciferase reporter assays, RNA pull-down, RT-qPCR and Western blotting showed that miR-1252 directly targeted and regulated the expression of KLF8. Circ-ILF2 plays an important role in CDDP resistance in OSCC. Circ-ILF2 exerts its function through the miR-1252/KLF8 pathway. In addition, tumour-associated macrophages (TAM) play important roles in cancer progressions, our results showed that circ-ILF2 in OSCC cells induced the M2 polarization of macrophages which provided new thoughts on immunotherapy. Our results suggest that circ-ILF2 may represent a potential therapeutic target in CDDP-resistant OSCC.

Pro-angiogenic photo-crosslinked silk fibroin hydrogel: a potential candidate for repairing alveolar bone defects.

OBJECTIVE: This study aimed to develop a pro-angiogenic hydrogel with in situ gelation ability for alveolar bone defects repair. METHODOLOGY: Silk fibroin was chemically modified by Glycidyl Methacrylate (GMA), which was evaluated by proton nuclear magnetic resonance (1H-NMR). Then, the photo-crosslinking ability of the modified silk fibroin was assessed. Scratch and transwell-based migration assays were conducted to investigate the effect of the photo-crosslinked silk fibroin hydrogel on the migration of human umbilical vein endothelial cells (HUVECs). In vitro angiogenesis was conducted to examine whether the photo-crosslinked silk fibroin hydrogel would affect the tube formation ability of HUVECs. Finally, subcutaneous implantation experiments were conducted to further examine the pro-angiogenic ability of the photo-crosslinked silk fibroin hydrogel, in which the CD31 and α-smooth muscle actin (α-SMA) were stained to assess neovascularization. The tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were also stained to evaluate inflammatory responses after implantation. RESULTS: GMA successfully modified the silk fibroin, which we verified by our 1H-NMR and in vitro photo-crosslinking experiment. Scratch and transwell-based migration assays proved that the photo-crosslinked silk fibroin hydrogel promoted HUVEC migration. The hydrogel also enhanced the tube formation of HUVECs in similar rates to Matrigel®. After subcutaneous implantation in rats for one week, the hydrogel enhanced neovascularization without triggering inflammatory responses. CONCLUSION: This study found that photo-crosslinked silk fibroin hydrogel showed pro-angiogenic and inflammation inhibitory abilities. Its photo-crosslinking ability makes it suitable for matching irregular alveolar bone defects. Thus, the photo-crosslinkable silk fibroin-derived hydrogel is a potential candidate for constructing scaffolds for alveolar bone regeneration.

Establishment of an endoplasmic reticulum stress-associated lncRNAs model to predict prognosis and immunological characteristics in hepatocellular carcinoma.

BACKGROUND: The endoplasmic reticulum stress (ERS) and unfolded protein response (UPR) pathways play an essential role in the pathophysiology of hepatocellular carcinoma (HCC), and activation of the UPR pathway is strongly associated with tumor growth. However, the function of ERS-associated long non-coding RNAs (lncRNAs) in HCC is less recognized. METHODS: We have used TCGA (The Cancer Genome Atlas) to obtain clinical and transcriptome data for HCC patients and the GSEA (Gene Set Enrichment Analysis) molecular signature database to get the ERS gene. ERS-associated prognostic lncRNA was determined using univariate Cox regression study. Then, least absolute shrinkage and selection operator and multivariate Cox regression study were used to construct ERS-associated lncRNAs risk model. Next, we use Kaplan-Meier (KM) survival study, time-dependent receiver operating characteristic (ROC) curve, univariate and multivariate Cox regression study to validate and evaluate the risk model. GSEA reveals the underlying molecular mechanism of the risk model. In addition, differences in Immune cell Infiltration Study, half-maximal inhibitory concentration (IC50) and immune checkpoints blockade (ICB) treatment between high and low risk groups were analyzed. RESULTS: We constructed a risk model consisting of 6 ERS-associated lncRNAS (containingMKLN1-AS, LINC01224, AL590705.3, AC008622.2, AC145207.5, and AC026412.3). The KM survival study showed that the prognosis of HCC patients in low-risk group was better than that in high-risk group. ROC study, univariate and multivariate Cox regression study showed that the risk model had good predictive power for HCC patients. Our verification sample verified the aforesaid findings. GSEA suggests that several tumor- and metabolism-related signaling pathways are associated with risk groups. Simultaneously, we discovered that the risk models may help in the treatment of ICB and the selection of chemotherapeutic drugs. CONCLUSIONS: In this article, we created an ERS-associated lncRNAs risk model to help prognostic diagnosis and personalized therapy in HCC.

