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1.
Environ Toxicol ; 38(9): 2204-2218, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37300850

ABSTRACT

Ionic liquids (ILs) are thought to have negative effects on human health. Researchers have explored the effects of ILs on zebrafish development during the early stages, but the intergenerational toxicity of ILs on zebrafish development has rarely been reported. Herein, parental zebrafish were exposed to different concentrations (0, 12.5, 25, and 50 mg/L) of [Cn mim]NO3 (n = 2, 4, 6) for 1 week. Subsequently, the F1 offspring were cultured in clean water for 96 h. [Cn mim]NO3 (n = 2, 4, 6) exposure inhibited spermatogenesis and oogenesis in F0 adults, even causing obvious lacunae in the testis and atretic follicle oocytes in ovary. After parental exposure to [Cn mim]NO3 (n = 2, 4, 6), the body length and locomotor behavior were measured in F1 larvae at 96 hours post-fertilization (hpf). The results showed that the higher the concentration of [Cn mim]NO3 (n = 2, 4, 6), the shorter the body length and swimming distance, and the longer the immobility time. Besides, a longer alkyl chain length of [Cn mim]NO3 had a more negative effect on body length and locomotor behavior. RNA-seq analysis revealed several downregulated differentially expressed genes (DEGs)-grin1b, prss1, gria3a, and gria4a-enriched in neurodevelopment-related pathways, particularly the pathway for neuroactive ligand-receptor interaction. Moreover, several upregulated DEGs, namely col1a1a, col1a1b, and acta2, were mainly associated with skeletal development. Expression of DEGs was tested by RT-qPCR, and the outcomes were consistent with those obtained from RNA-Seq. We provide evidence showing the effects of parental exposure to ILs on the regulation of nervous and skeletal development in F1 offspring, demonstrating intergenerational effects.


Subject(s)
Ionic Liquids , Water Pollutants, Chemical , Animals , Male , Female , Humans , Zebrafish/metabolism , Ionic Liquids/toxicity , Testis , Spermatogenesis , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/metabolism
2.
Clin Exp Metastasis ; 40(4): 309-320, 2023 08.
Article in English | MEDLINE | ID: mdl-37266842

ABSTRACT

Lipopolysaccharide-induced tumor necrosis factor alpha factor (LITAF) is a transcription factor that activates the transcription of TNF-α and regulates the inflammatory response. LITAF has been found to have potential anti-cancer effects of in several tumors. However, the role of LITAF in colorectal cancer (CRC) remains unclear. Through a comprehensive pan-cancer analysis of the Cancer Genome Atlas (TCGA), LITAF was identified as a differentially downregulated gene in CRC. We hypothesized that LITAF may participate in the modulation of CRC progression. The present study was aimed to investigate the expression profile of LITAF in CRC and its effect on metastatic behavior and stemness as well as the underlying molecular mechanism. The expression profile of LITAF in CRC, and its relationship with the prognosis of CRC were explored using public databases. LITAF expression was detected by quantitative real-time PCR (qRT-PCR), western blot, and immunohistochemistry. Furthermore, the effects of overexpression or knockdown of LITAF on cell proliferation, apoptosis, migration, invasion, and stemness of CRC cells were investigated in vitro. The regulatory effect of LITAF on forkhead Box O 1 (FOXO1)-sirtuin 1 (SIRT1) signaling axis was also explored. In addition, a xenograft mouse model was used to investigate the in-vivo role of LITAF. LITAF was downregulated in tumor tissues and its expression was associated with the prognosis, pathological stage and liver metastasis. In-vitro experiments confirmed that LITAF inhibited tumor cell proliferation, migration, invasion and stemness, and induced cell apoptosis. In vivo experiments demonstrated that LITAF inhibited the tumorigenicity and liver metastasis in tumor-bearing mice. Additionally, LITAF promoted FOXO1-mediated SIRT1 inhibition, thus regulating cancer stemness and malignant phenotypes. LITAF was silenced in CRC and it participated in the progression of CRC by inhibiting CRC cell stemness, and malignant phenotypes. Therefore, LITAF may serve as a novel biomarker of CRC prognosis.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Humans , Animals , Mice , Sirtuin 1/genetics , Sirtuin 1/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Lipopolysaccharides , Cell Proliferation/genetics , Colorectal Neoplasms/pathology , Liver Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , Cell Movement/genetics , Forkhead Box Protein O1/genetics , Forkhead Box Protein O1/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
3.
Clin Transl Med ; 13(3): e1208, 2023 03.
Article in English | MEDLINE | ID: mdl-36855778

