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1.
Clinics (Sao Paulo) ; 79: 100358, 2024.
Article in English | MEDLINE | ID: mdl-39265238

ABSTRACT

OBJECTIVES: To analyze the clinical significance of Toll-Like Receptor 7/Interleukin-23/Interleukin-17 (TLR7/IL-23/IL-17) signaling pathway in patients with Acute Respiratory Distress Syndrome (ARDS). METHOD: The clinical data of 85 patients with ARDS were retrospectively analyzed and set as the ARDS group, and the clinical data of 85 healthy participants during the same period were set as the healthy control group. Univariate and multivariate logistic regression were used to analyze risk the factors affecting the prognosis of ARDS patients. RESULTS: TheTLR7 mRNA expression and IL-23 and IL-17 levels in peripheral blood mononuclear cells were higher in the ARDS group than in the control group (p < 0.05). TLR7 mRNA expression, IL-23, IL-17, Surfactant Protein-D (SP-D), and Clara Cell protein-16 (CC-16) levels were the highest in the severe group, followed by the moderate group, and the lowest in the mild group, while Oxygenation Index (OI) was the lowest in the severe group, followed by the moderate group, and the highest in the mild group (p < 0.05). Multivariate logistic regression analysis found that the disease grade (severe), TLR7 mRNA expression, IL-23 level, and IL-17 level were the risk factors affecting the 28-d survival status of ARDS patients (OR > 1, p < 0.05). CONCLUSIONS: In ARDS patients, the TLR7/IL-23/IL-17 signaling pathway is activated. The expression of this pathway is closely related to the severity of the disease and the levels of lung injury markers, and it is a risk factor that may have a direct impact on the prognosis of ARDS patients.


Subject(s)
Interleukin-17 , Interleukin-23 , Respiratory Distress Syndrome , Signal Transduction , Toll-Like Receptor 7 , Humans , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/genetics , Interleukin-17/blood , Female , Male , Toll-Like Receptor 7/genetics , Middle Aged , Retrospective Studies , Interleukin-23/blood , Adult , Aged , Prognosis , Case-Control Studies , Severity of Illness Index , RNA, Messenger/analysis , Risk Factors , Leukocytes, Mononuclear/metabolism , Clinical Relevance
2.
Chem Rec ; 24(10): e202400013, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39318079

ABSTRACT

Over three decades ago, two independent groups of investigators identified free D-aspartic and later D-serine in specific brain nuclei and endocrine glands. This finding revealed a novel, non-proteinogenic role of these molecules. Moreover, the finding that aged proteins from the human eye crystallin, teeth, bone, blood vessels or the brain incorporate D-aspartic acids to specific primary protein sequences fostered the hypothesis that aging might be related to D-amino acid isomerization of body proteins. The experimental confirmation that schizophrenia and neurodegenerative diseases modify plasma free D-amino acids or tissue levelsnurtured the opportunity of using D-amino acids as therapeutic agents for several disease treatments, a strategy that prompted the successful current application of D-amino acids to human medicine.


Subject(s)
Amino Acids , Humans , Amino Acids/chemistry , Amino Acids/metabolism , Schizophrenia/drug therapy , Schizophrenia/metabolism , Serine/chemistry , Serine/metabolism , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/metabolism , Aging/metabolism , Stereoisomerism , Animals , D-Aspartic Acid/metabolism , D-Aspartic Acid/chemistry , Brain/metabolism , Clinical Relevance
3.
Ageing Res Rev ; 101: 102464, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39173916

ABSTRACT

A Disintegrin and Metalloproteinase 10 (ADAM10) is a crucial transmembrane protein involved in diverse cellular processes, including cell adhesion, migration, and proteolysis. ADAM10's ability to cleave over 100 substrates underscores its significance in physiological and pathological contexts, particularly in Alzheimer's disease (AD). This review comprehensively examines ADAM10's multifaceted roles, highlighting its critical function in the non-amyloidogenic processing of the amyloid precursor protein (APP), which mitigates amyloid beta (Aß) production, a critical factor in AD development. We summarize the regulation of ADAM10 at multiple levels: transcriptional, translational, and post-translational, revealing the complexity and responsiveness of its expression to various cellular signals. A standardized nomenclature for ADAM10 isoforms is proposed to improve clarity and consistency in research, facilitating better comparison and replication of findings across studies. We address the challenges in detecting ADAM10 isoforms using antibodies, advocating for standardized detection protocols to resolve discrepancies in results from different biological matrices. By highlighting these issues, this review underscores the potential of ADAM10 as a biomarker for early diagnosis and a therapeutic target in AD. By consolidating current knowledge on ADAM10's regulation and function, we aim to provide insights that will guide future research and therapeutic strategies in the AD context.


