Validation of the "obturator functioning scale" for Chinese-speaking patients with obturator prostheses after cancer-related maxillectomy.

Objective: The Obturator Functioning Scale (OFS) is a scale without formal measures of validity in any language. This study aimed to translate and adapt the OFS from English to Chinese and check its reliability and validity in Chinese-speaking patients with obturator prostheses after cancer-related maxillectomy. Methods: The 15-item Chinese preversion of the OFS was completed by 133 patients in three tertiary stomatological hospitals. Of these, 41 completed it again one week after the first measurement. The patients also completed the Chinese version of the University of Washington quality of life scale (UW-QOL, Version 4). Results: Item 12 ("upper lip feels numb") was deleted to achieve a better statistical fit. The 14-item Chinese version of the OFS (OFS-Ch) demonstrated high internal consistency (Cronbach's alpha = 0.908). The test-retest reliability coefficients for most items exceeded 0.90, indicating substantial reproducibility. Confirmatory factor analysis found that the scale consisted of three correlated factors: 1) eating (four items), 2) speech (five items), and 3) other problems (five items). This explained 70.2 % of the total variance using exploratory factor analysis. The scale was significantly convergent and discriminant and could validly discriminate between patients with Brown I and IId maxillary defects. Conclusions: Our results showed that the OFS-Ch scale is a valid tool for evaluating oral dysfunction and satisfaction with appearance for patients with the obturator prosthesis and identifying those at risk of poor obturator function in clinical settings.

Effect of laser remelting power on the microstructure and properties of vanadizing layer on AISI 52100 steel pin shaft.

The surface of AISI 52100 steel was pre-treated by laser remelting with different powers, and the vanadizing layer were prepared on remelted steel by pack cementation. The microstructure and properties of vanadizing layer were investigated by XRD, microhardness tester, metallographic microscope, scanning electron microscope, energy dispersive spectrometer, friction and wear tester. The critical load Lc was determined by observing the micro-scratch morphology of scratches through micro-scratch experiments, and its wear performance was studied. The results show that the hardness of remelting zone increase with the increase of laser power. When the laser power is 500 W, the microhardness is 424.6 HV0.2. The vanadizing layer formed on the remelting surfaces is uniform and dense. The layers are mainly composed of VCx phase and α-Fe/α'-Fe phase, the VC phase has the preferred orientation of (200) and (111) planes. There is a good metallurgical bonding between the vanadizing layer and the steel， and the thickness is 2.7 µm-12.15 µm, the microhardness is 2050.7 HV0.2-2350.9 HV0.2. When the laser remelting power is 300 W, the vanadizing layer is better in thickness, microhardness and average friction coefficient, the bonding force Lc between the vanadizing layer and the substrate is about 41.59 N, and the main failure mode is the spalling of the vanadizing layer. It can be concluded that laser remelting pre-treatment can greatly improve the hardness and wear resistance.

GLUD1 inhibits hepatocellular carcinoma progression via ROS-mediated p38/JNK MAPK pathway activation and mitochondrial apoptosis.

Glutamate dehydrogenase 1 (GLUD1) is an important enzyme in glutamine metabolism. Previously, we found GLUD1 was down-regulated in tumor tissues of hepatocellular carcinoma (HCC) patients by proteomics study. To explore its role in the progression of HCC, the expressional level of GLUD1 was firstly examined and presented as that both the protein and mRNA levels were down-regulated in tumor tissues compared to the normal liver tissues. GLUD1 overexpression significantly inhibited HCC cells proliferation, migration, invasion and tumor growth both in vitro and in vivo, while GLUD1 knocking-down promoted HCC progression. Metabolomics study of GLUD1 overexpressing and control HCC cells showed that 129 differentially expressed metabolites were identified, which mainly included amino acids, bases, and phospholipids. Moreover, metabolites in mitochondrial oxidative phosphorylation system (OXPHOS) were differentially expressed in GLUD1 overexpressing cells. Mechanistic studies showed that GLUD1 overexpression enhanced mitochondrial respiration activity and reactive oxygen species (ROS) production. Excessive ROS lead to mitochondrial apoptosis that was characterized by increased expression levels of p53, Cytochrome C, Bax, Caspase 3 and decreased expression level of Bcl-2. Furthermore, we found that the p38/JNK MAPK pathway was activated in GLUD1 overexpressing cells. N-acetylcysteine (NAC) treatment eliminated cellular ROS and blocked p38/JNK MAPK pathway activation, as well as cell apoptosis induced by GLUD1 overexpression. Taken together, our findings suggest that GLUD1 inhibits HCC progression through regulating cellular metabolism and oxidative stress state, and provide that ROS generation and p38/JNK MAPK pathway activation as promising methods for HCC treatment.

