Vinpocetine alleviates the abdominal aortic aneurysm progression via VSMCs SIRT1-p21 signaling pathway.

Abdominal aortic aneurysm (AAA) is a degenerative disease that caused mortality in people aged >65. Senescence plays a critical role in AAA pathogenesis. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. Our Previous study found cyclic nucleotide phosphodiesterase 1C (PDE1C) exacerbate AAA through aggravate vascular smooth muscle cells (VSMCs) senescence by downregulating Sirtuin1 (SIRT1) expression and activity. Vinpocetine as a selective inhibitor of PDE1 and a clinical medication for cerebral vasodilation, it is unclear whether vinpocetine can rely on SIRT1 to alleviate AAA. This study showed that pre-treatment with vinpocetine remarkably prevented aneurysmal dilation and reduced aortic rupture in elastase-induced AAA mice. In addition, the elastin degradation, MMP (matrix metalloproteinase) activity, macrophage infiltration, ROS production, collagen fibers remodeling, and VSMCs senescence were decreased in AAA treated with vinpocetine. While these effects were unable to exert in VSMCs-specific SIRT1 knockout AAA mice. Accordingly, we revealed that vinpocetine suppressed migration, proliferation, and senescence in VSMCs. Moreover, vinpocetine reduced SIRT1 degradation by inhibiting lysosome-mediated autophagy. In conclusion, this study indicated that vinpocetine may be as a potential drug for therapy AAA through alleviate VSMCs senescence via the SIRT1-dependent pathway.

Identification and profiling of the community structure and potential function of bacteria from the fruiting bodies of Sanghuangporus vaninii.

Sanghuangporus sp., a medicinal and edible homologous macrofungus known as 'forest gold', which has good effects on antitumor, hypolipidemia and the treatment of gynecological diseases. However, the natural resources of fruiting body are on the verge of depletion due to its long growth cycle and over exploitation. The growth and metabolism of macrofungi are known to depend on the diverse bacterial community. Here, we characterized the diversity and potential function of bacteria inhabiting in the fruiting body of the most widely applied S. vaninii using a combination method of high-throughput sequencing with pure culturing for the first time, and tested the biological activities of bacterial isolates, of which Illumina NovaSeq provided a more comprehensive results on the bacterial community structure. Total 33 phyla, 82 classes, 195 orders, 355 families, 601 genera and 679 species were identified in the fruiting body, and our results revealed that the community was predominated by the common Proteobacteria, Gammaproteobacteria, Burkholderiales, Methylophilaceae (partly consistent with pure-culturing findings), and was dominated by the genera of distinctive Methylotenera and Methylomonas (yet-uncultured taxa). Simultaneously, the functional analysis showed that companion bacteria were involved in the pathways of carbohydrate transport and metabolism, metabolism of terpenoids and polyketides, cell wall/membrane/envelope biogenesis, etc. Hence, it was inferred that bacteria associated with fruiting body may have the potential to adjust the growth, development and active metabolite production of host S. vaninii combined with the tested results of indole-3-acetic acid and total antioxidant capacity. Altogether, this report first provided new findings which can be inspiring for further in-depth studies to exploit bioactive microbial resources for increased production of Sanghuangporus, as well as to explore the relationship between medicinal macrofungi and their associated endophytes.

MK2206 attenuates atherosclerosis by inhibiting lipid accumulation, cell migration, proliferation, and inflammation.

Cardiovascular disease is a common comorbidity in patients with cancer, and the main leading cause of noncancer-related deaths in cancer survivors. Considering that current antitumor drugs usually induce cardiovascular injury, the quest for developing new antitumor drugs, especially those with cardiovascular protection, is crucial for improving cancer prognosis. MK2206 is a phase II clinical anticancer drug and the role of this drug in cardiovascular disease is still unclear. Here, we revealed that MK2206 significantly reduced vascular inflammation, atherosclerotic lesions, and inhibited proliferation of vascular smooth muscle cell in ApoE-/- mice in vivo. We demonstrated that MK2206 reduced lipid accumulation by promoting cholesterol efflux but did not affect lipid uptake and decreased inflammatory response by modulating inflammation-related mRNA stability in macrophages. In addition, we revealed that MK2206 suppressed migration, proliferation, and inflammation in vascular smooth muscle cells. Moreover, MK2206 inhibited proliferation and inflammation of endothelial cells. The present results suggest that MK2206, as a promising drug in clinical antitumor therapy, exhibits anti-inflammatory and antiatherosclerotic potential. This report provides a novel strategy for the prevention of cardiovascular comorbidities in cancer survivors.