Subject(s)
ADAM10 Protein , Alzheimer Disease , Protein Isoforms , Humans , Alzheimer Disease/metabolism , ADAM10 Protein/metabolism , Animals , Amyloid Precursor Protein Secretases/metabolism , Antibodies , Membrane Proteins/metabolism , Clinical Relevance
4.
Int J Mol Sci ; 25(12)2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38928478

ABSTRACT

Hereditary breast and ovarian cancer (HBOC) syndrome is a genetic condition that increases the risk of breast cancer by 80% and that of ovarian cancer by 40%. The most common pathogenic variants (PVs) causing HBOC occur in the BRCA1 gene, with more than 3850 reported mutations in the gene sequence. The prevalence of specific PVs in BRCA1 has increased across populations due to the effect of founder mutations. Therefore, when a founder mutation is identified, it becomes key to improving cancer risk characterization and effective screening protocols. The only founder mutation described in the Mexican population is the deletion of exons 9 to 12 of BRCA1 (BRCA1Δ9-12), and its description focuses on the gene sequence, but no transcription profiles have been generated for individuals who carry this gene. In this study, we describe the transcription profiles of cancer patients and healthy individuals who were heterozygous for PV BRCA1Δ9-12 by analyzing the differential expression of both alleles compared with the homozygous BRCA1 control group using RT-qPCR, and we describe the isoforms produced by the BRCA1 wild-type and BRCA1Δ9-12 alleles using nanopore long-sequencing. Using the Kruskal-Wallis test, our results showed a similar transcript expression of the wild-type allele between the healthy heterozygous group and the homozygous BRCA1 control group. An association between the recurrence and increased expression of both alleles in HBOC patients was also observed. An analysis of the sequences indicated four wild-type isoforms with diagnostic potential for discerning individuals who carry the PV BRCA1Δ9-12 and identifying which of them has developed cancer.


Subject(s)
Alleles , BRCA1 Protein , Hereditary Breast and Ovarian Cancer Syndrome , Humans , BRCA1 Protein/genetics , Female , Hereditary Breast and Ovarian Cancer Syndrome/genetics , Middle Aged , Genetic Predisposition to Disease , Adult , Founder Effect , Exons/genetics , Breast Neoplasms/genetics , Heterozygote , Mutation , Mexico , Ovarian Neoplasms/genetics , Clinical Relevance
6.
J Pediatr (Rio J) ; 100(5): 505-511, 2024.
Article in English | MEDLINE | ID: mdl-38604242

ABSTRACT

OBJECTIVE: Monitoring the disease status of Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (HLH) patients is crucial. This study aimed to investigate the different strategies and outcomes of patients with EBV-HLH and re-elevated EBV-DNA. METHOD: A retrospective analysis was conducted on 20 patients diagnosed with EBV-HLH. Clinical features, laboratory tests, treatments, plasma EBV-DNA levels, and outcomes were assessed. Three cases were highlighted for detailed analysis. RESULTS: Nine of the 20 patients had a re-elevation of EBV-DNA during treatment, and 55.5 % (5/9) experienced relapses. Patients with persistently positive plasma EBV-DNA (n = 4) and those with re-elevated EBV-DNA after conversion (n = 9) showed a significantly higher relapse rate compared to those with persistently negative EBV-HLH (n = 7) (p < 0.05). Among the highlighted cases, Case 1 exhibited plasma EBV-DNA re-elevation after four weeks of treatment without relapse, maintaining stability with the original treatment regimen, and eventually, his plasma EBV-DNA turned negative. In Case 2, plasma EBV-DNA was elevated again with a recurrence of HLH after L-DEP. Consequently, she underwent allogeneic hematopoietic stem cell transplantation and eventually achieved complete remission (CR) with negative plasma EBV-DNA. Case 3 experienced plasma EBV-DNA re-elevation after L-DEP but remained in CR, discontinuing chemotherapy without relapse. CONCLUSION: The re-elevation of plasma EBV-DNA during EBV-HLH treatment poses challenges in determining disease status and treatment strategies. Optimal management decisions require a combination of the level of elevated EBV-DNA, the intensity of hyperinflammation, and the patient's immune function.


