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1.
Int J Mol Sci ; 25(9)2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38731972

ABSTRACT

Vaccination is a public health cornerstone that protects against numerous infectious diseases. Despite its benefits, immunization implications on ocular health warrant thorough investigation, particularly in the context of vaccine-induced ocular inflammation. This review aimed to elucidate the complex interplay between vaccination and the eye, focusing on the molecular and immunological pathways implicated in vaccine-associated ocular adverse effects. Through an in-depth analysis of recent advancements and the existing literature, we explored various mechanisms of vaccine-induced ocular inflammation, such as direct infection by live attenuated vaccines, immune complex formation, adjuvant-induced autoimmunity, molecular mimicry, hypersensitivity reactions, PEG-induced allergic reactions, Type 1 IFN activation, free extracellular RNA, and specific components. We further examined the specific ocular conditions associated with vaccination, such as uveitis, optic neuritis, and retinitis, and discussed the potential impact of novel vaccines, including those against SARS-CoV-2. This review sheds light on the intricate relationships between vaccination, the immune system, and ocular tissues, offering insights into informed discussions and future research directions aimed at optimizing vaccine safety and ophthalmological care. Our analysis underscores the importance of vigilance and further research to understand and mitigate the ocular side effects of vaccines, thereby ensuring the continued success of vaccination programs, while preserving ocular health.


Subject(s)
Vaccination , Humans , Vaccination/adverse effects , Vaccination/methods , COVID-19 Vaccines/immunology , COVID-19 Vaccines/adverse effects , Eye/immunology , SARS-CoV-2/immunology , COVID-19/prevention & control , COVID-19/immunology , Vaccines/adverse effects , Vaccines/immunology , Animals , Eye Diseases/immunology , Eye Diseases/prevention & control
2.
Int J Mol Sci ; 25(6)2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38542203

ABSTRACT

Human T-cell leukemia virus type 1 (HTLV-1), a virus that affects 5-10 million people globally, causes several diseases, including adult T-cell leukemia-lymphoma and HTLV-1-associated uveitis (HU). HU is prevalent in Japan and often leads to secondary glaucoma, which is a serious complication. We investigated the efficacy of ripasudil, a Rho-associated coiled coil-forming protein kinase inhibitor, in alleviating changes in human trabecular meshwork cells (hTM cells) infected with HTLV-1. HTLV-1-infected hTM cells were modeled in vitro using MT-2 cells, followed by treatment with varying concentrations of ripasudil. We assessed changes in cell morphology, viability, and inflammatory cytokine levels, as well as NF-κB activation. The results showed that ripasudil treatment changed the cell morphology, reduced the distribution of F-actin and fibronectin, and decreased the levels of certain inflammatory cytokines, such as interleukin (IL)-6, IL-8, and IL-12. However, ripasudil did not significantly affect NF-κB activation or overall cell viability. These findings suggest that ripasudil has the potential to treat secondary glaucoma in patients with HU by modulating cytoskeletal organization and alleviating inflammation in HTLV-1-infected hTM cells. This study lays the foundation for further clinical studies exploring the effectiveness of ripasudil for the treatment of secondary glaucoma associated with HU.


Subject(s)
Glaucoma , Human T-lymphotropic virus 1 , Isoquinolines , Sulfonamides , Uveitis , Adult , Humans , NF-kappa B , Glaucoma/drug therapy , Glaucoma/etiology , Cytokines/therapeutic use , Interleukin-6 , rho-Associated Kinases
3.
Pathogens ; 12(12)2023 Dec 04.
Article in English | MEDLINE | ID: mdl-38133300

