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1.
J Alzheimers Dis ; 97(3): 1381-1392, 2024.
Article in English | MEDLINE | ID: mdl-38250768

ABSTRACT

BACKGROUND: Mitochondrial dysfunction plays a vital role in the progression of vascular dementia (VaD). We hypothesized that transfer of exogenous mitochondria might be a beneficial strategy for VaD treatment. OBJECTIVE: The study was aimed to investigate the role of mitochondrial therapy in cognitive function of VaD. METHODS: The activity and integrity of isolated mitochondria were detected using MitoTracker and Janus Green B staining assays. After VaD mice were intravenously injected with exogenous mitochondria, Morris water maze and passive avoidance tests were used to detect cognitive function of VaD mice. Haematoxylin and eosin, Nissl, TUNEL, and Golgi staining assays were utilized to measure neuronal and synaptic injury in the hippocampus of VaD mice. Detection kits were performed to detect mitochondrial membrane potential (ΔΨ), SOD activity and the levels of ATP, ROS, and MDA in the brains of VaD mice. RESULTS: The results showed that isolated mitochondria were intact and active. Mitochondrial therapy could ameliorate cognitive performance of VaD mice. Additionally, mitochondrial administration could attenuate hippocampal neuronal and synaptic injury, improve mitochondrial ΔΨ, ATP level and SOD activity, and reduce ROS and MDA levels in the brains of VaD mice. CONCLUSIONS: The study reports profitable effect of mitochondrial therapy against cognitive impairment of VaD, making mitochondrial treatment become a promising therapeutic strategy for VaD.


Subject(s)
Cognitive Dysfunction , Dementia, Vascular , Mice , Animals , Dementia, Vascular/metabolism , Reactive Oxygen Species/metabolism , Cognition , Cognitive Dysfunction/metabolism , Superoxide Dismutase/metabolism , Mitochondria , Adenosine Triphosphate/metabolism , Maze Learning/physiology , Hippocampus/metabolism
2.
Mol Neurobiol ; 2023 Dec 13.
Article in English | MEDLINE | ID: mdl-38087171

ABSTRACT

Enhancement of oxidative stress and resultant neuronal injury play important roles in initiating cognitive impairment during the aging process. Thus, attenuating oxidative injury is regarded as a profitable therapeutic strategy for age-associated cognitive impairment. Previous studies showed that gliclazide (Gli) had a protective role in neuronal injury from cerebral ischemia/reperfusion (I/R) injury. However, whether Gli has a profitable effect on age-associated cognitive impairment remains largely unclear. The present study showed that Gli held the potential to attenuate neuronal apoptosis in D-gal-induced senescent cells and aging mice. Additionally, Gli could alleviate synaptic injury and cognitive function in D-gal-induced aging mice. Further study showed that Gli could attenuate oxidative stress in D-gal-induced senescent cells and aging mice. The p38 MAPK pathway was predicted as the downstream target of Gli retarding oxidative stress using in silico analysis. Further studies revealed that Gli attenuated D-gal-induced phosphorylation of p38 and facilitated Nrf2 nuclear expression, indicating that the anti-oxidative property of Gli may be associated with the p38 MAPK pathway. The study demonstrates that Gli has a beneficial effect on ameliorating D-gal-induced neuronal injury and cognitive impairment, making this compound a promising agent for the prevention and treatment of age-associated cognitive impairment.

