Evaluation of the anti-aging potential of acetyl tripeptide-30 citrulline in cosmetics.

Acetyl tripeptide-30 citrulline, a commercialized bio-active peptide, is widely used in anti-wrinkle formulations. Volunteer-based tests have demonstrated that topical application of products containing acetyl tripeptide-30 citrulline significantly reduces the visibility of stretch marks. However, there is still a lack of research dedicated to systematically and holistically evaluating its cosmetic properties and elucidating its mechanisms of action. In this study, we assessed the cosmetic potential of acetyl tripeptide-30 citrulline using human immortalized keratinocytes (HaCaT) and mouse embryonic fibroblasts (3T3). Our findings reveal that acetyl tripeptide-30 citrulline exhibits anti-inflammatory and antioxidant activities in skin cells, particularly effective against the inflammatory markers cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), and the extent of inhibition of reactive oxygen species (ROS) production ranged from 95 % to 340 %. Moreover, acetyl tripeptide-30 citrulline specifically up-regulates Collagen IV and down-regulates matrix metalloproteinase-9 (MMP9), enhances the expression of skin barrier proteins transglutaminase 1 (TGM1) and filaggrin (FLG), thereby demonstrating its reparative capabilities. Additionally, acetyl tripeptide-30 citrulline increases the expression of the water channel protein aquaporin 3 (AQP3), thus improving skin hydration function. These results substantiate the previously proclaimed cosmetic attributes of acetyl tripeptide-30 citrulline and support its efficacy as an anti-aging agent in dermatological applications.

Effects of Network-based Positive Psychological Nursing Model on Negative Emotions, Cancer-related Fatigue, and Quality of Life in Cervical Cancer Patients with Post-operative Chemotherapy.

AIM: Cervical cancer patients with post-operative chemotherapy experience anxiety, depression, and cancer-related fatigue, leading to a decline in their quality of life and posing challenges to the rehabilitation of patients. Therefore, it is necessary to explore effective nursing methods. This study aimed to investigate the effects of a web-based positive psychological nursing model on negative emotions, cancer-related fatigue, self-management efficacy, treatment compliance, and quality of life among cervical cancer patients with post-operative chemotherapy. METHODS: This retrospective study included 101 cervical cancer patients who underwent surgical intervention at our hospital between January 2019 and December 2023. Patients who received the usual mode of care were included in the control group (n = 48), while those who received the web-based positive psychological care mode were included in the study group (n = 53). For all study subjects, various assessment indices were evaluated, including baseline characteristics, treatment adherence, and the Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Revised Piper Fatigue Scale (RPFS), the Chinese version of the Strategies Used by Patients to Promote Health (C-SUPPH), and European Organization for Research and Treatment of Cancer Quality of Life questionnaire -Core 30 (EORTC QLQ-C30). Additionally, anxiety/depression, cancer-related fatigue, self-management efficacy, treatment compliance, and quality of life were compared between the two groups. RESULTS: After the intervention, the HAMA score, HAMD score, and RPFS score were significantly decreased for both groups compared to before intervention (p < 0.05). However, the C-SUPPH score was significantly increased than before intervention (p < 0.05). We observed that HAMA, HAMD, and RPFS scores were substantially lower in the study group than those in the control group after intervention (p < 0.05). In contrast, C-SUPPH scores were significantly higher (p < 0.05). After the intervention, treatment compliance was significantly better in the study group compared to the control group. Furthermore, the EORTC QLQ-C30 score was substantially higher than that of the control group (p < 0.05). CONCLUSIONS: The network-based positive psychological nursing model can effectively alleviate negative emotions and cancer-related fatigue in cervical cancer patients who have undergone post-operative chemotherapy, thereby improving their quality of life. Additionally, this model improves patients' self-management effectiveness and treatment compliance. These findings provide novel insights into the nursing of cervical cancer patients with post-operative chemotherapy, underscoring its clinical significance.

