A Deep Learning Model for Accurate Diagnosis of Infection Using Antibody Repertoires.

The adaptive immune receptor repertoire consists of the entire set of an individual's BCRs and TCRs and is believed to contain a record of prior immune responses and the potential for future immunity. Analyses of TCR repertoires via deep learning (DL) methods have successfully diagnosed cancers and infectious diseases, including coronavirus disease 2019. However, few studies have used DL to analyze BCR repertoires. In this study, we collected IgG H chain Ab repertoires from 276 healthy control subjects and 326 patients with various infections. We then extracted a comprehensive feature set consisting of 10 subsets of repertoire-level features and 160 sequence-level features and tested whether these features can distinguish between infected individuals and healthy control subjects. Finally, we developed an ensemble DL model, namely, DL method for infection diagnosis (https://github.com/chenyuan0510/DeepID), and used this model to differentiate between the infected and healthy individuals. Four subsets of repertoire-level features and four sequence-level features were selected because of their excellent predictive performance. The DL method for infection diagnosis outperformed traditional machine learning methods in distinguishing between healthy and infected samples (area under the curve = 0.9883) and achieved a multiclassification accuracy of 0.9104. We also observed differences between the healthy and infected groups in V genes usage, clonal expansion, the complexity of reads within clone, the physical properties in the α region, and the local flexibility of the CDR3 amino acid sequence. Our results suggest that the Ab repertoire is a promising biomarker for the diagnosis of various infections.

A broad-spectrum multiepitope vaccine against seasonal influenza A and B viruses in mice.

BACKGROUND: Influenza viruses pose a persistent threat to global public health, necessitating the development of innovative and broadly effective vaccines. METHODS: This study focuses on a multiepitope vaccine (MEV) designed to provide broad-spectrum protection against different influenza viruses. The MEV, containing 19 B-cell linear epitopes, 7 CD4+ T cells, and 11 CD8+ T cells epitopes identified through enzyme-linked immunospot assay (ELISPOT) in influenza viruses infected mice, was administered through a regimen of two doses of DNA vaccine followed by one dose of a protein vaccine in C57BL/6 female mice. FINDINGS: Upon lethal challenge with both seasonal circulating strains (H1N1, H3N2, BV, and BY) and historical strains (H1N1-PR8 and H3N2-X31), MEV demonstrated substantial protection against different influenza seasonal strains, with partial efficacy against historical strains. Notably, the increased germinal centre B cells and antibody-secreting cells, along with robust T cell immune responses, highlighted the comprehensive immune defence elicited by MEV. Elevated hemagglutinin inhibition antibody was also observed against seasonal circulating and historical strains. Additionally, mice vaccinated with MEV exhibited significantly lower counts of inflammatory cells in the lungs compared to negative control groups. INTERPRETATION: Our results demonstrated the efficacy of a broad-spectrum MEV against influenza viruses in mice. Conducting long-term studies to evaluate the durability of MEV-induced immune responses and explore its potential application in diverse populations will offer valuable insights for the continued advancement of this promising vaccine. FUNDING: Funding bodies are described in the Acknowledgments section.

Effective omalizumab treatment influenced eosinophil function in severe allergic asthmatics.