3.
J Cancer Res Clin Oncol ; 149(13): 11295-11308, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37368120

ABSTRACT

PURPOSE: AFP appears to be negative in about 30% of overall hepatocellular carcinoma (HCC). Our study aimed to develop a nomogram model to diagnose AFP-negative HCC (AFPN-HCC). PATIENTS AND METHODS: The training set included 294 AFPN-HCC patients, 159 healthy objects, 63 patients with chronic hepatitis B(CHB), and 64 patients with liver cirrhosis (LC). And the validation set enrolled 137 healthy controls objects, 47 CHB patients and 45 patients with LC. LASSO, univariate, and multivariable logistic regression analysis were performed to construct the model and then transformed into a visualized nomogram. The receiver operating characteristic (ROC) curves, the calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were further used for validation. RESULTS: Four variables including age, PIVKA-II, platelet (PLT) counts, and prothrombin time (PT) were selected to establish the nomogram. The area under the curve (AUC) of the ROC to distinguish AFPN-HCC patients was 0.937(95% CI 0.892-0.938) in training set and 0.942(95% CI 0.921-0.963) in validation set. We also found that the model had high diagnostic value for small-size HCC (tumor size < 5 cm) (AUC = 0.886) and HBV surface antigen-positive AFPN-HCC (AUC = 0.883). CONCLUSIONS: Our model was effective for discrimination of AFPN-HCC from patients with benign liver diseases and healthy controls, and might be helpful for the diagnosis for AFPN-HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnosis , alpha-Fetoproteins , Liver Neoplasms/diagnosis , Liver Neoplasms/pathology , Biomarkers , Liver Cirrhosis/diagnosis , ROC Curve , Biomarkers, Tumor
4.
ACS Appl Mater Interfaces ; 15(20): 24377-24386, 2023 May 24.
Article in English | MEDLINE | ID: mdl-37183402

ABSTRACT

Silicon monoxide (SiO) has attracted growing attention as one of the most promising anodes for high-energy-density lithium-ion batteries (LIBs), benefiting from relatively low volume expansion and superior cycling performance compared to bare silicon (Si). However, the size of the SiO particle for commercial application remains uncertain. Besides, the materials and concepts developed on the laboratory level in half cells are quite different from what is necessary for practical operation in full cells. Herein, we investigate the electrochemical performance of SiO with different particle sizes between half cells and full cells. The SiO with larger particle size exhibits worse electrochemical performance in the half cell, whereas it demonstrates excellent cycling stability with a high capacity retention of 91.3% after 400 cycles in the full cell. The reasons for the differences in their electrochemical performance between half cells and full cells are further explored in detail. The SiO with larger particle size possessing superior electrochemical performance in full cells benefits from consuming less electrolyte and not being easier to aggregate. It indicates that the SiO with larger particle size is recommended for commercial application and part of the information provided from half cells may not be advocated to predict the cycling performances of the anode materials. The analysis based on the electrochemical performance of the SiO between half cells and full cells gives fundamental insight into further Si-based anode research.

5.
J Pathol ; 259(1): 1-9, 2023 01.
Article in English | MEDLINE | ID: mdl-36264226

ABSTRACT

Brain aging is closely related to neurodegenerative diseases. Circular RNAs (circRNAs) are a type of conserved RNAs with covalently closed continuous loops. Emerging evidence has shown that circRNAs are implicated in the biology of brain aging and the pathology of age-related neurodegenerative diseases. Here, we summarize current studies on circRNAs associated with brain aging and neurodegenerative diseases by discussing their expression features, pathophysiological roles, and mechanisms of action. We also discuss the potential challenges of circRNA-based therapy against brain aging and neurodegenerative diseases, as well as their potential as diagnostic biomarkers of neurodegenerative diseases. The review provides insights into current progress in the functions of circRNAs in the process of brain aging and neurodegenerative diseases. © 2022 The Pathological Society of Great Britain and Ireland.


Subject(s)
Neurodegenerative Diseases , RNA, Circular , Humans , RNA, Circular/genetics , Neurodegenerative Diseases/genetics , RNA/genetics , Aging/genetics , Brain
6.
J Gastrointest Surg ; 27(1): 56-66, 2023 01.
Article in English | MEDLINE | ID: mdl-36127552