ABSTRACT

Since the introduction of combination antiretroviral therapy (cART) in Japan in 2008, the spectrum of ocular manifestations in patients with human immunodeficiency virus (HIV) has changed. This study, conducted at Tokyo Medical and Dental University Hospital between January 2012 and August 2023, aimed to understand the epidemiology and clinical features of ocular manifestations in patients with HIV during the cART era. Of the 218 patients diagnosed with HIV, 23 (10.55%) exhibited ocular manifestations; all were male, aged 32-73. The most prevalent ocular complication was uveitis (60.67%). Notably, the prevalence of uveitis in this cART era has surged compared to earlier Japanese studies. Our data also suggest a potential direct link between uveitis and HIV, particularly in patients who have not yet undergone cART. However, cytomegalovirus retinitis, another prevalent ocular disease in our study, appeared more strongly associated with patients who commenced cART. Neither ocular condition was significantly correlated with CD4+ T-cell count. Importantly, our observed ocular manifestation prevalence (10.55%) was lower than that in previous studies, emphasizing the potential influence of cART and national healthcare support. These findings provide unique insights into the evolution of ocular manifestations in patients with HIV in Japan amidst cART availability.

4.
Vaccines (Basel) ; 11(10)2023 Oct 23.
Article in English | MEDLINE | ID: mdl-37897028

ABSTRACT

The association between vaccines and ocular disorders has attracted significant attention in scientific research. Numerous mainstream vaccines are associated with a range of uveitis types, including anterior, intermediate, and posterior uveitis. Additionally, they are associated with distinct ocular diseases such as multifocal choroiditis, Vogt-Koyanagi-Harada (VKH) disease, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and multiple evanescent white dot syndrome (MEWDS). These ocular conditions are often transient, with a vast majority of patients experiencing improvement after steroid intervention. To date, numerous cases of vaccine-induced uveitis have been reported. This study analyzed the correlation between antiviral vaccines, including the hepatitis B virus (HBV), human papillomavirus (HPV), measles-mumps-rubella (MMR), varicella zoster virus (VZV), and influenza vaccines, and different manifestations of uveitis. This is the first comprehensive study to offer a detailed analysis of uveitis types induced by antiviral vaccines. Through an extensive database search, we found a particularly strong link between influenza vaccines, followed by VZV and HPV vaccines. While anterior uveitis is common, conditions such as APMPPE, MEWDS, and VKH are particularly notable and merit careful consideration in clinical practice. Corticosteroid treatment was effective; however, half of the observed patients did not achieve full recovery, indicating potentially prolonged effects of the vaccine.

5.
Int Immunopharmacol ; 123: 110782, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37573688

ABSTRACT

BACKGROUND: Inflammasome has been reported to play an important role in the pathogenesis and progression of hematologic malignancies. As one of the backbone drugs for treating acute lymphoblastic leukemia (ALL), the anti-inflammatory effect of mercaptopurine (6-MP) and the impact of gut microbiome changes caused by 6-MP on anti-inflammasome remain unclear. OBJECTIVE: We aimed to explore the association between 6-MP therapeutic effects and microbiome-involved inflammatory responses in ALL mice models. STUDY DESIGN: ALL murine model was built by i.v. injecting murine L1210 cells into DBA/2 mice (model group). Two weeks after cell injections, 6-MP was orally administrated for 14 days (6-MP group). Fecal samples of mice were collected at different time points. Cecum short-chain fatty acids (SCFAs) concentrations were determined by LC-MS/MS method. Serum cytokines were measured using a cytometric bead array. Gut microbiota composition in mice was explored using 16S rRNA gene sequencing. RESULTS: The anti-tumor effect of 6-MP was proved in ALL mice models. The levels of pro-inflammatory factors IL-6 and TNFα significantly decreased after the administration of 6-MP. Cecum contents' acetate, propionate, and butyrate levels were negatively correlated with IL-6 (correlation coefficient: acetate, -0.24; propionate, -0.26; butyrate, -0.17) and TNFα (correlation coefficient: acetate, -0.45; propionate, -0.42; butyrate, -0.31) changes. Relative abundance changes of f_Lachnospiraceae.g_ASF356 and f_Peptococcaceae.g_uncultured were in accordance with the changes of butyrate levels and opposite to the changes of pro-inflammatory levels. CONCLUSION: The anti-inflammatory response of 6-MP influenced by intestinal microbiota and its metabolites SCFAs, especially butyrate, played an essential role in improving ALL progression.


