pH-Responsive antibacterial metal-phenolic network coating on hernia meshes.

Polypropylene (PP) mesh is widely used in hernioplasty, but it is prone to contamination by pathogenic bacteria. Here, we present an infection microenvironment-responsive metal-phenolic network (MPN) coating, which is made up of Cu2+ and tannic acid (TA) (referred to as CT coating), and is fabricated on PP meshes by layer-by-layer (LbL) assembly. The CT coating provided a robust protection for the PP mesh from pathogenic bacterial infection in a pH-responsive manner due to the pH-responsive disassembly kinetics of MPN complexes. Moreover, the PP meshes with ten CT coating cycles (PP-CT(10)) exhibited excellent stability in a physiological environment, with the killing ratio against "superbug" methicillin-resistant Staphylococcus aureus (MRSA) at pH 5.5 exceeding 99% even after 28 days of PBS (pH 7.4) immersion. In addition, the PP-CT(10) exhibited excellent in vivo anti-infective ability in a rodent subcutaneous implant MRSA infection model, and the results of histological and immunohistochemical analyses demonstrated that the reduced bacterial number alleviated the inflammatory response at implant sites. This study revealed that MPN coating is a promising strategy, which could provide a self-defensive ability for various implants to combat post-surgical infections in a pH-responsive manner.

The safety and efficacy of TACE combined with HAIC, PD-1 inhibitors, and tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: a retrospective study.

Objective: To assess the effectiveness and safety of transarterial chemoembolization (TACE) in combination with hepatic artery infusion chemotherapy (HAIC)、PD-1 inhibitors, and tyrosine kinase inhibitors(TKI) for unresectable hepatocellular carcinoma (HCC). Methods: A retrospective analysis was performed on 158 unresectable HCC patients admitted to the First Affiliated Hospital of Nanchang University between May 2019 and October 2022. The patients were split into two groups based on the type of treatment they received: TACE combined with HAIC,PD-1 and TKI group (THPK) and TACE combined with PD-1 and TKI group (TPK). The response was evaluated using modified solid tumor Efficacy Assessment Criteria (mRECIST). Kaplan-Meier curves were used to analyze the overall survival (OS). OS-influencing factors were identified using the Cox proportional risk regression model. Results: Finally, 63 patients who received THPK treatment and 60 patients who had TPK treatment were included. The THPK group had higher DCR (77.78% vs. 55.00%, P=0.007) and ORR (20.63% vs. 13.34%, P=0.282) than the TPK group did. The survival analysis curve also showed that the median OS was substantially longer in the THPK group than in the TPK group (OS: 21 months vs. 14 months, P=0.039). After multivariate Cox regression-corrected analysis, extrahepatic metastases (P=0.002) and methemoglobin >400 (P=0.041) were adverse influences on OS, but the THPK group (relative to the TPK group) was an independent favorable prognostic factor for OS (P=0.027). The results of the subgroup analysis showed that the addition of HAIC therapy to TPK treatment in patients with BCLC stage C, age ≦60 years, ECOG grade 0 and lobular distribution of tumors prolonged overall survival time and improved prognosis. Except for nausea, there was no difference in the adverse events between the two groups. Conclusion: In patients with unresectable HCC, the THPK group had a longer OS and similar adverse events compared to the TPK group. In the future, TACE-HAIC in combination with targeted and immunotherapy may be a more effective therapeutic option for hepatocellular carcinoma that cannot be surgically removed.

A hsa_circ_001726 axis regulated by E2F6 contributes to metastasis of hepatocellular carcinoma.

