A Hot Water Extract of Curcuma longa L. Improves Fasting Serum Glucose Levels in Participants with Low-Grade Inflammation: Reanalysis of Data from Two Randomized, Double-Blind, Placebo-Controlled Trials

The dietary spice Curcuma longa L. (C. longa), also known as turmeric, has various biological effects. A hot water extract of C. longa was shown to have anti-inflammatory activities in preclinical and clinical studies. Chronic low-grade inflammation is associated with the disruption of glucose homeostasis, but the effect of C. longa extract on glucose metabolism in humans is poorly understood. Therefore, we investigated the effect of C. longa extracts on serum glucose levels in the presence of low-grade inflammation. We reanalyzed our published data from two randomized, double-blind, placebo-controlled trials in overweight participants aged 50 to 69 years and performed a stratified analysis using the inflammatory marker high-sensitivity C-reactive protein (hsCRP). In both studies, participants took a test food with a hot water extract of C. longa (C. longa extract group, n = 45 per study) or without C. longa extract (placebo group, n = 45 per study) daily for 12 weeks, and we measured the levels of serum hsCRP and fasting serum glucose. The mean baseline hsCRP value was used to stratify participants into two subgroups: a low-hsCRP subgroup (baseline mean hsCRP < 0.098 mg/dL) and a high-hsCRP subgroup (baseline mean hsCRP ≥ 0.098 mg/dL). In the low-hsCRP subgroup, we found no significant difference in fasting serum glucose levels between the two groups in either study, but in the high-hsCRP subgroup, the C. longa extract group had significantly lower levels of serum hsCRP (p < 0.05) and fasting serum glucose (p < 0.05) than the placebo group in both studies. In conclusion, a hot water extract of C. longa may help to improve systemic glucose metabolism in people with chronic low-grade inflammation

Development of novel 123I-labeled pyridyl benzofuran derivatives for SPECT imaging of β-amyloid plaques in Alzheimer's disease.

Imaging of β-amyloid (Aβ) plaques in the brain may facilitate the diagnosis of cerebral β-amyloidosis, risk prediction of Alzheimer's disease (AD), and effectiveness of anti-amyloid therapies. The purpose of this study was to evaluate novel (123)I-labeled pyridyl benzofuran derivatives as SPECT probes for Aβ imaging. The formation of a pyridyl benzofuran backbone was accomplished by Suzuki coupling. [(123)I/(125)I]-labeled pyridyl benzofuran derivatives were readily prepared by an iododestannylation reaction. In vitro Aβ binding assays were carried out using Aβ(1-42) aggregates and postmortem human brain sections. Biodistribution experiments were conducted in normal mice at 2, 10, 30, and 60 min postinjection. Aβ labeling in vivo was evaluated by small-animal SPECT/CT in Tg2576 transgenic mice injected with [(123)I]8. Ex vivo autoradiography of the brain sections was performed after SPECT/CT. Iodinated pyridyl benzofuran derivatives showed excellent affinity for Aβ(1-42) aggregates (2.4 to 10.3 nM) and intensely labeled Aβ plaques in autoradiographs of postmortem AD brain sections. In biodistribution experiments using normal mice, all these derivatives displayed high initial uptake (4.03-5.49% ID/g at 10 min). [(125)I]8 displayed the quickest clearance from the brain (1.30% ID/g at 60 min). SPECT/CT with [(123)I]8 revealed higher uptake of radioactivity in the Tg2576 mouse brain than the wild-type mouse brain. Ex vivo autoradiography showed in vivo binding of [(123)I]8 to Aβ plaques in the Tg2576 mouse brain. These combined results warrant further investigation of [(123)I]8 as a SPECT imaging agent for visualizing Aβ plaques in the AD brain

Simultaneous Estimation of Gender Male and Atrial Fibrillation as Risk Factors for Adverse Outcomes Following Transcatheter Aortic Valve Implantation