Subject(s)
Microbiota , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Mice , Animals , Propionates , Tumor Necrosis Factor-alpha , Mercaptopurine/therapeutic use , Interleukin-6 , RNA, Ribosomal, 16S/genetics , Chromatography, Liquid , Mice, Inbred DBA , Tandem Mass Spectrometry , Fatty Acids, Volatile/metabolism , Butyrates , Acetates , Anti-Inflammatory Agents/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
6.
Int J Nanomedicine ; 18: 79-94, 2023.
Article in English | MEDLINE | ID: mdl-36636639

ABSTRACT

Background: Nanomedicines have significant advantages in enhancing the oral bioavailability of drugs, but a deeper understanding of the underlying mechanisms remains to be interpreted. Hence, the present study aims to explain the uptake and trafficking mechanism for 6-MP nanomedicines we previously constructed. Methods: 6-MP loaded poly(lactide-co-glycolide) (PLGA) nanomedicines (6-MPNs) were prepared by the multiple emulsion method. The transcytosis mechanism of 6-MPNs was investigated in Caco-2 cells, Caco-2 monolayers, follicle associated epithelium (FAE) monolayers and rats, including transmembrane pathway, intracellular trafficking, paracellular transport and the involvement of transporter. Results: Pharmacokinetics in rats showed that the area under the curve (AUC) of 6-MP in the 6-MPNs group (147.3 ± 42.89 µg/L·h) was significantly higher than that in the 6-MP suspensions (6-MPCs) group (70.31 ± 18.24 µg/L·h). The uptake of 6-MPNs in Caco-2 cells was time-, concentration- and energy-dependent. The endocytosis of intact 6-MPNs was mediated mainly through caveolae/lipid raft, caveolin and micropinocytosis. The intracellular trafficking of 6-MPNs was affected by endoplasmic reticulum (ER)-Golgi complexes, late endosome-lysosome and microtubules. The multidrug resistance associated protein 4 (MRP4) transporter-mediated transport of free 6-MP played a vital role on the transmembrane of 6-MPNs. The trafficking of 6-MPNs from the apical (AP) side to the basolateral (BL) side in Caco-2 monolayers was obviously improved. Besides, 6-MPNs affected the distribution and expression of zona occludens-1 (ZO-1). The transport of 6-MPNs in FAE monolayers was concentration- and energy-dependent, while reaching saturation over time. 6-MPNs improved the absorption of the intestinal Peyer's patches (PPs) in rats. Conclusion: 6-MPNs improve the oral bioavailability through multiple pathways, including active transport, paracellular transport, lymphatic delivery and MRP4 transporter. The findings of current study may shed light on the cellular uptake and transcellular trafficking mechanism of oral nanomedicines.


Subject(s)
Mercaptopurine , Nanoparticles , Humans , Rats , Animals , Caco-2 Cells , Biological Availability , Nanomedicine , Biological Transport , Membrane Transport Proteins , Multidrug Resistance-Associated Proteins/metabolism
8.
Asia Pac Psychiatry ; 15(1): e12523, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36596718