ABSTRACT

PURPOSE: To explore the expression and role of ATPase cation transporting 13A2 (ATP13A2) on hepatocellular carcinoma (HCC) progression and prognosis. METHODS: The level of ATP13A2 in 63 HCC tissues was evaluated by quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry. Then, the prognostic value of ATP13A2 for HCC was explored. GO and KEGG pathway enrichments were performed to predict ATP13A2-mediated biological functions. Besides, the correlations between ATP13A2 and key regulators involved in cell cycle and metastasis, the status of different tumor-infiltrating immune cells was investigated. RESULTS: ATP13A2 was frequently upregulated in 63 HCC tissues relatively to matched non-tumor tissues. The level of ATP13A2 significantly correlated with tumor stage and tumor grade. HCC patients with higher levels of ATP13A2 had a worse prognosis. Moreover, multivariate survival analysis supported ATP13A2 to be an independent prognostic factor for HCC. GO and KEGG analysis indicated a potential role of ATP13A2 on regulating cell cycle, metastasis, and immune infiltrates. Especially, the level of ATP13A2 was positively correlated with CCNB1, CCND3, CDC25B, CDK4, Vimentin, MMP9, MMP14, and LMNB2. A positive correlation was noticed between ATP13A2 and infiltration levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, dendritic cells, monocytes, M2 macrophages, and exhausted T cells in HCC. CONCLUSION: Upregulation of ATP13A2 is a common feature as well as an independent prognostic biomarker for HCC. ATP13A2 are associated with key regulators involved in cell cycle, metastasis, and immune infiltrates in HCC, and may act as a potential immunotherapy target for HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , CD8-Positive T-Lymphocytes , Prognosis , Biomarkers , Biomarkers, Tumor , Proton-Translocating ATPases
7.
Microbiol Spectr ; 10(6): e0155722, 2022 12 21.
Article in English | MEDLINE | ID: mdl-36314949

ABSTRACT

Increasing evidence indicates that interferon alpha (IFN-α) therapy is an effective treatment option for a subgroup of patients with chronic hepatitis B virus (HBV) infection. It has been confirmed that interferon-induced protein with tetratricopeptide repeats 3 (IFIT3), a member of the interferon-stimulated genes (ISGs), could inhibit the replication of various viruses. However, its effect on HBV replication is unclear. The present study sought to explore the role and mechanism of IFIT3 in IFN-α antiviral activities against HBV. IFIT3 mRNA levels in the peripheral blood of 108 treatment-naive patients and 70 healthy controls were analyzed first. The effect of IFIT3 on the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway under the dual intervention of IFN-α and HBV was also explored in vitro. Treatment-naive individuals exhibited elevated levels of IFIT3 mRNA compared to the controls (P < 0.0001). Mechanistically, the knockdown of IFIT3 inhibited the phosphorylation of signal transducer and activator of transcription 2 (STAT2), whereas the overexpression of IFIT3 produced the opposite effect in vitro. Meanwhile, the overexpression of IFIT3 enhanced the expression of IFN-α-triggered ISGs, including myxovirus resistance A (MxA), 2'-5'-oligoadenylate synthetase 1 (OAS1), and double-stranded RNA-activated protein kinase (PKR), while a weaker induction of IFN-α-triggered ISGs was observed in ruxolitinib-treated cells. After decreasing IFIT3 expression by validated small hairpin RNAs (shRNAs), the levels of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV DNA secreted by HepG2 cells transiently transfected with the pHBV1.2 plasmid were increased. Our findings suggest that IFIT3 works in a STAT2-dependent manner to promote the antiviral effect of IFN-α through the JAK-STAT pathway in HBV infection in both human hepatocytes and hepatocarcinoma cells. IMPORTANCE Our study contributes new insights into the understanding of the functions and roles of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3), which is one of the interferon-stimulated genes induced by hepatitis B virus infection in human hepatocytes and hepatocarcinoma cells, and may help to identify targeted genes promoting the efficacy of interferon alpha.


