The inputs of autochthonous organic carbon driven by mangroves reduce metal mobility and bioavailability in intertidal regions.

The significance of mangroves in carbon storage is widely acknowledged. However, the potential role of carbon enhancement driven by mangroves in mitigating the risk of metal exposure remains unclear. In this study, a natural mangrove reserve located in Futian was selected to investigate the potential role of autochthonous organic carbon on metal bioavailability. The presence of mangroves seemed to have little effect on the accumulations of Cu(II), Zn(II), Cr(VI/III), Pb(II), and Ni(II) in surface sediments. Metal mobility and bioavailability, however, were found to be directly influenced by the presence of mangroves. Compared with mudflat, mangrove sediments exhibited an obvious in the bioavailability of Cu(II), Zn(II), Cr(VI/III), Pb(II), and Ni(II) by 19-79 %, with the highest reduction occurring in the interior of mangroves dominated by K. obovata. Mangroves also significantly enhanced the accumulation of organic carbon in sediments, regardless of carbon components. Moreover, the results from random forest analysis further showed that autochthonous organic carbon was the most important carbon component that negatively related to metal bioavailability. In summary, this is the first study to provide a linkage between mangrove cover and increased autochthonous organic carbon input, which decreases metal bioavailability. The present data also suggest that mangroves are an efficient natural barrier to alleviate the risk of metal exposure in intertidal regions.

Day surgery unit robotics thoracic surgery: feasibility and management.

BACKGROUND: Day surgery has been widely carried out in medical developed countries such as Europe and the United States with high efficiency, safety and economy. The development of thoracic day surgery started late, and currently only a few top three hospitals carry thoracic day surgery. In recent years, with the continuous in-depth application of the concept of accelerated rehabilitation surgery (ERAS) in the field of surgery, thoracic surgery ERAS has also entered clinical practice with remarkable results. At present, the application of day surgery in the field of thoracic surgery is still in its infancy, and the application of robot-assisted thoracic surgery in thoracic surgery has brought new opportunities for the popularization of day surgery in thoracic surgery. METHODS: We retrospectively reviewed 86 patients underwent thoracic day surgery under the application of robot-assisted surgery system and through systematic randomization method choose 86 patients underwent conventional thoracic surgery under the application of robot-assisted surgery system at our Institute between 2020 and 2022. We analyzed the clinical and pathological features between the two groups. RESULTS: The clinical feature of location of the nodules, the size of nodules, pN, histology and postoperative complications were homogenous between the two groups. The average age was significantly higher in the conventional mode group, the ratio of male patients and the patients with history of smoking were significantly lower in day-surgery mode group. The major surgical method in conventional mode group was lobectomy resection (48.8%). While the segmental resection was the major surgical in day surgery mode group. The hospital stay and the time of drain was significant longer in conventional mode group. And the total medical cost in conventional was more than day-surgery mode group. While the histology and postoperative complications were homogenous between the two groups. CONCLUSION: Before this, day surgery and robotics assistant surgery in thoracic surgery had been proved feasibility and safety. However, there was no report of day surgery unit robotics assistant thoracic surgery. Our clinical practice demonstrated that the method of day surgery unit robotics thoracic surgery is feasibility and safety enough.

PSMA1, a Poor Prognostic Factor, Promotes Tumor Growth in Lung Squamous Cell Carcinoma.

Lung squamous cell carcinoma (LUSC) has a poor clinical prognosis and lacks effective targeted therapy. This study is aimed at investigating the role of PSMA1 (proteasome subunit alpha type-1) in LUSC. The differential expression genes (DEGs) in LUSC were retrieved from The Cancer Genome Atlas (TCGA) by "edgR" algorithm and by "limma" R package. Then, the relationship between genes and overall survival (OS) was explored by the least absolute shrinkage and selection operator (LASSO) and multivariate Cox (multi-Cox) regression. Next, the PSMA1 expression in tissues of LUSC was detected by IHC, qRT-PCR, and western blot (WB). Moreover, the effects of PSMA1 on the proliferation and viability of LUSC cell were explored by cell counting kit 8 (CCK-8) assays, colony formation assays, and flow cytometry (FCM) analysis. All 4421 DEGs were screened by TCGA database, and 26 genes associated with OS were selected by multi-Cox. Based on TCGA database, PSMA1 was highly expressed in tissues of LUSC patients, and OS and FP of patients with PSMA1 overexpression were significantly lower than those of patients with low PSMA1 expression. Furthermore, PSMA1 knockdown significantly decreased the proliferation of LUSC cells and promoted the apoptosis of LUSC cells, and these effects were reversed by PSMA1 overexpression. The results of this project supported that PSMA1 might be a critical gene regulating the development of LUSC and has the potential to be explored as a prognostic biomarker of LUSC.

