Search

Objective: This study aimed to investigate the potential molecular mechanism of SPDEF in immune evasion of colorectal cancer (CRC) and examine its impact on macrophage M2 polarization using the TCGA and GEO databases. Methods: By combining TCGA and GEO databases, differential gene expression between CRC samples and standard tissue samples was analyzed to screen for immune-related genes (IRGs) associated with the prognosis of CRC patients. A predictive risk model was constructed based on 18 key IRGs, which were then validated using the GEO dataset. The relationship between transcription factors and IRGs was further explored to investigate their regulatory network in CRC. In vivo and in vitro experiments were carried out to validate these regulatory relationships and explore the function of SPDEF and CCL28 in CRC. Results: Twelve key IRGs associated with clinical and pathological characteristics of CRC patients were identified. Among them, CCL28 significantly impacted macrophage infiltration in CRC cells and may be a critical factor in immune evasion. In both in vitro and in vivo experiments, overexpression of SPDEF upregulated CCL28 expression, thereby suppressing M2 polarization of macrophages and inhibiting CRC cell proliferation and tumor growth. Notably, interference with CCL28 could reverse the effect of SPDEF overexpression. Conclusion: SPDEF can suppress immune evasion of CRC cells by activating CCL28, which is achieved through the modulation of M2 polarization of macrophages. This provides a new research direction and potential therapeutic target for immunotherapy in CRC.

Abstract Nanomaterials are developing rapidly in the medical field, bringing new hope for treating various refractory diseases. Among them, polymer nanomaterials, with their excellent properties, have been used to treat various diseases, such as malignant tumors, diabetes, and nervous system diseases. Gastrointestinal cancer is among the cancers with the highest morbidity and mortality worldwide. Cancer stem cells are believed to play an important role in the occurrence and development of tumors. This article summarizes the characteristics of gastrointestinal cancer stem cells and reviews the latest research progress in treating gastrointestinal malignant tumors using polymer nanoparticles to target cancer stem cells. In addition, the review article highlights the potential of polymer nanoparticles in targeting gastrointestinal cancer stem cells.

Acute pancreatitis (AP) is a severe life-threatening inflammatory disease showing primary characteristics of excessive inflammatory response and oxidative stress. Based on the pathophysiology of AP, several anti-inflammatory and anti-oxidative stress agents have been studied. However, the low accumulated concentrations and scattered biodistributions limit the application of these agents. With the development of nanotechnology, functional nanomaterials can improve the bioavailability of drugs and extend their half-life by reducing immunogenicity to achieve targeted drug delivery. The biomaterial-based carriers can mediate the passive or active delivery of drugs to the target site for improved therapeutic effects, such as anti-oxidation and anti-inflammation for AP treatment. Other biomaterials-based nanomedicine may exhibit different functions with/without targeting effects. In this review, we have summarized the targeting and functional effects of biomaterials-based nanoagents specifically for AP treatment.

Cuprotosis, a newly proposed mechanism of cell death, can trigger acute oxidative stress that leads to cell death by mediating protein lipidation in the tricarboxylic acid cycle. However, cuprotosis-related long non-coding RNAs (CRLNCs) and their relationship with prognosis and the immunological landscape of colorectal cancer (CRC) are unclear. We have developed a lncRNA signature to predict survival time, immune infiltration, and sensitivity to chemotherapy. CRLNCs were screened using the Cor function of the R software and the differentially expressed lncRNAs were collected with the limma package. Differentially expressed long non-coding RNAs (lncRNAs) associated with prognosis were selected using univariate regression analysis. A prognostic signature was developed using the least absolute shrinkage and selection operator (LASSO) and multivariate regression analysis. Patients with CRC were divided into two groups based on the risk score. The low-risk group had a more favorable prognosis, higher expression of immune checkpoints, and a higher level of immune cell infiltration compared with the high-risk group. Furthermore, there was a close association between the risk score and the clinical stage, tumor mutational burden, cancer stem cell index, and microsatellite instability. We also assessed chemotherapy response in the two risk groups. Our study analyzed the role of CRLNCs in CRC and provided novel targets and strategies for CRC chemotherapy and immunotherapy.

Perineural invasion (PNI) is the process of neoplastic invasion of peripheral nerves and is considered to be the fifth mode of cancer metastasis. PNI has been detected in head and neck tumors and pancreatic, prostate, bile duct, gastric, and colorectal cancers. It leads to poor prognostic outcomes and high local recurrence rates. Despite the increasing number of studies on PNI, targeted therapeutic modalities have not been proposed. The identification of PNI-related biomarkers would facilitate the non-invasive and early diagnosis of cancers, the establishment of prognostic panels, and the development of targeted therapeutic approaches. In this review, we compile information on the molecular mediators involved in PNI-associated cancers. The expression and prognostic significance of molecular mediators and their receptors in PNI-associated cancers are analyzed, and the possible mechanisms of action of these mediators in PNI are explored, as well as the association of cells in the microenvironment where PNI occurs.

