Curcumin Conjugated Gold Nanoclusters as Perspective Therapeutics for Diabetic Cardiomyopathy.

Accumulation of lipids in the myocardium contributes to the development of cardiac dysfunctions and various chronic diseases, such as diabetic cardiomyopathy (DCM). Curcumin (Cur) can relieve lipid accumulation problems, but its efficiency is limited by poor water solubility and biocompatibility. Herein, gold nanoclusters (AuNCs) were used to improve the efficiency of Cur, and the conjugates Curcumin-AuNCs (AuCur) were developed. In the treatment of high-fat-induced myocardial cell damage, we found that AuCur could effectively reduce intracellular lipid accumulation, the increase of reactive oxygen species (ROS), the increase of mitochondrial division, and the increase of apoptosis compared with Cur. AuCur decreased the expression of the peroxisome proliferator-activated receptors-α subtype (PPARα), and the therapeutic effect of AuCur was canceled when the expression of PPARα was enhanced. For the above reasons, AuCur treated the toxic effect of high lipid on cardiomyocytes by regulating PPARα, providing a new idea and method for the treatment of DCM.

Medium & long-chain acylcarnitine's relation to lipid metabolism as potential predictors for diabetic cardiomyopathy: a metabolomic study.

BACKGROUND: Acylcarnitine is an intermediate product of fatty acid oxidation. It is reported to be closely associated with the occurrence of diabetic cardiomyopathy (DCM). However, the mechanism of acylcarnitine affecting myocardial disorders is yet to be explored. This current research explores the different chain lengths of acylcarnitines as biomarkers for the early diagnosis of DCM and the mechanism of acylcarnitines for the development of DCM in-vitro. METHODS: In a retrospective non-interventional study, 50 simple type 2 diabetes mellitus patients and 50 DCM patients were recruited. Plasma samples from both groups were analyzed by high throughput metabolomics and cluster heat map using mass spectrometry. Principal component analysis was used to compare the changes occurring in the studied 25 acylcarnitines. Multivariable binary logistic regression was used to analyze the odds ratio of each group for factors and the 95% confidence interval in DCM. Myristoylcarnitine (C14) exogenous intervention was given to H9c2 cells to verify the expression of lipid metabolism-related protein, inflammation-related protein expression, apoptosis-related protein expression, and cardiomyocyte hypertrophy and fibrosis-related protein expression. RESULTS: Factor 1 (C14, lauroylcarnitine, tetradecanoyldiacylcarnitine, 3-hydroxyl-tetradecanoylcarnitine, arachidic carnitine, octadecanoylcarnitine, 3-hydroxypalmitoleylcarnitine) and factor 4 (octanoylcarnitine, hexanoylcarnitine, decanoylcarnitine) were positively correlated with the risk of DCM. Exogenous C14 supplementation to cardiomyocytes led to increased lipid deposition in cardiomyocytes along with the obstacles in adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathways and affecting fatty acid oxidation. This further caused myocardial lipotoxicity, ultimately leading to cardiomyocyte hypertrophy, fibrotic remodeling, and increased apoptosis. However, this effect was mitigated by the AMPK agonist acadesine. CONCLUSIONS: The increased plasma levels in medium and long-chain acylcarnitine extracted from factors 1 and 4 are closely related to the risk of DCM, indicating that these factors can be an important tool for DCM risk assessment. C14 supplementation associated lipid accumulation by inhibiting the AMPK/ACC/CPT1 signaling pathway, aggravated myocardial lipotoxicity, increased apoptosis apart from cardiomyocyte hypertrophy and fibrosis were alleviated by the acadesine.

Radioprotective effects of cimetidine on rats irradiated by long-term, low-dose-rate neutrons and 60Co γ-rays.

BACKGROUND: Cimetidine, an antagonist of histamine type II receptors, has shown protective effects against γ-rays or neutrons. However, there have been no reports on the effects of cimetidine against neutrons combined with γ-rays. This study was carried out to evaluate the protective effects of cimetidine on rats exposed to long-term, low-dose-rate neutron and γ-ray combined irradiation (n-γ LDR). METHODS: Fifty male Sprague-Dawley (SD) rats were randomly divided into 5 groups: the normal control group, radiation model group, 20 mg/(kg · d) cimetidine group, 80 mg/(kg · d) cimetidine group and 160 mg/(kg · d) cimetidine group (10 rats per group). Except for the normal control group, 40 rats were simultaneously exposed to fission neutrons (252Cf, 0.085 mGy/h) for 22 h every day and γ-rays (60Co, 0.097 Gy/h) for 1.03 h once every three days, and the cimetidine groups were administered intragastrically with cimetidine at doses of 20, 80 and 160 mg/kg each day. Peripheral blood WBC of the rats was counted the day following exposure to γ-rays. The rats were anesthetized and sacrificed on the day following exposure to 252Cf for 28 days. The spleen, thymus, testicle, liver and intestinal tract indexes were evaluated. The DNA content of bone marrow cells and concanavalin A (ConA)-induced lymphocyte proliferation were measured. The frequency of micronuclei in polychromatic erythrocytes (fMNPCEs), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in the serum and liver tissues were detected. RESULTS: The peripheral blood WBC in the cimetidine groups was increased significantly on the 8th day and the 26th day compared with those in the radiation model group. The spleen, thymus and testicle indexes of the cimetidine groups were higher than those of the radiation model group. The DNA content of bone marrow cells and lymphocyte proliferation in the cimetidine groups were increased significantly, and fMNPCE was reduced 1.41-1.77 fold in cimetidine treated groups. The activities of SOD and GSH-Px in the cimetidine groups were increased significantly, and the content of MDA in the cimetidine groups was decreased significantly. CONCLUSIONS: The results suggested that cimetidine alleviated damage induced by long-term, low-dose-rate neutron and γ combined irradiation via antioxidation and immunomodulation. Cimetidine might be useful as a potent radioprotector for radiotherapy patients as well as for occupational exposure workers.