ABSTRACT

BACKGROUND: FBXL8 is a conserved F-box protein, belonging to the ubiquitin ligase complex, which promotes the development and progression of tumours. However, the regulation function and mechanism of FBXL8's involvement in colorectal cancer (CRC) remain unclear. METHODS: RT-PCR is used to detect gene expression levels. Protein levels were determined by western blotting and flow cytometry. The bindings of FBXL8 and p53 and ubiquitination levels were detected by cell transfection and immunoprecipitation. The transwell assay was used to measure the ability of cells to migrate and invade. Animal studies were used to verify the function of FBXL8 in vivo. RESULTS: The expression of FBXL8 was up-regulated in CRC tissues, and its overexpression was associated with poor prognosis in CRC patients. The up-regulation of FBXL8 promoted the proliferation, invasion and migration of CRC tumour cells and maintained the stem-cell characteristics of colorectal tumour cells. Further analysis demonstrated that FBXL8 targeted p53 and reduced its stability through ubiquitination. Knockout of FBXL8 down-regulated the proliferation, migration and stem-like properties of tumour cells. CRC mouse xenograft tumour model confirmed that FBXL8 gene knockout inhibited tumour formation and liver metastasis. CONCLUSION: FBXL8 was highly expressed in CRC. Mechanism studies have shown that FBXL8 degraded tumour suppressor gene p53 by ubiquitination. FBXL8 knockout inhibited the proliferation and stem characteristics of CRC cells, so SCF-FBXL8-TP53 has potential to be used as a therapeutic target for CRC in subsequent studies.


Subject(s)
Colorectal Neoplasms , F-Box Proteins , Liver Neoplasms , Tumor Suppressor Protein p53 , Animals , Humans , Mice , Colorectal Neoplasms/genetics , Disease Models, Animal , Liver Neoplasms/genetics , Mice, Knockout , Tumor Suppressor Protein p53/genetics , F-Box Proteins/genetics , Ubiquitination
4.
Int J Biochem Cell Biol ; 158: 106408, 2023 05.
Article in English | MEDLINE | ID: mdl-36990424

ABSTRACT

F-box and WD repeat domain containing 10 (FBXW10) is a member of the FBXW subgroup that contains the WD40 domain. FBXW10 has been rarely reported in colorectal cancer (CRC) and its mechanism is unclear. To investigate the role of FBXW10 in CRC, we conducted in vitro and in vivo experiments. Through the database and our clinical samples, we found that FBXW10 expression was up-regulated in CRC, and it was positively correlated with CD31 expression. CRC patients with high FBXW10 expression levels had a poor prognosis. Overexpression of FBXW10 up-regulated cell proliferation, migration and vascular formation, while knockdown of FBXW10 had the opposite effects. Studies on the mechanism of FBXW10 in CRC showed that FBXW10 could ubiquitinate large tumor suppressor kinase 2 (LATS2) and promote its degradation with the Fbox region of FBXW10 played an essential role in this process. In vivo studies demonstrated that knockout of FBXW10 inhibited tumor proliferation and reduced liver metastasis. In conclusion, our study proved that FBXW10 was significantly overexpressed in CRC and was involved in the pathogenesis of CRC by affecting angiogenesis and liver metastasis. Mechanistically, FBXW10 degraded LATS2 through ubiquitination. Therefore, FBXW10-LATS2 can be used as a therapeutic target for CRC in subsequent studies.


Subject(s)
Colorectal Neoplasms , F-Box Proteins , Liver Neoplasms , Humans , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Liver Neoplasms/genetics , Ubiquitination , Cell Proliferation/genetics , Colorectal Neoplasms/pathology , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , F-Box Proteins/genetics , F-Box Proteins/metabolism
5.
Ecol Evol ; 13(2): e9823, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36818527

