USP18 promotes colon adenocarcinoma progression via targeting the ERK-MNK signaling pathway.

BACKGROUND: Colorectal cancer is the third most common malignancy worldwide and is one of the leading causes of cancer-related mortality. Ubiquitin-specific peptidase 18 (USP18) protein has been reported to exert different tumor-related effects in distinct tumor types. Here, we initially investigated the expression and signaling pathways of USP18 in colon adenocarcinoma (COAD). METHODS: A quantitative real-time PCR was conducted to evaluate the mRNA level of USP18 in cultured cells. Immunohistochemical staining was used to explore the protein expression of USP18 in clinical COAD samples. Specific knockdown was achieved by transient transfection of small interfering RNAs into SW480 and HT29 cells using Lipo3000. Cell conting kit-8 assay, transwell assay and matrigel-transwell assays were conducted to evaluate proliferation, migration and invasion capacities, respectively. Western blotting was performed to analyze downstream signaling pathways. A chi-squared test and univariate and multivariate analyses were used to evaluate the clinical data. Xenografts from mice model were assessed to validate the in vitro findings. RESULTS: Higher USP18 level was identified in COAD tissues and was positively correlated with advanced tumor stage. High USP18 protein expression indicated poorer prognosis of COAD patients. Silencing USP18 suppressed COAD cell proliferation and invasion via destabilizing extracellular signal-regulated kinase (ERK) protein and suppressing ERK downstream pathways. Simultaneously silencing interferon-stimulated gene 15 (ISG15) with USP18 can partially rescue the tumor cell viability, indicating its involvement in USP18 signaling. The oncogenic effects of USP18 were also confirmed in mice models. CONCLUSIONS: USP18 plays oncogenic effects in colon adenocarcinoma via ISG15-ERK pathways. High USP18 expression indicates poor clinical outcomes for colon adenocarcinoma patients.

Prilling and Coating Strategy to Synthesize High-Performance Spherical NaNi0.4Fe0.2Mn0.4O2 Cathode Materials for Sodium Ion Batteries.

Low-cost sodium ion batteries are of great significance in large-scale energy storage applications. With its high energy density and simple synthesis process, layered transition-metal oxides have become one of the most likely sodium ion battery cathode materials to replace lithium ion batteries in the energy storage market. Here, we report a prilling and MoS2 coating strategy to prepare the spherical cathode material. The spherical micronano particles shorten the diffusion path of Na+, restrain the complexity phase transitions, and enhance the tap density of the materials. In addition, the MoS2 coating improves the electrical conductivity of the material and the structural stability of the cathode material in air. The initial specific discharge capacity is 148.4 mA h g-1 at 0.1 C, which can be maintained at 128.9 mA h g-1 after exposure to air for 10 days. This method dramatically improves the energy density and structural stability of the cathode material, which provides a new scheme for preparing high-performance sodium ion batteries.

High-Entropy Configuration Strategy to Build High Performance Na-Ion Layered Oxide Cathodes Derived from Simple Techniques.

Layered transition metal oxides are commonly used as the cathode materials in sodium-ion batteries due to their low cost and easy manufacturing. However, the application is hindered by poor rate performance and complex phase transitions. To address these challenges, a new seven-component high-entropy layered oxide cathode material, O3-NaNi0.25Fe0.15Mn0.3Ti0.1Sn0.05Co0.05Li0.1O2 (HEO) has been developed. The entropy stabilization effect plays a crucial role in improving the performance of electrochemical systems and the stability of structures. The HEO exhibits a specific discharge capacity of 154.1 mA h g-1 at 0.1 C and 94.5 mA h g-1 at 7 C. In-situ and ex-situ XRD results demonstrate that the HEO effectively retards complex phase transitions. This work provides a high-entropy design for the storage materials with a high energy density. Meanwhile, it eliminates industry doubts about the performance of sodium ion layered oxide cathode materials.

Predictors for acute exacerbation of interstitial pneumonia following lung cancer surgery: a multicenter study.

