Background: MEOX1 is a homeobox transcriptional factor, and plays essential roles in regulating somite development. Our previous study indicated that MEOX1 is a critical molecular target in mesenchymal-like cancer cells in PTEN-deficient Trastuzumab resistant breast cancer. Despite the potential implication of MEOX1 for the cancer progression, no previous studies examined its level and clinical significance in lung cancer tissues. In this study, we aimed to detect the MEOX1 expression and correlate its level with clinical outcome in non-small-cell lung cancer patients (NSCLC). Methods: MEOX1 gene expression in lung cancer was examined by using the Oncomine database. MEOX1 protein levels were evaluated by IHC using the corresponding primary antibody on two different commercial lung cancer tissue arrays. siRNA knockdown was used to elucidate the function of MEOX1. Results: Analysis of the Oncomine datasets identified that an elevation of MEOX1 in gene amplification in lung cancer tissues in comparison to normal lung tissues. Immunohistochemistical analysis demonstrated that MEOX1 was localized predominantly in the nucleus, and positive rate was 67.3% (111/165) in NSCLC samples. Statistical analysis revealed high levels of MEOX1 significantly correlated with Lymph Node Metastasis and Stage. Kaplan-Meier survival analysis showed that high levels of MEOX1 were significantly associated with unfavorable survival in NSCLC patients, and MEOX1 nucleus staining had worse survival, than did patients with overall expression in lung squamous cell carcinoma patients. Multivariate Cox's regression analysis found that MEOX1 was an independent poor prognostic predictor for patients with NSCLC. Silencing of MEOX1 by specific SiRNA significantly inhibited H460 and H1299 cell proliferation and sphere formation in serum-free medium. Conclusions: Our results firstly indentified that high levels of MEOX1 especially nuclear staining was an independent prognostic factor for NSCLC, and it served a essential roles in the regulation of cell proliferation and colony formation in vitro. It may represent a potential target for the NSCLC treatment.

Atherosclerosis (AS) is a chronic inflammatory disease, and macrophages play a key role in all phases of AS. Recent studies have shown that miR-221 is a biomarker for AS and stroke; however, the role and mechanism of miR-221 in AS are unclear. Herein, we found that miR-221 and NCoR levels were decreased in ox-LDL-treated THP-1-derived macrophages. In contrast, DNMT3b, IL-6, and TNF-α expression levels were increased under these conditions. Upregulation of miR-221 or NCoR could partially inhibit ox-LDL-induced IL-6 and TNF-α expression. Further studies showed that DNMT3b was a target of miR-221. DNMT3b inhibition also suppressed IL-6 and TNF-α expression and increased NCoR expression in the presence of ox-LDL. Moreover, DNMT3b was involved in ox-LDL-induced DNA methylation in the promoter region of NCoR. These findings suggest that miR-221 suppresses ox-LDL-induced inflammatory responses via suppressing DNMT3b-mediated DNA methylation in the promoter region of NCoR. These results provide a rationale for using intracellular miR-211 as a possible antiatherosclerotic target.

To demonstrate a specific skin dose limiting technique in radiotherapy treatment planning for esophageal cancer and carry out a comparative analysis combining with clinical cases.

Alzheimer's disease (AD), a common neurodegenerative disease in the elderly and the most prevalent cause of dementia, is characterized by progressive cognitive impairment. The prevalence of AD continues to increase worldwide, becoming a great healthcare challenge of the twenty-first century. In the more than 110 years since AD was discovered, many related pathogenic mechanisms have been proposed, and the most recognized hypotheses are the amyloid and tau hypotheses. However, almost all clinical trials targeting these mechanisms have not identified any effective methods to treat AD. Scientists are gradually moving away from the simple assumption, as proposed in the original amyloid hypothesis, to new theories of pathogenesis, including gamma oscillations, prion transmission, cerebral vasoconstriction, growth hormone secretagogue receptor 1α (GHSR1α)-mediated mechanism, and infection. To place these findings in context, we first reviewed the neuropathology of AD and further discussed new insights in the pathogenesis of AD.

