Pan-cancer analysis reveals correlation between RAB3B expression and tumor heterogeneity, immune microenvironment, and prognosis in multiple cancers.

RAB3B is essential for the transportation and secretion within cells. Its increased expression is linked to the development and progression of various malignancies. However, understanding of RAB3B's involvement in carcinogenesis is mostly limited to specific cancer subtypes. Hence, exploring RAB3B's regulatory roles and molecular mechanisms through comprehensive cancer datasets might offer innovative approaches for managing clinical cancer. To examine the potential involvement of RAB3B in the development of cancer, we analyzed data from various sources including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), cBioPortal, HPA, UALCAN, and tissue microarray (TAM). Using bioinformatics techniques, we examined the correlation between RAB3B expression and prognosis, tumor heterogeneity, methylation modifications, and immune microenvironment across different cancer types. Our findings indicate that elevated RAB3B expression can independently predict prognosis in many tumors and has moderate accuracy for diagnosing most cancers. In most cancer types, we identified RAB3B mutations that showed a significant correlation with tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and microsatellite instability (MSI). Abnormal DNA methylation patterns were also observed in most cancers compared to normal tissues. Additionally, we found significant correlations between RAB3B expression, immune cell infiltration, and immune scores across various cancers. Through pan-cancer analysis, we observed significant differences in RAB3B expression levels between tumors and normal tissues, making it a potential primary factor for cancer diagnosis and prognosis. The IHC results revealed that the expression of RAB3B in six types of tumors was consistent with the results of the pan-cancer analysis of the database. Furthermore, RAB3B showed potential associations with tumor heterogeneity and immunity. Thus, RAB3B can be utilized as an auxiliary diagnostic marker for early tumor detection and a prognostic biomarker for various tumor types.

Uterine Burkitt Lymphoma with Rare Extranodal Deposits in the Bone, Breast, and Sacral Canal: A Case Report.

Burkitt lymphoma is a highly invasive non-Hodgkin lymphoma. Sporadic Burkitt's lymphoma is commonly found in the abdomen. However, Burkitt lymphoma infiltrating the uterus is uncommon in occurrence. We report the results of 18F-FDG PET/CT examination of a 36-year-old woman. The report indicates that in addition to the strong uptake of FDG imaging agent in the uterus, bilateral cervical and abdominal lymph nodes also have strong activity. At the same time, it was also found that bilateral small breast nodules, sacral canal and multiple bones in the whole body showed a radiation uptake pattern similar to that of the uterus. 18F-FDG PET/CT imaging can help determine the extent of the disease and the affected body area, which is helpful to guide the treatment decision. This case report shows the application of 18F-FDG PET/CT imaging in the diagnosis, staging and post-treatment evaluation of Burkitt lymphoma of the uterus. It provides very useful information for clinicians and helps to improve the accuracy of diagnosis and treatment effect.

Clinical usefulness of the baby vision test in young children and its correlation with the Snellen chart.

AIM: To investigate the efficacy of a new visual acuity (VA) screening method, the baby vision test for young children. METHODS: A total 105 eyes of 65 children aged 2-8y were included in the study. Acuity testing was conducted using a standardized recognition acuity chart (Snellen visual chart: at 3 m) and the baby vision model assessment. The baby vision device includes a screen, a near infrared camera and a computer. Children were seated at a measured distance of 33-40 cm from a display for testing. VA was estimated according to the highest resolution the children could follow. Decimal VA data were converted to logarithm of the minimum angle of resolution (logMAR) for statistical analysis. The VA results for each child were recorded and analyzed for consistency. RESULTS: The mean VA measured using the Snellen visual chart was 0.62±0.32, and that assessed using the baby vision test was 0.66±0.27. The 95% limit of agreement was -0.609 to 0.695, with 95.2% (100/105) plots within the 95% limits of agreement. VA values of the baby vision test were significantly correlated with those of the Snellen chart (R=0.274, P=0.005). CONCLUSION: The baby vision test can be used as a relatively reliable method for estimating VA in young children. This new acuity assessment might be a valid predictor of optotype-measured acuity later in preverbal children.