ABSTRACT

Spatial vegetation patterns are associated with ecosystem stability and multifunctionality in drylands. Changes in patch size distributions (PSDs) are generally driven by both environmental and biological factors. However, the relationships between these factors in driving PSDs are not fully understood. We investigated 80 vegetation plots along an aridity gradient in the Alxa plateau, Northwest China. The sizes of vegetation patches were obtained from aerial images, and the heights of patch-forming species were measured in the field. Soil samples were collected on the bare ground between patches for determination of physiochemical properties. Point pattern analysis was used to infer plant-plant interactions. A model selection procedure was employed to select the best predictors for the shape of PSDs and biological factors (vegetation total cover, community plant height, and plant-plant interactions). We then used structural equation modeling to evaluate the direct and indirect effects of environmental and biological factors on the shape of PSDs. In our study area, two types of PSDs coexisted, namely those that best fit to power law distributions and those that best fit to lognormal distributions. Aridity was the main environmental factor, while community mean height and competition between plants were the main biological factors for the shape of PSDs. As aridity and community mean height increased, power law-like PSDs were exhibited, whereas competition led to deviations of PSDs from power laws. Aridity affected the shape of PSDs indirectly through changes in community mean height. Community mean height was correlated with competition, thereby indirectly affecting the shape of PSDs. Our results suggest the use of community functional traits as a link between the environment and plant-plant interactions, which may improve the understanding of the underlying mechanisms of PSD dynamics.

6.
Neurosci Bull ; 39(6): 1009-1026, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36680709

ABSTRACT

Anxiety disorders are currently a major psychiatric and social problem, the mechanisms of which have been only partially elucidated. The hippocampus serves as a major target of stress mediators and is closely related to anxiety modulation. Yet so far, its complex anatomy has been a challenge for research on the mechanisms of anxiety regulation. Recent advances in imaging, virus tracking, and optogenetics/chemogenetics have permitted elucidation of the activity, connectivity, and function of specific cell types within the hippocampus and its connected brain regions, providing mechanistic insights into the elaborate organization of the hippocampal circuitry underlying anxiety. Studies of hippocampal neurotransmitter systems, including glutamatergic, GABAergic, cholinergic, dopaminergic, and serotonergic systems, have contributed to the interpretation of the underlying neural mechanisms of anxiety. Neuropeptides and neuroinflammatory factors are also involved in anxiety modulation. This review comprehensively summarizes the hippocampal mechanisms associated with anxiety modulation, based on molecular, cellular, and circuit properties, to provide tailored targets for future anxiety treatment.


Subject(s)
Hippocampus , Neuropeptides , Humans , Hippocampus/physiology , Anxiety , Anxiety Disorders , Neurotransmitter Agents
7.
Protein Expr Purif ; 203: 106214, 2023 03.
Article in English | MEDLINE | ID: mdl-36526214

ABSTRACT

Hepatitis E is an emerging zoonotic disease, posing a severe threat to public health in the world. Since there are no specific treatments available for HEV infection, it is crucial to develop vaccine to prevent this infection. In this study, the truncated ORF2 encoded protein of 439aa∼617aa (HEV3-179) from HEV CCJD-517 isolates was expressed as VLPs in E. coli with diameters of approximate 20 nm. HEV3-179 protein was immunized with mice, and the results showed that a higher titre of antibody was induced in NIH mice in comparison with that of KM mice (P < 0.01) and BALB/c mice (P < 0.01). The induced antibody titer is much higher in subcutaneous immunization mice than that in the mice inoculated via abdominal immunization (P < 0.05) and muscles immunization (P < 0.01). Mice immunized with 12 µg and 6 µg candidate vaccine induced higher level of antibody titer than that of 3 µg dosage group (P < 0.01, P < 0.05). Antibody change curve showed that HEV IgG antibody titer increased from 14 days post immunization (dpi) to 1:262144 and reached the peak level on 42 dpi before gradually retreated with the same level antibody titer with 1:131072 until 84 dpi. Mice inoculated with HEV3-179 produced higher titer of cytokines than the mock group, and the concentration of IL-1ß (P < 0.01) and IFN-γ (P < 0.01) further increased after stimulated by candidate vaccine. The result indicated that HEV3-179 possesses good immunogenicity, which could be used as a potential candidate for future HEV vaccine development.


