BackgroundDiabetes is an autoimmunologic disease that may have a different background. The aim of our study was to show that type 1 diabetes is accompanied by changes in gene expression in peripheral blood mononuclear cells. We analyzed the genes characteristic of pancreatic islet cells and genes playing a big part in autoimmune diseases and cancer.DesignThe study included 21 patients and was performed to examine the expression of 9 genes. The patients were divided into 3 research groups: people with type 1 diabetes, people with diabetes after pancreas transplant, and a control group of healthy patients. To assess the level of expression, RNA material was obtained from peripheral blood collected from individuals qualified for the study.ResultsThe results of the study showed many interesting changes in the expression level of the analyzed genes. It was demonstrated that CASR gene expression was significantly higher in transplant patients than in diabetic patients. Differences in the level of activity are also noted in genes that take part in autoimmune diseases.ProposalProfiling gene expression in peripheral blood samples may be a useful and noninvasive diagnostic tool that allows early detection of changes leading to the onset or resumption of diabetes. 相似文献
BackgroundRecurrence and distant metastases remain a significant issue in locally advanced rectal cancer (LARC). Several multimodal strategies are assessed in clinical trials.Patients and MethodsPatients with mid/low magnetic resonance imaging–defined high-risk LARC were randomized to arm A (12-week bevacizumab + FOLFOX-4 then bevacizumab–5-fluorouracil [5-FU]–radiotherapy [RT] before total mesorectal excision [TME]) or arm B (bevacizumab-5-FU–RT then TME). Long-term efficacy and safety up to 5 years’ follow-up are reported. No comparison between arms was planned.ResultsOverall, 91 patients (46 in arm A and 45 in arm B) were included. Main results have been presented previously. During the late follow-up period (> 4 weeks after surgery), 4 patients (8.7%) in arm A and 4 (8.9%) in arm B experienced grade 3/4 adverse events related to bevacizumab; the most frequent were 2 anastomotic fistulas (both in arm A) and abscesses (1 in arm A and 2 in arm B). At 5 years’ follow-up, 9 (19.6%) and 11 (24.4%) patients in arms A and B developed a fistula in the year after surgery, and 2 (4.3%) in arm A at > 1 year after surgery. Most resolved before study end. Five-year disease-free survival was 70% and 64.3% in arms A and B, respectively. Five-year overall survival was 90.5% (95% confidence interval, 76.7, 96.3) in arm A and 72.7% (95% confidence interval, 56.0, 83.9) in arm B.ConclusionNeoadjuvant bevacizumab + FOLFOX-4 may have the potential to increase survival outcomes when followed by bevacizumab–5-FU–RT and TME in LARC. Bevacizumab–5-FU–RT then TME was associated with a higher-than-projected rate of anastomotic fistulas. Further research of neoadjuvant strategies in LARC is encouraged. 相似文献
BackgroundHiatal hernia is frequently encountered intraoperatively during bariatric surgery. There is scarce research pertaining to the diagnostic accuracy of a preoperative diagnostic modality in comparison to intraoperative diagnosis, along with patient characteristics and related factors contributing to hiatal hernia.ObjectiveTo identify the prevalence and associations of hiatal hernia in the bariatric patient population, we compared the diagnostic accuracy of upper gastrointestinal series and esophagogastroduodenoscopy with the intraoperative findings across various patient characteristics.SettingMetabolic and Bariatric Surgery Accreditation and Quality Improvement Program, Teaching Hospital, New York, USA.MethodsRetrospective study of patients from 2015 to 2018 who met National Institutes of Health criteria for bariatric surgery.ResultsThere were 1094 patients included (135 males, 959 females), with an age range of 18 to 74 years. The diagnostic accuracy was determined by a sensitivity of 64.71% (95% confidence interval [CI] .55–.70), specificity of 74.38% (95% CI .71–.70), positive predictive value of 29.86% (95% CI .24–.30), negative predictive value of 92.59% (95%CI .89–90), likelihood ratio of 2.526, and P value < .0001 for esophagogastroduodenoscopy; a sensitivity of 14.02% (95% CI .08–0), specificity of 98.23% (95% CI .96–.90), positive predictive value of 71.43% (95% CI .50–.80), negative predictive value of 78.35% (95% CI .74–.80), likelihood ratio 7.921, and P value < .0001 were used for upper gastrointestinal series. Hiatal hernia with age <60 years was 17.09% versus 48.44% at >60 years (P < .0001). Hiatal hernia incidence was 17% in Hispanics, 22.5% in Caucasians, and 23.10% in blacks.ConclusionThe prevalence of hiatal hernia is 18.92%. There is strong association between hiatal hernia and age and ethnicity and no association based on sex and body mass index. The diagnostic accuracy of upper gastrointestinal series is very low compared with that of esophagogastroduodenoscopy for hiatal hernia. Preoperative diagnosis of hiatal hernia in the bariatric population is not required based on our study. Not only does it lessen the economic burden, patient wait time, and discomfort of an additional study, but preoperative diagnosis does not change, alter, or aid in the intraoperative management of hiatal hernia considering the suboptimal accuracy of preoperative diagnostics, thus deeming them unwarranted. 相似文献
Introduction: The rising prevalence of musculoskeletal pathologies in developed countries has caused a dramatic impact on social welfare. Amidst these musculoskeletal pathologies is Rheumatoid arthritis (RA), a chronic systemic autoimmune disease that mostly affects the synovium. RA metabolic-associated alterations, including distorted adipokine production, enhance RA inflammatory environment. Among the altered adipokines, visfatin is particularly involved in RA inflammation and catabolism and stands out as an essential enzyme linked to critical cell features.
