Mesenchymal Stem Cells Accelerate Recovery of Acetic Acid-Induced Chronic Gastric Ulcer by Regulating Ekt/Akt/TRIM29 Axis.

Chronic gastric ulcer (CGU), a prevalent digestive disease, has a high incidence and is seriously harmful to human health. Mesenchymal stem cells (MSCs) have been proven to have beneficial therapeutic effects in many human diseases. Here, a CGU model induced by acetic acid in mice was used to evaluate the repair effects and potential mechanism of human umbilical cord-derived MSCs (hUC-MSCs) and hUC-MSCs derived conditioned medium (hUC-MSC-CM). We found that hUC-MSCs and hUC-MSC-CM treatment significantly repaired morphological characteristics of CGU, improved proliferation and decreased apoptosis of gastric cells, and promoted the generation of new blood vessels in granulation tissues. In addition, we could detect the homing of MSCs in gastric tissue, and MSCs may differentiate into Lgr5-positive cells. As well as this, in vitro experiments showed that hUC-MSC-CM could promote cell proliferation, stimulate cell cycle progression, and reduce the incidence of apoptosis. The transcriptome of cells and the iTRAQ proteome of gastric tissues suggest that MSCs may play a therapeutic role by increasing the expression of TRIM29. Additionally, it was found that knocking down TRIM29 significantly decreased the ameliorative effects of hUC-MSC-CM on cell apoptosis. As a result of further molecular experiments, it was found that TRIM29 is capable of phosphorylating Erk/Akt in specific cell type. As a whole, it appears that hUC-MSCs can be an effective therapeutic approach for promoting gastric ulcer healing and may exert therapeutic effects in the form of paracrine and differentiation into gastric cells.

The functional specificity of ERECTA-family receptors in Arabidopsis stomatal development is ensured by molecular chaperones in the endoplasmic reticulum.

Stomata are epidermal pores that control gas exchange between plants and the atmosphere. In Arabidopsis, the ERECTA family (ERECTAf) receptors, including ERECTA, ERECTA-LIKE 1 (ERL1) and ERL2, redundantly play pivotal roles in enforcing the 'one-cell-spacing' rule. Accumulating evidence has demonstrated that the functional specificities of receptors are likely associated with their differential subcellular dynamics. The endoplasmic reticulum (ER)-resident chaperone complex SDF2-ERdj3B-BiP functions in many aspects of plant development. We employed pharmacological treatments combined with cell biological and biochemical approaches to demonstrate that the abundance of ERECTA was reduced in the erdj3b-1 mutant, but the localization and dynamics of ERECTA were not noticeably affected. By contrast, the erdj3b mutation caused the retention of ERL1/ERL2 in the ER. Furthermore, we found that the function of SDF2-ERdj3B-BiP is implicated with the distinct roles of ERECTAf receptors. Our findings establish that the ERECTAf receptor-mediated signaling in stomatal development is ensured by the activities of the ER quality control system, which preferentially maintains the protein abundance of ERECTA and proper subcellular dynamics of ERL1/ERL2, prior to the receptors reaching their destination - the plasma membrane - to execute their functions.

Arabidopsis F-BOX STRESS INDUCED 4 is required to repress excessive divisions in stomatal development.

During the terminal stage of stomatal development, the R2R3-MYB transcription factors FOUR LIPS (FLP/MYB124) and MYB88 limit guard mother cell division by repressing the transcript levels of multiple cell-cycle genes. In Arabidopsis thaliana possessing the weak allele flp-1, an extra guard mother cell division results in two stomata having direct contact. Here, we identified an ethylmethane sulfonate-mutagenized mutant, flp-1 xs01c, which exhibited more severe defects than flp-1 alone, producing giant tumor-like cell clusters. XS01C, encoding F-BOX STRESS-INDUCED 4 (FBS4), is preferentially expressed in epidermal stomatal precursor cells. Overexpressing FBS4 rescued the defective stomatal phenotypes of flp-1 xs01c and flp-1 mutants. The deletion or substitution of a conserved residue (Proline166) within the F-box domain of FBS4 abolished or reduced, respectively, its interaction with Arabidopsis Skp1-Like1 (ASK1), the core subunit of the Skp1/Cullin/F-box E3 ubiquitin ligase complex. Furthermore, the FBS4 protein physically interacted with CYCA2;3 and induced its degradation through the ubiquitin-26S proteasome pathway. Thus, in addition to the known transcriptional pathway, the terminal symmetric division in stomatal development is ensured at the post-translational level, such as through the ubiquitination of target proteins recognized by the stomatal lineage F-box protein FBS4.