Subject(s)
Hepatitis E virus , Hepatitis E , Vaccines, Virus-Like Particle , Animals , Mice , Capsid Proteins/genetics , Capsid Proteins/immunology , Escherichia coli , Hepatitis E/prevention & control , Hepatitis E virus/genetics , Hepatitis E virus/immunology , Immunization , Recombinant Proteins/genetics , Artificial Virus-Like Particles/immunology , Vaccines, Virus-Like Particle/immunology
8.
Front Surg ; 9: 901615, 2022.
Article in English | MEDLINE | ID: mdl-36090320

ABSTRACT

Background: Nodal status is a vital prognostic factor for ampullary adenocarcinoma. This study was designed to evaluate the clinical significance of the positive nodes in this disease. Methods: Data from 110 patients who underwent curative pancreatoduodenectomy for ampullary adenocarcinoma between January 2007 and December 2018 were retrospectively collected and analyzed. Results: The median number of lymph nodes per patient was 32 (20-46). Metastatic lymph nodes were found in 84 (76.4%) patients. In patients with positive nodules, the most commonly involved nodes were the #13 (80.1%) and #17 (78.6%) nodes, followed by #12 (69.0%) and #8 nodes (57.1%). Patients with 3-4 positive nodes among #13, #17, #12, and #8 had lower survival rates than those with 0 or 1-2 nodes. Conclusion: Ampullary adenocarcinoma commonly spreads to #13, #17, #12, and #8 lymph nodes. These nodes affected the patients' survival rates dramatically.

9.
Front Plant Sci ; 13: 897528, 2022.
Article in English | MEDLINE | ID: mdl-35783961

ABSTRACT

For a long history, herbal medicines have made significant contributions to human health all around the world. However, the exploration of an effective approach to illustrate their inner quality remains a challenge. So, it is imperative to develop new methods and technologies to characterize and identify quality markers of herbal medicines. Taking Isatidis Radix, the dried root of Isatis indigotica as an example, desorption electrospray ionization (DESI), in combination with quadrupole-time-of-flight mass spectrometry (Q-TOF/MS), was applied in this work for the first time to reveal the comprehensive spatial distribution of metabolites and, further, to illustrate quality characters of this herbal medicine. After simple pretreatment, 102 metabolites including alkaloids, sulfur-containing compounds, phenylpropanoids, nucleosides, amino acids, organic acids, flavonoids, phenols, terpenes, saccharides, peptides, and sphingolipids were characterized, some of which were successfully localized and visualized in the transverse section of the root. Based on the ion images, samples with different quality characters were distinguished unambiguously by the pattern recognition method of orthogonal partial least squares discrimination analysis (OPLS-DA). Simultaneously, 11 major influencing components exerting higher ion intensities in superior samples were identified as the potential quality markers of Isatidis Radix. Desorption electrospray ionization (DESI) mass spectrometry imaging (MSI), together with chemometric analysis could not only improve the understanding of the plant biology of herbal medicines but also be beneficial in the identification of quality markers, so as to carry out better quality control of herbal medicines.

10.
World J Surg Oncol ; 20(1): 210, 2022 Jun 21.
Article in English | MEDLINE | ID: mdl-35729607

ABSTRACT

BACKGROUND: The risk of HCC is documented to be age-related. The outcomes of young HCC patients on postoperative prognosis are not well understood. The study aims to compare the characteristic differences between adolescent and young (AYA) and non-AYA HCC patients. METHODS: We performed a retrospective analysis of the clinical and pathological findings and the survival of 243 HCC patients who underwent operations between 2007 and 2018. RESULTS: The AYA group had a higher AFP level and a higher prevalence of family history of HCC or other cancers than the non-AYA group (P < 0.01 and P < 0.05). AYA patients had more unfavorable pathological characteristics including bigger lesion size, microvascular invasion, portal vein invasion, and hepatic capsule invasion. They also had a more unfavorable Edmondson grade and less tumor capsule formation (P < 0.01). Age was an independent predictor of survival in HCC patients. AYA patients had poorer disease-free and overall survival than non-AYA patients did (P < 0.01). Patients under 30 years old had an even poorer disease-free survival than those aged 30-40 (P = 0.047). CONCLUSIONS: AYA patients exhibited a higher recurrence rate and disease-related death rate with more unfavorable pathological characteristics. Enhanced follow-up for young HCC patients should be applied.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Adolescent , Adult , Carcinoma, Hepatocellular/pathology , Hepatectomy , Humans , Liver Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Prognosis , Retrospective Studies
11.
Ann Hum Biol ; 49(1): 27-34, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35254201

