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[Display omitted] • HEME diminishes BH induced apoptosis in SK-N-SH-MJD78 cells. • HEME decreases mutant ataxin-3 protein aggregation in tBH treated SCA3 cell model. • HEME modulates p53 and NF-κB activation in tBH treated SK-N-SH-MJD78 cells. • HEME increases survival and climbing ability in tBH treated SCA3 Flies. [ABSTRACT FROM AUTHOR]

Bone resorption around implants is quite common, and the maturity and popularization of computer-aided design and computer-aided manufacturing (CAD/CAM) technology have made the use of aftermarket abutment screws more widespread. This study aimed to explore the biomechanical influence of these two common factors on the internal stress of an implant system using three-dimensional finite element analysis (3D FEA). The FEA results indicated that under the same loading conditions, the use of an aftermarket screw had the greatest impact on the screw itself among the three components of the implant system, while the maximum stress increased by 6.3% and 10.5% in the bone integrity and bone loss models, respectively. Moreover, the marginal bone loss models had the greatest impact on the implant fixture, with a maximum stress increase of 51.8% on average. Evidently, the influence of bone loss might be far greater than that of the aftermarket screw; however, any factor could be enough to cause clinical failure. Therefore, we should pay more attention to the maintenance of the long-term peri-implant marginal bone integrity. [ABSTRACT FROM AUTHOR]

Three groups of zirconia abutments (n = 5) consisting of different connection designs or manufacturers were investigated (All-Zr, ASC-Zr, and AM-Zr groups). All-electric dynamic test instruments were used to place static loading on a specimen with a crosshead speed set at 1 mm/min. A Kruskal–Wallis test and a post hoc Mann–Whitney U test were used for statistical evaluation. The mean fracture resistance was 252.37 ± 82.79 N for the All-Zr group, 384.62 ± 45.24 N for ASC-Zr group, and 361.83 ± 90.31 N for the AM-Zr group. The difference of fracture resistance between the three groups was marginally significant (Kruskal–Wallis test, p = 0.054), with the ASC zirconia abutment tending to have higher fracture resistance than the full zirconia abutment. The modes of failure among the three types of abutments are different. The All-Zr group showed an oblique fracture line starting from the buccal aspect at the region of the implant platform. While the ASC-Zr and AM-Zr groups showed a relatively horizontal fracture line with a greater distance from the implant platform. The titanium inserts cannot significantly improve the fracture resistance of the zirconia abutment. However, they may alter the modes of failure, allowing buccal fracture surfaces of the zirconia abutments to be placed away from the implant platform, thereby protecting the implant–abutment connection. [ABSTRACT FROM AUTHOR]

(1) Background: Either pre-operative physical status or unstable hemodynamic changes has been reported to play a potential role in causing vital organ dysfunction. Therefore, we intended to investigate the impact of the American Society of Anesthesiologist (ASA) classification and intraoperative hemodynamic instability on non-surgical complications following orthopedic surgery. (2) Methods: We collected data on 6478 patients, with a mean age of 57.3 ± 16, who underwent orthopedic surgeries between 2018 and 2020. The ASA classification and hemodynamic data were obtained from an anesthesia database. Non-surgical complications were defined as a dysfunction of the vital organs. (3) Results: ASA III/IV caused significantly higher odds ratios (OR) of 17.49 and 40.96, respectively, than ASA I for developing non-surgical complications (p < 0.001). Non-surgical complications were correlated with a 20% reduction in systolic blood pressure (SBP), which was intraoperatively compared to the pre-operative baseline ((OR) = 1.38, p = 0.02). The risk of postoperative complications increased with longer durations of SBP < 100 mmHg, peaking at over 20 min ((OR) = 1.33, p = 0.34). (4) Conclusions: Extended intraoperative hypotension and ASA III/IV caused a significantly higher risk of adverse events occurring within the major organs. The maintenance of hemodynamic stability prevents non-surgical complications after orthopedic surgeries. [ABSTRACT FROM AUTHOR]

Contrast enhancement is a crucial image processing step for image quality control. However, images enhanced by conventional contrast enhancement methods can have negative effects on the performance of image quality control. The most commonly observed effects are over- and under-enhancement effects on images, which cause significant loss of fine textures in images. This paper developed a new contrast enhancement algorithm based on an entropy-preserving mapping prior that improves on conventional contrast enhancement methods. By creating a closed-form solution for enhancing the image contrast under this novel prior and learning the coefficients of the solution using an unsupervised learning strategy, an image’s contrast and texture can be effectively recovered. The experimental results verify that our proposed method clearly outperforms the existing state-of-the-art methods in terms of both quantitative estimation and qualitative human visual inspection. [ABSTRACT FROM AUTHOR]

