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The clinical advantage staging and underlying mechanisms of Wangbi Tablets against knee osteoarthritis(KOA) were studied based on the "disease-formula" interaction network. Firstly, the clinical symptoms and related genes corresponding to Wangbi Tablets and KOA in the acute, remission, and recovery phases were collected from clinical guidelines/consensus and SoFDA database, and the putative targets of Wangbi Tablets were obtained from ETCM 2.0. Then, Jaccard similarity and cosine similarity were employed to assess the similarities of clinical symptoms, genes, and enriched pathways between Wangbi Tablets and KOA in different phases. The "disease-formula" interaction network of the drug targets and disease genes was constructed, and the key targets were screened by topological feature calculation. KEGG and Reactome database were used for the functional enrichment of the key targets, on the basis of which the functional characteristics of Wangbi Tablets against KOA in the acute, remission, and recovery phases were predicted. Finally, the SW1353 cells exposed to lipopolysaccharide were used to decipher the mechanism of Wangbi Tablets against KOA. The results showed that 92/3 921, 138/3 708, 139/3 800, and 196/3 946 clinical symptoms and the related genes corresponded to KOA in the acute, remission, and recovery phases and Wangbi Tablets were collected from SoFDA, and 260 putative targets of Wangbi Tablets were obtained from ETCM 2.0. Wangbi Tablets had highest similarity of clinical symptoms, genes, and enriched pathways with KOA in the remission phase and the secondary highest similarity with KOA in the recovery phase. The key targets of Wangbi Tablets mainly participated in the regulation of immunity-inflammation imbalance and exerted pain-relieving and bone-protecting effects to alleviate symptoms such as knee joint pain, joint swelling, soreness, fatigue, and dysfunction. Intriguingly, the key targets of Wangbi Tablets possessed antioxidant effects during KOA in the acute and remission phases, while they maintained material and energy metabolism homeostasis and protected vessels during KOA in the recovery phase. The cell experiment indicated that Wangbi Tablets down-regulated the expression of interleukin(IL)-6, IL-1ß, tumor necrosis factor-α(TNF-α), and Bcl-2-associated X protein(Bax)/B-cell lymphoma 2(Bcl-2) via regulating the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) signaling pathway. The findings lay a theoretical foundation for further clarifying the clinical advantage stage and precise clinical application of Wangbi Tablets in treating KOA.
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Medicamentos Herbarios Chinos , Osteoartritis de la Rodilla , Comprimidos , Humanos , Medicamentos Herbarios Chinos/farmacología , Osteoartritis de la Rodilla/tratamiento farmacológico , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/metabolismoRESUMEN
[This corrects the article DOI: 10.3389/fimmu.2022.825426.].
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Crohn's disease (CD) is a chronic disorder of the digestive tract characterized by an uncontrolled immune-mediated inflammatory response in genetically predisposed individuals exposed to environmental risk factors. Although diet has been identified as one of the major environmental risk factors, the role of nutrients in the clinical management of CD patients has not yet been fully investigated. In this prospective observational study, fifty-four patients diagnosed with active Crohn's disease and undergoing anti-TNF-α biological therapy were enrolled and subjected to nutrient intake analysis through a daily food diary. Their nutrient intake and blood values were analyzed before and after 6 months of biological therapy. After 6 months of anti-TNF-α, four patients dropped out of the study, leaving 29 patients in clinical remission and 21 still with active disease that remained the same. The aim of this study was to identify nutrients whose intake or blood values may be associated with patients' responses to biological therapy. In the diet, patients remaining with active CD showed very similar nutrient dietary intake compared to patients achieving remission except for a trend for lower starting zinc intake, below the reference value. In the blood, instead, patients who did not respond to biological therapy showed significantly lower plasma values of iron and taurine before starting biological anti-TNF-α treatment.