TRIP6 a potential diagnostic marker for colorectal cancer with glycolysis and immune infiltration association.

Thyroid hormone receptor interactor 6 (TRIP6) it is an adaptor protein belonging to the zyxin family of LIM proteins, participating in signaling events through interactions with various molecules. Despite this, TRIP6's role in colorectal cancer (CRC), particularly its correlation with glucose metabolism and immune cell infiltration, remains unclear. Through the TCGA and GEO databases, we obtained RNA sequencing data to facilitate our in-depth study and analysis of TRIP6 expression. To investigate the prognostic value of TRIP6 in CRC, we also used univariate Cox regression analysis. In addition, this study also covered a series of analyses, including clinicopathological analysis, functional enrichment analysis, glycolysis correlation analysis, immunoinfiltration analysis, immune checkpoint analysis, and angiogenesis correlation analysis, to gain a comprehensive and in-depth understanding of this biological phenomenon. It has been found that TRIP6 expression is significantly upregulated in CRC and correlates with the stage of the disease. Its overexpression portends a worse survival time. Functional enrichment analysis reveals that TRIP6 is associated with focal adhesion and glycolysis. Mechanistically, TRIP6 appears to exert its tumorigenic effect by regulating the glycolysis-related gene GPI. A higher level of expression of TRIP6 is associated with an increase in the number of iDC immune cells and a decrease in the number of Th1 immune cells. Also, TRIP6 may promote angiogenesis in tumor cells by promoting the expression of JAG2. Our study uncovers the upregulation of TRIP6 in CRC, illuminating its prognostic and diagnostic value within this context. Furthermore, we examine the relationship between TRIP6 expression levels, glycolysis, angiogenesis and immune cell infiltration. This underscores its potential as a biomarker for CRC treatment and as a therapeutic target.

Discussion on the Influence of Gpx 4 Target in the Field of Cancer.

The current review was undertaken to collate data on Gpx4 inhibitors and the regulatory proteins related to Gpx4. Gpx4 plays an essential role in ferroptosis; it can be used to determine the Gpx4 as an indicator for determining tumor occurrence and as a means of treating cancer. Although there is no market for Gpx4 inhibitors, many researchers have conducted extensive research, and some compounds have entered clinical research. This article summarizes all papers related to Gpx4; hope this review can provide some new insights and ideas for researchers aiming to develop efficient and low-- toxicity Gpx4 inhibitors and provide some new ideas for cancer treatment.

SPC25 as a novel therapeutic and prognostic biomarker and its association with glycolysis, ferroptosis and ceRNA in lung adenocarcinoma.

OBJECTIVE: Spindle pole body component 25 (SPC25) is an important cyclin involved in chromosome segregation and spindle dynamics regulation during mitosis. However, the role of SPC25 in lung adenocarcinoma (LAUD) is unclear. MATERIALS AND METHODS: The differential expression of SPC25 in tumor samples and normal samples was analyzed using TIMER, TCGA, GEO databases, and the correlation between its expression and clinicopathological features and prognosis in LUAD patients. Biological pathways that may be enriched by SPC25 were analyzed using GSEA. In vitro cell experiments were used to evaluate the effect of knocking down SPC25 expression on LUAD cells. Correlation analysis and differential analysis were used to assess the association of SPC25 expression with genes related to cell cycle, glycolysis, and ferroptosis. A ceRNA network involving SPC25 was constructed using multiple database analyses. RESULTS: SPC25 was highly expressed in LUAD, and its expression level could guide staging and predict prognosis. GSEA found that high expression of SPC25 involved multiple cell cycles and glycolytic pathways. Knocking down SPC25 expression significantly affected the proliferation, migration and apoptosis of LUAD cells. Abnormal SPC25 expression levels can affect cell cycle progression, glycolytic ability and ferroptosis regulation. A ceRNA network containing SPC25, SNHG15/hsa-miR-451a/SPC25, was successfully predicted and constructed. CONCLUSIONS: Our findings reveal the association of up-regulation of SPC25 in LUAD and its expression with clinical features, prognosis prediction, proliferation migration, cell cycle, glycolysis, ferroptosis, and ceRNA networks. Our results indicate that SPC25 can be used as a biomarker in LUAD therapy and a target for therapeutic intervention.