Moringa oleifera is a promising plant species for oil and forage, but its genetic improvement is limited. Our current breeding program in this species focuses on exploiting the functional genes associated with important agronomical traits. Here, we screened reliable reference genes for accurately quantifying the expression of target genes using the technique of real-time quantitative polymerase chain reaction (RT-qPCR) in M. oleifera. Eighteen candidate reference genes were selected from a transcriptome database, and their expression stabilities were examined in 90 samples collected from the pods in different developmental stages, various tissues, and the roots and leaves under different conditions (low or high temperature, sodium chloride (NaCl)- or polyethyleneglycol (PEG)- simulated water stress). Analyses with geNorm, NormFinder and BestKeeper algorithms revealed that the reliable reference genes differed across sample designs and that ribosomal protein L1 (RPL1) and acyl carrier protein 2 (ACP2) were the most suitable reference genes in all tested samples. The experiment results demonstrated the significance of using the properly validated reference genes and suggested the use of more than one reference gene to achieve reliable expression profiles. In addition, we applied three isotypes of the superoxide dismutase (SOD) gene that are associated with plant adaptation to abiotic stress to confirm the efficacy of the validated reference genes under NaCl and PEG water stresses. Our results provide a valuable reference for future studies on identifying important functional genes from their transcriptional expressions via RT-qPCR technique in M. oleifera. [ABSTRACT FROM AUTHOR]

A new periplogenin cardenolide, periplogulcoside (1), together with three known cardenolides, was isolated from the seeds ofAntiaris toxicaria. The structure of the new compound was characterized as periplogenin-3-O-β-d-glucopyranosyl-(1 → 4)-β-d-glucopyranoside (1) by spectroscopic methods including 1D and 2D NMR, HR-TOF-MS, and CD spectrometry, and the known compounds were identified by comparison of their NMR and HR-TOF-MS data with those reported in the literature. Compound1showed significant cytotoxicity against Hela and HepG-2 cell lines. [ABSTRACT FROM PUBLISHER]

Heat shock proteins (HSPs), which function as chaperones, are activated in response to various environmental stressors. In addition to their role in diverse aspects of protein production, HSPs protect against harmful protein-related stressors. Calycosin exhibits numerous beneficial properties. This study aims to explore the protective effects of calycosin in the heart under heat shock and determine its underlying mechanism. H9c2 cells, western blot, TUNEL staining, flow cytometry, and immunofluorescence staining were used. The time-dependent effects of heat shock analyzed using western blot revealed increased HSP expression for up to 2h, followed by protein degradation after 4h. Hence, a heat shock damage duration of 4h was chosen for subsequent investigations. Calycosin administered post-heat shock demonstrated dose-dependent recovery of cell viability. Under heat shock conditions, calycosin prevented the apoptosis of H9c2 cells by upregulating HSPs, suppressing p-JNK, enhancing Bcl-2 activation, and inhibiting cleaved caspase 3. Calycosin also inhibited Fas/FasL expression and activated cell survival markers (p-PI3K, p-ERK, p-Akt), indicating their cytoprotective properties through PI3K/Akt activation and JNK inhibition. TUNEL staining and flow cytometry confirmed that calycosin reduced apoptosis. Moreover, calycosin reversed the inhibitory effects of quercetin on HSF1 and Hsp70 expression, illustrating its role in enhancing Hsp70 expression through HSF1 activation during heat shock. Immunofluorescence staining demonstrated HSF1 translocation to the nucleus following calycosin treatment, emphasizing its cytoprotective effects. In conclusion, calycosin exhibits pronounced protective effects against heat shock-induced damages by modulating HSP expression and regulating key signaling pathways to promote cell survival in H9c2 cells. [ABSTRACT FROM AUTHOR]