BACKGROUND: Acute exacerbation (AE) of interstitial lung disease (ILD) is one of the most serious complications during perioperative period of lung cancer resection. This study aimed to investigate the correlation between preoperative 2- deoxy-2-[18F]fluoro-D-glucose (18F-FDG) PET/CT findings and AE in lung cancer patients with ILD. METHODS: We retrospectively reviewed the data of 210 patients who underwent lung resection for non-small cell lung cancer. Relationships between clinical data and PET images and AE were evaluated. The patients were divided into an AE(+) and an AE(-) group for multivariate logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was conducted and the area under curve (AUC) was used to assess the predictive values. RESULTS: Among 210 patients, 48 (22.8%) were diagnosed with ILD based on chest CT. Among them, 9 patients (18.75%) developed AE after lung resection and were defined as AE(+) group. The course of ILD was longer in AE(+) group compared to AE(-) group. More patients in AE(+) group had a history of AE and chronic obstructive pulmonary disease (COPD) than in AE(-) group. The maximum standardized uptake value (SUVmax) of the noncancerous interstitial pneumonia (IP) area and cancers in AE(+) group was significantly higher compared to AE(-) group. Univariate logistic regression analysis showed that AE, COPD, SUVmax of the noncancerous IP area, SUVmax of cancer, surgical method were significantly correlated with AE. The course of ILD[OR(95%CI) 2.919; P = 0.032], SUVmax of the noncancerous IP area[OR(95%CI) 7.630;P = 0.012] and D-Dimer level[OR(95%CI) 38.39;P = 0.041] were identified as independent predictors for AE in patients with ILD after lung cancer surgery. When the three indicators were combined, we found significantly better predictive performance for postoperative AE than that of SUVmax of the noncancerous IP area alone [0.963 (95% CI 0.914-1.00); sensitivity, 100%, specificity 87.2%, P < 0.001 vs. 0.875 (95% CI 0.789 ~ 0.960); sensitivity, 88.9%, specificity, 76.9%, P = 0.001; difference in AUC = 0.088, Z = 1.987, P = 0.04]. CONCLUSION: The combination of the course of ILD, SUVmax of the noncancerous IP area and D-Dimer levels has high predictive value for the occurrence of AE in patients with concomitant interstitial lesions.

Syntaxin5 is essential for survival by ensuring midgut epithelial homeostsis and regulating feeding in Locusta migratoria.

Syntaxin5 (Syx5) belongs to SNAREs family, which play important roles in fusion of vesicles to target membranes. Most of what we know about functions of Syx5 originates from studies in fungal or vertebrate cells, how Syx5 operates during the development of insects is poorly understood. In this study, we investigated the role of LmSyx5 in the gut development of the hemimetabolous insect Locusta migratoria. LmSyx5 was expressed in many tissues, with higher levels in the gut. Knockdown of LmSyx5 by RNA interference (RNAi) considerably suppressed feeding in both nymphs and adults. The dsLmSyx5-injected locusts lost body weight and finally died at a mortality of 100%. Furthermore, hematoxylin-eosin staining indicated that the midgut is deformed in dsLmSyx5-treated nymphs and the brush border in midgut epithelial cells is severely damaged, suggesting that LmSyx5 is involved in morphogenesis of the midgut. TEM further showed that the endoplasmic reticulum of midgut cells have a bloated appearance. Taken together, these results suggest that LmSyx5 is essential for midgut epithelial homeostsis that affects growth and development of L. migratoria. Thus, Syx5 is a promising RNAi target for controlling L. migratoria, and even other pests.

Three alternative splicing variants of Loquacious play different roles in miRNA- and siRNA-mediated RNAi pathways in Locusta migratoria.