Background: Omalizumab is an effective anti-immunoglobulin E (IgE) treatment for allergic asthma. Eosinophil plays a critical role in the pathogenesis of allergic airway inflammation. This study aimed to explore the influence of effective omalizumab treatment on circulating eosinophils. Methods: Allergic asthmatics enrolled in the study were treated with omalizumab for at least 16 weeks and exhibited a good or excellent response according to the global evaluation of treatment effectiveness (GETE) assessed by each patient and specialist physician. For eosinophil functional evaluation, peripheral blood eosinophils were separated; and examined the expression of human leukocyte antigen (HLA)-DR and co-stimulatory molecules cluster of differentiation (CD) 80, CD86 and CD40 by Flow Cytometry and serum were to measure the concentration of eotaxin-1 before and after 16 weeks of omalizumab treatment. Results: Totally 32 allergic asthma patients who responded positively to omalizumab treatment were included. Omalizumab responders showed a significant decline in the expression of co-stimulatory molecules CD40, CD80, and CD86 on peripheral eosinophils and in serum eotaxin-1 concentration after treatment. Negative correlations (r=-0.61, P=0.048) were observed between the change in CD80+ eosinophils and the change in forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC)% predicted and maximal expiratory flow (MEF) 25% after omalizumab treatment. Omalizumab improved FEV1/FVC% predicted (3.88, P=0.033), fractional exhaled nitric oxide (FeNO, -22.24, P=0.028), asthma control test (ACT, 4.22, P<0.001), mini asthma quality of life questionnaire (mini-AQLQ, -14.44, P=0.019), Leicester cough questionnaire (LCQ, 3.03, P=0.009) and visual analogue scale (VAS) for allergic symptoms (-13.00, P=0.001) in patients with severe allergic asthma statistically; reduced mini rhino-conjunctivitis quality of life questionnaire (mini-RQLQ, -8.50, P=0.047), and self-rating anxiety scale (SAS, -5.08, P=0.040) in allergic asthmatics with concomitant allergic rhinitis (AR) or anxiety, respectively. Conclusions: Our findings show a unique role of omalizumab in reducing co-stimulatory molecules expression on eosinophil and serum eotaxin-1 levels in severe allergic asthmatics accompanied by improvement of multiple clinical parameters of allergic diseases.

A mosaic influenza virus-like particles vaccine provides broad humoral and cellular immune responses against influenza A viruses.

The development of a universal influenza vaccine to elicit broad immune responses is essential in reducing disease burden and pandemic impact. In this study, the mosaic vaccine design strategy and genetic algorithms were utilized to optimize the seasonal influenza A virus (H1N1, H3N2) hemagglutinin (HA) and neuraminidase (NA) antigens, which also contain most potential T-cell epitopes. These mosaic immunogens were then expressed as virus-like particles (VLPs) using the baculovirus expression system. The immunogenicity and protection effectiveness of the mosaic VLPs were compared to the commercial quadrivalent inactivated influenza vaccine (QIV) in the mice model. Strong cross-reactive antibody responses were observed in mice following two doses of vaccination with the mosaic VLPs, with HI titers higher than 40 in 15 of 16 tested strains as opposed to limited cross HI antibody levels with QIV vaccination. After a single vaccination, mice also show a stronger level of cross-reactive antibody responses than the QIV. The QIV vaccinations only elicited NI antibodies to a small number of vaccine strains, and not even strong NI antibodies to its corresponding vaccine components. In contrast, the mosaic VLPs caused robust NI antibodies to all tested seasonal influenza virus vaccine strains. Here, we demonstrated the mosaic vaccines induces stronger cross-reactive antibodies and robust more T-cell responses compared to the QIV. The mosaic VLPs also provided protection against challenges with ancestral influenza A viruses of both H1 and H3 subtypes. These findings indicated that the mosaic VLPs were a promising strategy for developing a broad influenza vaccine in future.

Association between CYP19A1 rs6493497 and rs936306 polymorphisms and depression susceptibility in the Chinese population.

Aim: The CYP19A1 gene encodes the key aromatase for estrogen biosynthesis, and this study aimed to explore the relationship between CYP19A1 rs6493497 and rs936306 polymorphisms and depression risk. Methods: CYP19A1 rs6493497 and rs936306 genotyping was performed on 502 depression patients and 504 healthy controls. Results: In the general population, no significant association was observed between the CYP19A1 rs6493497 variant and depression, whereas that CYP19A1 rs936306 variant significantly reduced depression risk in the recessive model. In subgroup analysis, a significant association of the CYP19A1 rs6493497 variant with reduced depression risk was found in males aged 46-65 in the genotype, dominant and additive models. Conclusion: The CYP19A1 rs936306 variant may reduce depression risk, and the rs6493497 variant is associated with decreased depression risk in males aged 46-65.

The cause of depression is complex and not fully elucidated; the research evidence suggests that changes in estrogen levels may partly account for the risk of the onset of depression. The CYP19A1 gene encodes the key enzyme for estrogen biosynthesis, and this study aimed to explore whether the two loci (rs6493497 and rs936306) variants of the CYP19A1 gene are associated with the risk of occurrence of depression. Five hundred two patients with depression and 504 healthy controls were enrolled. The results of this study indicate that the CYP19A1 gene rs936306 variant may reduce the risk of occurrence of depression, and the rs6493497 variant is associated with decreased depression risk in men aged 46­65.

