Predicting Rheumatoid Arthritis Development Using Hand Ultrasound and Machine Learning-A Two-Year Follow-Up Cohort Study.

BACKGROUND: The early diagnosis and treatment of rheumatoid arthritis (RA) are essential to prevent joint damage and enhance patient outcomes. Diagnosing RA in its early stages is challenging due to the nonspecific and variable clinical signs and symptoms. Our study aimed to identify the most predictive features of hand ultrasound (US) for RA development and assess the performance of machine learning models in diagnosing preclinical RA. METHODS: We conducted a prospective cohort study with 326 adults who had experienced hand joint pain for less than 12 months and no clinical arthritis. We assessed the participants clinically and via hand US at baseline and followed them for 24 months. Clinical progression to RA was defined according to the ACR/EULAR criteria. Regression modeling and machine learning approaches were used to analyze the predictive US features. RESULTS: Of the 326 participants (45.10 ± 11.37 years/83% female), 123 (37.7%) developed clinical RA during follow-up. At baseline, 84.6% of the progressors had US synovitis, whereas 16.3% of the non-progressors did (p < 0.0001). Only 5.7% of the progressors had positive PD. Multivariate analysis revealed that the radiocarpal synovial thickness (OR = 39.8), PIP/MCP synovitis (OR = 68 and 39), and wrist effusion (OR = 12.56) on US significantly increased the odds of developing RA. ML confirmed these US features, along with the RF and anti-CCP levels, as the most important predictors of RA. CONCLUSIONS: Hand US can identify preclinical synovitis and determine the RA risk. The radiocarpal synovial thickness, PIP/MCP synovitis, wrist effusion, and RF and anti-CCP levels are associated with RA development.

Proteomic-Based Discovery of Predictive Biomarkers for Drug Therapy Response and Personalized Medicine in Chronic Immune Thrombocytopenia.

Purpose: ITP is the most prevalent autoimmune blood disorder. The lack of predictive biomarkers for therapeutic response is a major challenge for physicians caring of chronic ITP patients. This study is aimed at identifying predictive biomarkers for drug therapy responses. Methods: 2D gel electrophoresis (2-DE) was performed to find differentially expressed proteins. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS) analysis was performed to identify protein spots. The Cytoscape software was employed to visualize and analyze the protein-protein interaction (PPI) network. Then, enzyme-linked immunosorbent assays (ELISA) were used to confirm the results of the proteins detected in the blood. The DAVID online software was used to explore the Gene Ontology and pathways involved in the disease. Results: Three proteins, including APOA1, GC, and TF, were identified as hub-bottlenecks and confirmed by ELISA. Enrichment analysis results showed the importance of several biological processes and pathway, such as the PPAR signaling pathway, complement and coagulation cascades, platelet activation, vitamin digestion and absorption, fat digestion and absorption, cell adhesion molecule binding, and receptor binding. Conclusion and Clinical Relevance. Our results indicate that plasma proteins (APOA1, GC, and TF) can be suitable biomarkers for the prognosis of the response to drug therapy in ITP patients.

Diffuse large B-cell lymphoma presenting as sternal mass in a patient with ankylosing spondylitis: a case report study.

Primary bone lymphoma is a rare entity that constitutes less than 1% of all non-Hodgkin lymphomas and 3-5% of malignant bone tumors. Chronic immune and inflammatory diseases carry a level of risk for the development of malignancies that is correlated with the disease severity. There is conflicting evidence regarding the risk of lymphoma in spondyloarthritis. Case presentation: The authors present a rare case of primary diffuse large B-cell lymphoma of the sternum in a 41-year-old Iranian woman with ankylosing spondylitis (AS). Physical examination revealed a 7×7.5 cm firm swelling of the anterior midline chest wall above the breasts, and MRI showed a lesion within the sternal marrow with an associated soft-tissue mass in the anterior aspect of the sternum. Following core-needle biopsy under ultrasound guidance, a histopathological study demonstrated diffuse sheets of large noncleaved atypical cells with large multilobated prominent nuclei and fine chromatin compatible with diffuse large B-cell lymphoma. Clinical discussion: Primary and exclusive involvement of the sternum is an uncommon presentation of lymphoma. Radiological, histological, and clinical characteristics of primary bone lymphoma can resemble those of other medical disorders. Although infrequent, existing evidence shows that AS seems to be associated with a small but significant risk for malignancy. Conclusion: Even though inflammatory involvement of the anterior chest wall could be a common clinical finding in patients with AS, it is recommended that anterior chest wall pain or any mass almost always needs comprehensive assessment and imaging evaluation in such patients to avoid any delayed diagnosis, misdiagnosis, and ensuing morbidity or mortality.