RNA interference (RNAi) is a specific post-transcriptional gene-silencing phenomenon, which plays an important role in the regulation of gene expression and the protection from transposable elements in eukaryotic organisms. In Drosophila melanogaster, RNAi can be induced by microRNA (miRNA), endogenous small interfering RNA (siRNA), or exogenous siRNA. However, the biogenesis of miRNA and siRNA in these RNAi pathways is aided by the double-stranded RNA binding proteins (dsRBPs) Loquacious (Loqs)-PB, Loqs-PD or R2D2. In this study, we identified three alternative splicing variants of Loqs, namely Loqs-PA, -PB, and -PC in the orthopteran Locusta migratoria. We performed in vitro and in vivo experiments to study the roles of the three Loqs variants in the miRNA- and siRNA-mediated RNAi pathways. Our results show that Loqs-PB assists the binding of pre-miRNA to Dicer-1 to lead to the cleavage of pre-miRNA to yield matured miRNA in the miRNA-mediated RNAi pathway. In contrast, different Loqs proteins participate in different siRNA-mediated RNAi pathways. In exogenous siRNA-mediated RNAi pathway, binding of Loqs-PA or LmLoqs-PB to exogenous dsRNA facilitates the cleavage of dsRNA by Dicer-2, whereas in endogenous siRNA-mediated RNAi pathway, binding of Loqs-PB or Loqs-PC to endogenous dsRNA facilitates the cleavage of dsRNA by Dicer-2. Our findings provide new insights into the functional importance of different Loqs proteins derived from alternative splicing variants of Loqs in achieving high RNAi efficiency in different RNAi pathways in insects.

NADPH-cytochrome P450 reductase knockdown decreases the response to precocene I in the migratory locust Locusta migratoria.

Precocene I is a juvenile hormone antagonist that needs to be activated via oxidative biotransformation catalyzed by cytochrome P450 (CYP). NADPH-cytochrome P450 reductase (CPR) supplies CYP with electrons in the oxidation-reduction process; however, its functional role in the activation of precocene I remains unexplored. Here, the representative characteristics of CPRs were analyzed in the CPR gene of Locusta migratoria (LmCPR), the result of model docking indicated that the hydrogen bonds were formed between reduced nicotinamide adenine dinucleotide phosphate (NADPH), flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN) and NADPH-, FAD-, FMN-domains of LmCPR, respectively. Treating the fourth-instar nymphs with precocene I decreased the juvenile hormone titers of nymphs to 0.55-fold of that in acetone-treated controls, and extended the interval time between fourth- and fifth-instar nymphs. 68.75% of the treated fourth-instar nymphs developed into precocious adults in the fifth-instar. LmCPR knockdown decreased the response to precocene I in the nymphs, the occurrence rate of precocious adults induced by precocene I treatment reduced by 23.11%. Therefore, LmCPR may be involved in the activation of precocene I in L. migratoria. In addition, we generated an active recombinant LmCPR protein using a prokaryotic expression system, its activity in reducing cytochrome c was 33.13 ± 11.50 nmol CytCred/min/µg protein. This study lays the foundation for further research on the role of LmCPR in precocene I activation.

Artesunate inhibits proliferation, migration, and invasion of thyroid cancer cells by regulating the PI3K/AKT/FKHR pathway.

This study characterized the effects of artesunate on thyroid cancer and partially identified the related molecular mechanisms. We determined the effect of artesunate on the proliferation of thyroid cancer cells using the MTT assay, cell colony formation experiments, and western blotting, and used flow cytometry to detect the apoptosis of cancer cells. Using a wound healing assay, Transwell chamber experiments, and western blotting, we determined the effect of artesunate on cancer cell migration. We also partially identified the molecular mechanism by co-cultivation of artesunate with the PI3K agonist 740Y-P. Artesunate significantly inhibited the growth, proliferation, migration, and invasion of thyroid cancer cells and promoted the apoptosis of cancer cells. Using co-cultivation with a PI3K agonist, we found that the inhibitory effect of artesunate on cancer cells was mainly due to suppression of the PI3K/AKT/FKHR signaling pathway. By inhibiting the PI3K/AKT/FKHR signaling pathway, artesunate induced apoptosis in thyroid cancer cells and inhibited their proliferation and migration.

