Characterization of SUSD3 as a novel prognostic biomarker and therapeutic target for breast cancer.

BACKGROUND: Breast cancer (BC) remains a significant global health challenge, contributing substantially to cancer-related deaths worldwide. Its prevalence and associated death rates remain alarmingly high, highlighting the persistent public health burden. The objective of this study was to systematically examine the involvement of SUSD3 (Sushi Domain-Containing 3) in BC, highlighting its crucial role in the pathogenesis and progression of this disease. METHODS: BC-related gene microarray data, along with corresponding clinicopathological information, were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Leveraging TIMER and HPA databases, we conducted comparative analyses to evaluate SUSD3 expression in BC. We then analyzed the association between SUSD3 and clinical traits, as well as the prognostic value of SUSD3. SUSD3-related differential expression genes (DEGs) were sent for analysis utilizing GO, KEGG, and GSEA. We utilized SUSD3 mRNA expression to assess immune cells' scores in BC tissues calculated by single-sample enrichment analyses based on "CIBERSORT" R package. Drug sensitivity analysis was used to screen potential drugs sensitive to SUSD3. R software was used for statistical analyses and graphical representation of the data. RESULTS: Our findings confirmed a significant upregulation of SUSD3 expression in BC, which correlated with a favorable prognosis. Clinical correlation analysis further emphasized the strong association between SUSD3 expression and key clinical parameters like estrogen receptor (ER) status, progesterone receptor (PR) status, stage, and T classification in breast cancer. Univariate and multivariate Cox regression analyses showed that SUSD3 could be used as an independent prognostic factor for BC. Differentially expressed genes (DEGs) co-expressed with SUSD3 were significantly associated with various biological processes, such as the cell cycle, DNA replication, p53 signaling pathway, cancer-related pathways, and Wnt signaling pathway, as indicated by gene set enrichment analysis (GSEA). Furthermore, our analysis demonstrated that SUSD3 generally exhibited negative associations with immune modulators. Drug sensitivity analysis revealed positive correlations between SUSD3 and the efficacy of Fulvestrant, Raloxifene, and Fluphenazine. CONCLUSION: The research emphasizes the significance of SUSD3 as a potential marker for BC, providing insights into the underlying molecular mechanisms implicated in tumorigenesis. SUSD3 holds promise in helping the classification of breast cancer pathological groups, predicting prognosis, and facilitating targeted therapy.

Characteristic of decreased bacterial diversity in psoriasis / [Característica da diminuição da diversidade bacteriana na psoríase]

Disturbance of commensal intestinal microbiota is related to chronic inflammatory dermatosis. We analyzed the diversity of the gut microbiota to characterize the biological variation of psoriasis (Ps). Significant differences of gut microbiome profiles were revealed in murine model with psoriasis by sequencing 16S rRNA V3-V4 variable region. Group comparisons included the imiquimod cream (IMQ group, n=8), the imiquimod cream and antibiotics (ATB) (PC+IMQ group, n=8) and the healthy control (CTRL group, n=8). The gut microbiota existed in Ps groups including IMQ group and PC+IMQ group encompassed less diversity than controls, which were attributed to decreased presence of several taxa. The two Ps groups were characterized by significant reduction in firmicutes. In this study, microbiota of psoriasis was defined by an increase presence of Bacteroides. After treated with ATB, we found substantial increase of Lactobacillales but significant decrease of Clostridiales and Coriobacteriales. Relative lower abundance of multiple intestinal bacteria was observed in Ps groups. Although part of genera were concomitantly reduced in both IMQ and PC+IMQ conditions, we discovered the specialty of PC+IMQ group samples was that contained lower abundance of beneficial taxa. Characteristics of gut microbiota profiles in Ps mice were comparable to profiles in patients with Ps, which were related to alteration of specific inflammatory proteins in disease groups but were significantly different from control group. Thus, this study emphasizes the role of intestinal microbiota in the pathogenesis of Ps and provides new insight for investigating association between intestinal microbes and immune inflammation.

