Melatonin modulates the effects of diethylstilbestrol (DES) on the anterior pituitary of the female Wistar rat.

We studied the anti-tumorigenic effect of melatonin in diethylstilbestrol (DES)-treated anterior pituitaries in rats. Twenty-one female Wistar rats were randomly allocated into three groups: vehicle control rats, DES-treated rats, and DES-treated rats co-administrated with melatonin beginning at week 13. At the end of 16 weeks, rats were weighed and decapitated for morphological studies, including an H+E staining-based score evaluation in regard to cell proliferation, angiogenesis, immunostaining for VEGF, MMP-9, and AQP-1, and electron microscopy. Compared with vehicle, long-term treatment of DES significantly reduced rat body weight and increased H+E score, both of which were counteracted by melatonin. Administration of melatonin also reduced the expression of VEGF and MMP-9, although no changes were detected in AQP-1 expression. In rats cotreated with melatonin, the RER loosened and accumulated more secretion granules. We thus concluded that melatonin can modulate the effects of DES on the rat anterior pituitary by downregulating expression of VEGF and MMP-9 and suppressing the release of secretion granules, suggesting a therapeutic potential in estrogen-induced pituitary malfunctions

Plasma medicine for neuroscience - An introduction

Plasma is an ionized gas. It is typically formed at high temperature. As a result of both the development of low-temperature plasma sources and a better understanding of complex plasma phenomena over the last decade, "plasma medicine" has become a booming interdisciplinary research topic of growing importance that explores enormous opportunities at the interface of chemistry, plasma physics, and biomedical sciences with engineering. This review presents the latest development in plasma medicine in the area of the central nervous system and aims to introduce cutting-edge plasma medicine to clinical and translational medical researchers and practitioners.</p

Trinuclear and Cyclometallated Organometallic Dinuclear Pt-Pyrazolato Complexes: A Combined Experimental and Theoretical Study

Two differently substituted pyrazole ligands have been investigated with regard to the topology of their Pt complexes: upon deprotonation, two mononuclear 1:2 PtII-pyrazole complexes&mdash;one of the sterically unhindered 4-Me-pzH and one of the bulky 3,5-tBu-pzH (pzH = pyrazole)&mdash;yield the corresponding 1:2 PtII-pyrazolato species; the former a triangular, trinuclear metallacycle (1), and the latter a dinuclear, half-lantern species (2) formed via the unprecedented cyclometallation of a butyl group. Stoichiometric oxidation of the colorless PtII2 complex produces the deep-blue, metal&ndash;metal bonded PtIII2 analog (3) with a rarely encountered unsymmetrical coordination across the Pt-Pt bond. All three complexes have been characterized by single crystal X-ray structure determination, 1H-NMR, IR, and UV-vis-NIR spectroscopic methods. The XPS spectra of the PtII2 and PtIII2 species are also reported. Density functional theory calculations were carried out to investigate the electronic structure, spectroscopic properties, and chemical bonding of the new complexes. The calculated natural population analysis charges and Wiberg bonding indices indicate a weak &sigma;-interaction in the case of 2 and a formal Pt-Pt single bond in 3

Melatonin modulates the effects of diethylstilbestrol (DES) on the anterior pituitary of the female Wistar rat.

We studied the anti-tumorigenic effect of melatonin in diethylstilbestrol (DES)-treated anterior pituitaries in rats. Twenty-one female Wistar rats were randomly allocated into three groups: vehicle control rats, DES-treated rats, and DES-treated rats co-administrated with melatonin beginning at week 13. At the end of 16 weeks, rats were weighed and decapitated for morphological studies, including an H+E staining-based score evaluation in regard to cell proliferation, angiogenesis, immunostaining for VEGF, MMP-9, and AQP-1, and electron microscopy. Compared with vehicle, long-term treatment of DES significantly reduced rat body weight and increased H+E score, both of which were counteracted by melatonin. Administration of melatonin also reduced the expression of VEGF and MMP-9, although no changes were detected in AQP-1 expression. In rats cotreated with melatonin, the RER loosened and accumulated more secretion granules. We thus concluded that melatonin can modulate the effects of DES on the rat anterior pituitary by downregulating expression of VEGF and MMP-9 and suppressing the release of secretion granules, suggesting a therapeutic potential in estrogen-induced pituitary malfunctions

Cytoprotective effect of atmospheric pressure helium plasma on oxygen and glucose deprivation-induced cell death in H9C2 cardiac myoblasts and primary neonatal rat cardiomyocytes