ABSTRACT

INTRODUCTION: This study aimed to investigate the prevalence of depression and anxiety, and associated factors, among Chinese children and adolescents aged 8-18 years who attend primary or high school. METHODS: A total of 23 005 primary and high school students were recruited from February to December, 2019 for this cross-sectional study. The questionnaire included demographic information, questions assessing suicidality, resilience, depression (Center for Epidemiological Studies Depression Scale for Children), and anxiety (Screen for Child Anxiety Related Disorders). Binary logistic regression was used to analyze the independent correlates of depression and anxiety. RESULTS: Overall, 13.06% of participants experienced depressive symptoms, 22.34% experienced anxiety symptoms, 26.34% experienced transient suicidal ideation, 2.23% had serious suicidal ideation, and 1.46% had a history of suicide attempts. Anxiety (odds ratio [OR], 4.935; 95% confidence interval [CI][4.442-5.485]), suicidality (OR, 2.671; 95% CI[2.203-3.237]), skipping breakfast (OR, 1.920; 95% CI[1.348-2.736]), sleep duration (OR, 0.470; 95% CI[0.398-0.556]) and self-expectations (OR, 1.924; 95% CI[1.550-2.389]) were associated with depression (all p < .05). Depression (OR, 4.424; 95% CI[3.983-4.914]), female sex (OR, 1.903; 95% CI[1.759-2.060]), school-based traumatic experience(s) (OR, 1.905; 95% CI[1.747-2.077]), relationships with teachers (OR, 1.575; 95% CI[1.103-2.249]), and suicidality (OR, 1.467; 95% CI[1.218-1.766]) were associated with anxiety symptoms (all p < .05). DISCUSSION: Depression and anxiety are common among school-age children and adolescents in China. Childhood school- and family-based traumatic experience(s), female sex, and lifestyle factors (eating breakfast, sleep duration, exercising, and Internet use) are significantly associated with mental health among children and adolescents. Developing interventions targeting these factors to protect students from depression and anxiety are needed.


Subject(s)
Depression , East Asian People , Adolescent , Child , Humans , Female , Cross-Sectional Studies , Depression/epidemiology , Depression/psychology , Prevalence , Risk Factors , Anxiety/epidemiology , Anxiety/psychology , Suicidal Ideation , Students/psychology
9.
BMC Cancer ; 21(1): 409, 2021 Apr 15.
Article in English | MEDLINE | ID: mdl-33858374

ABSTRACT

BACKGROUND: Carnitine palmitoyl transferase 1A (CPT1A), the key regulator of fatty acid oxidation, contributes to tumor metastasis and therapeutic resistance. We aimed to identify its clinical significance as a biomarker for the diagnosis and prediction of breast cancer. METHODS: Western blot, ELISA and in silico analysis were used to confirm CPT1A levels in breast cancer cell lines, cell culture medium and breast cancer tissues. Four hundred thirty breast cancer patients, 200 patients with benign breast disease, and 400 healthy controls were enrolled and randomly divided into a training set and a test set with a 7:3 ratio. Training set was used to build diagnostic models and 10-fold cross validation was used to demonstrate the performance of the models. Then test set was aimed to validate the effectiveness of the diagnostic models. ELISA was conducted to detect individual serum CPT1A levels. Receiver operating characteristic (ROC) curves were generated, and binary logistic regression analyses were performed to evaluate the effectiveness of CPT1A as a biomarker in breast cancer diagnosis. CPT1A levels between post-operative and pre-operative samples were also compared. RESULTS: CPT1A was overexpressed in breast cancer tissues, cell lines and cell culture medium. Serum CPT1A levels were higher in breast cancer patients than in controls and were significantly associated with metastasis, TNM stage, histological grading and molecular subtype. CPT1A levels were decreased in post-operative samples compared with paired pre-operative samples. Moreover, CPT1A exhibited a higher efficacy in differentiating breast cancer patients from healthy controls (training set: area under the curve, AUC, 0.892, 95% CI, 0.872-0.920; test set, AUC, 0.904, 95% CI, 0.869-0.939) than did CA15-3, CEA, or CA125. CONCLUSION: CPT1A is overexpressed in breast cancer and can be secreted out of breast cancer cell. Serum CPT1A is positively associated with breast cancer progression and could serve as an indicator for disease monitoring. Serum CPT1A displayed a remarkably high diagnostic efficiency for breast cancer and could be a novel biomarker for the diagnosis of breast cancer.