A perturbação da microbiota intestinal comensal está relacionada à dermatose inflamatória crônica. Analisamos a diversidade da microbiota intestinal para caracterizar a variação biológica da psoríase (Ps). Diferenças significativas do perfil microbiológico intestinal foram reveladas no modelo murino com psoríase pelo sequenciamento da região variável 16S rRNA V3-V4. As comparações de grupo incluíram o creme imiquimod (grupo IMQ, n=8), o creme imiquimod e antibióticos (ATB) (grupo PC+IMQ, n=8) e o controle saudável (grupo CTRL, n=8). A microbiota intestinal existia nos grupos Ps, incluindo o grupo IMQ e o grupo PC+IMQ englobava menos diversidade do que os controles, que foram atribuídos à diminuição da presença de vários taxa. Os dois grupos de Ps caracterizavam-se por uma redução significativa nos firicutes. Neste estudo, a microbiota da psoríase foi definida por um aumento da presença de bacteroides. Após o tratamento com ATB, encontramos um aumento substancial de Lactobacillales mas uma diminuição significativa de Clostridiales e Coriobacteriales. Uma menor abundância relativa de bactérias intestinais múltiplas foi observada nos grupos de Ps. Embora parte dos gêneros tenha sido concomitantemente reduzida tanto em condições IMQ como PC+IMQ, descobrimos que a especialidade das amostras do grupo PC+IMQ era que continham menor abundância de taxas benéficas. As características dos perfis de microbiota intestinal em ratos de Ps eram comparáveis aos perfis em pacientes com Ps, que estavam relacionados à alteração de proteínas inflamatórias específicas em grupos de doenças, mas eram significativamente diferentes do grupo controle. Assim, este estudo enfatiza o papel da microbiota intestinal na patogênese do Ps e fornece novos conhecimentos para investigar a associação entre micróbios intestinais e inflamação imunológica.

The efficacy and safety of ciclesonide for the treatment of perennial allergic rhinitis: a systematic review and meta-analysis / Eficácia e segurança da ciclesonida no tratamento da rinite alérgica perene: uma revisão sistemática e metanálise

Abstract Introduction: Allergic rhinitis is a chronic inflammatory disease which affects 1 out of 6 individuals. Perennial allergic rhinitis accounts for 40% of AR cases. Ciclesonide is one of the relatively new intranasal steroid for allergic rhinitis. Objective: The purpose of this study was to evaluate the efficacy and safety of ciclesonide in the treatment of perennial allergic rhinitis. Methods: We searched Pubmed, Scientific Citation Index, Embase, Clinical Trial Registries for randomized controlled trials and Cochrane Central Register of Controlled Trials to find out the randomized controlled Trial comparing ciclesonide with placebo for PAR. Results: Eight studies were included. In comparison with placebo groups, ciclesonide groups significantly decreased Reflective Total Nasal Symptom Score (MD = −0.56; 95% CI −0.72 to 0.39, p < 0.00001) with heterogeneity (p = 0.19, I2 = 24%), Instantaneous Total Nasal Symptom Score (MD = −0.57; 95% CI −0.75 to −0.39, p < 0.00001) with heterogeneity (p = 0.34, I2 = 11%). A significant effect for Reflective Nasal Symptom Score Subtotal (MD = −0.15; 95% CI −0.18 to −0.13, p < 0.00001) with heterogeneity (p = 0.12, I2 = 24%) was also demonstrated. Rhinoconjunctivitis quality of life questionnaire score (RQLQs) (MD = −0.27; 95% CI −0.39 to −0.15, p < 0.00001) with heterogeneity (p = 0.58, I 2 = 0%) in the treatment of ciclesonide was also significantly reduced. In addition, the difference in Treatment-Emergent Adverse Events between the two groups was not significant. Conclusion: Ciclesonide can improve perennial allergic rhinitis without increasing adverse events. Ciclesonide may be another valuable choice for perennial allergic rhinitis in the future.