Subject(s)
DNA, Viral , Epstein-Barr Virus Infections , Herpesvirus 4, Human , Lymphohistiocytosis, Hemophagocytic , Recurrence , Humans , Lymphohistiocytosis, Hemophagocytic/therapy , Lymphohistiocytosis, Hemophagocytic/blood , Lymphohistiocytosis, Hemophagocytic/virology , Retrospective Studies , Male , Epstein-Barr Virus Infections/blood , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/therapy , Female , DNA, Viral/blood , Child, Preschool , Child , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/isolation & purification , Infant , Adolescent , Treatment Outcome , Clinical Relevance
7.
Mucosal Immunol ; 17(4): 565-583, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38555027

ABSTRACT

Studies have reported the occurrence of gastrointestinal (GI) symptoms, primarily diarrhea, in COVID-19. However, the pathobiology regarding COVID-19 in the GI tract remains limited. This work aimed to evaluate SARS-CoV-2 Spike protein interaction with gut lumen in different experimental approaches. Here, we present a novel experimental model with the inoculation of viral protein in the murine jejunal lumen, in vitro approach with human enterocytes, and molecular docking analysis. Spike protein led to increased intestinal fluid accompanied by Cl- secretion, followed by intestinal edema, leukocyte infiltration, reduced glutathione levels, and increased cytokine levels [interleukin (IL)-6, tumor necrosis factor-α, IL-1ß, IL-10], indicating inflammation. Additionally, the viral epitope caused disruption in the mucosal histoarchitecture with impairment in Paneth and goblet cells, including decreased lysozyme and mucin, respectively. Upregulation of toll-like receptor 2 and toll-like receptor 4 gene expression suggested potential activation of local innate immunity. Moreover, this experimental model exhibited reduced contractile responses in jejunal smooth muscle. In barrier function, there was a decrease in transepithelial electrical resistance and alterations in the expression of tight junction proteins in the murine jejunal epithelium. Additionally, paracellular intestinal permeability increased in human enterocytes. Finally, in silico data revealed that the Spike protein interacts with cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride conductance (CaCC), inferring its role in the secretory effect. Taken together, all the events observed point to gut impairment, affecting the mucosal barrier to the innermost layers, establishing a successful experimental model for studying COVID-19 in the GI context.


Subject(s)
COVID-19 , Intestinal Mucosa , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Spike Glycoprotein, Coronavirus/metabolism , Spike Glycoprotein, Coronavirus/immunology , Animals , SARS-CoV-2/physiology , SARS-CoV-2/immunology , Humans , Mice , COVID-19/immunology , COVID-19/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/immunology , Jejunum/immunology , Jejunum/metabolism , Jejunum/pathology , Jejunum/virology , Molecular Docking Simulation , Enterocytes/metabolism , Enterocytes/virology , Immunity, Innate , Cytokines/metabolism , Disease Models, Animal , Male , Clinical Relevance
8.
J Pharm Pharmacol ; 76(6): 732-742, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38546507

ABSTRACT

OBJECTIVES: Angico gum (AG) (Anadenanthera colubrina var. Cebil [Griseb.] Altschul) is utilized by some Brazilian communities to alleviate symptoms from gastroesophageal reflux disease. Here, we aimed to investigate the "in vitro" topical protective capacity of AG on human esophageal mucosa. METHODS: Biopsies of the distal esophageal mucosa were collected from 35 patients with heartburn (24 non-erosive and 11 with erosive oesophagitis (EE)) and mounted in Üssing chambers. AG was applied topically, followed by exposure with acid solution (pH 2.0 or pH 1.0), where transepithelial electrical resistance (TER) and The transepithelial permeability for fluorescein was assessed. The incubation of the AG labeled with FITC in the esophageal mucosa was localized by fluorescence microscopy. KEY FINDINGS: Pretreatment with AG prevented the drop in TER induced by acid solution, as well as significantly decreases the fluorescein permeability in non-erosive patients. The protective effect of AG was sustained for up to 120 min both in biopsies of non-erosive and erosive esophagitis. Confocal microscope images showed mucosal luminal adherence of FITC-labeled AG. CONCLUSION: AG had a prolonged topical protective effect against acid solution in mucosal biopsies of patients with non-erosive and erosive esophagitis.


