Potential use of yeast protein in terms of biorefinery, functionality, and sustainability in food industry.

A growing demand for sustainable, alternative protein sources that are nutrient-dense, such as microorganisms, and insects, has gradually evolved. When paired with effective processing techniques, yeast cells contain substantial substances that could supply the population's needs for food, medicine, and fuel. This review article explores the potential of yeast proteins as a sustainable and viable alternative to animal and plant-based protein sources. It highlights the various yeast protein extraction methods including both mechanical and non-mechanical methods. The application of nanoparticles is one example of the fast-evolving technology used to damage microbial cells. SiO2 or Al2O3 nanoparticles break yeast cell walls and disrupt membranes, releasing intracellular bioactive compounds. Succinylation of yeast protein during extraction can increase yeast protein extraction rate, lower RNA concentration, raise yeast protein solubility, increase amino acid content, and improve yeast protein emulsification and foaming capabilities. Combining physical and enzymatic extraction methods generates the most representative pool of mannose proteins from yeast cell walls. Ethanol or isoelectric precipitation purifies mannose proteins. Mannoproteins can be used as foamy replacement for animal-derived components like egg whites due to their emulsification, stability, and foaming capabilities. Yeast bioactive peptide was separated by ultrafiltration after enzymatic hydrolysis of yeast protein and has shown hypoglycemic, hypotensive, and oxidative action in vitro studies. Additionally, the review delves into the physicochemical properties and stability of yeast-derived peptides as well as their applications in the food industry. The article infers that yeast proteins are among the promising sources of sustainable protein, with a wide range of potential applications in the food industry.

A General and Convenient Peptide Self-Assembling Mechanism for Developing Supramolecular Versatile Nanomaterials Based on The Biosynthetic Hybrid Amyloid-Resilin Protein.

Self-assembling peptides are valuable building blocks to fabricate supramolecular biomaterials, which have broad applications from biomedicine to biotechnology. However, limited choices to induce different globular proteins into hydrogels hinder these designs. Here, an easy-to-implement and tunable self-assembling strategy, which employs Ure2 amyloidogenic peptide, are described to induce any target proteins to assemble into supramolecular hydrogels alone or in combination with notable compositional control. Furthermore, the collective effect of nanoscale interactions among amyloid nanofibrils and partially disordered elastomeric polypeptides are investigated. This led to many useful macroscopic material properties simultaneously emerging from one pure protein material, i.e. strong adhesion to any substrates under wet conditions, rapidly self--assembling into robust and porous hydrogels, adaptation to remodeling processes, strongly promoting cell adhesion, proliferation and differentiation. Moreover, he demonstrated this supramolecular material's robust performance in vitro and vivo for tissue engineering, cosmetic and hemostasis applications and exhibited superior performance compared to corresponding commercial counterparts. To the best of his knowledge, few pure protein-based materials could meet such seemingly mutually exclusive properties simultaneously. Such versatility renders this novel supramolecular nanomaterial as next-generation functional protein-based materials, and he demonstrated the sequence level modulation of structural order and disorder as an untapped principle to design new proteins.

Prevalence of symptoms in children with acute lymphoblastic leukaemia: a systematic review and meta-analysis.

BACKGROUND: Children with acute lymphoblastic leukaemia (ALL) experience multiple symptoms that occur in complicated patterns and negatively affect patient outcomes. To date, no systematic review has been performed on the prevalence of symptoms in children with ALL. OBJECTIVE: The study aimed to report and analyse the prevalence of symptoms in children with ALL during treatment. METHODS: A systematic search was conducted in eight databases (PubMed, Ovid Embase, Web of Science, CINAHL, PsycINFO, China WanFang Database, China Science and Technology Journal Database, and China National Knowledge Infrastructure) for studies published between January 1, 2000, and August 12, 2023. The methodological quality of the included studies was evaluated and a meta-analysis was performed to pool the prevalence of symptoms. RESULTS: In total, 17 studies were included, from which 34 symptoms were identified. The symptom prevalence ranged between 1.5 and 91.0% and the most frequent symptoms observed were fatigue, lack of energy, dry mouth, lack of appetite, sweating, and feeling irritable, which occurred in at least 60% of the patients. CONCLUSIONS: Symptoms remain highly prevalent in paediatric patients with ALL, which provides support for the need for symptom assessment in the clinical setting. Specific intervention is urgently needed to mitigate the symptoms in children with ALL and help them cope with the symptom burden.