BACKGROUND: CircRNAs participate in the development of hepatocellular carcinoma (HCC). This work aims to explore the key tumor promoting circRNA as a gene therapy target. METHODS: The differentially expressed gene circRNAs in HCC tumor tissues was identified by mining GSE121714 dataset. EdU staining, wound healing, transwell invasion assay, TUNEL staining and western blotting examined proliferation, migration, invasion, apoptosis and epithelial mesenchymal transition (EMT). Xenograft mouse model and orthotopic transplantation tumor mouse model were constructed to verify the role of hsa_circ_001726 in growth and metastasis of HCC. The relationship among CCT2, E2F6, hsa_circ_001726, miR-671-5p and PRMT9 was identified by RNA-fluorescence in situ hybridization, luciferase reporter assay and RNA Immunoprecipitation. RESULTS: Eleven differentially expressed circRNAs were found in HCC tumors. Among them, hsa_circ_001726 was highly expressed in HCC tumors and cells, which was transcribed from CCT2. As a transcription factor of CCT2, E2F6 knockdown inactivated CCT2 promoter and reduced hsa_circ_001726 expression. Moreover, hsa_circ_001726 elevated PRMT9 expression by sponging miR-671-5p, and then activated Notch signaling pathway. Additionally, hsa_circ_001726 deficiency repressed malignant phenotypes of HCC cells, including proliferation, migration, invasion, EMT and apoptosis. In vivo, hsa_circ_001726 deficiency reduced tumor growth and lung metastasis of HCC in xenograft mouse models and orthotopic transplantation tumor mouse models. CONCLUSION: Hsa_circ_001726 functioned as an oncogene in HCC, which was derived from CCT2 and regulated by E2F6. Hsa_circ_001726 elevated PRMT9 expression by sponging miR-671-5p, and then activated Notch signaling pathway, thereby accelerating malignant phenotypes of HCC. Therefore, targeting hsa_circ_001726 may be a new avenue for HCC treatment.

Construction and validation of a predictive model for the risk of bowel resection in adults with incarcerated groin hernia.

BACKGROUND: It is difficult to definitively determine the degree of ischemia in the bowel in which an incarcerated groin hernia is embedded. Failure to diagnose and intervene promptly and accurately increases the rate of bowel resection and patient mortality. The aim of this study is to investigate the risk factors for incarcerated inguinal hernia complicating bowel necrosis with resection and to establish a predictive model as a reference for clinical work. METHODS: Patients with incarcerated groin hernia who were admitted to our hospital were retrospectively analyzed. They were divided into bowel resection and non-bowel resection groups based on whether bowel resection was performed in the surgical record and postoperative pathological results. Risk factors for the development of bowel resection in incarcerated groin hernia were analyzed by univariate analysis and multivariate logistic regression, respectively. The screened independent risk factors were used to establish a prediction model, and finally, the predictive ability and accuracy of the model were validated and the clinical benefit was analyzed. RESULTS: A total of 345 patients with incarcerated groin hernia were included, of whom 58 underwent bowel resection for bowel necrosis and 287 did not. Multifactorial logistic regression analysis identified bowel obstruction (OR, 7.285 [95% CI, 2.254-23.542], P = 0.001), peritonitis (OR, 16.786 [95% CI, 5.436-51.838], P = 0.000), duration of incarcerated groin hernia (OR, 1.009 [95% CI, 1. 001-1.018], P = 0.034), heart rate (OR, 1.109 [95% CI, 1.021-1.205], P = 0.014), and preoperative total protein (OR, 0.900 [95% CI, 0.836-0.969], P = 0.005) were independent risk factors for bowel resection in incarcerated groin hernia. The predictive value of the established prediction model was basically in agreement with the measured value with a consistency index of 0.938 (0.901-0.974) and had a good clinical benefit. CONCLUSION: Clinical screening and management of independent risk factors for bowel resection in patients with incarcerated groin hernia should be strengthened. The predictive model developed in this study has high diagnostic efficacy for bowel resection associated with incarcerated inguinal hernia, with the aim of reducing the incidence of bowel resection and unplanned secondary surgery.

Anatomical investigation of the pelvic urogenital fascia in 10 formalin-fixed female cadavers: novel insights into the laparoscopic total mesometrial resection.

PURPOSE: Previous anatomical studies of the urogenital fascia (UGF) have focused on males, and there is a lack of relevant anatomical studies on the distribution of the extraperitoneal UGF in females. METHODS: In this investigation, guided by the embryonic development of the female urogenital system, the ventral pelvic fascia structure of 10 female cadavers was dissected, and the distribution and morphology of female extraperitoneal UGF were observed, recorded in text, photographs and video, and 3D modeling was performed. RESULTS: We find that in the female extraperitoneal space there is a migratory fascial structure, the UGF, which surrounds the urogenital system and extends from the perinephric region to the pelvis along with the development of the urogenital organs. The two layers of the UGF are composed of loose connective tissue rich in fat that surrounds the urogenital organs, their accessory vascular structures, and the nerves of the abdominopelvic cavity. In the pelvis, it participates in the formation of the ligamentous structures around the rectum and uterus. Finally, it surrounds the bladder and gradually moves into the loose connective tissue of the medial umbilical fold. CONCLUSIONS: Sorting out the distribution characteristics of UGF has some reference value for studying the metastasis of gynecological tumors, the biomechanical structure of the female pelvis, and the surgical methods of gynecology, colorectal surgery, and hernia surgery.