Resumo Introdução: A rinite alérgica é uma doença inflamatória crônica que afeta um a cada seis indivíduos. A rinite alérgica perene é responsável por 40% dos casos de rinite alérgica. A ciclesonida é um dos corticosteroides intranasais mais novos para o tratamento dessa condição clínica. Objetivo: Avaliar a eficácia e segurança da ciclesonida no tratamento da rinite alérgica perene. Método: Uma busca foi feita nos bancos de dados Pubmed, Scientific Citation Index, Embase e Clinical Trial Registries por ensaios clínicos randomizados e Cochrane Central Register of Controlled Trials por estudos controlados randomizados que comparassem ciclesonida com placebo no tratamento da rinite alérgica perene. Resultados: Oito estudos foram incluídos. Em comparação com os grupos placebo, os grupos ciclesonida mostraram diminuição significante no escore do Reflective Total Nasal Symptom Score (DM = −0,56; IC 95%: −0,72 a −0,39, p < 0,00001) com heterogeneidade (p = 0,19, I2 = 24%), do Instantaneous Total Nasal Symptom Score (DM = −0,57; IC95%: −0,75 a −0,39, p < 0,00001) com heterogeneidade (p = 0,34, I2 = 11%). Um efeito significante no escore do Reflective Nasal Symptom Score Subtotal (DM = −0,15; IC 95%: −0,18 a −0,13, p < 0,00001) com heterogeneidade (p = 0,12, I2 = 24%) também foi demonstrado. O escore do Rhinoconjunctivitis Quality of Life Questionnaire score (RQLQs) (DM = −0,27; IC 95%: −0,39 a −0,15, p < 0,00001) com heterogeneidade (p = 0,58, I2 = 0%) também foi significantemente reduzido no tratamento com ciclesonida. Além disso, a diferença em relação aos eventos adversos emergentes do tratamento entre os dois grupos não foi significante. Conclusão: A ciclesonida pode melhorar a rinite alérgica perene sem aumentar os eventos adversos. Esse fármaco pode ser outra opção valiosa para a rinite alérgica perene no futuro.

The efficacy and safety of ciclesonide for the treatment of perennial allergic rhinitis: a systematic review and meta-analysis.

INTRODUCTION: Allergic rhinitis is a chronic inflammatory disease which affects 1 out of 6 individuals. Perennial allergic rhinitis accounts for 40% of AR cases. Ciclesonide is one of the relatively new intranasal steroid for allergic rhinitis. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of ciclesonide in the treatment of perennial allergic rhinitis. METHODS: We searched Pubmed, Scientific Citation Index, Embase, Clinical Trial Registries for randomized controlled trials and Cochrane Central Register of Controlled Trials to find out the randomized controlled Trial comparing ciclesonide with placebo for PAR. RESULTS: Eight studies were included. In comparison with placebo groups, ciclesonide groups significantly decreased Reflective Total Nasal Symptom Score (MD=-0.56; 95% CI -0.72 to 0.39, p<0.00001) with heterogeneity (p=0.19, I2=24%), Instantaneous Total Nasal Symptom Score (MD=-0.57; 95% CI -0.75 to -0.39, p<0.00001) with heterogeneity (p=0.34, I2=11%). A significant effect for Reflective Nasal Symptom Score Subtotal (MD=-0.15; 95% CI -0.18 to -0.13, p<0.00001) with heterogeneity (p=0.12, I2=24%) was also demonstrated. Rhinoconjunctivitis quality of life questionnaire score (RQLQs) (MD=-0.27; 95% CI -0.39 to -0.15, p<0.00001) with heterogeneity (p=0.58, I2=0%) in the treatment of ciclesonide was also significantly reduced. In addition, the difference in Treatment-Emergent Adverse Events between the two groups was not significant. CONCLUSION: Ciclesonide can improve perennial allergic rhinitis without increasing adverse events. Ciclesonide may be another valuable choice for perennial allergic rhinitis in the future.

Promising MS2 mediated virus-like particle vaccine against foot-and-mouth disease.

Foot-and-mouth disease (FMD) has caused severe economic losses to millions of farmers worldwide. In this work, the coding genes of 141-160 epitope peptide (EP141-160) of VP1 were inserted into the coat protein (CP) genes of MS2 in prokaryotic expression vector, and the recombinant protein self-assembled into virus-like particles (VLP). Results showed that the CP-EP141-160 VLP had a strong immunoreaction with the FMD virus (FMDV) antigen in vitro, and also had an effective immune response in mice. Further virus challenge tests were carried out on guinea pigs and swine, high-titer neutralizing antibodies were produced and the CP-EP141-160 VLP vaccine could protect most of the animals against FMDV.

