Establishment of Patient-Derived Xenograft Mouse Model with Human Osteosarcoma Tissues.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Despite the development of new treatment plans in recent years, the prognosis for osteosarcoma patients has not significantly improved. Therefore, it is crucial to establish a robust preclinical model with high fidelity. The patient-derived xenograft (PDX) model faithfully preserves the genetic, epigenetic, and heterogeneous characteristics of human malignancies for each patient. Consequently, PDX models are considered authentic in vivo models for studying various cancers in transformation studies. This article presents a comprehensive protocol for creating and maintaining a PDX mouse model that accurately mirrors the morphological features of human osteosarcoma. This involves the immediate transplantation of freshly resected human osteosarcoma tissue into immunocompromised mice, followed by successive passaging. The described model serves as a platform for studying the growth, drug resistance, relapse, and metastasis of osteosarcoma. Additionally, it aids in screening the target therapeutics and establishing personalized treatment schemes.

Pathological progression of osteoarthritis: a perspective on subchondral bone.

Osteoarthritis (OA) is a degenerative bone disease associated with aging. The rising global aging population has led to a surge in OA cases, thereby imposing a significant socioeconomic burden. Researchers have been keenly investigating the mechanisms underlying OA. Previous studies have suggested that the disease starts with synovial inflammation and hyperplasia, advancing toward cartilage degradation. Ultimately, subchondral-bone collapse, sclerosis, and osteophyte formation occur. This progression is deemed as "top to bottom." However, recent research is challenging this perspective by indicating that initial changes occur in subchondral bone, precipitating cartilage breakdown. In this review, we elucidate the epidemiology of OA and present an in-depth overview of the subchondral bone's physiological state, functions, and the varied pathological shifts during OA progression. We also introduce the role of multifunctional signal pathways (including osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL)/receptor activator of nuclear factor-kappa B (RANK), and chemokine (CXC motif) ligand 12 (CXCL12)/CXC motif chemokine receptor 4 (CXCR4)) in the pathology of subchondral bone and their role in the "bottom-up" progression of OA. Using vivid pattern maps and clinical images, this review highlights the crucial role of subchondral bone in driving OA progression, illuminating its interplay with the condition.

Clinical Efficacy of Small Needle Knife Therapy on Stage I-II Frozen Shoulder.

Frozen shoulder is a kind of aseptic inflammatory disease of the shoulder caused by strain, trauma, and other reasons, resulting in shoulder joint pain and limited function. The protocol presented here demonstrates the operation of a small needle knife in treating frozen shoulders, including patient management, material preparation, positioning, operation, and postoperative care. The purpose of this protocol is to relieve the pain and functional limitations and improve the living ability of patients with frozen shoulders. In our study, 76 stage I-II frozen shoulder patients who met the inclusion criteria were randomly divided into a control group and a treatment group (n=38). Patients in the control group received functional exercise, while the treatment group received small needle knife therapy with functional exercise. The visual analogue scores (VAS), the Constant and Murley scores (CMS), and the thickness of the coracohumeral ligament (CHL) under ultrasound were evaluated. After small needle knife therapy, the VAS score was significantly lower in the treatment group (5.11 ± 0.89) than in the control group (5.49 ± 0.65; t=-2.065, p<0.05); the CMS score was significantly higher in the treatment group (64.72 ± 4.78) than in the control group (60.97 ± 6.00; t=2.947, p<0.05); the CHL thickness was significantly decreased in the treatment group (2.38 ± 0.36) than in the control group (2.57 ± 0.42; t=-2.117, p<0.05). These results indicate that the small needle knife significantly relieved the pain symptoms, improved the shoulder function, reduced the CHL thickness, and improved the quality of life and, therefore, had significant therapeutic efficacy in stage I-II frozen shoulder patients.

Left Ventricle Segmentation in Echocardiography with Transformer.