Subject(s)
Esophageal Mucosa , Gastroesophageal Reflux , Humans , Gastroesophageal Reflux/drug therapy , Gastroesophageal Reflux/prevention & control , Esophageal Mucosa/drug effects , Esophageal Mucosa/pathology , Esophageal Mucosa/metabolism , Male , Female , Middle Aged , Adult , Permeability , Electric Impedance , Administration, Topical , Biopolymers , Aged , Fluorescein/administration & dosage , Esophagus/drug effects , Esophagus/pathology , Esophagus/metabolism , Heartburn/drug therapy , Heartburn/prevention & control , Clinical Relevance
9.
Clin Anat ; 37(8): 886-899, 2024 Nov.
Article in English | MEDLINE | ID: mdl-38469730

ABSTRACT

Current advances in the management of the autonomic nervous system in various cardiovascular diseases, and in treatments for pain or sympathetic disturbances in the head, neck, or upper limbs, necessitate a thorough understanding of the anatomy of the cervicothoracic sympathetic trunk. Our objective was to enhance our understanding of the origin and distribution of communicating branches and visceral cervicothoracic sympathetic nerves in human fetuses. This was achieved through a comprehensive topographic systematization of the branching patterns observed in the cervical and upper thoracic ganglia, along with the distribution of communicating branches to each cervical spinal nerve. We conducted detailed sub-macroscopic dissections of the cervical and thoracic regions in 20 human fetuses (40 sides). The superior and cervicothoracic ganglia were identified as the cervical sympathetic ganglia that provided the most communicating branches on both sides. The middle and accessory cervical ganglia contributed the fewest branches, with no significant differences between the right and left sides. The cervicothoracic ganglion supplied sympathetic branches to the greatest number of spinal nerves, spanning from C5 to T2. The distribution of communicating branches to spinal nerves was non-uniform. Notably, C3, C4, and C5 received the fewest branches, and more than half of the specimens showed no sympathetic connections. C1 and C2 received sympathetic connections exclusively from the superior ganglion. Spinal nerves that received more branches often did so from multiple ganglia. The vertebral nerve provided deep communicating branches primarily to C6, with lesser contributions to C7, C5, and C8. The vagus nerve stood out as the cranial nerve with the most direct sympathetic connections. The autonomic branching pattern and connections of the cervicothoracic sympathetic trunk are significantly variable in the fetus. A comprehensive understanding of the anatomy of the cervical and upper thoracic sympathetic trunk and its branches is valuable during autonomic interventions and neuromodulation. This knowledge is particularly relevant for addressing various autonomic cardiac diseases and for treating pain and vascular dysfunction in the head, neck, and upper limbs.


Subject(s)
Ganglia, Sympathetic , Humans , Ganglia, Sympathetic/anatomy & histology , Fetus/anatomy & histology , Sympathetic Nervous System/anatomy & histology , Cervical Vertebrae/anatomy & histology , Spinal Nerves/anatomy & histology , Cadaver , Female , Clinical Relevance
10.
J Pediatr (Rio J) ; 100(4): 384-391, 2024.
Article in English | MEDLINE | ID: mdl-38547930

ABSTRACT

OBJECTIVE: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. METHOD: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. RESULTS: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4 % (p = 0.006). CONCLUSION: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.


Subject(s)
Lymphoma , Mutation , Humans , Male , Female , Retrospective Studies , Child , China/epidemiology , Lymphoma/immunology , Lymphoma/genetics , Child, Preschool , Infant , Adolescent , Clinical Relevance
11.
J Cancer Res Clin Oncol ; 150(2): 70, 2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38305916

ABSTRACT

PURPOSE: To assess the role of the p160 family, AR, and AR-V7 in different initial presentations of prostate cancer and their association with clinical endpoints related to tumor progression. METHODS: The study sample comprises 155 patients who underwent radical prostatectomy and 11 healthy peripheral zone biopsies as the control group. Gene expression was quantified by qPCR from the tissue specimens. The statistical analysis investigated correlations between gene expression levels, associations with disease presence, and clinicopathological features. Additionally, ROC curves were applied for distinct PCa presentations, and time-to-event analysis was used for clinical endpoints. RESULTS: The AR-V7 diagnostic performance for any PCa yielded an AUC of 0.77 (p < 0.05). For locally advanced PCa, the AR-V7 AUC was 0.65 (p < 0.05). Moreover, the metastasis group had a higher expression of SRC-1 than the non-metastatic group (p < 0.05), showing a shorter time to metastasis in the over-expressed group (p = 0.005). Patients with disease recurrence had super-expression of AR levels (p < 0.0005), with a shorter time-to-recurrence in the super-expression group (p < 0.0001). CONCLUSION: Upregulation of SRC-1 indicates a higher risk of progression to metastatic disease in a shorter period, which warrants further research to be applied as a clinical tool. Additionally, AR may be used as a predictor for PCa recurrence. Furthermore, AR-V7 may be helpful as a diagnostic tool for PCa and locally advanced cancer, comparable with other investigated tools.