ABSTRACT

BACKGROUND: A body shape index (ABSI) has been proven to be related to a population's CVD incidence. However, the application of this indicator has produced different results. AIM: This study aimed to evaluate the applicability of the ABSI in predicting the incidence of CVD in rural Xinjiang, China, and compare it with waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and body mass index (BMI). SUBJECTS AND METHODS: 5375 people aged 18 years or older were included in the study. We used the Cox proportional hazard model to evaluate the relationship between WC, WHR, WHtR, BMI, and ABSI and the incidence of CVD, the area under the curve (AUC) to evaluate the predictive power of each anthropometric index for the incidence of CVD, and restricted cubic splines are used to analyse the trend relationship between anthropometric indicators and the incidence of CVD. RESULTS: After multivariate adjustment, standardised WC, WHR, WHtR, BMI, and ABSI all positively correlated with the incidence of CVD. WC had the highest HR (95% CI) value, 1.64 (1.51-1.78), and AUC (95% CI) value, 0.7743 (0.7537-0.7949). ABSI had the lowest HR (95% CI) value, 1.21(1.10-1.32), and AUC (95% CI) value, 0.7419 (0.7208-0.7630). In the sex-specific sensitivity analysis, the predictive ability of traditional anthropometric indicators for the incidence of CVD is higher than that of ABSI. CONCLUSIONS: In the rural areas of Xinjiang, the traditional anthropometric indicators of WC had better ability to predict the incidence of CVD than ABSI.


Subject(s)
Cardiovascular Diseases , Body Mass Index , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , China/epidemiology , Cohort Studies , Female , Humans , Male , Obesity/epidemiology , Risk Factors , Waist Circumference , Waist-Height Ratio , Waist-Hip Ratio
12.
Cell Death Dis ; 12(10): 930, 2021 10 12.
Article in English | MEDLINE | ID: mdl-34642302

ABSTRACT

Colorectal tumorigenesis is a heterogeneous disease driven by multiple genetic and epigenetic alterations. F-box and WD repeat domain containing 11 (FBXW11) is a member of the F-box protein family that regulates the ubiquitination of key factors associated with tumor growth and aggressiveness. Our study aimed to explore the role of FBXW11 in the development and metastasis of colorectal cancer (CRC). FBXW11 was overexpressed in colorectal tumor tissues and its overexpression was associated with a poor prognosis of CRC patients. The upregulation of FBXW11 not only promoted cell proliferation, invasion, and migration, but also contributed to maintaining stem-cell features in colorectal tumor cells. Further analysis revealed that FBXW11 targeted hypermethylated in cancer 1 (HIC1) and reduced its stability in CRC cells through ubiquitination. Moreover, the expression of sirtuin 1 (SIRT1), a deacetylase in tumor cells was upregulated by FBXW11 via regulating HIC1 expression. The mouse xenograft models of CRC confirmed that FBXW11 knockdown impeded colorectal tumor growth and liver metastasis in vivo. In summary, our study identified FBXW11 as an oncogenic factor that contributed to stem-cell-like properties and liver metastasis in CRC via regulating HIC1-mediated SIRT1 expression. These results provide a rationale for the development of FBXW11-targeting drugs for CRC patients.


Subject(s)
Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Kruppel-Like Transcription Factors/metabolism , Liver Neoplasms/secondary , Neoplastic Stem Cells/metabolism , Sirtuin 1/genetics , Transcription, Genetic , Ubiquitin-Protein Ligases/metabolism , beta-Transducin Repeat-Containing Proteins/metabolism , Aged , Animals , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Colorectal Neoplasms/pathology , Female , HEK293 Cells , Humans , Male , Mice, Inbred BALB C , Mice, Nude , Neoplastic Stem Cells/pathology , Prognosis , Protein Stability , Sirtuin 1/metabolism , Up-Regulation/genetics , Xenograft Model Antitumor Assays
13.
BMC Public Health ; 21(1): 1940, 2021 10 26.
Article in English | MEDLINE | ID: mdl-34696765

