IntroductionLittle is known about the risk of hypertension in patients with the early stage of type 2 diabetes. We investigated the risk of hypertension in participants with newly diagnosed type 2 ...diabetes and prediabetes.Research design and methodsThis is a retrospective cohort study consisting of 2136 middle-aged participants (1022 with normal fasting glucose/normal glucose tolerance (NFG/NGT), 418 with impaired fasting glucose (IFG), 466 with impaired glucose tolerance (IGT) and 230 with diabetes) and 3426 elderly participants (1762 with NFG/NGT, 599 with IFG, 781 with IGT, and 284 with diabetes). All participants underwent 75 g oral glucose tolerance tests at baseline.ResultsOver a median 59-month follow-up period, 459 middle-aged and 1170 elderly participants developed hypertension. In middle-aged participants, the odds of incident hypertension were significantly higher in those with IFG (OR 1.40; p=0.019), IGT (OR 1.49; p=0.004), and diabetes (OR 1.55; p=0.013) than those with NFG/NGT, which was no longer significant after adjustment for body mass index. Subgroup analysis showed that the risk of hypertension was significantly higher in diabetes than NFG/NGT only in participants without obesity. Conversely, obesity was a risk factor of hypertension only in those with IFG and NFG/NGT. In elderly participants, there was no difference in the risk of hypertension among the NFG/NGT, IFG, IGT and diabetes groups.ConclusionsThe risk of hypertension is modest in participants with newly diagnosed type 2 diabetes and prediabetes. Our findings suggest that the early stages of type 2 diabetes and prediabetes may be a key period for reducing hypertension, given the pronounced risk of hypertension in patients with diabetes reported in previous studies. In terms of reducing the risk for hypertension, obesity treatment might be advantageous in the early stages rather than the advanced stages of impaired glucose metabolism.
CD4
Foxp3
regulatory T cells (Tregs) are essential for homeostasis in the colon, but the mechanism by which local environmental cues determine the localization of colonic Tregs is unclear. Here, we ...administer indigo naturalis (IN), a nontoxic phytochemical aryl hydrocarbon receptor (AhR) agonist used for treating patients with ulcerative colitis (UC) in Asia, and we show that IN increases Helios
Tregs and MHC class II
epithelial cells (ECs) in the colon. Interactions between Tregs and MHC class II
ECs occur mainly near the crypt bottom in the steady state, whereas Tregs dramatically increase and shift toward the crypt top following IN treatment. Moreover, the number of CD25
T cells is increased near the surface of ECs in IN-treated UC patients compared with that in patients treated with other therapies. We also highlight additional AhR-signaling mechanisms in intestinal ECs that determine the accumulation and localization of Helios
Tregs in the colon.
Tissue inhibitors of metalloproteinases (TIMPs) are endogenous matrix metalloproteinase inhibitors. TIMP1 is produced by cancer cells and has pleiotropic activities. However, its role and source in ...multiple myeloma (MM) are unclear. Here, we evaluated TIMP1 protein and mRNA levels in bone marrow (BM) plasma cells and assessed the effects of TIMP1 expression on fibroblast invasive capacity using three-dimensional spheroid cell invasion assays.
mRNA and protein levels were elevated when patients progressed from monoclonal gammopathy of undetermined significance or smouldering myeloma to MM. Furthermore, TIMP1 levels decreased at complete response and TIMP1 protein levels increased with higher international staging.
mRNA levels were markedly higher in extramedullary plasmacytoma and MM with t(4;14). Overall survival and post-progression survival were significantly lower in MM patients with high TIMP1 protein. Recombinant TIMP1 did not directly affect MM cells but enhanced the invasive capacity of fibroblasts; this effect was suppressed by treatment with anti-TIMP1 antibodies. Fibroblasts supported myeloma cell invasion and expansion in extracellular matrix. Overall, these results suggested that MM-derived TIMP1 induces the invasive phenotype in fibroblasts and is involved in disease progression. Further studies are required to elucidate the specific roles of TIMP1 in MM and facilitate the development of novel therapies targeting the TIMP1 pathway.
Intra-tumor heterogeneity (genotypic and functional diversity among cancer cells within the same tumor) represents one of the key challenges in cancer medicine. As heterogeneity of cancer cells ...constitutes an important parameter in the development of therapy resistance, an accurate assessment of intra-tumor heterogeneity is essential for the prediction of drug resistance and development of effective treatment. In this review, we evaluate primary patient derived-tumor organoid technology as a new tool for colorectal cancer research and treatment. Furthermore, we discuss organoid use to understand intra-tumor heterogeneity, both in terms of mutational diversification and of diversification in drug sensitivity. Finally, we address the exciting recent results that show that tumor organoid technology is highly predictive for drug response in metastatic colorectal cancer.