Participation in physical activity in patients 1-4 years post total joint replacement in the Dominican Republic.

BACKGROUND: To address both the growing burden of joint disease and the gaps in medical access in developing nations, medical relief organizations have begun to launch programs to perform total joint replacement (TJR) on resident populations in developing countries. One outcome of TJR of particular interest is physical activity (PA) since it is strongly linked to general health. This study evaluates the amount of postoperative participation in PA in low-income patients who received total joint replacement in the Dominican Republic and identifies preoperative predictors of postoperative PA level. METHODS: We used the Yale Physical Activity Survey (YPAS) to assess participation in postoperative PA 1-4 years following total knee or hip replacement. We compared the amount of aerobic PA reported by postoperative TJR patients with the levels of PA recommended by the CDC and WHO. We also analyzed preoperative determinants of postoperative participation in aerobic PA in bivariate and multivariate analyses. RESULTS: 64 patients out of 170 eligible subjects (52/128 TKR and 14/42 THR) who received TJR between 2009-2012 returned for an annual follow-up visit in 2013, with a mean treatment-to-follow-up time of 2.1 years. 43.3% of respondents met CDC/WHO criteria for sufficient participation in aerobic PA. Multivariate analyses including data from 56 individuals identified that patients who were both younger than 65 and at least two years postoperative had an adjusted mean activity dimensions summary index (ADSI) 22.9 points higher than patients who were 65 or older and one year postoperative. Patients who lived with friends or family had adjusted mean ADSI 17.2 points higher than patients living alone. Patients who had the most optimistic preoperative expectations of outcome had adjusted mean ADSI scores that were 19.8 points higher than those who were less optimistic. CONCLUSION: The TJR patients in the Dominican cohort participate in less PA than recommended by the CDC/WHO. Additionally, several associations were identified that potentially affect PA in this population; specifically, participants who are older than 65, recently postoperative, less optimistic about postoperative outcomes and who live alone participate in less PA.

Cytokines and tumor metastasis gene variants in oral cancer and precancer in Puerto Rico.

OBJECTIVES: A cross-sectional epidemiological study explored genetic susceptibility to oral precancer and cancer in Puerto Rico (PR). MATERIALS AND METHODS: Three hundred three individuals with a benign oral condition, oral precancer (oral epithelial hyperplasia/hyperkeratosis, oral epithelial dysplasia), or oral squamous cell carcinoma (SCCA) were identified via PR pathology laboratories. A standardized, structured questionnaire obtained information on epidemiological variables; buccal cells were collected for genetic analysis. Genotyping was performed using Taqman® assays. Allelic frequencies of single nucleotide polymorphisms (SNPs) were evaluated in cytokine genes and genes influencing tumor metastasis. Risk estimates for a diagnosis of oral precancer or SCCA while having a variant allele were generated using logistic regression. Adjusted models controlled for age, gender, ancestry, education, smoking and alcohol consumption. RESULTS: Relative to persons with a benign oral lesion, individuals with homozygous recessive allelic variants of tumor necrosis factor (TNF-α) -238 A/G SNP had a reduced odds of having an oral precancer (ORadjusted = 0.15; 95% CI 0.03-0.70). The transforming growth factor beta-1 (TGFß-1 -509 C/T) polymorphism was inversely associated with having an oral SCCA among persons homozygous for the recessive variant (ORcrude = 0.27; 95% CI 0.09-0.79). The matrix metalloproteinase gene (MMP-1) variant, rs5854, was associated with oral SCCA; participants with even one variant allele were more likely to have oral SCCA (ORadjusted = 2.62, 95% CI 1.05-6.53) compared to people with ancestral alleles. CONCLUSION: Our exploratory analyses suggest that genetic alterations in immune system genes and genes with metastatic potential are associated with oral precancer and SCCA risk in PR.