SP2-induced circPUM1 modulates chemoresistance and nature killer cell toxicity in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a type of tumour found in the cavity that is characterized by differentiation and metastasis to the lymph nodes. Although diagnosis strategy and clinical treatment have recently improved, the outcomes for OSCC patients remain unsatisfactory. This study verified the characteristics of circPUM1 in OSCC cells, subsequently generating dysregulated circPUM1 cell models, showing that circPUM1 promoted chemoresistance and natural killer (NK) cell toxicity. Furthermore, the transcription factor SP2 regulated the expression of circPUM1 in OSCC cells, circPUM1 acted as a molecular sponge for miR-770-5p. Moreover, Nucleosome Assembly Protein 1 Like 1 (NAP1L1) is a downstream target for miR-770-5p and essential for circPUM1-mediated cisplatin resistance and NK cell cytotoxicity in OSCC cells. The network composed of SP2, circPUM1, miR-770-5p and NAP1L1 in OSCC appears to be a promising avenue for the development of novel targets for diagnosing or treating OSCC.

Non-pharmacological and nonsurgical interventions in male urinary incontinence: A scoping review.

AIMS: To describe and synthesize non-pharmacological and nonsurgical interventions for male urinary incontinence from the existing literature. METHODS: A scoping review was conducted following the methodology suggested by Arksey and O'Malley: (1) identification of the research questions; (2) identification of relevant studies using a three-step search recommended by JBI: an initial search within PubMed and CINAHL, a comprehensive literature search within PubMed, CINAHL, EMBASE, PsycINFO, Cochrane Library, and literature search of references lists; (3) study selection; (4) data extraction and charting; (5) collation, summarization, and reporting of the results. The PRISMA-ScR Checklist was used to report. RESULTS: A total of 4602 studies were identified, of which 87 studies were included. Approximately 78% were randomized controlled trials. More than 88% of the participants were men with prostate cancer. Exercising pelvic floor muscles 30 times per day for 12 weeks was the most frequently reported. Parameters of electrical stimulation were typically set up to 50 Hz and 300 µs for frequency and width of pulse, respectively, and lasted for 15 min. Pure pelvic floor muscle training, Pilates, Yoga, whole body vibration, diaphragm/abdominal muscle training, micturition interruption exercise, acupuncture, and auriculotherapy showed positive effects on reducing urinary incontinence. CONCLUSION: The findings suggested implementing pelvic floor muscle training alone before or after surgery can both prompt the recovery of continence in men after prostate cancer surgery. The decision to use biofeedback or electrical stimulation to enhance the therapeutic effect of pelvic floor muscle training should be approached with caution. More rigorous designed studies are needed to validate the effectiveness of Traditional Chinese Medicine techniques and diverse novel methods. RELEVANCE TO CLINICAL PRACTICE: Physicians and nurses need to be up to date on the latest evidence-based non-pharmacological and nonsurgical interventions in male urinary incontinence and select appropriate interventions based on available medical resources and patient preferences.

Circ_0067997 boosted the growth while repressed the apoptosis of SGC-7901/DDP cells via repressing miR-615-5p/AKT1 pathway.

BACKGROUND: Gastric cancer (GC) remains a huge challenge to the heathy of human beings, largely due to lacking of effective therapeutic measures. Though an oncogenic role for circular RNAs (circRNAs) circ_0067997 in the progression of GC has been described recently, the molecular modulatory mechanism of it still remains to be further explored. The aim of present study is to examine the molecular network of circ_0067997 in GC. METHODS: qRT-PCR was carried out to determine the mRNA levels of circ_0067997, miR-615-5p and AKT1 in cisplatin (DDP)-insensitive or sensitive GC tumor tissues and cells, while the correlations among the contents of these molecules were determined by statistical analysis. The expression of circ_0067997 was manipulated by short-hairpin RNA and lentiviral-mediated approaches, while that of miR-615-5p was achieved by the application of its inhibitor or mimic. The in vivo action of circ_0067997 on tumor formation was determined by measuring tumor weight/volume/size and analyzing tumor apoptosis through TUNEL staining in mouse xenograft model and, while the in vitro effects of this circRNA and its target miR-615-5p on the cell survival and death were separately evaluated by CCK-8 assay and flow cytometry. Additionally, luciferase reporter assays were executed to determine the sequentially regulatory relationships of circ_0067997, miR-615-5p, and AKT1. RESULTS: Our data demonstrated that the level of circ_0067997 level was increased in DDP-insensitive GC tissues and cell line, while miR-615-5p presented the opposite results. Moreover, the relationships between circ_0067997 and miR-615-5p levels, circ_0067997 and AKT1 contents presented negative and positive correlations in clinic samples, respectively. Importantly, circ_0067997 was found to repress miR-615-5p expression, consequently leading to increased growth while reduced apoptosis of GC cells in the presence of DDP. Furthermore, the validated sequential regulation was circ_0067997 modulating miR-615-5p adjusting AKT1. CONCLUSIONS: This study demonstrated that circ_0067997 functioned as a sponge of miR-615-5p to target AKT1 expression, thereby enhancing the growth and restricting the apoptosis of DDP-insensitive GC cells. These new findings offered a valuable target for the detection and management of GC.