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Enfermedad de Crohn , Humanos , Biomarcadores , Enfermedad de Crohn/tratamiento farmacológico , Inmunoterapia , Inhibidores del Factor de Necrosis Tumoral , Estudios ProspectivosRESUMEN
Shortly after diagnosis of type 1 diabetes mellitus (T1DM) and initiation of insulin therapy, many patients experience a transient partial remission (PR) phase, also known as the honeymoon phase. This phase presents a potential therapeutic opportunity due to its association with immunoregulatory and ß cell-protective mechanisms. However, the lack of biomarkers makes its characterization difficult. In this review, we cover the current literature addressing the discovery of new predictive and monitoring biomarkers that contribute to the understanding of the metabolic, epigenetic, and immunological mechanisms underlying PR. We further discuss how these peripheral biomarkers reflect attempts to arrest ß cell autoimmunity and how these can be applied in clinical practice.
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Diabetes Mellitus Tipo 1 , Células Secretoras de Insulina , Humanos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Insulina/uso terapéutico , Biomarcadores , Autoinmunidad , Células Secretoras de Insulina/metabolismoRESUMEN
In type 1 diabetes (T1D), pancreatic beta cells are destroyed by the immune system, causing chronic hyperglycemia and micro and macrovascular complications. However, some people experience a 'honeymoon' phase (or partial remission) after being diagnosed with type 1 diabetes. During this phase, a substantial amount of insulin is still produced by the pancreas, helping to reduce blood sugar levels and the requirement for external insulin. The clinical significance of this phase lies in the potential for pharmacological and non-pharmacological interventions during this time frame to either slow down or arrest beta-cell destruction. Clearly, we need to continue researching novel therapies like immunomodulatory agents, but we also need to look at potentially effective therapies with acceptable side effects that can serve as a complement to the medicines currently being studied. Physical activity and exercise, regardless of its type, is one of the factors its impact on the control of diabetes is being investigated and promising results have been achieved. Although there are still limited reports in this regard, there is some evidence to suggest that regular physical exercise could prolong the honeymoon period in both adults and children. In this review, having described the immune base of type 1 diabetes, we outline the benefits of exercise on the general health of individuals with T1D. Moreover, we centered on the honeymoon and current evidence suggesting the effects of physical activity and exercise on this phase duration.
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Diabetes Mellitus Tipo 1 , Hiperglucemia , Células Secretoras de Insulina , Niño , Adulto , Humanos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Insulina/uso terapéutico , Hiperglucemia/tratamiento farmacológico , Ejercicio FísicoRESUMEN
Objective:To explore the core syndrome type and Chinese herbal medicine combination in Ulcerative Colitis (UC) remission phase based on the real and effective clinical data of the outpatient information system of the hospital.Methods:Medical records of patients with UC in remission who received Traditional Chinese Medicine (TCM) oral intervention from August 1, 2018 to October 31, 2021 in Jiangsu Provincial Hospital of Traditional Chinese Medicine were collected. Medcase V3.2 data record mining system was used, and the enhanced FPGrowth algorithm was used to build a strengthened association rule data mining model. Xminer Operation Tool was used for mining and logical analysis, and Medcase Chart was used for deconstruction analysis and graphical representation of quantitative trend data. Based on the statistical analysis results, the core syndrome types, pathogenesis evolution rules, and core TCM compatibility law in remission stage of UC were explored.Results:A total of 302 patients were collected. Diarrhea, bloody stool, mucus stool, fatigue, light tongue, fine pulse, paroxysmal abdominal pain, and colonoscopy found intestinal polyps were the core symptoms in UC remission phase. Spleen Qi Deficiency Syndrome, Spleen Deficiency and Dampness Syndrome, Spleen Deficiency and Toxin Accumulation Syndrome were the core syndrome type. In Spleen Qi Deficiency Syndrome, the core drug combinationed Codonopsis Radix, Atractylodis Macrocephalae Rhizoma, Poria, Glycyrrhizae Radix et Rhizoma, Aucklandiae Radix, Amomi Fructus, Angelicae Sinensis Radix, and Paeoniae Radix Alba. In Spleen Deficiency and Dampness Syndrome, the core drug combinationed Codonopsis Radix, Atractylodis Macrocephalae Rhizoma, Poria, Glycyrrhizae Radix et Rhizoma, Aucklandiae Radix, Coptidis Rhizoma, Amomi Fructus, and Saposhnikoviae Radix. In Spleen Deficiency and Toxin Accumulation Syndrome, the core drug combinationed Codonopsis Radix, Astragali Radix, Atractylodis Macrocephalae Rhizoma, Citri Reticulatae Pericarpium, Mume Fructus, Sophorae Flos, Coptidis Rhizoma, and Saposhnikoviae Radix.Conclusion:Spleen deficiency was the core syndrome type in UC remission phase. The Chinese herbal medicine treatment options included replenishing qi supplemented with harmonizing the stomach, promoting blood circulation, stopping bleeding, removing dampness, clearing heat, and relieving depression.