Use of Telehealth Services for Prenatal Care in Mississippi: Comparison of Pre-COVID-19 Pandemic and Pandemic Obstetric Management.

Background: The SARS-CoV-2 (COVID-19) pandemic resulted in major shifts in service delivery for patient care not involving COVID-19 illness. The preexisting telehealth infrastructure in Mississippi allowed the state to rapidly expand the scope of telehealth programs. Little research has been done to examine the use of telehealth during the COVID-19 pandemic and its impact on the delivery of care during pregnancy and outcomes associated with pregnancy. The objectives of this study are to (1) describe prenatal care practices during the height of the first wave of the COVID-19 pandemic, compared to the immediate prepandemic time period, and (2) explore maternal and birth outcomes during these time periods. Methods: This study was conducted as a retrospective historical cohort study from medical records at one Maternal Care Level IV (Regional Perinatal Health Care Center) in Mississippi and its affiliated centers. The participant cohort was inclusive of women who received prenatal care prior to a single birth delivery between May 1, 2020, and January 31, 2021. The pandemic cohort was defined through the timeframe of the included participants' end-term prenatal care, with reference to the beginning of the COVID-19 pandemic. The prepandemic cohort received a majority of their prenatal care prior to the COVID-19 pandemic. Results: There were 1,894 women included. Among them, 620 (32.77%) completed the majority of their end-term pregnancy in the pre-COVID-19 time period and 1,272 (67.23%) completed the end-term pregnancy during the pandemic. The odds ratio for patients from the pandemic cohort of scheduling telehealth visits compared to not scheduling telehealth visits is 8.19 (95% CI: 3.98, 16.86) times the odds ratio for patients from the prepandemic cohort. The pandemic exposure as well as infant's gestational age and very low birth weight (VLBW) show significant effects on the infant's living status in the univariate logistic regression. However, after controlling for the infant's gestational age and VLBW, we did not detect a significant effect of pandemic exposure. Conclusion: This study demonstrated a very small reliance of telehealth for the medical supervision of pregnant women during the COVID-19 pandemic. This is likely because of the essential physical examinations that occur in women who are considered to be at high risk for poor maternal and birth outcomes. Additional studies on the impact of COVID-19 infection on maternal and infant outcomes are also needed as there may be important risk factors not yet identified for poor maternal or birth outcomes.

A ras-related nuclear protein Ran participates in the 20E signaling pathway and is essential for the growth and development of Locusta migratoria.

The small GTPase Ran is a member of the Ras superfamily of small GTP-binding proteins, which plays a key role in the translocation of RNA and proteins through the nuclear pore complex. In this study, the full-length cDNA sequence of LmRan gene was obtained, which consists of 648-nucleotides open reading frame (ORF) and encodes 215 amino acids. RT-qPCR results revealed that LmRan was expressed in all developmental days and tissues investigated. Injection of dsLmRan into 4th and 5th instar nymphs, resulted in a significant down-regulation of LmRan transcripts, respectively. All dsLmRan-injected nymphs died before molting. Further hematoxylin and eosin staining of the integument showed that there was no apolysis occurred after silencing LmRan. In addition, the weight of dsLmRan-injected nymphs was significantly lower than that of the control group, and the gastric caecum and midgut was severely smaller. Especiallly, the mRNA level of LmCYP302a1, LmCYP315a1 and LmCYP314a1 responsible for 20E synthesis, LmE75 and LmE74 genes involved in the 20E signaling pathway, LmGfat, LmUAP1 and LmCHT10 genes involved in chitin metabolism pathway were dramatically decreased in the dsLmRan-injected nymphs. Together, the results indicated that LmRan participate in the 20E signaling pathway, which is essential for the growth and development of locusts.

Group I CDAs are responsible for a selective CHC-independent cuticular barrier in Locusta migratoria.