Analysis of Staged Features of Gastritis-Cancer Transformation and Identification of Potential Biomarkers in Gastric Cancer.

Purpose: This work aims to elucidate the staged characteristics during gastritis-cancer transformation based on the transcriptome and use bioinformatics to identify potential biomarkers. Patients and Methods: We collected blood samples from healthy controls, patients with non-atrophic gastritis, atrophic gastritis, and gastric cancer, and tissue samples from patients with gastric cancer, respectively. RNA-seq was then performed. Differentially expressed genes, weighted gene co-expression network analysis and functional enrichment analysis were used to illustrate the staged characteristics of gastritis-cancer transformation. Genes with diagnostic potential were further identified in combination with ROC analysis. Additionally, for the gastric cancer stage, the gene expression of the collected tissue transcriptome was validated using the Cancer Genome Atlas and combined with survival analysis to identify potential biomarkers. Results: The 279 overlapping genes among the differentially expressed genes of NAG, AG and CA indicated that the expression characteristics of different stages were different. However, the 2243 overlapping genes of differential genes between adjacent stages indicated a certain consistency in the expression characteristics of stage development. The core functions of different stages have strong stage specificity and basically have no similarities. Twenty genes with diagnostic potential for AG or CA were obtained, respectively, and no gene could effectively differentiate NAG samples. Thirty-four potential biomarkers for gastric cancer were identified, of which 14 genes have not been reported, including ACTG2, C1QTNF2, NCAPH and SORCS1. Conclusion: There may be a stable development mechanism in the process of gastritis-carcinoma transformation, resulting in the differences in the performance of each stage. The newly discovered staging features and potential biomarkers in this work can provide references for related research.

The role of GSTM1 gene polymorphism in pathophysiology, evaluation, and management of constipation of anorectal outlet obstruction.

Constipation of anorectal outlet obstruction may be caused by mechanical or functional causes. This complication is a debilitating disease that needs proper and timely treatment. Many studies have shown that there is a direct link between constipation and intestinal cancer. One of the most effective ways to prevent or diagnose intestinal cancer is through genetic studies. Evaluation of people's polymorphism shows how much they are at risk for cancer. Therefore, in this study, the GSTM1 gene polymorphism was evaluated in patients with constipation of anorectal outlet obstruction to assess better and manage this disease and investigate the possibility of anorectal cancer in these people. In this regard, 40 people with constipation of anorectal outlet obstruction were compared with 40 healthy people. In the case group (patients), in addition to demographic and clinical evaluations, the anorectal manometric test was used to diagnose the pathology of the disease. Results showed that out of 40 patients with constipation of anorectal outlet obstruction, 5 cases (12.5%) had megarectum, 7 cases (17.5%) had anismus, 10 cases (25%) had Hirschsprung's disease, 5 cases (12.5%) had descending perineum syndrome, 6 cases (15%) had rectal prolapse, 4 cases (10%) had enterocele, and 3 cases (7.5%) were with rectocele. Also, the results of GSTM1 gene deletion polymorphism showed that patients with constipation of anorectal outlet obstruction were almost two times more exposed to the null genotype than the control group (P <0.04). Therefore, in people with both constipation of anorectal outlet obstruction and null genotype (i.e., deletion in the GSTM1 gene), because they do not have glutathione-S transferase, they appear to be at higher risk for anorectal cancer than healthy people with the same genotype.