Arginine methylation of HSPA8 by PRMT9 inhibits ferroptosis to accelerate hepatitis B virus-associated hepatocellular carcinoma progression.

BACKGROUND: The hepatitis B virus X (HBx) protein is an established cause of hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC). Whether arginine methylation regulates ferroptosis involved in HBx-induced HCC progression has not been reported. This study aimed to explore whether HBx-regulated protein arginine methyltransferase 9 (PRMT9) mediates the involvement of ferroptosis in the development of HCC. METHODS AND RESULTS: HBx inhibited ferroptosis through promoting PRMT9 expression in HCC cells. PRMT9 suppressed ferroptosis to accelerate HCC progression in vivo. PRMT9 targeted HSPA8 and enhanced arginine methylation of HSPA8 at R76 and R100 to regulate ferroptosis in HCC. HSPA8 overexpression altered the transcriptome profile of HepG2 cells, in particular, ferroptosis and immune-related pathways were significantly enriched by differentially expressed genes, including CD44. HSPA8 overexpression up-regulated CD44 expression and knockdown of CD44 significantly reversed the inhibition of ferroptosis caused by PRMT9 overexpression. CONCLUSIONS: In conclusion, HBx/PRMT9/HSPA8/CD44 axis is a vital signal pathway regulating ferroptosis in HCC cells. This study provides new opportunities and targets for the treatment of HBV-induced HCC.

Case Report: Transvaginal specimen extraction following totally laparoscopic D2 distal gastrectomy for gastric cancer in a patient with situs inversus totalis: with video.

Because of its significant advantage of fast postoperative recovery, natural orifice specimen extraction surgery (NOSES) has attracted increasing attention worldwide. However, the NOSES in gastric cancer (GC) treatment still needs more clinical practice, especially for the rare anatomical anomaly. Situs inversus totalis (SIT) is a rare autosomal recessive anatomical anomaly with an incidence ranging between 1/8,000 and 1/25,000 births. We present a video of transvaginal specimen extraction following totally laparoscopic D2 distal gastrectomy performed in a 59-year-old woman known to have SIT. Preoperative investigations revealed that the patient had early GC at the antrum. A gastroscopy report from the local hospital showed signet-ring cell carcinoma. The preoperative computed tomography scan revealed irregular thickening of the gastric wall at the junction of the greater curvature and antrum without metastasis to the lymph nodes. In total, laparoscopic D2 distal gastrectomy was performed with transvaginal specimen extraction. Billroth II with Braun anastomosis was performed for reconstruction. The length of the operation was 240 min without intraoperative complications and with minimal blood loss of 50 ml. The patient was uneventfully discharged on postoperative Day 7. The final pathology confirmed signet-ring cell carcinoma confined to the mucosal muscle without metastasis in 16 lymph nodes. Transvaginal specimen extraction following totally laparoscopic D2 distal gastrectomy can be safely performed in patients with SIT and has similar surgical outcomes to usual laparoscopic gastrectomy.

The characteristics of the urogenital fascia in the retrorectal space based on male cadaveric dissection and its clinical application.

BACKGROUND: The architecture of retrorectal fasciae is complex, as determined by different anatomical concepts. The aim of this study was to examine the anatomical characteristics of the inferomedial extension of the urogenital fascia (UGF) involving the pelvis to explore its relationship with the adjacent fasciae. Furthermore, we have expounded on the clinical application of UGF. METHOD: For our study, we examined 20 adult male pelvic specimens fixed in formalin, including 2 entire pelvic specimens and 18 semipelvic specimens. Our department has performed 466 laparoscopic rectal cancer procedures since January 2020. We reviewed the surgical videos involving UGF preservation and analyzed the anatomy of the UGF. RESULTS: The bilateral hypogastric nerves ran between the visceral and parietal layers of the UGF. The visceral fascia migrated ventrally at the fourth sacral vertebra, which formed the rectosacral fascia together with the fascia propria of the rectum; the parietal layer continually extended to the pelvic diaphragm, terminating at the levator ani muscle. At the third to fourth sacral vertebra level, the two layers constituted the lateral ligaments. CONCLUSION: The double layers of the UGF are vital structures for comprehending the posterior fascia relationship of the rectum. The upper segment between the fascia propria of the rectum and the visceral layer has no evident nerves or blood vessels and is regarded as the " holy plane" for the operation.