Dibutyl phthalate released by solitary female locusts mediates sexual communication at low density.

Sex pheromones play a crucial role in mate location and reproductive success. Insects face challenges in finding mates in low-density environments. The population dynamics of locusts vary greatly, ranging from solitary individuals to high-density swarms, leading to multiple-trait divergence between solitary and gregarious phases. However, differences in sexual communication between solitary and gregarious locusts have not been sufficiently explored. Herein, we found that solitary locusts but not gregarious ones heavily rely on a single compound, dibutyl phthalate (DBP), for sexual communication. DBP is abundantly released by solitary female locusts and elicits strong attraction of male solitary and gregarious locusts. Solitary adult males display much higher electrophysiological responses to DBP than adult females. Additionally, LmigOr13 was identified as the DBP-specific odorant receptor expressed in neurons housed in basiconic sensilla. Male LmigOr13-/- mutants generated by CRISPR/Cas9 have low electrophysiological responses and behavioral attraction to DBP in both laboratory and field cage experiments. Notably, the attractiveness of DBP to male locusts becomes more evident at lower population densities imposed by controlling the cage size. This finding sheds light on the utilization of a sex pheromone to promote reproductive success in extremely low-density conditions and provides important insights into alternative approaches for population monitoring of locusts.

Delta-like ligand 3: A promising target against small cell lung cancer.

This commentary highlighted the current knowledge about novel DLL3-targeting agents for refractory small cell lung cancer.

A pH-triggered N-oxide polyzwitterionic nano-drug loaded system for the anti-tumor immunity activation research.

Triple negative breast cancer (TNBC) has the characteristics of low immune cell infiltration, high expression of tumor programmed death ligand 1 (PD-L1), and abundant cancer stem cells. Systemic toxicity of traditional chemotherapy drugs due to poor drug selectivity, and chemotherapy failure due to tumor drug resistance and other problems, so it is particularly important to find new cancer treatment strategies for TNBC with limited treatment options. Both the anti-tumor natural drugs curcumin and ginsenoside Rg3 can exert anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells, reducing PD-L1 expression, and reducing cancer stem cells. However, they have the disadvantages of poor water solubility, low bioavailability, and weak anti-tumor effect of single agents. We used vinyl ether bonds to link curcumin (Cur) with N-O type zwitterionic polymers and at the same time encapsulated ginsenoside Rg3 to obtain hyperbranched zwitterionic drug-loaded micelles OPDEA-PGED-5HA@Cur@Rg3 (PPH@CR) with pH response. In vitro cell experiments and in vivo animal experiments have proved that PPH@CR could not only promote the maturation of dendritic cells (DCs) and increase the CD4+ T cells and CD8+ T cells by inducing ICD in tumor cells but also reduce the expression of PD-L1 in tumor tissues, and reduce cancer stem cells and showed better anti-tumor effects and good biological safety compared with free double drugs, which is a promising cancer treatment strategy.

Proteomic and metabolomic profiling of plasma predicts immune-related adverse events in older patients with advanced non-small cell lung cancer.

The clinical success of immune checkpoint inhibitors is compromised by the fact of immune-related adverse events (irAEs), especially for older patients. To identify predictive biomarkers for older patients with irAEs, we used multiplex immunoassay and flow cytometry and liquid chromatography-tandem mass spectrometry to test immune factors and plasma protein and metabolites levels in non-small cell lung cancer (NSCLC) patients. The results showed that older patients with irAEs displayed lower CD28, CD4+ T cell, and B cell and higher interleukin (IL)-10 and CCL2 levels at baseline. Besides, lower aldolase, fructose-bisphosphate B (ALDOB), higher ST6GAL1, and lower lactate/pyruvate ratio at baseline were found in older patients with irAEs. Based on metabolomic markers, predictive models were developed to distinguish patients with grade 2-4 irAEs from grade 0-1 (Area under curve, AUC = 0.831) and to distinguish patients with grade 3-4 irAEs from grade 2 (AUC = 1). Our results confirmed the predictive value of plasma metabolites for irAEs in older patients with NSCLC.

