Integrated Bioinformatics Analysis for Revealing CBL is a Potential Diagnosing Biomarker and Related Immune Infiltration in Parkinson's Disease.

Purpose: There is growing evidence that the immune system plays an important role in the progression of Parkinson's disease, the second most common neurodegenerative disorder. This study aims to address the comprehensive understanding of the immunopathogenesis of Parkinson's disease and explore new inflammatory biomarkers. Patients and Methods: In this study, Immune-related differential expressed genes (DEIRGs) were obtained from GEO database and Immport database. The hub gene was screened in DEIRGs using LASSO regression and random forest algorithm, and the mRNA expression of the identified hub gene was validated using clinical blood samples. Results: We obtained a total of 157 DEIRGs that played an important role in the immune response. The results of immune cell infiltration analysis showed that the degree of memory B cells infiltration was higher in PD patients, while the degree of Monocytes, resting mast cells and M0 macrophages infiltration was lower (p<0.05). A total of 8 hub genes were screened by machine learning methods, and RT-PCR results showed that the expression level of CBL gene in PD was significantly increased (p<0.05). Conclusion: Our findings suggest that CBL is a new potential diagnostic biomarker for PD and that abnormal immune cell infiltration may influence PD development.

The spatial patterns and driving mechanisms of blue carbon 'loss' and 'gain' in a typical mangrove ecosystem: A case study of Beihai, Guangxi Province of China.

The role of mangroves in carbon sequestration is critical in mitigating climate change. For better identifying the carbon conservation hotspots of mangroves influenced by environmental factors, the spatial distribution and driving mechanisms of mangrove vegetation and soil carbon sequestration, as well as the future carbon dynamics of mangroves, required clarification. Firstly, we assessed the spatial pattern of vegetation biomass and soil depth-varied soil total organic carbon (TOC) in Xiaoguansha, Guangxi Province of China, and its relationships with duration of inundation (DTI) were explored. Additionally, the carbon storage capacity of adjacent mangrove tidal flats as potential carbon reservoirs was quantified. Thirdly, freshwater, and nutrient inputs, biotic factors of mangrove, and soil composition were selected as impact factors, and their mechanisms in carbon sequestration were elucidated by using Partial least squares path modeling (PLS-PM). Finally, medium values of environmental factors on mangrove carbon sequestration were revealed, based on which future loss and gain patterns of carbon sequestration under the combined effects were fully discussed. The results showed that: (1) The Above-ground biomass (AGB) and TOC densities were 32.89 Mg C/ha and 185.10 Mg C/ha in the study area, and both were enriched in the Interior areas. The carbon sequestration in the tidal flats was equivalented to >1/5 of total carbon sequestration of mangroves. (2) DTI was the most critical factor affecting the carbon sequestration pattern and was found to be positive correlated with AGB and TOC via changing soil contents (SC), whereas it exhibits a negative correlation with AGB and TOC through influencing canopy density (CD). CD and TP were identified as significant predictors. (3) Median analysis indicated that future carbon 'gain' area will move nearshore, whereas the carbon-rich intertidal area may undergo carbon loss. This study provided new insights and scientific understanding for management of mangrove blue carbon function.

Prognostic value of CYFRA 21 - 1 and Ki67 in advanced NSCLC patients with wild-type EGFR.

BACKGROUND: The prognostic value of cytokeratin 19 fragment (CYFRA 21 - 1) and Ki67 in advanced non-small cell lung cancer (NSCLC) patients with wild-type epidermal growth factor receptor (EGFR) remains to be explored. METHODS: In this study, 983 primary NSCLC patients from January 2016 to December 2019 were retrospectively reviewed. Finally, 117 advanced NSCLC patients with wild-type EGFR and 37 patients with EGFR mutation were included and prognostic value of CYFRA 21 - 1 and Ki67 were also identified. RESULTS: The patients age, smoking history and the Eastern Corporative Oncology Group (ECOG) performance scores were significantly different between CYFRA21-1 positive and negative groups (p < 0.05), while no significant differences were found in Ki67 high and low groups. The results of over survival (OS) demonstrated that patients with CYFRA21-1 positive had markedly shorter survival time than CYFRA21-1 negative (p < 0.001, For whole cohorts; p = 0.002, For wild-type EGFR). Besides, patients with wild-type EGFR also had shorter survival times than Ki67 high group. Moreover, In CYFRA 21 - 1 positive group, patients with Ki67 high had obviously shorter survival time compared to patients with Ki67 low (median: 24vs23.5 months; p = 0.048). However, Ki67 could not be used as an adverse risk factor for patients with EGFR mutation. Multivariate cox analysis showed that age (HR, 1.031; 95%CI, 1.003 ~ 1.006; p = 0.028), Histopathology (HR, 1.760; 95%CI,1.152 ~ 2.690; p = 0.009), CYFRA 21 - 1 (HR, 2.304; 95%CI,1.224 ~ 4.335; p = 0.01) and Ki67 (HR, 2.130; 95%CI,1.242 ~ 3.652; p = 0.006) served as independent prognostic risk factor for advanced NSCLC patients. CONCLUSIONS: Our finding indicated that CYFRA 21 - 1 was an independent prognostic factor for advanced NSCLC patients and Ki67 status could be a risk stratification marker for CYFRA 21 - 1 positive NSCLC patients with wild-type EGFR.