The "Y"-shaped Denonvilliers' fascia and its adjacent relationship with the urogenital fascia based on a male cadaveric anatomical study.

BACKGROUND: Controversies regarding the anatomical structure of Denonvilliers' fascia and its relationship with surrounding fasciae have sparked a heated discussion, especially concerning whether Denonvilliers' fascia is multilayered. This study aimed to expound on the anatomical structure of Denonvilliers' fascia and its correlation with the peritoneum from the sagittal view and clarify the complex fascial relationship. METHODS: Our study was performed on 20 adult male pelvic specimens fixed in formalin, including 2 entire pelvic specimens and 18 semipelvic specimens. The local adjacent organs and fasciae were dissected, and Denonvilliers' fascia was observed and removed for histological examination. RESULTS: Denonvilliers' fascia was typically single-layered and tough. On the sagittal plane, the peritoneum constituting the peritoneal reflection and Denonvilliers' fascia formed a "Y" shape. Denonvilliers' fascia originated from the peritoneal reflection, extended along the ventral side of the seminal vesicles and prostate, continuing caudally; its bilateral sides closely connected to the urogenital fascia (UGF) of the pelvic wall. In addition, histology preliminarily indicated that the basal cell layers of the peritoneum and Denonvilliers' fascia were continuous and formed a "Y" shape. Furthermore, the basal cells of the two peritonea extended to Denonvilliers' fascia, creating a fused double-layered structure. Some tiny blood vessels or a network of such vessels extended from the peritoneum to Denonvilliers' fascia. CONCLUSION: Denonvilliers' fascia, the extension of the peritoneum in the pelvic floor, appears as a single-layered "Y"-shape on the sagittal plane. Our study provides new support for the peritoneal fusion theory. Understanding the anatomical characteristics of Denonvilliers' fascia and its relationship with the UGF is of guiding significance for inexperienced colorectal surgeons to conduct rectal cancer surgery.

A new approach to enter Retzius space in laparoscopic transabdominal preperitoneal bilateral inguinal hernia repair.

BACKGROUND: To investigate the feasibility, safety and efficacy of the right-side approach to enter Retzius space in laparoscopic transabdominal preperitoneal bilateral inguinal hernia repair. METHODS: Retrospective analysis was performed on 189 patients who were diagnosed with bilateral inguinal hernia preoperatively or intraoperatively and underwent selective TAPP in the General Surgery I Section of Shaanxi Provincial People's Hospital from January 2015 to September 2020. 94 cases were performed using the right-side approach (research group), and 95 cases with conventional approach (control group). Intraoperative and postoperative conditions of the two groups were observed and compared. RESULTS: All operation were completed successfully. The operative time of research group was significantly shorter than that of control group (128.8 ± 35.4 vs 144.1 ± 40.9 min, P = 0.006). There were no significant differences in postoperative hospital stay, VAS score on first postoperative day, incidence of seroma and hematoma, urinary retention and other complications (P > 0.05). None of the patients occured hernia recurrence, mesh infection, intestinal obstruction and other complications. CONCLUSIONS: The right-side approach to enter Retzius space is safe and feasible in TAPP surgery of bilateral inguinal hernia. Compared with the conventional approach, it can shorten the operative time and has certain advantages.

TRPM8 contributes to liver regeneration via mitochondrial energy metabolism mediated by PGC1α.

Impairment of liver regeneration leads to severe morbidity in acute and chronic severe liver disease. Transient receptor potential melastain 8 (TRPM8) is involved in a variety of processes, including temperature sensing, ion homeostasis, and cell proliferation. However, whether TRPM8 contributes to liver regeneration is still unclear. We assessed the effect and mechanism of TRPM8 in liver regeneration and hepatocyte proliferation in vivo and in vitro. In this study, we found that TRPM8 deficiency impairs liver regeneration in mice. Mechanistically, the results revealed that mitochondrial energy metabolism was attenuated in livers from TRPM8 knockout (KO) mice. Furthermore, we found that TRPM8 contributes to the proliferation of hepatocytes via PGC1α. Taken together, this study shows that TRPM8 contributes to liver regeneration in mice after hepatectomy. Genetic approaches and pharmacological approaches to regulate TRPM8 activity may be beneficial to the promotion of liver regeneration.