Protective effects of Amauroderma rugosum on dextran sulfate sodium-induced ulcerative colitis through the regulation of macrophage polarization and suppression of oxidative stress.

BACKGROUND: Amauroderma rugosum (AR) is a medicinal mushroom commonly used to treat inflammation, gastric disorders, epilepsy, and cancers due to its remarkable anti-inflammatory and anti-oxidative properties. This study was designed to evaluate the pharmacological effects of AR and its underlying mechanism of action against ulcerative colitis (UC) in vitro and in vivo. METHODS: A UC mouse model was established by administration of dextran sulfate sodium (DSS). AR extract was administered intragastrically to mice for 7 days. At the end of the experiment, histopathology, macrophage phenotype, oxidative stress, and inflammatory status were examined in vivo. Furthermore, RAW 264.7, THP-1, and Caco-2 cells were used to elucidate the mechanism of action of AR in vitro. RESULTS: AR extract (0.5-2 mg/mL) significantly suppressed lipopolysaccharide (LPS) and interferon-gamma (IFN-γ)-induced M1 macrophage (pro-inflammatory) polarization in both RAW 264.7 and THP-1 cells. LPS-induced pro-inflammatory mediators (nitric oxide, TNF-α, IL-1ß, MCP-1, and IL-6) were reduced by AR extract in a concentration-dependent manner. Similarly, AR extract downregulated MAPK signaling activity in LPS-stimulated RAW 264.7 cells. AR extract elicited a concentration-dependent increase in the mRNA expression of M2 (anti-inflammatory) phenotype markers (CD206, Arg-1, Fizz-1, and Ym-1) in RAW 264.7 cells. Moreover, AR extract suppressed DSS-induced ROS generation and mitochondrial dysfunction in Caco-2 cells. The in vivo experiment revealed that AR extract (200 mg/kg) increased colon length compared to the DSS-treated group. In addition, disease activity index, spleen ratio, body weight, oxidative stress, and colonic inflammation were markedly improved by AR treatment in DSS-induced UC mice. Finally, AR suppressed M1 and promoted M2 macrophage polarization in UC mice. CONCLUSION: The AR extract protected against DSS-induced UC by regulating macrophage polarization and suppressing oxidative stress. These valuable findings suggest that adequate intake of AR can prevent and/or treat UC.

Comparison of Aroma and Taste Profiles of Kiwi Wine Fermented with/without Peel by Combining Intelligent Sensory, Gas Chromatography-Mass Spectrometry, and Proton Nuclear Magnetic Resonance.

Kiwi wine (KW) is tipically made by fermenting juice from peeled kiwifruit, resulting in the disposal of peel and pomace as by-products. However, the peel contains various beneficial compounds, like phenols and flavonoids. Since the peel is edible and rich in these compounds, incorporating it into the fermentation process of KW presents a potential solution to minimize by-product waste. This study compared the aroma and taste profiles of KW from peeled (PKW) and unpeeled (UKW) kiwifruits by combining intelligent sensory technology, GC-MS, and 1H-NMR. Focusing on aroma profiles, 75 volatile organic compounds (VOCs) were identified in KW fermented with peel, and 73 VOCs in KW without peel, with 62 VOCs common to both. Among these compounds, rose oxide, D-citronellol, and bornylene were more abundant in UKW, while hexyl acetate, isoamyl acetate, and 2,4,5-trichlorobenzene were significantly higher in PKW. For taste profiles, E-tongue analysis revealed differences in the taste profiles of KW from the two sources. A total of 74 molecules were characterized using 1H-NMR. UKW exhibited significantly higher levels of tartrate, galactarate, N-acetylserotonin, 4-hydroxy-3-methoxymandelate, fumarate, and N-acetylglycine, along with a significantly lower level of oxypurinol compared to PKW. This study seeks to develop the theoretical understanding of the fermentation of kiwifruit with peel in sight of the utilization of the whole fruit for KW production, to increase the economic value of kiwifruit production.