We developed and tested a parallel plate shear cell that can be mounted on top of an inverted microscope to perform confocal real-space measurements on complex fluids under shear. To follow structural changes in time, a plane of zero velocity is created by letting the plates move in opposite directions. The location of this plane is varied by changing the relative velocities of the plates. The gap width is variable between 20 and 200 μm with parallelism better than 1 μm. Such a small gap width enables us to examine the total sample thickness using high numerical aperture objective lenses. The achieved shear rates cover the range of 0.02–103 s-1. This shear cell can apply an oscillatory shear with adjustable amplitude and frequency. The maximum travel of each plate equals 1 cm, so that strains up to 500 can be applied. For most complex fluids, an oscillatory shear with such a large amplitude can be regarded as a continuous shear. We measured the flow profile of a suspension of silica colloids in this shear cell. It was linear except for a small deviation caused by sedimentation. To demonstrate the excellent performance and capabilities of this new setup we examined shear induced crystallization and melting of concentrated suspensions of 1 μm diameter silica colloids. [ABSTRACT FROM AUTHOR]

Abstract: Propolis, which has been used widely in folk medicine, has been shown to exhibit various biological activities but its immunoregulatory and anti-inflammatory activities in intact animals have not been well studied. We investigated these activities of propolis using an ovalbumin-induced asthma animal model. Mice were immunized and sensitized by exposure to ovalbumin (OVA) antigen and administered with low- (65mg/kg body weight) and high-dose (325mg/kg body weight) propolis water extracts by tube feeding. The serum OVA-specific IgE titer and cytokine profiles in cultured splenocytes and bronchoalveolar lavage fluids (BALF) were analyzed. The number of eosinophils in BALF was counted. Here we demonstrate that propolis extracts can suppress the serum levels of OVA-specific IgE and IgG1, and airway hyperresponsiveness (AHR) in OVA-sensitized mice. There are no significant differences in the concentration of eotaxin or the number of eosinophils in BALF among the four groups. However, the higher dose of propolis extracts decreases the level of IL-5 in BALF. The splenocytes from mice administered with propolis extracts (low- and high-dose groups) exhibit a strong inhibition of IL-10 secretion and up-regulation of IFN-γ secretion in splenocytes stimulated with concanavalin A (ConA). In addition, cytokine (IFN-γ, IL-6, and IL-10) secretion in OVA-stimulated splenocytes from the propolis groups was significantly lower than that in the control group. These results suggest that propolis extracts may be a potential novel therapeutic agent for asthma. [Copyright &y& Elsevier]

Peri-implantitis is a common implant-supported prosthesis complication, and marginal bone loss affects the stress distribution in implant systems. This three-dimensional finite element analysis study investigated how bone loss affects the implant assembly; in particular, models including two implant systems with different connection systems (external or internal hexagon), abutment materials (titanium or zirconia), and bone loss levels (0, 1.5, 3, or 5 mm) were created. We observed that the maximum von Mises stress distinctly increased in the groups with bone loss over 1.5 mm compared to the group without bone loss, regardless of the connection system or abutment material used. Moreover, the screw stress patterns with bone loss progression were determined more by the connection systems than by the abutment materials, and the magnitude of the stress on the fixture was affected by the connection systems with a similar pattern. The highest stress on the screw with the external hexagon connection system increased over 25% when bone loss increased from 3 to 5 mm, exceeding the yield strength of the titanium alloy (Ti–6Al–4V) when 5 mm bone loss exists; clinically, this situation may result in screw loosening or fracture. The highest stress on the fixture, exceeding the yield strength of pure titanium, was noted with the internal hexagon connection system and 1.5 mm bone loss. Titanium and zirconia abutments—both of which are clinically durable—presented similar screw and fixture stress patterns. Therefore, clinicians should pay more attention to maintaining the peri-implant bone to achieve the long-term stability of the implant-supported prosthesis. [ABSTRACT FROM AUTHOR]