Circulating lnc-LOC as a novel noninvasive biomarker in the treatment surveillance of acute promyelocytic leukaemia.

BACKGROUND: Acute promyelocytic leukaemia (APL) is a unique subtype of acute myeloid leukaemia (AML) characterized by haematopoietic failure caused by the accumulation of abnormal promyelocytic cells in bone marrow (BM). However, indispensable BM biopsy frequently afflicts patients in leukaemia surveillance, which increases the burden on patients and reduces compliance. This study aimed to explore whether the novel circulating long noncoding RNA LOC100506453 (lnc-LOC) could be a target in diagnosis, assess the treatment response and supervise the minimal residual disease (MRD) of APL, thereby blazing a trail in noninvasive lncRNA biomarkers of APL. METHODS: Our study comprised 100 patients (40 with APL and 60 with non-APL AML) and 60 healthy donors. BM and peripheral blood (PB) sample collection was accomplished from APL patients at diagnosis and postinduction. Quantitative real-time PCR (qRT-PCR) was conducted to evaluate lnc-LOC expression. A receiver operating characteristic (ROC) analysis was implemented to analyse the value of lnc-LOC in the diagnosis of APL and treatment monitoring. For statistical analysis, the Mann-Whitney U test, a t test, and Spearman's rank correlation test were utilized. RESULTS: Our results showed that BM lnc-LOC expression was significantly different between APL and healthy donors and non-APL AML. lnc-LOC was drastically downregulated in APL patients' BM after undergoing induction therapy. Lnc-LOC was upregulated in APL cell lines and downregulated after all-trans retinoic acid (ATRA)-induced myeloid differentiation, preliminarily verifying that lnc-LOC has the potential to be considered a treatment monitoring biomarker. PB lnc-LOC was positively correlated with BM lnc-LOC in APL patients, non-APL AML patients and healthy donors and decreased sharply after complete remission (CR). However, upregulated lnc-LOC was manifested in relapsed-refractory patients. A positive correlation was revealed between PB lnc-LOC and PML-RARα transcript levels in BM samples. Furthermore, we observed a positive correlation between PB lnc-LOC and BM lnc-LOC expression in APL patients, suggesting that lnc-LOC can be utilized as a noninvasive biomarker for MRD surveillance. CONCLUSIONS: Our study demonstrated that PB lnc-LOC might serve as a novel noninvasive biomarker in the treatment surveillance of APL, and it innovated the investigation and application of newly found lncRNAs in APL noninvasive biomarkers used in diagnosis and detection.

Exploring Prognostic Signatures of Hepatocellular Carcinoma and the Potential Implications in Tumor Immune Microenvironment.

OBJECTIVE: The objective of this study is to construct a prognostic model using genetic markers of liver cancer and explore the signature genes associated with the tumor immune microenvironment. METHODS: Cox proportional hazards regression analysis was carried out to screen the significant HR using the dataset of TCGA Liver Cancer (LIHC) gene expression data. Then LASSO (least absolute shrinkage and selection operator) was performed to select the minimal variables with significant HR of genes. Thus, the prognostic model was constructed by the minimal variables with their HR. Time-dependent receiver-operating characteristic (ROC) curve and area under the ROC curve (AUC) value was used to assess the prognostic performance. Then the patients were divided into high and low-risk groups by the median of the model. Survival analysis was performed on the two groups with testing and an independent dataset. Furthermore, enrichment analysis of signature mRNAs and lncRNAs and their co-expression genes was performed. Then, Spearman rank correlation was used to calculate the correlation between immune cells and genes in the prognostic model, and abundance difference of the immune cells in high and low risks groups was tested. RESULTS: A total of 5989 genes with significant HR were identified. 6 key genes (three mRNAs: DHX37, SMIM7, and MFSD1, three lncRNAs: PIWIL4, KCNE5, and LOC100128398) screened by LASSO were used to construct the model with their HR value respectively. The AUC values of 1 and 5-year overall survival were 0.78 and 0.76 in discovery data and 0.67 and 0.68 in testing data. Survival analysis performed significantly discriminated high and low groups with testing and independent data. Furthermore, many immune cells such as nTreg found a significant correlation with the genes in the prognostic model, and many immune cells showed significantly different abundance in high and low-risk groups. CONCLUSION: In the study, we used Univariate Cox analyses and LASSO algorithm with TCGA gene expression data to construct the prognostic model in liver cancer patients. The prognostic model comprised of three mRNAs, including DHX37, SMIM7, MFSD1, and three lncRNAs, including PIWIL4, KCNE5, and LOC100128398. Furthermore, these gene expression levels were associated with the abundance of some immune cells, such as nTreg. Also, many immune cells have significantly different abundance in high and low-risk groups. All these results indicated that the combination with all these six genes could be the potential biomarker for the prognosis of liver cancer.