Surgical vs nonsurgical treatment for esophageal squamous cell carcinoma in patients older than 70 years: a propensity score matching analysis.

PURPOSE: With the rising life expectancy and an aging population, it has become increasingly important to investigate treatments suitable for older adult patients with esophageal cancer. This study investigated whether older adult patients who underwent esophagectomy had better clinical outcomes than those who were nonsurgically treated. METHODS: We retrospectively analyzed patients with esophageal squamous cell carcinoma (ESCC) who were 70 years or older and underwent esophagectomy, radiotherapy (RT), and/or chemoradiotherapy (CRT) between January 2018 and December 2019. Patients were divided into 2 groups: the surgery group (S group) and the nonsurgery group (NS group). We then compared the clinical outcomes of the 2 groups. RESULTS: After a median follow-up duration of 36.6 months, the S group showed better overall survival (OS). The 3-year OS was 59% in the S group and 27% in the NS group (hazard ratio [HR], 0.397; 95% CI, 0.278-0.549; P < .0001). In the S group, the median progression-free survival was 38.3 months (95% CI, 30.6-46.1) compared with 12.3 months in the NS group (HR, 0.511; 95% CI, 0.376-0.695; P < .0001). In addition, the number of adverse events in the NS group was higher than that in the S group (P < .001). CONCLUSION: Overall, patients with ESCC at the age of ≥70 years who underwent esophagectomy had significantly better clinical outcomes than those who underwent nonsurgical treatment with RT and/or CRT.

Characterization of a polysaccharide from Amauroderma rugosum and its proangiogenic activities in vitro and in vivo.

Amauroderma rugosum (AR), also known as "Blood Lingzhi" in Chinese, is a basidiomycete belonging to the Ganodermataceae family. Four polysaccharide fractions were systematically isolated and purified from AR. Subsequently, their compositions were examined and analyzed via high-performance gel permeation chromatography (HPGPC), analysis of the monosaccharide composition, Fourier-transform infrared spectroscopy (FT-IR), and 1H nuclear magnetic resonance (NMR). The zebrafish model was then used to screen for proangiogenic activities of polysaccharides by inducing vascular insufficiency with VEGF receptor tyrosine kinase inhibitor II (VRI). The third fraction of AR polysaccharides (PAR-3) demonstrated the most pronounced proangiogenic effects, effectively ameliorating VRI-induced intersegmental vessel deficiency in zebrafish. Concurrently, the mRNA expression levels of vascular endothelial growth factor (VEGF)-A and VEGF receptors were upregulated by PAR-3. Moreover, the proliferation, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs) were also stimulated by PAR-3, consistently demonstrating that PAR-3 possesses favorable proangiogenic properties. The activation of the Akt, ERK1/2, p38 MAPK, and FAK was most likely the underlying mechanism. In conclusion, this study establishes that PAR-3 isolated from Amauroderma rugosum exhibits potential as a bioresource for promoting angiogenesis.

Impact of Peripheral Anterior Synechiae on the Outcome of Combined Phacoemulsification, Goniosynechialysis, and Goniotomy for Primary Angle Closure Glaucoma and Cataract: A Multicenter Observational Study.

