Proteomic tools were used to identify the key proteins that might be associated with bronchial asthma(BA). Firstly, the serum samples from healthy adults and asthmatic patients were collected. Tandem Mass Tag~(TM)(TMT), which removes high-abundance structures and nonspecific proteins, was employed to identify the differentially expressed proteins between asthmatic patients and healthy adults. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were carried out for the differentially expressed proteins. The core proteins in the asthma group were screened out by protein-protein interaction(PPI) analysis. Then the core proteins were verified by Western blot for 3 patients with bronchial asthma and 3 healthy adults. A total of 778 differentially expressed proteins were screened out, among which 32 proteins contained quantitative information, including 18 up-regulated proteins and 14 down-regulated proteins. The differentially expressed proteins were enriched in 28 KEGG signaling pathways. The PPI analysis showed that 10 proteins(GDN, 1433 Z, VWF, HEMO, CERU, A1 AT, TSP1, G3 P, IBP7, and KPYM) might be involved in the pathogenesis of bronchial asthma. Compared with those in healthy adults, the expression levels of SLC25 A4, SVEP1, and KRT25 in the sera of asthmatic patients were up-regulated(P<0.05). Therefore, it is hypothesized that a variety of immune signaling pathways and differentially expressed proteins play a role in the pathogenesis of BA, which provides potential target information for the treatment of BA.
Adult ; Humans ; Proteomics ; Gene Ontology ; Proteins ; Disease Susceptibility ; Asthma/genetics*

As a stable genetic marker of human, blood group is expressed in a polymorphic system in the population. Blood group and pathogens mainly produce effects through the interaction between antigens and antibodies. On the one hand, they can promote pathogen colonization, invasion or evasion of host clearance mechanism, and on the other hand, they can make some hosts less susceptible to corresponding pathogens. By exploring the molecular mechanism between the blood group system and pathogenic microorganisms, it can provide a scientific basis for the treatment of human related diseases and the development of vaccines.
Blood Group Antigens/genetics* ; Disease Susceptibility ; Humans

Angiotensin-Converting Enzyme 2/metabolism* ; COVID-19/virology* ; Disease Susceptibility ; Humans ; SARS-CoV-2/pathogenicity* ; Species Specificity

BACKGROUND: World Health Organization (WHO) recommends that viral load ([VL) is a primary tool that clinicians and researchers have used to monitor patients on antiretroviral therapy (ART), an antiviral drug against retroviruses. Whereas, CD4 cell counts can only be used to monitor clinical response to ART in the absence of VL testing service. Therefore, this study is aimed to assess the level of immunological status and virological suppression, and identify associated factors among human immunodeficiency virus ([HIV)-infected adults who were taking antiretroviral drugs of combination regimen know as highly active antiretroviral therapy (HAART). METHODS: A hospital-based cross-sectional study was conducted at the University of Gondar comprehensive specialized referral hospital from February to April 2018. A total of 323 adult participants on HAART were selected using a systematic random sampling technique and enrolled into the study. Blood samples for viral load determination and CD4 cell count were collected. Binary logistic regression analysis was used to determine factors associated with immunologic status and virological suppression in HIV patients on HAART. Odds ratio with 95% CI was used to measure the strength of association. RESULTS: Virological suppression (VL level < 1000 copies/ml) was found in 82% (95% CI 77.7, 86.1) of study participants, and it has been associated with CD4 cell count between 350 and 499 cells/mm (adjusted odds ratio (AOR) = 2.56; 95% CI 1.14, 5.75) and > 499 cells/mm (AOR = 7.71; 95% CI 3.48, 17.09) at VL testing and current age > 45 years old (AOR = 5.99; 95% CI 2.12, 16.91). Similarly, favorable immunological status (≥ 400 cells/mm for male and ≥ 466 cells/mm for female) was observed in 52.9% (95% CI 47.4, 58.8) of the study participants. Baseline CD4 cell count of > 200 cells/mm, age at enrollment of 26 through 40 years old, and urban residence were significantly associated with favorable immunological status. CONCLUSION Though the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery.
Adult ; Aged ; Antiretroviral Therapy, Highly Active ; statistics & numerical data ; CD4 Lymphocyte Count ; Cross-Sectional Studies ; Disease Susceptibility ; immunology ; Ethiopia ; Female ; Humans ; Male ; Middle Aged ; Viral Load ; Young Adult