Subject(s)
Hepatitis B, Chronic , Hepatitis B , Humans , Interferon-alpha/metabolism , Interferon-alpha/pharmacology , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Janus Kinases/metabolism , Janus Kinases/pharmacology , STAT2 Transcription Factor/metabolism , Signal Transduction , STAT Transcription Factors/metabolism , STAT Transcription Factors/pharmacology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Hepatitis B Surface Antigens , RNA, Messenger , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/pharmacology
8.
Emerg Microbes Infect ; 11(1): 2486-2501, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36102940

ABSTRACT

Hepatitis B virus (HBV) exists as quasispecies (QS). However, the evolutionary characteristics of haplotypes of HBV X gene in the hepatocellular carcinoma (HCC) microenvironment remain unclear. Mutations across X gene are essential for the tumorigenicity of HBV X protein (HBx). However, the functional phenotypes of many mutant HBx remain unknown. This study aims to compare the characteristics of X gene evolution between tumour and non-tumour tissues in HCC patients and investigate the tumorigenic phenotype of HBx harbouring mutation T81P/S101P/L123S. This study included 24 HCC patients. Molecular cloning of X gene was performed to analyse characteristics of haplotypes in liver tissues. HCC cell lines stably expressing wild-type or mutant HBx and subcutaneous tumour xenograft mouse model were used to assess HBx-T81P/S101P/L123S tumorigenicity. The mean heterogeneity of HBV QS across X gene in tumour tissues was lower than that in non-tumour tissues. A location bias was observed in X gene clones with genotype C or D in tumour tissues compared to those with genotype B. Mutations in genotype-C or - D clones were mainly clustered in the dimerization region and aa110-aa140 within the transactivation region. A novel mutation combination at residues 81, 101 and 123 was identified in tumour tissues. Further, HBx-T81P/S101P/L123S promotes cell proliferation and increases genomic instability, which was mediated by MYC. This study elucidates the compartmentalized evolution patterns of HBV X gene between intra tumour and non-tumour tissues in HCC patients and provides a new mechanism underlying HBV-driven hepatocarcinogenesis, suggesting a potential viral marker for monitoring HCC.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis B , Liver Neoplasms , Humans , Mice , Animals , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Hepatitis B virus/genetics , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Genetic Association Studies , Tumor Microenvironment
10.
Iran J Kidney Dis ; 16(4): 215-227, 2022 07.
Article in English | MEDLINE | ID: mdl-35962636

ABSTRACT

Chronic kidney disease is a public health problem. The purpose of this study was to compare the effects of sevelamer and calciumbased binders on mortality of hemodialysis patients. PubMed, EMBASE and Web of Science were searched for related articles published before May 14, 2020. We included six studies with 43330 participants, of which 21147 and 22183 received calciumbased phosphate binders and sevelamer, respectively. In the analysis of unadjusted data, sevelamer could lower cardiovascular mortality. When adjusted HRs was pooled, the cardiovascular mortality did not differ significantly in the sevelamer and calcium-based phosphate binders groups. Additionally, the all-cause mortality rate in sevelamer group was different from that in calcium-based phosphate binders group. However, sevelamer could not lower all-cause mortality in terms of the adjusted data. No significant difference was found in calcium and phosphorus between calcium-based phosphate binders and sevalmer. Sensitivity analysis showed that partial results of the study were inconsistent. There was no difference in the effect of sevelamer and calciumbased phosphate binders on the risk of all-cause mortality in patients with hemodialysis, after adjusting confounders. However, given the instability of the results, the results need to be further confirmed by a large sample and high quality RCTs.  DOI: 10.52547/ijkd.6814.


Subject(s)
Calcium , Cardiovascular Diseases , Calcium, Dietary , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Chelating Agents/adverse effects , Humans , Phosphates , Renal Dialysis/adverse effects , Sevelamer/therapeutic use
11.
Front Microbiol ; 13: 862130, 2022.
Article in English | MEDLINE | ID: mdl-35479612