Subject(s)
Biomarkers, Tumor , Breast Neoplasms/diagnosis , Breast Neoplasms/enzymology , Carnitine O-Palmitoyltransferase/metabolism , Adult , Aged , Breast Diseases/diagnosis , Breast Diseases/enzymology , Breast Neoplasms/mortality , Carnitine O-Palmitoyltransferase/blood , Case-Control Studies , Cell Line, Tumor , Enzyme-Linked Immunosorbent Assay , Female , Humans , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Prognosis , ROC Curve , Reproducibility of Results
10.
J Invest Dermatol ; 141(9): 2141-2150, 2021 09.
Article in English | MEDLINE | ID: mdl-33741391

ABSTRACT

In skin lesions caused by pemphigus, a group of life-threatening autoimmune bullous diseases, an over-representation of CD4+ tissue-resident memory T (TRM) cells was found. We sought to investigate the contributions of CD4+ TRM cells to the severity and refractoriness of pemphigus and their role in local immunological pathogenesis. Our data showed that CD4+ TRM cells accumulated significantly in pemphigus skin lesions. These CD4+ TRM cells expressed a specific set of T follicular helper cell‒related costimulatory molecules. We also found that CD4+ TRM cells remaining in the lesions produced IL-17A and IL-21. In vitro, CD4+ TRM cells exhibited strong support and assistance to autoantibody production. Through transcriptomic sequencing and bioinformatics analysis, we identified that the transcription factor IRF4 was responsible for IL-21 overexpression and autoantibody production. Our results showed that T follicular helper-like CD4+ TRM cells in pemphigus lesions promoted local autoantibody production, resulting in the formation and recurrence of lesions, which supports targeting this cell subset in pemphigus treatment. IRF4 might serve as a potential therapeutic target.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Germinal Center/immunology , Pemphigus/immunology , T-Lymphocytes, Helper-Inducer/immunology , Aged , Aged, 80 and over , Cells, Cultured , Female , Gene Expression Profiling , Humans , Immunologic Memory , Interferon Regulatory Factors/genetics , Interferon Regulatory Factors/metabolism , Interleukin-17/metabolism , Interleukins/metabolism , Male , Middle Aged , Phenotype
11.
Int J Nanomedicine ; 16: 1127-1141, 2021.
Article in English | MEDLINE | ID: mdl-33603372

ABSTRACT

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children. It requires a long and rigorous course of chemotherapy treatments. 6-Mercaptopurine (6-MP) is one of the primary drugs used in chemotherapy. Unfortunately, its efficacy has been limited due to its insolubility, poor bioavailability and serious adverse effects. To overcome these drawbacks, we constructed 6-mercaptopurine (6-MP)-loaded nanomedicines (6-MPNs) with biodegradable poly(lactide-co-glycolide) (PLGA) to enhance the anticancer efficacy of 6-MP. METHODS: We prepared the 6-MPNs using a double-emulsion solvent evaporation method, characterizing them for the physicochemical properties. We then investigated the plasma, intestinal region and other organs in Sprague Dawley (SD) rats for pharmacokinetics. Additionally, we evaluated its anticancer efficacy in vitro on the human T leukemia cell line Jurkat and in vivo on the ALL model mice. RESULTS: The 6-MPNs were spherical in shape with uniform particle size and high encapsulation efficiency. The in vitro release profile showed that 6-MPNs exhibited a burst release that a sustained release phase then followed. The apoptosis assay demonstrated that 6-MPNs could improve the in vitro cytotoxicity in Jurkat cells. Pharmacokinetics profiles revealed that 6-MPNs had improved oral bioavailability. Tissue distribution experiments indicated that 6-MPNs increased the duodenum absorption of 6-MP, at the same time having a low accumulation of the toxic metabolites of 6-MP. The in vivo pharmacodynamics study revealed that 6-MPNs could prolong the survival time of the ALL model mice. The prepared 6-MPNs, therefore, have superior properties in terms of anticancer efficacy against ALL with reduced systemic toxicity. CONCLUSION: Our nanomedicines provide a promising delivery strategy for 6-MP; they offer a simple preparation method and high significance for clinical translation.