The p53 protein activates promoters containing p53 binding sites, and it represses other promoters. We examined the effect of p53 on bcl-2 expression in both the DHL-4 B cell line and the K562 erythroleukemia line. Transient transfection analyses revealed that wild-type p53 repressed the bcl-2 full-length promoter. The region of the bcl-2 promoter that was responsive to p53 was mapped to the bcl-2 P2 minimal promoter region, and we showed that p53 and the TATA binding protein bound to the bcl-2 TATA sequence. The TATA binding protein, p53, histone deacetylase-1 and mSin3a could be co-immunoprecipitated from K562 cell nuclear extract. The TATA binding protein and mSin3a could be recovered in a complex at the bcl-2 promoter TATA sequence, however, the formation of this complex was not dependent on the presence of p53. Treatment of K562 cells with the histone deacetylase inhibitor, trichostatin A, resulted in an increase in bcl-2 promoter activity whether p53 was present or not. Therefore, we demonstrated that p53 and the histone deacetylases repress the bcl-2 promoter independently. Similar results were obtained when endogenous bcl-2 mRNA or protein levels were measured in response to either p53 or trichostatin A, and p53 expression resulted in enhanced apoptosis. RNase protection assays demonstrated that transcription from the endogenous 3′ bcl-2 promoter was decreased by p53. The regions of p53 that were required for repression of the bcl-2 promoter were defined. We conclude that the TATA sequence in the bcl-2 P2 minimal promoter is the target for repression by p53, and that the interaction between p53 and TBP is most likely responsible for the repression. Mutation of p53 may play a role in the up-regulation of bcl-2 expression in some B cell lymphomas. Oncogene (2001) 20, 240–251. [ABSTRACT FROM AUTHOR]

The signal transduction pathway through which tumour necrosis factor (TNF) induces apoptosis in leukaemic cells may involve activation of cytosolic phospholipase A2 (cPLA2). The steroids dexamethasone (Dex) and 1,25(OH)2 D3 both render U937 leukaemic cells resistant to TNF-induced apoptosis. In this study, we found that Dex inhibited both spontaneous and TNF-induced activation of cPLA2. Dex had no direct effect on cellular cPLA2 levels, but facilitated cPLA2 degradation upon subsequent stimulation of cells with TNF. In addition, Dex increased synthesis of the endogenous cPLA2 inhibitor lipocortin 1 (LC1). An antisense oligonucleotide to LC1 could completely abrogate Dex-induced resistance to the cytotoxic action of TNF. Constitutive LC1 levels were relatively higher in myeloid leukaemic blasts showing resistance to TNF than TNF-sensitive myeloid leukaemic cell lines. Our data suggest that Dex confers the resistance of U937 cells to TNF-induced apoptosis by upregulating intracellular levels of LC1 and by facilitating a negative-feedback loop, which is activated upon stimulation with TNF. High constitutive levels of LC1 in leukaemic blasts may protect them against immune-mediated killing. [ABSTRACT FROM AUTHOR]

Triplex DNA nanostructures are one of the most emerging and fascinating self-assembled nanostructures due to their unique nanoparticle-like organization and inherit characteristics. They have attracted numerous interests recently because of their versatile and powerful utility in diverse areas of science and technology, such as clinical or disease diagnosis and stimuli-based drug delivery. This review addresses particularly the utilization of DNA triplexes in the development of biosensors for detecting nucleic acid; strategies in sensing pH, protein activity, ions, or molecules. Finally, an outlook for potential applications of triplex DNA nanoswitches is provided. [ABSTRACT FROM AUTHOR]

Residual alveolar ridge resorption often occurs after tooth extraction, which causes issues requiring further prothesis rehabilitation. A treatment concept referred to as all-on-four, involving fixed dentures supported with four implants, was recently developed. The current study aimed to determine the effect of changing bone atrophy and implant length in all-on-four treatments on stress and strain in the surrounding bone of the implant. A three-dimensional finite element method was used in this research. The stress analysis was conducted with von Mises stress values. Two types of synthetic jawbone models with mild and moderate atrophy were used. Furthermore, two different implant lengths with a similar implant design and diameter were selected, and they were classified into eight models. Then, the bone model was assessed via a computed tomography (CT) scan and was transformed into a virtual model in Geomagic and SolidWorks with implant rebuilding. After modifying bone atrophy, the von Mises stresses in the surrounding bone of the implant were as follows: mild type 2 < mild type 3 < moderate type 3 < moderate type 4. The bone quantity change rate increased more than when bone conditions were limited. Compared with changes in implant lengths, the stresses in the peri-implant surrounding bone were generally higher in the 9 mm implant length group than in the 11.5 mm group. However, the results did not significantly differ. In conclusion, the von Mises stress and strain increased in the models with moderate atrophy and low-density trabecular bone. Hence, bone atrophy and its presurgical diagnosis in long-term implant prognosis are crucial. [ABSTRACT FROM AUTHOR]