ABSTRACT

The application of biosynthesized nano-selenium fertilizers to crops can improve their nutrient levels by increasing their selenium content. However, microorganisms with a high selenite tolerance and rapid reduction rate accompanied with the production of selenium nanoparticles (SeNPs) at the same time have seldom been reported. In this study, a bacterial strain showing high selenite resistance (up to 300 mM) was isolated from a lateritic red soil and identified as Proteus mirabilis QZB-2. This strain reduced nearly 100% of 1.0 and 2.0 mM selenite within 12 and 18 h, respectively, to produce SeNPs. QZB-2 isolate reduced SeO3 2 - to Se0 in the cell membrane with NADPH or NADH as electron donors. Se0 was then released outside of the cell, where it formed spherical SeNPs with an average hydrodynamic diameter of 152.0 ± 10.2 nm. P. mirabilis QZB-2 could be used for SeNPs synthesis owing to its simultaneously high SeO3 2 - tolerance and rapid reduction rate.

12.
Thromb Res ; 213: 34-42, 2022 05.
Article in English | MEDLINE | ID: mdl-35279504

ABSTRACT

BACKGROUND: Totally implantable venous access ports (PORTs) and peripherally inserted central catheters (PICCs) are associated with an increased risk of venous thromboembolism (VTE). It is not known which type of catheter is most at risk of thrombosis. OBJECTIVE: We aimed to study the incidence of PORT-related VTE and PICC-related VTE in cancer patients by a meta-analysis. METHODS: A systematic search was performed using PubMed, Embase, Web of Science and the Cochrane Library. Cohort studies and randomized controlled trials (RCTs) comparing PORT-related VTE and PICC-related VTE in cancer patients were included. Quality was assessed using the Cochrane Collaboration tool for RCTs and the Newcastle-Ottawa Scale (NOS) for cohort studies. Random-effects meta-analysis was used to calculate odd ratio (OR). Sensitivity and subgroup analyses were conducted. RESULTS: In total, 22 studies comprising 11,940 patients were retrieved. Our meta-analysis of 22 studies suggested that the risk of PORT-related VTE was lower than that of PICC-related VTE in cancer patients (OR = 0.38, 95% CI: 0.25-0.58). The subgroup analysis showed that the risk of PORT-related VTE and PICC-related VTE is different in different regions. In the non-Asian countries, PORTs were associated with a decreased risk of VTE compared with PICCs. (OR = 0.41, 95%CI: 0.27-0.61). However, there was no significant difference in the risk of PORT-related VTE and PICC-related VTE in the Asian countries (OR = 0.23, 95% CI: 0.05-1.12). CONCLUSIONS: PORTs are associated with a lower risk of VTE than PICCs in cancer patients. The risk of VTE and benefits should be considered when selecting PORTs or PICCs for cancer patients.


Subject(s)
Catheterization, Central Venous , Catheterization, Peripheral , Central Venous Catheters , Neoplasms , Venous Thromboembolism , Catheterization, Central Venous/adverse effects , Catheterization, Peripheral/adverse effects , Central Venous Catheters/adverse effects , Humans , Neoplasms/complications , Randomized Controlled Trials as Topic , Risk Factors , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology
14.
Aging Cell ; 20(9): e13451, 2021 09.
Article in English | MEDLINE | ID: mdl-34363729

ABSTRACT

Age-related cognitive decline in neurodegenerative diseases, such as Alzheimer's disease (AD), is associated with the deficits of synaptic plasticity. Therefore, exploring promising targets to enhance synaptic plasticity in neurodegenerative disorders is crucial. It has been demonstrated that methyl-CpG binding protein 2 (MeCP2) plays a vital role in neuronal development and MeCP2 malfunction causes various neurodevelopmental disorders. However, the role of MeCP2 in neurodegenerative diseases has been less reported. In the study, we found that MeCP2 expression in the hippocampus was reduced in the hippocampus of senescence-accelerated mice P8 (SAMP8) mice. Overexpression of hippocampal MeCP2 could elevate synaptic plasticity and cognitive function in SAMP8 mice, while knockdown of MeCP2 impaired synaptic plasticity and cognitive function in senescence accelerated-resistant 1 (SAMR1) mice. MeCP2-mediated regulation of synaptic plasticity may be associated with CREB1 pathway. These results suggest that MeCP2 plays a vital role in age-related cognitive decline by regulating synaptic plasticity and indicate that MeCP2 may be promising targets for the treatment of age-related cognitive decline in neurodegenerative diseases.