Real-world treatment and outcome patterns of patients with mantle cell lymphoma in China: A large, multicenter retrospective analysis.

BACKGROUND: Mantle cell lymphoma (MCL) is an uncommon heterogeneous subtype of B cell non-Hodgkin lymphoma, and clinical features in MCL appear regional characteristics. MCL treatment opinions are not uniform between countries or regions within Asia and China, and Asian patient-specific data for MCL treatment are fewer. The study aims to explore the clinical characteristics, treatment patterns and prognosis of MCL patients in China. METHODS: A total of 805 patients diagnosed with MCL between April 1999 and December 2019 at 19 comprehensive hospitals in China were included in this retrospective analysis. Kaplan-Meier method coupled with the log-rank test was used for univariate analysis, and COX proportional hazards model was used for multivariate analysis (MVA). p < 0.05 was consided statistically significant. All outputs were produced using R version 4.1.0. RESULTS: The median age of the cohort was 60.0 years with a male-to-female ratio of 3.36:1. Five-year progression-free survival (PFS) and overall survival (OS) rates were 30.9% and 65.0%, respectively. High-intermediate/high-risk group according to MIPI-c, without high-dose cytarabine, lack of Auto-SCT as consolidation and maintenance treatment and SD/PD in initial treatment remained statistically relevant to poor PFS on MVA, and ki67 ≥50%, B symptoms, high-intermediate/high risk group according to MIPI-c, without high-dose cytarabine, lack of maintenance treatment, SD/PD in initial treatment and relapse/refractory state were independently associated with poorer OS on MVA. CONCLUSIONS: First-line high dose cytarabine exposure, auto-SCT as consolidation therapy obtained survival benefits in Chinese population. Our study further confirmed the value of maintenance treatment and explored the application of new drug treatment and bendamustine in R/R MCL patients.

Interleukin 35: protective role and mechanism in type 1 diabetes.

Interleukin 35 (IL-35), a cytokine secreted by regulatory T (Treg) cells from the differentiation of conventional CD4+ T cells, is a member of the IL-12 family. The IL-12 family of cytokines exhibits an anti-inflammatory property. IL-35 has recently been shown to influence the immune modulation in various diseases, including inflammatory bowel disease, Graves' disease, rheumatoid arthritis, colitis, psoriasis, and type 1 diabetes (T1D). T1D is an immune-related disease caused by destruction of pancreatic ß cells, characterized by an absolute lack of insulin. Recently, studies have suggested that protective effects of IL-35 work by improving blood glucose levels and preventing an attack of inflammatory factors on the islets. The protective mechanism may be closely related to the anti-inflammatory properties of IL-35, which include regulating macrophage phenotype, suppressing T cell proliferation, decreasing the differentiation of Th17 cells, increasing the Treg cell population, and inducing IL-35-producing regulatory T cells (iTr35). Here, we review the protective effects and mechanisms of action of IL-35 in T1D.

Synthesis and evaluation of in vitro and in vivo anti-Toxoplasma gondii activity of tetraoxane-substituted ursolic acid derivatives.

A series of derivatives of ursolic acid (UA) were synthesised, the anti-Toxoplasma gondii activity was tested, and the selectivity index (SI) of these compounds was calculated to determine the derivative with the best anti-Toxoplasma gondii activity. Compound A7 showed the best activity against the Toxoplasma gondii (IC50 in T. gondii infected GES-1 cells: 9.1 ± 7.2 µM), better than the lead compound UA and the positive control drug Spiramycin. Compound A7 was selected for further in vivo research: A7 was tested for its effect on the inhibition rate of tachyzoites in mice and its biochemical parameters, such as alanine aminotransferase, aspartate aminotransferase, glutathione, and malondialdehyde were determined. Compound A7 was evaluated for its anti-Toxoplasma activity and partial damage to the liver. Therefore, the results show that compound A7 could be a potential lead compound for developing a novel anti-Toxoplasma gondii molecule.