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Objective: To propose a new definition of partial remission (PR) for patients with type 1 diabetes (T1D) of all-ages using insulin dose and glycated albumin (GA), and find the optimal cut-off values for stimulated C-peptide to diagnose PR in different age-groups. Research Design and Methods: Patients with newly diagnosed T1D (n=301) were included. GA/insulin dose was used to diagnose PR, and insulin dose-adjusted glycated albumin (IDAGA) was proposed to facilitate clinical application. The optimal diagnostic levels of IDAGA and stimulated C-peptide were determined in different age-groups (≤ 12y, 12-18y and ≥ 18y). Furthermore, the diagnostic consistency between different PR definitions was studied. Results: GA≤ 23%/insulin dose ≤ 0.5u/kg/day was used to define PR, and IDAGA (GA (%) + 40 * insulin dose(u/kg/day)) ≤ 40 was feasible in all age-groups. Whereas, the optimal diagnostic level showed difference for stimulated C-peptide (265.5, 449.3 and 241.1 pmol/L for the ≤ 12y, 12-18y and ≥ 18y age-group, respectively). About 40% of patients met the PR definition by stimulated C-peptide but not GA/insulin dose or IDAGA, who showed dyslipidemia and higher insulin resistance. Conclusions: A new definition of the PR phase is proposed using GA/insulin dose, and the calculated IDAGA≤ 40 applies to all age-groups. The stimulated C-peptide to diagnose PR is the highest in the 12-18y age-group, which reflects the effect of puberty on metabolism. For patients with insulin resistance, it is not recommended to use stimulated C-peptide alone to diagnose PR.
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Diabetes Mellitus Tipo 1 , Resistencia a la Insulina , Péptido C , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Hemoglobina Glucada/análisis , Productos Finales de Glicación Avanzada , Humanos , Insulina/metabolismo , Insulina/uso terapéutico , Albúmina Sérica , Albúmina Sérica GlicadaRESUMEN
The partial remission (PR) phase, a period experienced by most patients with type 1 diabetes (T1D) soon after diagnosis, is characterized by low insulin requirements and improved glycemic control. Given the great potential of this phase as a therapeutic window for immunotherapies because of its association with immunoregulatory mechanisms and ß-cell protection, our objective was to find peripheral immunological biomarkers for its better characterization, monitoring, and prediction. The longitudinal follow-up of 17 pediatric patients with new-onset T1D over one year revealed that, during the PR phase, remitter patients show increased percentages of effector memory (EM) T lymphocytes, terminally differentiated EM T lymphocytes, and neutrophils in comparison to non-remitter patients. On the contrary, remitter patients showed lower percentages of naïve T lymphocytes, regulatory T cells (TREG), and dendritic cells (DCs). After a year of follow-up, these patients also presented increased levels of regulatory B cells and transitional T1 B lymphocytes. On the other hand, although none of the analyzed cytokines (IL-2, IL-6, TGF-ß1, IL-17A, and IL-10) could distinguish or predict remission, IL-17A was increased at T1D diagnosis in comparison to control subjects, and remitter patients tended to maintain lower levels of this cytokine than non-remitters. Therefore, these potential monitoring immunological biomarkers of PR support that this stage is governed by both metabolic and immunological factors and suggest immunoregulatory attempts during this phase. Furthermore, since the percentage of TREG, monocytes, and DCs, and the total daily insulin dose at diagnosis were found to be predictors of the PR phase, we next created an index-based predictive model comprising those immune cell percentages that could potentially predict remission at T1D onset. Although our preliminary study needs further validation, these candidate biomarkers could be useful for the immunological characterization of the PR phase, the stratification of patients with better disease prognosis, and a more personalized therapeutic management.