Accurate outcome prediction following transcatheter aortic valve implantation (TAVI) has gained further importance along with expanding its indication to patients with a lower surgical risk. Although previous studies have evaluated the prognostic impacts of gender and atrial fibrillation (AF) in TAVI patients, these two factors have rarely been addressed simultaneously. This retrospective observational study based on a multicenter TAVI registry involved 1088 patients who underwent TAVI between May, 2010 and February, 2020 at 3 hospitals in Japan. Participants were divided into 4 groups by gender and pre-existing AF, such as Female AF (−) (n = 559), Male AF (−) (n = 266), Female AF (+) (n = 187) and Male AF (+) (n = 76). Primary and secondary endpoints were death due to any and cardiovascular cause, and the composite of all-cause death and heart failure hospitalization, respectively. The median follow-up period was 538 days. Cumulative incidences of primary and secondary endpoints were lower in the Female AF (−) group compared to the other 3 groups. Adjusted multivariate Cox proportional hazard analyses showed an independent association of either or both of male gender and AF with adverse outcomes, when compared to the group with none of these (hazard ratios and 95% confidence intervals vs. Female AF (−) (reference) for all-cause death of Male AF (−): 2.7, 1.6–4.6, p < 0.001, Female AF (+): 3.5, 2.1–6.0, p < 0.001, and Male AF (+): 3.9, 1.9–7.8, p < 0.001), while there was no evidence of their synergistic prognostic impact. Male gender and being complicated by AF independently, but not synergistically, predicted poor long-term outcomes in patients undergoing TAVI

Predictors for all-cause mortality in men after transcatheter aortic valve replacement: A report from the LAPLACE-TAVI registry

Background: Information regarding the outcomes of transcatheter aortic valve replacement (TAVR) in men is limited. This study aimed to investigate short- to mid-term outcomes and prognostic predictors in this population. Method and Results: The data of 519 men were analyzed from 1,693 consecutive patients with symptomatic severe aortic stenosis who underwent TAVR at six hospitals between April 2010 and July 2020. The primary endpoint was all-cause mortality at 30 days after TAVR. The mean age and Society of Thoracic Surgeons (STS) score were 83.7 ± 5.9 years and 6.3 ± 4.7%, respectively. Overall, 23.5% of patients consumed alcohol with a frequency of > 1 drinks/week, and 12.1% consumed alcohol with a frequency of > 8 drinks/week, while 66.1% were former smokers and 4.2% were current smokers. Mortality at 30 days was 0.8%. During the median follow-up period of 448 days, the estimated survival rates at 1 year post-TAVR was 90.7 ± 1.4%. In multivariate analysis, the serum albumin level [hazard ratio (HR): 2.20, 95% confidence interval (CI):1.36–3.62, p = 0.001], atrial fibrillation (HR: 1.79, 95% CI: 1.13–2.82, p = 0.012), and STS score (HR: 1.33, 95% CI: 1.06–1.67, p = 0.015) were independently associated with all-cause mortality following TAVR. Adjusted hazard ratios of current smoking, heavy drinking, and presence of cancer were 1.05 (95% CI: 0.36–2.98),1.37 (95% CI: 0.75–2.48), and 1.13 (95% CI: 0.75–2.48), respectively. Conclusion: Our study demonstrated that serum albumin levels, atrial fibrillation, and STS score were independently associated with all-cause mortality following TAVR in men

¹⁸F-Labeled Phenyldiazenyl Benzothiazole for in Vivo Imaging of Neurofibrillary Tangles in Alzheimer's Disease Brains

We synthesized and evaluated (<i>E</i>)-4-((6-(2-(2-(2-fluoroethoxy)­ethoxy)­ethoxy)­benzo­[<i>d</i>]­thiazol-2-yl)­diazenyl)-<i>N</i>,<i>N</i>-dimethylaniline (FPPDB) as a probe for the imaging of neurofibrillary tangles (NFTs) in patients with Alzheimer's disease (AD). In assays using thioflavin S (ThS) as a competitive ligand, FPPDB competed with ThS well and showed high affinity for both tau and Aβ_1–42 aggregates (<i>K</i>_i = 13.0 and 20.0 nM, respectively). The results of saturation binding assays also verified that FPPDB bound to both tau and Aβ_1–42 aggregates with high affinity (<i>K</i>_d = 44.8 nM and <i>B</i>_max = 45.8 pmol/nmol protein for tau aggregates and <i>K</i>_d = 45.4 nM and <i>B</i>_max = 38.9 pmol/nmol protein for Aβ_1–42 aggregates). Furthermore, [¹⁸F]­FPPDB substantially labeled NFTs and senile plaques in AD brain sections but not control brain sections. In biodistribution experiments using normal mice, [¹⁸F]­FPPDB displayed higher uptake (4.28% ID/g at 2 min postinjection) into and washout (2.53% ID/g at 60 min postinjection) from the brain with time. On the basis of the chemical structure of FPPDB, further increases in selective binding to tau aggregates may lead to the development of more useful probes for the imaging of NFTs in AD brains