The Mechanism of Volatile Oil of Rhodiola tangutica against Hypoxia-Induced Pulmonary Hypertension in Rats Based on RAS Pathway.

Materials and Methods: Seventy-five male Sprague-Dawley (SD) rats were separated into control (Ctr), hypoxia (Hyp), and Hyp+VORA treatment (100 mg/kg/d, 80 mg/kg/d, and 40 mg/kg/d) groups in random. To achieve the chronic hypoxia condition, rats were kept inside the hypobaric chamber with automatically adjusted inner pressure as well as oxygen content equal to those of 4500 m in altitude for 4 continuous weeks. After 4 weeks, the rats' physiological parameters were determined (mean pulmonary artery pressure (mPAP); right ventricular hypertrophy index (RVHI)). Based on hematoxylin and eosin (HE) staining and transmission electron microscope (TEM), morphological features of their lung tissues were also analyzed. Proliferation of pulmonary arterial smooth muscle cells (PASMCs) was detected by MTS Cell Proliferation Colorimetric assay. The levels of glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) in PASMCs were detected through corresponding kits, respectively. The protein levels in PASMCs and HPH rats were evaluated by Western blot (WB). Chemical components of VORA were detected through gas chromatography-mass spectrometer (GC-MS). Results: After induced by hypoxia for 4 weeks, the mPAP and RVHI levels were increased significantly in hypoxia group in contrast to the Ctr group, indicating the establishment of HPH rat model. The subsequent administration of VORA decreased the mPAP and RVHI level. The vascular wall thickness and lumen size were also decreased after treated by VORA compared with Hyp group. Meanwhile, VORA suppressed the proliferation and oxidant stress in PASMCs. Therefore, the effect of VORA on decreasing vascular wall thickening and lumen size could be related to its antiproliferation effect on PASMCs. In addition, compared to the Hyp group, VORA downregulated the ACE, AngII, and AT1R protein expressions but increased ACE2 and MAS protein expressions (P < 0.05). A total of 48 constituents in VORA were identified by GC-MS in comparison with reference standards as well as the reference pieces of literatures. Conclusions: HPH rat model as established based on the significant increased mPAP and RVHI. VORA presented a significant antihypoxia function plus an inhibiting effect on PASMC proliferation induced by hypoxia. Moreover, VORA treatment inhibited oxidative stress among PASMCs. With regard to the mechanism, VORA reduced ACE, AngII, and AT1R protein expressions but increased ACE2 and MAS protein expressions. There were 48 constituents in VORA identified by GC-MS.

Corydalis decumbens Can Exert Analgesic Effects in a Mouse Neuropathic Pain Model by Modulating MAPK Signaling.

Objectives: This study is aimed at investigating the analgesic effect of the administration of Corydalis decumbens (CD) in a mouse model of postherpetic neuralgia (PHN) and at elucidating its mechanism of analgesic action. Methods: Adult Kunming (KM) mice were randomly divided into control, CD, and vehicle-treated groups. Neuropathic pain was induced with a single intraperitoneal injection of resiniferatoxin (RTX). Thermal hyperalgesia was assessed with a hot/cold plate test, and mechanical allodynia was evaluated using von Frey filaments. The activation states of astrocytes, microglia, and the mitogen-activated protein kinase (MAPK) pathway in the spinal cord were determined by immunofluorescence staining and Western blot analysis of Iba-1, GFAP, phospho-p38, and phospho-Jun N-terminal kinase (JNK). Results: RTX diminished thermal sensitivity and gradually increased sensitivity to tactile stimulation. The expression of Iba-1, GFAP, phospho-p38 MAPK, and phospho-JNK was upregulated in the RTX-induced postherpetic neuralgia mouse model. Systemic treatment with CD significantly ameliorated thermal sensitivity and mechanical hyperalgesia and was accompanied by a reduction in the expression of Iba-1 and GFAP and reduced phosphorylation of p38 and JNK. Conclusions: This study suggests that CD is effective at ameliorating mechanical hyperalgesia in PHN mice and that its mechanism of action may involve modulation of MAPK phosphorylation and glial cell activation. Thus, CD may be a promising alternative therapy for PHN.

Correction: Allometric relationships between leaf and bulb traits of Fritillaria przewalskii Maxim. grown at different altitudes.

[This corrects the article DOI: 10.1371/journal.pone.0239427.].

Allometric relationships between leaf and bulb traits of Fritillaria przewalskii Maxim. grown at different altitudes.

Plants adapt to high altitudes by adjusting the characteristics of their above and underground organs. Identifying the species-specific plant traits changed in response to altitude is essential for understanding ecophysiological processes at the ecosystem level. Multiple studies analyzed the effects of altitude on above and underground organ traits in different species. Yet, little is known about those responses in the alpine Fritillaria przewalskii Maxim. (Liliaceae). F. przewalskii is a perennial medicinal plant with meager annual growth and vanishing wild populations. We analyzed leaf and bulb functional traits, and their allometric relationships in F. przewalskii plants grown at three altitudes: 3000, 2700, and 2400 m. Leaf thickness, leaf biomass, leaf biomass allocation, and the aboveground:underground ratio increased significantly with increasing altitude. Conversely, bulb allocation decreased at higher altitudes. The altitude influenced the allometric growth trajectories of specific leaf and bulb traits: higher altitudes led to thicker and broader leaves and changed the shape of the bulbs from more circular, which is ideal (at 2700 m), to more elongated (at 3000 m). Those variations had remarkable ecological significance. Hence, bulb biomass is the largest at 2700 m of altitude for which their vertical and longitudinal ratio is unaffected. which is economically favorable. Our findings show that F. przewalskii has a notable potential of growth and morphological plasticity along the altitude gradient and that 2700 m might be ideal for developing its artificial cultivation.