Role of IL-25 on Eosinophils in the Initiation of Th2 Responses in Allergic Asthma.

Background: Eosinophils act as a secondary antigen-presenting cell (APC) to stimulate Th cell responses against antigens. IL-25 plays a significant role in eosinophil activation in allergic asthma. The role of IL-25 on the classic APC functions of dendritic cells has been elucidated. However, whether IL-25 facilitates eosinophils for antigen presentation is unknown. Objective: To elucidate the role of IL-25 on eosinophils antigen presenting function during allergic asthma and its related mechanism. Methods: Eosinophils from allergic asthma subjects were cultured with IL-25 and HDM to identify the co-stimulator molecules expression. Co-cultures of patient eosinophils and autologous naïve CD4+ T cells in the same culture system were to explore whether eosinophils had the capacity to promote Th cell differentiation in response to IL-25 engagement. In asthma mouse model, IL-25-/- mice were exposed to HDM to investigate the effect of IL-25 on eosinophils during the sensitization phase. The impact of IL-25 on the capacity for eosinophils taking up antigens was evaluated. Mouse bone marrow derived eosinophils (BmEOS) were co-cultured with naïve CD4+T cells sorted from spleens under HDM and IL-25 stimulation to identify T cell differentiation. Results: IL-25 upregulated HLA-DR, PD-L1, and OX-40L expression on eosinophils from allergic asthma patients. IL-25 and HDM co-sensitized eosinophils promoted Th2 differentiation. In mouse model, IL-25-/- mice experienced restrained allergic pulmonary inflammation and reduced eosinophils recruitment and antigen uptake capacity during the early sensitization phase. In vitro, IL-25 promoted antigen uptake by eosinophils. In BmEOS and naïve CD4+T cells co-culture, IL-25 accreted the proportion of CD4+Th2 cells, which was absent in CD4+T cells culture alone. Conclusion: Our data identify a novel role of IL-25 in enhancing eosinophils antigen uptake and co-stimulator molecules expression to induce Th2 priming in the context of allergic inflammation.

Effective Infection with Dengue Virus in Experimental Neonate and Adult Mice through the Intranasal Route.

Dengue virus, the causative agent of dengue fever, life-threatening hemorrhagic fever, and shock syndrome, is mainly transmitted to humans through mosquito vectors. It can also be transmitted through atypical routes, including needle stick injury, vertical transmission, blood transfusion, and organ transplantation. In addition, sporadic cases which have no clear infectious causes have raised the respiratory exposure concerns, and the risks remain unclear. Here, we analyze the respiratory infectivity of the dengue virus in BALB/c suckling and adult immunodeficient mice by the intranasal inoculation of dengue virus serotype 2. The infected mice presented with clinical symptoms, including excitement, emaciation, malaise, and death. Viremia was detected for 3 days post inoculation. Histopathological changes were observed in the brain, liver, and spleen. The virus showed evident brain tropism post inoculation and viral loads peaked at 7 days post inoculation. Furthermore, the virus was isolated from the infected mice; the sequence homology between the origin and isolates was 99.99%. Similar results were observed in adult IFN-α/ß receptor-deficient mice. Overall, dengue virus can infect suckling mice and adult immune-deficient mice via the nasal route. This study broadens our perception of atypical dengue transmission routes and provides evidence of nasal transmission of dengue virus in the absence of mosquito vectors.

Meteorological change and hemorrhagic fever with renal syndrome epidemic in China, 2004-2018.

Hemorrhagic fever with renal syndrome (HFRS), caused by hantavirus, is a serious public health problem in China. Despite intensive countermeasures including Patriotic Health Campaign, rodent control and vaccination in affected areas, HFRS is still a potential public health threat in China, with more than 10,000 new cases per year. Previous epidemiological evidence suggested that meteorological factors could influence HFRS incidence, but the studies were mainly limited to a specific city or region in China. This study aims to evaluate the association between monthly HFRS cases and meteorological change at the country level using a multivariate distributed lag nonlinear model (DLNM) from 2004 to 2018. The results from both univariate and multivariate models showed a non-linear cumulative relative risk relationship between meteorological factors (with a lag of 0-6 months) such as mean temperature (Tmean), precipitation, relative humidity (RH), sunshine hour (SH), wind speed (WS) and HFRS incidence. The risk for HFRS cases increased steeply as the Tmean between - 23 and 14.79 °C, SH between 179.4 and 278.4 h and RH remaining above 69% with 50-95 mm precipitation and 1.70-2.00 m/s WS. In conclusion, meteorological factors such as Tmean and RH showed delayed-effects on the increased risk of HFRS in the study and the lag varies across climate factors. Temperature with a lag of 6 months (RR = 3.05) and precipitation with a lag of 0 months (RR = 2.08) had the greatest impact on the incidence of HFRS.