Comparison of the sense of spousal support, anxiety, depression and their relationship to fear of cancer recurrence between lymphoma patients and their spouses: A cross-sectional study in China.

PURPOSE: To investigate the level of fear of cancer recurrence (FCR) in spouses of patients with lymphoma and its relationship with patients' FCR, as well as the correlations between FCR, sense of spousal support (SSS), anxiety, and depression in the couples. METHODS: A cross-sectional study of 233 couples where one partner had lymphoma was conducted from May 2021 to February 2022. Participants provided demographic information and completed the Spouse Support Inventory and Hospital Anxiety and Depression Scale. The Fear of Progression Questionnaire (for patients) and Fear of Progression Questionnaire for Partners (for spouses) were used to measure FCR. Descriptive analyses, t-tests, variance analysis, Spearman's correlation analysis, and multiple linear regression analysis was performed. RESULTS: The prevalence of FCR, anxiety, and depression in patients was 37.7%, 68.7%, and 83.3%, respectively. The prevalence of FCR, anxiety, and depression in spouses was 56.2%, 78.1%, and 81.1%, respectively. Spouses' FCR scores were higher than those of patients, whereas patients' SSS and anxiety scores were higher than those of their spouses. Multiple linear regression analysis showed that patients' anxiety and SSS, as well as spouses' FCR were significantly associated with patients' FCR. Variables significantly associated with higher FCR among spouses were anxiety, per capita monthly household income, and patients' FCR. CONCLUSIONS: Patients with lymphoma and their spouses have a certain degree of FCR, anxiety, and depression. FCR levels in spouses are higher than in patients. IMPLICATIONS FOR CANCER SURVIVORS: Psychological support interventions for couples may be effective in reducing FCR and facilitating family adaptation to cancer.

Never forsake-The positive experiences of dyadic coping among patients with acute leukemia and their spouses: A qualitative study.

PURPOSE: This study aimed to explore the positive experiences of dyadic coping between patients with acute leukemia and their spouses in China, and to highlight the target factors that could promote coping and adaptation. METHODS: A qualitative descriptive study was employed. This study was conducted at a tertiary hospital in China from September 2021 to February 2022. A purposive sampling method was used to select participants, and 17 patients diagnosed with acute leukemia and their spouses were interviewed. Qualitative data were analyzed using the content analysis method. This study followed the COREQ checklist. RESULTS: This study's data were categorized into five themes and twelve subthemes: (1) adapting to a new role-couples used role adjustments to adapt; (2) commitment to companionship-patients benefit from spousal commitment in word or in deed; (3) active communication-allows couples to get to know each other better; (4) white lies-shield partner from negative information; (5) seeking external support-outside of couple cohesion. In sum, positive dyadic coping experiences between couples follow the marital commitment of "never forsake." CONCLUSIONS: This study contributes new knowledge to the understanding of the dyadic coping experiences of patients with acute leukemia and their spouses within the Chinese social-cultural context and contributes to cross-cultural comparisons. The results can be used to design and implement couple-based intervention programs to support couples by enhancing their mutual support to cope with and adjust to acute leukemia effectively.

TP53 mutation detected in circulating exosomal DNA is associated with prognosis of patients with hepatocellular carcinoma.