PRCIS: The combination of phacoemulsification, goniosynechialysis and goniotomy is an effective treatment for primary angle closure glaucoma patients with cataract, and this is not linked to the extent of preoperative peripheral anterior synechiae. PURPOSE: To evaluate the impact of the extent of peripheral anterior synechiae (PAS) on the effectiveness and safety of combined phacoemulsification (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes with primary angle closure glaucoma (PACG) and cataract. PATIENTS AND METHODS: This study included patients diagnosed with PACG and cataracts who underwent combined PEI and 120 degrees GSL plus GT (PEI+GSL+GT) between April 2020 and October 2022 at 10 ophthalmic institutes. Eligible patients were divided into 3 groups based on the extent of PAS: 180°≤PAS<270°, 270°≤PAS<360°, and PAS=360°. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. The study defined complete success as postoperative IOP within the 6-18 mm Hg range and a 20% reduction from baseline without the use of topical medications. Qualified success was defined in the same way as complete success, but it allowed for the use of ocular hypotensive medications. RESULTS: Three hundred four eyes of 283 patients were included. The mean follow-up was 12.50±1.24 months. All groups experienced a significant reduction in IOP after the surgery ( P <0.05). There were no significant differences in final IOP, number of medications, and cumulative complete and qualified success rates among the 3 groups ( P >0.05). The groups with 270°≤PAS<360°had a higher frequency of hyphema compared with 180°≤PAS<270° ( P = 0.044). CONCLUSIONS: PEI+GSL+GT has proven to be an effective treatment for PACG with cataracts over a 1 year period. However, the outcome was not correlated with the preoperative extent of PAS.

Clinical outcome and prognostic factors of T4N0M0 colon cancer after R0 resection: A retrospective study.

BACKGROUND: Paradoxically, patients with T4N0M0 (stage II, no lymph node metastasis) colon cancer have a worse prognosis than those with T2N1-2M0 (stage III). However, no previous report has addressed this issue. AIM: To screen prognostic risk factors for T4N0M0 colon cancer and construct a prognostic nomogram model for these patients. METHODS: Two hundred patients with T4N0M0 colon cancer were treated at Tianjin Medical University General Hospital between January 2017 and December 2021, of which 112 patients were assigned to the training cohort, and the remaining 88 patients were assigned to the validation cohort. Differences between the training and validation groups were analyzed. The training cohort was subjected to multivariate analysis to select prognostic risk factors for T4N0M0 colon cancer, followed by the construction of a nomogram model. RESULTS: The 3-year overall survival (OS) rates were 86.2% and 74.4% for the training and validation cohorts, respectively. Enterostomy (P = 0.000), T stage (P = 0.001), right hemicolon (P = 0.025), irregular review (P = 0.040), and carbohydrate antigen 199 (CA199) (P = 0.011) were independent risk factors of OS in patients with T4N0M0 colon cancer. A nomogram model with good concordance and accuracy was constructed. CONCLUSION: Enterostomy, T stage, right hemicolon, irregular review, and CA199 were independent risk factors for OS in patients with T4N0M0 colon cancer. The nomogram model exhibited good agreement and accuracy.

Inhibition of miR-9 Combined With Cisplatin Targeting APE1 Against Angiogenesis in Osteosarcoma.

Osteosarcoma (OS) is a highly malignant tumor, and chemotherapy resistance suggests poor prognosis in OS patients. In this study, the authors discovered that miR-9 has a pro-angiogenic role in OS. The anti-angiogenic effects of cisplatin were greatly increased when miR-9 was suppressed in OS. In addition, the authors demonstrated that miR-9 plays a pro-angiogenic role by targeting apoptosis-inducing factor 1 (APE1) in OS. Importantly, our in vivo experiments showed that inhibition of miR-9 combined with cisplatin could suppress xenograft tumor growth by targeting APE1 and decreasing angiogenesis in OS. In summary, our results suggest that miR-9 plays a role as a tumor promoter, and inhibiting miR-9 and APE1 is a new strategy for inhibiting OS angiogenesis and chemotherapy resistance.

Artificial intelligence-based MRI radiomics and radiogenomics in glioma.