Subject(s)
Prostatic Neoplasms , Humans , Male , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Clinical Relevance , Disease Progression , Neoplasm Recurrence, Local/genetics , Protein Isoforms/metabolism , Receptors, Androgen/genetics , Prostatic Neoplasms/diagnosis
12.
Clinics (Sao Paulo) ; 79: 100327, 2024.
Article in English | MEDLINE | ID: mdl-38330788

ABSTRACT

AIM: miR-141-5p expression in patients with Early Spontaneous Abortion (ESA) and its correlation with hormone levels during pregnancy were investigated. METHODS: A total of 70 pregnant women with ESA were selected as the research group, and 70 normal pregnant women who chose abortion for non-medical reasons were selected as the Con group. Serum ß-HCG, Progesterone (P), and Estrogen (E2) were detected by enzyme-linked immunosorbent assay. Differentially expressed miRNAs were screened by miRNA microarray analysis. miR-141-5p expression was detected by RT-qPCR, and its correlation with serum ß-HCG, P, and E2 levels was analyzed. The diagnostic value of miR-141-5p for ESA was evaluated by the ROC curve. RESULTS: Serum ß-HCG, P, and E2 were decreased and serum miR-141-5p was increased in patients with ESA. Pearson correlation analysis showed that serum ß-HCG, P, and E2 levels were negatively correlated with miR-141-5p expression levels. ROC curve showed that miR-141-5p had a diagnostic value for ESA. CONCLUSIONS: miR-141-5p is related to hormone levels during pregnancy and is expected to become a new candidate diagnostic marker for ESA.


Subject(s)
Abortion, Spontaneous , MicroRNAs , Humans , Female , Pregnancy , Abortion, Spontaneous/diagnosis , Clinical Relevance , MicroRNAs/genetics , Biomarkers , Progesterone
13.
Clin Transl Oncol ; 26(6): 1519-1531, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38206516

ABSTRACT

BACKGROUND: Although it has been shown that cyclin dependent kinase inhibitor 2A (CDKN2A) plays a significant role in a number of malignancies, its clinicopathological value and function in small cell lung cancer (SCLC) is unclear and warrants additional research. METHODS: The clinical significance of CDKN2A expression in SCLC was examined by multiple methods, including comprehensive integration of mRNA level by high throughput data, Kaplan-Meier survival analysis for prognostic value, and validation of its protein expression using in-house immunohistochemistry. RESULTS: The expression of CDKN2A mRNA in 357 cases of SCLC was evidently higher than that in the control group (n = 525) combing the data from 20 research centers worldwide. The standardized mean difference (SMD) was 3.07, and the area under the curve (AUC) of summary receiver operating characteristic curve (sROC) was 0.97 for the overexpression of CDKN2A. ACC, COAD, KICH, KIRC, PCPG, PRAD, UCEC, UVM patients with higher CDKN2A expression had considerably worse overall survival rates than those with lower CDKN2A expression with the hazard ratio (HR) > 1. CONCLUSION: CDKN2A upregulation extensively enhances the carcinogenesis and progression of SCLC.


Subject(s)
Biomarkers, Tumor , Cyclin-Dependent Kinase Inhibitor p16 , Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Lung Neoplasms/mortality , Lung Neoplasms/genetics , Small Cell Lung Carcinoma/pathology , Small Cell Lung Carcinoma/metabolism , Small Cell Lung Carcinoma/genetics , Small Cell Lung Carcinoma/mortality , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Prognosis , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Female , Male , Kaplan-Meier Estimate , ROC Curve , RNA, Messenger/genetics , RNA, Messenger/metabolism , Middle Aged , Survival Rate , Prospective Studies , Aged , Case-Control Studies , Clinical Relevance
14.
Clin Transl Oncol ; 26(3): 664-681, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37537510