Exosome DNA (exoDNA) can be used for liquid biopsy. This study was the first to use droplet digital PCR (ddPCR) to detect tumor-specific mutations in exoDNA and to evaluate the prognosis of hepatocellular carcinoma (HCC) patients. 60 HCC patients were enrolled in the study. We used ddPCR to detect c.747 G > T mutation in TP53 gene. We analyzed the correlation between detectable mutation in exoDNA and clinicopathologic characteristics using Multivariate logistics regression analysis. We performed Cox regression to assess the correlation between mutation frequency (mutant droplets/total droplets, MD/TD) and prognostic. We found that 48 of 60 patients had c.747 G > T mutation in TP53 gene in exoDNA (80.0%). We found that detectable mutation in exoDNA and age were associated with microvascular invasion (MVI) (P < .01). The ROC curve analysis revealed that the best cutoff value of mutation frequency to predict MVI was 67% (sensitivity 48.15%, specificity 93.94%,), the corresponding AUC was 0.761 (95%CI, 0.640-0.866; P < .01). Furthermore, we found that patients suffered high-frequency mutation (>67%) had shorted median recurrence-free survival (RFS) with 63 days (range, 53-202 days), compared with 368 days (range, 51-576 days) for patients with low-frequency mutation (<67%) (HR:4.61; 95% CI, 1.70-12.48; P = 0 .003). We also found that high-frequency mutation was associated with poor prognosis though patients had better pathological characteristics, such as AFP (<400 ng/mL), Liver cirrhosis (Negative), Tumor thrombus (Negative), Tumor numbers (Single) and Post-operation TACE (Executed). We provided evidence that the mutations in exoDNA might be used to predict patients with poor RFS.Abbreviations: TP53: Tumor protein p53; ExoDNA: Exosomal DNA; HCC: Hepatocellular carcinoma; ddPCR: Droplet digital Polymerase Chain Reaction (PCR); MD/TD: The ratio of mutant droplets/total droplets; AFP: Alpha-fetoprotein; MVI: Microvascular invasion; RFS: Recurrence-free survival.

STING and TLR7/8 agonists-based nanovaccines for synergistic antitumor immune activation.

Immunostimulatory therapies based on pattern recognition receptors (PRRs) have emerged as an effective approach in the fight against cancer, with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity tumor environment. The agonist cyclic dinucleotides (CDNs) of the stimulator of interferon gene (STING) are a group of very promising anticancer molecules that increase tumor immunogenicity by activating innate immunity. However, the tumor immune efficacy of CDNs is limited by several factors, including relatively narrow cytokine production, inefficient delivery to STING, and rapid clearance. In addition, a single adjuvant molecule is unable to elicit a broad cytokine response and thus cannot further amplify the anticancer effect. To address this problem, two or more agonist molecules are often used together to synergistically enhance immune efficacy. In this work, we found that a combination of the STING agonist CDGSF and the Toll-like receptor 7/8 (TLR7/8) agonist 522 produced a broader cytokine response. Subsequently, we developed multicomponent nanovaccines (MCNVs) consisting of a PC7A polymer as a nanocarrier encapsulating the antigen OVA and adjuvant molecules. These MCNVs activate bone marrow-derived dendritic cells (BMDCs) to produce multiple proinflammatory factors that promote antigen cross-presentation to stimulate specific antitumor T-cell responses. In in vivo experiments, we observed that MCNVs triggered a strong T-cell response in tumor-infiltrating lymphocytes, resulting in significant tumor regression and, notably, a 100% survival rate in mice through 25 days without other partnering therapies. These data suggest that our nanovaccines have great potential to advance cancer immunotherapy with increased durability and potency. Electronic Supplementary Material: Supplementary material (synthesis of CDGSF, 522, PC7A and OVA; preparation of MCNVs; representative gating strategies for flow cytometry) is available in the online version of this article at 10.1007/s12274-022-4282-x.

Overcoming STING Agonists Barriers: Peptide, Protein, and Biomembrane-based Biocompatible Delivery Strategies.

After development for more than ten years, stimulator of interferon genes (STING), a representative of pattern recognition receptors (PRRs), is now entering the stage of widespread applications. Along with the evolution of STING agonists of cyclic dinucleotides (CDNs) and non-nucleotide molecules, the stability of agonists has been improved. However, their poor performance in clinical trials triggers urgent demands for highly effective delivery strategies to further improve the cellular permeability, tissue targetability and retention. In this review, we summarized the recent progress of STING agonists applications and delivery strategies with a focus on the biocompatible platforms of peptide, protein and biomembrane, providing a novel vision for the STING field and future direction.

Stability of oil-in-water emulsions with eggplant flesh pulp (Solanum melongena L.) emulsifier: Effects of storage time, pH, ionic strength, and temperature.