Intermittent hypoxia promotes hippocampal neurogenesis and produces antidepressant-like effects in adult rats.

Increasing evidence indicates that stimulating hippocampal neurogenesis could provide novel avenues for the treatment of depression, and recent studies have shown that in vitro neurogenesis is enhanced by hypoxia. The aim of this study was to investigate the potential regulatory capacity of an intermittent hypobaric hypoxia (IH) regimen on hippocampal neurogenesis and its possible antidepressant-like effect. Here, we show that IH promotes the proliferation of endogenous neuroprogenitors leading to more newborn neurons in hippocampus in adult rats. Importantly, IH produces antidepressant-like effects in multiple animal models screening for antidepressant activity, including the forced swimming test, chronic mild stress paradigm, and novelty-suppressed feeding test. Hippocampal x-ray irradiation blocked both the neurogenic and behavioral effects of IH, indicating that IH likely produces antidepressant-like effects via promoting neurogenesis in adult hippocampus. Furthermore, IH stably enhanced the expression of BDNF in hippocampus; both the antidepressant-like effect and the enhancement of cell proliferation induced by IH were totally blocked by pharmacological and biological inhibition of BDNF-TrkB (tyrosine receptor kinase B) signaling, suggesting that the neurogenic and antidepressant-like effects of IH may involve BDNF signaling. These observations might contribute to both a better understanding of physiological responses to IH and to developing IH as a novel therapeutic approach for depression.

Knowledge-based virtual screening of HLA-A*0201-restricted CD8+ T-cell epitope peptides from herpes simplex virus genome.

A novel knowledge-based method is developed to virtually screen potential HLA-A*0201 binders from large-scale peptide candidates. This method utilizes the information from both the crystal structures and experimental affinities of various peptides bound with HLA-A*0201 to construct a single-position mutation free energy profile for accurately characterizing HLA-A*0201-peptide interaction and for effectively predicting the binding affinities of peptides to HLA-A*0201. We employ this method to analyze physicochemical properties and structural implication underlying the specific recognition and association between the HLA-A*0201 and a large panel of peptide segments generated from the herpes simplex virus type 1 (HSV-1) genome, and to evaluate the binding potencies of these peptide candidates to HLA-A*0201. As a result, 288 out of 38,020 candidates are predicted as the potential high-affinity binders of HLA-A*0201, from which three most promising peptides are picked out for further development of potent vaccines against HSV-1. In addition, we also demonstrate that this newly proposed method can successfully identify 8 known binders and 3 known nonbinders from the glycoproteins D and K of HSV-1.

Fuzi polysaccharide-1 produces antidepressant-like effects in mice.

Current antidepressants are clinically effective only after several weeks of administration. We show that Fuzi polysaccharide-1 (FPS), a new water-soluble polysaccharide isolated from Fuzi, which has been used to treat mood disorders in traditional Chinese medicine for centuries, increases the number of newborn cells in the dentate gyrus in adult mice, and most of these cells subsequently differentiate into new neurons. We also found that FPS administration reduces immobility in the forced swim test, and latency in the novelty suppressed-feeding test. Moreover, a 14-d regimen with FPS reverses avoidance behaviour and inhibition of hippocampal neurogenesis induced by chronic defeat stress. In contrast, imipramine, a well known antidepressant, reverses this avoidance behaviour only after 4 wk of continuous administration. Finally, acute treatment with FPS had no effect on brain monoamine levels in frontal cortex but significantly increases BDNF in the hippocampus, while the antidepressant effect and enhancement of cell proliferation induced by FPS administration were totally blocked by K252a, an inhibitor of trkB in a chronic social defeat depression model, suggesting that the neurogenic and antidepressant effects of FPS may involve BDNF signalling. In conclusion, our findings suggest that FPS could be developed as a putative antidepressant with a rapid onset of action.