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Diabetes Mellitus Tipo 1 , Biomarcadores/metabolismo , Niño , Citocinas/uso terapéutico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/terapia , Humanos , Insulina/uso terapéutico , Interleucina-17 , Inducción de RemisiónRESUMEN
AIMS: Studies suggest that type 1 diabetes (T1D) contributes to impaired insulin sensitivity (IS). Most children with T1D experience partial remission but the knowledge regarding the magnitude and implications of impaired IS in this phase is limited. Therefore, we investigate the impact of IS on the partial remission phase. METHODS: In a longitudinal study of children and adolescents, participants were seen at three clinical visits during the first 14.5 months after diagnosis of T1D. Partial remission was defined as IDAA1c (HbA1c (%) + 4*daily insulin dose) ≤ 9. Beta-cell function was considered significant by a stimulated c-peptide > 300 pmol/L. Participants were characterized by (i) remission or non-remission and (ii) stimulated c-peptide levels above or below 300 pmol/L. IS, body mass index (BMI), total body fat, sex, age, pubertal status and ketoacidosis at onset were compared. RESULTS: Seventy-eight children and adolescents aged 3.3-17.7 years were included. At 14.5 months post-diagnosis, 54.5% of the participants with stimulated c-peptide > 300 pmol/L were not in partial remission. Participants not in remission had significant lower IS 2.5 (p = 0.032), and 14.5 (p = 0.022) months after diagnosis compared to participants in partial remission with similar c-peptide levels. IS did not fluctuate during the remission phase. CONCLUSIONS: A number of children and adolescents have impaired IS in the remission phase of paediatric T1D and are not in remission 14.5 months after diagnosis despite stimulated c-peptide > 300 pmol/L.
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Índice de Masa Corporal , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hemoglobina Glucada/metabolismo , Resistencia a la Insulina/fisiología , Insulina/uso terapéutico , Inducción de Remisión/métodos , Adolescente , Niño , Preescolar , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Pronóstico , Estudios Retrospectivos , Factores de TiempoRESUMEN
Ulcerative colitis (UC) is a frequent type of inflammatory bowel disease, characterized by periods of remission and exacerbation. Gut dysbiosis may influence pathophysiology and clinical response in UC. The purpose of this study was to evaluate whether gut microbiota is related to the active and remission phases of pancolitis in patients with UC as well as in healthy participants. Fecal samples were obtained from 18 patients with UC and clinical-endoscopic evidenced pancolitis (active phase n = 9 and remission phase n = 9), as well as 15 healthy participants. After fecal DNA extraction, the 16S rRNA gene was amplified and sequenced (Illumina MiSeq), operational taxonomic units were analyzed with the QIIME software. Gut microbiota composition revealed a higher abundance of the phyla Proteobacteria and Fusobacteria in active pancolitis, as compared with remission and healthy participants. Likewise, a marked abundance of the genus Bilophila and Fusobacteria were present in active pancolitis, whereas a higher abundance of Faecalibacterium characterized both remission and healthy participants. LEfSe analysis showed that the genus Roseburia and Faecalibacterium were enriched in remission pancolitis, and genera Bilophila and Fusobacterium were enriched in active pancolitis. The relative abundance of Fecalibacterium and Roseburia showed a higher correlation with fecal calprotectin, while Bilophila and Fusobacterium showed AUCs (area under the curve) of 0.917 and 0.988 for active vs. remission pancolitis. The results of our study highlight the relation of gut dysbiosis with clinically relevant phases of pancolitis in patients with UC. Particularly, Fecalibacterium, Roseburia, Bilophila, and Fusobacterium were identified as genera highly related to the different clinical phases of pancolitis.