Subject(s)
Mercaptopurine/chemistry , Mercaptopurine/pharmacokinetics , Nanomedicine , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Administration, Oral , Animals , Apoptosis , Cell Proliferation , Female , Humans , Mercaptopurine/administration & dosage , Mice , Mice, Inbred NOD , Mice, SCID , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Rats , Rats, Sprague-Dawley , Tissue Distribution , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
12.
J Control Release ; 324: 341-353, 2020 08 10.
Article in English | MEDLINE | ID: mdl-32422212

ABSTRACT

Chemotherapy post cancer surgery has important clinical significance for reducing the chance of recurrent-metastasis. However, postoperative chemotherapy efficacy is hampered by poor targeting capability and dose-limiting toxicity of chemo-drugs. Herein, we report a bio-mimetic platelet membrane-cloaked paclitaxel nanocrystal system (PPNCs), which consists of spherical paclitaxel nanocrystals (PNCs) as a high-dose drug core, polyethylene glycol-conjugated paclitaxel (PEG-PTX) as an amphiphilic molecule to adjust the surface hydrophilicity of PNCs and the shell of platelet membrane that can target surgical coagulation site. The in vitro characterization of PPNCs exhibited uniform particle size distribution, high drug loading, and good stability, which are crucial for effective drug delivery. At cell levels, PPNCs showed greater cellular uptake and higher cytotoxicity in 4T1 breast cancer cells than bare PNCs. In vivo, the nanoparticles could deliver high-dose chemo-drugs and target the coagulation site caused by surgery or vascular disrupting agents, resulting in enhanced anti-tumor efficacy and reduced systemic toxicities. In general, the PPNCs system can be served as a promising and efficient drug delivery system for postoperative chemotherapy.


Subject(s)
Antineoplastic Agents , Nanoparticles , Cell Line, Tumor , Paclitaxel , Particle Size , Polyethylene Glycols
13.
14.
Microbiologyopen ; 9(3): e991, 2020 03.
Article in English | MEDLINE | ID: mdl-31961499

ABSTRACT

Pseudomonas aeruginosa encodes three type VI secretion systems (T6SSs), namely H1-, H2-, and H3-T6SS. P. aeruginosa hemolysin-coregulated protein (Hcp) is the effector protein and the hallmark of T6SS. Although T6SS is ubiquitous and affects ecology and human health, its general mechanism and physiological role are still not fully understood. Therefore, in this study, we investigated the impact of the P. aeruginosa T6SS on biofilm formation and environmental adaptation. To this end, we collected P. aeruginosa clinical isolates, divided them into strong biofilm formation (SBF) and nonbiofilm formation (NBF) groups based on their biofilm-forming ability, and compared their associated clinical characteristics. The duration of hospitalization was longer in patients infected with SBF than those infected with NBF strains. The expression levels of T6SS-related genes (hcp1 and hcp3) and a quorum-sensing gene (lasR) were higher in the SBF group as compared to those in the NBF group. In addition, the expression level of lasR was negatively associated with that of hcp1, but was positively associated with those of hcp2 and hcp3. Moreover, we evaluated the expression of T6SS- and biofilm-associated genes in planktonic and biofilm cells of the P. aeruginosa strain PAO1, and constructed strain PAO1△clpV1 to study the adaptation characteristics of H1-T6SS. The expression levels of hcp1, hcp2, hcp3, lasR, and other biofilm-associated genes were significantly higher in PAO1 biofilm cells as compared to those of planktonic cells. However, except for swarming ability as a vital feature for biofilm formation, there were no significant differences in the biofilm-forming ability and expression of biofilm-associated genes, adherence ability, growth characteristics, resistance to acid and osmotic pressure, surface structure, and morphology between the PAO1△clpV1 and PAO1 wild-type strains. Collectively, our results suggest that T6SS might play a role in biofilm formation and that H1-T6SS does not contribute to environmental adaptation in P. aeruginosa.