Antiproliferative and apoptotic effects of conditioned medium released from human amniotic epithelial stem cells on breast and cervical cancer cells.

INTRODUCTION: Human amniotic membrane (hAM) and its cells have been proposed for several clinical applications, including cancer therapy. However, reports on the anticancer effects of human amniotic epithelial stem cells-conditioned media (hAECs-CM) are limited. This work aims to evaluate the anticancer effects of hAECs-CM on cervical cancer and breast cancer cell lines in vitro. METHODS: Human term placentas were gained from uncomplicated Cesarean sections from healthy donor women. After amnion peeling from the chorion, its epithelial stem cells were isolated and cultured, and its conditioned medium (CM) was collected for experiments. MTT assay was performed to assess cancer cells viability. Migration rate of cancer cells was examined via wound healing assay. Cell-cycle distribution and apoptosis were determined using flow cytometry. RESULTS: Based on MTT assay hAECs-CM was cytotoxic against cancerous cell lines in a dose-time-dependent manner. After 48 h of treatment with hAECs-CM pure, the cell viability of breast cancer cells includes MCF-7 and MDA-MB-231 reached to 73.2% and 65.5%, respectively. In the same situation, HeLa cervical cancer cell line revealed the lowest viability by 47.3%. The wound-healing assay displayed an incomplete wound closure of scratched MDA-MB-231 cells and significant inhibition of cell migration after hAECs-CM treatment. The results also revealed that hAECs-CM exerted anti-proliferation activity by prompting cell cycle arrest and apoptosis of cancer cells.Conclusions: hAECs-CM is a potent candidate for inducing apoptosis and simultaneously inhibition of the proliferation and migration of cancer cells via inhibiting cell cycle blockade.

Periodontal ligament stem cells as a promising therapeutic target for neural damage.

BACKGROUND: The damaged neuronal cells of adult mammalian lack the regenerative ability to replace the neuronal connections. Periodontal ligament stem cells (PDLSCs) are the promising source for neuroregenerative applications that can improve the injured microenvironment of the damaged neural system. They provide neuronal progenitors and neurotrophic, anti-apoptotic and anti-inflammatory factors. In this study, we aimed to comprehensively explore the various neuronal differentiation potentials of PDLSCs for application in neural regeneration therapy. MAIN TEXT: PDLSCs have superior potential to differentiate into various neural-like cells through a dedifferentiation stage followed by differentiation process without need for cell division. Diverse combination of nutritional factors can be used to induce the PDLSCs toward neural lineage. PDLSCs when coupled with biomaterials could have significant implications for neural tissue repair. PDLSCs can be a new clinical research target for Alzheimer's disease treatment, multiple sclerosis and cerebral ischemia. Moreover, PDLSCs have beneficial effects on retinal ganglion cell regeneration and photoreceptor survival. PDLSCs can be a great source for the repair of injured peripheral nerve through the expression of several neural growth factors and differentiation into Schwann cells. CONCLUSION: In conclusion, these cells are an appealing source for utilizing in clinical treatment of the neuropathological disorders. Although significant in vitro and in vivo investigations were carried out in order for neural differentiation evaluation of these cells into diverse types of neurons, more preclinical and clinical studies are needed to elucidate their therapeutic potential for neural diseases.

Communication between stromal and hematopoietic stem cell by exosomes in normal and malignant bone marrow niche.