Design and fabrication of a focus-tunable liquid cylindrical lens based on electrowetting.

In this study, a focus-tunable liquid cylindrical lens based on electrowetting was designed and fabricated. The cylindrical cavity usually used in common electrowetting zoom spherical lenses was replaced by a 20 mm × 10 mm × 8 mm cuboid cavity, in which the interface of two liquids formed a toroid owing to the electrowetting effect. The proposed liquid cylindrical lens can serve as either a converging or diverging lens with the response time under 110 ms by changing the supplied voltage. The zoom lens we fabricated worked stably under 0-110 V voltage for a long time, guaranteeing that the focal length of the liquid cylindrical lens can range within (-∞, -148.36 mm) ∪ (697.21 mm, +∞). By combining the liquid lens that we designed with a simple fixed cylindrical lens, a cylindrical lens system with an arbitrary focal length suitable for various tasks in beam manipulation can be realized.

Robotic-assisted thoracic surgery following neoadjuvant chemoimmunotherapy in patients with stage III non-small cell lung cancer: A real-world prospective cohort study.

Objective: Stage III non-small cell lung cancer (NSCLC) is a heterogeneous group of diseases. For this subset of patients, clinical management is still under debate and prognosis remains poor so far. In the present study, we aimed to evaluate the feasibility and safety of robotic-assisted thoracic surgery after neoadjuvant chemoimmunotherapy in stage III NSCLC. Methods: A real-world prospective cohort study was performed in a single-center setting from April 2021 to May 2022. Patients who were diagnosed with resectable or potentially resectable stage IIIA-B NSCLC and received neoadjuvant chemoimmunotherapy followed by robotic-assisted thoracic surgery were enrolled. Pathological response to neoadjuvant chemoimmunotherapy, treatment-related adverse events, and surgical outcomes of these patients were evaluated. Results: A total of 44 patients who underwent robotic-assisted thoracic surgery after three doses of neoadjuvant chemoimmunotherapy were included in this study. Of these, 36 of 44 (81.8%) patients had a major pathological response, and 26 (59.1%) had a pathological complete response based on pathological examination of surgical specimen. Eight patients (18.2%) suffered grade 3 treatment-related adverse events, including neutropenia (n = 4), increased aminotransferases (n = 3), anemia (n = 1), and cutaneous capillary endothelial proliferation (n = 1). Robotic-assisted thoracic surgery was performed subsequently, and R0 resection was achieved in all patients. Only two (4.5%) patients required conversion to thoracotomy. Surgical complications occurred in five (11.4%) patients, including air leak (n = 3), chylothorax (n = 2), and surgical site infection (n = 1). There was no re-surgery or postoperative mortality within 90 days. Conclusion: Robotic-assisted thoracic surgery following neoadjuvant chemoimmunotherapy showed good feasibility and safety in stage III NSCLC. It was not associated with unexpected perioperative morbidity or mortality and may be a promising therapeutic option in stage III NSCLC. These results need further confirmation by more large-scale clinical trials.