The use of aftermarket computer-aided design/computer-assisted manufacturing (CAD/CAM) prosthesis components in dental implants has become popular. This study aimed to (1) compare the accuracy of aftermarket CAD/CAM screws with that of original equipment manufacturer (OEM) abutment screws and (2) examine the biomechanical effects of different abutment screws used with zirconia abutment in an implant fixture by using three-dimensional finite element analysis (FEA). Significantly different measurements were obtained for the aftermarket CAD/CAM and OEM screws. The FEA results indicated that under the same loading condition, the maximum stress of the aftermarket CAD/CAM screws was 15.9% higher than that of the OEM screws. Moreover, the maximum stress position occurred in a wide section of the OEM screws but in the narrowest section of the aftermarket screws. The stress of the OEM zirconia abutment was 14.9% higher when using the aftermarket screws than when using the OEM screws. The effect of the manufacturing differences between aftermarket and OEM screws on the clinical effect of aftermarket screws is unpredictable. Therefore, aftermarket screws should be cautiously used clinically. [ABSTRACT FROM AUTHOR]

Background: CD24+CK19+/CD24+SOX9+ resident liver cells are activated and expanded after chronic liver injury in a ductular reaction. However, the sources and functions of these cells in liver damage remain disputed. Results: The current study combined genetic lineage tracing with in vitro small-molecule-based reprogramming to define liver progenitor cells (LPCs) derived from hepatic parenchymal and non-parenchymal tissues. tdTom+ hepatocytes were isolated from ROSA26tdTomato mice following AAV8-Tbg-Cre-mediated recombination, EpCAM+ biliary epithelial cells (BECs) from wild-type intrahepatic bile ducts and ALB/GFP−EpCAM− cells were isolated from AlbCreERT/R26GFP mice. A cocktail of small molecules was used to convert the isolated cells into LPCs. These in vitro cultured LPCs with CD24 and SOX9 expression regained the ability to proliferate. Transcriptional profiling showed that the in-vitro cultured LPCs derived from the resident LPCs in non-parenchymal tissues expressed Lipocalin-2 (Lcn2) at high levels. Accordingly, endogenous Cd24a+Lcn2+ LPCs were identified by integration of sc-RNA-sequencing and pathological datasets of liver dysfunction which indicates that LPCs produced by ductular reactions might also originate from the resident LPCs. Transplantation of in-vitro cultured Cd24a+Lcn2+ LPCs into CCl4-induced fibrotic livers exacerbated liver damage and dysfunction, possibly due to LCN2-dependent macrophage inflammatory response. Conclusions: CD24+LCN2+ LPCs constituted the expanding ductular reaction and contributed to macrophage-mediated inflammation in chronic liver damage. The current findings highlight the roles of LPCs from distinct origins and expose the possibility of targeting LPCs in the treatment of chronic hepatic diseases. [ABSTRACT FROM AUTHOR]

Remifentanil is a potent, short-acting opioid analgesic drug that can protect tissues from ischemia and reperfusion injury though anti-inflammatory effects. However, the utility of remifentanil in liver regeneration after hepatectomy is not known. Using a 70% hepatectomy mouse model (PHx), we found that preconditioning animals with 4 μg/kg remifentanil enhanced liver regeneration through supporting hepatocyte proliferation but not through anti-inflammatory effects. These effects were also phenocopied in vitro where 40 mM remifentanil promoted the proliferation of primary mouse hepatocyte cultures. We further identified that remifentanil treatment increased the expression of β-arrestin 2 in vivo and in vitro. Demonstrating specificity, remifentanil preconditioning failed to promote liver regeneration in liver-specific β-arrestin 2 knockout (CKO) mice subjected to PHx. While remifentanil increased the expression of activated (phosphorylated)-ERK and cyclin D1 in PHx livers, their levels were not significantly changed in remifentanil-treated CKO mice nor in WT mice pretreated with the ERK inhibitor U0126. Our findings suggest that remifentanil promotes liver regeneration via upregulation of a β-arrestin 2/ERK/cyclin D1 axis, with implications for improving regeneration process after hepatectomy. [ABSTRACT FROM AUTHOR]