Nutrition and energy are essential for poultry growth and production performance. Fasting and refeeding have been widely used to study the effects of nutrition, energy, and related mechanisms in chicken. Previous studies have shown that geese have a strong capacity for fat synthesis and storage; thus, changes in the goose liver transcriptome may be different from those in chicken assessed with a model of fasting and refeeding. However, the responses of the goose liver transcriptome to fasting and refeeding have not yet been addressed. In this study, 36 70-day-old Si Ji geese with similar body weight were randomly assigned to three groups: control (ad libitum feeding), fasting (fasted for 24 h), and refeeding (fast for 24 h followed by 2-h feeding) groups. After treatment, eight geese per group were sacrificed for sample collection. Liver samples from four geese in each group were subjected to transcriptome analysis, followed by validation of differentially expressed genes (DEGs) using quantitative polymerase chain reaction with the remaining samples. As a result, 155 DEGs (73 up-regulated) were identified between the control and fasting groups, and 651 DEGs (321 up-regulated) were identified between the fasting and refeeding groups. The enrichment analyses of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways showed that fasting mainly influenced material metabolism in the liver, especially lipid metabolism; in contrast, refeeding affected not only lipid metabolism but also glucose and amino acid metabolism. In addition, the peroxisome proliferator-activated receptor (PPAR) signaling pathway may play an important role in lipid metabolism. In conclusion, fasting and refeeding have a strong effect on lipid metabolism in the goose liver; specifically, fasting promotes fatty acid oxidation and inhibits fatty acid synthesis, and refeeding has the opposite effect. The model of fasting and refeeding is suitable for goose nutrition studies.

Abstract Exosomes are extracellular vesicles secreted by various cells, mainly composed of lipid bilayers without organelles. In recent years, an increasing number of researchers have focused on the use of exosomes for drug delivery. Targeted drug delivery in the body is a promising method for treating many refractory diseases such as tumors and Alzheimer's disease (AD). Finding a suitable drug delivery carrier in the body has become a popular research today. In various drug delivery studies, the exosomes secreted by mesenchymal stem cells (MSC-EXOs) have been broadly researched due to their immune properties, tumor-homing properties, and elastic properties. While MSC-EXOs have apparent advantages, some unresolved problems also exist. This article reviews the studies on MSC-EXOs for drug delivery, summarizes the characteristics of MSC-EXOs, and introduces the primary production and purification methods and drug loading methods to provide solutions for existing problems and suggestions for future studies.

Clinically, periodontitis is a chronic nonspecific inflammation that leads to damaged teeth and their supporting gum tissues. Although many studies on periodontitis have been conducted, therapy with natural products is still rare. Silibinin has been proven to have anti-inflammatory and antioxidant activities. However, the effects of silibinin on lipopolyssacharide (LPS)-induced inflammation in periodontal ligaments (PDLs) have not yet been investigated. In this study, the PDLs were treated with silibinin (10, 20, and 40 μM) in the presence of LPS. The results showed that silibinin treatment reduced the levels of NO, PGE2, IL-6, TNF-α, MMP-1, and MMP-3 and enhanced the activities of superoxide dismutase (SOD) and glutathione (GSH). Moreover, silibinin treatment downregulated RANKL levels and upregulated OPG and ALP levels. In summary, silibinin protected PDLs against LPS-induced inflammation, oxidative stress, and osteogenic differentiation.

Colorectal cancer (CRC) is a common clinical disease with a poor prognosis and a high recurrence rate. Chemotherapy is important to inhibit the post-surgical recurrence of CRC patients. But many limitations restrict the further application of chemotherapy. In this study, sorafenib (Sor) and metformin (Met) co-loaded poly(ethylene glycol)-block-poly(L-glutamic acid-co-L-phenylalanine) [mPEG-b-P(Glu-co-Phe)] micelles were developed. The characterizations, drug release, in vivo biodistribution, and pharmacokinetics of the micelles were analyzed. The treatment efficacy of the dual-drug loaded micelles was evaluated in a subcutaneous colon cancer mice model. Sor is a common molecular target agent that can inhibit the mitogen-activated protein kinase (MAPK) pathway to treat solid tumors. Met can also regulate the MAPK pathway and inhibit the expression of the phosphorylated extracellular signal-regulated kinase (p-ERK). Moreover, both Sor and Met play important roles in cell cycle arrest. The integration of these two drugs aims to achieve synergistic effects against colon cancer. The micelles can be targeted to cancer cells and possess longer blood circulation time. The two agents can be released rapidly in the tumor sites. The in vivo study showed that the micelles can prevent tumor progression by inhibiting the expressions of p-ERK and cyclin D1. This study indicated that the Sor/Met-loaded micelles are suitable for CRC treatment.