Left ventricular ejection fraction (LVEF) plays as an essential role in the assessment of cardiac function, providing quantitative data support for the medical diagnosis of heart disease. Robust evaluation of the ejection fraction relies on accurate left ventricular (LV) segmentation of echocardiograms. Because human bias and expensive labor cost exist in manual echocardiographic analysis, computer algorithms of deep-learning have been developed to help human experts in segmentation tasks. Most of the previous work is based on the convolutional neural networks (CNN) structure and has achieved good results. However, the region occupied by the left ventricle is large for echocardiography. Therefore, the limited receptive field of CNN leaves much room for improvement in the effectiveness of LV segmentation. In recent years, Vision Transformer models have demonstrated their effectiveness and universality in traditional semantic segmentation tasks. Inspired by this, we propose two models that use two different pure Transformers as the basic framework for LV segmentation in echocardiography: one combines Swin Transformer and K-Net, and the other uses Segformer. We evaluate these two models on the EchoNet-Dynamic dataset of LV segmentation and compare the quantitative metrics with other models for LV segmentation. The experimental results show that the mean Dice similarity of the two models scores are 92.92% and 92.79%, respectively, which outperform most of the previous mainstream CNN models. In addition, we found that for some samples that were not easily segmented, whereas both our models successfully recognized the valve region and separated left ventricle and left atrium, the CNN model segmented them together as a single part. Therefore, it becomes possible for us to obtain accurate segmentation results through simple post-processing, by filtering out the parts with the largest circumference or pixel square. These promising results prove the effectiveness of the two models and reveal the potential of Transformer structure in echocardiographic segmentation.

Effects of resistance and balance exercises for athletic ability and quality of life in people with osteoporotic vertebral fracture: Systematic review and meta-analysis of randomized control trials.

Purpose: This study aimed to use meta-analysis to determine the impact of resistance and balance training on athletic ability and quality of life for patients with osteoporotic vertebral fracture (OVF). Methods: This study followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) criteria for systematic reviews and meta-analyzes. The PubMed, Web of science, Cochrane, Embase, and CNKI databases were searched for randomized controlled trials (RCTs) up to September 2022. The search strategy was related to the intervention measures, population, and results, and was structured around the search terms: "Exercise," "Osteoporotic vertebral fracture," and "activities of function." Two reviewers strictly implemented the inclusion and exclusion criteria. Subgroup analyzes of age and training duration were performed for the main outcomes. Results: We included 12 RCTs (n = 1,289) of resistance and balance training in patients with OVF. Compared with controls, the intervention group showed improvements on the Quality of Life Questionnaire issued by the European Foundation for Osteoporosis, visual analog pain scale, Timed Up and Go, falls efficacy scale international (FES-I), kyphosis, and functional reach. On subgroup analysis, the effect was more significant when training continued >10 weeks. Conclusion: Resistance and balance exercise training improved function and balance, and reduced fall risk in patients with OVF. We recommend resistance and balance training for at least 10 weeks. Future multicenter, large sample trials are needed for more reliable conclusions.

Connexin 37 Regulates the Kv1.3 Pathway and Promotes the Development of Atherosclerosis.

Objective: To investigate the mechanism of Connexin 37 (Cx37) and Kv1.3 pathways in atherosclerosis (AS). Methods: ApoE-/- mice were given a high-fat diet to establish atherosclerosis (AS) model, and macrophages in mice were isolated and extracted to transfect Cx37 vectors with silencing or overexpressing, and Kv1.3 pathway blockers were used to inhibit the pathway activity. The indexes of body weight, blood glucose, and blood lipid of mice were collected. The protein and mRNA expression levels of Cx37 and Kv1.3 were detected by reverse transcription-PCR (RT-PCR), Western blot, and immunofluorescence technique. Oil red O staining was used to observe plaque area. Masson staining was used to detect collagen content. The concentrations of chemokine CCL7 were quantified using the ELISA kits. CCK8 was used to detect cell proliferation. Results: Cx37 and Kv1.3 were highly expressed in macrophages of AS mice, and the expression of Kv1.3 and CCL7 decreased after Cx37 was silenced, and the proliferation of macrophages was also decreased. Wild-type mice and AS model mice were treated with Cx37 overexpression vectors and Kv1.3 pathway blocking, and it was found that Cx37 overexpression could improve the blood lipid and blood glucose levels and increase the area of AS in AS mice. However, blocking the activity of Kv1.3 pathway can reduce the levels of blood lipid and blood glucose, increase the body weight of mice, and reduce the area of AS mice. Blocking the activity of Kv1.3 pathway can slow down the plaque development of AS mice and make its indexes close to wild-type mice. And the use of Kv1.3 pathway blockers on the basis of overexpression of Cx37 indicated that inhibition of Kv1.3 pathway activity did not affect the expression of Cx37, but could inhibit the collagen content in the plaque area of AS mice, inhibit the expression of chemokine CCL7, and reverse the effect of Cx37 overexpression. Conclusion: Cx37 can improve the activity of macrophages by regulating the expression of chemokines and the activity of Kv1.3 pathway in AS mice, and enrich macrophages in inflammatory tissues and expand the area of plaque formation.