The Comprehensive Analysis Identified an Autophagy Signature for the Prognosis and the Immunotherapy Efficiency Prediction in Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a fatal malignancy in the world. Growing evidence demonstrated that autophagy-related genes regulated the immune cell infiltration and correlated with the prognosis of LUAD. However, the autophagy-based signature that can predict the prognosis and the efficiency of checkpoint immunotherapy in LUAD patients is yet to be discovered. Methods: We used conventional autophagy-related genes to screen candidates for signature construction in TCGA cohort and 9 GEO datasets (tumor samples, n=2181; normal samples, n=419). An autophagy-based signature was constructed, its correlation with the prognosis and the immune infiltration of LUAD patients was explored. The prognostic value of the autophagy-based signature was validated in an independent cohort with 70 LUAD patients. Single-cell sequencing data was used to further characterize the various immunological patterns in tumors with different signature levels. Moreover, the predictive value of autophagy-based signature in PD-1 immunotherapy was explored in the IMvigor210 dataset. At last, the protective role of DRAM1 in LUAD was validated by in vitro experiments. Results: After screening autophagy-related gene candidates, a signature composed by CCR2, ITGB1, and DRAM1 was established with the ATscore in each sample. Further analyses showed that the ATscore was significantly associated with immune cell infiltration and low ATscore indicated poor prognosis. Meanwhile, the prognostic value of ATscore was validated in our independent LUAD cohort. GSEA analyses and single-cell sequencing analyses revealed that ATscore was associated with the immunological status of LUAD tumors, and ATscore could predict the efficacy of PD-1 immunotherapy. Moreover, in vitro experiments demonstrated that the inhibition of DRAM1 suppressed the proliferation and migration capacity of LUAD cells. Conclusion: Our study identified a new autophagy-based signature that can predict the prognosis of LUAD patients, and this ATscore has potential applicative value in the checkpoint therapy efficiency prediction.

CHIP-mediated CIB1 ubiquitination regulated epithelial-mesenchymal transition and tumor metastasis in lung adenocarcinoma.

CIB1 is a homolog of calmodulin that regulates cell adhesion, migration, and differentiation. It has been considered as an oncogene in many tumor cells; however, its role in lung adenocarcinoma (LAC) has not been studied. In this study, the expression levels of CIB1 in LAC tissues and adjacent normal tissues were examined by immunohistochemistry, and the relationship between CIB1 expression and patient clinicopathological characteristics was analyzed. The effects of CIB1 on epithelial-mesenchymal transition (EMT), migration, and metastasis of LAC cells were determined in vitro and vivo. Proteins interacting with CIB1 were identified using electrospray mass spectrometry (LS-MS), and CHIP was selected in the following assays. Carboxyl-terminus of Hsp70-interacting protein (CHIP) is a ubiquitin E3 ligase. We show that CHIP can degrade CIB1 via promoting polyubiquitination of CIB1 and its subsequent proteasomal degradation. Besides, lysine residue 10 and 65 of CIB1 is the ubiquitinated site of CIB1. Furthermore, CHIP-mediated CIB1 downregulation is critical for the suppression of metastasis and migration of LAC. These results indicated that CHIP-mediated CIB1 ubiquitination could regulate epithelial-mesenchymal and tumor metastasis in LAC.

MICAL2 is a novel nucleocytoplasmic shuttling protein promoting cancer invasion and growth of lung adenocarcinoma.

MICAL2 is a tumor-promoting factor involved in cell migration, invasion, deformation, and proliferation not yet fully explored in lung adenocarcinoma (LUAD). This study demonstrated that MICAL2 was overexpressed and cytoplasm-enriched in LUAD tissues. Moreover, high cytoplasmic MICAL2 and/or total MICAL2 expression levels were positively correlated with lymphatic metastasis and shorter overall survival in LUAD patients. MICAL2 promoted LUAD cell proliferation, migration, invasion, and epithelial to mesenchymal transition-all of which involved the AKT and myosin-9 pathways. Furthermore, MICAL2 was identified as a nucleoplasm shuttling protein dependent on myosin-9 and its C-terminal fragment. MICAL2-ΔC-enriched in the nucleus-had less impact on tumor malignancy in LUAD cells in vitro and in vivo. Tumor promotion by MICAL2 was reduced by nuclear-export inhibitor, myosin-9 inhibitor, or si-myosin-9-all of which effectively inhibited MICAL2's nuclear export. Finally, the expression and subcellular location as well as clinical significance of MICAL2 and myosin-9 were analyzed across TCGA data and LUAD tissue arrays. Our data revealed that MICAL2 overexpression and nuclear export were associated with cancer progression; inhibiting its expression and/or nuclear export may provide a new target for LUAD therapy.

Salt tolerance and exclusion in the mangrove plant Avicennia marina in relation to root apoplastic barriers.