Embryonic developmental process and clinical anatomy of the preperitoneal fascia and its clinical significance.

PURPOSE: Many researchers have different views on the origin and anatomy of the preperitoneal fascia. The purpose of this study is to review studies on the anatomy related to the preperitoneal fascia and to investigate the origin, structure, and clinical significance of the preperitoneal fascia in conjunction with previous anatomical findings of the genitourinary fascia, using the embryogenesis of the genitourinary system as a guide. METHODS: Publications on the preperitoneal and genitourinary fascia are reviewed, with emphasis on the anatomy of the preperitoneal fascia and its relationship to the embryonic development of the genitourinary organs. We also describe previous anatomical studies of the genitourinary fascia in the inguinal region through the fixation of formalin-fixed cadavers. RESULTS: Published literature on the origin, structure, and distribution of the preperitoneal fascia is sometimes inconsistent. However, studies on the urogenital fascia provide more than sufficient evidence that the formation of the preperitoneal fascia is closely related to the embryonic development of the urogenital fascia and its tegument. Combined with previous anatomical studies of the genitourinary fascia in the inguinal region of formalin-fixed cadavers showed that there is a complete fascial system. This fascial system moves from the retroperitoneum to the anterior peritoneum as the preperitoneal fascia. CONCLUSIONS: We can assume that the preperitoneal fascia (PPF) is continuous with the retroperitoneal renal fascia, ureter and its accessory vessels, lymphatic vessels, peritoneum of the bladder, internal spermatic fascia, and other peritoneal and pelvic urogenital organ surfaces, which means that the urogenital fascia (UGF) is a complete fascial system, which migrates into PPF in the preperitoneal space and the internal spermatic fascia in the inguinal canal.

Transient Receptor Potential Vanilloid-1 (TRPV1) Alleviates Hepatic Fibrosis via TGF-ß Signaling.

Hepatic fibrosis is a major global health problem and considered a leading cause of liver-related morbidity and mortality worldwide. Although previous studies have suggested that transient receptor potential vanilloid-1 (TRPV1) is protective against cardiac and renal fibrosis, its functional role in hepatic fibrosis has remained elusive. Herein, we characterize the effects of TRPV1 on carbon tetrachloride- (CCl4-) induced mice, in vitro transforming growth factor-ß- (TGF-ß-) treated hepatic stellate cells (HSCs), and human fibrosis specimens. Finally, our results demonstrated the significant TRPV1 downregulation in human liver fibrosis tissues. Knocking out TRPV1 significantly increased the expression of various hepatic fibrosis markers, while the expression of these biomarkers declined markedly in capsaicin-activated mice. Moreover, our study revealed that knocking down TRPV1 would enhance the promotive effect of TGF-ß on HSC proliferation, cell cycle, cell apoptosis, and ECM expression. Also, such promotive effect can be partially reversible by capsaicin, an exogenous activator of TRPV1. Collectively, the obtained data suggest that TRPV1 may alleviate CCl4-induced hepatic fibrosis and attenuate the effect of TGF-ß on HSC activation, proliferation, and apoptosis, which overall implies that targeting TRPV1 channel activity may be an effective therapeutic strategy for treating hepatic fibrosis.

TRPM8 deficiency attenuates liver fibrosis through S100A9-HNF4α signaling.