La3 B6 O13 (OH) was obtained by a high-pressure/high-temperature experiment at 6 GPa and 1673 K. The compound crystallizes in the space group P21 (no. 4) with the lattice parameters a=4.785(2), b=12.880(4), c=7.433(3) Å, and β=90.36(10)°, and is built up of corner- as well as edge-sharing BO4 tetrahedra. It represents the first acentric high-pressure borate containing these B2 O6 entities. The compound develops borate layers of "sechser"-rings with the La3+ cations positioned between the layers. Single-crystal and powder X-ray diffraction, vibrational and MAS NMR spectroscopy, second-harmonic generation (SHG) and thermoanalytical measurements, as well as computational methods were used to affirm the proposed structure and the B2 O6 entities.

Maternal separation (MS), a stressful event in early life, has been linked to neuropsychiatric disorders later in life, especially depression. In this study we investigated whether treatment with electroacupuncture (EA) could ameliorate depression-related manifestations in adult animals that had adverse early life experiences. We demonstrated depression-like behavior deficiencies in a sucrose preference test and a forced swimming test in a rat model with neonatal MS. Repeated EA treatment at the acupoints Baihui (GV20) and Yintang (GV29) during adulthood was shown to be remarkably attenuated above behavioral deficits. Using unbiased genome-wide RNA sequencing to investigate alterations in the transcriptome of the prefrontal cortex (PFC), we explored the altered gene sets involved in circadian rhythm and neurotransmitter transporter activity in MS rats, and their expression tended to be reversed after EA treatment. In addition, we analyzed the interaction network of differentiated lncRNA- or circRNA-miRNA-mRNA by using the principle of competitive endogenous RNA (ceRNA). These results suggest that EA at GV20 and GV29 ameliorates depression-related manifestations by regulating the expression of multiple genes.

Nucleobases serve as ideal targets where drugs bind and exert their anticancer activities. Cisplatin (cisPt) preferentially coordinates to 2'-deoxyguanosine (dGuo) residues within DNA. The dGuo adducts that are formed alter the DNA structure, contributing to inhibition of function and ultimately cancer cell death. Despite its success as an anticancer drug, cisPt has a number of drawbacks that reduce its efficacy, including repair of adducts and drug resistance. Some approaches to overcome this problem involve development of compounds that coordinate to other purine nucleobases, including those found in RNA. In this work, amino acid-linked platinum(II) (AAPt) compounds of alanine and ornithine (AlaPt and OrnPt, respectively) were studied. Their reactivity preferences for DNA and RNA purine nucleosides (i.e., 2'-deoxyadenosine (dAdo), adenosine (Ado), dGuo, and guanosine (Guo)) were determined. The chosen compounds form predominantly monofunctional adducts by reacting at the N1, N3, or N7 positions of purine nucleobases. In addition, features of AAPt compounds that impact the glycosidic bond stability of Ado residues were explored. The glycosidic bond cleavage is activated differentially for AlaPt-Ado and OrnPt-Ado isomers. Formation of unique adducts at non-canonical residues and subsequent destabilization of the glycosidic bonds are important features that could circumvent platinum-based drug resistance.

A simple modification converts an electrospray ion source to an ambient-pressure helium plasma ionization source without the need of additional expensive hardware. Peaks for active ingredients were observed in the spectra recorded from intact pharmaceutical tablets placed in this source. A flow of heated nitrogen was used to thermally desorb analytes to gas phase. The desorption temperatures were sometimes as low as 50 °C. For example, negative-ion spectra recorded from an aspirin tablet showed peaks at m/z 137 (salicylate anion) and 179 (acetylsalicylate anion) which were absent in the background spectra. The overall ion intensity increased as the desorption gas temperature was elevated. Within the same acquisition experiment, both positive- and negative-ion signals for acetaminophen were recorded from volatiles emanating from Tylenol tablets by switching the polarity of the capillary back and forth. Moreover, different preparations of acetaminophen tablets could be distinguished by their ion-intensity thermograms.

Understanding and exploring the functional modules (FMs) consisting of local atomic groups can promote the development of the materials with functional performances. Oxygen-containing tetrahedral modules are popular in deep-ultraviolet (DUV) optical materials, but their weak optical anisotropy is adverse to birefringence. Here, the fluorooxosulfate group is proved as a new birefringence-enhanced FM for the first time. The birefringence of fluorooxosulfates can be 4.8-15.5 times that of sulfates with the same metal cations while maintaining a DUV band gap. The polarizing microscope measurement confirms the birefringence enhancement by using the millimeter crystals experimentally. The theoretical studies from micro and macro levels further reveal a novel universal strategy that the fluorine induced anisotropic electronic distribution in fluorooxo-tetrahedral group is responsible for the enhancement of birefringence. This study will guide the future discovery of DUV optical materials with enlarged birefringence.