A broadband achromatic metalens array for integral imaging in the visible.

Integral imaging is a promising three-dimensional (3D) imaging technique that captures and reconstructs light field information. Microlens arrays are usually used for the reconstruction process to display 3D scenes to the viewer. However, the inherent chromatic aberration of the microlens array reduces the viewing quality, and thus, broadband achromatic imaging remains a challenge for integral imaging. Here, we realize a silicon nitride metalens array in the visible region that can be used to reconstruct 3D optical scenes in the achromatic integral imaging for white light. The metalens array contains 60 × 60 polarization-insensitive metalenses with nearly diffraction-limited focusing. The nanoposts in each high-efficiency (measured as 47% on average) metalens are delicately designed with zero effective material dispersion and an effective achromatic refractive index distribution from 430 to 780 nm. In addition, such an achromatic metalens array is composed of only a single silicon nitride layer with an ultrathin thickness of 400 nm, making the array suitable for on-chip hybrid-CMOS integration and the parallel manipulation of optoelectronic information. We expect these findings to provide possibilities for full-color and aberration-free integral imaging, and we envision that the proposed approach may be potentially applicable in the fields of high-power microlithography, high-precision wavefront sensors, virtual/augmented reality and 3D imaging.

Xuesaitong May Protect Against Ischemic Stroke by Modulating Microglial Phenotypes and Inhibiting Neuronal Cell Apoptosis via the STAT3 Signaling Pathway.

BACKGROUND: Xuesaitong mainly comprises Panax notoginseng saponins and has shown a promising feature in an acute ischemic stroke model; however, its effect on long-term recovery following stroke, and the related mechanisms, are unknown. METHODS: The objective of this study was to investigate the long-term protective effects of xuesaitong against ischemic stroke and its effect on microglial polarization. Experimental cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 45 min, and C57BL/6 mice were immediately injected with xuesaitong or vehicle through the caudal vein at the onset of cerebral reperfusion consecutively for 14 days. The animals were randomly divided into three groups: a sham-operated group, vehicle-treated group and xuesaitong-treated group at a dose of 15µg/g. Subsequently, 2,3,5-triphenyltetrazolium chloride staining was used to assess infarct volume, and adhesive removal tests and balance beam tests were used to evaluate neurological deficits at days 1, 3, 7 and 14 following ischemia. Reverse-transcriptase polymerase chain reaction and immunofluorescence staining for M1 markers (CD16, iNOS) and M2 markers (CD206, arginase-1) were performed to characterize phenotypic changes in microglia. Elisa was used to determine the release of pro-inflammatory and anti-inflammatory cytokines. TUNEL staining was conducted to detect neuronal cell apoptosis, and western blots were used to determine the activation of signal transducer and activator of transcription 3 (STAT3). RESULTS: Our results revealed that xuesaitong treatment, compared with vehicle treatment, significantly reduced cerebral infarct volume 1 and 3 days after MCAO and resulted in significant improvements in long-term neurological outcomes. Furthermore, xuesaitong treatment, compared with vehicle treatment, significantly reduced M1 markers and elevated M2 markers 7 and 14 days after MCAO at both the mRNA and protein level in ipsilateral brain tissue. This finding was also accompanied by a reduction in neuronal cell apoptosis and p-STAT3 transcription factor levels in the xuesaitong-treated group compared with the vehicle-treated group. CONCLUSION: We demonstrated that xuesaitong has long-term neuroprotective effects against ischemic stroke, possibly by promoting the polarization of microglia to an M2 phenotype and by inhibiting neuronal cell death via down-regulation of the STAT3 signaling pathway, providing new evidence that xuesaitong might be a promising therapeutic strategy for ischemic stroke.

L-3-n-Butylphthalide reduces ischemic stroke injury and increases M2 microglial polarization.