Salt tolerance and the possible functions of suberization on salt exclusion and secretion were examined in a dominant mangrove plant, Avicennia marina. The results showed that low salinities (10‰ and 20‰) almost has no negative effect on A. marina, however significant growth inhibitions were observed in the seedlings grown in higher salinities (30‰ and 40‰). With the increases of salinity, increased tissue Na+ content and enhanced salt secretion by glands were observed. Obvious suberization thickening were detected both in the exodermis and endodermis of the roots after salt pretreatment when compared to the roots without salt treatment. More importantly, the present data further confirmed that these root apoplastic barriers would directly decrease Na+ loading into xylem. Higher salt tolerance was observed in the seedlings pre-cultivated by salty tide when compared to fresh water cultivated A. marina. In summary, this study suggests a barrier property of suberization in dealing with salt exclusion in mangroves, a moderate salt pre-treatment may benefit plant withstanding high salinity.

Risk factors associated with prolonged air leak after video-assisted thoracic surgery pulmonary resection: a predictive model and meta-analysis.

BACKGROUND: This study aimed to establish a predictive model for prolonged air leak (PAL) after video-assisted thoracic surgery (VATS) lung resection; and additionally, to present a meta-analysis of the relevant literature to estimate the association between various clinical factors and PAL. METHODS: A retrospective, case-control study was conducted using univariate analysis and logistic regression based on 493 medical records from patients who underwent VATS lung resection between January 2015 and August 2017 at our institution. PAL was defined as air leak more than 5 days after lung surgery. Subsequently, a nomogram was established as a predictive model. Relevant studies were screened from PubMed, Embase and Cochrane for relevant studies and data was extracted from those enrolled. Pooled odds ratios or weighted mean differences with corresponding 95% confidence intervals were calculated to estimate the association between various clinical factors and PAL. RESULTS: Incidence of PAL after VATS lung resection was observed in 54 (10.8%) of 493 patients. Logistic regression revealed that smoking (P=0.014), pulmonary function (P=0.011), pleural adhesion (P<0.001), stapling length (P<0.001), early postoperative drainage (P=0.002) were significantly associated with PAL. Our meta-analysis, including 17 eligible studies and 14 potential risk factors, further validating our findings. Upper lobectomy was determined to be a significant risk factor for PAL in Europeans and North Americans (OR =2.03, P<0.001), but not in Asians (OR =1.04, P=0.610). Importantly, the constructed nomogram demonstrated a good predictive ability (C-index =0.858). CONCLUSIONS: Lung stapling length and early postoperative drainage are important indicators for the evaluation of PAL occurrence. Upper pulmonary resection is a factor with particular regional differences as its association with PAL is not significant within Asian populations. Our nomogram, incorporating multiple factors, provided a simple and practical predictive model with value for clinical application.

Overexpressed C14orf166 associates with disease progression and poor prognosis in non-small-cell lung cancer.

Chromosome 14 ORF 166 (C14orf166), a protein involved in the regulation of RNA transcription and translation, has been reported to possess the potency to promote tumorigenesis; however, the role of C14orf166 in non-small-cell lung cancer (NSCLC) remains unknown. The purpose of the present study was to assess C14orf166 expression and its clinical significance in NSCLC. Immunohistochemical staining, quantitative real-time PCR (qRT-PCR), and Western blotting were used to detect the C14orf166 protein and mRNA expression levels in NSCLC tissues compared with adjacent normal tissues, as well as in NSCLC cells lines compared with normal human bronchial epithelial cells (HBE). Then, the correlations between the C14orf166 expression levels and the clinicopathological features of NSCLC were analyzed. Additionally, the Cox proportional hazard model was used to evaluate the prognostic significance of C14orf166. We found that C14orf166 expression increased in carcinoma tissues compared with their adjacent normal tissues at the protein (P<0.001) and mRNA levels (P<0.001). High expression of C14orf166 was significantly associated with the T stage (P=0.006), lymph node metastasis (P=0.001), advanced TNM stage (P<0.001), and chemotherapy (P<0.001). Moreover, according to the survival analysis, patients with overexpressed C14orf166 were inclined to experience a shorter overall survival and disease-free survival time (P<0.001). Multivariate COX analysis implied that C14orf166 was an independent prognostic biomarker. Taken together, our findings indicate that the overexpression of C14orf166 may contribute to the disease progression of NSCLC, represent a novel prognostic predictor and help high-risk patients make better decisions for subsequent therapy.

In Situ Network Formation in PBT Vitrimers via Processing-Induced Deprotection Chemistry.