Schwannoma is a type of tumor originating from Schwann cells of peripheral nerves. In this study, we report a rare case of two giant connected retroperitoneal schwannomas. The patient presented to our department with a 1-day history of abdominal pain and without other symptoms. There were no abnormalities in the patient’s tumor markers. Abdominal plain computed tomography (CT) revealed two (combined) retroperitoneal masses appearing as soft tissue-density shadows with uneven internal density, cystic low-density shadows, and patchy calcification shadows. The larger mass measured approximately 12.0 cm × 12.3 cm in size. The tumors were completely excised by a reasonable surgical approach while the surrounding organs closely related to the tumor were preserved. Postoperative pathology confirmed that the tumors were benign schwannomas. In the 18-month follow-up, the patient had no recurrences and was asymptomatic. We summarize the diagnosis and treatment of two rare combined giant retroperitoneal schwannomas in a single patient. Laparotomy for the management of retroperitoneal giant schwannomas may be safe and effective.

Nutrition and energy levels have an important impact on animal growth, production performance, disease occurrence and health recovery. Previous studies indicate that melanocortin 5 receptor (MC5R) is mainly involved in the regulations of exocrine gland function, lipid metabolism and immune response in animals. However, it is not clear how MC5R participates in the nutrition and energy metabolism of animals. To address this, the widely used animal models, including the overfeeding model and the fasting/refeeding model, could provide an effective tool. In this study, the expression of MC5R in goose liver was first determined in these models. Goose primary hepatocytes were then treated with nutrition/energy metabolism-related factors (glucose, oleic acid and thyroxine), which is followed by determination of MC5R gene expression. Moreover, MC5R was overexpressed in goose primary hepatocytes, followed by identification of differentially expressed genes (DEGs) and pathways subjected to MC5R regulation by transcriptome analysis. At last, some of the genes potentially regulated by MC5R were also identified in the in vivo and in vitro models, and were used to predict possible regulatory networks with PPI (protein–protein interaction networks) program. The data showed that both overfeeding and refeeding inhibited the expression of MC5R in goose liver, while fasting induced the expression of MC5R. Glucose and oleic acid could induce the expression of MC5R in goose primary hepatocytes, whereas thyroxine could inhibit it. The overexpression of MC5R significantly affected the expression of 1381 genes, and the pathways enriched with the DEGs mainly include oxidative phosphorylation, focal adhesion, ECM–receptor interaction, glutathione metabolism and MAPK signaling pathway. Interestingly, some pathways are related to glycolipid metabolism, including oxidative phosphorylation, pyruvate metabolism, citrate cycle, etc. Using the in vivo and in vitro models, it was demonstrated that the expression of some DEGs, including ACSL1, PSPH, HMGCS1, CPT1A, PACSIN2, IGFBP3, NMRK1, GYS2, ECI2, NDRG1, CDK9, FBXO25, SLC25A25, USP25 and AHCY, was associated with the expression of MC5R, suggesting these genes may mediate the biological role of MC5R in these models. In addition, PPI analysis suggests that the selected downstream genes, including GYS2, ECI2, PSPH, CPT1A, ACSL1, HMGCS1, USP25 and NDRG1, participate in the protein–protein interaction network regulated by MC5R. In conclusion, MC5R may mediate the biological effects caused by changes in nutrition and energy levels in goose hepatocytes through multiple pathways, including glycolipid-metabolism-related pathways.

The Liaohe Group, which is a significant lithostratigraphic unit within the Paleoproterozoic Jiao-Liao-Ji Belt situated between the Longgang and Liaonan-Nangrim blocks, comprises the Langzishan, Li’eryu, Gaojiayu, Dashiqiao, and Gaixian formations, which are characterized mainly by a clastic-rich sequence with an interlayered bimodal-volcanic sequence, carbonate-rich sequence, and (meta-)pelite-rich sequence. Currently, the tectonic background and evolution of the Liaohe Group remain contentious. Based on the study of detrital zircon geochronology and the zircon trace element characteristics in the Langzishan and Li’eryu formations in the North Liaohe Group in the Lianshanguan area, NE China, this paper reveals the formations’ provenances, depositional ages, and relationships with Paleoproterozoic granitoids (the Liao-Ji granites). The present results, in conjunction with previous studies, indicate that the depositional age of the Langzishan Formation is 2136 Ma and that of the Li’eryu Formation is 1974 Ma. The provenances of the Langzishan Formation and the Li’eryu Formation are mainly characterized by Neoarchean-to-early-Paleoproterozoic basement rocks (~2.6–2.4 Ga) and the Liao-Ji granites (~2.2–2.0 Ga), respectively. Moreover, the coeval mafic and metasedimentary rocks of the Liaohe Group exhibit characteristics of an extensional environment, which is represented by the tectonic setting of a back-arc basin. Notably, the Upper Langzishan Formation records a prominent shift in sedimentary environment from a passive continental margin to an active continental margin. In terms of the tectonic evolution of the North Liaohe Group and the Jiao-Liao-Ji Belt, our proposed model suggests that the Archean basement rocks in the northern part of the continental block, along with a limited contribution from the Paleoproterozoic Liao-Ji granites, served as the primary sources for the Langzishan Formation. Subsequently, the rapid deposition of the Li’eryu Formation was influenced by intense magmatism and subsequent erosion of the subduction-related magmatic arc (the Liao-Ji granites) within a back-arc basin environment. Lastly, the deposition of clastic materials from the Longgang blocks and the Liao-Ji granites resulted in the formation of the Gaojiayu, Dashiqiao, and Gaixian formations.