ABSTRACT

BACKGROUND: This study aimed to describe the prevalence of metabolically healthy obesity (MHO) and metabolically unhealthy normal weight (MUNW) rural adults in Xinjiang and to explore their influencing factors. METHODS: We selected 13,525 Uyghur, Kazakh and Han participants in Kashi, Yili and Shihezi areas in Xinjiang from 2009 to 2010. Weight status was classified according to body mass index. Metabolic phenotype was further defined based on the National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: The prevalence of normal weight, overweight, and obesity were 51.6, 30.2, and 14.4%, respectively. The mean age of the population was 45.04 years. The prevalence of MHO was 5.5% overall and was 38.5% among obese participants. The prevalence of MUNW was 15.5% overall and was 30.1% among normal weight participants. A metabolically healthy phenotype among obese individuals was positively associated with females and vegetable consumption ≥4 plates per week. However, this was inversely associated with higher age, red meat consumption ≥2 kg per week, and larger waist circumference (WC). Conversely, a metabolically unhealthy phenotype among normal-weight individuals was positively associated with higher age, red meat consumption ≥2 kg per week, and larger WC; this was however inversely associated with vegetable consumption ≥4 plates per week. CONCLUSIONS: The prevalence of MHO among obese adults in Xinjiang is higher than that of Han adults, while the prevalence of MUNW among normal weight adults is lower than that among Han adults. In obese and normal weight participants, higher age, more red meat consumption, and larger WC increase the risk of metabolic abnormality, and more vegetable consumption reduces the risk of metabolic abnormality.


Subject(s)
Metabolic Syndrome , Obesity, Metabolically Benign , Adult , Body Mass Index , Female , Humans , Middle Aged , Obesity/epidemiology , Phenotype , Prevalence , Risk Factors , Waist Circumference
14.
Bioengineered ; 12(1): 172-182, 2021 12.
Article in English | MEDLINE | ID: mdl-33371790

ABSTRACT

Tumor immunity is closely associated with the prognosis of tumors, including osteosarcoma (OS). The aim of the present study was to construct an immune-related prognostic index (PI) to predict the prognosis of OS. Herein, OS expression data were sourced from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. We divided the OS patients into nonmetastatic and metastatic groups, allowing differentially immune-related genes (DIRGs) to be selected. After DIRGs were further investigated by enrichment analysis, four keys prognostic IRGs (CD79A, CSF3R, MTNR1B and NPPC) were identified using a Cox proportional hazards model. Then, an immune-related prognostic index was constructed. Finally, gene set enrichment analysis (GSEA) was employed to further explore the underlying mechanisms. The difference in tumor-infiltrating immune cell (TIIC) abundance was also discussed. In our study, eight upregulated genes and 30 downregulated genes were identified. Several Gene Ontology (GO) terms and the most significantly enriched KEGG pathways were immune-associated functions and pathways. Four genes, including CD79A, CSF3R, MTNR1B and NPPC, were used to establish a risk assessment model for evaluating OS prognosis. GSEA revealed that the risk score was related to cytokine receptor interaction and to the chemokine and B cell receptor signaling pathways. Furthermore, high risk markedly related to the infiltration of several immune cell types, including M2 macrophages, naïve CD4 T cells, and CD8 T cells. In sum, we developed a survival model for OS. The underlying molecular mechanisms of the high-risk group may affect immune-related biological processes and TIICs.Abbreviations TARGET: Therapeutically Applicable Research To Generate Effective Treatments; PI: Prognostic index; OS: Osteosarcoma; DIRGs: Differentially immune-related genes; GSEA: Gene set enrichment analysis; TIIC: Tumor-infiltrating immune cell.


Subject(s)
Bone Neoplasms , Osteosarcoma , Biomarkers, Tumor/genetics , Biomarkers, Tumor/immunology , Bone Neoplasms/diagnosis , Bone Neoplasms/genetics , Bone Neoplasms/immunology , Bone Neoplasms/mortality , Cytokines/genetics , Cytokines/metabolism , Gene Expression Regulation, Neoplastic/genetics , Gene Expression Regulation, Neoplastic/immunology , Humans , Osteosarcoma/diagnosis , Osteosarcoma/genetics , Osteosarcoma/immunology , Osteosarcoma/mortality , Prognosis , Receptors, Cytokine/genetics , Receptors, Cytokine/metabolism , Transcriptome/genetics , Transcriptome/immunology
15.
BMC Endocr Disord ; 20(1): 110, 2020 Jul 22.
Article in English | MEDLINE | ID: mdl-32698889

