Obesity, a primary influence on health condition, causes numerous comorbidities and complications and, therefore, pharmacotherapy is considered a strategy for its treatment. However, the adverse effects of most chemical drugs targeting weight loss complicate their approval by regulatory authorities. Recently, interest has increased in the development of ingredients from natural sources with fewer adverse effects for preventing and ameliorating obesity. This review provides an overview of current anti-obesity drugs and natural products with anti-obesity properties as well as their mechanisms of action, which include interfering with nutrient absorption, decreasing adipogenesis, increasing energy expenditure (thermogenesis), appetite suppression, modifying intestinal microbiota composition, and increasing fecal fat excretion.
We propose that the forward and reverse halves of a flash-induced protein-protein electron transfer (ET) photocycle should exhibit differential responses to dynamic interconversion of configurations when the most stable configuration is not the most reactive, because the reactants exist in different initial configurations: the flash-photoinitiated forward ET process begins with the protein partners in an equilibrium ensemble of configurations, many of which have little or no reactivity, whereas the reactant of the thermal back ET (the charge-separated intermediate) is formed in a nonequilibrium, ''activated'' protein configuration. We report evidence for this proposal in measurements on (i) mixed-metal hemoglobin hybrids, (ii) the complex between cytochrome c peroxidase and cytochrome c, and (iii and iv) the complexes of myoglobin and isolated hemoglobin ␣-chains with cytochrome b 5. For all three systems, forward and reverse ET does respond differently to modulation of dynamic processes; further, the response to changes in viscosity is different for each system. cytochrome c ͉ dynamics ͉ hemoglobin ͉ myoglobin ͉ cytochrome c peroxidase T he long-range transfer of a single electron from donor to acceptor in a condensed phase is a fascinating and widely studied process (1, 2). Much of this work seeks to understand the electron transfer (ET) process itself. However, when the ET event involves a dynamic protein-protein interface, the observed kinetics frequently are controlled not by the ET process itself, but by the dynamics of recognition and binding and͞or conversion within an ensemble of bound configurations (3, 4).Studies of interprotein ET (3, 5-10) began with the implicit assumption of a protein-protein binding-energy landscape with a single reactive complex (Fig. 1A Left), implying a direct correlation between binding and reactivity. When the landscape for complex formation has several discrete minima ( Fig. 1 A Center) the reactive conformation may differ from the most stable one, in which case the observed ET kinetics are controlled by the rates and͞or energetics of conformational conversion within a complex (11-13). Recent studies of ET between myoglobin (Mb) and cytochrome b 5 (Fe 3ϩ b 5 ), which bind to each other by weak electrostatic interactions, disclosed a new dynamic docking paradigm in protein-protein reaction dynamics: the landscape involves numerous configurations of similar affinity, only a subset of which is active in ET (Fig. 1 A Right) (4, 14).A majority of these studies have used a photocycle in which laser-flash excitation of the metallo-porphyrin in a metalsubstituted (M ϭ Zn or Mg) hemoprotein to its triplet excited state ( 3 D) triggers ET from the triplet to the metal center of an acceptor protein (A) across a protein-protein interface, with rate constant, k f , Eq. 1:[1]The acceptor metal center of A typically is a ferri-heme center, Given the exponentially steep fall-off in the matrix element for ET between the two redox centers (19,20), there will be only a subset of conformation...
Parathyroidectomy (PTX) is an effective treatment for severe secondary hyperparathyroidism (SHPT); however, persistent SHPT may occur because of supernumerary and ectopic parathyroids. Here a diagnostic accuracy study of intraoperative and perioperative serum intact parathyroid hormone (iPTH) was performed to predict successful surgery in 501 patients, who received total PTX + autotransplantation without thymectomy. Serum iPTH values before incision (io-iPTH0), 10 and 20 min after removing the last parathyroid (io-iPTH10, io-iPTH20), and the first and fourth day after PTX (D1-iPTH, D4-iPTH) were recoded. Patients whose serum iPTH was >50 pg/mL at the first postoperative week were followed up within six months. Successful PTX was defined if iPTH was <300 pg/mL, on the contrary, persistent SHPT was regarded. There were 86.4% patients underwent successful PTX, 9.8% remained as persistent SHPT and 3.8% were undetermined. Intraoperative serum iPTH demonstrated no significant differences in two subgroups with or without chronic hepatitis. Receiver operating characteristic (ROC) curves showed that >88.9% of io-iPTH20% could predict successful PTX (area under the curve [AUC] 0.909, sensitivity 78.6%, specificity 88.5%), thereby avoiding unnecessary exploration to reduce operative complications. D4-iPTH >147.4 pg/mL could predict persistent SHPT (AUC 0.998, sensitivity 100%, specificity 99.5%), so that medical intervention or reoperation start timely.
Obesity is a global disease that causes many metabolic disorders. However, effective agents for the prevention or treatment of obesity remain limited. This study investigated the anti-obesity effect and mechanism of chitosan oligosaccharide capsules (COSCs) on rats suffering from obesity induced by a high-fat diet (HFD). After the eight-week administration of COSCs on obese rats, the body weight gain, fat/body ratio, and related biochemical indices were measured. The hepatic expressions of the leptin signal pathway (JAK2-STAT3) and gene expressions of adipogenesis-related targets were also determined. Our data showed that COSCs can regulate body weight gain, lipids, serum alanine aminotransferase, and aspartate aminotransferase, as well as upregulate the hepatic leptin receptor-b (LepRb) and the phosphorylation of JAK2 and STAT3. Meanwhile, marked increased expressions of liver sterol regulatory element-binding protein-1c, fatty acid synthase, acetyl-CoA carboxylase, 3-hydroxy-3-methylglutaryl-CoA reductase, adiponectin, adipose peroxisome proliferator-activated receptor γ, CCAAT-enhancer binding protein α, adipose differentiation-related protein, and SREBP-1c were observed. The results suggested that COSCs activate the JAK2-STAT3 signaling pathway to alleviate leptin resistance and suppress adipogenesis to reduce lipid accumulation. Thus, they can potentially be used for obesity treatment.
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