Dedifferentiated liposarcoma (DDLPS) is a rare subtype of liposarcoma with a poor prognosis. This current case report describes a rectal DDLPS in a 68-year-old Chinese male that presented with lower abdominal pain and weight loss. Computed tomography and magnetic resonance imaging were undertaken to evaluate the tumour. The patient underwent radical resection of the rectal tumour, sigmoid colostomy and partial ureterectomy. The tumour was positive for mouse double minute 2 by immunohistochemistry. The patient healed well but refused chemotherapy postoperatively for economic reasons. The tumour recurred and metastasized 4 weeks after the operation. After relevant treatment, the patient's condition deteriorated and he died of shock, metabolic acidosis, hyperlactataemia and acute renal failure. The case report also reviews the literature in terms of the clinical diagnosis, treatment and pathological characteristics of rectal DDLPS with the aim of improving the level of diagnosis and treatment.

The inverse process of diffuse optical tomography (DOT) is ill-posed, which has a significant effect on the quality of the reconstructed results. In this paper, the polarization characteristics of light are introduced into the inverse solution model of DOT to increase the solution constraints and improve the imaging quality. The spectral element method is used to numerically solve the vector radiative transfer equation, which is used to simulate the propagation of polarized light in a scattering medium. The DOT reverse solution algorithm based on the polarization component is constructed so that the Stokes vector can be used for absorption coefficient and scattering coefficient reconstruction. The simulation and experimental results show that when polarized light is used for incidence, using the intensity component and the multi-polarization component to solve the DOT inverse model can improve the reconstruction accuracy of the medium absorption coefficient distribution and the DOT image quality.

It is known that nutrition and immunity are connected, but the mechanism is not very clear. Endogenous retroviruses (ERV) account for 8 to 10% of the human and mouse genomes and play an important role in some biological processes of animals. Recent studies indicate that the activation of ERV can affect the expression of the immunity- or inflammation-related genes, and the activities of ERV are subjected to regulation of many factors including nutritional factors. Therefore, we hypothesize that nutritional status can affect the expression of the immunity- or inflammation-related genes via ERV. To verify this hypothesis, the nutritional status of animals was altered by fasting or overfeeding, and the expression of intact ERV (ERVK18P, ERVK25P) and immunity- or inflammation-related genes (DDX41, IFIH1, IFNG, IRF7, STAT3) in the liver was determined by quantitative PCR, followed by overexpressing ERVK25P in goose primary hepatocytes and determining the expression of the immunity- or inflammation-related genes. The data showed that compared with the control group (no fasting), the expression of ERV and the immunity- or inflammation-related genes was increased in the liver of the fasted chickens but decreased in the liver of the fasted geese. Moreover, compared with the control group (routinely fed), the expression of ERV and the immunity- or inflammation-related genes was increased in the liver of the overfed geese. In addition, overexpression of ERVK25P in goose primary hepatocytes can induce the expression of the immunity- or inflammation-related genes. In conclusion, these findings suggest that ERV mediate the effects of fasting and overfeeding on the expression of the immunity- or inflammation-related genes, the mediation varied with poultry species, and ERV and the immunity- or inflammation-related genes may be involved in the development of goose fatty liver. This study provides a potential mechanism for the connection between nutrition and immunity.

