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Journal of the International AIDS... Aug 2019Hepatitis C virus (HCV) is a major public health threat. Although the recent availability of highly effective directly acting antivirals created optimism towards HCV...
INTRODUCTION
Hepatitis C virus (HCV) is a major public health threat. Although the recent availability of highly effective directly acting antivirals created optimism towards HCV elimination, there is ongoing transmission of HCV in men who have sex with men (MSM). We here report current epidemiological trends and synthesise evidence on behavioural, network, cellular and molecular host factors associated with sexual transmission of HCV, in particular the role of HIV-1 co-infection. We discuss prevention opportunities focusing on the potential of HCV treatment.
METHODS
We searched MEDLINE, fact sheets from health professional bodies and conference abstracts using appropriate keywords to identify and select relevant reports.
RESULTS AND DISCUSSION
Recent studies strongly suggest that HCV is transmitted via sexual contact in HIV-positive MSM and more recently in HIV-negative MSM eligible for or on pre-exposure prophylaxis. The reinfection risk following clearance is about 10 times the risk of primary infection. International connectedness of MSM transmission networks might contribute to ongoing reinfection. Some of these networks might overlap with networks of people who inject drugs. Although, the precise mechanisms facilitating sexual transmission remain unclear, damage to the mucosal barrier in the rectum could increase susceptibility. Mucosal dendritic cell subsets could increase HCV susceptibility by retaining HCV and transmitting the virus to other cells, allowing egress into blood and liver. Early identification of new HCV infections is important to prevent onward transmission, but early diagnosis of acute HCV infection and prompt treatment is hampered by the slow rate of HCV antibody seroconversion, which in rare cases may take more than a year. Novel tests such as testing for HCV core antigen might facilitate early diagnosis.
CONCLUSIONS
High-risk sexual behaviour, network characteristics, co-infection with sexually transmitted infections like HIV-1 and other concomitant bacterial and viral sexually transmitted infections are important factors that lead to HCV spread. Targeted and combined prevention efforts including effective behavioural interventions and scale-up of HCV testing and treatment are required to halt HCV transmission in MSM.
Topics: Coinfection; HIV Infections; HIV-1; Hepacivirus; Hepatitis C; Hepatitis C Antibodies; Humans; Male; Sexual and Gender Minorities; Sexually Transmitted Diseases
PubMed: 31468692
DOI: 10.1002/jia2.25348 -
World Journal of Gastroenterology Jul 2019Hepatocellular carcinoma (HCC) has been revealed as the second most common cause of cancer-related deaths worldwide. The introduction of cell-based immunotherapy,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatocellular carcinoma (HCC) has been revealed as the second most common cause of cancer-related deaths worldwide. The introduction of cell-based immunotherapy, including dendritic cells (DCs) and cytokine-induced killer cells (CIKs), has brought HCC patients an effective benefit. However, the efficacy and necessity of cellular immunotherapy after different interventional therapy remains to be further explored.
AIM
To investigate the efficacy of cellular immunotherapy, involving DCs and CIKs, combined with different conventional treatments of HCC.
METHODS
We performed a literature search on PubMed and Web of Science up to February 15, 2019. Long-term efficacy (overall survival and recurrence) and short-term adverse effects were investigated to assess the effectiveness of immunotherapy with DCs and/or CIKs. Review Manager 5.3 was used to perform the analysis.
RESULTS
A total of 22 studies involving 3756 patients selected by eligibility inclusion criteria were forwarded for meta-analysis. Combined with the conventional clinical treatment, immunotherapy with DCs and/or CIKs was demonstrated to significantly improve overall survival at 6 mo [risk ratio (RR) = 1.07; 95% confidence interval (CI): 1.01-1.13, = 0.02], 1 year (RR = 1.12; 95%CI: 1.07-1.17, < 0.00001), 3 years (RR = 1.23; 95%CI: 1.15-1.31, < 0.00001) and 5 years (RR = 1.26; 95%CI: 1.15-1.37, < 0.00001). Recurrence rate was significantly reduced by cellular immunotherapy at 6 mo (RR = 0.50; 95%CI: 0.36-0.69, < 0.0001) and 1 year (RR = 0.82; 95%CI: 0.75-0.89, < 0.00001). Adverse effect assessment addressed that immunotherapy with DCs and/or CIKs was accepted as a safe, feasible treatment.
CONCLUSION
Combination immunotherapy with DCs, CIKs and DC/CIK with various routine treatments for HCC was evidently suggested to improve patients' prognosis by increasing overall survival and reducing cancer recurrence.