Overwhelming evidence suggests that microglia play an important role in ischemic injury and they polarize into two different phenotypes with distinct functions after ischemic stroke. We performed the present study to investigate whether L-3-n butylphthalide (NBP) has an effect on microglial polarization. Mice were subjected to transient middle cerebral artery occlusion (MCAO) for 45 min, and then immediately after reperfusion were treated with NBP or vehicle via the caudal vein for 7 consecutive days. 2,3,5-Triphenyltetrazolium chloride (TTC) staining showed that NBP treatment resulted in a tendency to decrease cerebral infarct volume at 1 day after MCAO, and significant decreased infarct volume at 3 days after MCAO. Sensorimotor function was evaluated by the adhesive removal test and balance beam test, which were superior in NBP-treated mice compared with vehicle-treated mice at 1 and 3 days after MCAO. Immunofluorescent staining further indicated that NBP treatment significantly increased the number of CD206+/Iba1+ M2 microglia/macrophages and reduced the number of CD16+/Iba1+ M1 cells at 3 and 7 days after MCAO reperfusion. Western blot also showed an elevation of M2 marker (arginase-1) in NBP-treated brains at 7 days after MCAO. In conclusion, our results clearly show that NBP treatment significantly mitigates ischemic brain damage and promotes recovery of neurological function in early phase after ischemic stroke, probably by skewing M1 microglia/macrophages polarization towards M2 phenotype. Thus, our study provides new evidence that NBP might be a promising candidate for ameliorating injury caused by ischemic stroke.

TOPK Promotes Microglia/Macrophage Polarization towards M2 Phenotype via Inhibition of HDAC1 and HDAC2 Activity after Transient Cerebral Ischemia.

T-LAK-cell-originated protein kinase (TOPK) is a newly identified member of the mitogen-activated protein kinase family. Our previous study has showed that TOPK has neuroprotective effects against cerebral ischemia-reperfusion injury. Here, we investigated the involvement of TOPK in microglia/ macrophage M1/M2 polarization and the underlying epigenetic mechanism. The expression profiles, co-localization and in vivo interaction of TOPK, M1/M2 surface markers, and HDAC1/HDAC2 were detected after middle cerebral artery occlusion models (MCAO). We demonstrated that TOPK, the M2 surface markers CD206 and Arg1, p-HDAC1, and p-HDAC2 showed a similar pattern of in vivo expression over time after MCAO. TOPK co-localized with CD206, p-HDAC1, and p-HDAC2 positive cells, and was shown to bind to HDAC1 and HDAC2. In vitro study showed that TOPK overexpression in BV2 cells up-regulated CD206 and Arg1, and promoted the phosphorylation of HDAC1 and HDAC2. In addition, TOPK overexpression also prevented LPS plus IFN-γ-induced M1 transformation through reducing release of inflammatory factor of M1 phenotype TNF-α, IL-6 and IL-1ß, and increasing TGF-ß release and the mRNA levels of TGF-ß and SOCS3, cytokine of M2 phenotype and its regulator. Moreover, the increased TNF-α induced by TOPK siRNA could be reversed by HDAC1/HDAC2 inhibitor, FK228. TOPK overexpression increased M2 marker expression in vivo concomitant with the amelioration of cerebral injury, neurological functions deficits, whereas TOPK silencing had the opposite effects, which were completely reversed by the FK228 and partially by the SAHA. These findings suggest that TOPK positively regulates microglia/macrophage M2 polarization by inhibiting HDAC1/HDAC2 activity, which may contribute to its neuroprotective effects against cerebral ischemia-reperfusion injury.

Diagnostic and Immunosuppressive Potential of Elevated Mir-424 Levels in Circulating Immune Cells of Ischemic Stroke Patients.