ABSTRACT

INTRODUCTION: Cluster of differentiation 166 (CD166), a cancer stem cell (CSC) marker, and human epidermal growth factor receptor 2 (HER-2) are expressed in a diversity of malignancies and is associated with tumor progression. Although studies regarding the importance of CSC markers and HER-2 in gastric cancer (GC) have rapidly developed, their clinicopathological, prognosis, and diagnosis value still remain unsatisfying in GC. Therefore, the present study aims to investigate the clinical, prognostic, and diagnostic significance of CD166 and HER-2 in different histological types of GC. MATERIALS AND METHODS: Bioinformatic analysis was applied to determine the clinical importance of CD166 and HER-2 expression based on their tissue localization in primary GC tumors and the normal adjacent samples. The expression patterns, clinical significance, prognosis, and diagnosis value of CD166 and HER-2 proteins in tissue microarrays (TMAs) of 206 GC samples, including Signet Ring Cell (SRC) and intestinal types and also 28 adjacent normal tissues were evaluated using immunohistochemistry (IHC). RESULTS: The results indicated that the expression of CD166 (membranous and cytoplasmic) and HER-2 were significantly up-regulated in tumor cells compared to adjacent normal tissues (P = 0.010, P < 0.001, and P = 0.011, respectively). A statistically significant association was detected between a high level of membranous expression of CD166 and lymphovascular invasion (P = 0.006); We also observed a statistically significant association between high cytoplasmic expression of CD166 protein and more invasion of the subserosa (P = 0.040) in the SRC type. In contrast, there was no correlation between the expression of HER-2 and clinicopathologic characteristics. Both CD166 and HER-2 showed reasonable accuracy and high specificity as diagnostic markers. CONCLUSION: Our results confirmed that increased membranous and cytoplasmic expression of CD166 showed clinical significance in the SRC type and is associated with the progression of the disease and more aggressive tumor behaviors. These findings can be used to assist in designating subgroups of patients that require different follow-up strategies, and also, they might be utilized as the prognostic or diagnostic biomarkers in these types of GC for prospective clinical application.


Subject(s)
Clinical Relevance , Receptor, ErbB-2 , Stomach Neoplasms , Humans , Biomarkers, Tumor/metabolism , Stomach Neoplasms/pathology , Prospective Studies , Prognosis
15.
J Pediatr (Rio J) ; 100(1): 108-115, 2024.
Article in English | MEDLINE | ID: mdl-37778397

ABSTRACT

OBJECTIVE: This study aimed to investigate the clinical significance of serum microRNA-146a and pro-inflammatory factors in children with Mycoplasma pneumoniae pneumonia after azithromycin treatment. microRNA-146a is known to regulate inflammatory responses, and excessive inflammation is a primary characteristic of MPP. METHODS: Children with MPP received conventional symptomatic therapy along with intravenous administration of azithromycin for one week. Serum levels of microRNA-146a and pro-inflammatory factors were measured using RT-qPCR and ELISA kits, respectively. The correlation between microRNA-146a and pro-inflammatory factors was analyzed by the Pearson method. Pulmonary function indexes were assessed using a pulmonary function analyzer, and their correlation with microRNA-146a and pro-inflammatory factors after treatment was evaluated. Children with MPP were divided into effective and ineffective treatment groups, and the clinical significance of microRNA-146a and pro-inflammatory factors was evaluated using receiver operating characteristic curves and logistic multivariate regression analysis. RESULTS: Serum microRNA-146a was downregulated in children with MPP but upregulated after azithromycin treatment, contrasting with the trend observed for pro-inflammatory factors. MicroRNA-146a showed a negative correlation with pro-inflammatory cytokines. Pulmonary function parameters were initially reduced in children with MPP, but increased after treatment, showing positive/inverse associations with microRNA-146a and pro-inflammatory factors. Higher microRNA-146a and lower pro-inflammatory factors predicted better efficacy of azithromycin treatment. MicroRNA-146a, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) were identified as independent factors influencing treatment efficacy. CONCLUSION: Azithromycin treatment in children with MPP upregulates microRNA-146a, downregulates pro-inflammatory factors, and effectively improves pulmonary function.