Imaging features, clinical characteristics and neonatal outcomes of pregnancy luteoma: A case series and literature review.

INTRODUCTION: This study aimed to investigate the imaging features, clinical characteristics and neonatal outcomes of pregnancy luteoma. MATERIAL AND METHODS: We retrospectively analyzed patients with pregnancy luteoma admitted to the First Affiliated Hospital of Sun Yat-sen University between January 2003 and December 2022. We recorded their imaging features, clinical characteristics and neonatal outcomes. Additionally, we reviewed relevant studies in the field. RESULTS: In total, 127 cases were identified, including eight from our hospital and 119 from the literature. Most patients (93/127, 73.23%) were of reproductive age, 20-40 years old, and 66% were parous. Maternal hirsutism or virilization (such as deepening voice, acne, facial hair growth and clitoromegaly) was observed in 29.92% (38/127), whereas 59.06% of patients (75/127) were asymptomatic. Abdominal pain was reported in 13 patients due to compression, torsion or combined ectopic pregnancy. The pregnancy luteomas, primarily discovered during the third trimester (79/106, 74.53%), varied in size ranging from 10 mm to 20 cm in diameter. Seventy-five cases were incidentally detected during cesarean section or postpartum tubal ligation, and 39 were identified through imaging or physical examination during pregnancy. Approximately 26.61% of patients had bilateral lesions. The majority of pregnancy luteomas were solid and well-defined (94/107, 87.85%), with 43.06% (31/72) displaying multiple solid and well-circumscribed nodules. Elevated serum androgen levels (reaching values between 1.24 and 1529 times greater than normal values for term gestation) were observed in patients with hirsutism or virilization, with a larger lesion diameter (P < 0.001) and a higher prevalence of bilateral lesions (P < 0.001). Among the female infants born to masculinized mothers, 68.18% (15/22) were virilized. Information of imaging features was complete in 22 cases. Ultrasonography revealed well-demarcated hypoechoic solid masses with rich blood supply in 12 of 19 cases (63.16%). Nine patients underwent magnetic resonance imaging (MRI) or computed tomography (CT), and six exhibited solid masses, including three with multi-nodular solid masses. CONCLUSIONS: Pregnancy luteomas mainly manifest as well-defined, hypoechoic and hypervascular solid masses. MRI and CT are superior to ultrasonography in displaying the imaging features of multiple nodules. Maternal masculinization and solid masses with multiple nodules on imaging may help diagnose this rare disease.