Our previous study demonstrated that microRNA-424 (miR-424) protected against experimental stroke through inhibition of microglial proliferation and activation by targeting cell cycle proteins. The purpose of this study was to further explore the clinical significance of miR-424 in peripheral immune cells of patients with acute ischemic stroke (AIS). Blood samples were collected from 40 patients within 6 hours of symptom onset and 27 control subjects. MiR-424 levels in lymphocytes, neutrophils and plasma were determined by quantitative realtime-PCR. The diagnostic sensitivity and specificity of miR-424 for stroke was evaluated by receiver operator characteristic (ROC) curve. The correlation between miR-424 levels and clinical data was analyzed using Pearson's correlation test. Plasma levels of inflammatory mediators (TNF-α, IL-10) and neurotrophic factor (IGF-1) were detected by ELISA. Notably, miR-424 expression levels in lymphocytes and neutrophils increased after stroke, suggestive of its diagnostic value in ischemic stroke. MiR-424 levels in neutrophils were negatively correlated with infarct volume. Lymphocytic miR-424 levels were negatively correlated with the number of lymphocytes and the expression of cyclin-dependent kinase CDK6. Moreover, plasma TNF-α and IGF-1 levels increased and decreased, respectively, in stroke patients, and miR-424 levels in lymphocytes and neutrophils were both inversely correlated with plasma TNF-α, IL-10, or IGF-1 levels. In summary, miR-424 levels in peripheral immune cells has diagnostic potential for ischemic stroke, and might affect the severity of acute stroke by depressing the peripheral inflammatory response through CDK6-dependent pathway in lymphocytes or CDK6-independent pathway neutrophils.

miR-51 regulates GABAergic synapses by targeting Rab GEF GLO-4 and lysosomal trafficking-related GLO/AP-3 pathway in Caenorhabditis elegans.

A deficit of GABA (γ-aminobutyric acid) transmission will lead to epilepsy and other cognitive disorders. Recent evidence has shown that neuronal miRNAs affect various synapses, including GABAergic synapses. However, the miRNAs that control GABAergic synapses remain not fully understood. Here, we identified miR-51, a member of Caenorhabditis elegans miR-99/100 family, as a key regulator of GABAergic synapses. Loss of mir-51 increased PTZ (Pentylenetetrazole) and aldicarb hypersensitivities, and decreased the number of GABAergic synapses and abundance of GABAA receptors. A Rab guaninenucleotide exchange factor (GEF) GLO-4, a well-known component in lysosomal trafficking-related GLO-4/GLO-1/AP-3 (GLO/AP-3) pathway, was discovered to be the direct target of miR-51. Rescue experiments showed that GLO-4 expressed in GABAergic motor neurons functioned as a suppressor of miR-51. Disruption of glo-1 or AP-3 gene apm-3 attenuated the defects of GABAergic synapse in mir-51 mutants, suggesting miR-51 regulated GABAergic synapses through GLO/AP-3 pathway. The present study implies the essential roles of miRNAs on the nervous pathologies characterized by mis-regulated GABA signaling, such as epilepsy.

Long Noncoding RNA H19 Promotes Neuroinflammation in Ischemic Stroke by Driving Histone Deacetylase 1-Dependent M1 Microglial Polarization.

BACKGROUND AND PURPOSE: Long noncoding RNA H19 is repressed after birth, but can be induced by hypoxia. We aim to investigate the impact on and underlying mechanism of H19 induction after ischemic stroke. METHODS: Circulating H19 levels in stroke patients and mice subjected to middle cerebral artery occlusion were assessed using real-time polymerase chain reaction. H19 siRNA and histone deacetylase 1 (HDAC1) plasmid were used to knock down H19 and overexpress HDAC1, respectively. Microglial polarization and ischemic outcomes were assessed in middle cerebral artery occlusion mice and BV2 microglial cells subjected to oxygen-glucose deprivation. RESULTS: Circulating H19 levels were significantly higher in stroke patients compared with healthy controls, indicating high diagnostic sensitivity and specificity. Moreover, plasma H19 levels showed a positive correlation with National Institute of Health Stroke Scale score and tumor necrosis factor-α levels. After middle cerebral artery occlusion in mice, H19 levels increased in plasma, white blood cells, and brain. Intracerebroventricular injection of H19 siRNA reduced infarct volume and brain edema, decreased tumor necrosis factor-α and interleukin-1ß levels in brain tissue and plasma, and increased plasma interleukin-10 concentrations 24 hours poststroke. Additionally, H19 knockdown attenuated brain tissue loss and neurological deficits 14 days poststroke. BV2 cell-based experiments showed that H19 knockdown blocked oxygen-glucose deprivation-driven M1 microglial polarization, decreased production of tumor necrosis factor-α and CD11b, and increased the expression of Arg-1 and CD206. Furthermore, H19 knockdown reversed oxygen-glucose deprivation-induced upregulation of HDAC1 and downregulation of acetyl-histone H3 and acetyl-histone H4. In contrast, HDAC1 overexpression negated the effects of H19 knockdown. CONCLUSIONS: Our findings indicate that H19 promotes neuroinflammation by driving HDAC1-dependent M1 microglial polarization, suggesting a novel H19-based diagnosis and therapy for ischemic stroke.