In this study, we investigated the stability of oil-in-water emulsions prepared using eggplant flesh pulp (EFP) as natural emulsifier. The effects of time and environmental stresses on the stability of emulsions with different EFP concentrations were evaluated using the creaming indices (CIs), particle sizes, and zeta potentials of the emulsions. The emulsions with EFP concentrations of up to 1.50% remained stable for at least 90 days. The CIs, mean particle diameters (MPDs ]d3,2 ]), and zeta potentials of the emulsions with adequate EFP concentrations remained unchanged in the pH range of 3-9. Microstructure observations revealed that flocculation occurred for the emulsion with an EFP concentration of 1.50% at pH 3, whereas flocculation and coalescence occurred in the emulsion with a low EFP concentration of 0.50%. Upon increasing the concentration of NaCl from 0 to 0.5 M, the MPDs (d3,2 ) of the emulsions with EFP concentrations of 1.00% and 1.50% remained nearly constant (57 and 48 µm, respectively). Moreover, the MPDs (d3,2 ) and zeta potentials of the emulsions with EFP concentrations of 1.00% and 1.50% did not change significantly upon increasing temperature from 4 to 100°C. Hence, the emulsions with adequate EFP concentrations presented long storage times and were stable under various environmental stresses. Our results indicate that EFP is an effective and inexpensive emulsifier that can confer emulsions long-term storage stability and good resistance to environmental stresses. PRACTICAL APPLICATION: Eggplant, which is a common crop, is a rich source of natural materials. In this study, eggplant flesh pulp (EFP) was prepared via mechanical homogenization and its emulsifying properties for oil-in-water emulsions were evaluated. Our results demonstrated that the EFP-stabilized oil-in-water emulsions featured long storage times and were stable under environmental stresses (pH, ionic strength, and temperature). These properties render EFP-stabilized emulsions suitable as delivery systems for encapsulating and releasing nonpolar active ingredients in food products.

Regulation of liquid-liquid phase separation with focus on post-translational modifications.

Liquid-liquid phase separation (LLPS), a type of phase transition that is important in organisms, is a unique means of forming biomolecular condensates. LLPS plays a significant role in transcription, genome organisation, immune response and cell signaling, and its dysregulation may cause neurodegenerative diseases and cancers. Exploring the regulatory mechanism of LLPS contributes to the understanding of the pathogenic mechanism of abnormal phase transition and enables potential therapeutic targets to be proposed. Many factors have been found to regulate LLPS, of which post-translational modification (PTM) is among the most important. PTMs can change the structure, charge, hydrophobicity and other properties of the proteins involved in phase separation and thereby affect the phase transition behaviour. In this review, we discuss LLPS and the regulatory effects of PTMs, RNA and molecular chaperones in a phase separation system. We introduce several common PTMs (including phosphorylation, arginine methylation, arginine citrullination, acetylation, ubiquitination and poly(ADP-ribosyl)ation), highlight recent advances regarding their roles in LLPS and describe the regulatory mechanisms behind these features. This review provides a detailed overview of the field that will help further the understanding of and interventions in LLPS.

Black phosphorous nanosheet: A novel immune-potentiating nanoadjuvant for near-infrared-improved immunotherapy.

Intrinsic immune behaviors of nanomaterials and immune systems promote research on their adjuvanticity and the design of next generation nanovaccine-based immunotherapies. Herein, we report a promising multifunctional nanoadjuvant by exploring the immune-potentiating effects of black phosphorus nanosheets (BPs) in vitro and in vivo. The facile coating of BPs with phenylalanine-lysine-phenylalanine (FKF) tripeptide-modified antigen epitopes (FKF-OVAp@BP) enables the generation of a minimalized nanovaccine by integrating high loading capacity, efficient drug delivery, comprehensive dendritic cell (DC) activation, and biocompatibility for cancer immunotherapy. Systemic immunization elicits potent antitumor cellular immunity and significantly augments checkpoint blockade (CPB) against melanoma in a mouse model. Furthermore, near-infrared (NIR) photothermal effects of BPs create an immune-favorable microenvironment for improved local immunization. This study offers new insight into the integration of immunoactivity and photothermal effects for enhanced cancer immunotherapy by using a nanoadjuvant and thus potentially advances the design and application of multifunctional adjuvant materials for cancer nanotreatment.