Increased serum levels of miR-214 in patients with PCa with bone metastasis may serve as a potential biomarker by targeting PTEN.

MicroRNAs (miRNAs/miRs) are identified to serve key functions in the progression of various tumors. miR-214 is aberrantly expressed in various types of cancer. In the present study, the function of miR-214 and its feasibility as a potential non-invasive biomarker for patients with prostate cancer (PCa) in a hyperplasia group and a control group were investigated. First, RNA was isolated from the serum of 75 patients with PCa with bone metastasis, 65 patients with PCa with no bone metastasis and 70 healthy controls. The level of miR-214 expression was significantly upregulated in the serum of the bone metastasis group compared with the healthy control and non-bone metastasis groups. Expression levels of alkaline phosphatase (ALP), bone sialoprotein (BSP), collagen type I pyridine crosslinking peptide (ICTP) were also evaluated. The results indicated that serum levels of BSP, ALP and ICTP were increased in the bone metastasis group compared with that in the non-bone metastasis group, hyperplasia group and the control group (P<0.05). The expression level of miR-214 is positively associated with poorly differentiated tumors in patients with PCa with a Gleason score >7 (P<0.05). Western blot analysis demonstrated that phosphatase and tensin homolog (PTEN) was a target gene of miR-214. Additionally, silencing of PTEN significantly increased the invasive ability of PC3 cells even when miR-214 expression was inhibited. In summary, serum miR-214 expression may serve as a potential novel non-invasive biomarker for PCa screening through targeting PTEN.

Associations of Caspase-3 gene polymorphism with lumbar disc herniation.

To investigate Caspase-3 gene polymorphisms (rs4647693 G/A, rs4647610 A/G, and rs12108497 T/C) and susceptibility to lumbar intervertebral disc herniation (LDH). The genotype frequency distributions of the polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 107 LDH patients (case group) and 121 healthy individuals (control group). SHEsis software was used to conduct gene linkage disequilibrium and haplotype analysis. Regression analysis was used to analyze possible risk factors for LDH. Statistically significant differences in family history of LDH, amateur sports, leisure activities, bed types, and spine load grade were found between the case and control groups. The distribution of allele and genotype frequencies of rs4647693 G/A, rs4647610 A/G, and rs12108497 T/C polymorphisms of Caspase-3 were significantly different between the case and control groups. Haplotype analysis showed that the G-G-C (rs4647693-rs4647610-rs12108497) haplotype might be a risk factor for LDH, whereas the A-A-T haplotype might be a protective factor (p < 0.05). Binary logistic regression analysis showed that the GA+AA genotype of rs4647693 was negatively associated with the risk of LDH, whereas high spine load grade was positively associated with the risk of LDH. These findings revealed that rs4647693 G/A, rs4647610 A/G, and rs12108497 T/C polymorphisms of Caspase-3 may be associated with susceptibility to LDH and that interaction and modification effects may exist between Caspase-3 polymorphisms.

Expression of the stem cell marker, Nanog, in human endometrial adenocarcinoma.

The embryonic stem cell self-renewal gene, Nanog, has been shown to be expressed in several tumor types and to regulate tumor development. The aim of this study was to carry out a detailed analysis of Nanog expression in human endometrial adenocarcinoma (EAC). Immunohistochemical analysis and reverse transcription-polymerase chain reaction were used to characterize Nanog, Sox2, and Oct4 expression in tissue arrays containing EAC, benign endometrium samples, and tumorosphere cells. Tumorosphere formation of EAC-derived cells in the stem cell culture medium was also analyzed. Nanog expression was then analyzed in secondary tumors initiated by the injection of tumorospheres or tumorosphere-derived differentiated cells into 15 female nude mice. Apoptosis and cell proliferation were detected in the fluorescence-activated cell sorter and 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide experiments, respectively. The Nanog protein was expressed in a majority of EAC samples (45 of 55, 81.8%), but not in benign endometrium samples (0 of 26, 0.0%). Oct4 and Sox2 were also commonly expressed in EAC samples (42 of 55, 76.4% and 39 of 55, 70.9%, respectively). Subsets of cancer cells from all EAC samples (15 of 15, 100%) exhibited the capacity to form Nanog-positive tumorospheres. The tumorospheres also expressed Nanog, Oct4, and Sox2 mRNA and showed a higher proliferation potential than differentiated cells. All 15 mice that were injected with tumorosphere cell-formed tumors, whereas only 3 of 15 mice injected with differentiated cells derived from tumorospheres developed tumors. All secondary xenograft tumors still expressed Nanog protein and Nanog, Oct4, and Sox2 mRNA, and had higher proliferation and lower apostosis than did differentiated cells. Overexpression of Nanog in EACs suggests that Nanog may represent a potential therapeutic target for EAC. In addition, Nanog may be useful as a biomarker in an immunohistochemical panel to differentiate between EAC and benign endometrial tissues. The expression of Nanog in tumorospheres may be indicative of the presence of a population of endometrial cancer stem cells, and its expression in xenograft tumors suggests that Nanog may also be associated with tumor metastasis.