Enhanced immune response of a bicistronic DNA vaccine expressing fusion antigen Hsp65-Esat-6 of Mycobacterium Tuberculosis with GM-CSF as a molecular adjuvant

This study aimed to construct a bicistronic DNA vaccine expressing fusion antigen Hsp65-Esat-6 of Mycobacterium tuberculosis with cytokine GM-CSF as a molecular adjuvant (pIRES-Hsp65-ESAT-6-GM-CSF, pIRHEG), and the immune response in mice. C57BL/6 mice were immunized with the recombinant plasmid to detect the titer of antibodies, lymphocyte proliferation, the ratio of CD4+, CD8+T cell and IFN ~ γﻌIL-2 secretion. The titer of antibody, lymphocyte proliferation, the ratio of CD4+T and CD8+T cells and IFN ~ γ, IL-2 secretion of pIRHEG group was significant higher than other recombinant plasmid groups, which significant differed by statistical mean. The bicistronic DNA vaccine could induce an effective immune response in mice and could be used as vital ingredient of a new tuberculosis vaccine candidate.

Self-reported ethnicity and genetic ancestry in relation to oral cancer and pre-cancer in Puerto Rico.

BACKGROUND: Hispanics are known to be an extremely diverse and genetically admixed ethnic group. The lack of methodologies to control for ethnicity and the unknown admixture in complex study populations of Hispanics has left a gap in understanding certain cancer disparity issues. Incidence rates for oral and pharyngeal cancer (OPC) in Puerto Rico are among the highest in the Western Hemisphere. We conducted an epidemiological study to examine risk and protective factors, in addition to possible genetic susceptibility components, for oral cancer and precancer in Puerto Rico. METHODOLOGY/PRINCIPAL FINDINGS: We recruited 310 Puerto Rico residents who had been diagnosed with either an incident oral squamous cell carcinoma, oral precancer, or benign oral condition. Participants completed an in-person interview and contributed buccal cells for DNA extraction. ABI Biosystem Taqman™ primer sets were used for genotyping 12 ancestry informative markers (AIMs). Ancestral group estimates were generated using maximum likelihood estimation software (LEADMIX), and additional principal component analysis was carried out to detect population substructures. We used unconditional logistic regression to assess the contribution of ancestry to the risk of being diagnosed with either an oral cancer or precancer while controlling for other potential confounders. The maximum likelihood estimates showed that study participants had a group average ancestry contribution of 69.9% European, 24.5% African, and 5.7% detectable Native American. The African and Indigenous American group estimates were significantly higher than anticipated. Neither self-identified ethnicity nor ancestry markers showed any significant associations with oral cancer/precancer risk in our study. CONCLUSIONS/SIGNIFICANCE: The application of ancestry informative markers (AIMs), specifically designed for Hispanics, suggests no hidden population substructure is present based on our sampling and provides a viable approach for the evaluation and control of ancestry in future studies involving Hispanic populations.

Reduction of the amount of intestinal secretory IgA in fulminant hepatic failure

Intestinal barrier dysfunction plays an important role in spontaneous bacterial peritonitis. In the present study, changes in the intestinal barrier with regard to levels of secretory immunoglobulin A (SIgA) and its components were studied in fulminant hepatic failure (FHF). Immunohistochemistry and double immunofluorescent staining were used to detect intestinal IgA, the secretory component (SC) and SIgA in patients with FHF (20 patients) and in an animal model with FHF (120 mice). Real-time PCR was used to detect intestinal SC mRNA in the animal model with FHF. Intestinal SIgA, IgA, and SC staining in patients with FHF was significantly weaker than in the normal control group (30 patients). Intestinal IgA and SC staining was significantly weaker in the animal model with FHF than in the control groups (normal saline: 30 mice; lipopolysaccharide: 50 mice; D-galactosamine: 50 mice; FHF: 120 mice). SC mRNA of the animal model with FHF at 2, 6, and 9 h after injection was 0.4 ± 0.02, 0.3 ± 0.01, 0.09 ± 0.01, respectively. SC mRNA of the animal model with FHF was significantly decreased compared to the normal saline group (1.0 ± 0.02) and lipopolysaccharide group (0.89 ± 0.01). The decrease in intestinal SIgA and SC induced failure of the intestinal immunologic barrier and the attenuation of gut immunity in the presence of FHF.

