Global distribution of zoonotic digenetic trematodes: a scoping review.

BACKGROUND: Digenetic trematodes, including blood flukes, intestinal flukes, liver flukes, lung flukes, and pancreatic flukes, are highly diverse and distributed widely. They affect at least 200 million people worldwide, so better understanding of their global distribution and prevalence are crucial for controlling and preventing human trematodiosis. Hence, this scoping review aims to conduct a comprehensive investigation on the spatio-temporal distribution and epidemiology of some important zoonotic digenetic trematodes. METHODS: We conducted a scoping review by searching PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure, and Wanfang databases for articles, reviews, and case reports of zoonotic digenetic trematodes, without any restrictions on the year of publication. We followed the inclusion and exclusion criteria to identify relevant studies. And relevant information of the identified studies were collected and summarized. RESULTS: We identified a total of 470 articles that met the inclusion criteria and were included in the review finally. Our analysis revealed the prevalence and global distribution of species in Schistosoma, Echinostoma, Isthmiophora, Echinochasmus, Paragonimus, Opisthorchiidae, Fasciolidae, Heterophyidae, and Eurytrema. Although some flukes are distributed worldwide, developing countries in Asia and Africa are still the most prevalent areas. Furthermore, there were some overlaps between the distribution of zoonotic digenetic trematodes from the same genus, and the prevalence of some zoonotic digenetic trematodes was not entirely consistent with their global distribution. The temporal disparities in zoonotic digenetic trematodes may attribute to the environmental changes. The gaps in our knowledge of the epidemiology and control of zoonotic digenetic trematodes indicate the need for large cohort studies in most countries. CONCLUSIONS: This review provides important insights into the prevalence and global distribution of some zoonotic digenetic trematodes, firstly reveals spatio-temporal disparities in these digenetic trematodes. Countries with higher prevalence rate could be potential sources of transmitting diseases to other areas and are threat for possible outbreaks in the future. Therefore, continued global efforts to control and prevent human trematodiosis, and more international collaborations are necessary in the future.

Graves' disease and the risk of five autoimmune diseases: A Mendelian randomization and colocalization study.

BACKGROUND: Epidemiological studies have consistently demonstrated a high prevalence of concurrent autoimmune diseases in individuals with Graves' disease (GD). OBJECTIVE: The objective of this study is to establish a causal association between GD and autoimmune diseases. METHODS: We employed a two-sample Mendelian randomization (MR) to infer a causal association between GD and five autoimmune diseases, namely rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Crohn's disease (CD), ulcerative colitis (UC), and amyotrophic lateral sclerosis (ALS), in the East Asian and European population. Genetic correlations were explored through linkage disequilibrium score regression analysis (LDSC). Finally, colocalization analyses were performed to investigate possible genetic foundations. RESULTS: Bidirectional MR analysis indicated that genetically predicted GD increased the risk of RA (Odds Ratio (OR): 1.34, 95 % Confidence Interval (CI): 1.21 to 1.47, P < 0.001) and SLE (OR: 1.21, 95%CI: 1.08 to 1.35, P < 0.001) in the East Asian population. In contrast, we found that genetically predicted RA (OR: 1.14, 95%CI: 1.05 to 1.24, P = 0.002) and SLE (OR: 1.10, 95%CI: 1.03 to 1.17, P = 0.003) were associated with a higher risk of GD. The results have been partially validated in European cohorts. Colocalization analysis suggested the potential existence of shared causal variants between GD and other autoimmune diseases. In particular, gene ARID5B may play an important role in the incidence of autoimmune diseases. CONCLUSION: This study has confirmed that GD was associated with RA and SLE and found a possible key gene ARID5B. It may be necessary to strengthen detection to prevent the occurrence of comorbidities in clinical practice.

Recognition of the inducible, secretory small protein OsSSP1 by the membrane receptor OsSSR1 and the co-receptor OsBAK1 confers rice resistance to the blast fungus.