Areas covered: We discuss the potential mechanism supporting the contribution of visfatin to RA and the association between RA and obesity. We discuss the repurposing of cancer-tested drugs to inhibit visfatin in the context of RA. Additionally, we address the possibility of combining these drugs with current RA therapy. Finally, we explore the future of visfatin as an RA biomarker or therapeutic target.
Expert opinion: Inhibition of visfatin has become an interesting therapeutic approach for RA pathology. Such a feat has already been attained in oncology using small molecule inhibitors, which suggest that a similar course of action would be worth pursuing in the RA context. Visfatin will become an important biomarker and therapeutic target for RA. 相似文献
This study was designed to evaluate the role of nitric oxide (NO) in FK506-induced nephrotoxicity by administering an inhibitor of NO synthesis, Nω-nitro-L-arginine methyl ester (L-NAME) to rats treated with FK506. After one week of treatment with FK506 (3.2 mg/kg/day, intramuscularly) and/or L-NAME (5 mg/100 mL of L-NAME in the drinking water), the arterial pressure, urinary NOx, and parameters for renal function were measured, and histological analysis of the kidney was made. In the L-NAME without FK506 group, L-NAME administration effectively inhibited urinary NOx excretion and increased mean arterial pressure (MAP) without any change in renal function. In the FK506 without L-NAME group, FK506 treatment showed increase in urinary NOx excretion and mild renal dysfunction. In the FK506 with L-NAME group, urinary NOx excretion was decreased by L-NAME administration and renal function was significantly worsened than FK506 without L-NAME group. The plasma creatinine, BUN and urinary N-acetyl-β-D-glucosaminidase increased 2-, 3-, and 3-fold, respectively and the creatinine clearance was reduced by 50% as compared with that in the FK506 without L-NAME group. Histological analysis revealed severe interstitial fibrosis and tubular atrophy in the FK506 + L-NAME treatment group. Thus, results suggest that NO synthesis is enhanced in the kidney during FK506-induced nephrotoxicity and that NO synthesis inhibition aggravates FK506-induced nephrotoxicity. NO may play a protective role attributable to the balance of vasoactive substances in FK506-induced nephrotoxicity. 相似文献
Biliary tract cancers (BTCs) are a group of invasive neoplasms, with increasing incidence and dismal prognosis. In advanced disease, the standard of care is represented by first-line chemotherapy with cisplatin and gemcitabine. In subsequent lines, no clear recommendations are currently available, highlighting the need for novel therapeutic approaches.The PI3K/AKT/mTOR pathway is a core regulator of cell metabolism, growth and survival, and is involved in BTCs carcinogenesis and progression. Mutations, gene copy number alterations and aberrant protein phosphorylation of PI3K, AKT, mTOR and PTEN have been thoroughly described in BTCs and correlate with poor survival outcomes.Several pre-clinical evidences state the efficacy of PI3K/AKT/mTOR pathway inhibitors in BTCs, both in vitro and in vivo. In the clinical setting, initial studies with rapamycin analogs have shown interesting activity with an acceptable toxicity profile. Novel strategies evaluating AKT and PI3K inhibitors have risen serious safety concerns, pointing out the need for improved patient selection and increased target specificity for the clinical development of these agents, both alone and in combination with chemotherapy.This review extensively describes the role of the PI3K/AKT/mTOR pathway in BTCs and examines the rationale of its targeting in these tumors, with particular focus on clinical activity, toxicities and perspectives on further development of PI3K/AKT/mTOR pathway inhibitors. 相似文献