The feasibility of delivering mitochondria intranasally so as to bypass the blood–brain barrier in treating Parkinson's disease (PD), was evaluated in unilaterally 6-OHDA-lesioned rats. Intranasal infusion of allogeneic mitochondria conjugated with Pep-1 (P-Mito) or unconjugated (Mito) was performed once a week on the ipsilateral sides of lesioned brains for three months. A significant improvement of rotational and locomotor behaviors in PD rats was observed in both mitochondrial groups, compared to sham or Pep-1-only groups. Dopaminergic (DA) neuron survival and recovery > 60% occurred in lesions of the substantia nigra (SN) and striatum in Mito and P-Mito rats. The treatment effect was stronger in the P-Mito group than the Mito group, but the difference was insignificant. This recovery was associated with restoration of mitochondrial function and attenuation of oxidative damage in lesioned SN. Notably, P-Mito suppressed plasma levels of inflammatory cytokines. Mitochondria penetrated the accessory olfactory bulb and doublecortin-positive neurons of the rostral migratory stream (RMS) on the ipsilateral sides of lesions and were expressed in striatal, but not SN DA neurons, of both cerebral hemispheres, evidently via commissural fibers. This study shows promise for intranasal delivery of mitochondria, confirming mitochondrial internalization and migration via RMS neurons in the olfactory bulb for PD therapy. [ABSTRACT FROM AUTHOR]

Sepsis increases the risk of the liver injury development. According to the research works, coenzyme Q10 exhibits hepatoprotective properties in vivo as well as in vitro. Current work aimed at investigating the protective impacts of coenzyme Q10 against liver injury in septic BALB/c mice. The male BALB/c mice were randomly segregated into 4 groups: the control group, the coenzyme Q10 treatment group, the puncture and cecal ligation group, and the coenzyme Q10+cecal ligation and puncture group. Cecal ligation and puncture was conducted after gavagaging the mice with coenzyme Q10 during two weeks. Following 48 h postcecal ligation and puncture, we estimated hepatic biochemical parameters and histopathological changes in hepatic tissue. We evaluated the expression of factors associated with autophagy, pyroptosis, and inflammation. Findings indicated that coenzyme Q10 decreased the plasma levels in alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase in the cecal ligation and puncture group. Coenzyme Q10 significantly inhibited the elevation of sequestosome-1, interleukin-1β, oligomerization domain-like receptor 3 and nucleotide-binding, interleukin-6, and tumor necrosis factor-α expression levels; coenzyme Q10 also increased beclin 1 levels. Coenzyme Q10 might be a significant agent in the treatment of liver injury induced by sepsis. [ABSTRACT FROM AUTHOR]

Rhynchophylline (RIN) is a significant active component isolated from the Chinese herbal medicine Uncaria rhynchophylla. The overproduction of soluble amyloid β protein (Aβ) oligomers in the hippocampus is closely involved in impairments in cognitive function at the early stage of Alzheimer's disease (AD). Growing evidences show that RIN possesses neuroprotective effects against Aβ-induced neurotoxicity. However, whether RIN can prevent soluble Aβ 1-42 -induced impairments in spatial cognitive function and synaptic plasticity is still unclear. Using the combined methods of behavioral tests, immunofluorescence and electrophysiological recordings, we characterized the key neuroprotective properties of RIN and its possible cellular and molecular mechanisms against soluble Aβ 1-42 -related impairments in rats. Our findings are as follows: (1) RIN efficiently rescued the soluble Aβ 1-42 -induced spatial learning and memory deficits in the Morris water maze test and prevented soluble Aβ 1-42 -induced suppression in long term potentiation (LTP) in the entorhinal cortex (EC)-dentate gyrus (DG) circuit. (2) Excessive activation of extrasynaptic GluN2B-NMDAR and subsequent Ca 2+ overload contributed to the soluble Aβ 1-42 -induced impairments in spatial cognitive function and synaptic plasticity. (3) RIN prevented Aβ 1-42 -induced excessive activation of extrasynaptic NMDARs by reducing extrasynaptic NMDARs -mediated excitatory postsynaptic currents and down regulating GluN2B-NMDAR expression in the DG region, which inhibited Aβ 1-42 -induced Ca 2+ overload mediated by extrasynanptic NMDARs. The results suggest that RIN could be an effective therapeutic candidate for cognitive impairment in AD. [ABSTRACT FROM AUTHOR]