Although the network dynamics and mechanical properties of poly(butylene terephthalate) vitrimers can to some extent be controlled via chemical and physical approaches, it remains a challenge to be able to process PBT vitrimers with the same processing conditions via, for example, injection molding as neat PBT. Here, it is shown that the use of protected pentaerythritol as a latent cross-linker and the use of a Zn(II) transesterification catalyst allows for the in situ dynamic network formation in PBT during processing, with a delayed onset of gelation. This process can be controlled by adjusting the processing temperature, (protected) cross-linker content, and the type of protection group. This solvent-free deprotection strategy opens the way to high production rates of PBT vitrimer products via injection molding with the combination of low viscosity during processing and vitrimer characteristics in the final product.

Clinical Characteristics and Prognostic Factors of Small Intestine Angiosarcoma: a Retrospective Clinical Analysis of 66 Cases.

BACKGROUND/AIMS: Primary angiosarcoma of the small intestine is a rare neoplasia, and there are limited data from systematic analyses. The aim of this study is to describe the clinical and pathological characteristics in addition to the prognostic factors for this rare neoplasia. METHODS: We retrospectively collected the clinical records and prognostic information of 66 patients with small intestine angiosarcoma reported between 1970 and 2017. We used the Chi-square test, the log-rank test, and Cox regression analyses to evaluate the data. RESULTS: There were 66 patients diagnosed with small intestine angiosarcoma. The onset age ranged from 24-92 years old. There were 24 patients diagnosed before the year 2000, and 42 patients were diagnosed after 2000. The data indicated that 49 cases were diagnosed as primary disease, and the remaining 15 cases were secondary disease. The main clinical symptoms were nonspecific and included gastrointestinal (GI) bleeding and abdominal pain. Additionally, we found multi-center foci were one of the characteristics of this disease. Radiation-induced small intestine angiosarcoma (RSIA) is a special type of disease with a similar prognosis. This type was more frequent in females and decreased after the year 2000. We also found that GI bleeding was less common in RSIA cases. The log-rank test results revealed that old-age, poor differentiation, and GI bleeding were associated with worse prognosis. Surgical treatment showed a trend toward a prolonged survival time. However, the result was not statistically significant. Our results show treatment with adjuvant therapy improved prognosis. The multivariate Cox analysis demonstrated adjuvant therapy was an independent indicator of a favorable outcome in small intestine angiosarcoma patients. CONCLUSION: Pay attention to the unexplained gastrointestinal bleeding could lead to a faster diagnosis and control of small intestine angiosarcoma. Furthermore, treatments including adjuvant therapy can effectively improve the prognosis.

Overexpressed PTOV1 associates with tumorigenesis and progression of esophageal squamous cell carcinoma.

PTOV1 has been demonstrated to play an extensive role in many types of cancers. This study takes the first step to clarify the potential relationship between esophageal squamous cell carcinoma and PTOV1 expression and highlight the link between PTOV1 and the tumorigenesis, progression, and prognosis of esophageal squamous cell carcinoma. PTOV1 expression was detected by quantitative reverse transcription polymerase chain reaction and western blotting or immunohistochemical staining in esophageal squamous cell carcinoma cell lines, esophageal squamous cell carcinoma tissues, and its paired adjacent non-cancerous tissues. Moreover, we have analyzed the relationship between PTOV1 expression and clinicopathological features of esophageal squamous cell carcinoma. Survival analysis and Cox regression analysis were used to assess its prognostic significance. We found that PTOV1 expression was significantly higher in the esophageal squamous cell carcinoma cell lines and tissues at messenger RNA level (p < 0.001) and protein level (p < 0.001). Gender, tumor size, or differentiation was tightly associated with the PTOV1 expression. Lymph node involvement (p < 0.001) and TNM stage (p < 0.001) promoted a high PTOV1 expression. A prognostic significance of PTOV1 was also found by Log-rank method, and the overexpression of PTOV1 was related to a shorter OS and DFS. Multiple Cox regression analysis indicated overexpressed PTOV1 as an independent indicator for adverse prognosis. In conclusion, this study takes the lead to demonstrate that the overexpressed PTOV1 plays a vital role in the tumorigenesis and progression of esophageal squamous cell carcinoma, and it is potentially a valuable prognostic predicator and new chemotherapeutic target for esophageal squamous cell carcinoma.