Extracellular vesicles (EVs) have been regarded as important tools for cell-cell communication. They act as carriers for the transfer of various molecules such as genes, proteins and miRNA. EVs shift and transfer their ingredients to target cells in an active form. These particles have prominent roles in modulation of bone marrow (BM) niche; therefore they can regulate proliferation, differentiation, and other properties of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). This review discusses the different roles of EVs on BM niche; HPCs fate regulation and downstream effects of them on HSCs. Moreover, cellular and molecular mechanisms of BM microenvironment cross-talking are explained in healthy and malignant settings.

Identification of Candidate Biomarkers for Idiopathic Thrombocytopenic Purpura by Bioinformatics Analysis of Microarray Data.

Idiopathic Thrombocytopenic Purpura (ITP) is a multifactorial disease with decreased count of platelet that can lead to bruising and bleeding manifestations. This study was intended to identify critical genes associated with chronic ITP. The gene expression profile GSE46922 was downloaded from the Gene Expression Omnibus database to recognize Differentially Expressed Genes (DEGs) by R software. Gene ontology and pathway analyses were performed by DAVID. The biological network was constructed using the Cytoscape. Molecular Complex Detection (MCODE) was applied for detecting module analysis. Transcription factors were identified by the PANTHER classification system database and the gene regulatory network was constructed by Cytoscape. One hundred thirty-two DEGs were screened from comparison newly diagnosed ITP than chronic ITP. Biological process analysis revealed that the DEGs were enriched in terms of positive regulation of autophagy and prohibiting apoptosis in the chronic phase. KEGG pathway analysis showed that the DEGs were enriched in the ErbB signaling pathway, mRNA surveillance pathway, Estrogen signaling pathway, and Notch signaling pathway. Additionally, the biological network was established, and five modules were extracted from the network. ARRB1, VIM, SF1, BUB3, GRK5, and RHOG were detected as hub genes that also belonged to the modules. SF1 also was identified as a hub-TF gene. To sum up, microarray data analysis could perform a panel of genes that provides new clues for diagnosing chronic ITP.

Neuronal differentiation of rat hair follicle stem cells: the involvement of the neuroprotective factor Seladin-1 (DHCR24).

BACKGROUND: The seladin-1 (selective Alzheimer disease indicator-1), also known as DHCR24, is a gene found to be down-regulated in brain region affected by Alzheimer disease (AD). Whereas, hair follicle stem cells (HFSC), which are affected in with neurogenic potential, it might to hypothesize that this multipotent cell compartment is the predominant source of seladin-1. Our aim was to evaluate seladin-1 gene expression in hair follicle stem cells. METHODS: In this study, bulge area of male Wistar rat HFSC were cultured and then characterized with Seladin-1 immunocytochemistry and flow cytometry on days 8 to 14. Next, 9-11-day cells were evaluated for seladin-1 gene expression by real-time PCR. RESULTS: Our results indicated that expression of the seladin-1 gene (DHCR24) on days 9, 10, and 11 may contribute to the development of HFSC. However, the expression of this gene on day 11 was more than day 10 and on 10th day was more than day 9. Also, we assessed HFSC on day 14 and demonstrated these cells were positive for ß-ш tubulin, and seladin-1 was not expressed in this day. CONCLUSION: HFSC express seladin-1 and this result demonstrates that these cells might be used to cell therapy for AD in future.

Molecular approaches in obesity studies.

The prevalence of obesity as one of the most health concerns has increased globally. This kind of disease has been accounted for several diseases such as type 2 diabetes, different types of cancer, heart disease, and Alzheimer. Obesity is a multifactorial disease that both environmental factors and genetics play important role in its susceptibly. In molecular biology, characterization of the adipocyte secretome is important in signaling to other organs and in regulating energy balance for evaluating underlines mechanism. Since better understanding of this disease lead to both preventive and post treatment of obesity which is achieved by molecular evaluations, this review underlies the importance of some molecular approaches in the field of obesity.