TRAF5 regulates intestinal mucosal Th1/Th17 cell immune responses via Runx1 in colitis mice.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disease associated with CD4+ Th1 and Th17 cell immune responses. Tumour necrosis factor-associated factor 5 (TRAF5) deficiency has been shown to aggravate DSS-induced colitis. However, the potential role of TRAF5 in regulating CD4+ T cell immune responses in the pathogenesis of IBD remains unclear. TRAF5-/- CD4+ CD45RBhigh T cells and WT CD4+ CD45RBhigh T cells were transferred to Rag2-/- mice via intravenous (i.v.) tail injection, respectively, to establish a chronic colitis model. Adeno-associated virus (AAV)-mediated gene knockout technique was used to knock out runt-associated transcription factor 1 (Runx1) expression in vivo. Specific cytokines of Th1 and Th17 cells were detected by quantitative RT-PCR, immunohistochemistry, ELISA, and flow cytometry. In T-cell transfer colitis mice, the Rag2-/- mice reconstituted with TRAF5-/- CD4+ CD45RBhigh T cells showed more severe intestinal inflammation than the WT control group, which was characterised by increased expression of INF-γ, TNF-α, IL-17a. Furthermore, we found that the INF-γ+ CD4+ , IL17a+ CD4+ , and INF-γ+ IL17a+ CD4+ T cells in the intestinal mucosa of Rag2-/- mice reconstituted with TRAF5-/- CD4+ CD45RBhigh T cells were significantly higher than those of the WT control group by flow cytometry. Mechanistically, knockout Runx1 inhibited the differentiation of TRAF5-/- CD4+ T cells into Th1 and Th17 cells in the intestinal mucosa of T-cell transfer colitis mice. TRAF5 regulates Th1 and Th17 cell differentiation and immune response through Runx1 to participate in the pathogenesis of colitis. Thus targeting TRAF5 in CD4+ T cells may be a novel treatment for IBD.

Pharmacological investigation of indole alkaloids from Alstonia scholaris against chronic glomerulonephritis.

BACKGROUND: As one of the most commonly used folk medicines in "Dai" ethno-medicine system, Alstonia scholaris (l.) R. Br. has also been used for treat "water related diseases", such as chronic kidney disease. However, few study was reported for it on the intervention of chronic glomerulonephritis (CGN). PURPOSE: To investigate the effect and potential mechanism of indole alkaloids from A. scholaris leaves in ICR mice with adriamycin nephropathy, as well as providing experimental evidence for the further application. METHODS: ICR Mice were selected for injections of adriamycin (ADR) to induce the CGN model and administered total alkaloids (TA) and four main alkaloids continuously for 42 and 28 days, respectively. The pharmacological effects were indicated by serum, urine, and renal pathological observations. The targets and pathways of indole alkaloids on CGN intervention were predicted using the network pharmacology approach, and the immortalized mice glomerular podocyte (MPC5) cells model stimulated by ADR was subsequently selected to further verify this by western blotting and RT-qPCR methods. RESULTS: TA and four major compounds dramatically reduced the levels of urinary protein, serum urea nitrogen (BUN), and creatinine (CRE) in ADR - induced CGN mice, while increasing serum albumin (ALB) and total protein (TP) levels as well as ameliorating kidney damage. Moreover, four alkaloids effected on 33 major target proteins and 153 pathways in the CGN, among which, PI3K-Akt as the main pathway, an important pathway for kidney protection by network pharmacology prediction, and then the four target proteins - HRAS, CDK2, HSP90AA1, and KDR were screened. As a result, Val-and Epi can exert a protective effect on ADR-stimulated MPC5 cells injury at a concentration of 50 µM. Furthermore, the proteins and RNA expression of HRAS, HSP90AA1, and KDR were down-regulated, and CDK2 was up-regulated after the intervention of Val-and Epi, which were supported by Western blotting and RT-qPCR. Additionally, Val-and Epi inhibited ROS production in the MPC5 cells model. CONCLUSION: This study is the first to confirm the potential therapeutic effect of alkaloids from A. scholaris on CGN. TA with major bioactive components (vallesamine and 19­epi-scholaricine) could exert protective effects against the ADR-induced CGN by regulating four key proteins: HRAS, CDK2, HSP90AA1, and KDR of the PI3K-Akt pathway.

Prognosis of laparoscopic surgery for colorectal cancer in middle-aged patients.