Weekday of Surgery Affects Postoperative Complications and Long-Term Survival of Chinese Gastric Cancer Patients after Curative Gastrectomy.

Many factors have been reported to affect the long-term survival of gastric carcinoma patients after gastrectomy; the present study took the first attempt to find out the potential role of weekday carried out surgery in the postoperative prognosis of gastric cancer patients. 463 gastric cancer patients have been followed up successfully. Pearson χ2 test was used for univariate analyses. Survival curves were constructed by using Kaplan-Meier method and evaluated by using the log-rank test. The Cox proportional hazard regression model was used to find out the risk factors, and subgroup analysis was conducted to rule out confounding factors. We found that the patients who underwent gastrectomy on the later weekday (Wednesday-Friday) more easily suffered from a higher postoperative morbidity. Weekday of surgery was one of the independent indicators for the prognosis of patients after gastric cancer surgery. However, the role of weekday of surgery was significantly weakened in the complications group. In conclusion, surgery performed in the later weekday was more likely to lead to increased postoperative complications and an unfavorable role in prognosis of Chinese gastric cancer patients after curative gastrectomy.

Expression and clinical significance of C14orf166 in esophageal squamous cell carcinoma.

C14orf166, a 28 kD protein regulating RNA transcription and translation, may serve a critical role in oncogenesis. The aim of the current study was to explore the association between C14orf166 expression and esophageal squamous cell carcinoma (ESCC) and to draw attention to the association between C14orf166 and the initiation, progression and prognosis of ESCC. C14orf166 expression in ESCC and paired normal tissues was detected by immunohistochemical staining, western blotting and reverse transcription­quantitative polymerase chain reaction, and the association between C14orf166 expression and clinicopathological characters of ESCC was analyzed. Survival analysis was used to assess the prognostic significance of C14orf166 and it was observed that C14orf166 expression was higher in the ESCC tissues when compared with adjacent non­cancerous tissues at protein (P<0.001) and mRNA levels (P<0.001). There was a significant difference in T stage, lymph node metastasis and TNM stage in patients categorized according to different C14orf166 expression levels. The overexpression of C14orf166 was associated with a shorter overall survival and disease­free survival, and multivariate analysis indicated that C14orf166 was an independent prognostic indicator. The present study indicates that the expression of C14orf166 is elevated in ESCC, and is potentially a valuable prognostic predictor for ESCC.

Expression and clinical significance of Apollon in esophageal squamous cell carcinoma.

Apollon, an unusually large member of the inhibitors of apoptosis protein family, may be important for oncogenesis development. The aim of the present study was to assess the association between esophageal squamous cell carcinoma (ESCC) and Apollon expression levels, and to highlight the association between Apollon and the occurrence, development and prognosis of ESCC. Apollon expression was detected by immunohistochemical staining and reverse transcription-quantitative polymerase chain reaction in ESCC tissues, adjacent non­cancerous tissues and paired normal tissues respectively, in order to analyze the association between Apollon expression and the clinicopathological features of ESCC. Survival analysis was used to assess the prognostic significance of Apollon expression. It was determined that the mRNA and protein expression levels of Apollon were significantly higher in the carcinoma tissues compared with the adjacent non­cancerous tissues and normal control tissues (P<0.001). There was a significant difference in lymph node involvement and the tumor, nodes, and metastases stage in patients categorized according to different Apollon expression levels. The prognostic significance of Apollon was also determined using the log­rank method. The overexpression of Apollon was associated with shorter overall survival and disease-free survival rates. The present study indicates that Apollon expression is associated with the biological characteristics of ESCC, and may be a valuable prognostic factor and a novel chemotherapeutic target for ESCC treatment.

miR-675-5p enhances tumorigenesis and metastasis of esophageal squamous cell carcinoma by targeting REPS2.