MicroRNA-384-5p protects against cardiac hypertrophy via the ALPK3 signaling pathway.

Heart failure is a condition caused by a variety of pathophysiological factors. One important pathological change of chronic heart failure is myocardial hypertrophy. In recent years, several studies have found that dysregulated microRNAs are involved in regulating the pathological process of heart failure. In this study, cardiac hypertrophy models were constructed using isoproterenol (ISO)-/angiotensin-II (Ang-II) to explore the role of miR-384-5p in cardiac hypertrophy and its molecular mechanism in vivo and in vitro. Echocardiography, invasive pressure-volume analysis and hematoxylin-eosin staining were used to explore cardiac structure and function. ALPK3 mRNA and protein expression were detected using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot analysis and miR-384-5p expression were assessed via RT-qPCR. Our findings determined that miR-384-5p was notably decreased in cardiac hypertrophic tissues and cells, and overexpression of miR-384-5p could ameliorate pressure overload. Furthermore, ALPK3 was determined to downregulate the ALPK3 expression to aggravate cardiomyocyte hypertrophy. Our findings provided a potential therapeutic target for the treatment of cardiac hypertrophy.

A novel approach of fabricating monodispersed spherical MoSiBTiC particles for additive manufacturing.

It is very challenging to fabricate spherical refractory material powders for additive manufacturing (AM) because of their high melting points and complex compositions. In this study, a novel technique, freeze-dry pulsated orifice ejection method (FD-POEM), was developed to fabricate spherical MoSiBTiC particles without a melting process. Elemental nanopowders were dispersed in water to prepare a high-concentration slurry, which was subsequently extruded from an orifice by diaphragm vibration and frozen instantly in liquid nitrogen. After a freeze-drying process, spherical composite particles with arbitrary composition ratios were obtained. The FD-POEM particles had a narrow size range and uniform elemental distribution. Mesh structures were formed within the FD-POEM particles, which was attributed to the sublimation of ice crystals. Furthermore, owing to their spherical morphology, the FD-POEM particles had a low avalanche angle of 42.6°, exhibiting good flowability. Consequently, the combination of FD-POEM and additive manufacturing has great potential for developing complex refractory components used in industrial applications.

Structural transformations of growing thin colloidal crystals in confined space via convective assembly.

The structural evolution of growing thin colloidal crystals in a confined space via the convective assembly technique has been investigated. The thin colloidal crystals were grown in a wedge-shaped cell, where the height of the cell increased with increased crystal growth. Triangle and square patterns, denoted as [111]- and [100]-oriented grains, respectively, were formed alternately as the height of the cell increased. The structural transformation was associated with an increase in the number of layers when the n-layer [100]-oriented grains changed to n + 1-layer [111]-oriented grains. Between the different grain structures, a stripe pattern was observed, which was a transitional region, where particle configuration gradually changed. The structural transformation occurred through the continuous change of particle configuration rather than through the abrupt formation of a grain boundary. The interval of the strip pattern lengthened as the number of layers increased, which is understood to be the structure with the highest packing density. The findings of the study give a better insight into convective assembly in a confined space, and also contribute to the greater structural control of colloidal crystals, useful for a number of applications.

Decreased Mortality with Beta-Blocker Therapy in HFpEF Patients Associated with Atrial Fibrillation.