Magnetic resonance imaging and 18F-fludeoxyglucose positron emission tomography/computed tomography findings of retroperitoneal clear cell carcinoma with an unknown primary site: A case report.

Herein, we report a case of retroperitoneal clear cell carcinoma (RCCC) with an unknown primary site that was confirmed via pathology. A 46-year-old man presented with low-grade fever, hyperhidrosis, and nightly fatigue that had occurred for the last 20 days. His weight had decreased significantly within the past 2 months (approximately 12 kg). On abdominal ultrasound, a mass was observed near the left renal hilum. In addition, enhanced magnetic resonance imaging (MRI) of the abdomen revealed a retroperitoneal nodular mass; however, no abnormalities in either kidney or adrenal glands were observed. 18F-fludeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) demonstrated an intensely FDG-avid retroperitoneal mass, the maximum standardized uptake value (SUVmax) was 19.6. On March 8, 2021, left retroperitoneal lesion resection, retroperitoneal lymph node dissection, and double kidney exploration were performed under general anesthesia. A post-operative pathological examination revealed Poorly differentiated clear cell carcinoma (left retroperitoneal) and metastatic lymph nodes. Immunohistochemical findings showed that the tumor originated from the kidney. At 6-month follow-up, reexamination of the patient revealed retroperitoneal lesion recurrence; however, no abnormalities were observable via enhanced computed tomography (CT) of both kidneys. To our knowledge, there have been no previous reports of RCCC of unknown origin.

Arginine ADP-ribosyltransferase 1 Regulates Glycolysis in Colorectal Cancer via the PI3K/AKT/HIF1α Pathway.

OBJECTIVE: Arginine ADP-ribosyltransferase 1 (ART1) is involved in the regulation of a diverse array of pathophysiological processes, including proliferation, invasion, apoptosis, autophagy and angiogenesis of colorectal cancer (CRC) cells. However, how ART1 regulates glycolysis in CRC remains elusive. METHODS: To elucidate the role of ART1 in glycolysis in CRC, we assessed the protein level of ART1, hypoxia-inducible factor 1α (HIF1α), and glucose transporter type 1 (GLUT1) in 61 CRC tumor tissue specimens obtained from patients with different 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) uptake as analyzed by PET/CT before surgery. Colon adenocarcinoma CT26 cells with ART1 knockdown and overexpression were established, respectively, and the molecular mechanism underlying the effect of ART1 on glycolysis in CRC was determined both in vivo and in vitro. RESULTS: The expression of ART1 and GLUT1 was significantly associated with FDG uptake (P=0.037 and P=0.022, respectively) in CRC tissues. Furthermore, the expression of hexokinase 2 (HK2) and lactate dehydrogenase (LDH) was upregulated in ART1-overexpressed CT26 cells, but was downregulated in ART1-knockdown CT26 cells. The volume and weight of subcutaneously transplanted tumors were markedly increased in the ART1-overexpressed BALB/c mice group and decreased in the ART1-knockdown group. In CT26 cells, the overexpression of ART1 promoted the expression levels of HK2 and LDH, and knockdown of ART1 suppressed them in the CT26 tumors. In both normal and hypoxic conditions, ART1 expression was associated with the protein level of phospho-serine/threonine kinase (p-AKT), HIF1α, and GLUT1 but not with that of AKT in CT26 cells and subcutaneous transplanted tumors. CONCLUSION: ART1 plays a crucial role in the elevation of glucose consumption in CT26 cells and may regulate GLUT1-dependent glycolysis in CRC via the PI3K/AKT/HIF1α pathway.

The role of histone chaperone spty2d1 in human colorectal cancer.