BACKGROUND: Liver fibrosis represent a major global health care burden. Data emerging from recent advances suggest TRPM8, a member of the transient receptor potential (TRP) family of ion channels, plays an essential role in various chronic inflammatory diseases. However, its role in liver fibrosis remains unknown. Herein, we assessed the potential effect of TRPM8 in liver fibrosis. METHODS: The effect of TRPM8 was evaluated using specimens obtained from classic murine models of liver fibrosis, namely wild-type (WT) and TRPM8-/- (KO) fibrotic mice after carbon tetrachloride (CCl4) or bile duct ligation (BDL) treatment. The role of TRPM8 was systematically evaluated using specimens obtained from the aforementioned animal models after various in vivo and in vitro experiments. RESULTS: Clinicopathological analysis showed that TRPM8 expression was upregulated in tissue samples from cirrhosis patients and fibrotic mice. TRPM8 deficiency not only attenuated inflammation and fibrosis progression in mice but also helped to alleviate symptoms of cholangiopathies. Moreover, reduction in S100A9 and increase in HNF4α expressions were observed in liver of CCl4- and BDL- treated TRPM8-/- mice. A strong regulatory linkage between S100A9 and HNF4α was also noticed in L02 cells that underwent siRNA-mediated S100A9 knockdown and S100A9 overexpressing plasmid transfection. Lastly, the alleviative effect of a selective TRPM8 antagonist was confirmed in vivo. CONCLUSIONS: These findings suggest TRPM8 deficiency may exert protective effects against inflammation, cholangiopathies, and fibrosis through S100A9-HNF4α signaling. M8-B might be a promising therapeutic candidate for liver fibrosis.

Urogenital fascia anatomy study in the inguinal region of 10 formalin-fixed cadavers: new understanding for laparoscopic inguinal hernia repair.

PURPOSE: To investigate the urogenital fascia (UGF) anatomy in the inguinal region, to provide anatomical guidance for laparoscopic inguinal hernia repair (LIHR). METHODS: The anatomy was performed on 10 formalin-fixed cadavers. The peritoneum and its deeper fascial tissues were carefully dissected. RESULTS: The UGF's bilateral superficial layer extended and ended in front of the abdominal aorta. At the posterior axillary line, the superficial layer medially reversed, with extension represented the UGF's deep layer. The UGF's bilateral deep layer medially extended beside the vertebral body and then continued with the transversalis fascia. The ureters, genital vessels, and superior hypogastric plexus moved between both layers. The vas deferens and spermatic vessels, ensheathed by both layers, moved through the deep inguinal ring. From the deep inguinal ring to the midline, the superficial layer extended to the urinary bladder's posterior wall, whereas the deep layer extended to its anterior wall. Both layers ensheathed the urinary bladder and extended along the medial umbilical ligament to the umbilicus and in the sacral promontory, extended along the sacrum, forming the presacral fascia. The superficial layer formed the rectosacral fascia at S4 sacral vertebra, and the deep layer extended to the pelvic diaphragm, terminating at the levator ani muscle. CONCLUSION: The UGF ensheaths the kidneys, ureters, vas deferens, genital vessels, superior hypogastric plexus, seminal vesicles, prostate, and urinary bladder. This knowledge of the UGF's anatomy in the inguinal region will help find correct LIHR targets and reduce bleeding and other complications.

Inhibition of the transient receptor potential vanilloid 3 channel attenuates carbon tetrachloride-induced hepatic fibrosis.

Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP superfamily. Previous studies have demonstrated that TRPV3 is associated with myocardial fibrosis. However, the role of TRPV3 in hepatic fibrosis and its underlying mechanisms are still unclear. This study aimed to elucidate the underlying effects of TRPV3 on hepatic fibrosis at multiple biological levels. First, immunohistochemical staining was performed to examine TRPV3 expression in human hepatic cirrhosis tissues. Then, we established a CCl4-induced hepatic fibrosis mouse model. The TRPV3 selective agonist drofenine and its inhibitor, forsythoside B, were intraperitoneally injected to investigate the relationship between TRPV3 and liver fibrosis progression. Finally, in vitro studies were performed using hepatic stellate cells (HSCs) to discover the potential molecular biological mechanisms. Immunohistochemistry revealed TRPV3 overexpression in liver cirrhosis. In the liver fibrosis groups, TRPV3 inhibitor treatment significantly reduced liver fibrosis, while TRPV3 agonist exacerbated its progression. In HSCs, knocking down TRPV3 with siRNA impaired DNA synthesis and cell proliferation and increased cell apoptosis. Furthermore, we found that knockdown of TRPV3 could reduce the lectin like oxidized lowdensity lipoprotein receptor-1 (LOX-1) protein levels. Our research suggests that lower expression or functional levels of TRPV3 can ameliorate the inflammatory response and fibrotic tissue proliferation.