Chitin deacetylases including CDA1 and CDA2, containing a chitin deacetylase domain and an LDL domain, have been reported to be essential for cuticle structure differentiation in different insect species. However, it is yet unexplored whether CDA1 and CDA2 activity is needed for the function of the cuticle as a barrier against pathogen and xenobiotics penetration. In this study, we studied the efficiency of fungal infection in the migratory locust Locusta migratoria in dependence of LmCDA1 and LmCDA2 function. Second instar nymphs injected with dsRNA against LmCDA1 and LmCDA2 transcripts were less resistant against the infection by the fungus Metarhizium anisopliae than control nymphs. At the same time, permeability to organophosphorus pesticides was increased in these nymphs. Interestingly, the CHC amounts at the cuticle surface were unaffected upon LmCDA1 and LmCDA2 reduction. These results suggest that the barrier function of the locust cuticle not only depends on surface CHCs, but also on an intact procuticle.

Epigenetic abnormalities of classical Hodgkin lymphoma and its effect on immune escape.

Classical Hodgkin lymphoma (cHL) is a particular kind of malignant tumour that originates from the B cells. The malignant phenotype of cHL is, at least in part, maintained by epigenetic aberrations, which primarily consist of abnormal histone methylation and acetylation. Progress has been made in clinical trials concerning the histone deacetylases inhibitors (HDACis) in cHL. Also, some demethylation regimens could serve the purpose of preventing and treating tumours. Programmed death-ligand receptor 1 (PD-L1, CD274) inhibitors or apoptosis receptor 1 (PD-1, CD279) inhibitors are used in treating patients with relapsed cHL in recent years. Academic researches indicated that PD-1/PD-L1 inhibitors, including nivolumab and pembrolizumab, demonstrate remarkable activity in relapsed cHL. In addition, in recent years, a close association between epigenetic aberrations and immune escape has been explored in cHL. DNA methyltransferase (DNMT) inhibitors, HDACis, and immune checkpoint blockade exhibit synergistic effects. Thus, this review aims to provide an overview on the epigenetic abnormalities of cHL and its effect on immune escape, in order to explore the optimal combination approach to treat the disease. SIGNIFICANCE OF THE STUDY: Cancer Statistics 2018 reported that more than 8000 new cases of Hodgkin lymphoma were diagnosed. In recent years, PD-1/PD-L1 inhibitors for cHL have been utilized, and the therapeutic strategies of HDACis combined with PD-1/PD-L1 inhibitors have been raised. It is critical for improving the efficacy and decreasing the toxicity in treating the patients with cHL.

An Overlooked Paleotetraploidization in Cucurbitaceae.

Cucurbitaceae plants are of considerable biological and economic importance, and genomes of cucumber, watermelon, and melon have been sequenced. However, a comparative genomics exploration of their genome structures and evolution has not been available. Here, we aimed at performing a hierarchical inference of genomic homology resulted from recursive paleopolyploidizations. Unexpectedly, we found that, shortly after a core-eudicot-common hexaploidy, a cucurbit-common tetraploidization (CCT) occurred, overlooked by previous reports. Moreover, we characterized gene loss (and retention) after these respective events, which were significantly unbalanced between inferred subgenomes, and between plants after their split. The inference of a dominant subgenome and a sensitive one suggested an allotetraploid nature of the CCT. Besides, we found divergent evolutionary rates among cucurbits, and after doing rate correction, we dated the CCT to be 90-102 Ma, likely common to all Cucurbitaceae plants, showing its important role in the establishment of the plant family.

Predicting temporal propagation of seasonal influenza using improved gaussian process model.

Influenza rapidly spreads in seasonal epidemics and imposes a considerable economic burden on hospitals and other healthcare costs. Thus, predicting the propagation of influenza accurately is crucial in preventing influenza outbreaks and protecting public health. Most current studies focus on the spread simulation of influenza. However, few studies have investigated the dependencies between meteorological variables and influenza activity. This study develops a non-parametric model based on Gaussian process regression for influenza prediction considering meteorological effect to capture temporal dependencies hidden in influenza time series. To identify the most explanatory external variables, L1-regularization is applied to identify meteorology factor subsets, and three types of covariance functions are designed to characterize non-stationary and periodic behavior in influenza activity. The dependencies of diseases and meteorology are modeled through the designed cross-covariance function. A real case in Shenzhen, China was studied to validate our proposed model along with comparisons to recently developed multivariate statistical models for influenza prediction. Results show that our proposed influenza prediction approach achieves superior performance in terms of one-week-ahead prediction of influenza-like illness.