A novel STING agonist for cancer immunotherapy and a SARS-CoV-2 vaccine adjuvant.

A novel STING agonist, CDGSF, ipsilaterally modified with phosphorothioate and fluorine, was synthesized. The phosphorothioate in CDGSF might be a site for covalent conjugation. Injection of CDGSF generated an immunogenic ("hot") tumor microenvironment to suppress melanoma, more efficiently than dithio CDG. In particular, immunization with SARS-CoV-2 spike protein using CDGSF as an adjuvant elicited an exceptionally high antibody titer and a robust T cell response, overcoming the drawbacks of aluminum hydroxide. These results highlighted the therapeutic potential of CDGSF for cancer immunotherapy and the adjuvant potential of the STING agonist in the SARS-CoV-2 vaccine for the first time.

Pam3CSK4-CDGSF Augments Antitumor Immunotherapy by Synergistically Activating TLR1/2 and STING.

Cyclic dinucleotides (CDNs), agonists of stimulator of interferon genes (STING), are promising agents for immunotherapy. However, the application of CDNs has been limited by their instability and low transmembrane efficiency. Here, we introduced a conjugated adjuvant of STING and TLR1/2, Pam3CSK4-CDGSF. Conjugating CDGSF with Pam3CSK4 increased the stability and intracellular delivery. In addition, by synergistically activating the STING and TLR pathways, Pam3CSK4-CDGSF was able to enhance immune activation. Both humoral and cellular immune responses were triggered by Pam3CSK4-CDGSF plus OVA (V4), and tumor growth was significantly inhibited after V4 administration. More importantly, V4 can also boost the antigen-specific CD8+ T cell response for cancer cell killing. Thus, the conjugated STING and TLR1/2 agonist Pam3CSK4-CDGSF can serve as a potent adjuvant for vaccine construction to augment antitumor immunotherapy.

Gastrointestinal mixed adenoneuroendocrine carcinoma: a population level analysis of epidemiological trends.

BACKGROUND: The rise in incidence and mortality of gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC) has not been well focused. The aim of our study was to examine epidemiological trends in incidence and incidence-based (IB) mortality of gastrointestinal MANEC at a population level. METHODS: The incidence and IB mortality of gastrointestinal MANEC as well as data on affected patients from 2000 to 2016 were obtained from the Surveillance, Epidemiology, and End Results database. Trends in incidence and IB mortality were assessed using Joinpoint regression. The Kaplan-Meier method and log-rank test were used for survival analysis. Cox proportional hazards regression was used to identify independent predictors of mortality. RESULTS: 581 patients diagnosed with gastrointestinal MANEC were enrolled. Gastrointestinal MANEC incidence was 0.23 cases per 1,000,000 individuals in 2000 and 1.16 cases per 1,000,000 individuals in 2016, with an annual percent change (APC) of 8.0% (95% CI 5.7-10.3%, P < 0.05). IB mortality also showed a sustained increase (APC 12.9%, 95% CI 9.0-16.8%, P < 0.05). In Cox regression analysis, age at diagnosis, tumor grade and stage, lymph node metastasis, surgery, and tumor size were independently associated with mortality. Median survival was 75 months (95% CI 60-128 months). Median survival of appendiceal MANEC was significantly longer than that of cecal MANEC (115 vs. 31 months; P < 0.001). CONCLUSIONS: We found a sustained and rapid increase both in incidence and IB mortality of gastrointestinal MANEC, manifesting that there has been no significant improvement in patient outcomes, nor progress in prevention and treatment. Additional resources should be devoted to gastrointestinal MANEC research.

Agonists and inhibitors of the STING pathway: Potential agents for immunotherapy.