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Bacterias/clasificación , Colitis Ulcerosa/microbiología , Colitis/microbiología , Disbiosis/microbiología , Heces/microbiología , Microbioma Gastrointestinal , Adulto , Bacterias/genética , Biodiversidad , ADN Bacteriano , Femenino , Voluntarios Sanos , Humanos , Complejo de Antígeno L1 de Leucocito/análisis , Masculino , ARN Ribosómico 16S , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Beneficial effects of physical activity (PA) are confirmed in patients with all types of long-lasting diabetes. The possibility of PA to be a factor prolonging remission phase in children with new-onset type 1 diabetes (T1D) has not yet been thoroughly studied. OBJECTIVE: The aim of the study was to elucidate the influence of regular PA on prevalence of partial remission (PR), metabolic control, daily insulin requirement (DIR), and C-peptide secretion in children newly diagnosed with T1D. METHODS: A total of 125 children diagnosed with T1D were studied prospectively for 2 years. Patients were controlled every 3 months and advised with PA according to ISPAD recommendations. Anthropometric parameters, HbA1c, C-peptide level and DIR were analyzed. Patients' PA level was assessed using a self-designed questionnaire. RESULTS: We classified 43% of participants as physically-active. In this group, lower HbA1c after 2 years, lower DIR after 3, 6 months, and after 2 years (all P < .05) were found. At discharge from hospital, the prevalence of DIR < 0.5 U/kg/24 h with near normoglycemia was similar in both groups. Then, we observed higher PR prevalence in active group lasting over time and resulting in 44% vs 13% after 2 years (P < .001). C-peptide after 2 years was comparable in both groups, with higher prevalence of clinically significant levels (>0.2 nmoL/L) in active group: 79.6% vs 61.4% (P = .029). CONCLUSIONS: These data support the view that regular PA may essentially contribute to extending PR time in pediatric diabetes, and may therefore lead to a better long-term metabolic control of the disease.
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Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/rehabilitación , Ejercicio Físico/fisiología , Adolescente , Edad de Inicio , Niño , Conducta Infantil/fisiología , Preescolar , Diabetes Mellitus Tipo 1/etiología , Femenino , Conductas Relacionadas con la Salud/fisiología , Humanos , Masculino , Polonia/epidemiología , Inducción de Remisión , Medición de Riesgo , Factores de TiempoRESUMEN
CONTEXT: Partial remission (PR) in type 1 diabetes (T1D) is accompanied by downregulation of the immune response. Programmed cell death-1 (PD-1) and its ligand (PD-L1) are important immunosuppressive molecules, but their changes in the PR phase are unclear. OBJECTIVE: We investigated the dynamic changes of PD-1/PD-L1 expression on T cells around the PR phase in T1D. METHODS: Ninety-eight T1D patients were recruited cross-sectionally and grouped according to PR status into nonremitters (individuals who did not undergo PR during the disease course; n = 39), pre-PR (n = 15), mid-PR (n = 30), and post-PR (n = 14) subgroups. PR was defined according to C-peptide level ≥300 pmol/L or index of insulin-adjusted hemoglobin A1c ≤9 as recommended. Among all the 98 patients, 29 newly diagnosed individuals were prospectively followed up for 1 year. The dynamic changes of PD-1/PD-L1 expression, frequency of regulatory T cells (Tregs) and IL-35+ Tregs among peripheral CD4/CD8+ T cells were determined. RESULTS: PD-1/PD-L1 on CD4+/CD8+ T cells showed a dynamic change around the PR phase: lowest in pre-PR phase, restored in mid-PR phase, and declined again in post-PR phase. Conversely, this pattern did not occur for nonremitters. Notably, PD-1 expression on CD8+ T cells in mid-PR was positively correlated with the length of the PR phase. The percentages of circulating Tregs and IL-35+ Tregs showed no relation to PR. CONCLUSIONS: The PR phase is associated with restoration of PD-1/PD-L1 on CD4+ and CD8+ T cells, suggesting that PD-1/PD-L1 may be a potential target for prolonging this phase in T1D.