The plant apoplast, which serves as the frontline battleground for long-term host-pathogen interactions, harbors a wealth of disease resistance resources. However, the identification of the disease resistance proteins in the apoplast is relatively lacking. In this study, we identified and characterized the rice secretory protein OsSSP1 (Oryza sativa secretory small protein 1). OsSSP1 can be secreted into the plant apoplast, and either in vitro treatment of recombinant OsSSP1 or overexpression of OsSSP1 in rice could trigger plant immune response. The expression of OsSSP1 is suppressed significantly during Magnaporthe oryzae infection in the susceptible rice variety Taibei 309, and OsSSP1-overexpressing lines all show strong resistance to M. oryzae. Combining the knockout and overexpression results, we found that OsSSP1 positively regulates plant immunity in response to fungal infection. Moreover, the recognition and immune response triggered by OsSSP1 depend on an uncharacterized transmembrane OsSSR1 (secretory small protein receptor 1) and the key co-receptor OsBAK1, since most of the induced immune response and resistance are lost in the absence of OsSSR1 or OsBAK1. Intriguingly, the OsSSP1 protein is relatively stable and can still induce plant resistance after 1 week of storage in the open environment, and exogenous OsSSP1 treatment for a 2-week period did not affect rice yield. Collectively, our study reveals that OsSSP1 can be secreted into the apoplast and percepted by OsSSR1 and OsBAK1 during fungal infection, thereby triggering the immune response to enhance plant resistance to M. oryzae. These findings provide novel resources and potential strategies for crop breeding and disease control.

Corrigendum: Identification and validation of immune-related methylation clusters for predicting immune activity and prognosis in breast cancer.

[This corrects the article DOI: 10.3389/fimmu.2021.704557.].

Therapeutic effect of ustekinumab on patients with extra-intestinal manifestations of Crohn's disease.

INTRODUCTION: Ustekinumab serves as an important alternative option for patients with various extraintestinal manifestations (EIMs), which leads to poor quality of life and heavy burden of care. Therefore, a comprehensive review summarizing the efficacy and safety of ustekinumab in patients with CDassociated EIMs is needed to provide reference for clinical medication and help with the appliance of precision medicine. AREAS COVERED: In this review, we collected and summarized the efficacy and paradoxical side effects of ustekinumab in patients with CDassociated EIMs including musculoskeletal, cutaneous, ocular, and hepatobiliary manifestations. This literature review was performed using PubMed to identify and collect relevant studies published in English. EXPERT OPINION: The effectiveness of ustekinumab on patients with CDassociated EIMs is mainly reflected in musculoskeletal and cutaneous manifestations compared to ocular or hepatobiliary manifestations. Relevant data from large scale cohort studies and prospective randomized trials are needed to further demonstrate the efficacy and safety of ustekinumab in patients with multiple EIMs.

Identification and Validation of Immune-Related Methylation Clusters for Predicting Immune Activity and Prognosis in Breast Cancer.

The role of DNA methylation of breast cancer-infiltrating immune cells has not been fully explored. We conducted a cohort-based retrospective study analyzing the genome-wide immune-related DNA methylation of 1057 breast cancer patients from the TCGA cohort and GSE72308 cohort. Based on patients' overall survival (OS), a prognostic risk score system using 18 immune-related methylation genes (IRMGs) was established and further validated in an independent cohort. Kaplan-Meier analysis showed a clear separation of OS between the low- and high-risk groups. Patients in the low-risk group had a higher immune score and stromal score compared with the high-risk group. Moreover, the characteristics based on 18-IRMGs signature were related to the tumor immune microenvironment and affected the abundance of tumor-infiltrating immune cells. Consistently, the 18-IRMGs signatures showed similar influences on immune modulation and survival in another external validation cohort (GSE72308). In conclusion, the proposed 18-IRMGs signature could be a potential marker for breast cancer prognostication.

Identification and validation of a combined hypoxia and immune index for triple-negative breast cancer.

The interaction between hypoxia and immune status has been confirmed in various cancer settings, and corresponding treatments have been investigated. However, reliable biomarkers are needed for individual treatment, so we sought to develop a novel scoring system based on hypoxia and immune status. Prognostic hypoxia-immune status-related signatures of patients with triple-negative breast cancer (TNBC) were identified in The Cancer Genome Atlas (TCGA) (N = 158), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (N = 297), and GSE58812 (N = 107). LASSO Cox regression was used for model construction. Hypoxia and immune status expression profiles were analyzed, and infiltrating immune cells were compared. Quantitative real-time PCR (qRT-PCR) was used for validation in the Sun Yat-sen University Cancer Center (SYSUCC) cohort, and immunofluorescence was applied for the detection of hypoxia and immune markers in cancer tissues. Ten cross-cohort prognostic hypoxia-immune signatures were included to construct the comprehensive index of hypoxia and immune (CIHI) in the METABRIC cohort. Two subgroups of patients with distinct hypoxia-immune status conditions were identified using CIHI: hypoxiahigh /immunelow and hypoxialow /immunehigh , with a significantly better overall survival (OS) rate in the latter (P < 0.01). The prognostic value of CIHI was further validated in the TCGA, GSE58812, and SYSUCC cohorts (P < 0.01). Hypoxia-immune signatures were significantly differentially expressed between the two groups, and more active immune responses were observed in the hypoxialow /immunehigh group. Cytotoxic lymphocytes were inversely correlated with CIHI in silico. Differentially expressed CA-IX and stromal PD-L1 were detected between subgroups of the SYSUCC cohort. A hypoxia-immune-based cross-cohort classifier for predicting prognosis was developed and validated, which may guide hypoxia modifier treatment and immunotherapy for TNBC.