Topics: Carcinoma, Hepatocellular; Clinical Trials as Topic; Combined Modality Therapy; Cytokine-Induced Killer Cells; Dendritic Cells; Feasibility Studies; Humans; Immunotherapy, Adoptive; Liver Neoplasms; Neoplasm Recurrence, Local; Prognosis; Survival Analysis; Treatment Outcome
PubMed: 31367163
DOI: 10.3748/wjg.v25.i27.3649 -
F1000Research 2018Hidradenitis suppurativa (HS) is a chronic inflammatory disease with significant morbidity and impact on quality of life. Our understanding of the pathophysiology is...
Hidradenitis suppurativa (HS) is a chronic inflammatory disease with significant morbidity and impact on quality of life. Our understanding of the pathophysiology is incomplete, impairing efforts to develop novel therapeutic targets. Immunohistochemistry studies have produced conflicting results and no systematic evaluation of study methods and results has been undertaken to date. This systematic review aimed to collate and describe all reports of immunohistochemical staining in HS. This systematic review was registered with PROSPERO and conducted in line with the PRISMA reporting guidelines. Potential bias was assessed using the NIH Criteria and antibodies used across various studies were tabulated and compared. : A total of 22 articles were identified describing results from 494 HS patients and 168 controls. 87 unique immunohistochemical targets were identified. The overall quality of studies was sub-optimal with staining intensity confounded by active treatment. Conflicting data was identified and able to be reconciled through critical evaluation of the study methodology. : Keratinocyte hyperplasia with loss of cytokeratin markers co-localizes with inflammation comprising of dendritic Cells, T-lymphocytes and macrophages, which are known to play central roles in inflammation in HS. Primary follicular occlusion as a pathogenic paradigm and the principal driver of HS is unclear based upon the findings of this review. Inflammation as a primary driver of disease with secondary hyperkeratosis and follicular occlusion is more consistent with the current published data.
Topics: Animals; Desmocollins; Female; Hidradenitis Suppurativa; Humans; Hyperplasia; Inflammation; Keratosis; Male; Membrane Glycoproteins; Mice; Quality of Life; Ubiquitin-Protein Ligases
PubMed: 31281635
DOI: 10.12688/f1000research.17268.2 -
Experimental Gerontology Sep 2019Immunosenescence contributes to a decreased capacity of the immune system to respond effectively to infections or vaccines in the elderly. The full extent of the...
Immunosenescence contributes to a decreased capacity of the immune system to respond effectively to infections or vaccines in the elderly. The full extent of the biological changes that lead to immunosenescence are unknown, but numerous cell types involved in innate and adaptive immunity exhibit altered phenotypes and function as a result of aging. These manifestations of immunosenescence at the cellular level are mediated by dysregulation at the genetic level, and changes throughout the immune system are, in turn, propagated by numerous cellular interactions. Environmental factors, such as nutrition, also exert significant influence on the immune system during aging. While the mechanisms that govern the onset of immunosenescence are complex, systems biology approaches allow for the identification of individual contributions from each component within the system as a whole. Although there is still much to learn regarding immunosenescence, systems-level studies of vaccine responses have been highly informative and will guide the development of new vaccine candidates, novel adjuvant formulations, and immunotherapeutic drugs to improve vaccine responses among the aging population.
Topics: Adaptive Immunity; Aged; B-Lymphocytes; Dendritic Cells; Humans; Immune System; Immunity, Innate; Immunosenescence; Systems Biology; T-Lymphocytes; Vaccination
PubMed: 31201918
DOI: 10.1016/j.exger.2019.110632 -
Schizophrenia Bulletin Feb 2020Changed synapse density has been suggested to be involved in the altered brain connectivity underlying schizophrenia (SCZ) pathology. However, postmortem studies... (Meta-Analysis)
Meta-Analysis
Changed synapse density has been suggested to be involved in the altered brain connectivity underlying schizophrenia (SCZ) pathology. However, postmortem studies addressing this topic are heterogeneous and it is not known whether changes are restricted to specific brain regions. Using meta-analysis, we systematically and quantitatively reviewed literature on the density of postsynaptic elements in postmortem brain tissue of patients with SCZ compared to healthy controls. We included 3 outcome measurements for postsynaptic elements: dendritic spine density (DSD), postsynaptic density (PSD) number, and PSD protein expression levels. Random-effects meta-analysis (31 studies) revealed an overall decrease in density of postsynaptic elements in SCZ (Hedges's g: -0.33; 95% CI: -0.60 to -0.05; P = .020). Subgroup analyses showed reduction of postsynaptic elements in cortical but not subcortical tissues (Hedges's g: -0.44; 95% CI: -0.76 to -0.12; P = .008, Hedges's g: -0.11; 95% CI: -0.54 to 0.35; P = .671) and specifically a decrease for the outcome measure DSD (Hedges's g: -0.81; 95% CI: -1.37 to -0.26; P = .004). Further exploratory analyses showed a significant decrease of postsynaptic elements in the prefrontal cortex and cortical layer 3. In all analyses, substantial heterogeneity was present. Meta-regression analyses showed no influence of age, sex, postmortem interval, or brain bank on the effect size. This meta-analysis shows a region-specific decrease in the density of postsynaptic elements in SCZ. This phenotype provides an important cellular hallmark for future preclinical and neuropathological research in order to increase our understanding of brain dysconnectivity in SCZ.