Erythropoietin attenuates axonal injury after middle cerebral artery occlusion in mice.

OBJECTIVE: Erythropoietin (EPO) confers potent neuroprotection against ischemic injury through a variety of mechanisms. However, the protective effect of EPO on axons after cerebral ischemia in adult mice is rarely covered. The purpose of this study was to investigate the potential neuroprotective effects of EPO on axons in mice after cerebral ischemia. METHODS: A total of 30 adult male C57 BL/6 mice were treated with EPO (5000 IU/kg) or vehicle after transient middle cerebral artery occlusion (MCAO). The mortality rate of each experimental group was calculated. Neurological function was assessed by Rota-rod test. Frozen sections from each mouse brain at 14 days after reperfusion were used to evaluate the fluorescent intensity of myelin basic protein (MBP) and neurofilament 200 (NF-200). Immunofluorescence staining and Western blotting were used to assess the protein level of ß-amyloid precursor protein (ß-APP) and glial fibrillary acidic protein (GFAP), a marker of mature astrocytes. The protein levels of the myelin-derived growth inhibitory proteins, neurite growth inhibitor-A (Nogo-A), myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (OMG) were also examined by Western blot after MCAO. RESULTS: The survival rate of the vehicle group 14 days after cerebral ischemia-reperfusion was 50%, which increased to 80% after EPO treatment at the start of reperfusion. EPO improved neurobehavioral outcomes at days 3 and 7 after MCAO was compared with the vehicle group (P < 0.05). Furthermore, EPO ameliorated demyelination, demonstrated by upregulation of the MBP/NF-200 ratio. Meanwhile, increased levels of ß-APP, GFAP, Nogo-A, and MAG after MCAO were reduced by EPO treatment (P < 0.05). CONCLUSION: EPO treatment attenuates axonal injury and improves neurological function after cerebral ischemia in adult mice.

MicroRNA-99a-5p in circulating immune cells as a potential biomarker for the early diagnosis of ischemic stroke.

OBJECTIVES: We have previously shown the neuroprotective function of microRNA-99a-5p in experimental stroke. Here, we explore its diagnostic potential for acute stroke patients. MATERIALS AND METHODS: MiR-99a-5p levels in circulating from acute stroke patients and control were measured by real-time polymerase chain reaction. Pearson's correlation and receiver operator characteristic (ROC) curves were used to analyze clinical significance of miR-99a-5p and its sensitivity and specificity for stroke diagnosis. RESULTS: We demonstrated that miR-99a-5p expression was upregulated in neutrophils of both ischemic stroke and hemorrhage patients, while was only increased in the lymphocytes of hemorrhage patients. ROC analysis revealed that the miR-99a-5p level in neutrophils and lymphocytes had a moderate diagnostic value for stroke. Moreover, a positive correlation existed between plasma miR-99a-5p levels and neutrophil numbers or neutrophil/lymphocyte ratio. Meanwhile, miR-99a-5p levels in neutrophils were negatively correlated with thrombin time, while positively correlated with D-dimer and urea levels. Lymphocytic miR-99a-5p levels were positively correlated with platelet mean volume and distribution width. CONCLUSION: This study demonstrated that miR-99a-5p levels in circulating immune cells might facilitate the diagnosis of ischemic stroke.