Subject(s)
Adaptation, Physiological , Biofilms/growth & development , Environment , Pseudomonas aeruginosa/physiology , Type VI Secretion Systems , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Gene Expression Profiling , Gene Expression Regulation, Bacterial , Hydrogen-Ion Concentration , Mutation , Pseudomonas aeruginosa/ultrastructure , Virulence Factors/genetics
15.
J Invest Dermatol ; 140(2): 309-318.e8, 2020 02.
Article in English | MEDLINE | ID: mdl-31476317

ABSTRACT

Pemphigus is an organ-specific autoimmune disease that targets skin and/or mucous membranes. Our previous study showed that infiltrating lymphocytes in pemphigus vulgaris (PV) lesions produce anti-desmoglein (Dsg) 1/3 antibodies after in vitro culture. In this study, we found diffuse ectopic lymphoid-like structures (ELSs) commonly present in the lesions of both PV and pemphigus foliaceus. Notably, pemphigus lesions contained centroblasts, plasmablasts, and plasma cells, which recapitulated the different stages of B cell differentiation. Elevated mRNA expression levels of the differentiation-related transcription factors BLIMP-1, IRF4, and BCL-6 were observed in pemphigus lesions. Moreover, B cell receptor repertoire analysis revealed the clonal expansion of the lesional B cells. Lesional B cells might recirculate among lesions, lymph nodes, and peripheral blood. Increased mRNA expression levels of multiple chemokines in pemphigus lesions and elevated expression levels of chemokine receptors on lesional B cells were also observed. Collectively, these results show that the ELSs in pemphigus lesions might act as a niche, supporting in situ B cell differentiation and clonal expansion.


Subject(s)
B-Lymphocytes/immunology , Cell Differentiation/immunology , Pemphigus/immunology , Skin/immunology , Tertiary Lymphoid Structures/immunology , Adult , Aged , Animals , Biopsy , Cell Differentiation/genetics , Cells, Cultured , Clonal Selection, Antigen-Mediated/genetics , Clonal Selection, Antigen-Mediated/immunology , Disease Models, Animal , Female , Gene Expression Regulation/immunology , Humans , Interferon Regulatory Factors/metabolism , Lymphocyte Activation/genetics , Lymphocyte Activation/immunology , Male , Mice, SCID , Middle Aged , Pemphigus/blood , Pemphigus/pathology , Positive Regulatory Domain I-Binding Factor 1/metabolism , Primary Cell Culture , Proto-Oncogene Proteins c-bcl-6/metabolism , Skin/cytology , Skin/pathology
18.
Oncotarget ; 8(25): 41518-41528, 2017 Jun 20.
Article in English | MEDLINE | ID: mdl-28514747

ABSTRACT

BACKGROUND: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and PET/CT have become two of the most powerful tools for malignant lymphoma exploration, but their diagnostic role in primary central nervous system lymphoma (PCNSL) is still disputed. The purpose of our study is to identify the usefulness of 18F-FDG PET and PET/CT for detecting PCNSL. RESULTS: A total of 129 patients, obtained from eight eligible studies, were included for this systematic review and meta-analysis. The performance of 18F-FDG PET and PET/CT for diagnosing PCNSL were as follows: the pooled sensitivity was 0.88 (95% CI: 0.80-0.94), specificity was 0.86 (95% CI: 0.73-0.94), positive likelihood ratio (PLR) was 3.99 (95% CI: 2.31-6.90), negative likelihood ratio (NLR) was 0.11 (95% CI: 0.04-0.32), and diagnostic odds ratio (DOR) was 33.40 (95% CI: 10.40-107.3). In addition, the area under the curve (AUC) and Q index were 0.9192 and 0.8525, respectively. MATERIALS AND METHODS: PubMed/MEDLINE, Embase and Cochrane Library were systematically searched for potential publications (last updated on July 16th, 2016). Reference lists of included articles were also checked. Original articles that reported data on patients who were suspected of having PCNSL were considered suitable for inclusion. The sensitivities and specificities of 18F-FDG PET and PET/CT in each study were evaluated. The Stata software and Meta-Disc software were employed in the process of data analysis. CONCLUSIONS: 18F-FDG PET and PET/CT showed considerable accuracy in identifying PCNSL in immunocompetent patients and could be a valuable radiological diagnostic tool for PCNSL.