Identification of the hub gene BUB1B in hepatocellular carcinoma via bioinformatic analysis and in vitro experiments.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers and the fourth leading cause of cancer-related deaths in the world. Although the treatment of HCC has made great progress in recent years, the therapeutic effects on HCC are still unsatisfactory due to difficulty in early diagnosis, chemoresistance and high recurrence rate post-surgery. METHODS: In this study, we identified differentially expressed genes (DEGs) based on four Gene Expression Omnibus (GEO) datasets (GSE45267, GSE98383, GSE101685 and GSE112790) between HCC and normal hepatic tissues. A protein-protein interaction (PPI) network was established to identify the central nodes associated with HCC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the central nodes were conducted to find the hub genes. The expression levels of the hub genes were validated based on the ONCOMINE and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Additionally, the genetic alterations of the hub genes were evaluated by cBioPortal. The role of the hub genes on the overall survival (OS) and relapse survival (RFS) of HCC patients was evaluated by Kaplan-Meier plotter. At last, the mechanistic role of the hub genes was illustrated by in vitro experiments. RESULTS: We found the following seven hub genes: BUB1B, CCNB1, CCNB2, CDC20, CDK1, MAD2L1 and RRM2 using integrated bioinformatics analysis. All of the hub genes were significantly upregulated in HCC tissues. And the seven hub genes were associated with the OS and RFS of HCC patients. Finally, in vitro experiments indicated that BUB1B played roles in HCC cell proliferation, migration, invasion, apoptosis and cell cycle by partially affecting mitochondrial functions. CONCLUSIONS: In summary, we identified seven hub genes that were associated with the expression and prognosis of HCC. The mechanistic oncogenic role of BUB1B in HCC was first illustrated. BUB1B might play an important role in HCC and could be potential therapeutic targets for HCC.

Role of HGF/c-Met in the treatment of colorectal cancer with liver metastasis.

The system of hepatocyte growth factor (HGF) and its receptor c-Met plays a critical role in tumor invasive growth and metastasis. The mortality rate of colorectal cancer (CRC), one of the most commonly diagnosed malignancies, is increased by it gradual development into metastasis, most frequently in the liver. Overexpression of c-Met, the protein tyrosine kinase receptor for the HCF/scatter factor, has been implicated in the progression and metastasis of human colorectal carcinoma. In this study, we aimed to investigate the role of c-Met in CRC liver metastasis and illustrate the clinical impact of regulating HGF/c-Met signaling in patients with CRC liver metastasis. We found that (I) higher levels of c-Met expression (mRNA and Protein) in CRC liver metastasis than primary CRC by assessing the patient tissue samples; (II) a positive correlation of c-Met expression with tumor stages of CRC liver metastasis, as well as c-Met expression in CRC, live metastasis concurred with regional lymph node metastasis; (III) the clinical impact of downregulation of HGF/c-Met signaling on the reduction of proliferation and invasion in CRC liver metastasis. Therefore, we demonstrate that the regulation of HGF/c-Met pathways may be a promising strategy in the treatment of patients with CRC liver metastasis.

miRNA-495 suppresses proliferation and migration of colorectal cancer cells by targeting FAM83D.

microRNAs (miRNAs) have been reported to play crucial roles in malignant tumor progression, including cell development, proliferation, and progression. Increasing evidence suggests that miR-495 functions as either an oncogene or tumor suppressor in several tumor types. However, its biological role in the development of colorectal cancer (CRC) still remains unclear. In this study, we found that miR-495 expression level was remarkably down-regulated in CRC tissues samples and cell lines when compared to adjacent normal tissues and cell line by using qRT-PCR detection. Ectopic expression of miR-495 by mimic transfection significantly suppressed CRC cell proliferation and colony formation, inhibited migration and invasion, and induced apoptosis according to CCK-8, colony formation, transwell, and flow cytometry assays. Furthermore, bioinformatics and luciferase reporter assays verified that family with sequence similarity 83, member D (FAM83D) was a direct target of miR-495 in CRC cells, and FAM83D was confirmed to be upregulated in human CRC tissues and reversely correlated with miR-495 expression. In addition, rescue experiments revealed that restoration of FAM84D could partially abrogate the inhibitory effect of miR-495 overexpression on CRC cell proliferation and metastasis. Further mechanic investigations also verified that the PTEN/P13K/AKT/mTOR pathway was involved in the miR-495/FAM83D-mediated CRC cell progression. Our findings identified that miR-495 acted as a critical tumor suppressor by directly targeting FAM83D during CRC development and therefore represented as a potential biomarker for CRC therapy.