Background: The prognosis of middle-aged patients with colorectal cancer (CRC) treated by laparoscopic resection (LR) is unclear. This study aimed to evaluate the survival outcomes of LR compared with open resection (OR) for middle-aged patients with CRC. Patients and Methods: This retrospective cohort study used the data from a database of all consecutive colorectal resections performed between January 2009 and December 2017. Propensity score matching (PSM) was performed to handle the selection bias based on age, gender, body mass index, tumour location, AJCC stage and admission year. Univariate and multivariate COX regression model was used to identify risk factors of overall survival (OS) and disease-free survival (DFS). Results: After PSM, 154 patients were included in each group. Compared with the OR group in the total cohort, there were better survival outcomes in the LR group for 5-year OS and 5-year DFS (both P < 0.001). These differences were observed for Stage II and III diseases and for all CRC, irrespective of location. The multivariate analysis showed that tumour ≥5 cm (hazard ratio [HR] = 1.750, 95% confidence interval [CI]: 1.026-2.986, P = 0.040), Stage III (HR = 14.092, 95% CI: 1.894-104.848, P = 0.010) and LR (HR = 0.300, 95% CI: 0.160-0.560, P < 0.001) were independently associated with OS. Pre-operative carcinoembryonic antigen ≥5 ng/ml (HR = 3.954, 95% CI: 1.363-11.473, P = 0.011), Stage III (HR = 6.206, 95% CI: 1.470-26.200, P = 0.013) and LR (HR = 0.341, 95% CI: 0.178-0.653, P = 0.001) were independently associated with DFS. Conclusions: In middle-aged patients with CRC, LR achieves better survival than OR. Complications are similar, except for less blood loss and shorter post-surgical hospital stay with LR.

Does matching degree matter for proximal femoral intramedullary nail on reoperation rate in intertrochanteric fractures?

INTRODUCTION: Previous articles reported on the tip-apex distance, lag screw placement, fracture pattern, reduction quality, osteoporosis and other factors associated with second surgery. The current study focused on investigating the association of the matching degree between proximal femoral intramedullary nail and femoral medullary cavity on reoperation rate. PATIENTS AND METHODS: A retrospective cohort study was conducted. It included patients with intertrochanteric fracture who were treated with proximal femoral anti-rotatory intramedullary nail (PFNA) between January 2016 and April 2021. The gap between the intramedullary nail and the femoral medullary cavity was equal to the difference in diameter between the two. According to the gap size, all patients were divided into three groups, as follows: high-matching group: gap ≤ 2 mm; middle-matching group: 2 < gap < 4 mm; and low-matching group: gap ≥ 4 mm. The mean gap was measured through standard images. The primary observational index was whether the reoperation was needed, and secondary observational indexes included operative time, length of hospital stay. Patient characteristics were recorded, as follows: age, sex, follow-up time, fracture pattern, reduction grade and length of intramedullary nail. RESULTS: A total of 203 eligible patients were recorded, including 78 males (38.4%) and 125 females (61.6%). They had a mean age of 77.8 ± 9.9 years old and an average follow-up time of 58.1 ± 24.0 weeks. Twenty-seven patients (13.3%) needed a second operation. Coxa varus combined with screw cutting was the most common reason for reoperation (11 cases). Unstable fracture pattern with poor reduction grade tended to contribute to reoperation, whose odds ratio (OR) was 6.61 (95% confidence interval [CI], 1.98-22.09; P = 0.002). The three groups had 11 cases (13.7%), 12 cases (13.8%) and 4 cases (11.1%) of reoperation, respectively, and logistic regression showed no significant association was noted between matching degree of intramedullary nail and reoperation rate. CONCLUSIONS: The matching degree between proximal femoral intramedullary nail and femoral medullary cavity did not seem to be an important factor for reoperation, which offered more options of intramedullary nail size intraoperatively and reduced implants stock from inventory.

Comparisons of foramen ovale flap in the fetuses with true and false positive diagnosis of coarctation of the aorta.