The specific genetic subtypes that gliomas exhibit result in variable clinical courses and the need to involve multidisciplinary teams of neurologists, epileptologists, neurooncologists and neurosurgeons. Currently, the diagnosis of gliomas pivots mainly around the preliminary radiological findings and the subsequent definitive surgical diagnosis (via surgical sampling). Radiomics and radiogenomics present a potential to precisely diagnose and predict survival and treatment responses, via morphological, textural, and functional features derived from MRI data, as well as genomic data. In spite of their advantages, it is still lacking standardized processes of feature extraction and analysis methodology among different research groups, which have made external validations infeasible. Radiomics and radiogenomics can be used to better understand the genomic basis of gliomas, such as tumor spatial heterogeneity, treatment response, molecular classifications and tumor microenvironment immune infiltration. These novel techniques have also been used to predict histological features, grade or even overall survival in gliomas. In this review, workflows of radiomics and radiogenomics are elucidated, with recent research on machine learning or artificial intelligence in glioma.

ST14 interacts with TMEFF1 and is a predictor of poor prognosis in ovarian cancer.

TMEFF1 is a new protein involved in the physiological functions of the central nervous system, and we previously reported TMEFF1 can promote ovarian cancer. ST14 was determined to be involved in the processes of epidermal differentiation, epithelial cell integrity, and vascular endothelial cell migration, etc. The relationship between ST14 and TMEFF1 in the ovary remains unknown. In this study, we detected the expression of ST14 and TMEFF1 in 130 different ovarian cancer tissues through immunohistochemistry. We determined ST14 and TMEFF1 were highly expressed in ovarian cancer, indicating a higher degree of tumor malignancy and a worse prognosis. Tissues significantly expressing ST14 also highly expressed TMEFF1, and the expression of the two proteins was positively correlated. Consistently, immunofluorescence double staining demonstrated the co-localization of ST14 and TMEFF1 in the same region, and immunoprecipitation confirmed the interaction between ST14 and TMEFF1. TMEFF1 expression was also reduced after knocking down ST14 through Western blot. MTT, wound healing and Transwell assays results determined that knockdown of ST14 inhibited proliferation, migration and invasion of ovarian cancer cells in vitro, but the inhibitory effect was restored after adding TMEFF1 exogenous protein. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways analysis showed that ST14 and its related genes were enriched in the processes of epithelial formation, intercellular adhesion, protein localization, and mitosis regulation. We also clarified the kinase, microRNA, and transcription factor target networks and the impact of genetic mutations on prognosis. Overall, high expression of ST14 and TMEFF1 in ovarian cancer predicts higher tumor malignancy and a worse prognosis. ST14 and TMEFF1 co-localize and interact with each other in ovarian cancer. ST14 can regulate TMEFF1 expression to promote proliferation, migration and invasion of ovarian cancer cells. We speculate that the relationship between ST14 and TMEFF1 in ovarian cancer could become a potential target for anti-cancer therapy.

Consolidation chemotherapy after definitive concurrent chemoradiotherapy in patients with inoperable esophageal squamous cell carcinoma: a multicenter non-inferiority phase III randomized clinical trial.

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.

Longitudinal patient-reported outcomes after minimally invasive McKeown esophagectomy for patients with esophageal squamous cell carcinoma.

PURPOSE: Surgery for esophageal squamous cell carcinoma (ESCC) is characterized by a poor prognosis and high complication rate, resulting in a heavy symptom burden and poor health-related quality of life (QOL). We evaluated longitudinal patient-reported outcomes (PROs) to analyze the correlations between symptoms and QOL and their changing characteristics during postoperative rehabilitation. METHODS: We investigated patients with ESCC who underwent minimally invasive McKeown esophagectomy at Sichuan Cancer Hospital between April 2019 and December 2019. Longitudinal data of the clinical characteristics and PROs were collected. The MD Anderson Symptom Inventory and European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires were used to assess symptoms and QOL and compare the trajectories of PROs during the investigation. RESULTS: A total of 244 patients with ESCC were enrolled in this study. Regarding QOL, role and emotional functions returned to baseline at 1 month after surgery, and cognitive and social functions returned to baseline at 3 months after surgery. However, physical function and global QOL did not return to baseline at 1 year after surgery. At 7 days and 1, 3, 6, and 12 months after surgery, the main symptoms of the patients were negatively correlated with physical, role, emotional, cognitive, and social functions and the overall health status (P < 0.05). CONCLUSION: Patients with ESCC experience reduced health-related QOL and persisting symptoms after minimally invasive McKeown esophagectomy, but a recovery trend was observed within 1 month. The long-term QOL after esophagectomy is acceptable.