Regorafenib induces NOX5-mediated endoplasmic reticulum stress and potentiates the anti-tumor activity of cisplatin in non-small cell lung cancer cells.

Lung cancer is one of the most commonly diagnosed cancers worldwide. Although cisplatin-based chemotherapy regimens serve a pivotal role in non-small cell lung cancer (NSCLC) treatment, drug resistance and serious side effects limited its further clinical application. Regorafenib, a small-molecule multi-kinase inhibitor, was demonstrated to have promising anti-tumor activity in various solid tumors. In the present study, we found that regorafenib markedly enhanced cisplatin-induced cytotoxicity in lung cancer cells by activating reactive oxygen species (ROS)-mediated endoplasmic reticulum stress (ER Stress), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signaling pathways. Regorafenib increased ROS generation by promoting NADPH oxidase 5 (NOX5) expression, and knocking down NOX5 attenuated ROS-mediated cytotoxicity of regorafenib in lung cancer cells. Additionally, mice xenograft model validated that synergistic anti-tumor effects of combined treatment with regorafenib and cisplatin. Our results suggested that combination therapy with regorafenib and cisplatin may serve as a potential therapeutic strategy for some NSCLC patients.

Epigenetic Regulation of Corneal Epithelial Differentiation by TET2.

Epigenetic DNA modification by 5-hydroxymethylcytosine (5hmC), generated by the Ten-eleven translocation (TET) dioxygenases, regulates diverse biological functions in many organ tissues, including the mammalian eye. For example, 5hmC has been shown to be involved in epigenetic regulation of retinal gene expression. However, a functional role of 5hmC in corneal differentiation has not been investigated to date. Here, we examined 5hmC and TET function in the human cornea. We found 5hmC highly expressed in MUC16-positive terminally differentiated cells that also co-expressed the 5hmC-generating enzyme TET2. TET2 knockdown (KD) in cultured corneal epithelial cells led to significant reductions of 5hmC peak distributions and resulted in transcriptional repression of molecular pathways involved in corneal differentiation, as evidenced by downregulation of MUC4, MUC16, and Keratin 12. Additionally, integrated TET2 KD RNA-seq and genome-wide Reduced Representation Hydroxymethylation Profiling revealed novel epigenetically regulated genes expressed by terminally differentiated cells, including KRT78, MYEOV, and MAL. In aggregate, our findings reveal a novel function of TET2 in the epigenetic regulation of corneal epithelial gene expression and identify novel TET2-controlled genes expressed in differentiated corneal epithelial cells. These results point to potential roles for TET2 induction strategies to enhance treatment of corneal diseases associated with abnormal epithelial maturation.

Heat-Killed Staphylococcus aureus Induces Bone Mass Loss through Telomere Erosion.

The mechanism of systemic osteoporosis caused by chronic infection is not completely clear, and there is a lack of reasonable interventions for this disease. In this study, heat-killed S. aureus (HKSA) was applied to simulate the inflammation caused by the typical clinical pathogen and to explore the mechanism of systemic bone loss caused by it. In this study, we found that the systemic application of HKSA caused bone loss in mice. Further exploration found that HKSA caused cellular senescence, telomere length shortening, and telomere dysfunction-induced foci (TIF) in limb bones. As a well-known telomerase activator, cycloastragenol (CAG) significantly alleviated HKSA-induced telomere erosion and bone loss. These results suggested that telomere erosion in bone marrow cells is a possible mechanism of HKSA-induced bone loss. CAG may protect against HKSA-induced bone loss by alleviating telomere erosion in bone marrow cells.

ARHGAP21 Is Involved in the Carcinogenic Mechanism of Cholangiocarcinoma: A Study Based on Bioinformatic Analyses and Experimental Validation.