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Antígeno B7-H1/metabolismo , Biomarcadores/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Diabetes Mellitus Tipo 1/patología , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos T Reguladores/inmunología , Adolescente , Adulto , Anciano , Glucemia/análisis , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Estudios de Casos y Controles , Niño , Preescolar , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/metabolismo , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Lactante , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Inducción de Remisión , Adulto JovenRESUMEN
Type 1 diabetes mellitus (T1DM) is characterized by irreversible islet ß cell destruction. During the progression of this disease, some patients with T1DM experience a phase of remission known as honeymoon or partial remission (PR) that is mainly characterized by satisfactory glycemic control and the transient recovery of islet ß cell function. This special phase is a good model for studying the mechanism of ß cell protection, might serve as a proper intervention period for immunotherapy, and may be related to disease prognosis. This special stage is highly valuable for studies aiming to identify possible targets that may be used to cure T1DM. An in-depth understanding of the diagnosis, epidemiology, and possible mechanisms of the PR phase is highly needed. In general, patients enter the PR phase approximately 3 months after starting insulin therapy, and this phase could be sustained for 6 to 9 months. Current research increasingly focuses on the metabolic and immunological aspects to constantly update our understanding of this phase. This review concentrates on the PR phase of T1DM to provide a comprehensive outlook of its epidemiology, diagnostic criteria, and underlying immune metabolic mechanisms.
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Diabetes Mellitus Tipo 1/epidemiología , Hipoglucemiantes/farmacología , Insulina/farmacología , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/metabolismo , Humanos , Pronóstico , Inducción de RemisiónRESUMEN
The remission phase (or honeymoon period) is a spontaneous "temporary cure stage" in type 1 diabetes course, which provides a good human model for studying ß-cell protection. The exact mechanisms are still uncertain, but one of the generally recognized mechanisms is that correction of "glucotoxicity" by exogenous insulin therapy leads to "ß-cell rest" and ß-cell recovery. Beyond this, the remission phase is accompanied by changes in various immune cells and immune molecules, indicating downregulation of immune response, and induction of immune tolerance. The role of hyperglycemia rectification in the regulation of immune response should be emphasized because glucose metabolism is critical to maintain the normal function of immune system. Here, recent evidence of immune modulation based on the rectification of hyperglycemia from multiple aspects such as immune cells, inflammatory cytokines, biomolecules, and cell antigenicity was reviewed. It should be noteworthy that the interaction between glucose metabolism and immune plays an important role in the pathogenesis of the remission phase. The best intervention strategy may be the combination of strict glycemic control and immune modulation to protect ß-cell function as early as possible.