Formation and osteoblast behavior of HA nano-rod/fiber patterned coatings on tantalum in porous and compact forms.

The novel bilayered coatings, comprising hydroxyapatite (HA) nano-rods/fibers as an outer-layer and the CaTa2O6-based matrix as an inner-layer, were fabricated on Ta in porous and compact forms using microarc oxidation and hydrothermal treatment (HT). The formation mechanism and change in the topography of the HA nano-rods/fibers were investigated. Moreover, the evolution of structure and adhesive strength, apatite-inducing ability, and cytocompatibility of the nano-rod/fiber patterned coatings together with Ta were also explored. During HT, the HA nanorods directly nucleated on the CaTa2O6-based matrix and grew in length to nanofibers with HT time. Meanwhile, the orientation of the nano-rods/fibers on the resultant HT3h, HT6h and HT24h coatings also changed, appearing to be quasi-vertical, bent, and parallel to the underlying substrate, respectively, corresponding to the widening of inter-rod/fiber spacing. The coatings adhered firmly to Ta substrates with long-term adhesive strength stability, and exhibited a superior apatite-inducing ability. The survival and proliferation of osteoblasts were significantly enhanced on the quasi-upright HA nanorod patterned HT3h coating, however, greatly inhibited on the paralleled HA nanofiber patterned HT24h coating compared to Ta. The difference may have resulted from the stable cell adhesion on the HT3h coating and enhanced cell apoptosis caused by unstable cell adhesion on the HT24h coating, owing to the narrow interrod spacing for the former and the wide interfiber spacing for the latter.

[Expression of plasma miR-106a in colorectal cancer and its clinical significance].

OBJECTIVE: To detect plasma miR-106a level in patients with colorectal cancer (CRC) and analyze its correlation to the clinicopathological features and disease diagnosis. METHODS: miRNA expression profiling was performed using miRNA microarray chip for 3 colorectal adenocarcinoma samples and matched normal tissues. Plasma samples was collected from 50 colorectal cancer patients for quantitative analysis of miR-106a using real-time RT-PCR using 47 plasma samples from healthy volunteer as the control. Forty plasma samples were collected from these patients 7 days after operation to examine the changes in miR-106a expression. RESULTS: miR-106a was differentially expressed in colorectal adenocarcinoma compared to normal tissues. The plasma levels of miR-106a expression were significantly higher in the cancer patients than in the healthy control group (P=0.012). miR-106a expression significantly decreased after the operation compared with its preoperative level (P<0.01), and no correlation was found between preoperative plasma miR-106a and the clinicopathological features including lymph node metastasis and TNM stage (P>0.05). miR-106a showed a receiver operating characteristic (ROC) curve area of 66.1%, a sensitivity of 62.3%, and a specificity of 68.2% in discriminating colorectal cancer patients from the control subjects. CONCLUSION: plasma miR-106a is up-regulated in CRC patients, suggesting its potential value for the diagnosis of CRC.

Thermal shock resistance of skin tissue.

Understanding the mechanisms of skin behavior under thermal shock is crucial for medical treatments. However, no reasonable criteria are available for the maximum thermal loadings that skin tissue can survive. To address this, in this paper we analyzed thermal and neural behaviors of skin tissue exposed to thermal loadings by introducing the thermal shock resistance (a parameter widely used for engineering materials) of skin for the first time. Skin thermal shock resistance was analyzed according to two distinct criteria: (1) maximum local temperature at epidermis-dermis (ED) interface defined as the thermal threshold of skin thermal pain; (2) maximum thermal damage at ED interface defined as the first degree burn where irreversible skin damage occurs. Numerical simulation was performed and the results show that the thermal shock resistance of skin tissue depends on the Biot number (which characterizes the features of thermal shock). These results indicate that skin thermal shock resistance can be used as an efficient tool to predict thermal damage (e.g., burn) and the corresponding pain level induced by noxious thermal loadings (e.g., clinical thermal treatments).