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Adult ; Aged ; Aged, 80 and over ; Aging ; genetics ; immunology ; Betacoronavirus ; CD4-Positive T-Lymphocytes ; metabolism ; Cell Lineage ; Chromatin Assembly and Disassembly ; Coronavirus Infections ; immunology ; Cytokine Release Syndrome ; etiology ; immunology ; Cytokines ; biosynthesis ; genetics ; Disease Susceptibility ; Flow Cytometry ; methods ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Rearrangement ; Humans ; Immune System ; cytology ; growth & development ; immunology ; Immunocompetence ; genetics ; Inflammation ; genetics ; immunology ; Mass Spectrometry ; methods ; Middle Aged ; Pandemics ; Pneumonia, Viral ; immunology ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcriptome ; Young Adult

BACKGROUND: The purpose of this study was to analyze the relationship between the gene mutation patterns by the GenoType MTBDRplus (MTBDRplus) assay and the phenotypic drug susceptibility test (pDST) results of isoniazid (INH) and prothionamide (Pto). METHODS: A total of 206 patients whose MTBDRplus assay results revealed katG or inhA mutations were enrolled in the study. The pDST results were compared to mutation patterns on the MTBDRplus assay. RESULTS: The katG and inhA mutations were identified in 68.0% and 35.0% of patients, respectively. Among the 134 isolated katG mutations, three (2.2%), 127 (94.8%) and 11 (8.2%) were phenotypically resistant to low-level INH, high-level INH, and Pto, respectively. Among the 66 isolated inhA mutations, 34 (51.5%), 18 (27.3%) and 21 (31.8%) were phenotypically resistant to low-level INH, high-level INH, and Pto, respectively. Of the 34 phenotypic Pto resistant isolates, 21 (61.8%), 11 (32.4%), and two (5.9%) had inhA, katG, and both gene mutations. CONCLUSION: It is noted that Pto may still be selected as one of the appropriate multidrug-resistant tuberculosis regimen, although inhA mutation is detected by the MTBDRplus assay until pDST confirms a Pto resistance. The reporting of detailed mutation patterns of the MTBDRplus assay may be important for clinical practice, rather than simply presenting resistance or susceptibility test results.
Biological Assay ; Disease Susceptibility ; Genotype ; Humans ; Isoniazid ; Mycobacterium ; Mycobacterium tuberculosis ; Prothionamide ; Research Design ; Tuberculosis, Multidrug-Resistant

BACKGROUND: As intravenous thrombolysis (IVT) has very restricted inclusion criteria, eligible patients of IVT constitute a very small proportion and studies about their mortality are rare. The long-term mortality in a patients with contraindication of ineligible patients of IVT still under the debate. So, we investigated the proportion of patients with contraindication of IVT and the short and long-term mortality of them in AIS on emergency department comparing with the long-term effect of IVT in patients with moderate-to-severe stroke.METHODS: Using acute stroke assessment indication registry & Health Insurance Review and Assessment Service database, a total of 5,407 patients with NIHSS≥5 were selected from a total of 169 acute stroke care hospital nationwide during October-December 2011 and March-June 2013. We divided AIS patients into two groups: 1) IVT group who received IVT within 4.5 hours, and 2) non-IVT group who did not receive the IVT because of contraindications. And we divided the subgroups according to the reason of contraindication of IVT. The 5-year survival rate of each group was assessed using Kaplan-Meyer survival analysis.RESULTS: Of the 5,407 patients, a total of 1,027 (19%) patients who received IVT using r-tPA within 4.5 h after onset. Compared with the IVT group, hazard ratios of non-IVT group were 1.33 at 3 months, 1.53 at 1 year and 1.47 at 5 years (p<.001). A total of 4,380 patients did not receive IVT because of the following contraindications to IVT. 1) Time restriction: 3,378 (77.1 %) patients were admitted after 4.5 h following stroke onset, and 144 (3.3%) patients failed to determine the stroke onset time. 2) Mild symptoms:137 (3.1%) patients had rapid improvement or mild stroke on emergency room, 3) Bleeding diathesis or non-adjustable hypertension: 53 (1.2%) patients showed a bleeding tendency or severe hypertension. Compared with the IVT group, the subgroups of non-IVT group showed consistently high mortality during short and long term follow up. Mild symptom and bleeding diathesis or non-adjustable hypertension subgroup in the non-IVT group consistently showed the higher mortality than time restriction subgroup during the short and long-term follow-up (log-rank p<.001). Patients who had rapid improvement or mild stroke on emergency department had the higher mortality than time restriction group in short and long term follow up.CONCLUSION: The AIS patients with rapid improvement or mild stroke on emergency room had higher mortality than ineligible patients of IVT due to time restriction during the short and long-term follow-up. A further management and special support on emergency department is needed for these patients with initially mild stroke and rapid improvement in AIS to reduce the poor outcome.
Disease Susceptibility ; Emergency Medical Services ; Emergency Service, Hospital ; Follow-Up Studies ; Hemorrhage ; Humans ; Hypertension ; Insurance, Health ; Mortality ; Prognosis ; Stroke ; Survival Rate ; Thrombolytic Therapy ; Tissue Plasminogen Activator