BACKGROUND: There are no proven effective treatments that can reduce the mortality in heart failure with preserved ejection fraction (HFpEF), probably due to its heterogeneous nature which will weaken the effect of therapy in clinical studies. We evaluated the effect of beta-blocker treatment in HFpEF patients associated with atrial fibrillation (AF), which is a homogeneous syndrome and has seldom been discussed. METHODS: This retrospective cohort study screened 955 patients diagnosed with AF and HFpEF. Patients with a range of underlying heart diseases or severe comorbidities were excluded; 191 patients were included and classified as with or without beta-blocker treatment at baseline. The primary outcome was all-cause mortality and rehospitalization due to heart failure. Kaplan-Meier curves and multivariable Cox proportional-hazards models were used to evaluate the differences in outcomes. RESULTS: The mean follow-up was 49 months. After adjustment for multiple clinical risk factors and biomarkers for prognosis in heart failure, patients with beta-blocker treatment were associated with significantly lower all-cause mortality (hazard ratio (HR) = 0.405, 95% confidence interval (CI) = 0.233-0.701, p=0.001) compared with those without beta-blocker treatment. However, the risk of rehospitalization due to heart failure was increased in the beta-blocker treatment group (HR = 1.740, 95% CI = 1.085-2.789, p=0.022). There was no significant difference in all-cause rehospitalization between the two groups (HR = 1.137, 95% CI = 0.803-1.610, p=0.470). CONCLUSIONS: In HFpEF patients associated with AF, beta-blocker treatment is associated with significantly lower all-cause mortality, but it increased the risk of rehospitalization due to heart failure.

Complete Genome of Vibrio neocaledonicus CGJ02-2, An active Compounds Producing Bacterium Isolated from South China Sea.

Strain CGJ02-2 was isolated from the coral reefs in South China sea and deposited in South China Sea Institute of Oceanology, Chinese Academy of Sciences. Active compounds including indole, ρ-hydroxybenzaldehyde were isolated from this strain. To explore the biosynthetic way of these compounds and search gene clusters, the complete genome of this strain was sequenced by Single Molecule, Real-Time (SMRT) technology. It was de novo assembled to two circular chromosomes of 3,400,283 bp with GC% 44.77 and 1,845,572 bp with GC% 44.59 respectively and classified as Vibrio alginolyticus. In silico phenotype features of Vibrio alginolyticus CGJ02-2 were also analyzed. The biosynthetic pathway of ρ-hydroxybenzaldehyde and indole in this strain were postulated. Gene clusters of four secondary metabolites including bacteriocin, ectoine, siderophore, arylpolyene were identified. This study provides helpful information for further utilizing Vibrio alginolyticus CGJ02-2 as a source of valuable bioactive compounds.

Effects of Solution Flow on the Growth of Colloidal Crystals.

For the versatile potential applications of colloidal crystals, precisely controlling their growth is required to achieve properties such as high crystallinity and large-area crystals. Because colloidal crystallization is a self-assembly process of dispersed particles in a solution, solution flow directly and markedly changes the behavior of particles. Thus, the effects of solution flow on the growth of colloidal crystals were investigated in the present study. We found three different effects of solution flow on the growth of colloidal crystals: enlarging the first layer, facilitating the growth of superlattice structures, and forming a new circular packing structure. Specifically, in the single-component system, because the flow speed is lower closer to the bottom of the cell, the second and further layers dissolve owing to the large flow speed, whereas the first layer remains undissolved at the appropriate flow speed. The dissolved particles (particles that are detached from the crystals and returned back into the aqueous medium) are transported near the first layer, where they facilitate the growth of the first layer. In a binary system, when colloidal crystals with different particles are neighboring each other, the flow dissolves the surface of each crystal, which forms a dense, melt-like phase between crystals, from which a superlattice structure such as AB2 grows. The flow often moves the second layer more than the first layer because the flow speed varies with the distance from the bottom. This causes the second layer to slide above the first layer of the neighboring crystals composed of different particle sizes, which transform from the initial face-centered cubic structure of the first layer into a circular pattern with strain. These findings contribute to establishing a sophisticated control method for growing colloidal crystals.

Small RNA-mediated Cry toxin silencing allows Bacillus thuringiensis to evade Caenorhabditis elegans avoidance behavioral defenses.