Subject(s)
Central Nervous System Neoplasms/diagnostic imaging , Fluorodeoxyglucose F18 , Lymphoma/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Positron-Emission Tomography/methods , Central Nervous System Neoplasms/immunology , Central Nervous System Neoplasms/pathology , Humans , Immunocompetence , Lymphoma/immunology , Lymphoma/pathology , Radiopharmaceuticals
19.
Oncotarget ; 8(7): 10836-10844, 2017 Feb 14.
Article in English | MEDLINE | ID: mdl-28122333

ABSTRACT

Academic stress (AS) is one of the most important health problems experienced by students, but no biomarker of the potential psychological or physical problems associated with AS has yet been identified. As several cross-sectional studies have shown that psychiatric conditions accelerate aging and shorten telomere length (TL), we explored whether AS affected TL.Between June 2014 and July 2014, we recruited 200 junior high school students with imminent final examinations for participation in this study. The students were divided into three subgroups (mild, moderate, and severe anxiety) using the Sarason Test Anxiety Scale (TAS). Saliva samples were collected for TL measurement via quantitative polymerase chain reaction (qPCR).Students from both a specialized and a general school suffered from anxiety (p > 0.05). A total 35% had severe anxiety (score: 26.09±3.87), 33% had moderate anxiety (16.98±2.64), and 32% had mild anxiety (7.89±1.92). The TAS values differed significantly (p < 0.05) among the three subgroups, but the TLs of saliva cells differed only slightly (p > 0.05): 1.14±0.46 for those with severe anxiety, 1.02±0.40 for those with moderate anxiety, and 1.12±0.45 for those with mild anxiety.Previous reports have found that AS is very common in Asian adolescents. We found no immediate telomere shortening in adolescents with AS. Longitudinal observations are required to determine if TL is affected by AS.


Subject(s)
Anxiety/psychology , Stress, Psychological , Telomere Shortening/genetics , Telomere/genetics , Adolescent , DNA/genetics , DNA/metabolism , Educational Status , Female , Humans , Male , Saliva/cytology , Surveys and Questionnaires
20.
Discov Med ; 22(121): 181-188, 2016 10.
Article in English | MEDLINE | ID: mdl-27875669

ABSTRACT

BACKGROUND: In recent years, the application of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) for voluntary cancer screening of asymptomatic individuals is becoming more and more popular in China. However, the utility of such screening is still controversial. METHODS: This study enrolled a total of 1,572 asymptomatic individuals who underwent FDG PET/CT as a part of cancer screening program in Shanghai Ruijin Hospital, between January 2010 and December 2014. Whole set of clinical data of each case was retrospectively collected. The cancer detection rate, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FDG PET/CT were calculated, according to the cancer data obtained from histopathological examinations or at least 12-month clinical follow-up. RESULTS: Among the 1,572 subjects, malignant tumors were found in 27 cases (1.72%). The cancer detection rate was 2.74% among subjects who were older than 50 years, 4.72% among those who had a family history of malignant tumors, and 2.77% among those whose tumor markers were positive. These rates were higher than those among other subjects (p<0.05). The detection rate of FDG PET/CT in asymptomatic cancer screening was 1.44%, and the sensitivity, specificity, PPV, and NPV were estimated to be 85.19%, 99.68%, 82.14%, and 99.75%, respectively. CONCLUSION: Considering its less cost-efficient performance, we do not recommend using FDG PET/CT for cancer screening in asymptomatic population. Nevertheless, FDG PET/CT might be a powerful cancer screening modality with the selection of high-risk group, and an optimal combination of the modalities should be provided in order to maximize diagnostic performance with lower costs.


Subject(s)
Glucose-6-Phosphate/analogs & derivatives , Mass Screening/methods , Neoplasms/diagnostic imaging , Positron-Emission Tomography , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Glucose-6-Phosphate/administration & dosage , Humans , Male , Middle Aged , Retrospective Studies
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