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OBJECTIVE: To evaluate and differentially diagnose erosive skeletal lesions located on multiple joints of an individual archaeologically recovered in 2017. MATERIALS: Skeletal remains of a well-preserved skeleton dating to the 12th-13th centuries from the medieval church of San Biagio in Cittiglio (Varese, northern Italy). METHODS: Macroscopic and radiographic imaging. RESULTS: Erosive marginal symmetrical lesions are present on the metatarsophalangeal, metacarpophalangeal and interphalangeal joints of an adult male, aged 55-75 years. Osteolytic changes, in the form of pocket erosions, surface resorptions and pseudocyst formations, are also macroscopically observed on some carpal and tarsal bones and on several large peripheral joints. CONCLUSIONS: A careful differential diagnosis of the lesions and their macroscopic and radiological appearance is suggestive of a case of rheumatoid arthritis-like polyarthropathy. SIGNIFICANCE: This case contributes to the debate regarding the antiquity of erosive polyarthropathies, providing additional evidence for the existence of these diseases in the Old World prior to the European discovery of the Americas. LIMITATIONS: Small sample size limits discussion of the scope of the disease in antiquity. SUGGESTIONS FOR FURTHER RESEARCH: This case highlights the need for further macroscopic, radiographic, and biomolecular studies of pre-modern European skeletal samples to investigate the hypothesized pre-existence of these pathological conditions in Europe prior to 1492.
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Artritis Reumatoide/historia , Osteoartritis/historia , Anciano , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/patología , Huesos del Carpo/diagnóstico por imagen , Huesos del Carpo/patología , Historia Medieval , Humanos , Italia , Masculino , Persona de Mediana Edad , Osteoartritis/diagnóstico por imagen , Osteoartritis/patología , Radiografía , Esqueleto/diagnóstico por imagen , Esqueleto/patología , Huesos Tarsianos/diagnóstico por imagen , Huesos Tarsianos/patologíaRESUMEN
Circulating microRNAs (miRNAs) have been implicated in several pathologies including type 1 diabetes. In the present study, we aimed to identify circulating miRNAs affected by disease duration in children with recent onset type 1 diabetes. Forty children and adolescents from the Danish Remission Phase Cohort were followed with blood samples drawn at 1, 3, 6, 12, and 60 months after diagnosis. Pancreatic autoantibodies were measured at each visit. Cytokines were measured only the first year. miRNA expression profiling was performed by RT-qPCR. The effect of disease duration was analyzed by mixed models for repeated measurements adjusted for sex and age. Eight miRNAs (hsa-miR-10b-5p, hsa-miR-17-5p, hsa-miR-30e-5p, hsa-miR-93-5p, hsa-miR-99a-5p, hsa-miR-125b-5p, hsa-miR-423-3p, and hsa-miR-497-5p) were found to significantly change in expression (adjusted p-value < 0.05) with disease progression. Three pancreatic autoantibodies, ICA, IA-2A, and GAD65A, and four cytokines, IL-4, IL-10, IL-21, and IL-22, were associated with the miRNAs at different time points. Pathway analysis revealed associations with various immune-mediated signaling pathways. Eight miRNAs that were involved in immunological pathways changed expression levels during the first five years after diagnosis and were associated with variations in cytokine and pancreatic antibodies, suggesting a possible effect on the immunological processes in the early phase of the disease.
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AIM: Aim of this study was to compare the gene expression of Interleukin 12 members in two phase of IBD. BACKGROUND: Inflammatory bowel disease (IBD) is a well-known gastrointestinal disorder in the world that fluctuates between remission and flare-up phases. Each of these phases has an individual immune system response profile. Therefore, analyzing the interleukins (IL) expression status improves the diagnosis and the classification of the IBD cases. METHODS: In this a case-control study, among 400 patients whom admitted to the IBD clinic, forty nine IBD patients were included. Patients were divided into three categories based on 1) the phase of the disease, 2) the type of IBD, Ulcerative colitis (UC) or Crohn's disease (CD), and 3) the therapeutic pathways. Using the real-time PCR method, the expression levels of IL-12A, IL-12B, IL-23A, and IL-27 were examined in the peripheral blood mononuclear cell (PBMC) and compared to the pre-described subgroups. RESULTS: the data showed upregulation in the expression levels of IL-12A and IL-12B in the remission phase in comparison with the flare-up. However, no significant changes were obtained from the evaluation of IL-23A and IL-27. In addition, the mRNA levels of the target genes in the subgroups of Category 2 as well as Category 3 were similar. CONCLUSION: Our results showed that expression patterns of the IL-12A and IL-12B genes varied between the remission and flare-up phases for the IBD patients, and may be considered as potential biomarkers for the detection and the classification of IBD cases.