Spinal cord ischemia-reperfusion injury (SCII) is one of the most serious complications of clinical aortic aneurysm and vascular malformation surgery. Long noncoding RNA (lncRNA) is involved in the progression of SCII, whereas long noncoding RNA HOX transcript antisense RNA (lncRNA HOTAIR) is unclear in SCII. This study is aimed at confirming the role and related mechanism of HOTAIR in SCII. Later on, a model of SCII was established by clamping the aortic arch for 14 minutes. RNA expression of HOTAIR was detected via qRT-PCR at 12 h, 24 h, 36 h, and 48 h after SCII. The Tarlov scoring system and TUNEL assay were used to evaluate neurological function and neuronal apoptosis. Oxidative stress factor levels were assessed according to the instructions of the kit. Inflammatory cytokines were assessed by ELISA. Western blot was used to detect levels of p65, p-p65, I-κBα, and p-I-κBα. We found HOTAIR was raised in SCII rats. si-HOTAIR was able to reverse SCII-induced oxidative stress in SCII rats. The HMGB1 expression was upregulated in SCII tissues and negatively correlated with HOTAIR. HMGB1 was able to partially reverse si-HOTAIR inhibition of oxidative stress, inflammatory injury, and neuronal cell apoptosis in SCII. In addition, the ROS/NF-κB signaling pathway is involved in HOTAIR/HMGB1 regulation of SCII. In a word, HOTAIR inhibition is able to inhibit oxidative stress, inflammatory injury, and neuronal apoptosis in SCII through downregulation of the high mobility group protein B1(HMGB1), which is achieved by inhibiting the ROS/NF-κB signaling pathway. The HOTAIR/HMGB1/ROS/NF-κB molecular pathway may be a new mechanism for the treatment of SCII.

Qinggong Shoutao Wan (QGSTW) is a pill used as a traditional medicine to treat age-associated memory decline (AAMI). However, its potential mechanisms are unclear.

Transcription factors (TFs) have been introduced to drive the highly efficient differentiation of human-induced pluripotent stem cells (hiPSCs) into lineage-specific oligodendrocytes (OLs). However, effective strategies currently rely mainly on genome-integrating viruses. Here we show that a synthetic modified messenger RNA (smRNA)-based reprogramming method that leads to the generation of transgene-free OLs has been developed. An smRNA encoding a modified form of OLIG2, in which the serine 147 phosphorylation site is replaced with alanine, OLIG2S147A, is designed to reprogram hiPSCs into OLs. We demonstrate that repeated administration of the smRNA encoding OLIG2 S147A lead to higher and more stable protein expression. Using the single-mutant OLIG2 smRNA morphogen, we establish a 6-day smRNA transfection protocol, and glial induction lead to rapid NG2+ OL progenitor cell (OPC) generation (>70% purity) from hiPSC. The smRNA-induced NG2+ OPCs can mature into functional OLs in vitro and promote remyelination in vivo. Taken together, we present a safe and efficient smRNA-driven strategy for hiPSC differentiation into OLs, which may be utilized for therapeutic OPC/OL transplantation in patients with neurodegenerative disease.