A retrospective study involving eight African pygmy hedgehogs histopathologically diagnosed with granulosa cell tumors was conducted. The age at onset was 2.2–4.5 years, with a median age of 3.6 ...years. The most common clinical signs were hematuria and abdominal distension, which were observed in >50% cases. Exploratory laparotomy was performed in all cases, and ovariohysterectomy or excision of the abdominal mass was performed. Patients with only hematuria survived for >250 days after surgery, whereas those with initial ascites showed recurrence of ascites or tumor growth and survived for approximately 130 days after surgery. Intraperitoneal injection of carboplatin was performed in three recurrent cases. In one of these three cases, the tumor mass disappeared. Hence, carboplatin can be considered a potential antineoplastic drug for the treatment of granulosa cell tumors.
Objective Atrial fibrillation (AF) is the most common cause of tachycardia-induced cardiomyopathy (TIC). However, which patients with AF are prone to developing TIC remains unclear. In this study, we ...investigated the clinical features of AF patients with TIC. Methods This single-center study included 722 patients with AF (average age, 63.1±10.2 years old; 191 women) who underwent radiofrequency catheter ablation. We defined TIC as an initial left ventricular ejection fraction (LVEF) of <40% and a >20% recovery of the LVEF after successful AF ablation and compared the clinical characteristics between the TIC and control groups. Results The proportions of type 2 diabetes (30.5% vs. 14.7%), renal dysfunction (34.2% vs. 23.8%), hypertension (67.1% vs. 54.8%), and persistent AF (62.2% vs. 32.2%) were significantly higher in the TIC group (n=82) than in the control group (n=640). The atrioventricular nodal effective refractory period (AVNERP) (303±72 ms vs. 332±86 ms; p=0.017) was significantly shorter in the TIC group than in the control group. A multivariable analysis found that persistent AF odds ratio (OR), 3.19; 95% confidence interval (CI), 1.94-5.24, renal dysfunction (OR, 1.87; 95% CI, 1.06-3.32), and type 2 diabetes (OR, 2.30; 95% CI, 1.31-4.05) were significantly associated with TIC. Conclusion Comorbid renal dysfunction and type 2 diabetes were clinical features of AF patients with TIC. Persistent AF, and short AVNERP may be involved in the development of TIC.
The rostro-caudal polarity within a somite is primarily determined by the on/off state of Notch signaling, but the mechanism by which Notch is repressed has remained elusive. Here, we present genetic ...and biochemical evidence that the suppression of Notch signaling is essential for the establishment of rostro-caudal polarity within a somite and that Mesp2 acts as a novel negative regulator of the Notch signaling pathway. We generated a knock-in mouse in which a dominant-negative form of Rbpj is introduced into the Mesp2 locus. Intriguingly, this resulted in an almost complete rescue of the segmental defects in the Mesp2-null mouse. Furthermore, we demonstrate that Mesp2 potently represses Notch signaling by inducing the destabilization of mastermind-like 1, a core regulator of this pathway. Surprisingly, this function of Mesp2 is found to be independent of its function as a transcription factor. Together, these data demonstrate that Mesp2 is a novel component involved in the suppression of Notch target genes.
Survey of tortoises with urolithiasis in Japan TAKAMI, Yoshinori; KOIEYAMA, Hitoshi; SASAKI, Nobuo ...
Journal of Veterinary Medical Science,
2021, Volume:
83, Issue:
3
Journal Article
Peer reviewed
Open access
Urolithiasis is a disease often seen in tortoises at veterinary hospitals, however there have been no comprehensive research reports of tortoises with urolithiasis in Japan. In this study, we ...analyzed tortoises diagnosed with urolithiasis at three domestic veterinary hospitals. Based on medical records, we assessed the diagnostic method, species, sex, body weight, dietary history, husbandry, clinical signs, clinical examination, treatment for urolithiasis, and clinical outcome. The total number of cases in the 3 facilities was 101. As for species of tortoises, the most common was the African spurred tortoise (Centrochelys sulcata) with 42 cases (41.6%), followed by the Indian star tortoise (Geochelone elegans) with 30 cases (29.7%). Six other species were confirmed to have calculi. Almost all cases (99 cases, 98%) had a single calculus, and only 2 had multiple calculi. The prevalence of urolithiasis for the total number of tortoises having visited to one institution during the same period was 5.1%. Of the 86 cases that underwent calculi removal, 64 (74.4%) were successfully removed via the vent, and the efficacy of this method was confirmed. Nineteen cases (22%) were approached via plastronotomy, among which only 2 died postoperatively. In this study, we could not clarify the relationship between calculi formation and diets or other husbandry factors.
Subarachnoid hemorrhage (SAH) frequently results in several serious complications, such as cerebral vasospasm. We previously reported the effect of trehalose on vasospasm, inflammatory responses, and ...lipid peroxidation induced by blood exposure. Herein, to further elucidate the mechanism of action of trehalose, we investigated whether or not post-administration of trehalose can directly influence blood clotting in the cistern. As a result of trehalose injection after the onset of experimental SAH, blood clotting around the basilar artery was clearly inhibited. We also found that trehalose positively impacted coagulation and fibrinolysis parameters in rat, rabbit and human plasma in vitro. These findings suggest that trehalose has suppressive effects on blood clotting in addition to vasospasm, inflammatory responses, and lipid peroxidation after SAH.
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