ABSTRACT

BACKGROUND: Some studies have shown that a high level of bilirubin is a protective factor against metabolic syndrome (MS), while a high level of transaminase is a risk factor for MS. However, the existing results are inconsistent and few cohort studies have been published. METHODS: Using an ambispective cohort study, 565 Kazakhs from Xinjiang, China were selected as the study subjects. The baseline serum bilirubin and transaminase levels of the subjects were divided into quartiles and the relationship between these values and the incidence of MS was analyzed. The definition of MS was based on the Joint Interim Statement (JIS) diagnostic criteria. RESULTS: The average follow-up time for the subjects was 5.72 years. The cumulative incidence of MS was 36.11% (204 of the 565 subjects), and the incidence density was 63.10/1000 person-years. Multivariate Cox regression analysis showed that the levels of total bilirubin (TBIL) and indirect bilirubin (IBIL) were negatively correlated with the occurrence of MS, Compared to the lowest quartile level (Q1), the hazard ratios of MS the TBIL levels at the Q2-Q4 quartiles were: 0.47 (0.31-0.71), 0.53 (0.35-0.79), and 0.48 (0.32-0.72), respectively, while IBIL levels at the Q2-Q4 quartiles showed an MS hazard ratio of 0.48 (0.32-0.72), 0.54(0.36-0.81), and 0.52 (0.35-0.77), respectively, all at a 95% confidence level. However, no relationship was found between transaminase levels and the incidence of MS. CONCLUSION: Serum TBIL and IBIL levels were negatively correlated with the incidence of MS in a Kazakh population in China.


Subject(s)
Bilirubin/blood , Biomarkers/blood , Metabolic Syndrome/blood , Metabolic Syndrome/epidemiology , Adult , China/epidemiology , Cohort Studies , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Prognosis , Risk Factors
16.
Oxid Med Cell Longev ; 2020: 5136957, 2020.
Article in English | MEDLINE | ID: mdl-32566086

ABSTRACT

The goal of this review was to summarize reported studies focusing on cellular reductive stress-induced mitochondrial dysfunction, cardiomyopathy, dithiothreitol- (DTT-) induced reductive stress, and reductive stress-related free radical reactions published in the past five years. Reductive stress is considered to be a double-edged sword in terms of antioxidation and disease induction. As many underlying mechanisms are still unclear, further investigations are obviously warranted. Nonetheless, reductive stress is thought to be caused by elevated levels of cellular reducing power such as NADH, glutathione, and NADPH; and this area of research has attracted increasing attention lately. Albeit, we think there is a need to conduct further studies in identifying more indicators of the risk assessment and prevention of developing heart damage as well as exploring more targets for cardiomyopathy treatment. Hence, it is expected that further investigation of underlying mechanisms of reductive stress-induced mitochondrial dysfunction will provide novel insights into therapeutic approaches for ameliorating reductive stress-induced cardiomyopathy.


Subject(s)
Cardiomyopathies/pathology , Cardiomyopathies/physiopathology , Mitochondria/pathology , Oxidative Stress , Animals , Humans , Oxidation-Reduction , Reactive Oxygen Species/metabolism , Signal Transduction
17.
ACS Appl Mater Interfaces ; 12(29): 32321-32327, 2020 Jul 22.
Article in English | MEDLINE | ID: mdl-32573192

ABSTRACT

There is an urgent clinical need for multicolor imaging of single cancer cells (no ensemble averaging) for identifying heterogenous expression of predictive biomarkers. Specifically, the comprehensive characterization of single disseminated tumor cells (sDTCs) responsible for metastatic relapse is the key to personalized therapy for patients. Current bioimaging methods lack the necessary multicolor capacity and suffer from background/autofluorescence. Both these central limitations can be overcome by immuno-SERS microscopy using SERS nanotags conjugated to antibodies. Here, we demonstrate the proof of concept for 6-color iSERS microscopy on the same single cancer cell. Human epidermal growth factor receptor 2 (HER2), the most prominent breast cancer marker, is localized on the membrane of single SkBr-3 cells, which overexpress HER2 and are an accepted model for sDTCs in breast cancer. This work paves the way for future multicolor/multitarget imaging for characterizing heterogeneous protein expression at the single-cell level.


Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/pathology , Color , Receptor, ErbB-2/analysis , Single-Cell Analysis , Cell Line, Tumor , Female , Humans , Particle Size , Spectrum Analysis, Raman , Surface Properties
18.
Sci Total Environ ; 722: 137849, 2020 Jun 20.
Article in English | MEDLINE | ID: mdl-32179300