Subject(s)
Cognitive Dysfunction/metabolism , Disease Models, Animal , Methyl-CpG-Binding Protein 2/metabolism , Age Factors , Animals , Cellular Senescence , Cognition , Cognitive Dysfunction/genetics , Cognitive Dysfunction/pathology , Hippocampus/metabolism , Hippocampus/pathology , Methyl-CpG-Binding Protein 2/genetics , Mice , Neuronal Plasticity
15.
Int J Biol Sci ; 17(10): 2380-2398, 2021.
Article in English | MEDLINE | ID: mdl-34326682

ABSTRACT

Tamoxifen (TAM) resistance has indicated a significant challenge during endocrine therapy for hormone-sensitive breast cancer. Thus, it is significant to elucidate the molecular events endowing TAM resistance to endocrine therapy. In this study, we found that epithelial-mesenchymal transition (EMT) was an important event to confer TAM resistance, and attenuating EMT by elevating connexin (Cx) 43 expression could reverse TAM resistance. Specifically, Cx43 overexpression improved TAM sensitivity, while Cx43 depletion facilitated TAM insensitivity by modulating EMT in T47D TAM-resistant and -sensitive cells, and transplanted xenografts. Importantly, we found a novel reciprocal regulation between Cx43 and c-Src/PI3K/Akt pathway contributing to EMT and TAM resistance in breast cancer. Moreover, we identified that Cx43 deficiency was significantly correlated with poor relapse-free survival in patients undergoing TAM treatment. Therefore, Cx43 represents a prognostic marker and an attractive target for breast cancer treatments. Therapeutic strategies designed to increase or maintain Cx43 function may be beneficial to overcome TAM resistance.


Subject(s)
Breast Neoplasms/drug therapy , Connexin 43/metabolism , Epithelial-Mesenchymal Transition/genetics , Signal Transduction/drug effects , Tamoxifen/pharmacology , Animals , Antineoplastic Agents, Hormonal/pharmacology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Class I Phosphatidylinositol 3-Kinases/genetics , Class I Phosphatidylinositol 3-Kinases/metabolism , Connexin 43/genetics , Drug Resistance, Neoplasm/drug effects , Female , Humans , MCF-7 Cells , Mice, Inbred BALB C , Mice, Nude , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Survival Analysis , Xenograft Model Antitumor Assays , src-Family Kinases/genetics , src-Family Kinases/metabolism
16.
Cell Mol Immunol ; 18(2): 461-471, 2021 02.
Article in English | MEDLINE | ID: mdl-33432062

ABSTRACT

Pegylated interferon-alpha (PegIFNα) therapy has limited effectiveness in hepatitis B e-antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. However, the mechanism underlying this failure is poorly understood. We aimed to investigate the influence of bile acids (BAs), especially taurocholic acid (TCA), on the response to PegIFNα therapy in CHB patients. Here, we used mass spectrometry to determine serum BA profiles in 110 patients with chronic HBV infection and 20 healthy controls (HCs). We found that serum BAs, especially TCA, were significantly elevated in HBeAg-positive CHB patients compared with those in HCs and patients in other phases of chronic HBV infection. Moreover, serum BAs, particularly TCA, inhibited the response to PegIFNα therapy in HBeAg-positive CHB patients. Mechanistically, the expression levels of IFN-γ, TNF-α, granzyme B, and perforin were measured using flow cytometry to assess the effector functions of immune cells in patients with low or high BA levels. We found that BAs reduced the number and proportion and impaired the effector functions of CD3+CD8+ T cells and natural killer (NK) cells in HBeAg-positive CHB patients. TCA in particular reduced the frequency and impaired the effector functions of CD3+CD8+ T and NK cells in vitro and in vivo and inhibited the immunoregulatory activity of IFN-α in vitro. Thus, our results show that BAs, especially TCA, inhibit the response to PegIFNα therapy by impairing the effector functions of CD3+CD8+ T and NK cells in HBeAg-positive CHB patients. Our findings suggest that targeting TCA could be a promising approach for restoring IFN-α responsiveness during CHB treatment.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Hepatitis B e Antigens/metabolism , Hepatitis B virus/immunology , Hepatitis B, Chronic/immunology , Interferon-alpha/pharmacology , Killer Cells, Natural/immunology , Taurocholic Acid/pharmacology , Animals , Antiviral Agents/pharmacology , CD8-Positive T-Lymphocytes/drug effects , Case-Control Studies , Cholagogues and Choleretics/pharmacology , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/metabolism , Hepatitis B, Chronic/virology , Humans , Killer Cells, Natural/drug effects , Mice , Mice, Inbred C57BL
17.
Dis Markers ; 2020: 5417598, 2020.
Article in English | MEDLINE | ID: mdl-32733618