Effects of different-intensity laser acupuncture at two adjacent same-meridian acupoints on nitric oxide and soluble guanylate cyclase releases in human.

OBJECTIVES: The aim of this study was to detect the influences of LA at nonacupoint and two adjacent acupoints of pericardium meridian on the releases of NO and sGC in 20 healthy subjects. METHODS: Different intensities (12, 24, 48 mW) of infrared laser were used for irradiating Jianshi (PC5), Ximen (PC4) acupoints and nonacupoint for 20, 40 minutes, respectively. Semi-circular tubes were taped to the skin surface and filled with NO-scavenging compound for 20 minutes to capture NO and sGC, which were measured using spectrophotometry in a blinded fashion. RESULTS: As the increase in the intensity of LA stimulation, the levels of NO releases over acupoints all were significantly increased, NO releases in nonacupoints following the same treatment only changed slightly, sGC amounts were observably enhanced over acupoints, but did not any change in nonacupoint area. Different intensities of LA treatments can sensitively affect the NO and sGC releases over acupoints. This indicated that LA-induced releases of the NO and sGC were specific to acupoints. CONCLUSIONS: This is the first evidence reporting that LA induced significant elevations of NO-sGC releases over acupoints, and the enhanced signal molecules contribute to local circulation, which improves the beneficial effects of the therapy.

Changes in Nitric Oxide Releases of the Contralateral Acupoint during and after Laser Acupuncture at Bilateral Same-Name Acupoints in Human.

OBJECTIVE: The purpose of the study was to examine the effects of laser acupuncture (LA) at right Neiguan (RPC6)/left Neiguan (LPC6) acupoints on the releases of nitric oxide (NO) in the treated and contralateral/nontreated PC6, compared to the nonacupoint control area. METHODS: 24 mW LA at RPC6, LPC6, and nonacupoint in 22 healthy subjects for 40 min: sterilized dialysis tube was taped to the nontreated PC6/nonacupoint during the treatment and immediately taped to the treated and nontreated PC6/nonacupoint after LA removal. NO-scavenging compound was injected into the tube for 40 min to absorb the molecular which was tested by spectrophotometry in a blinded fashion. RESULTS: LA-induced NO releases over PC6 acupoints for the nontreated and treated sides all significantly increased after LA removal, but for the nontreated acupoints they did not change during LA stimulation. LA at RPC6 induced the more release of the NO at contralateral side than stimulating LPC6, but not on nonacupoints. The results suggest that LA-induced NO release over contralateral acupoint and NO release resulting from the lateralized specificity all are different and specific to the acupoint within different time course. CONCLUSIONS: LA-evoked NO release over acupoints could improve the neurogenic, endothelial activity of the vessel wall to further facilitate microcirculation.

Investigation on the interaction of letrozole with herring sperm DNA through spectroscopic and modeling methods.

The interaction of letrozole, an efficient and safe aromatase inhibitor, with herring sperm DNA (hsDNA) was investigated in vitro through spectroscopy analysis and molecular modeling to elucidate the binding mechanism of anticancer drugs and DNA. The binding constant and the number of binding sites were 2.13 × 10(4) M(-1) and 1.09, respectively, at 298 K. Thermodynamic parameters (ΔG, ΔH and ΔS) exhibited negative values, which indicated that binding was spontaneous and Van der Waals forces and hydrogen bond were the main interaction forces. Fourier transform infrared spectroscopy and other spectroscopy analysis methods illustrated that letrozole could intercalate into the phosphate backbone of hsDNA and interact with the nitrogenous bases. Consistent with the experimental findings, molecular modeling results demonstrated that the interaction was dominated by intercalation and hydrogen bonding. Copyright © 2015 John Wiley & Sons, Ltd.