Subject(s)
MicroRNAs , Pneumonia, Mycoplasma , Child , Humans , Azithromycin/therapeutic use , Mycoplasma pneumoniae , Clinical Relevance , Pneumonia, Mycoplasma/drug therapy , MicroRNAs/therapeutic use
16.
Am J Med Genet A ; 194(3): e63430, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37872709

ABSTRACT

Clinical interpretation of genetic variants in the context of the patient's phenotype is a time-consuming and costly process. In-silico analysis using in-silico prediction tools, and molecular modeling have been developed to predict the influence of genetic variants on the quality and/or quantity of the resulting translated protein, and in this way, to alert clinicians of disease likelihood in the absence of previous evidence. Our objectives were to evaluate the success rate of the in-silico analysis in predicting the disease-causing variants as pathogenic and the single-nucleotide variants as neutral, and to establish the reliability of in-silico analysis for determining pathogenicity or neutrality of von Willebrand factor gene-associated genetic variants. Using in-silico analysis, we studied pathogenicity in 31 disease-causing variants, and neutrality in 61 single-nucleotide variants from patients previously diagnosed as type 2 von Willebrand disease. Disease-causing variants and non-synonymous single-nucleotide variants were explored by in-silico tools that analyze the amino acidic sequence. Intronic and synonymous single-nucleotide variants were analyzed by in-silico methods that evaluate the nucleotidic sequence. We found a consistent agreement between predictions achieved by in-silico prediction tools and molecular modeling, both for defining the pathogenicity of disease-causing variants and the neutrality of single-nucleotide variants. Based on our results, the in-silico analysis would help to define the pathogenicity or neutrality in novel genetic variants observed in patients with clinical and laboratory phenotypes suggestive of von Willebrand disease.


Subject(s)
von Willebrand Diseases , von Willebrand Factor , Humans , von Willebrand Factor/genetics , von Willebrand Factor/metabolism , Clinical Relevance , Reproducibility of Results , von Willebrand Diseases/diagnosis , von Willebrand Diseases/genetics , Nucleotides
17.
Crit Rev Oncol Hematol ; 194: 104232, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38101717

ABSTRACT

Prostate cancer (PCa) is the second most frequent type of cancer in men and assessing circulating tumor cells (CTCs) by liquid biopsy is a promising tool to help in cancer early detection, staging, risk of recurrence evaluation, treatment prediction and monitoring. Blood-based liquid biopsy approaches enable the enrichment, detection and characterization of CTCs by biomarker analysis. Hence, comprehending the molecular markers, their role on each stage of cancer development and progression is essential to provide information that can help in future implementation of these biomarkers in clinical assistance. In this review, we studied the molecular markers most associated with PCa CTCs to better understand their function on tumorigenesis and metastatic cascade, the methodologies utilized to analyze these biomarkers and their clinical significance, in order to summarize the available information to guide researchers in their investigations, new hypothesis formulation and target choice for the development of new diagnostic and treatment tools.


Subject(s)
Neoplastic Cells, Circulating , Prostatic Neoplasms , Male , Humans , Clinical Relevance , Biomarkers, Tumor , Neoplastic Cells, Circulating/pathology , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/genetics , Carcinogenesis/genetics , Cell Transformation, Neoplastic
18.
Int J Mol Sci ; 24(23)2023 Nov 22.
Article in English | MEDLINE | ID: mdl-38068923

ABSTRACT

In this review, we provide a general overview of the current panorama of mining strategies for multi-omics data to investigate lncRNAs with an actual or potential role as biological markers in cancer. Several multi-omics studies focusing on lncRNAs have been performed in the past with varying scopes. Nevertheless, many questions remain regarding the pragmatic application of different molecular technologies and bioinformatics algorithms for mining multi-omics data. Here, we attempt to address some of the less discussed aspects of the practical applications using different study designs for incorporating bioinformatics and statistical analyses of multi-omics data. Finally, we discuss the potential improvements and new paradigms aimed at unraveling the role and utility of lncRNAs in cancer and their potential use as molecular markers for cancer diagnosis and outcome prediction.


Subject(s)
Neoplasms , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Multiomics , Clinical Relevance , Neoplasms/genetics , Computational Biology
19.
Rev Assoc Med Bras (1992) ; 69(12): e20230568, 2023.
Article in English | MEDLINE | ID: mdl-37971119