Background: Accurate diagnosis of coaractation of aorta (CoA) remains challenging because of its relatively low sensitivity and specificity. It is difficult to distinguish true CoA from a normal physiological right-sided dominance or ventricular discrepancy caused by intracardiac minor anomalies. Redundant foramen ovale flap (RFOF) may cause ventricular disproportion. Methods: All fetuses suspected with CoA on routine screening ultrasound were retrospectively reviewed and allotted into two groups: postnatally confirmed CoA (true positive group) and prenatally suspected CoA but without CoA postnatally (false positive group). Sixty-nine normal fetuses were included as a normal group (normal group). The diameters of FOF and left atrium (LA) were measured in the four-chamber view and FOF/LA ratio ≥0.65 was considered as RFOF. Cardiac parameters between groups were compared. Results: Fifty-seven fetuses undergoing echocardiography for suspicion of CoA were enrolled; 11 (19.2%) had CoA postnatally. A significant linear relationship was identified between ventricular discrepancy degree and FOF prominence (P<0.001, R=0.48). A significant linear relationship was also identified between the RFOF and disproportion of the great arteries (P<0.001, R=0.42). FOF prominence significantly differed between groups true positive and false positive (P<0.001). RFOF occurred significantly differently in the true positive and false positive groups (56.5% vs. 0.91%, P=0.002). Cardiac parameters, including the aortic valve (AO) z-score (P=0.785), aortic isthmus (AOi) z-score (P=0.944), pulmonary artery (PA) z-score (P=0.693), PA/AO ratios (P=0.055), left ventricle (LV) z-score (P=0.192) and right ventricle (RV)/LV ratios (P=0.225), were comparable between fetuses with and without CoA after birth except RV z-score (P=0.035). Conclusions: There is no statistical difference of cardiac parameters between fetuses with and without CoA after birth except RV diameter. The proportion of fetuses with RFOF is significantly greater in patients without CoA. Fetal echocardiography including bulging of the FOF in the LA should be investigated for suspected CoA to decrease false positive diagnosis of CoA.

NUP153 promotes HCC cells proliferation via c-Myc-mediated downregulation of P15INK4b.

BACKGROUND AND AIM: Nucleoporin NUP153 (NUP153) is involved in the regulation of nuclear transportation, mitosis, and tumor progression in various cancer cells. we aimed to investigate the roles of NUP153 in hepatocellular carcinoma (HCC). METHODS: NUP153 expression level and its relationship with clinical prognosis were analyzed based on The Cancer Genome Atlas (TCGA). Quantitative real-time PCR (qRT-PCR), Western Blot (WB), and Immunohistochemistry (IHC) were used to assess NUP153 expression in tissues and cell lines. Loss-of-function experiments were implemented for exploring the roles of NUP153 in HCC cells. Ultimately, how NUP153 exerted biological functions was plumbed by performing rescue assays in HCC. RESULTS: NUP153 expressed highly in HCC tissues and cell lines. Silencing NUP153 inhibited cellular multiplication, G1/S transition, migration, and triggered cytoskeletal rearrangement of Huh7 and HepG2 cells. Knockdown NUP153 caused up-regulation of mRNA and protein levels of P15, and siRNA deprivation of P15 partially reversed the function of low-level NUP153 in HCC. Meanwhile, silencing NUP153 caused down-regulation of mRNA and protein levels of c-Myc. Furthermore, the up-regulation of P15 and cell G1/S phase arrest induced by silencing NUP153 were partially reversed by overexpression of c-Myc. CONCLUSIONS: NUP153 increases the proliferation ability of cells via the c-Myc/P15 axis in HCC.

High Expression of WWP1 Associates with Tumor Progression in Papillary Thyroid Cancer.

Background: WWP1 (WW domain-containing E3 ubiquitin protein ligase 1) is increased in several kinds of carcinomas, but the influence of WWP1 in papillary thyroid cancer (PTC) is not well understood. Materials and Methods: The expression of WWP1 in PTC tissues and cells was detected by real-time reverse transcription PCR. The biological role of WWP1 on PTC cell growth, apoptosis, migration, and invasion ability was assessed with the Cell Counting Kit-8, colony forming, flow cytometry, wound healing, and transwell assays, respectively. Results: The expression of WWP1 mRNA and protein is increased in PTC tissue samples and cells. There is close correlation between the up expression of WWP1 and clinical parameters, such as tumor size, TNM, and distant metastasis. Knockdown of WWP1 blocks cell proliferation, migration, and invasion, causes cell cycle arrest, and induces apoptosis in PTC cells. Knockdown of WWP1 increases PTEN level and reduces p-PI3K and p-Akt level in PTC cells. Conclusions: Knockdown of WWP1 suppressed cell proliferation, migration, and invasion of PTC cell by downregulating the expression of p-PI3K and p-Akt, contributing to their understanding the pathogenesis of PTC.