Chitin in Arthropods: Biosynthesis, Modification, and Metabolism.

Chitin is a structural constituent of extracellular matrices including the cuticle of the exoskeleton and the peritrophic matrix (PM) of the midgut in arthropods. Chitin chains are synthesized through multiple biochemical reactions, organized in several hierarchical levels and associated with various proteins that give their unique physicochemical characteristics of the cuticle and PM. Because, arthropod growth and morphogenesis are dependent on the capability of remodeling chitin-containing structures, chitin biosynthesis and degradation are highly regulated, allowing ecdysis and regeneration of the cuticle and PM. Over the past 20 years, much progress has been made in understanding the physiological functions of chitinous matrices. In this chapter, we mainly discussed the biochemical processes of chitin biosynthesis, modification and degradation, and various enzymes involved in these processes. We also discussed cuticular proteins and PM proteins, which largely determine the physicochemical properties of the cuticle and PM. Although rapid advances in genomics, proteomics, RNA interference, and other technologies have considerably facilitated our research in chitin biosynthesis, modification, and metabolism in recent years, many aspects of these processes are still partially understood. Further research is needed in understanding how the structural organization of chitin synthase in plasma membrane accommodate chitin biosynthesis, transport of chitin chain across the plasma membrane, and release of the chitin chain from the enzyme. Other research is also needed in elucidating the roles of chitin deacetylases in chitin organization and the mechanism controlling the formation of different types of chitin in arthropods.

Progress and prospects of arthropod chitin pathways and structures as targets for pest management.

Chitin is a structural component of the arthropod cuticular exoskeleton and the peritrophic matrix of the gut, which play crucial roles in growth and development. In the past few decades, our understanding of the composition, biosynthesis, assembly, degradation, and regulation of chitinous structures has increased. Many chemicals have been developed that target chitin biosynthesis (benzoyphenyl ureas, etoxazole), chitin degradation (allosamidin, psammaplin), and chitin regulation (benzoyl hydrazines), thus resulting in molting deformities and lethality. In addition, proteins that disrupt chitin structures, such as lectins, proteases, and chitinases have been utilized to halt feeding and induce mortality. Chitin-degrading enzymes, such as chitinases are also useful for improving the efficacy of bio-insecticides. Transgenic plants, baculoviruses, fungi, and bacteria have been engineered to express chitinases from a variety of organisms for control of arthropod pests. In addition, RNA interference targeting genes involved in chitin pathways and structures are now being investigated for the development of environmentally friendly pest management strategies. This review describes the chemicals and proteins used to target chitin structures and enzymes for arthropod pest management, as well as pest management strategies based upon these compounds, such as plant-incorporated-protectants and recombinant entomopathogens. Recent advances in RNA interference-based pest management, and how this technology can be used to target chitin pathways and structures are also discussed.

Hierarchically Aligning 10 Legume Genomes Establishes a Family-Level Genomics Platform.

Mainly due to their economic importance, genomes of 10 legumes, including soybean (Glycine max), wild peanut (Arachis duranensis and Arachis ipaensis), and barrel medic (Medicago truncatula), have been sequenced. However, a family-level comparative genomics analysis has been unavailable. With grape (Vitis vinifera) and selected legume genomes as outgroups, we managed to perform a hierarchical and event-related alignment of these genomes and deconvoluted layers of homologous regions produced by ancestral polyploidizations or speciations. Consequently, we illustrated genomic fractionation characterized by widespread gene losses after the polyploidizations. Notably, high similarity in gene retention between recently duplicated chromosomes in soybean supported the likely autopolyploidy nature of its tetraploid ancestor. Moreover, although most gene losses were nearly random, largely but not fully described by geometric distribution, we showed that polyploidization contributed divergently to the copy number variation of important gene families. Besides, we showed significantly divergent evolutionary levels among legumes and, by performing synonymous nucleotide substitutions at synonymous sites correction, redated major evolutionary events during their expansion. This effort laid a solid foundation for further genomics exploration in the legume research community and beyond. We describe only a tiny fraction of legume comparative genomics analysis that we performed; more information was stored in the newly constructed Legume Comparative Genomics Research Platform (www.legumegrp.org).