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To screen and evaluate the TCM in the treatment of bronchial asthma. Methods Retrieved the journals from China National Knowledge Infrastructure, the Vip Database, Wanfang Data and the Chinese Biomedical Literature Database (Sino Med) . The time limitation ran from January 1, 1987 to December 31, 2016. Extracted the indicators of the assessment based on the evaluating and screening system of country feasible TCM technology. Results a total of 150 treatment techniques were screened.They mostly were Chinese compound formula or point-application therapy. The score was between 24.857 and 34.304. Application of evaluating and screening system of country feasible TCM technology can screen and evaluate the feasible technologiesin the treatment of remission phase of bronchial asthma.
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Type 1 diabetes (T1D) is a metabolic disease of unknown aetiology that results from the autoimmune destruction of the ß-cells. Clinical onset with classic hyperglycaemic symptoms occurs much more frequently in children and young adults, when less than 30% of ß-cells remain. Exogenous insulin administration is the only treatment for patients. However, due to glucose dysregulation, severe complications develop gradually. Recently, an increase in T1D incidence has been reported worldwide, especially in children. Shortly after diagnosis, T1D patients often experience partial remission called "honeymoon phase," which lasts a few months, with minor requirements of exogenous insulin. In this stage, the remaining ß-cells are still able to produce enough insulin to reduce the administration of exogenous insulin. A recovery of immunological tolerance to ß-cell autoantigens could explain the regeneration attempt in this remission phase. This mini-review focuses on the remission phase in childhood T1D. Understanding this period and finding those peripheral biomarkers that are signs of immunoregulation or islet regeneration could contribute to the identification of patients with a better glycaemic prognosis and a lower risk of secondary complications. This remission phase could be a good checkpoint for the administration of future immunotherapies.
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Diabetes Mellitus Tipo 1/sangre , Insulina/sangre , Biomarcadores/sangre , Péptido C/sangre , Niño , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Humanos , Insulina/uso terapéutico , Inducción de RemisiónRESUMEN
AIM: Gluten-free diet has shown promising effects in preventing type 1 diabetes (T1D) in animals as well as beneficial effects on the immune system. Gluten-free diet at diabetes onset may alter the natural course and outcome of autoimmune diseases such as T1D. METHODS: In a 12-month study, 15 children newly diagnosed with T1D were instructed to follow a gluten-free diet. Questionnaires were used to evaluate adherence to the gluten-free diet. Partial remission (PR) was defined by insulin dose-adjusted A1c (IDAA1c) ≤9 or stimulated C-peptide (SCP) >300 pmol/L measured 90 min after a liquid mixed meal at the inclusion, six and 12 months after onset. The intervention group was compared with two previous cohorts. Linear mixed models were used to estimate differences between cohorts. RESULTS: After 6 months, more children on a gluten-free diet tended to have SCP values above 300 pmol/L compared to the European cohort (p = 0.08). The adherence to a gluten-free diet decreased during the 12-month study period. After 1 year there was no difference in SCP levels or percentage in remission according to SCP (p > 0.1). Three times as many children were still in PR based on IDAA1c (p < 0.05). Twelve months after onset HbA1c were 21 % lower and IDAA1c >1 unit lower in the cohort on a gluten-free diet compared to the two previous cohorts (p < 0.001). CONCLUSION: Gluten-free diet is feasible in highly motivated families and is associated with a significantly better outcome as assessed by HbA1c and IDAA1c. This finding needs confirmation in a randomized trial including screening for quality of life. (Clinicaltrials.gov number NCT02284815).