ABSTRACT

BACKGROUND: Circulating long noncoding RNAs (lncRNAs) have been demonstrated to serve as diagnostic biomarkers for various cancers. We aimed to elucidate the diagnostic efficacy of eight serum lncRNAs HULC, MALAT1, Linc00152, PTENP1, PTTG3P, SPRY4-IT1, UBE2CP3, and UCA1 and their combinations for the diagnosis of hepatocellular carcinoma (HCC). METHODS: A total of 129 patients with HCC, 49 patients with liver cirrhosis, 27 patients with chronic hepatitis B, and 93 healthy controls were enrolled in this study. The levels of serum lncRNAs were assessed by quantitative real-time polymerase chain reaction. The correlations between serum lncRNAs and clinicopathological characteristics were further analyzed. The receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to estimate the diagnostic capacity of serum lncRNAs and their combination with AFP for HCC. A logistic regression model was performed to establish a multiple-lncRNA panel. RESULTS: The levels of serum HULC, MALAT1, Linc00152, PTTG3P, SPRY4-IT1, UBE2CP3, and UCA1 were significantly higher in HCC patients than in patients with benign liver diseases and healthy controls, whereas serum PTENP1 was significantly decreased in HCC patients compared with healthy participants. Positive correlations between serum Linc00152 and GGT, serum PTTG3P and GGT, and serum SPRY4-IT1 and ALT were noted in HCC patients. ROC analysis revealed that all these lncRNAs had a significantly predictive value for HCC except for PTENP1. The best performance of single lncRNA was obtained by Linc00152 with an AUC of 0.877. When combined with AFP, the combination of Linc00152 and AFP gained the highest accuracy, yielding an AUC of 0.906. Through logistic regression analysis, the panel consisting of serum linc00152, UCA1, and AFP provided the greatest predictive ability, obtaining an AUC of 0.912 with 82.9% sensitivity and 88.2% specificity. CONCLUSION: The panel of serum Linc00152, UCA1, and AFP demonstrates a novel and noninvasive biomarker with relatively high sensitivity and specificity for HCC diagnosis.


Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/diagnosis , RNA, Long Noncoding/blood , alpha-Fetoproteins/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/genetics , Case-Control Studies , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/blood , Liver Neoplasms/genetics , Logistic Models , Male , Middle Aged , ROC Curve , Sensitivity and Specificity , Young Adult
18.
Ageing Res Rev ; 60: 101058, 2020 07.
Article in English | MEDLINE | ID: mdl-32234545

ABSTRACT

Although efforts have been made to develop therapeutic approaches, the clinical management of AD maintains a major challenge. CircRNAs are highly abundant and evolutionarily conserved in neuronal tissues in mammals. Accumulating data suggest that circRNAs regulate biological and pathological processes by sponging miRNAs, binding to RBPs, modulating mRNA stability, and being translated into peptides in various diseases, serving as biomarkers and potential therapeutic targets. Growing evidence demonstrates that circRNAs have been implicated in the pathogenesis of AD. Here, we summarized current studies on circRNAs involved in AD pathology, providing a theoretical basis for the use of circRNAs in AD treatment and diagnosis.