Cancer stem cells (CSCs) are undifferentiated cancer cells with a high tumorigenic activity, the ability to undergo self-renewal, and a multilineage differentiation potential. Clinical evidence suggests that CSCs in a tumor mass are the cellular determinants to promote cancer invasion and metastasis. MicroRNAs (miRNAs) have emerged as important modulators of cancer stem cell characteristics. Unveiling the candidate miRNAs that regulate CSCs may provide novel therapeutic targets against cancer. We analyzed the miRNA expression profiles regulating the cancer stem-like cell characteristics in gastric cancer. Gastric cancer stem cells (GCSCs) were sorted using the stem cell marker CD44 by fluorescence-activated cell sorting. Functional studies revealed that CD44(+) cells formed more sphere colonies and showed higher invasiveness than CD44(-) cells. miRNA microarray analysis revealed that miR‑196a‑5p was significantly upregulated in CD44(+) cells than CD44(-) cells. Suppression of miR‑196a‑5p led to decreased colony formation and invasion of GCSCs. miR‑196a‑5p decreased the expression of Smad4 by targeting 3'-UTR of the mRNA. The expression of Smad4 in gastric cancer tissues was correlated with differentiation state of tumors, TNM stage and depth of invasion. The stimulation of epithelial-mesenchymal transition (EMT) by miR‑196a‑5p in cancer stem-like cells was abolished by overexpression of Smad4. Collectively, these data demonstrate that miR‑196a‑5p has a key role in EMT and invasion by targeting Smad4 in GCSCs. miR‑196a‑5p may serve as a potential target for gastric cancer therapy.

Atherosclerosis is the leading cause of cardiovascular disease with a high mortality worldwide. Understanding the atherosclerosis pathogenesis and identification of efficient diagnostic signatures remain major problems of modern medicine. This study aims to screen the potential diagnostic genes for atherosclerosis.

Fire-needle moxibustion (FNM) is an ancient method of external therapy that combines acupuncture with moxibustion, and has the property of high temperature resistance. Insomnia is a major public health problem and strongly associated with a high prevalence, impact on daily life, comorbidity with other disorders, and societal costs. The clinical practice demonstrates that FNM has a therapeutic effect on insomnia. Here we will provide a protocol to evaluate the effectiveness and safety of FNM for insomnia.

Bone marrow-mesenchymal stem cells (BM-MSCs) possess immunomodulatory properties in the brain. However, it remains unclear whether intravenously transplanted BM-MSCs have a neuromodulator effect on the activation of microglias after ischemic stroke. This study aimed to investigate the immunomodulatory effect of BM-MSCs on the regulation of brain microglial inactivation during the acute phase of stroke.

Background: Alpha-enolase is an important glycolytic enzyme, and its aberrant expression has been associated with multiple tumor progression. However, few studies investigated the expression of alpha-enolase and its clinical significance in pancreatic cancer (PC). Objectives: To evaluate alpha-enolase level in PC tissues by immunohistochemical (IHC) analysis, and investigate the association of alpha-enolase expression with clinicopathologic features. Methods: The alpha-enolase levels in pancreatic cancer tissues were analyzed by using the Oncomine database. The expression of alpha-enolase, Ki67 and p53 in pancreatic cancer and adjacent normal tissues were evaluated by IHC using the corresponding primary antibodies on the commercial tissue arrays. We also examined their association with clinicopathologic parameters, and explored their prognostic value in PC. Results: We identified an elevation of alpha-enolase mRNA level in pancreatic cancer independent datasets from Oncomine. IHC analysis showed that alpha-enolase protein levels were elevated in 47% (n=100) PC tissue samples, but there was weak or no staining in the normal tissues. Statistical analysis revealed that high levels of alpha-enolase were significantly associated with Stage and Lymph node metastasis. Correlation analysis indicated that over-expression of alpha-enolase was positively associated with Ki67 expression and inversely correlated with p53 expression. Furthermore, membranous expression of alpha-enolase was also observed in 29.8% (14/47) total alpha-enolase positive samples, and was significantly associated with Lymph node metastasis. Kaplan-Meier survival analysis demonstrated that high total alpha-enolase expression was significantly associated with unfavorable survival, while membranous alpha-enolase expression was significantly associated with better survival of PC patients. Multivariate Cox analysis demonstrated that total alpha-enolase expression was an independent prognostic factor for PC patients. Conclusions: Our results suggested that alpha-enolase level was significantly elevated in pancreatic cancer tissues, which was closely associated with PC progression. It might be a candidate target for targeted pancreatic cancer treatments.