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the impact of sarcopenia on prognosis in patients with gastric cancer in order to explore the relationship between sarcopenia and postoperative complications as well as durations of hospital stay and intensive care unit. METHODS: A total of 175 patients who visited the oncology clinic between 2017 and 2022 with respect to their radiological images, demographic data, and laboratory parameters were perused. The OsiriX software was used to measure the skeletal muscle area that was divided by the body height in order to obtain the skeletal muscle index. RESULTS: A total of 50.28% of 175 patients (41 females and 134 males, with a mean age of 63.5 years) who met the inclusion criteria in the study were sarcopenic. Significant differences appeared between sarcopenic and non-sarcopenic patients with respect to durations of both hospital stay (p<0.01) and intensive care unit stay (p<0.01) (multivariate analysis). Furthermore, patients with sarcopenia had significantly frequent postoperative complications in comparison with those without sarcopenia. Among the patients with sarcopenia, decreased levels of hemoglobin and albumin as well as lymphocytes were encountered in terms of inflammatory markers; nevertheless, no significant differences were determined among other inflammatory markers. CONCLUSION: In patients undergoing treatment for gastric cancer, sarcopenia increases postoperative complications and prolongs hospital and intensive care stays during the treatment process.


Subject(s)
Sarcopenia , Stomach Neoplasms , Male , Female , Humans , Middle Aged , Sarcopenia/complications , Stomach Neoplasms/complications , Stomach Neoplasms/surgery , Clinical Relevance , Muscle, Skeletal , Postoperative Complications/etiology , Retrospective Studies , Risk Factors
20.
Invest. educ. enferm ; 41(3): 141-150, 20231103. ilus, tab
Article in English | LILACS, BDENF - Nursing, COLNAL | ID: biblio-1518856

ABSTRACT

Objective. Within the context of evidence-based practice, this article exposes the reflection on the understanding and usefulness of the information provided by the research findings shared in reports and research publications, exposing differences based on the interpretation of statistical significance and clinical significance. Content synthesis. Basic aspects of the meaning and use of the information reported by research on p value (statistical significance) and the value and usefulness of these results are analyzed and exemplified, contrasting the value for the practice of an additional judgment on clinical significance. In addition to establishing conceptual differences, the need is highlighted for nurses to have the competencies to differentiate and apply each of them according to the clinical contexts of their potential implementation. Conclusion. The real usefulness of research about interventions within the context of nursing care is given by its real application and reach for the practice and benefit for patients. For this to occur, nurses must interpret adequately the information provided by scientific publications and other research reports.


Objetivo. En el contexto de una práctica basada en evidencia, este artículo expone la reflexión sobre la comprensión y utilidad de la información que proveen los hallazgos de investigación reportados en informes y publicaciones de investigación, exponiendo las diferencias a partir de la interpretación de la significancia estadística y significancia clínica. Síntesis del contenido. Se analizan y ejemplifican aspectos básicos sobre el significado y uso de la información que reportan las investigaciones sobre valor p (significancia estadística) y el valor y utilidad de estos resultados contrastando el valor para la práctica de un juicio adicional sobre significancia clínica. Además de establecer diferencias conceptuales, se resalta la necesidad de que las enfermeras tengan las competencias para diferenciar y aplicar cada uno de ellos según los contextos clínicos de su potencial implementación. Conclusión. La real utilidad de la investigación sobre intervenciones en el contexto del cuidado de enfermería está dada por su real aplicación y alcance para la práctica y el beneficio para los pacientes. Para que ello ocurra, las enfermeras deben interpretar adecuadamente la información que proveen las publicaciones científicas y otros reportes de investigación.


Objetivo. No contexto de uma prática baseada em evidências, este artigo apresenta a reflexão sobre a compreensão e utilidade da informação fornecida pelos resultados da investigação relatados em relatórios de investigação e publicações, expondo as diferenças com base na interpretação da significância estatística e da significância clínica. Síntese de conteúdo. Aspectos básicos sobre o significado e uso das informações relatadas pelas pesquisas sobre valor p (significância estatística) e o valor e utilidade desses resultados são analisados e exemplificados, contrastando o valor para a prática de um julgamento adicional sobre significância clínica. Além de estabelecer diferenças conceituais, destaca-se a necessidade de o enfermeiro ter competências para diferenciar e aplicar cada uma delas de acordo com os contextos clínicos de seu potencial implementação. Conclusão. A real utilidade da investigação sobre intervenções no contexto dos cuidados de enfermagem é dada pela sua real aplicação e âmbito de prática e benefício para os pacientes. Para que isso ocorra, os enfermeiros devem interpretar adequadamente as informações fornecidas pelas publicações científicas e outros relatórios de pesquisa.


Subject(s)
Humans , Male , Female , Nursing Research , Data Interpretation, Statistical , Evidence-Based Practice , Clinical Relevance , Nursing, Practical
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