Since being discovered in 2008, the STING (stimulator of interferon genes) pathway has gradually been recognized as a central and promising target for immunotherapy. The STING pathway can be stimulated by cyclic dinucleotides (CDNs), leading to the type I interferons (IFN) production for immunotherapy for cancer or other diseases. However, the negative charges, hydrophilicity, and instability of CDNs have hindered their further applications. In addition, chronic activation of the STING pathway has been found to be involved in autoimmune diseases as IFN overproduction. Thus, research and development of STING agonists and inhibitors has been a hot field for the treatment of several diseases. The past several years, especially 2018, has seen increasingly rapid advances in this field. Here, this review summarizes the synthesis and modification of CDNs, the identification of nonnucleotide agonists, the recent progress in delivery systems and the medical applications, such as personalized vaccine adjuvants, in detail. In addition, in this review, we summarize the STING inhibitors' advances from two aspects, covalent, and noncovalent inhibitors.

Fully Synthetic Invariant NKT Cell-Dependent Self-Adjuvanting Antitumor Vaccines Eliciting Potent Immune Response in Mice.

Constructing an effective therapeutic cancer vaccine is very attractive and promising for cancer immunotherapy. However, the poor immunogenicity of tumor antigens and suppression of the immune system in the tumor microenvironment are two major obstacles for developing effective cancer vaccines. Invariant NKT cells (iNKT cells), which are essential bridges between the innate and adaptive immune systems, can be rapidly activated by their agonists and, consequently, evoke whole immune systems. Herein, we conjugated a potent agonist of the iNKT cell, α-galactosylceramide (α-GalCer), with the tumor-associated MUC1 glycopeptide antigens as novel self-adjuvanting cancer vaccines through click chemistry. Immunological studies revealed that the mouse immune system was potently evoked and that high levels of tumor-specific IgG antibodies were elicited by vaccine conjugates without an external adjuvant. The produced antibodies could specifically recognize and bind to antigen-expressing cancer cells and, subsequently, induce cytotoxicity through complement-dependent cytotoxicity. Thus, the insertion of α-GalCer significantly improved the immunogenicity of the MUC1 glycopeptide and induced strong antigen-specific antitumor responses, indicating that α-GalCer is an effective built-in adjuvant for constructing potent chemical synthetic antitumor vaccines.

Cofilin-1, peroxiredoxin-1, and galectin-3: Major proteins released by macrophages infected with Corynebacterium pseudotuberculosis.

Corynebacterium pseudotuberculosis, a broad host-spectrum zoonotic pathogen, causes caseous lymphadenitis (CLA) in small ruminants and is responsible for considerable economic losses in the livestock industry worldwide. Macrophages play a pivotal role in the immunopathogenesis of CLA. However, the immunoregulatory mechanisms of macrophages against C. pseudotuberculosis remains poorly understood. In the present study, for the first time, the partial exoproteome of murine peritoneal macrophages infected with C. pseudotuberculosis was profiled and the differential expression of the identified proteins was analyzed. In macrophages, infection with C. pseudotuberculosis, rather than with heat-killed bacteria, induced release of diverse proteins. Three unconventional proteins: cofilin-1, peroxiredoxin-1, and galectin-3 were significantly expressed and released by infected macrophages into the culture supernatant. These proteins are involved in the host inflammatory response and may be responsible for the excessive inflammation of CLA. In C. pseudotuberculosis-infected macrophages, the release of cofilin-1 and peroxiredoxin-1 was predominant at later stages of infection, while the release of galectin-3 was independent of time. Taken together, the present work contributes to our understanding of the functional role of macrophage response to C. pseudotuberculosis infection.

Critical roles of NLRP3 inflammasome in IL-1ß secretion induced by Corynebacterium pseudotuberculosis in vitro.