Development and validation of a prognostic classifier based on HIF-1 signaling for hepatocellular carcinoma.

HIF-1 (hypoxia-inducible factor 1) signaling played a vital role in HCC (hepatocellular carcinoma) prognosis. We aimed to establish an accurate risk scoring system for HCC prognosis prediction and treatment guidance. 424 samples from TCGA (The Cancer Genome Atlas) and 445 samples from GSE14520 dataset were included as the derivation and validation cohort, respectively. In the derivation cohort, prognostic relevant signatures were selected from sixteen HIF-1 related genes and LASSO regression was adopted for model construction. Tumor-infiltrating immune cells were calculated using CIBERSORT algorithm. HIF-1 signaling significantly increased in HCC samples compared with normal tissues. Scoring system based on SLC2A1, ENO1, LDHA and GAPDH exhibited a continuous predictive ability for OS (overall survival) in HCC patients. PCA and t-SNE analysis confirmed a reliable clustering ability of risk score in both cohorts. Patients were classified into high-risk and low-risk groups and the survival outcomes between the two groups showed significant differences. In the derivation cohort, Cox regression indicated the scoring system was an independent predictor for OS, which was validated in the validation cohort. Different infiltrating immune cells fraction and immune scores were also observed in different groups. Herein, a novel integrated scoring system was developed based on HIF-1 related genes, which would be conducive to the precise treatment of patients.

Adenocarcinoma with mixed subtypes is a rare but aggressive histologic subtype in colorectal cancer.

BACKGROUND: Although numerous studies have investigated the clinicopathologic and prognostic relevance of mucinous adenocarcinoma (MAC) and signet-ring cell carcinoma (SRCC) compared with classic adenocarcinoma (CA), little is known about the prognosis of adenocarcinoma with mixed subtypes (AM) and the differences among these four subtypes. METHODS: The statistics of colorectal cancer registered in the Surveillance, Epidemiology and End Results (SEER) database were retrieved and analyzed. We also compared the clinicopathologic and prognostic relevance between CA, SRCC, MAC, and AM. RESULTS: The frequencies of these four subtypes were 69.9% (CA, n = 15,812), 25.1% (MAC, n = 5689), 3.6% (SRCC, n = 814) and 1.4% (AM, n = 321), respectively. All of MAC, SRCC, and AM were significantly related with aggressive features. Only SRCC and AM were identified as independent poor prognostic markers for overall survival by multivariate analysis. The aggressiveness of AM was between MAC and SRCC according to the clinicopathologic associations. The prognosis of AM was significantly worse than MAC but comparable with SRCC. CONCLUSIONS: We confirmed the clinicopathologic relevance with aggressive features of MAC and SRCC, as well as poor prognostic relevance of SRCC by analyzing a large study population data set. Furthermore, we identified AM as a rare but aggressive histologic subtype in colorectal cancer, to which particular attention should be given in clinical practice.

Genetic variants of interleukin 17A are functionally associated with increased risk of age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly populations worldwide. Inflammation, among many factors, has been suggested to play an important role in AMD pathogenesis. Interleukin 17 (IL-17) is a proinflammatory cytokine that has been implicated in the pathogenesis of various autoimmune diseases. In the current study, we examined two single nucleotide polymorphisms (SNPs), rs2275913G/A and rs3748067C/T, in the IL-17A gene between AMD patients and healthy controls. Results showed that rs2275913AA genotype and rs3748067TT genotype were associated with increased susceptibility to AMD (hazard ratio [HR], 1.75; 95 % confidence interval [CI], 1.07 to 3.02; P=0.023, and HR, 2.12; 95 % CI, 1.26 to 4.01; P=0.004; data were adjusted for age and sex). Next, we investigated the functional relevance of the two SNPs. In vitro stimulated peripheral blood mononuclear cells (PBMCs) from subjects possessing the rs2275913AA genotype produced significantly more IL-17 than those with the GG genotype. However, PBMCs with rs3748067TT genotype revealed significantly higher IL-17 production than those with rs3748067CC genotype only in AMD patients but not in controls. These data indicate IL-17A polymorphisms are associated with increased risk of AMD probably by affecting gene expression.