CX3CL1 rs170364 gene polymorphism has a protective effect against major depression by enhancing its transcriptional activity.

Studies have shown that adult hippocampal neurogenesis may be a cause of depression. CX3CL1 is a chemokine that plays an important role in adult neurogenesis. This study aimed to investigate the relationship between CX3CL1 polymorphisms (rs170364) and the risk of depression. A case-control study of 502 patients with major depression and 504 gender-matched and age-matched healthy controls was performed. All subjects were recruited from the Chinese Han population. Next-generation sequencing was used to genotype the CX3CL1 rs170364 locus. In addition, the effect of the rs170364 polymorphism on transcription of CX3CL1 was investigated through the use of luciferase reporter constructs and in vitro analysis in SH-SY5Y cells. Our results demonstrated that the T allele and GT + TT genotype of the CX3CL1 rs170364 locus were associated with a reduced risk of major depression. Subgroup analysis found that this significant association was consistently found in females but not in males. In vitro experiments found that the rs170364 mutation enhanced the transcriptional activity of CX3CL1. These results suggest that T allele and GT + TT genotypes of the CX3CL1 rs170364 locus may be a protective factor against the onset of depression in the Chinese Han population, especially in females. SNP rs170364 enhances the transcriptional activity of CX3CL1.

The Epac2 coding gene (RAPGEF4) rs3769219 polymorphism is associated with protection against major depressive disorder in the Chinese Han population.

BACKGROUND: Adult hippocampal neurogenesis has been demonstrated to be associated with the occurrence of major depressive disorder (MDD). A recent study indicated that deletion of the Epac2 gene (RAPGEF4) caused downregulation of hippocampal neurogenesis. This study aimed to analyze the association between genetic variants of the RAPGEF4 gene and the risk of MDD. METHODS: We recruited 502 patients with MDD and 504 healthy controls who matched for age and gender. Genomic DNA was extracted from whole blood samples and genotyping was performed by next-generation sequencing. In addition, we conducted subgroup analysis according to the gender and recurrence, respectively. RESULTS: We found no significant association between RAPGEF4 gene rs3769219 variant and MDD in all subjects. However, the A-allele and GA + AA genotypes at rs3769219 were significantly associated with a reduced risk of MDD in the male population but not in the female population. Similarly, our study identified the A-allele and GA + AA genotypes at rs3769219 as protective factors for recurrent MDD (rMDD). CONCLUSION: Our findings suggest that RAPGEF4 gene rs3769219 mutation is associated with a reduced risk of MDD in male population and rMDD in total population.

ZTW-41, a Potent Indolizinoquinoline-5,12-Dione Derivative Against Drug-Resistant Staphylococci and Enterococci Bacteria.

ZTW-41, an indolizinoquinoline-5,12-dione derivative, was investigated for antibacterial activity against Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA). In our study, the MIC90s (minimum inhibitory concentrations) of ZTW-41 against MRSA (MRSA, n = 200), methicillin-sensitive S. aureus (MSSA, n = 100), Enterococcus faecalis (E. faecalis, n = 32), and Enterococcus faecium (E. faecium n = 32) were 0.25, 0.25, 0.125, and 8 µg/mL, respectively, whereas the MBC90s (minimum bactericidal concentrations) were 2, 1, 1, and >32 µg/mL, respectively. ZTW-41 maintained its potency at different pH levels (range 5-9) and in starting inoculum size up to 107 CFU/mL. The presence of human serum (25-75%) increased ZTW-41 MICs by two- to eightfold. Time-kill curves showed that ZTW-41 had bactericidal activity against MRSA, MSSA, and E. faecalis strains within 8 hours, and rebound growth occurred after 8 hours except at higher multiples of the MIC (4 × and 8 × ). In the acute toxicity study, no mortality or signs of toxicity was noted in mice after 14 days of observation at doses <50 mg/kg. ZTW-41 exhibited good selectivity indices (SIs) (SI = IC50/MIC90) ranging from 1.12 to 71.76 against clinical isolates, demonstrating excellent therapeutic selectivity in MRSA, MSSA, and E. faecalis strains. Moreover, the in vivo efficacy (effective dose [ED]50 = 6.59 mg/kg) of ZTW-41 was found comparable with vancomycin. Collectively, our favorable results supported ZTW-41 as a promising investigational candidate for treating drug-resistant bacteria infection.