Evaluating the Clinical Performance of a Dual-Target Stool DNA Test for Colorectal Cancer Detection.

The dual-target stool DNA test, iColocomf, has potential utility for colorectal cancer (CRC) detection, but its clinical accuracy has not been validated on larger groups. We therefore evaluated the performance of iColocomf in a multicenter clinical trial. In this double-blinded case-control study, 1164 participants from three independent hospitals, including 320 CRC patients, 148 adenomas, 396 interfering diseases, and 300 healthy controls were enrolled. The primary indicators of sensitivity, specificity, and accuracy were estimated. Stool samples of participants were collected and tested by the assay. The test results were then verified by Sanger sequencing and retesting of resected participants. The sensitivity and specificity for CRC detection were 95.31% and 96.67%, respectively, with an accuracy of 90.29%. When combining the interfering diseases, the specificity was 88.39%. No statistically significant variations of positive detection rates were observed for the test in different patients' clinical features. For advanced adenomas (n = 38) and nonadvanced adenomas (n = 110), the sensitivities were 63.16% and 33.64%, respectively. The average accuracy was 99.62% for the methylation status of 375 samples verified by Sanger sequencing, and 94.12% for 34 participants who received the test after surgical resection. The iColocomf test showed robust performance for the early detection of colorectal cancer and potential monitoring ability in clinical practice.

Cancer­associated fibroblast­derived LRRC15 promotes the migration and invasion of triple­negative breast cancer cells via Wnt/ß­catenin signalling pathway regulation.

Triple­negative breast cancer (TNBC) is a highly aggressive tumour subtype associated with poor prognosis. The function of leucine­rich repeat­containing protein 15 (LRRC15), a member of the leucine­rich repeat superfamily, in TNBC has not yet been elucidated. The aim of this study was to identify the combined role of LRRC15 and Wnt/ß­catenin signalling pathway in the development of TNBC. The expression of LRRC15 in TNBC tissues was analysed using data from The Cancer Genome Atlas. Cell migration and invasion assays were conducted to study the function of LRRC15 in TNBC. The expression of Wnt/ß­catenin signalling proteins was analysed via western blotting. The effect of LRRC15 on ß­catenin nuclear localisation was measured by performing western blotting and luciferase assays. It was found that high LRRC15 expression was associated with poor prognosis in patients with TNBC. High expression of LRRC15 in cancer­associated fibroblasts (CAFs) promoted cell migration and invasion in TNBC cells. In addition, TNBC cells with LRRC15 overexpression in CAFs showed an aberrant increase in ß­catenin activity concomitant with nuclear localisation of ß­catenin, which inhibited its degradation. These results showed that LRRC15 promoted tumour migration and invasion in TNBC cells by regulating the Wnt/ß­catenin signalling pathway.

OsWAK112, A Wall-Associated Kinase, Negatively Regulates Salt Stress Responses by Inhibiting Ethylene Production.

The wall-associated kinase (WAK) multigene family plays critical roles in various cellular processes and stress responses in plants, however, whether WAKs are involved in salt tolerance is obscure. Herein, we report the functional characterization of a rice WAK, WAK112, whose expression is suppressed by salt. Overexpression of OsWAK112 in rice and heterologous expression of OsWAK112 in Arabidopsis significantly decreased plant survival under conditions of salt stress, while knocking down the OsWAK112 in rice increased plant survival under salt stress. OsWAK112 is universally expressed in plant and associated with cell wall. Meanwhile, in vitro kinase assays and salt tolerance analyses showed that OsWAK112 possesses kinase activity and that it plays a negative role in the response of plants to salt stress. In addition, OsWAK112 interacts with S-adenosyl-L-methionine synthetase (SAMS) 1/2/3, which catalyzes SAM synthesis from ATP and L-methionine, and promotes OsSAMS1 degradation under salt stress. Furthermore, in OsWAK112-overexpressing plants, there is a decreased SAMS content and a decreased ethylene content under salt stress. These results indicate that OsWAK112 negatively regulates plant salt responses by inhibiting ethylene production, possibly via direct binding with OsSAMS1/2/3.