Background and Objectives: Rho GTPase-activating protein (RhoGAP) is a negative regulatory element of Rho GTPases and participates in tumorigenesis. Rho GTPase-activating protein 21 (ARHGAP21) is one of the RhoGAPs and its role in cholangiocarcinoma (CCA) has never been disclosed in any publications. Materials and Methods: The bioinformatics public datasets were utilized to investigate the expression patterns and mutations of ARHGAP21 as well as its prognostic significance in CCA. The biological functions of ARHGAP21 in CCA cells (RBE and Hccc9810 cell) were evaluated by scratch assay, cell counting kit-8 assay (CCK8) assay, and transwell migration assay. In addition, the underlying mechanism of ARHGAP21 involved in CCA was investigated by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and the most significant signaling pathway was identified through gene set enrichment analysis (GSEA) and the Western blot method. The ssGSEA algorithm was further used to explore the immune-related mechanism of ARHGAP21 in CCA. Results: The ARHGAP21 expression in CCA tissue was higher than it was in normal tissue, and missense mutation was the main alteration of ARHGAP21 in CCA. Moreover, the expression of ARHGAP21 had obvious differences in patients with different clinical characteristics and it had great prognostic significance. Based on cell experiments, we further observed that the proliferation ability and migration ability of the ARHGAP21-knockdown group was reduced in CCA cells. Several pathological signaling pathways correlated with proliferation and migration were determined by GO and KEGG analysis. Furthermore, the PI3K/Akt signaling pathway was the most significant one. GSEA analysis further verified that ARHGAP21 was highly enriched in PI3K/Akt signaling pathway, and the results of Western blot suggested that the phosphorylated PI3K and Akt were decreased in the ARHGAP21-knockdown group. The drug susceptibility of the PI3K/Akt signaling pathway targeted drugs were positively correlated with ARHGAP21 expression. Moreover, we also discovered that ARHGAP21 was correlated with neutrophil, pDC, and mast cell infiltration as well as immune-related genes in CCA. Conclusions: ARHGAP21 could promote the proliferation and migration of CCA cells by activating the PI3K/Akt signaling pathway, and ARHGAP21 may participate in the immune modulating function of the tumor microenvironment.

Pro-angiogenic photo-crosslinked silk fibroin hydrogel: a potential candidate for repairing alveolar bone defects

Abstract Objective: This study aimed to develop a pro-angiogenic hydrogel with in situ gelation ability for alveolar bone defects repair. Methodology: Silk fibroin was chemically modified by Glycidyl Methacrylate (GMA), which was evaluated by proton nuclear magnetic resonance (1H-NMR). Then, the photo-crosslinking ability of the modified silk fibroin was assessed. Scratch and transwell-based migration assays were conducted to investigate the effect of the photo-crosslinked silk fibroin hydrogel on the migration of human umbilical vein endothelial cells (HUVECs). In vitro angiogenesis was conducted to examine whether the photo-crosslinked silk fibroin hydrogel would affect the tube formation ability of HUVECs. Finally, subcutaneous implantation experiments were conducted to further examine the pro-angiogenic ability of the photo-crosslinked silk fibroin hydrogel, in which the CD31 and α-smooth muscle actin (α-SMA) were stained to assess neovascularization. The tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also stained to evaluate inflammatory responses after implantation. Results: GMA successfully modified the silk fibroin, which we verified by our 1H-NMR and in vitro photo-crosslinking experiment. Scratch and transwell-based migration assays proved that the photo-crosslinked silk fibroin hydrogel promoted HUVEC migration. The hydrogel also enhanced the tube formation of HUVECs in similar rates to Matrigel®. After subcutaneous implantation in rats for one week, the hydrogel enhanced neovascularization without triggering inflammatory responses. Conclusion: This study found that photo-crosslinked silk fibroin hydrogel showed pro-angiogenic and inflammation inhibitory abilities. Its photo-crosslinking ability makes it suitable for matching irregular alveolar bone defects. Thus, the photo-crosslinkable silk fibroin-derived hydrogel is a potential candidate for constructing scaffolds for alveolar bone regeneration.

CircMAT2B Induced by TEAD1 Aggravates the Warburg Effect and Tumorigenesis of Oral Squamous Cell Carcinoma through the miR-942-5p/HSPD1 Axis.

Oral squamous cell carcinoma (OSCC) is one of the most lethal cancers worldwide. The high morbidity and mortality of OSCC are a great burden to global health-care systems. Therefore it is important to understand the underlying molecular mechanisms of OSCC initiation and progression. This study aimed to investigate the role of circMAT2B in OSCC progression and its molecular mechanisms. First, the expression and circularization of circMAT2B in OSCC cells were verified. Subsequently, knockdown of circMAT2B was shown to inhibit OSCC cell proliferation, migration, invasion, and the Warburg effect. Bioinformatics prediction, RNA-pull down, and luciferase reporter gene assays led to the identification of a novel TEAD1/circMAT2B/miR-942-5p/HSPD1 axis in OSCC progression. In conclusion, the novel TEAD1/circMAT2B/miR-942-5p/HSPD1 axis is a potential target for OSCC.