Tianhuang formula regulates adipocyte mitochondrial function by AMPK/MICU1 pathway in HFD/STZ-induced T2DM mice.

BACKGROUND: Tianhuang formula (THF) is a Chinese medicine prescription that is patented and clinically approved, and has been shown to improve energy metabolism, but the underlying mechanism remains poorly understood. The purpose of this study is to clarify the potential mechanisms of THF in the treatment of type 2 diabetes mellitus (T2DM). METHODS: A murine model of T2DM was induced by high-fat diet (HFD) feeding combined with low-dose streptozocin (STZ) injections, and the diabetic mice were treated with THF by gavaging for consecutive 10 weeks. Fasting blood glucose (FBG), serum insulin, blood lipid, mitochondrial Ca2+ (mCa2+) levels and mitochondrial membrane potential (MMP), as well as ATP production were analyzed. The target genes and proteins expression of visceral adipose tissue (Vat) was tested by RT-PCR and western blot, respectively. The underlying mechanism of the regulating energy metabolism effect of THF was further explored in the insulin resistance model of 3T3-L1 adipocytes cultured with dexamethasone (DXM). RESULTS: THF restored impaired glucose tolerance and insulin resistance in diabetic mice. Serum levels of lipids were significantly decreased, as well as fasting blood glucose and insulin in THF-treated mice. THF regulated mCa2+ uptake, increased MMP and ATP content in VAT. THF increased the mRNA and protein expression of AMPK, phosphorylated AMPK (p-AMPK), MICU1, sirtuin1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). THF could increase the mCa2+ level of 3T3-L1 adipocytes and regulate mitochondrial function. The protein expression of AMPK, p-AMPK, mCa2+ uniporter (MCU) and MICU1 decreased upon adding AMPK inhibitor compound C to 3T3-L1 adipocytes and the protein expression of MCU and MICU1 decreased upon adding the MCU inhibitor ruthenium red. CONCLUSIONS: These results demonstrated that THF ameliorated glucose and lipid metabolism disorders in T2DM mice through the improvement of AMPK/MICU1 pathway-dependent mitochondrial function in adipose tissue.

Follicle-Stimulating Hormone Accelerates Atherosclerosis by Activating PI3K/Akt/NF-κB Pathway in Mice with Androgen Deprivation.

OBJECTIVE: Follicle-stimulating hormone (FSH) level changes may be another reason for increasing the risk of cardiovascular disease. In this study, we aimed to investigate the role of FSH in atherosclerosis and its underlying mechanism. METHODS: ApoE-/- mice were divided into 4 groups, namely, the sham group, bilaterally orchidectomized group, FSH group, and testosterone-only group. Blood lipid and hormone levels were tested, aorta Oil Red O staining; the levels of NF-κB, Akt, eNOS, and FSH receptors in the aorta were measured by Western blotting. Expression of VCAM-1 was detected via Western blotting and immunohistochemical staining. Human umbilical vein endothelial cells (HUVECs) were used to induce endothelial injury model by adding FSH, and the levels of NF-κB, Akt, eNOS, and FSHR were tested in HUVECs. RESULTS: FSH treatment exacerbated atherosclerotic lesions in ApoE-/- mice. Moreover, FSH could promote the expression of VCAM-1 protein in HUVECs, and this effect was possibly mediated by the activation of NF-κB, while NF-κB activation was further enhanced by the activation of the PI3K/Akt/eNOS pathway. FSH failed to activate Akt and NF-κB in the presence of the PI3K inhibitor LY294002 in HUVECs. CONCLUSION: FSH promoted the development of atherosclerosis by increasing VCAM-1 protein expression via activating PI3K/Akt/NF-κB pathway.

Study of Scraping with Copper Stone Based on Theory of Midnight-Noon Ebb-Flow in Angina Pectoris with Coronary Heart Disease of Qi Stagnation and Blood Stasis.