FKBP11 promotes cell proliferation and tumorigenesis via p53-related pathways in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the causes of cancer-related death worldwide. The abnormal proliferation ability of OSCC has become one of the major reasons for its poor prognosis. FK-506 binding protein 11 (FKBP11) is abnormally expressed in malignant tumors and affects many biological processes. The purpose of this study is to investigate the effect of FKBP11 on cell proliferation in OSCC and explore the possible regulatory mechanism. The expression of FKBP11 was detected by western blotting (WB) and/or real-time PCR in OSCC and paracancerous normal tissues in tongue squamous cell carcinoma (TSCC) cell lines, revealing high expression in OSCC and CAL-27 cells. Furthermore, FKBP11 knockdown inhibited the proliferation of CAL-27 cells by CCK-8 and colony formation assays. G2/M arrest and induction of apoptosis were observed using flow cytometry, Hoechst 33258 and Calcein-AM/PI staining, accompanied by changes in some cell cycle- and apoptosis-related proteins, including CDK1, Cyclin B1, p21, p27, p53, Bax, Bcl-2 and Caspase-3. Additionally, the expression of these proteins can be reversed by the use of pifithrin-α (PFT-α), a p53 inhibitor. An in vivo xenograft model further confirmed that FKBP11 enhanced OSCC progression. In conclusion, FKBP11 could promote cell proliferation by regulating G2/M phase and apoptosis via the p53/p21/p27 and p53/Bcl-2/Bax pathways, respectively, which suggests that it may be a new candidate target for the treatment of OSCC.

Actin-Like Protein 8 Promotes the Progression of Triple-Negative Breast Cancer via Activating PI3K/AKT/mTOR Pathway.

OBJECTIVE: The purpose of this study was to investigate the function of actin-like protein 8 (ACTL8) on triple-negative breast cancer (TNBC) and its potential mechanisms. METHODS: In our study, ACTL8 expression and the prognostic values of ACTL8 were evaluated via the dataset from the Cancer Genome Atlas (TCGA). At the same time, the expression of ACTL8 in TNBC cells was measured by Western blot and qRT-PCR. Then, the effects of ACTL8 on the growth and metastasis of TNBC were investigated by using 5-ethynyl-20-deoxyuridine (EdU), colony formation, flow cytometry, wound healing and transwell assays. Mechanistically, Western blot was performed to confirm the interaction between ACTL8 and phosphatidylinositol 3'-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway in TNBC. RESULTS: ACTL8 expression was upregulated in TNBC and associated with the poor prognosis of TNBC. Silencing ACTL8 suppressed the proliferation, migration and invasion, also promoted the apoptosis in MDA-MB-231 and BT-549 cells. Moreover, we found that silencing ACTL8 could inhibit the activation of PI3K/AKT/mTOR signaling pathway in MDA-MB-231 and BT-549 cells. Meanwhile, the impact of silencing ACTL8 on the proliferation, apoptosis, migration and invasion was enhanced by PI3K/AKT/mTOR pathway inhibitor (Wortmannin) and reversed by PI3K/AKT/mTOR pathway activator (740Y-P). CONCLUSION: Our data demonstrated that ACTL8 may facilitate the proliferation, migration and invasion, while inhibiting apoptosis through activating PI3K/Akt/mTOR signaling pathway in TNBC.

Sox4 represses host innate immunity to facilitate pathogen infection by hijacking the TLR signaling networks.