Overfeeding causes severe steatosis but not inflammation in goose liver, suggesting existence of protective components. Previous studies have shown that some intestinal microbes and their metabolites damage intestinal structural integrity and function, thus causing inflammation in the development of human and mouse nonalcoholic fatty liver disease. Therefore, this study hypothesizes that intestinal structural integrity of goose is maintained during overfeeding, which may provide goose fatty liver a protective mechanism against inflammation. To test this hypothesis, 48 seventy-day-old healthy Landes male geese were overfed (as overfeeding group) or normally fed (as control group). Blood and intestine (jejunum, ileum, and cecum) samples were harvested on the 12th and 24th d of overfeeding. Data showed that goose fatty liver was successfully induced by 24 d of overfeeding. Hematoxylin-eosin staining analysis indicated that the arrangement of villi and crypts in the intestine was orderly, and the intestinal structure was intact with no pathological symptoms in the 2 groups. Enzyme-linked immunosorbent assay and quantitative PCR analysis indicated no significant differences in the expression of tight junction and inflammation-related genes as well as plasma lipopolysaccharide concentration between the groups. Ileal hypertrophy and cecal atrophy were observed in the overfed vs. control geese, probably because of change of sphingolipid metabolism. Activation of apoptotic pathway may help cecum avoid necrosis-induced inflammation. In conclusion, healthy and intact intestine provides a layer of protection for goose fatty liver against inflammation. Sphingolipid metabolism may be involved in the adaptation of ileum and cecum to overfeeding. The hypertrophy of ileum makes it an important contributor to the development of goose fatty liver. The atrophy and decline in the function of cecum may be caused by apoptosis induced by overfeeding.

Abstract Background To describe the clinical characteristics and management for Fournier’s gangrene. Experience summary and literature references are provided for future treatment improvement. Methods We retrospectively reviewed the cases diagnosed with Fournier’s gangrene in our department from June 2016 to June 2019. Clinical data, including manifestation, diagnosis, treatment and outcomes for Fournier’s gangrene were presented. Results There were 12 patients enrolled in this paper, with the average age of 60 years old. It showed a male predominance with male-to-female ratio of 6:1. The average of laboratory risk indicator for necrotizing fasciitis (LRINEC) score was 10.1. Diabetes mellitus was the main predisposing disease. 11 patients received emergency debridement and 1 patient died of sepsis on the 2nd day after admission. The mortality rate was 8.3%. 6 cases developed complications, including sepsis, pneumonia, renal and heart failure. Negative pressure wound therapy (NPWT) was applied in 10 cases, while the rest 1 received normal daily dressing changes because of fecal contamination. Flaps were utilized in 2 patients to cover the defect, including one with advancement flap and one with pudendal-thigh flap, while others received secondary suture, secondary healing, skin graft or combined management. No relapse was observed during the follow-up visits. Conclusions Fournier’s gangrene is a life-threatening infection that requires early diagnosis and surgery intervention. The predisposing disease, clinical manifestation and LRINEC score should be taken into comprehensive consideration, which is helpful for timely diagnosis. Moreover, further successful treatment depends on the aggressive debridement, broad-spectrum antibiotics therapy, wound management and closure choice.

Fatty liver hemorrhagic syndrome (FLHS), usually occurring in hens in the late laying period, can lower egg yield and even cause death. Similar to nonalcoholic fatty liver disease in humans, FLHS may begin with simple hepatic steatosis. It is known that gut microbiota is important to the development of nonalcoholic fatty liver disease, but the relationship between FLHS and gut bacteria remains unclear. In this study, bacteria compositions in the ileum and cecum were determined by 16S rDNA sequencing analysis in the groups of hens with vs. without hepatic steatosis (average liver fat contents were 0.34 mmol/g protein or 2.6% vs. 0.84 mmol/g protein or 6.0%). These hens were in the 2 tails of the liver fat content distribution with each tail accounting for 10% of the test population containing 90 66-wk-old healthy Rhode Island Red laying hens raised under routine feeding regimen. The results showed that liver weight but not the weights of the body, heart and abdominal fat were significantly different between the groups. Moreover, bacterial diversity was not significantly different between the groups, but bacterial diversity in the cecum was higher than that in the ileum. Proteobacteria was the most dominant phylum in the ileum, whereas Proteobacteria, Firmicutes, and Bacteroidetes were the most dominant phyla in the cecum. Some bacteria were common to the ileum and cecum, but some were unique. Furthermore, some bacteria were significantly different in abundance between the groups, that is the group without hepatic steatosis had more bacteria inhibiting host energy absorption or benefiting intestinal health, whereas the group with hepatic steatosis had more conditionally pathogenic or harmful bacteria. In conclusion, hepatic steatosis in laying hens is associated with intestinal bacterial composition (bacterial abundance) but not bacterial diversity. The identified common and unique bacteria are related to the functional characteristics of the ileum and cecum. The decrease of beneficial bacteria and the increase of harmful bacteria in the intestine of laying hens may increase FLHS incidence by promoting hepatic steatosis.