Background: Metastasis to long distance organs is the main reason leading to morality of tongue squamous cell carcinoma (TSCC); however, the molecular mechanisms are still unknown. High mobility group AT-hook 2 (HMGA2) is highly expressed in multiple metastatic carcinomas, in which it contributes to cancer progression, metastasis and poor prognosis by upregulating Snail expression and inducing epithelial mesenchymal transition (EMT). This study focuses on investigating the role and mechanism of regulation of HMGA2 in the metastasis of TSCC. Methods: HMGA2 mRNA and protein expression were examined in TSCC specimens by quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry (IHC). Western blotting, IHC and immunofluorescence were also used to measure the expression and localization of EMT marker E-Cadherin and Vimentin both in TSCC cells and tissues. Knockdown assay was performed in vitro in TSCC cell lines using small interfering RNAs and the functional assay was carried out to determine the role of HMGA2 in TSCC cell migration and invasion. Results: TSCC mRNA and protein expression were significantly up-regulated in tumor tissues when compared to adjacent non-tumor tissues, and the overexpression of HMGA2 was closely correlated with lymph nodes metastasis. Clinicopathological analysis indicated that HMGA2 expression was associated with clinical stage (P = 0.001), lymph node metastasis (P = 0.000), histological differentiation (P = 0.002) and survival (P = 0.000). Silencing the HMGA2 expression in Cal27 and UM1 resulted in the inhibition of cell migration and invasion, meanwhile down-regulation of HMGA2 impaired the phenotype of EMT in TSCC cell lines and tissues. The Multivariate survival analysis indicates that HMGA2 can be an independent prognosis biomarker in TSCC. Conclusion: Our findings demonstrate that HMGA2 promotes TSCC invasion and metastasis; additionally, HMGA2 is an independent prognostic factor which implied that HMGA2 can be a biomarker both for prognosis and therapeutic target of TSCC. [ABSTRACT FROM AUTHOR]

Highlights: [•] To investigate I. suffruticosa extracts on expression of GSTP and NQO1 in hepatocytes. [•] Suffruticosa extracts increased GSTP and NQO1 levels and GSTP promoter activity in hepatocyte. [•] Suffruticosa extracts up-regulated binding affinity of Nrf2 with GPEI and ARE activation. [•] ERK inhibitor abolished I. suffruticosa extracts induced GSTP and NQO-1 expression. [•] Suffruticosa extracts increased GSH levels in mouse liver, RBC and hepatocytes. [ABSTRACT FROM AUTHOR]

Background: Post-operative anxiety is common and may have significant impact on the post-operative recovery of the patients. Theatre nurse visits before surgery has been shown to reduce patient's anxiety levels following general surgery. Aim: To investigate the effect of pre-operative visits and counselling by intensive care unit (ICU) nurses on patient's anxiety levels following carotid endarterectomy. Methods: This is an open-label and randomized clinical trial. Patients undergoing carotid endarterectomy were divided into study (n =60) and control group (n =60). For the study group, in addition to routine pre-operational counselling by the surgeons, ICU nurses visited the patients and provided a structured counselling the day before surgery. For the control group, only routine pre-operative counselling was provided. Anxiety levels were assessed by Zung self-rating anxiety scale (SAS) the day before surgery and on the day after being discharged from ICU to the ward. Results: The two groups were comparable in age, sex, surgical methods, and duration of ICU stays. Following the surgery, the mean SAS score in the control group increased from 50.5±5.4 to 58.5±7.3 (p =0.03), whereas the mean SAS score in the study group reduced from 51.5±4.3 to 45.1±6.5 (p =0.02). The proportion of patients with anxiety symptoms in the control group was higher than in the study group following the surgery (58.3% vs. 33.3%, p =0.001). Conclusions: Pre-operative visits and counselling by ICU nurses could reduce patient's anxiety levels following carotid endarterectomy. [ABSTRACT FROM AUTHOR]

Summary: N-α-acetyltransferase 10 protein, Naa10p, is an N-acetyltransferase known to be involved in cell cycle control. We found that Naa10p was expressed lower in varieties of malignancies with lymph node metastasis compared with non-lymph node metastasis. Higher Naa10p expression correlates the survival of lung cancer patients. Naa10p significantly suppressed migration, tumor growth, and metastasis independent of its enzymatic activity. Instead, Naa10p binds to the GIT-binding domain of PIX, thereby preventing the formation of the GIT-PIX-Paxillin complex, resulting in reduced intrinsic Cdc42/Rac1 activity and decreased cell migration. Forced expression of PIX in Naa10-transfected tumor cells restored the migration and metastasis ability. We suggest that Naa10p functions as a tumor metastasis suppressor by disrupting the migratory complex, PIX-GIT- Paxillin, in cancer cells. [Copyright &y& Elsevier]