Clinicopathological features and prediction values of HDAC1, HDAC2, HDAC3, and HDAC11 in classical Hodgkin lymphoma.

Histone deacetylases (HDACs) are involved in multiple physical and pathological processes in classical Hodgkin lymphoma (cHL). The prognostic value of HDACs in cHL patients has not been discussed. The aim of the current study is to investigate the HDAC1, HDAC2, HDAC3, and HDAC11 expressions, and to evaluate the correlation of HDAC1, HDAC2, HDAC3, and HDAC11 expressions with the survival rate in cHL patients. We retrospectively analyzed clinicopathological data of 28 patients who were diagnosed with cHL between August 2002 and March 2010. Immunohistochemistry was used to detect the expression of HDAC1, HDAC2, HDAC3, and HDAC11 in these patients. The results showed that HDAC1, HDAC3, and HDAC11 were expressed at a higher level in Hodgkin Reed-Sternberg cells, whereas HDAC2 was expressed at a lower level in Hodgkin Reed-Sternberg cells. The expression of HDAC2 had a relationship with pathological type (P=0.012). There was also a correlation between the expression of HDAC11 and the erythrocyte sedimentation rate (P=0.054). Other clinicopathological parameters had no significant correlation with the expression of HDAC1, HDAC2, HDAC3, and HDAC11 in terms of survival (P>0.05). The 10-year total survival rate by Cox multivariate analysis, after taking into account all clinical and pathologic factors, showed that bulky disease retained significance (P=0.028). Higher expression of HDAC1 predicted shorter progression-free survival and overall survival (OS) in cHL patients (P<0.05, in both cases), and higher expression of HDAC11 might be correlated with lower OS (P=0.05). The study showed that the expressions of HDAC2 and HDAC11 have a particular relationship with the pathologic subtype. Increased expression of HDAC1 was correlated negatively with progression-free survival and OS, and increased expression of HDAC11 had a borderline relationship with the OS rate in patients with cHL.

Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway.

BACKGROUND: Osteopontin (OPN) is highly expressed in colorectal cancer (CRC) and is associated with disease progression in vivo. High levels of OPN have been demonstrated to predict low survival rates in CRC. Autophagy is a process of self-digestion, which is thought to play a significant role in carcinogenesis. However, the mechanisms of OPN's effects on CRC cell autophagy have not been elucidated. Therefore, we aimed to investigate possible mechanisms of OPN's effects on CRC autophagy. METHODS: HCT116 cell proliferation, apoptosis, and migration and invasion ability were identified by cell counting k¡t-8 assay, flow cytometry, wound healing assay, and transwell chamber invasion assay, respectively. The ratios of proteins LC3-II/LC3-I, P62, and Atg7 were analyzed by Western-blot. Expressions of Beclin-1, Atg4b, Bnip3, and Vps34, both in transcriptional and translational levels, were analyzed and compared by RT-PCR and Western blot. Immunofluorescence and co-focusing experiments were used to investigate the formation of autophagosomes. RESULTS: The results showed that OPN can promote cell proliferation, migration, and invasion, as well as inhibit cell apoptosis. It was also demonstrated that OPN could inhibit cell autophagy. Further experiments revealed that the inhibitory effect of OPN on autophagy could be reversed by blocking the p38 MAPK pathway in HCT116 cells. CONCLUSION: OPN is involved in HCT116 cell progression and is capable of inhibiting cell autophagy possibly by activating the p38 MAPK signaling pathway, implying that OPN could be a potential novel molecular therapeutic biomarker in patients with CRC.