Toll-like receptors (TLRs) are essential for the protection of the host from pathogen infections by initiating the integration of contextual cues to regulate inflammation and immunity. However, without tightly controlled immune responses, the host will be subjected to detrimental outcomes. Therefore, it is important to balance the positive and negative regulations of TLRs to eliminate pathogen infection, yet avert harmful immunological consequences. This study revealed a distinct mechanism underlying the regulation of the TLR network. The expression of sex-determining region Y-box 4 (Sox4) is induced by virus infection in viral infected patients and cultured cells, which subsequently represses the TLR signaling network to facilitate viral replication at multiple levels by a distinct mechanism. Briefly, Sox4 inhibits the production of myeloid differentiation primary response gene 88 (MyD88) and most of the TLRs by binding to their promoters to attenuate gene transcription. In addition, Sox4 blocks the activities of the TLR/MyD88/IRAK4/TAK1 and TLR/TRIF/TRAF3/TBK1 pathways by repressing their key components. Moreover, Sox4 represses the activation of the nuclear factor kappa-B (NF-κB) through interacting with IKKα/α, and attenuates NF-kB and IFN regulatory factors 3/7 (IRF3/7) abundances by promoting protein degradation. All these contributed to the down-regulation of interferons (IFNs) and IFN-stimulated gene (ISG) expression, leading to facilitate the viral replications. Therefore, we reveal a distinct mechanism by which viral pathogens evade host innate immunity and discover a key regulator in host defense.

Clinical study of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen in the treatment of advanced esophageal cancer.

OBJECTIVE: this study aimed to investigate the clinical efficacy and feasibility of the treatment of advanced esophageal cancer with a combination of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen. METHODS: forty-five patients with advanced esophageal cancer were enrolled and were randomly divided into two groups: a treatment group and a control group. Patients in the treatment group were treated with a 125I particle-integrated esophageal covered stent and hyperbaric oxygen, while patients in the control group were treated with a 125I particle-integrated esophageal covered stent. The clinical effects and long-term survival time of the two groups were observed. RESULTS: in the treatment group, the complete remission (CR) rate and partial remission (PR) rate of local lesions were 19.2 % and 61.5 %, respectively, and the total effective rate was 80.7 %. In the control group, the CR rate and PR rate of local lesions were 10.5 % and 52.6 %, respectively, and the total effective rate was 63.1 %. The total effective rate was higher in the treatment group than in the control group, which was statistically significant (p < 0.05). CONCLUSION: the combination of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen shows a good short- and long-term efficacy in the treatment of advanced esophageal cancer.

MiR-27a-3p overexpression mitigates inflammation and apoptosis of lipopolysaccharides-induced alveolar epithelial cells by targeting FOXO3 and suppressing the activation of NAPDH/ROS.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is multiple inflammatory injury lung disease. MiR-27a-3p alleviates lung injury, whether miR-27a-3p could affect the lung inflammation is not clear. Therefore, we established the lipopolysaccharides (LPS)-induced alveolar epithelial cell model to simulate ARDS inflammation in vitro to investigate the effect of miR-27a-3p in ARDS. METHODS: After LPS-induced alveolar epithelial cell model was established and FOXO3 was proved to be targeted by miR-27a-3p, the miR-27a-3p mimic, inhibitor, or FOXO3-overexpression plasmids were transfected into the cells. The effects of miR-27a-3p and FOXO3 on cell viability and apoptosis were then evaluated. The levels of apoptosis-/inflammation-related factors, miR-27a-3p, and FOXO3 were further analyzed. Also, the activities of reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NAPDH) in cells were examined. RESULTS: MiR-27a-3p was down-regulated in LPS-induced alveolar epithelial cells. The decreased-cell viability of the LPS-induced cells was increased by miR-27a-3p mimic while inhibited by FOXO3. The enhanced-apoptosis, and up-regulated Bax and C caspase-3 were reduced by miR-27a-3p mimic while inhibited by FOXO3; the down-regulated Bcl-2 of the LPS-induced cells was increased by miR-27a-3p mimic while inhibited by FOXO3. The up-regulated IL-6, IL-8, ROS, and NAPDH in the LPS-induced cells were reduced by miR-27a-3p mimic while inhibited by FOXO3. Besides, FOXO3 reversed the effect of miR-27a-3p mimic on the LPS-induced cells. CONCLUSION: MiR-27a-3p targeted FOXO3 to mitigated inflammation and apoptosis of LPS-induced alveolar epithelial cells via suppressing NAPDH/ROS activation.