Recently H19 has been demonstrated to be up-regulated in esophageal squamous cell carcinoma (ESCC) and shown to be the precursor of miR-675 that encodes miR-675-5p conservatively. miR-675 is overexpressed in many human cancers; however, the function of miR-675-5p is largely unknown in ESCC. In this study, we found that miR-675-5p expression was significantly increased in ESCC tissues and cell lines and related with ESCC progression and poor prognosis. We also showed here that down-regulation of miR-675-5p in ESCC cells dramatically induced cell G1 arrest and reduced cell proliferation, colony formation, migration and invasion in vitro as well as tumorigenesis and tumor metastasis in vivo. We subsequently identified that REPS2 was a target gene of miR-675-5p. We found that inhibition of miR-675-5p up-regulated the expression of REPS2, inhibited RalBP1/RAC1/CDC42 signaling pathway. Inversely, interference of REPS2 abrogated the effect induced by miR-675-5p inhibition, which resembled the function of miR-675-5p up-regulation. Taken together, our findings suggested that miR-675-5p might play an oncogenic role in ESCC through RalBP1/RAC1/CDC42 signaling pathway by inhibiting REPS2 and might serve as a valuable prognostic biomarker and therapeutic target for ESCC patients.

Differential levels of cathepsin B and L in serum between young and aged healthy people and their association with matrix metalloproteinase 2.

OBJECTIVE: Most publications describe cathepsin B and L as tumor and metastasis factors. These proteases also play a very important role in aging process. The aim of this study was to evaluate the serum level of cathepsin B and L with aging and their association with matrix metalloproteinase 2 (MMP2), which was reported to associate with age-related diseases. METHODS: This research was conducted using blood samples provided by healthy people (n=90, 63 men and 27 women). Subjects were subdivided into groups with respect to age: young (about 18-30 years old, n=30), middle age (about 36-50 years old, n=30), and aged (above 56 years old, n=30). Altered serum level of cathepsin B, cathepsin L, and MMP2 with aging was studied by enzyme-linked immunosorbent assay (ELISA) and Western blotting using discriminative antibodies specific for each factor. RESULTS: ELISA and Western blotting revealed that the serum level of cathepsin L and MMP2, but not cathepsin B significantly decreased in aged group compared with young group. Cathepsin L positively correlates with MMP2 among the whole healthy people (r(2)=0.869, p<0.0001). CONCLUSION: The serum level of cathepsin L decreased with age, while cathepsin B remained no significant difference between young and aged individuals. In addition, cathepsin L positively correlates with MMP2. PRACTICE: The cathepsin L may be used as a monitoring index in age-related diseases. IMPLICATIONS: In addition to cathepsin B, cathepsin L may be also involved in the aging process.

Down-regulation of miR-675-5p contributes to tumor progression and development by targeting pro-tumorigenic GPR55 in non-small cell lung cancer.

BACKGROUND: microRNAs are small noncoding RNAs that modulate a variety of cellular processes by regulating multiple targets, which can promote or inhibit the development of malignant behaviors. Accumulating evidence suggests that miR-675-5p plays important roles in human carcinogenesis. However, its precise biological role remains largely elusive. This study examined the role of miR-675-5p in non- small cell lung cancer (NSCLC). METHODS: The expression of miR-675-5p was analyzed by real-time quantitative PCR (qRT-PCR). The effect of miR-675-5p on proliferation was evaluated through MTT and colony formation assays, and cell migration and invasion were evaluated through transwell assays. The expression of target proteins and downstream molecules was analyzed by western blotting and immunohistochemical staining. The luciferase reporter assay was used to assess the target genes of miR-675-5p in non-small cell lung cancer cells. RESULTS: The expression levels of miR-675-5p in NSCLC tissues were significantly reduced compared to those in adjacent non-cancerous tissues (P < 0.001). The expression of miR-675-5p in patients with non-small cell lung cancer had a negative correlation with lymph node metastasis (P < 0.01) and TNM stage (P < 0.05). Down-regulation of miR-675-5p promoted cell growth, proliferation, colony formation, invasion and migration, and promoted the tumorigenicity graft growth of nude mice in vivo (P < 0.01); whereas up-regulation of miR-675-5p had the contrary effects. The luciferase reporter assay showed that GPR55 was a direct target gene of miR-675-5p. Overexpression of miR-675-5p can lead to the down-regulation of GPR55 and its signaling pathway, whereas the effect can be reversed by down-regulation of miR-675-5p expression. CONCLUSIONS: miR-675-5p functions as a novel tumor suppressor in NSCLC and the anti-oncogenic activity may involve its inhibition of the target gene GPR55. These findings suggest the possibility for miR-675-5p as a therapeutic target in NSCLC.