CYP19A1 rs2470152 polymorphism increases susceptibility to depression in Chinese Han population.

Estrogen plays a vital role in the pathogenesis of depression. The cytochrome p450 (CYP) 19A1 gene encodes aromatase, which is responsible for a key step in estrogen production. Previous studies suggested that CYP19A1 polymorphisms increase the risk of depression in the Japanese population. The current study aimed to investigate the correlation between the CYP19A1 rs2470152 polymorphism and the risk of depression in Chinese Han population. In total, 1006 Chinese Han subjects were recruited in this case-control study, including 502 patients diagnosed with depression and 504 healthy gender- and age-matched (from 18-65 years) controls. Genotyping was performed using multiplex PCR and high-throughput sequencing to assess the effects of the CYP19A1 rs2470152 (G > A) polymorphism on the risk of depression in the entire cohort and the subjects were further stratified by gender. No significant differences were observed in allele and genotype frequencies of CYP19A1 rs2470152 between total cases and controls (P > 0.05). However, the CYP19A1 rs2470152 polymorphism in the recessive model (AA vs. GG + GA) was associated with increased risk of depression (χ2 = 4.077, P = 0.043, OR = 1.347, 95% CI = 1.008-1.798). After subjects stratification by gender, neither genotypes nor genetic models showed significant differences between cases and controls (all P > 0.05). The results indicated that the CYP19A1 rs2470152 (G > A) polymorphism in the recessive model (AA vs. GG + GA) was correlated with increased risk of depression in Chinese Han population.

Association between NR3C1 rs41423247 polymorphism and depression: A PRISMA-compliant meta-analysis.

BACKGROUND: A dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is closely related to the occurrence of depression. The glucocorticoid receptor, also known as the nuclear receptor subfamily 3, group C, member 1 (NR3C1), provides negative feedback to the HPA axis by binding to glucocorticoids. Some studies have demonstrated an association between the NR3C1 rs41423247 polymorphism and depression, but results from other studies have been controversial. METHOD: In this study, the association between the NR3C1 rs41423247 polymorphism and depression was evaluated by a meta-analysis using the RevMan 5.3 software, and the Stata 10.0 software was used for sensitivity analysis and publication bias test. According to the inclusion criteria, related studies in databases were retrieved and screened. RESULTS: In total, 9 articles were selected, including 1630 depressed patients and 3362 controls. The meta-analysis showed that homozygous mutation of NR3C1 rs41423247 was associated with depression in the total population (OR = 0.77, 95% CI = 0.64-0.94, P = .01) and in Caucasians (OR = 0.78, 95% CI = 0.63-0.96, P = .02). CONCLUSION: This meta-analysis demonstrates that the NR3C1 rs41423247 homozygous mutation may be a risk factor for depression.

CYP2J2 participates in atherogenesis by mediating cell proliferation, migration and foam cell formation.

Atherosclerosis (AS) is a common pathological basis for the development of various cardiovascular and cerebrovascular diseases, however, currently, no effective treatment against AS has been established. It has previously been suggested that intravascular cytochrome P450 (CYP) oxidase is involved in the pathogenesis of AS. The present study investigated the role of cytochrome P450, family 2, subfamily J, polypeptide 2 (CYP2J2), the most common subtype of CYP oxidase in the human body, in the occurrence and development of AS. CYP2J2 was overexpressed in human umbilical vein endothelial cells (HUVECs), human arterial smooth muscle cells (HASMCs), and human peripheral monocyte­derived foam cells by lentiviral infection. The mRNA and protein levels were measured by reverse­transcription quantitative polymerase chain reaction and western blotting, respectively. Cell proliferation and migration were determined by MTS and Transwell assays, respectively. Furthermore, lipid accumulation was detected with Oil red O staining. The concentrations of total and free cholesterol were measured using a quantitation kit. Following lentiviral infection, CYP2J2 was successfully overexpressed in HUVEC, HASMC and foam cells. CYP2J2 overexpression promoted proliferation and migration in HUVECs and suppressed these actions in HASMCs. In addition, it suppressed oxidized low­density lipoprotein­induced foam cell formation. In conclusion, it was hypothesized that CYP2J2 may have a protective role in AS, as proliferation of HASMCs and the formation of foam cells are notable characteristics of AS.