Pathogen avoidance behavior protects animal hosts against microbial pathogens. Pathogens have evolved specific strategies during coevolution in response to such host defenses. However, these strategies for combatting host avoidance behavioral defenses remain poorly understood. Here, we used Caenorhabditis elegans and its bacterial pathogen Bacillus thuringiensis as a model and determined that small RNA (sRNA)-mediated Cry toxin silencing allowed pathogens to evade host avoidance behavioral defenses. The B. thuringiensis strain YBT-1518, which encodes three nematicidal cry genes, is highly toxic to C. elegans. However, the expression of the most potent toxin, Cry5Ba, was silenced in this strain when YBT-1518 was outside the host. Cry5Ba silencing was due to the sRNA BtsR1, which bound to the RBS site of the cry5Ba transcript via direct base pairing and inhibited Cry5Ba expression. Upon ingestion by C. elegans, Cry5Ba was expressed in vivo by strain YBT-1518. Cry5Ba silencing may allow B. thuringiensis to avoid nematode behavioral defenses and then express toxins once ingested to kill the host and gain a survival advantage. Our work describes a novel model of sRNA-mediated regulation to aid pathogens in combating host avoidance behavioral defenses.

Improving myocardial fractional flow reserve in coronary atherosclerosis via CX37 gene silence: a preclinical validation study in pigs.

OBJECTIVES: The purpose of this study was to evaluate the effect of CX37 gene silence on myocardial fractional flow reserve (FFR). METHODS: A total of 90 male pigs were randomly divided into saline, mock and 3 different doses (5, 10 and 20 µl) of CX37 viral suspension groups that could induce coronary plaque formation with high-fat diet. After performing myocardial FFR by intravascular ultrasound, different doses of CX37 viral suspension, saline and mock small interfering RNA (siRNA) were transfected into the related coronary. The FFR, the myocardial enzymes and the cardiac structures and functions of the pigs were detected at baseline, 4th, 8th and 12th week after transfection, respectively. RESULTS: Repeated measures analysis of variance comparison showed that the difference in the FFR among the 5 groups was statistically significant (F = 27.0, P < 0.01). Post hoc analysis showed that FFR were highest in the siRNA CX37 group (20 µl), followed by the siRNA CX37 group (10 µl) and the siRNA CX37 group (5 µl), and lowest in the mock and saline groups. Left ventricular end-diastolic diameter was significantly smaller and ejection fraction was obviously higher in the 3 siRNA CX37 groups compared with the untreated groups. CONCLUSIONS: Our study showed that FFR levels increased along with decreased doses of siRNA CX37 lentivirus, indicating that siRNA CX37 lentivirus may reduce the risk of coronary atherosclerosis and provide a potential approach to treat coronary heart disease.

Heterogeneous Nucleation of Colloidal Crystals on a Glass Substrate with Depletion Attraction.

The heterogeneous nucleation of colloidal crystals with attractive interactions has been investigated via in situ observations. We have found two types of nucleation processes: a cluster that overcomes the critical size for nucleation with a monolayer, and a method that occurs with two layers. The Gibbs free energy changes (ΔG) for these two types of nucleation processes are evaluated by taking into account the effect of various interfacial energies. In contrast to homogeneous nucleation, the change in interfacial free energy, Δσ, is generated for colloidal nucleation on a foreign substrate such as a cover glass in the present study. The Δσ and step free energy of the first layer, γ1, are obtained experimentally based on the equation deduced from classical nucleation theory (CNT). It is concluded that the ΔG of q-2D nuclei is smaller than of monolayer nuclei, provided that the same number of particles are used, which explains the experimental result that the critical size in q-2D nuclei is smaller than that in monolayer nuclei.

Two-Dimensional Nucleation on the Terrace of Colloidal Crystals with Added Polymers.