Increasing evidence has demonstrated that the secretion of cytokines may be associated with cigarette smoke-induced immunomodulatory effects, but a comprehensive analysis of the cytokine profile for cigarette smoke condensate (CSC) exposure is lacking. The aims of this study were to (1) examine the release of 20 cytokines induced by CSC from 12 brands of cigarettes in macrophages cells (Ana-1) and (2) to investigate the general characteristics of the immunomodulatory effects of CSC. Luminex technology was used to simultaneously determine the levels of 20 cytokines (interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ), keratinocyte-derived Chemokine (KC), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α (MIP-1α), induced protein 10 (IP-10), tumor necrosis factor α (TNF-α), vascular endothelial growth factor (VEGF), monkine inducible by γ interferon (MIG), and fibroblast growth factor (FGF)-basic) in the supernatants from Ana-1 cells treated with the CSC. The results showed that the release of eight cytokines was altered (IL-5, IL-6, IL-12, TNF-α, VEGF, IP-10, MCP-1, and MIP-1α) compared with the control. These cytokines fall into two major subtypes: proinflammatory cytokines, including IL-5, IL-6, IL-12, TNF-α, and VEGF, and chemokines, including IP-10, MCP-1, and MIP-1α. Compared with control, the remaining 12 cytokines were not significantly affected by CSC from the 12 brands of cigarettes. As a general characteristic, CSC exerts potently suppressive immunomodulatory effects on cytokine production of Ana-1 cells. Proinflammatory cytokines and chemokines may account for or contribute to the immunosuppressive properties of CSC.

The present study developed an oral hepatocyte growth factor (HGF) gene therapy strategy for gastric ulcers treatment. An attenuated Salmonella typhimurium that stably expressed high HGF (named as TPH) was constructed, and the antiulcerogenic effect of TPH was evaluated in a rat model of gastric ulcers that created by acetic acid subserosal injection. From day 5 after injection, TPH (1 × 10⁹ cfu), vehicle (TP, 1 × 10⁹ cfu), or sodium bicarbonate (model control) was administered orally every alternate day for three times. Then ulcer size was measured at day 21 after ulcer induction. The ulcer area in TPH-treated group was 10.56 ± 3.30 mm², which was smaller when compared with those in the TP-treated and model control groups (43.47 ± 4.18 and 56.25 ± 6.38 mm², respectively). A higher level of reepithelialization was found in TPH-treated group and the crawling length of gastric epithelial cells was significantly longer than in the other two groups (P < 0.05). The microvessel density in the ulcer granulation tissues of the TPH-treated rats was 39.9 vessels/mm², which was greater than in the TP-treated and model control rats, with a significant statistical difference. These results suggest that TPH treatment significantly accelerates the healing of gastric ulcers via stimulating proliferation of gastric epithelial cells and enhancing angiogenesis on gastric ulcer site.

This study examined the significance of macrophage autophagy in extracellular matrix metalloproteinase inducer (EMMPRIN)-mediated atherosclerosis (AS). Apolipoprotein E-deficient (ApoE-/-) mice were fed a western diet to establish an AS model. EMMPRIN and p62/Sequestosome-1(SQSTM1) expression were evaluated in plaque macrophages from the AS mice using immunofluorescence. The EMMPRIN and p62/SQSTM1 protein expression levels in macrophages increased with the increasing vulnerability of the atherosclerotic plaques. RAW264.7 cells and ApoE-/- mice Bone Marrow-derived macrophages were transfected with different small interfering RNAs (siRNAs) or plasmids, or treated with different drugs in the presence or absence of oxidized low-density lipoprotein (oxLDL). The protein levels of the targets were evaluated using western blotting (WB), and the autophagosomes were observed under a transmission electron microscope (TEM). Over-expressed EMMPRIN dramatically inhibited oxLDL-mediated autophagy. EMMPRIN also negatively regulated autophagy primarily through the nuclear factor-kappa B (NF-κB) signalling pathway. In turn, activated NF-κB up-regulated EMMPRIN expression. Inhibition of EMMPRIN decreased cell apoptosis and the release of inflammatory cytokines via the promotion of macrophage autophagy. Infection with an adenovirus delivering the EMMPRIN-siRNA ameliorated AS, promoted macrophage autophagy in plaques and reduced the serum TNF-α, IL-6, MCP-1 and NF-κB expression levels in the AS mice. Chloroquine (CQ) reversed these effects. This study revealed for the first time that the feedback loop of the "EMMPRIN/NF-κB" pathway plays an important role in atherosclerotic plaques via modulation of autophagy in macrophages, which might provide a potential strategy for the clinical treatment of AS.