Lower activation-induced T-cell apoptosis is related to the pathological immune response in secondary infection with hetero-serotype dengue virus.

The available evidence suggests that dengue virus-specific T lymphocytes and cytokine storm play a pivotal role in the immunopathogenesis of plasma leakage. Investigations are underway to identify the immune profiles associated with increased or decreased risk for severe disease. In this study, CD14+ cells from the peripheral blood mononuclear cells (PBMCs) of patients who recovered from DENV-1 infection were infected with DENV-1 or DENV-2 and co-cultured with memory T cells. We found that secondary infection with DENV-2 suppresses the cell reproductive capacity but forms more cell clones and more functional cells to produce more proinflammatory factors (IFN-γ, TNF-α, IL-6, IL-8, IL-12 and IL-17) and less regulatory cytokines (IL-10, TGF-ß) which results in higher viral replication compared to secondary infection with DENV-1. Memory dengue virus-specific T cells which are induced in a primary dengue virus infection are reactivated by the heterologous serotype of dengue virus and antigen-presenting cells (APCs) during a secondary infection. Dramatically, less apoptosis and more continuous activation of T cells in secondary infection with hetero-serotype DENV were observed. This discovery which has not been reported previously may be the reasonable and vital interpretation for the cytokine storm and severe symptoms observed in secondary infection with DENV. In summary, secondary infection with hetero-serotype DENV elicits the relatively pathological immune response while secondary infection with homologous-serotype DENV induces the relatively protective immune response by activation-induced cell death (AICD) of T cells.

Association between CYP17A1 rs3824755 and rs743572 gene polymorphisms and Alzheimer's disease in the Chinese Han population.

The CYP17A1 gene encodes cytochrome P450c17α, an enzyme that catalyzes the formation of sex hormones, which have been linked to the pathogenesis of Alzheimer's disease (AD). An association between the CYP17A1 rs743572 single nucleotide polymorphism (SNP) and AD has been reported; however, the findings are controversial. In the present study, we investigated the association between rs743572 and another SNP, rs3824755, and AD risk in a Chinese Han population (n=207 patients and 239 controls), and their interaction with the apolipoprotein E (APOE) e4 allele. We found that the C allele and GC+CC genotypes of rs3824755 conferred protection against AD only in APOE e4 carriers. Both rs3824755 and rs743572 polymorphisms showed interactions with APOE e4. The C allele and GC+CC genotypes of rs3824755 acted as protective factors that decreased the risk of APOE e4 in AD. The CYP17A1 rs743572G allele and AG+GG genotypes were found to be potential risk factors that act synergetically with APOE e4. Moreover, the CA and GG haplotypes were protective and conferred a slight risk, respectively, in APOE e4 carriers. These results indicate that CYP17A1 rs3824755 and rs743572 are associated with AD in the Chinese Han population and act in combination with APOE e4.

The CYP19A1 rs3751592 variant confers susceptibility to Alzheimer disease in the Chinese Han population.

BACKGROUND: The CYP19A1 enzyme (aromatase) encoded by the cytochrome P450 (CYP) 19A1 gene influences the final step in the biosynthesis of estrogen, which has been associated with Alzheimer disease (AD). It is possible that genetic polymorphisms in CYP19A1 could influence the risk of AD by altering the expression of CYP19A1. The ε4 allele of the apolipoprotein E (APOE) gene, which is the most significant known genetic risk factor for AD, may mask the effects of other loci. METHODS: To assess the potential association of CYP19A1 gene polymorphisms with the risk of AD, we conducted a case-control study in a Chinese Han population by recruiting 463 cases, including 207 patients diagnosed with AD and 256 healthy people matched for sex and age. RESULTS: In APOE ε4 carriers, the distributions of the G allele and the AG + GG genotype of CYP19A1 rs3751592 in patients differed significantly (P < 0.05) from those in healthy people. However, no difference was observed in the distribution of CYP19A1 rs1065778 between the patient and control populations, regardless of their APOE ε4 status. CONCLUSION: The results demonstrated that the rs3751592 A/G polymorphism of the CYP19A1 gene was associated with the incidence of AD in a Chinese Han population, which suggests that CYP19A1 rs3751592 is a predisposing genetic factor for AD.