Topics: Brain; Humans; Schizophrenia; Synapses
PubMed: 31192350
DOI: 10.1093/schbul/sbz060 -
International Journal of Environmental... Apr 2019: This study was conducted to identify the association between polymorphism in with the susceptibility of severe dengue. : A comprehensive search was conducted to... (Meta-Analysis)
Meta-Analysis
: This study was conducted to identify the association between polymorphism in with the susceptibility of severe dengue. : A comprehensive search was conducted to identify all eligible papers in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Google Scholar. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were used to assess the association. Subgroup analyses were performed by ethnicity. Sensitivity analyses were performed through employing different statistical models (fixed versus random effect model). : A total of nine papers and 12 studies, with 1520 severe dengue and 1496 clinical dengue infection were included. The overall meta-analysis revealed significant associations between rs4804803 and severe dengue under the recession ( versus : OR = 0.44, 95%CI, 0.23-0.82) and a codominant model ( versus : OR = 0.43, 95%CI, 0.23-0.81), but sensitivity analysis indicated that the significant pooled ORs were not robust. The subgroup analysis suggested that the carrier of G in was a risk factor for severe dengue under dominant ( versus : OR = 1.86,95%CI, 1.01-3.45), superdominant ( versus : OR = 1.81,95%CI, 1.02-3.21) and a codominant ( versus : OR=1.82,95%CI, 1.02-3.26) models in Asians, while it was a protective factor for severe dengue in South-central Americans under recessive ( versus : OR = 0.27,95%CI, 0.10-0.70) and codominant ( versus : OR=0.24,95%CI, 0.09-0.64) models. The results from subgroup analysis were robust. : Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin () promoter-336G/A () polymorphism is association with severe dengue, and it acts in different directions for Asians and South-central Americans.
Topics: Asian People; Cell Adhesion Molecules; China; Genetic Predisposition to Disease; Humans; Lectins, C-Type; Odds Ratio; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Receptors, Cell Surface; Risk Factors; Severe Dengue; South America
PubMed: 31027310
DOI: 10.3390/ijerph16081475 -
F1000Research 2018The pathogenesis of hidradenitis suppurativa (HS) remains unclear. In order to develop effective treatment strategies, a deeper understanding of pathophysiology is...
The pathogenesis of hidradenitis suppurativa (HS) remains unclear. In order to develop effective treatment strategies, a deeper understanding of pathophysiology is needed. This is impaired by multiple small studies with inconsistent methodologies and the impact of co-occurring pro-inflammatory conditions such as smoking and obesity. This systematic review aimed to collate all published reports of cytokine studies in tissue, blood, serum and exudate. It was registered with PROSPERO (Registration number CRD42018104664) performed in line with the PRISMA checklist. 19 studies were identified comprising 564 individual HS patients and 198 control patients examining 81 discrete cytokines. Methodology was highly varied and the quality of studies was generally low. There was a large degree of variance between the measured levels of cytokines. 78.2% of cytokines demonstrated heterogeneity by the chi-squared test for homogeneity and hence meta-analysis was not deemed appropriate. However, a strong and significant IL-17 signalling component was identified. Cytokines consistently elevated in lesional, peri-lesional and unaffected tissue are identified and discussed. Areas for further investigation include the role of dendritic cells in HS; the contribution of obesity, smoking, diabetes and the microbiome to cytokine profiles in HS; and examining the natural history of this disease through longitudinal measurements of cytokines over time.
Topics: Adult; Cytokines; Demography; Female; Hidradenitis Suppurativa; Humans; Inflammation Mediators; Male; Middle Aged; Models, Biological; Publication Bias; Young Adult
PubMed: 30828428
DOI: 10.12688/f1000research.17267.1 -
British Journal of Cancer Apr 2019Various immune cells have been suggested as prognostic markers for cancer patients. In this article, we present a systematic review and meta-analysis of studies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Various immune cells have been suggested as prognostic markers for cancer patients. In this article, we present a systematic review and meta-analysis of studies assessing the prognostic value of tissue-infiltrating immune cells in oral cancer and discuss the reporting quality of these studies.
METHODS
We performed a systematic literature search and included studies using immunohistochemistry and survival analysis to assess the prognostic value of tumour-infiltrating T cells, B cells, macrophages, dendritic cells, mast cells and natural killer cells in oral cancer. We performed meta-analysis of studies providing necessary statistical data and investigated the studies' adherence to the REporting recommendations for tumour MARKer prognostic studies (REMARK) guidelines.