Tumor dormancy, a state of tumor, is clinically undetectable and the outgrowth of dormant tumor cells into overt metastases is responsible for cancer-associated deaths. However, the dormancy-related molecular mechanism has not been clearly described. Some researchers have proposed that cancer stem cells (CSCs) and disseminated tumor cells (DTCs) can be seen as progenitor cells of tumor dormancy, both of which can remain dormant in a non-permissive soil/niche. Nowadays, research interest in the cancer biology field is skyrocketing as mesenchymal stem cells (MSCs) are capable of regulating tumor dormancy, which will provide a unique therapeutic window to cure cancer. Although the influence of MSCs on tumor dormancy has been investigated in previous studies, there is no thorough review on the relationship between MSCs and tumor dormancy. In this paper, the root of tumor dormancy is analyzed and dormancy-related molecular mechanisms are summarized. With an emphasis on the role of the MSCs during tumor dormancy, new therapeutic strategies to prevent metastatic disease are proposed, whose clinical application potentials are discussed, and some challenges and prospects of the studies of tumor dormancy are also described.

Abstract Background Acute liver failure (ALF) is a serious threat to the life of people all over the world. Finding an effective way to manage ALF is important. Human liver stem cells (HLSCs) are early undifferentiated cells that have been implicated in the regeneration and functional reconstruction of the liver. In this study, we aimed to evaluate the protective effects of the HLSC line HYX1 against concanavalin A (ConA)-induced acute liver injury. Methods HYX1 cells were characterized by microscopy, functional assays, gene expression, and western blot analyses. We showed that HYX1 cells can differentiate into hepatocytes. We intraperitoneally injected HYX1 cells in mice and administered ConA via caudal vein injection 3, 6, 12, 24, and 48 h later. The effects of HYX1 cell transplantation were evaluated through blood tests, histology, and flow cytometry. Results HYX1 cells reduced the levels of alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in serum and dramatically decreased the severity of liver injuries. Mechanistically, HYX1 cells promoted myeloid-derived suppressor cell (MDSC) migration into the spleen and liver, while reducing CD4+ T cell levels in both tissues. In addition, HYX1 cells suppressed the secretion of proinflammatory cytokines, such as tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), but led to increased interleukin-10 (IL-10) production. Conclusions These results confirm the efficacy of HLSCs in the prevention of the ConA-induced acute liver injury through modulation of MDSCs and CD4+ T cell migration and cytokine secretion.

Radical resection with or without adjuvant chemotherapy is a common option for stage II and III colorectal cancer. Few reports exist regarding gastric tumorigenesis, including gastric cancer, gastric intraepithelial neoplasia, and gastric stromal tumor, in patients who received this protocol as the standard treatment for colorectal cancer. We present two cases of gastric tumorigenesis in patients with colorectal cancer following radical resection combined with adjuvant chemotherapy. Both patients underwent gastrectomy and D2 lymphadenectomy for their gastric tumors; neither patient developed recurrence up to 2 years after treatment. These cases indicate that patients should be monitored closely for gastric tumorigenesis after treatment for colorectal cancer. Early detection and active surgical treatment can provide satisfactory results for colorectal cancer followed by gastric tumorigenesis. Long-term follow-up and regular examinations, especially gastroscopy, are necessary to detect gastric tumorigenesis after colorectal cancer. The focus on monitoring colorectal cancer alone in colorectal cancer patients should be changed to include a broader range of cancers in addition to precancers and other tumors, such as gastric stromal tumor.

Pancreatic cancer is a lethal disease characterized by highly dense stroma fibrosis. Only 15–20% of patients with pancreatic cancer have resectable tumors, and only around 20% of them survive to 5 years. Traditional cancer treatments have little effect on their prognosis, and successful surgical resection combined with effective perioperative therapy is the main method for maximizing long-term survival. For this reason, chemotherapy is an adjunct treatment for resectable cancer and is the main therapy for incurable pancreatic cancer, including metastatic pancreatic adenocarcinoma. However, there are various side effects of chemotherapeutic medicine and low drug penetration because the complex tumor microenvironment limits the application of chemotherapy. As a novel strategy, polymer nanoparticles make it possible to target the tumor microenvironment, release cytotoxic agents through various responsive reactions, and thus overcome the treatment barrier. As drug carriers, polymer nanoparticles show marked advantages, such as increased drug delivery and efficiency, controlled drug release, decreased side effects, prolonged half-life, and evasion of immunogenic blockade. In this review, we discuss the factors that cause chemotherapy obstacles in pancreatic cancer, and introduce the application of polymer nanoparticles to treat pancreatic cancer.