Colorectal cancer (CRC) remains a major public health concern, associated with a high rate of morbidity and mortality. Several factors have been implicated in its occurrence and development, which includes histone chaperones. The role of spty2d1 (spt2)-a novel histone chaperone protein-has rarely been investigated in CRC. Therefore, we demonstrated in this study that spt2 undergoes different genetic alterations in colorectal adenocarcinoma datasets and that it was associated with the proliferation of colon carcinoma. Spt2 silencing can reduce the ability of proliferation and increase the rate of apoptosis of LoVo cells. Regarding the overall survival associated with spt2, only the quartile disease-free survival of colon adenocarcinoma (COAD) was found to be statistically significant, while that of rectum adenocarcinoma (READ) was not. The positive (+++) expression of spt2 was correlated with a deeper invasion depth in colorectal adenocarcinoma, and this effect was more pronounced in COAD. These data collectively suggest that spt2 can influence the progression and prognosis in some subtypes of colorectal adenocarcinoma. Therefore, we propose spt2 as a potential target for application in enhancing the overall therapeutic efficacy in some specific subtypes of colorectal adenocarcinoma.

Comprehensive Analysis of GLUT1 Immune Infiltrates and ceRNA Network in Human Esophageal Carcinoma.

BACKGROUND: Glucose transporter 1 (GLUT1) is encoded by the solute carrier family 2A1 (SLC2A1) gene and is one of the glucose transporters with the greatest affinity for glucose. Abnormal expression of GLUT1 is associated with a variety of cancers. However, the biological role of GLUT1 in esophageal carcinoma (ESCA) remains to be determined. METHODS: We analyzed the expression of GLUT1 in pan-cancer and ESCA as well as clinicopathological analysis through multiple databases. Use R and STRING to perform GO/KEGG function enrichment and PPI analysis for GLUT1 co-expression. TIMER and CIBERSORT were used to analyze the relationship between GLUT1 expression and immune infiltration in ESCA. The TCGA ESCA cohort was used to analyze the relationship between GLUT1 expression and m6A modification in ESCA, and to construct a regulatory network in line with the ceRNA hypothesis. RESULTS: GLUT1 is highly expressed in a variety of tumors including ESCA, and is closely related to histological types and histological grade. GO/KEGG functional enrichment analysis revealed that GLUT1 is closely related to structural constituent of cytoskeleton, intermediate filament binding, cell-cell adheres junction, epidermis development, and P53 signaling pathway. PPI shows that GLUT1 is closely related to TP53, GIPC1 and INS, and these three proteins all play an important role in tumor proliferation. CIBERSORT analysis showed that GLUT1 expression is related to the infiltration of multiple immune cells. When GLUT1 is highly expressed, the number of memory B cells decreases. ESCA cohort analysis found that GLUT1 expression was related to 7 m6A modifier genes. Six possible crRNA networks in ESCA were constructed by correlation analysis, and all these ceRNA networks contained GLUT1. CONCLUSION: GLUT1 can be used as a biomarker for the diagnosis and treatment of ESCA, and is related to tumor immune infiltration, m6A modification and ceRNA network.

Monoterpene indole alkaloids from the roots of Bousigonia mekongensis and their anti-diabetic nephropathy activity.

Four new monoterpene indole alkaloids (1-4) together with six known alkaloids (5-10) were isolated from the roots of Bousigonia mekongensis. Compounds 3 and 4 were the first examples of condylocarpan-adenine type alkaloids obtained from natural plant resource. Their structures were elucidated on the basis of spectroscopic data. All compounds were evaluated for their inhibiting glucose-induced mesanginal cell proliferation and protecting high glucose-evoked podocyte injury activities. (-)-demethoxycarbonyldihydrogambirtannine (5) can significantly antagonize glucose-induced podocyte injury with EC50 value of 6.5 ± 1.2 µM.

Role of mono-ADP-ribosylation histone modification (Review).