Atmospheric pressure plasma jet (APPJ) has shown excellent potential prospects in biomedical applications, based on the production of reactive oxygen species and reactive nitrogen species (RNS) from APPJ emissions. The current research focused on the protective effect of APPJ on oxygen and glucose deprivation (OGD)-induced cell death in both the H9C2 cardiac myoblast cell line, a frequently used cardiac cell line in cardioprotective studies, and primary neonatal rat cardiomyocytes (NRCMs). Cells were treated with APPJ for different durations, cultured for 6 h and then subjected to OGD for 18 h before their use in assays. We found that APPJ treatment could maintain H9C2 cell viability and reduce cell apoptosis in a dose-dependent manner in cells subjected to the OGD conditions. To confirm the cardioprotective effect of APPJ on primary NRCM, we first identified the 'safe dose' of APPJ treatment by evaluating the cytotoxicity of APPJ on primary NRCMs in normal culture conditions. Under the 'safe dose' of APPJ treatment, we also found that the APPJ treatment could maintain NRCM viability under OGD conditions and reduce CK-MB and cTnI release from cardiomyocytes. Further studies revealed that the cytoprotective effect of APPJ may be related to NO production induced by APPJ treatment. Our results gave the first evidence of the cardiotoxicity and cytoprotective effect of APPJ on cardiomyocytes against OGD injury, and furthermore, contributed to new insights into the potential medical applications of plasma in cardiovascular diseases

Atmospheric pressure plasma treatments protect neural cells from ischemic stroke-relevant injuries by targeting mitochondria

Most studies regarding plasma biomedicine applications mainly focus on the oxidative and/or nitrative stress on bacteria, cancer cells, and other treatment objects. In this study, we evaluate the protective effect of appropriate atmospheric pressure plasma jet (APPJ) treatments on oxygen and glucose deprivation (OGD)-induced neural cell apoptosis, which is a major pathological process during ischemic stroke, based on the physiological functions of NO. Results show that APPJ treatment reduces the OGD-induced apoptosis by weakening typical OGD injury consequences including loss of mitochondrial membrane potential, the release of cytochrome c from the mitochondria into the cytoplasm, lower antiapoptotic Bcl-2 expression, and upregulating the proapoptotic protein Bax. Furthermore, APPJ increased intracellular NO production, which is closely related to the cytoprotective effect of APPJ.</p

Inhalation of Atmospheric-Pressure Gas Plasma Attenuates Brain Infarction in Rats With Experimental Ischemic Stroke

Previous studies suggest the potential efficacy of neuroprotective effects of gaseous atmospheric-pressure plasma (APP) treatment on neuronal cells. However, it remains unclear if the neuroprotective properties of the gas plasmas benefit the ischemic stroke treatment, and how to use the plasmas in the in vivo ischemic stroke models. Rats were subjected to 90 min middle cerebral artery occlusion (MCAO) to establish the ischemic stroke model and then intermittently inhaled the plasma for 2 min at 60 min MCAO. The regional cerebral blood flow (CBF) was monitored. Animal behavior scoring, magnetic resonance imaging (MRI), 2,3,5-triphenyltetrazolium chloride (TTC) staining, and hematoxylin and eosin (HE) staining were performed to evaluate the therapeutic efficacy of the gas plasma inhalation on MCAO rats. Intermittent gas plasma inhalation by rats with experimental ischemic stroke could improve neurological function, increase regional CBF, and decrease brain infarction. Further MRI tests showed that the gas plasma inhalation could limit the ischemic lesion progression, which was beneficial to improve the outcomes of the MCAO rats. Post-stroke treatment with intermittent gas plasma inhalation could reduce the ischemic lesion progression and decrease cerebral infarction volume, which might provide a new promising strategy for ischemic stroke treatment.</p

Mechanisms of atmospheric pressure plasma protection of neuronal cells under simulated ischemic stroke conditions

Physico-chemical and biological effects of atmospheric pressure plasmas (APPs) find numerous applications in biotechnology, medicine, and other fields. Recent studies revealed APPs' potential for ischemic stroke treatment through the protection of neuronal cells from injuries. However, the mechanisms of the plasma neuroprotection effects still remain unknown. This study reveals the key mechanisms of APP plasma jet (APPJ) enabled reduction of neuronal cell death caused by oxygen and glucose deprivation (OGD) under stroke-relevant conditions. Plasma reduced OGD induced apoptosis of SH-SY5Y neuronal cells is based on reactive oxygen and nitrogen species production and on nitric oxide related activation of the cyclic guanosine monophosphate (cGMP) and cGMP-dependent protein kinase G (PKG) pathway, followed by the Bcl-2/Bax level modulation and caspase3/9 activity inhibition. In addition, the protective effect of APPJ treatment on OGD injured SH-SY5Y cells could be abolished by cGMP pathway inhibitor LY83583 pretreatment. Collectively, our findings highlight that the mechanism of the neuroprotection effects of the plasma treatment is closely related to the intracellular cGMP/PKG pathway, which provide experimental and theoretical references for future studies on plasma medicine. </p