Chronic Pediatric Immune Thrombocytopenia Is Not Associated With Herpes Virus Infection Status.

Background: Immune thrombocytopenia (ITP) is characterized by non-chronic (transient, <12 months) and chronic (≥12 months) decline in the number of platelets. Herpes virus infections have been shown, in many studies, to be associated with the development of ITP. However, it remains unclear whether the herpes virus infection status is associated with the chronic ITP. Methods: We reviewed 480 primary pediatric patients with ITP in the period from January 2017 to December 2019. The prevalence of herpes virus antibodies including the Cytomegalovirus (CMV), Herpes simplex virus 1 (HSV-1), Herpes simplex virus 2 (HSV-2), and Epstein Barr virus were recorded. The levels of serum complement C3 and C4, T (CD3+, CD4+, CD8+), B (CD19+) lymphocytes, and natural killer (CD16+ 56+) cells were also analyzed. Multivariate analysis was used to evaluate the associations between chronic ITP and herpes virus infection status. Results: Compared with non-chronic, patients with chronic ITP had older age (≥3 years), lower levels of hemoglobin and complement C3, and lower probability of CMV and HSV-2 infections (IgM positive; p < 0.05). Patients with herpes virus infection had lower serum platelet counts (p < 0.001), lower complement C3 levels and lower CD4+/CD8+ cells ratio (p < 0.05). Furthermore, platelet counts were positively correlated with CD4+/CD8+ cells ratios (r = 0.519; p = 0.0078), and negatively correlated with T cells (CD3+: r = -0.458, p = 0.0213; CD8+: r = -0.489, p = 0.0131). Multivariate analysis showed that age (OR, 1.644; 95%CI, 1.007-2.684; p = 0.047) was an adverse risk factor for chronic ITP and CMV IgM positive (OR, 0.241; 95%CI, 0.072-0.814; p = 0.022) had lower risk of chronic ITP development, while other herpes virus infection statuses and clinical features were not. Conclusion: Although herpes virus infections were associated with the onset of ITP, our findings indicated that herpes virus infection status might not be a risk factor for chronic ITP.

LncRNA HOXA11-AS regulates calcium oxalate crystal-induced renal inflammation via miR-124-3p/MCP-1.

Long noncoding RNA (lncRNA) has been suggested to play an important role in a variety of diseases over the past decade. In a previous study, we identified a novel lncRNA, termed HOXA11-AS, which was significantly up-regulated in calcium oxalate (CaOx) nephrolithiasis. However, the biological function of HOXA11-AS in CaOx nephrolithiasis remains poorly defined. Here, we demonstrated that HOXA11-AS was significantly up-regulated in CaOx nephrolithiasis both in vivo and in vitro. Gain-/loss-of-function studies revealed that HOXA11-AS inhibited proliferation, promoted apoptosis and aggravated cellular damage in HK-2 cells exposed to calcium oxalate monohydrate (COM). Further investigations showed that HOXA11-AS regulated monocyte chemotactic protein 1 (MCP-1) expression in HK-2 cell model of CaOx nephrolithiasis. In addition, online bioinformatics analysis and dual-luciferase reporter assay results showed that miR-124-3p directly bound to HOXA11-AS and the 3'UTR of MCP-1. Furthermore, rescue experiment results revealed that HOXA11-AS functioned as a competing endogenous RNA to regulate MCP-1 expression through sponging miR-124-3p and that overexpression of miR-124-3p restored the inhibitory effect of proliferation, promotion effects of apoptosis and cell damage induced by HOXA11-AS overexpression. Taken together, HOXA11-AS mediated CaOx crystal-induced renal inflammation via the miR-124-3p/MCP-1 axis, and this outcome may provide a good potential therapeutic target for nephrolithiasis.

Decreased miR-124-3p promoted breast cancer proliferation and metastasis by targeting MGAT5.

Non-coding RNAs (ncRNAs) have been shown to regulate gene expression involved in tumor progression of multiple malignancies. Numerous studies have indicated that N-acetylglucosaminyltransferase V (MGAT5), is an important tumorigenesis and metastasis-associated enzyme in breast cancer (BC). But, the underlying molecular mechanisms by which ncRNAs modulate MGAT5 expression in BC remain undetermined. In this study, we demonstrated that miR-124 expression at a low level in BC tissue was associated with poor prognosis of BC patients. Meanwhile, miR-124 reduced BC cell proliferation and metastasis. MGAT5 was confirmed as a direct target of miR-124. MGAT5 restoration attenuated the inhibitory effects of miR-124 on BC proliferation and metastasis in vitro and vivo. Overall, we provide new insight into the mechanisms by which miR-124 inhibits BC progression, suggesting the potential of miR-124 and MGAT5 as biomarkers for early diagnosis of breast cancer to provide innovative ideas and methods for the diagnosis and treatment of BC.