PURPOSE: Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease. MATERIALS AND METHODS: A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibswere subjected to a novel integrative “omic” approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger. A first-stepwhole-exome sequencing on tumor and normal tissue did not identify mutations in known driver genes. Building on the idea of a germline oligogenic origin of lung cancer, we performed whole-exome sequencing of DNA from patients' peripheral blood and their unaffected sibs. Finally, RNA-sequencing analysis in tumoral and matched non-tumoral tissues was carried out in order to investigate the clonal profile and the pathogenic role of the identified variants. RESULTS: Filtering for rare variants with Combined Annotation Dependent Depletion (CADD) > 25 and potentially damaging effect, we identified rare/private germline deleterious variants in 11 cancer-associated genes, none ofwhich, except one, sharedwith the healthy sib, pinpointing to a “private” oligogenic germline signature. Noteworthy, among these, two mutated genes, namely ACACA and DEPTOR, turned to be potential targets for therapy because related to known drivers, such as BRCA1 and EGFR. CONCLUSION: In the era of precision medicine, this report emphasizes the importance of an “omic” approach to uncover oligogenic germline signature underlying cancer development and to identify suitable therapeutic targets as well.
Carcinoma, Squamous Cell* ; Disease Susceptibility ; DNA ; Epithelial Cells* ; Exome ; Female* ; High-Throughput Nucleotide Sequencing ; Humans ; Lung Neoplasms ; Lung* ; Multifactorial Inheritance ; Precision Medicine* ; Smoking

PURPOSE: After the introduction of Haemophilus influenzae type b (Hib) vaccine in 1995 in Korea, it was included in the national immunization program in 2013. In the post-Hib vaccine era, some studies in other countries reported that invasive Hib disease affects adults, especially the elderly and immunocompromised persons, more often than it affects children. To evaluate disease susceptibility, quantitative and qualitative analysis of anti-polyribosylribitol phosphate (PRP) antibodies were carried out in Korean adults aged 20 to 85 years. METHODS: Sera were collected from 39 healthy adults (20 to 50 years of age) and from 30 elderly adults (75 to 85 years of age) who did not have immune-compromising conditions. The concentration of anti-PRP immunoglobulin G (IgG) and serum bactericidal indices (SBIs) were measured by enzyme-linked immunosorbent assay and serum bactericidal assay. RESULTS: Geometric mean concentrations of anti-PRP IgG and geometric mean SBIs were 0.88 µg/mL (95% confidence interval [CI], 0.17 to 3.85) and 354 (95% CI, 50 to 2,499) in young adults and 1.67 µg/mL (95% CI, 0.53 to 5.24) and 449 (95% CI, 146 to 1,376) in elderly adults, respectively. When the threshold of seropositivity for anti-PRP IgG was applied as 0.15 or 1.0 µg/mL, which is the protective antibody level in children, seropositive rates were 87.2% or 53.8% in young adults and 100% or 60% in elderly adults. The seropositivity rates of the SBI (SBI ≥4) were 82.1% and 100% in the groups, respectively. CONCLUSIONS: Most subjects in the adult and elderly adult groups display immunity to Hib based on quantitative and qualitative antibody levels, but not all. Because high immunization and low Hib circulation rates may reduce the natural Hib immunity in the population, monitoring Hib immunity as well as disease are needed continuously.
Adult* ; Aged ; Antibodies* ; Child ; Disease Susceptibility ; Enzyme-Linked Immunosorbent Assay ; Haemophilus influenzae type b* ; Haemophilus influenzae* ; Haemophilus* ; Humans ; Immunization ; Immunization Programs ; Immunoglobulin G ; Korea ; Young Adult

The proposal that diabetes plays a role in the development of heart failure is supported by the increased risk associated with this disease, even after correcting for all other known risk factors. However, the precise mechanisms contributing to the condition referred to as diabetic cardiomyopathy have remained elusive, as does defining the disease itself. Decades of study have defined numerous potential factors that each contribute to disease susceptibility, progression, and severity. Many recent detailed reviews have been published on mechanisms involving insulin resistance, dysregulation of microRNAs, and increased reactive oxygen species, as well as causes including both modifiable and non-modifiable risk factors. As such, the focus of the current review is to highlight aspects of each of these topics and to provide specific examples of recent advances in each area.
Diabetic Cardiomyopathies ; Disease Susceptibility ; Energy Metabolism ; Heart Failure ; Insulin Resistance ; Metabolic Diseases ; MicroRNAs ; Mitochondria, Heart ; Reactive Oxygen Species ; Risk Factors ; Stress, Physiological