The current knowledge regarding ADP-ribosylation modifications of histones, particularly mono-ADP-ribosylation modifications, is limited. However, recent studies have identified an increasing number of mono-ADP-ribosyltransferases and the role of mono-ADP-ribosylation has become a hot research topic. In particular, histones that are substrates of several mono-ADP-ribosyltransferases and mono-ADP-ribosylated histones were indicated to be involved in numerous physiological or pathological processes. Compared to poly-ADP-ribosylation histone modification, the use of mono-ADP-ribosylation histone modification is restricted by the limited methods for research into its function in physiological or pathological processes. The aim of the present review was to discuss the details regarding mono-ADP-ribosylation modification of histones and the currently known functions thereof, such as cell physiological and pathological processes, including tumorigenesis.

Exogenous Local Hyperthermia at 41℃ Is Effective to Eliminate Mouse Model of Sporotrichosis, Independent of Neutrophil Extracellular Traps Formation.

BACKGROUND: Local hyperthermia is recommended for the treatment of patients with fixed cutaneous sporotrichosis, though the effectiveness and mechanisms of action remain elusive. While neutrophils represent the main inflammatory cells associated with sporotrichosis lesions, the issue of whether hyperthermia is involved with interactions between neutrophils and Sporothrix globosa remains unclear. OBJECTIVE: To evaluate the effect of local hyperthermia on sporotrichosis and determine whether local hyperthermia involves effects of neutrophils against Sporothrix. METHODS: For the in vivo study, mice were infected with yeast cells of S. globosa followed by treatment with local hyperthermia. In vitro, an isolated Sporothrix strain was co-cultured with or without neutrophils and subjected under different temperatures. Immunofluorescence was used to assess the formation of neutrophil extracellular trap (NETs) were formed under these different culture conditions and the number of fungi colony forming units were compared. RESULTS: Hyperthermia was significantly more effective in clearing the lesions in the mouse model, as compared to sham treatment. Neutrophils failed to exert any fungicidal effects against S. globosa in response to hyperthermia. Moreover, NETs were formed after interaction with S. globosa, and the percentage of NETs formed was not significantly different at 41℃ or 37℃. CONCLUSION: While hyperthermia could serve as an effective therapy for fixed cutaneous sporotrichosis, this ability does not involve the formation of NETs.

Analysis of Mono-ADP-Ribosylation Levels in Human Colorectal Cancer.

BACKGROUND: Colorectal cancer remains a major public health problem with high morbidity and mortality rates. In the search for the mechanisms of colorectal cancer occurrence and development, increasing attention has been focused on epigenetics. The overall level of Mono-ADP-ribosylation, an epigenetic, has not been investigated now. The aim of our study was to analysis of the overall level of mono-ADP-ribosylation in colorectal cancer. METHODS: Immunohistochemistry was used to investigate the level of mono-ADP-ribosylation in colorectal cancer and normal colorectal adjacent tissue from 64 CRC patients. The data of patient demographic, clinical and pathological characteristics were acquired and analyzed. RESULTS: Mono-ADP-ribosylation was present in both colorectal adenocarcinoma and normal colorectal tissue. The overall level of mono-ADP-ribosylation in colorectal cancer was significantly higher than that in normal colorectal adjacent tissue. In the nucleus, the majority of samples in the high-level group were colorectal adenocarcinoma (55/64), but the opposite was true for normal colorectal tissues (7/32). In particular, increases in the level of mono-ADP-ribosylation in the cytoplasm of colorectal cancer cells was associated with a greater invasion depth of the tumor. CONCLUSION: The increased level of mono-ADP-ribosylation in colorectal cancer enhances tumor invasion, which suggests that mono-ADP-ribosylation is involved in the development of colorectal cancer and may become a new direction to solve the problem of colorectal cancer.

Transcriptome sequencing analysis of mono­ADP­ribosylation in colorectal cancer cells.