Impact of Metastatic Lymph Nodes on Survival of Patients with pN1-Category Esophageal Squamous Cell Carcinoma: A Long-Term Survival Analysis.

BACKGROUND: The morbidity and mortality rates of esophageal squamous cell carcinoma (ESCC) are high in China. The overall survival (OS) of patients with ESCC is related to lymph node (LN) metastasis (LNM). This study aimed to discuss the impact of metastasis in LN stations on the OS of patients with pathologic N1 (pN1) ESCC. METHODS: Data were obtained from the Esophageal Cancer Case Management database of Sichuan Cancer Hospital and Institute (SCCH-ECCM). Additionally, data of patients with pN1-category ESCC collected between January 2010 and December 2017 were retrospectively analyzed. RESULTS: Data from 807 patients were analyzed. The median OS of the patients with one metastatic LN (group 1) was 49.8 months (95 % confidence interval [CI], 30.8-68.9 months), whereas the OS of those with two metastatic LNs (group 2) was only 33.3 months (P = 0.0001). Moreover, group 1 did not show a significantly longer OS than group 2.1 (patients with 2 metastatic LNs in 1 LNM station; P = 0.5736), but did show a significantly longer OS than group 2.2 (patients with 2 metastatic LNs in 2 LNM stations; P < 0.0001). After propensity score-matching, the 5-year survival rate for group 1 was 28 %, whereas that for group 2 was 14 % (P = 0.0027). CONCLUSIONS: The OS for the patients with one metastatic LN in one LNM was not significantly longer than for the patients with two metastatic LNs in one LNM station. Patients with one LNM station had a significantly longer OS than those with two LNM stations. Thus, the number of LNM stations is a significant determinant of OS in pN1 ESCC.

USP5 facilitates bladder cancer progression by stabilizing the c-Jun protein.

BACKGROUND: Bladder cancer is the second most common genitourinary malignancy worldwide. The death rate of bladder cancer has increased every year. However, the molecular mechanism of bladder cancer is not sufficiently studied. Deubiquitinating enzymes (DUBs) play an important role in carcinogenesis. Several studies have demonstrated that USP5 associated with malignancy and pathological progression in hepatocellular carcinoma, colorectal and non-small cell lung cancer. However, the role of USP5 in bladder cancer need to be explored. METHODS: The USP5 expression was analysed using the web server GEPIA. To explore USP5 function in bladder cancer, we constructed USP5-knockout cell lines in T24 cells. A FLAG-USP5 (WT USP5) plasmid and a plasmid FLAG-USP5 C335A (catalytic-inactive mutant) used to overexpress USP5 in EJ cells. CCK8, colony formation, transwell and scratch assays were used to assess cell viability, proliferation and migration. RNA sequencing (RNA-seq) and dual-luciferase reporter assays were performed to screen the pathway. Coimmunoprecipitation and immunofluorescence were used to explore the interaction between USP5 and c-Jun. Cycloheximide (CHX) chase assays were performed to establish the effect of USP5 on c-Jun stability. Xenograft mouse model was used to study the role of USP5 in bladder cancer. RESULTS: USP5 expression is increased in bladder cancer patients. Genetic ablation of USP5 markedly inhibited bladder cancer cell proliferation, viability, and migration both in vitro and in vivo. RNA-seq and luciferase pathway screening showed that USP5 activated JNK signalling, and we identified the interaction between USP5 and c-Jun. USP5 was found to activate c-Jun by inhibiting its ubiquitination. CONCLUSIONS: Our results show that high USP5 expression promotes bladder cancer progression by stabilizing c-Jun and that USP5 is a potential therapeutic target in bladder cancer.