RESULTS
Of the 1960 articles identified, 33 were eligible for this systematic review and 8 were included in the meta-analysis. CD163+ M2 macrophages and CD57+ natural killer cells were the most promising predictors of survival in oral cancer patients. Many studies lacked important information on their design and conduct.
CONCLUSION
Deficiencies in the reporting of study design and conduct make it difficult to draw reliable conclusions about the suggested markers. The prognostic value of CD163+ M2 macrophages and CD57+ natural killer cells should be validated in large, standardised studies.
Topics: B-Lymphocytes; Dendritic Cells; Humans; Killer Cells, Natural; Lymphocytes, Tumor-Infiltrating; Macrophages; Mast Cells; Mouth Neoplasms; Prognosis; Squamous Cell Carcinoma of Head and Neck; T-Lymphocytes
PubMed: 30808992
DOI: 10.1038/s41416-019-0409-6 -
PloS One 2019TIM-family proteins are expressed on different immune cells such as dendritic cells, macrophages, type 1 and 2 T helper (Th) cells. Therefore, they have the ability to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
TIM-family proteins are expressed on different immune cells such as dendritic cells, macrophages, type 1 and 2 T helper (Th) cells. Therefore, they have the ability to contribute to the various intracellular signals and immune responses, importantly the regulation of Th1 and Th17 cell differentiation, which plays a remarked role in fight against inflammatory and autoimmune diseases. Association of TIM family gene polymorphisms with rheumatoid arthritis (RA) has been frequently investigated. The findings however are not entirely consistent. Therefore, we carried out the present meta-analysis to examine the association between RA and the following TIM family gene polymorphisms: rs41297579, rs1036199, rs10515746, and rs7700944.
METHODS
A systematic search of Scopus, PubMed, and Web of Science databases was conducted through December 2018. Combined odds ratios (OR) with their corresponding 95% confidence intervals (CI) were calculated under different possible genetic models.
RESULTS
A total of eight case-control studies were included in the present meta-analysis. The results demonstrated significant association of RA with TIM-3 rs1036199 polymorphism under dominant (OR, 1.93, 95% CI, 1.43-2.61) and allelic models (OR, 1.74, 95% CI, 1.31-2.30). None of the other examined polymorphisms indicated significant association with RA.
CONCLUSIONS
The present meta-analysis revealed that the TIM-3 rs1036199 polymorphism might confer susceptibility to RA. Further studies are required to reassert our findings.
Topics: Arthritis, Rheumatoid; Genetic Association Studies; Genetic Predisposition to Disease; Hepatitis A Virus Cellular Receptor 1; Hepatitis A Virus Cellular Receptor 2; Humans; Membrane Proteins; Polymorphism, Single Nucleotide
PubMed: 30730912
DOI: 10.1371/journal.pone.0211146 -
Frontiers in Immunology 2018Chemerin [ [retinoic acid receptor responder 2], TIG2 [tazarotene induced gene 2 (TIG2)]] is a multifunctional cytokine initially described in skin cultures upon...
Chemerin [ [retinoic acid receptor responder 2], TIG2 [tazarotene induced gene 2 (TIG2)]] is a multifunctional cytokine initially described in skin cultures upon exposure to the synthetic retinoid tazarotene. Its secreted pro-form, prochemerin, is widely expressed, found systemically, and is readily converted into active chemerin by various proteases. Subsequent studies elucidated major roles of chemerin as both a leukocyte chemoattractant as well as an adipokine. Chemerin's main chemotactic receptor, the G-protein coupled receptor CMKLR1, is expressed on macrophages, dendritic, and NK cells. With respect to its role in immunology, chemerin mediates trafficking of these cells to sites of inflammation along its concentration gradient, and likely helps coordinate early responses, as it has been shown to have antimicrobial and angiogenic properties, as well. Recently, there has been mounting evidence that chemerin is an important factor in various cancers. As with its role in immune responses-where it can act as both a pro- and anti-inflammatory mediator-the potential functions or correlations chemerin has in or with cancer appears to be context dependent. Most studies, however, suggest a downregulation or loss of chemerin/ in malignancies compared to the normal tissue counterparts. Here, we perform a comprehensive review of the literature to date and summarize relevant findings in order to better define the roles of chemerin in the setting of the tumor microenvironment and tumor immune responses, with an ultimate focus on the potential for therapeutic intervention.
Topics: Animals; Chemokines; Dendritic Cells; Down-Regulation; Gene Expression Regulation, Neoplastic; Humans; Intercellular Signaling Peptides and Proteins; Killer Cells, Natural; Macrophages; Neoplasm Proteins; Neoplasms; Receptors, Chemokine
PubMed: 30555465
DOI: 10.3389/fimmu.2018.02772