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"T -L Lee"
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SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease
Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor’s glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.
SGLT2 inhibitors, a class of type 2 diabetes medication, reduce cardiovascular events in patients beyond expectation from blood sugar control. Here the authors report a randomized controlled trial showing that SGLT2 inhibitors reduce inflammasome activation in peripheral macrophages, which may contribute to the cardiovascular protection.
Journal Article
The development of the American public accountancy profession : Scottish chartered accountants and the early American public accountancy profession
\"This book presents a unique series of research biographies of professional accountants who immigrated to the United States and developed their careers there in the late nineteenth, and early twentieth, century. Until now, little has been written about the positive impact of immigrant professionals on American life.\"--Jacket.
Book
Dapagliflozin attenuates diabetes-induced diastolic dysfunction and cardiac fibrosis by regulating SGK1 signaling
Background
Recent studies have reported improved diastolic function in patients administered sodium-glucose cotransporter 2 inhibitors (SGLT2i). We aimed to investigate the effect of dapagliflozin on left ventricular (LV) diastolic function in a diabetic animal model and to determine the molecular and cellular mechanisms underlying its function.
Methods
A total of 30 male New Zealand white rabbits were randomized into control, diabetes, or diabetes+dapagliflozin groups (
n
= 10/per each group). Diabetes was induced by intravenous alloxan. Cardiac function was evaluated using echocardiography. Myocardial samples were obtained for histologic and molecular evaluation. For cellular evaluation, fibrosis-induced cardiomyoblast (H9C2) cells were obtained, and transfection was performed for mechanism analysis (serum and glucocorticoid-regulated kinase 1 (SGK1) signaling analysis).
Results
The diabetes+dapagliflozin group showed attenuation of diastolic dysfunction compared with the diabetes group. Dapagliflozin inhibited myocardial fibrosis via inhibition of SGK1 and epithelial sodium channel (ENaC) protein, which was observed both in myocardial tissue and H9C2 cells. In addition, dapagliflozin showed an anti-inflammatory effect and ameliorated mitochondrial disruption. Inhibition of SGK1 expression by siRNA decreased and ENaC and Na+/H+ exchanger isoform 1 (NHE1) expression was confirmed as significantly reduced as siSGK1 in the diabetes+dapagliflozin group.
Conclusions
Dapagliflozin attenuated left ventricular diastolic dysfunction and cardiac fibrosis via regulation of SGK1 signaling. Dapagliflozin also reduced macrophages and inflammatory proteins and ameliorated mitochondrial disruption.
Journal Article
Everything here is beautiful
\"Two sisters--Miranda, the older, responsible one, always her younger sister's protector; Lucia, the headstrong, unpredictable one, whose impulses are huge and, often, life changing. When their mother dies and Lucia starts hearing voices, it is Miranda who must find a way to reach her sister. But Lucia impetuously plows ahead, marrying a bighearted, older man only to leave him, suddenly, to have a baby with a young Latino immigrant. She moves her new family from the States to Ecuador and back again, but the bitter constant is that she is, in fact, mentally ill. Lucia lives life on a grand scale, until, inevitably, she crashes to earth. Miranda leaves her own self-contained life in Switzerland to rescue her sister again--but only Lucia can decide whether she wants to be saved. The bonds of sisterly devotion stretch across oceans--but what does it take to break them? Told in alternating points of view, Everything Here Is Beautiful is, at its heart, the story of a young woman's quest to find fulfillment and a life unconstrained by her illness. But it's also an unforgettable, gut-wrenching story of the sacrifices we make to truly love someone--and when loyalty to one's self must prevail over all\"-- Provided by publisher.
Book
The healing art of tai chi : becoming one with nature
\"Is tai chi a stretching exercise, deep-breathing program, martial art, dance or prayer? Yes, it's all those and more. Tai chi, like many ancient Eastern practices, does not fit strict Western categories. Tai chi, together with the extraordinary self-healing method developed by Dr Lee, offers relief for stress, breathing disorders, muscular ailments, chronic headaches, and a variety of modern office- and sports-related complaints, as well as for deep emotional distress. Few today are as well positioned to explain the healing powers of tai chi as Dr. Martin Lee, a renowned engineering physicist and tai chi master. He and his wife, Emily, also a tai chi master, are the only Americans to have studied with Yu Pen-Shih, one of China's foremost ch'i kung masters. Dr. Lee has developed a groundbreaking practical program that combines Eastern and Western approaches to wellness, which he calls \"physical philosophy.\" Its goal is to help people become \"one with nature,\" a Buddhist term for the natural restoration of true health. The rewards of one-with-nature tai chi are inner happiness, self-control, self-realization, and self-healing. Each one of these benefits receives individual attention, complete with the 64 tai chi forms, thoroughly illustrated with photographs and diagrams. The central focus is on the flow of energy -- the chi, or \"inner breath\" -- that tai chi evokes through Lee's four basic instructions: Relax. Breathe. Feel the earth. Do nothing extra. Here is a valuable health, exercise, and meditation program that combines ancient spiritual insights with advanced scientific knowledge and important original discoveries\"-- Provided by publisher.
Book
Forest elephant movement and habitat use in a tropical forest-grassland mosaic in Gabon
Poaching of forest elephants (Loxodonta cyclotis) for ivory has decimated their populations in Central Africa. Studying elephant movement can provide insight into habitat and resource use to reveal where, when, and why they move and guide conservation efforts. We fitted 17 forest elephants with global positioning system (GPS) collars in 2015 and 2016 in the tropical forest-grassland mosaic of the Wonga Wongué Presidential Reserve (WW), Gabon. Using the location data, we quantified movement distances, home ranges, and habitat use to examine the environmental drivers of elephant movements and predict where elephants occur spatially and temporally. Forest elephants, on average, traveled 2,840 km annually and had home ranges of 713 km2, with males covering significantly larger home ranges than females. Forest elephants demonstrated both daily and seasonal movement patterns. Daily, they moved between forest and grassland at dawn and dusk. Seasonally, they spent proportionally more time in grassland than forest during the short-wet season when grasses recruit. Forest elephants also traveled faster during the short-wet season when fruit availability was greatest, likely reflecting long, direct movements to preferred fruiting tree species. Forest elephants tended to select areas with high tree and shrub density that afford cover and browse. When villages occurred in their home ranges elephants spent a disproportionate amount of time near them, particularly in the dry season, probably for access to agricultural crops and preferred habitat. Given the importance of the grassland habitat for elephants, maintenance of the forest-grassland matrix is a conservation priority in WW. Law enforcement, outreach, and education should focus on areas of potential human-elephant conflict near villages along the borders of the reserve. GPS-tracking should be extended into multi-use areas in the peripheries of protected areas to evaluate the effects of human disturbance on elephant movements and to maintain connectivity among elephant populations in Gabon.
Journal Article