Subject(s)
Alzheimer Disease , MicroRNAs , RNA, Circular , Alzheimer Disease/genetics , Animals , Biomarkers , Humans , MicroRNAs/genetics
19.
Clin Chim Acta ; 502: 120-127, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31891671

ABSTRACT

BACKGROUND AND AIM: Recently, the role of albumin-bilirubin (ALBI) score in chronic hepatitis B (CHB) has not been well-understood. We aimed to investigate the association of ALBI score with natural history of chronic HBV infection and treatment response of CHB patients. METHODS: The ALBI score in a cohort of 849 individuals including 721 chronic HBV-infected patients naïve to anti-HBV treatment in different phases and 128 healthy controls were estimated. Additionally, the dynamic changes of ALBI score of 243 hepatitis B e antigen (HBeAg)-positive CHB patients treated with pegylated interferon-alpha (PEG-IFN-α) or nucleos(t)ide analogues (NAs) were tested for 72 weeks. RESULTS: ALBI score differed among phases, with the highest score in HBeAg-positive CHB patients, followed by HBeAg-negative CHB patients, HBeAg-positive chronic HBV infection, and HBeAg-negative chronic HBV infection. Besides, CHB patients harbouring high baseline ALBI score exhibited a relatively stronger therapeutic response to PEG-IFN-α or NAs. Moreover, the rate of HBeAg and HBsAg loss in patients with ALBI grade 2 was persistently higher than that in patients with ALBI grade 1 throughout the course of treatment. Furthermore, ALBI score was an independent predictor of sustained response achievement. The combined use of ALBI score, HBeAg and ALT could enhance the predictive value of treatment response. CONCLUSIONS: ALBI score differed significantly across the natural course of chronic HBV infection and was correlated with PEG-IFN-α and NAs treatment response in HBeAg-positive CHB patients, which suggested that ALBI score could be useful as an auxiliary clinical factor to determine the initiation of therapy and predict stronger antiviral treatment response.


Subject(s)
Albumins/analysis , Antiviral Agents/therapeutic use , Bilirubin/analysis , Hepatitis B, Chronic/diagnosis , Interferon-alpha/therapeutic use , Nucleosides/therapeutic use , Adult , Cohort Studies , Female , Hepatitis B e Antigens/analysis , Hepatitis B, Chronic/drug therapy , Humans , Liver Function Tests , Male , Nucleosides/analogs & derivatives
20.
Ann Vasc Surg ; 63: 457.e1-457.e5, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31622761

ABSTRACT

Cavernous hemangioma, a benign soft tissue and intramuscular tumor, is commonly located in the head, neck, and maxillofacial regions. They can sometimes occur in the limbs and trunk, although rarely. Treatment of cavernous hemangiomas includes surgical and nonsurgical means. Cases of extensive diffused cavernous hemangiomas of an entire limb are rare. In this case presentation, we report the case of chronic diffused cavernous hemangioma associated with venous calculi of the right upper limb and back in a 31-year-old Chinese man. Due to the long history, chronic articular impairments and extensive damage to the skeletal and musculature, surgical amputation of the limb was performed. The aim of this report is to provide further understanding of treatment prioritization and the risks of delayed treatment of cavernous hemangiomas.


Subject(s)
Back/blood supply , Calculi/etiology , Hemangioma, Cavernous/complications , Upper Extremity/blood supply , Vascular Calcification/etiology , Veins , Adult , Amputation, Surgical , Back/surgery , Calculi/diagnostic imaging , Calculi/surgery , Hemangioma, Cavernous/diagnostic imaging , Hemangioma, Cavernous/surgery , Humans , Male , Time Factors , Time-to-Treatment , Treatment Outcome , Upper Extremity/surgery , Vascular Calcification/diagnostic imaging , Vascular Calcification/surgery , Veins/diagnostic imaging , Veins/surgery
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