Abstract Peri-implant disease is a chronic inflammation of the soft and hard tissues around a dental implant, resulting from bacterial infection. Recent evidence indicates that some pro-inflammatory cytokines and chemokines released by immunocytes are substantially responsible for the progress and consequence of inflammation. High mobility group box 1 (HMGB1) is released into the extracellular matrix and acts as a key pro-inflammatory factor during injury, necrosis and inflammation. A higher concentration of HMGB1 has been found in gingival crevicular fluid from inflammatory gingival tissue than from healthy sites. HMGB1 mRNA and protein are overexpressed in murine periodontal ligament fibroblasts stimulated with lipopolysaccharide (LPS) and IL-1β. Thus, this study sought to assess HMGB1 expression in peri-implant crevicular fluid (PICF) at each stage of peri-implant disease and to investigate the correlation between HMGB1 and peri-implant disease progress. The results demonstrated that the HMGB1 expression level in PICF is indicative of the progress of peri-implant disease and hence may be a useful diagnostic and prognostic biomarker for peri-implant tissue.

A considerable body of evidence has shown that inflammation plays an important role in the process of stroke rehabilitation and development of poststroke depression (PSD). However, the specific molecular and cellular mechanisms involved remain unclear. In this review, we summarize how neuroinflammation affects stroke rehabilitation and PSD. We mainly focus on the immune/inflammatory response, involving astrocytes, microglia, monocyte-derived macrophages, cytokines (tumor necrosis factor alpha, interleukin 1), and microRNAs (microRNA-124, microRNA 133b). This review provides new insights into the effect of inflammation on the process of stroke rehabilitation and PSD and potentially offer new therapeutic targets of stroke and PSD.

KRAS, NRAS and BRAF are kinases involved in the RAS-RAF-MAPK signaling pathway and also potential tumor-driven genes. Patients with KRAS/NRAS/BRAF mutations are resistant to anti-EGFR monoclonal antibody therapy. The main purpose of this study is to investigate the mutation status and distribution of KRAS/NRAS/BRAF in Chinese colorectal and gastric cancers, and to explore the histopathological changes and related immunohistochemical marker changes caused by these mutations. The mutation status of KRAS (exons 2, codon 12/13), NRAS (exons 2/3/4, codon 12/13/59/61/117/146) and BRAF (exons 15, codon 600) were detected by amplification refractory mutation system polymerase chain reaction (ARMS-PCR) in 86 colon cancer, 140 rectal cancer and 34 gastric cancer tissues. Then, the frequencies and distribution of KRAS/NRAS/BRAF mutations were described in detail. Furthermore, the relationship between KRAS/NRAS/BRAF mutations and the features of histopathological and related immunohistochemical markers were analyzed. The results showed that KRAS/NRAS/BRAF mutation rates in colon cancer were 44.2, 1.2, and 3.5%; in rectal cancer were 37.1, 4.3, and 0.7%; in gastric cancer were none, none and 2.9%. The mutation rate of KRAS in female (48.8%) is significantly higher than that of male (27.8%), and the mutation rate increased with the higher degree of differentiation. Additionally, the mutation rate of BRAF detected by ARMS-PCR (1.77%) was significantly lower than that by immunohistochemistry (4.11%). It also showed that the KRAS/NRAS/BRAF mutation status had a certain relationship with the expression of some immunohistochemical markers. This study provides more data support for clinical research on KRAS/NRAS/BRAF mutation in CRCs or gastric cancers.

Background. It has been found that single-nucleotide polymorphisms (SNPs) of microRNA might be involved in the development of inflammatory bowel diseases (IBDs). However, the related retrospective research has not been reported. In this work, we performed a meta-analysis to derive a more precise estimation of the associated relationship. Methods. We searched the studies on the association of SNPs of microRNA with the hereditary susceptibility of IBD in PubMed and Embase; eligible research was selected by screening the abstract and full text. The meta-analysis was performed based on the statistical software Stata 14.0, and besides, the odds ratio and 95% confidence interval were calculated to evaluate the strength of the association. Results. 159 papers were acquired from the PubMed and Embase databases, and five eligible articles containing nine case-control studies were selected. In the study, we first found that the association between miRNA-196a2 rs11614913 and IBD was insignificant. Then, the susceptibility of miRNA-146a rs2910146 to IBD increased significantly in allelic comparison, homozygote model, heterozygote model, and dominant model. Moreover, a positive relationship between miRNA-499 rs3746444 and IBD was identified in the homozygote model. Conclusion. Our findings demonstrated that miRNA-146a rs2910146 (G>C) polymorphism was associated with the susceptibility to IBD and miRNA-196a2 rs11614913 (T>C) and miRNA-499 rs3746444 (A>G) did not reveal an obvious relationship with the IBD susceptibility.

Switchable metasurfaces with fast responses and high efficiency are highly desirable in various applications. In this paper, we propose and analyze a novel electro-optical switch based on continuous metasurface embedded in Si substrate. The simulative results indicate that the embedded and continuous metasurface structure is able to increase the interaction volume between the metal antennas and the surrounding substrate, hence enhances the tuning effect when changing the refractive index of Si by an injection current, resulting in fully switching between anomalous and normal reflections, and achieving a high extinction ratio even under a smaller refractive index variation.