Reduction of the amount of intestinal secretory IgA in fulminant hepatic failure.

Intestinal barrier dysfunction plays an important role in spontaneous bacterial peritonitis. In the present study, changes in the intestinal barrier with regard to levels of secretory immunoglobulin A (SIgA) and its components were studied in fulminant hepatic failure (FHF). Immunohistochemistry and double immunofluorescent staining were used to detect intestinal IgA, the secretory component (SC) and SIgA in patients with FHF (20 patients) and in an animal model with FHF (120 mice). Real-time PCR was used to detect intestinal SC mRNA in the animal model with FHF. Intestinal SIgA, IgA, and SC staining in patients with FHF was significantly weaker than in the normal control group (30 patients). Intestinal IgA and SC staining was significantly weaker in the animal model with FHF than in the control groups (normal saline: 30 mice; lipopolysaccharide: 50 mice; D-galactosamine: 50 mice; FHF: 120 mice). SC mRNA of the animal model with FHF at 2, 6, and 9 h after injection was 0.4 ± 0.02, 0.3 ± 0.01, 0.09 ± 0.01, respectively. SC mRNA of the animal model with FHF was significantly decreased compared to the normal saline group (1.0 ± 0.02) and lipopolysaccharide group (0.89 ± 0.01). The decrease in intestinal SIgA and SC induced failure of the intestinal immunologic barrier and the attenuation of gut immunity in the presence of FHF.

Characterization of calreticulin expression in mouse endometrium during embryo implantation.

Calreticulin (CRT), a Ca(2+)-binding storage protein and chaperone in the endoplasmic reticulum, modulates cell adhesiveness and integrin-dependent Ca(2+) signaling. However, the role of CRT during implantation remains poorly understood. In the present study, we characterized the expression of CRT mRNA and the protein in mouse endometria from pregnancy DI to D7. Real-Time PCR and in situ hybridization results showed that the levels of CRT mRNA in the endometria of pregnant mice were significantly higher than those of non-pregnant mice (P<0.05), and increased gradually from pregnancy DI to D4, reaching the máximum level on D4, followed by a plateau from D4 to D7. Using immunofluorescence histochemistry and western blot, changes of CRT expression in the endometria of pregnant mice were consistent with the expression of CRT mRNA. Furthermore, antisense CRT oligodeoxynucleotide was injected into the uterus horns of pregnant mice (D3) to investígate its effect on embryo implantation. The result showed that the number of implanted embryos markedly decreased in the side of uterine horns receiving antisense CRT oligodeoxynucleotide(í(>)<0.05). These findings suggest that CRT may play an important role in embryo implantation in mice.

Characterization of Calreticulin Expression in Mouse Endometrium during Embryo Implantation

Calreticulin (CRT), a Ca2+-binding storage protein and chaperone in the endoplasmic reticulum, modulates cell adhesiveness and integrin-dependent Ca2+ signaling. However, the role of CRT during implantation remains poorly understood. In the present study, we characterized the expression of CRT mRNA and the protein in mouse endometria from pregnancy DI to D7. Real-Time PCR and in situ hybridization results showed that the levels of CRT mRNA in the endometria of pregnant mice were significantly higher than those of non-pregnant mice (P<0.05), and increased gradually from pregnancy DI to D4, reaching the máximum level on D4, followed by a plateau from D4 to D7. Using immunofluorescence histochemistry and western blot, changes of CRT expression in the endometria of pregnant mice were consistent with the expression of CRT mRNA. Furthermore, antisense CRT oligodeoxynucleotide was injected into the uterus horns of pregnant mice (D3) to investígate its effect on embryo implantation. The result showed that the number of implanted embryos markedly decreased in the side of uterine horns receiving antisense CRT oligodeoxynucleotide(í><0.05). These findings suggest that CRT may play an important role in embryo implantation in mice.