ABSTRACT

Soil nitrogen (N) mineralization is a microbially-mediated biogeochemical process that is strongly influenced by changing climates. However, little information is available on the mechanisms behind the response of N mineralization to prolonged warming coupled with drought in soils covered by biocrusts. We used open top chambers to investigate the rate of soil N transformation (ammonification, nitrification and mineralization), enzyme activity and gene abundance in response to warming coupled with reduced precipitation over three years (2016-2018). Warming and drought significantly reduced the N transformation rate, extracellular enzyme activity, and gene abundance in moss-covered soil. For cyanobacteria-covered soil, however, it inhibited enzyme activity and increased the abundance of the nitrification-related genes and therefore nitrification rate. Our treatments had no obvious effects on N transformation and enzyme activity, but reduced gene abundance in bare soil. Biocrusts may facilitate N transformation while the degradation of moss crust caused by climate warming will dampen any regulating effect of biocrusts on the belowground microbial community. Furthermore, belowground microbial communities can mediate N transformation under ongoing warming and reduced precipitation by suppressing ammonification- and nitrification-related gene families, and by stimulating nitrification-related gene families involved in cyanobacteria-covered soil. This study provides a basis for identifying the functional genes involved in key processes in the N cycle in temperate desert ecosystems, and our results further highlight the importance of different biocrusts organisms in the N cycle in temperate deserts as Earth becomes hotter and drier.


Subject(s)
Soil Microbiology , Soil , Ecosystem , Genes, Microbial , Nitrogen
19.
J Biophotonics ; 13(3): e201960034, 2020 03.
Article in English | MEDLINE | ID: mdl-31605507

ABSTRACT

Programmed cell death-ligand 1 (PD-L1) is an important predictive biomarker. The detection of PD-L1 can be crucial for patients with advanced cancer where the use of immunotherapy is considered. Here, we demonstrate the use of immuno-SERS microscopy (iSERS) for localizing PD-L1 on single cancer SkBr-3 cells. A central advantage of iSERS is that the disturbing autofluorescence from cells and tissues can be efficiently minimized by red to near-infrared laser excitation. In this study we employed Au/Au core/satellite nanoparticles as SERS nanotags because of their remarkable signal brightness and colloidal stability upon red laser excitation. False-color iSERS images of the positive and negative controls clearly reveal the specific localization of PD-L1 with SERS nanotag-labeled antibodies.


Subject(s)
Metal Nanoparticles , Nanoparticles , Neoplasms , B7-H1 Antigen , Gold , Humans , Microscopy , Spectrum Analysis, Raman
20.
Mediators Inflamm ; 2019: 3592620, 2019.
Article in English | MEDLINE | ID: mdl-31686981

ABSTRACT

OBJECTIVE: This study is aimed at evaluating the diagnostic value of blood lipid indicators (BLIs) for insulin resistance (IR) among major ethnic groups in Xinjiang, China, to identify the most valuable indicators and appropriate cut-off points for each ethnic group and to lay the foundation for the early detection, diagnosis, and treatment of metabolic diseases in remote rural areas. METHODS: Overall, 418 Uygurs, 331 Kazakhs, and 220 Hans were randomly included in our study. The homeostasis model assessment was the gold standard for identifying IR. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value, and the nomogram was utilized to analyze the predictive value. The size of the area under the curve (AUC) reflected the accuracy of screening and prediction. RESULTS: Differences in races were observed in terms of IR and BLIs, and the Kazakhs had the highest IR level at 5.27 mmol/L. The correlation between IR and BLIs differed among the three races. For the Kazakhs and Hans, all BLIs, except total cholesterol (TC), were correlated to IR. However, for the Uygurs, only the triglyceride (TG) level, TG/high-density lipoprotein cholesterol (HDL-C) ratio, and TC/HDL-C ratio were associated with IR. After further adjustment of confounding factors, these indicators were still correlated to IR. BLIs that independently correlated to IR in the three nationalities had a certain diagnostic value for IR. In terms of the AUC size, the TG level was the highest in Uygurs, the TG/HDL-C ratio was the highest for Kazakhs and Hans, and the corresponding best cut-off points for IR were 1.515, 1.230, and 1.495 mmol/L, respectively. In addition, for each race, when the indicators with a certain diagnostic value were combined, the diagnostic value for IR was higher. CONCLUSION: BLIs had a certain diagnostic value for IR and could be used as a screening tool for IR among Uygurs, Kazakhs, and Hans in Xinjiang. These findings are extremely important for the prevention and treatment of IR and metabolic diseases in remote rural areas.


Subject(s)
Insulin Resistance/physiology , China , Cholesterol/blood , Ethnicity , Female , Humans , Lipoproteins, HDL/blood , Male , Poverty , ROC Curve , Triglycerides/blood
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