Corynebacterium pseudotuberculosis is a prominent human and animal pathogen causing chronic inflammatory diseases. Interleukin-1ß (IL-1ß) is involved in the response to such pathogenic infections. However, the mechanism by which IL-1ß is secreted during C. pseudotuberculosis infection remains unclear. This study aimed to investigate the mechanism underlying IL-1ß secretion by macrophages infected with C. pseudotuberculosis. Herein, we firstly revealed that nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 (Casp1) play critical roles in IL-1ß secretion rather than IL-1ß precursor (pro-IL-1ß) expression in C. pseudotuberculosis-infected macrophages. Toll like receptor 4 (TLR4) is partially involved in IL-1ß secretion, while absent in melanoma 2 (AIM2) is not involved in IL-1ß secretion by C. pseudotuberculosis-infected macrophages. In addition, nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinases (p38 MAPK) inhibitors almost attenuated IL-1ß secretion, implying that NF-κB and p38MAPK pathway are involved in IL-1ß secretion in C. pseudotuberculosis-infected macrophages. Furthermore, C. pseudotuberculosis were significantly more numerous in Nlrp3-/-, Asc-/-, and Casp-1-/- macrophages than in WT macrophages at 24 h after infection (P < 0.05), indicating that NLRP3 inflammasome components limit C. pseudotuberculosis replication in macrophages. Together, these data provide novel insights into the mechanisms underlying IL-1ß secretion in C. pseudotuberculosis-infected macrophages and further the current understanding of the host pro-inflammatory immune response against this pathogen.

MicroRNA­181c suppresses growth and metastasis of hepatocellular carcinoma by modulating NCAPG.

Purpose: Numerous studies have shown that the expression of microRNA-181c (miR-181c) is inhibited in various cancers, which suggests that it has a cancer suppressive effect. In the current study, we evaluated the regulation and characteristics of miR-181c in human hepatocellular carcinoma (HCC). Materials and methods: Samples of tumor tissues and adjacent non-tumor tissues were collected from 52 patients with HCC, and expression levels of miR-181c in these samples were investigated via quantitative real-time polymerase chain reaction. HCC cell migration and invasion were investigated via wound healing assays and transwell assays. HCC cell apoptosis rates were assessed via flow cytometry, and HCC proliferation was assessed via 5-ethynyl-20-deoxyuridine assays. In vivo tumors were initiated by subcutaneously inoculating HCC cells into nude mice. And various biomarkers were investigated via western blotting. Results: In microarray datasets and tumor tissues, significant downregulation of miR-181c was apparent compared with non-tumorous adjacent tissues. Expression of miR-181c in HCC cells was also significantly lower than it was in normal human liver cells. miR-181c regulated the migration, invasion, apoptosis, and proliferation of HCC cell lines in vitro, and tumor development in vivo. Observations also suggest that miR-181c regulates NCAPG in HCC cells, and its expression affects cellular invasion, migration, proliferation, and apoptosis. There was a negative correlation between miR-181c expression and NCAPG in HCC tissue samples. Conclusion: miR-181c exhibits tumor-suppression via the regulation of NCAPG levels.

Non-functional pancreatic neuroendocrine tumours: emerging trends in incidence and mortality.

BACKGROUND: Our aim was to determine the epidemiology and recent changes in the trends of non-functional pancreatic neuroendocrine tumours (NF-pNETs) at the population level. In addition, we explored the risk factors that are associated with survival duration. METHODS: Cases were identified form the Surveillance, Epidemiology, and End Results (SEER) Programme database from 2000 to 2014. Data on incidence and incidence-based (IB) mortality for NF-pNET were obtained from this database. Secular trends in age-adjusted incidence and IB mortality were determined by using the Joinpoint Regression program. Data analyses were performed using chi-square tests, Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: Overall, 4766 patients diagnosed with NF-pNET with a median age of 59 years were identified through our descriptive criteria. Caucasian patients accounted for the majority of the study population, and the proportion of patients with distant disease significantly decreased during our study period. Overall, there was an increase in incidence and IB mortality for NF-pNET; however, the rate of increase decreased during the recent years. In addition, the incidence trends of NF-pNET located in the pancreatic head significantly increased, and rates fo increase in IB mortality for NF-pNET in the pancreatic tail decreased in recent years. Additionally, the 1-, 5-, and 10-year survival rates were 79.0, 51.8, 38.1%, respectively. Furthermore, patient age, tumour grade, stage at diagnosis, tumour size, tumour site and resection were associated with mortality. CONCLUSION: Despite increases in incidence and IB mortality, the rate of change in IB mortality for NF-pNET has decreased in recent years. Survival duration displayed a secular increase during the overall period, and the prognosis and survival duration of patients were closely related to the time of diagnosis, age of the patients and size and location of the tumour. Appropriate treatment adjustments based on tumour stage may thus facilitate improvements in patient outcomes.