Beneficial effects of a novel shark-skin collagen dressing for the promotion of seawater immersion wound healing.

BACKGROUND: Wounded personnel who work at sea often encounter a plethora of difficulties. The most important of these difficulties is seawater immersion. Common medical dressings have little effect when the affected area is immersed in seawater, and only rarely dressings have been reported for the treatment of seawater-immersed wounds. The objective of this study is to develop a new dressing which should be suitable to prevent the wound from seawater immersion and to promote the wound healing. METHODS: Shark skin collagen (SSC) was purified via ethanol de-sugaring and de-pigmentation and adjusted for pH. A shark skin collagen sponge (SSCS) was prepared by freeze-drying. SSCS was attached to an anti-seawater immersion polyurethane (PU) film (SSCS + PU) to compose a new dressing. The biochemical properties of SSC and physicochemical properties of SSCS were assessed by standard methods. The effects of SSCS and SSCS + PU on the healing of seawater-immersed wounds were studied using a seawater immersion rat model. For the detection of SSCS effects on seawater-immersed wounds, 12 SD rats, with four wounds created in each rat, were divided into four groups: the 3rd day group, 5th day group, 7th day group and 12th day group. In each group, six wounds were treated with SSCS, three wounds treated with chitosan served as the positive control, and three wounds treated with gauze served as the negative control. For the detection of the SSCS + PU effects on seawater-immersed wounds, 36 SD rats were divided into three groups: the gauze (GZ) + PU group, chitosan (CS) + PU group and SSCS + PU group, with 12 rats in each group, and two wounds in each rat. The wound sizes were measured to calculate the healing rate, and histomorphology and the immunohistochemistry of the CD31 and TGF-ß expression levels in the wounded tissues were measured by standard methods. RESULTS: The results of Ultraviolet-visible (UV-vis) spectrum, Fourier-transform infrared (FTIR) spectrum, circular dichroism (CD) spectra, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and amino acid composition analyses of SSC demonstrated that SSC is type I collagen. SSCS had a homogeneous porous structure of approximately 200 µm, porosity rate of 83.57% ± 2.64%, water vapor transmission ratio (WVTR) of 4500 g/m2, tensile strength of 1.79 ± 0.41 N/mm, and elongation at break of 4.52% ± 0.01%. SSCS had significant beneficial effects on seawater-immersed wound healing. On the 3rd day, the healing rates in the GZ negative control, CS positive control and SSCS rats were 13.94% ± 5.50%, 29.40% ± 1.10% and 47.24% ± 8.40%, respectively. SSCS also enhanced TGF-ß and CD31 expression in the initial stage of the healing period. The SSCS + PU dressing effectively protected wounds from seawater immersion for at least 4 h, and accelerated re-epithelialization, vascularization and granulation formation of seawater-immersed wounds in the earlier stages of wound healing, and as well as significantly promoted wound healing. The SSCS + PU dressing also enhanced expression of TGF-ß and CD31. The effects of SSCS and SSCS + PU were superior to those of both the chitosan and gauze dressings. CONCLUSIONS: SSCS has significant positive effects on the promotion of seawater-immersed wound healing, and a SSCS + PU dressing effectively prevents seawater immersion, and significantly promotes seawater-immersed wound healing.

Growth inhibition and induction of early apoptosis by arenicolsterol A, a novel cytotoxic enolic sulphated sterol from the marine annelid, Arenicola cristata.

Arenicolsterol A (ASA), a novel cytotoxic enolic sulphated sterol, was isolated from the marine annelid, Arenicola cristata (AC). Growth inhibition of this compound on cancer cell lines was determined by MTT assay and suppression of tumour stem cells colony formation. The results showed that ASA was selectively cytotoxic on HeLa cell line (IC(50) = 6.00 +/- 1.16 micromol L(- 1) on HeLa cell line, IC(50) = 10.85 +/- 0.97 micromol L(- 1) on 929 cell line and 14.72 +/- 1.55 micromol L(- 1) on NCI-h6 cell line). In addition, the apoptosis induced by ASA was verified from monitoring the stainability with Annexin V and propidium iodine by a fluorescence-activated cell sorter. The experimental data confirmed that ASA could induce apoptosis in HeLa cells by arresting early stage in apoptosis. Meanwhile, the apoptosis was found to be correlative with the inhibition of the protein tyrosine phosphatases (cdc25A, cdc25B, JSP1, etc). Therefore, ASA might be a novel promising precursor of anticancer medicines.