[Comparative study of time-correlated temperature and back-scattered light intensity for human Hegu acupoint and non-acupoint tissue irradiated by near-infrared laser].

Characteristics and differences of temperature and back-scattered light intensity in different depths of 0.2, 0.4, 0.6, 0.8 and 1 mm for both human Hegu acupoint and non-acupoint tissue irradiated by 808 nm diode laser at the different power of 15, 25 and 35 mW were studied. The temperature and the back-scattered light intensity in different depths of 0.2, 0.4, 0.6, 0.8 and 1 mm for human Hegu acupoint and non-acupoint tissue were measured by using the infrared thermography and optical coherence tomography. The result shows few differences in the temperature and the back-scattered light intensity of human Hegu acupoint and non-acupoint tissue before irradiation. The temperature and back-scattered light intensity of Hegu acupoint and the non-acupoint after irradiation were significantly higher, and the temperature and back-scattered light intensity of Hegu acupoint significantly were higher than the non-acupoint areas. At 0-40 min after the irradiation, the temperature and back-scattered light intensity of Hegu acupoint and the non-acupoint area will fluctuate and gradually decrease with the passage of time. From the results above, it is clearly seen that Hegu acupoint is different from non-acupoint both in the back-scattered light intensity and temperature after irradiation, and Hegu acupoint is more sensitive to laser irradiation than non-acupoint tissue.

[Low level laser irradiation in the visible spectra induces HeLa cells proliferation].

The aim of this in vitro study was to evaluate the effects of low level laser irradiation on the proliferation of HeLa cells using 405 nm diode laser, 514 nm argon laser, 633 nm He-Ne laser, or 785 nm diode laser, The cells were seeded on 96-well microplates for 24 h in 5% fetal bovine serum containing medium, then irradiated with the laser at dose of 100 and 1 000 J x m(-2), respectively. At the time point of 24, 48, 72 h after irradiation, cell viability was assessed by MTT assay. The results show that 405, 633 and 785 nm laser irradiation induces wavelength-dependent and time-dependent proliferation. 633 nm laser irradiation results in a stimulatory proliferation effect that is most significant, whereas 514 nm laser irradiation produces little increase in cell proliferation. Low level laser irradiation increases cell proliferation in a dose-dependent manner. 1 000 J x m(-2) laser irradiation is more effective in increasing cell proliferation than 100 J x m(-2) laser irradiation using 405 nm diode laser, 633 nm He-Ne laser, or 785 nm diode laser, but not as effective as using 514 nm argon laser.

Ganoderma lucidum polysaccharide accelerates refractory wound healing by inhibition of mitochondrial oxidative stress in type 1 diabetes.

BACKGROUND/AIMS: Refractory wounds in diabetic patients constitute a serious complication that often leads to amputation with limited treatment regimens. The present study was designed to determine the protective effect of Ganoderma lucidum polysaccharide (Gl-PS) on diabetic wound healing and investigate underlying mechanisms. METHODS: Streptozotocin (STZ)-induced type 1 diabetic mice with full-thickness excisional wounds were intragastrically administered with 10, 50 or 250 mg/kg/day of Gl-PS. RESULTS: Gl-PS dose-dependently rescued the delay of wound closure in diabetic mice. 50 and 250 mg/kg/day of Gl-PS treatment significantly increased the mean perfusion rate around the wound in diabetic mice. Diabetic conditions markly increased mitochondrial superoxide anion (O(2)·(-)) production, nitrotyrosine formation, and inducible nitric oxide synthase (iNOS) activity in wound tissues, which were normalized with Gl-PS treatment. In diabetic wound tissues, the protein level of manganese superoxide dismutase (MnSOD) was unchanged whereas MnSOD activity was inhibited and its nitration was potentiated; Gl-PS administration suppressed MnSOD nitration and increased MnSOD and glutathione peroxidase (GPx) activities. Moreover, Gl-PS attenuated the redox enzyme p66Shc expression and phosphorylation dose-dependently in diabetic mice skin. CONCLUSION: Gl-PS rescued the delayed wound healing and improved wound angiogenesis in STZ-induced type 1 diabetic mice, at least in part, by suppression of cutaneous MnSOD nitration, p66Shc and mitochondrial oxidative stress.