Colorectal cancer (CRC) is a global health concern. The role of epigenetics in tumors has garnered increasing interest. ADP ribosylation is an epigenetic modification that is associated with a variety of biological functions and diseases, and its association with tumor development and progression has been hypothesized. However, due to the limitations of available techniques and methods, ADP ribosylation of specific sites is difficult to determine. In previous studies, it was shown that arginine­117 of histone 3 (H3R117) in Lovo cells can be modified by mono­ADP­ribosylation. This site was mutated and Lovo cells overexpressing this mutant construct were established. In the present study, the expression of differentially expressed genes (DEGs) between untransfected Lovo cells and H3R117A Lovo cells was analyzed. A total of 58,174 DEGs were identified, of which 2,324 were significantly differentially expressed (q­value <0.05; fold change >2). Functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment was used to analyze the functions and possible roles of the DEGs. The DEGs were enriched in pathways associated with metabolic process, catalytic activity, organelle and chromatin structure, and dynamics. Through this comprehensive and systematic analysis, the role of mono­ADP­ribosylation in CRC was examined, providing a foundation for future studies.

Profiling thiol metabolites in myocardial infarction human serum by stable isotope labeling assisted liquid chromatography-mass spectrometry.

Myocardial Infarction (MI) is one of the most common causes of deaths worldwide. Thiols have been reported to play a key role in physiological and pathological processes of MI. Comprehensive analysis of thiols would be conducive to fully elucidate the relation between thiols and MI. In the current study, we analyze the metabolomic differences of thiols in serum between MI patients (n = 30) and healthy controls (HCs, n = 30) by stable isotope labeling-dispersive solid phase extraction-liquid chromatography-full scan-Orbitrap-mass spectrometry analysis (IL-DSPE-LC-full scan-Orbitrap MS) method. We detected 300 potential thiols in serum of MI patients and HCs, among which, 67 thiols were positively or putatively identified. Furthermore, we found that the levels of 71 thiols in serum exhibited significant difference between MI patients and HCs. In the transsulfuration pathway, we observed that Cys and Hcys were upregulated, while GSH were downregulated. Our results provide a comprehensive understanding of thiols metabolome in human serum between MI patients and HCs.

PARG regulates the proliferation and differentiation of DCs and T cells via PARP/NF­κB in tumour metastases of colon carcinoma.

The present study investigated the effect of poly(ADP­ribose) glycohydrolase (PARG) on the immune response in tumour metastases of colon carcinoma. CT26 cells were transfected with lentivirus PARG­short hairpin RNA (shRNA). A liver metastasis model of colon carcinoma was successfully established by splenic subcapsular inoculation of the various groups of CT26 cells into BALB/c mice. Next, changes in the liver metastases of colon carcinoma nodules and alterations in the survival times were observed in tumour­bearing mice. The numbers of B220+DEC205+ dendritic cells (B220+DEC205+DC) and CD11c+CD11b+ dendritic cells (CD11c+CD11b+DC) in the spleen and liver were measured by the double­label immunofluorescence assay. The distribution pattern of CD4+T cells and CD8+T cells in the spleen and liver was investigated by immunofluorescence staining. The expression levels of PARG, PARP and nuclear factor­κB (NF­κB) proteins in spleen transplant tumours and liver metastases of colon carcinoma were detected by western blotting. An ELISA was used to detect the levels of IL­10 and TGF­ß in the serum of tumour­bearing mice and from the supernatant of tumour cells. The numbers and grading of metastatic liver nodules in the PARG­silenced group were clearly lower than those in the control group. The survival time of the PARG­silenced group mice was longer than that in the control group. In the PARG­silenced group, the levels of B220+DEC205+DC in the spleen and liver were lower and the numbers of CD11c+CD11b+DC in the spleen and liver were more than those in the control group. The ratio of CD4+/CD8+ in the spleen and liver in the PARG­silenced group was increased compared with that in the control group (P<0.05). The levels of PARG, PARP and NF­κB in spleen transplant tumours and liver metastases of colon carcinoma were lower in the PARG­silenced group than in the control group. In addition, the levels of IL­10 and TGF­ß in the serum of tumour­bearing mice and supernatants of tumour cells were both reduced in the PARG­silenced group compared with those in the control group. The present research suggests that the liver metastases of colon carcinoma could be restrained by silencing PARG. Likely, the silencing of PARG could suppress the expression of PARP and NF­κB and subsequently suppress the secretion of IL­10 and TGF­α, finally affecting the proliferation and differentiation of DC and T cells.