Angina pectoris (AP) with coronary heart disease (CHD) is one of the common cardiovascular diseases in clinical practice, which can be classified as "chest paralysis" in Chinese medicine according to its symptoms, and it is described in many ancient documents. Ancient Chinese medicine believes that the main pathogenesis of the disease is poor blood flow leading to paralysis of the heart and veins, so it is often treated by activating blood and removing blood stasis. In this study, 120 patients with AP of CHD of Qi stagnation and blood stasis type were randomly divided into the observation (n = 60) and the control group (n = 60). In the control group, basic care, conventional treatment, and unselected copper acupuncture scraping were used, while in the observation group, copper acupuncture scraping was performed at the right time of the heart meridian (11 : 00-13 : 00) on the basis of the control group, and all patients received the treatment for a total duration of 4 weeks. We collected data on the traditional Chinese medical (TCM) syndrome score, frequency and duration of angina attacks, nitroglycerin dosage, inflammatory factor levels, and hematological indices pretreatment and posttreatment in both groups. Patients' adverse effects during treatment were recorded, and the clinical efficacy and ECG efficacy in both groups were evaluated after 4 weeks. We used SPSS.20 statistical software to statistically analyze the above data, and the results showed that the clinical efficacy and ECG efficacy of the observation group were significantly higher than the control group posttreatment. After treatment, the TCM symptom score, angina attack frequency, attack duration and nitroglycerin dosage, serum interleukin-8 (IL-8), hypersensitive C-reactive protein (hs-CRP), and tumor necrosis factor-α (TNF-α) levels, whole blood viscosity (WBV), plasma viscosity (PV), fibrinogen (FIB), and hematocrit (Hct) were significantly lower in both groups compared with those posttreatment. And the observation group showed a greater decrease when compared with the control group. The results also showed that the overall incidence of adverse reactions was lower in both groups during the treatment period. The above results indicate that while ensuring high safety, the copper stone based on theory of midnight-noon ebb-flow can more effectively improve the symptoms and inflammatory response of the body and reduce the viscosity of the blood in AP with CHD of Qi stagnation and blood stasis, and it has better therapeutic effects.

Colorimetric human papillomavirus DNA assay based on the retardation of avidin-induced aggregation of gold nanoparticles.

A colorimetric assay for human papillomavirus (HPV) DNA was developed based on the retardation of the avidin-induced aggregation of gold nanoparticles (AuNPs) by HPV DNA. Positively charged avidin acts as a coagulant for AuNP aggregation. In the presence of the target DNA, however, the aggregation of AuNPs is retarded owing to electrosteric stabilization as a result of the hybridization of the target and probe DNA. In the absence of HPV DNA, the stabilization effect caused by the biotinylated probe DNA is weak, resulting in NP aggregation and a color change from red to purple. Aggregation may be easily observed with bare eyes or spectrophotometrically at about 560 nm. The visual detection limit is 1 nM. The assay was used for the determination of HPV DNA after polymerase chain reaction (PCR) amplification without any further purification. Graphical abstract Schematic presentation of the avidin-induced aggregation of unmodified gold nanoparticles (AuNPs) which leads to a color change from red to purple. In the presence of dsDNA, however, the aggregation is remarkably retarded.

A dansyl-rhodamine chemosensor for Fe(III) based on off-on FRET.

A novel fluorescent chemosensor bearing a rhodamine and a dansyl moiety was developed for highly selective detection of Fe(3+) based on fluorescence resonance energy transfer (FRET) mechanism. Binding of Fe(3+) to the chemosensor induced spirolactam ring opening in the rhodamine moiety and subsequent off-on FRET from the dansyl energy donor to the rhodamine energy acceptor due to the spectral overlap between the emission of the dansyl moiety and the absorption of the ring opened rhodamine moiety. Job's plot analysis indicated a 1:1 binding stoichiometry between the chemosensor and Fe(3+). The association constant was estimated to be 2.72×10(3) M(-1) according to the Benesi-Hildebrand method. With the feature of easy synthesis, simple structural skeleton and excellent sensing ability, the newly synthesized chemosensor provided the potential for applying as a highly selective fluorescent probe in complex samples containing various competitive metal ions and developing other metal ion chemosensors to fulfill various needs of biological and environmental field.