The inability of the yeast Saccharomyces cerevisiae to ferment xylose effectively under anaerobic conditions is a major barrier to economical production of lignocellulosic biofuels. Although genetic approaches have enabled engineering of S. cerevisiae to convert xylose efficiently into ethanol in defined lab medium, few strains are able to ferment xylose from lignocellulosic hydrolysates in the absence of oxygen. This limited xylose conversion is believed to result from small molecules generated during biomass pretreatment and hydrolysis, which induce cellular stress and impair metabolism. Here, we describe the development of a xylose-fermenting S. cerevisiae strain with tolerance to a range of pretreated and hydrolyzed lignocellulose, including Ammonia Fiber Expansion (AFEX)-pretreated corn stover hydrolysate (ACSH). We genetically engineered a hydrolysate-resistant yeast strain with bacterial xylose isomerase and then applied two separate stages of aerobic and anaerobic directed evolution. The emergent S. cerevisiae strain rapidly converted xylose from lab medium and ACSH to ethanol under strict anaerobic conditions. Metabolomic, genetic and biochemical analyses suggested that a missense mutation in GRE3, which was acquired during the anaerobic evolution, contributed toward improved xylose conversion by reducing intracellular production of xylitol, an inhibitor of xylose isomerase. These results validate our combinatorial approach, which utilized phenotypic strain selection, rational engineering and directed evolution for the generation of a robust S. cerevisiae strain with the ability to ferment xylose anaerobically from ACSH.

Mammalian target of rapamycin complex 1 and 2 (mTORC1/2) are overactive in colorectal carcinomas; however, the first generation of mTOR inhibitors such as rapamycin have failed to show clinical benefits in treating colorectal carcinoma in part due to their effects only on mTORC1. The second generation of mTOR inhibitors such as PP242 targets mTOR kinase; thus, they are capable of inhibiting both mTORC1 and mTORC2. To examine the therapeutic potential of the mTOR kinase inhibitors, we treated a panel of colorectal carcinoma cell lines with PP242. Western blotting showed that the PP242 inhibition of mTORC2-mediated AKT phosphorylation at Ser 473 (AKT(S473)) was transient only in the first few hours of the PP242 treatment. Receptor tyrosine kinase arrays further revealed that PP242 treatment increased the phosphorylated epidermal growth factor receptor (EGFR) at Tyr 1068 (EGFR(T1068)). The parallel increase of AKT(S473) and EGFR(T1068) in the cells following PP242 treatment raised the possibility that EGFR phosphorylation might contribute to the PP242 incomplete inhibition of mTORC2. To test this notion, we showed that the combination of PP242 with erlotinib, an EGFR small molecule inhibitor, blocked both mTORC1 and mTORC2 kinase activity. In addition, we showed that the combination treatment inhibited colony formation, blocked cell growth and induced apoptotic cell death. A systemic administration of PP242 and erlotinib resulted in the progression suppression of colorectal carcinoma xenografts in mice. This study suggests that the combination of mTOR kinase and EGFR inhibitors may provide an effective treatment of colorectal carcinoma.

Crystals of the title compound, [Fe(C8H7N3)3]2[PMo12O40]·6H2O, prepared under hydrothermal conditions, are isotypic with the Mn2+ and Cd2+ analogues. The Fe2+ cation is in a distorted octahedral coordination by six N atoms from three chelating 3-(2-pyridyl)-1H-pyrazole ligands. The heteropolyanion [PMo12O40]4− is a one-electron reduced species in which two O atoms of the central PO4 group (overline{1} symmetry) are equally disordered about an inversion centre. N—H...O and O—H...O hydrogen bonds make a contribution to the crystal packing. The Fe—N bond lengths [2.085 (19)—2.15 (2) Å] are somewhat shorter than the Mn—N and Cd—N bond lengths [2.224 (6)–2.283 (5) and 2.316 (7)–2.334 (6) Å, respectively]. All other bond lengths and angles and the hydrogen-bonding motifs are very similar in the isotypic structures.

Metabolomics has been widely used to identify changes in relevant differential metabolites. The metabolites of Saccharomyces cerevisiae cells supplemented with ferulic acid and p-coumaric acid were prepared and extracted. Untargeted metabolomics analysis of saccharomyces cerevisiae metabolites was performed. In addition, GNPS, Respect and MassBank databases were used to search and compare the information in the whole database. It was found that 100 and 92 different metabolites were significantly changed (P value < 0.05, VIP value > 1,) in Saccharomyces cerevisiae cells treated with ferulic acid and p-coumaric acid respectively. Including isothiocyanate, L-threonine, adenosine, glycerin phospholipid choline, niacinamide and palmitic acid. These metabolites with significant differences were enriched by KEGG pathway using MetPA database. [ABSTRACT FROM AUTHOR]