Understanding nucleation dynamics is important both fundamentally and technologically in materials science and other scientific fields. Two-dimensional (2D) nucleation is the predominant growth mechanism in colloidal crystallization, in which the particle interaction is attractive, and has recently been regarded as a promising method to fabricate varieties of complex nanostructures possessing innovative functionality. Here, polymers are added to a colloidal suspension to generate a depletion attractive force, and the detailed 2D nucleation process on the terrace of the colloidal crystals is investigated. In the system, we first measured the nucleation rate at various area fractions of particles on the terrace, ϕarea. In situ observations at single-particle resolution revealed that nucleation behavior follows the framework of classical nucleation theory (CNT), such as single-step nucleation pathway and existence of critical size. Characteristic nucleation behavior is observed in that the nucleation and growth stage are clearly differentiated. When many nuclei form in a small area of the terrace, a high density of kink sites of once formed islands makes growth more likely to occur than further nucleation because nucleation has a higher energy barrier than growth. The steady-state homogeneous 2D nucleation rate, J, and the critical size of nuclei, r*, are measured by in situ observations based on the CNT, which enable us to obtain the step free energy, γ, which is an important parameter for characterizing the nucleation process. The γ value is found to change according to the strength of attraction, which is tuned by the concentration of the polymer as a depletant.

Detection of the cryptic prophage-like molecule pBtic235 in Bacillus thuringiensis subsp. israelensis.

Bacillus thuringiensis has long been recognized to carry numerous extrachromosomal molecules. Of particular interest are the strains belonging to the B. thuringiensis subsp. israelensis lineage, as they can harbor at least seven extrachromosomal molecules. One of these elements seems to be a cryptic molecule that may have been disregarded in strains considered plasmid-less. Therefore, this work focused on this cryptic molecule, named pBtic235. Using different approaches that included transposition-tagging, large plasmid gel electrophoresis and Southern blotting, conjugation and phage-induction experiments, in combination with bioinformatics analyses, it was found that pBtic235 is a hybrid molecule of 235,425 bp whose genome displays potential plasmid- and phage-like modules. The sequence of pBtic235 has been identified in all sequenced genomes of B. thuringiensis subsp. israelensis strains. Here, the pBtic235 sequence was considered identical to that of plasmid pBTHD789-2 from strain HD-789. Despite the fact that the pBtic235 genome possesses 240 putative CDSs, many of them have no homologs in the databases. However, CDSs coding for potential proteins involved in replication, genome packaging and virion structure, cell lysis, regulation of lytic-lysogenic cycles, metabolite transporters, stress and metal resistance, were identified. The candidate plasmidial prophage pBtic235 exemplifies the notable diversity of the extrachromosomal realm found in B. thuringiensis.

The Genome Sequence of Alcaligenes faecalis NBIB-017 Contains Genes with Potentially High Activities against Erwinia carotovora.

Alcaligenes faecalisNBIB-017, a Gram-negative bacterium, was isolated from soil in China. Here, we provide the complete genome sequence of this bacterium, which possesses a high number of genes encoding antibacterial factors, including proteins and small molecular peptides.

Taxol prevents myocardial ischemia-reperfusion injury by inducing JNK-mediated HO-1 expression.

CONTEXT: Ischemia/hypoxia and reperfusion impair mitochondria and produce a large amount of reactive oxygen species (ROS), which lead to mitochondrial and brain damage. Furthermore, heme oxygenase-1 (HO-1) as a cytoprotective gene protects cells against ROS-induced cell death in ischemia-reperfusion injury. Induction of HO-1 is involved in cytoprotective effects of taxol. OBJECTIVE: We hypothesize that taxol protects cardiac myocytes possibly by preserving myocardial mitochondrial function and inducing HO-1 expression through the JNK pathway. MATERIALS AND METHODS: In this project, the perfused Langendorff hearts isolated from rats were randomly divided into five groups: control, ischemic, ischemic + taxol (0.1 µM), ischemic + taxol (0.3 µM), and ischemic + taxol (1 µM). Briefly, following a 15 min equilibration period, the control group was subject to normoxic perfusion for 120 min; the ischemia group, normoxic reperfusion for 120 min after 30 min ischemia; the taxol groups, normoxic reperfusion for 120 min after 30-min ischemia with taxol (0.1, 0.3, or 1 µM). The microtubule disruption score, ROS levels, and the activity of mitochondrial electron transport chain complexes I and III were examined by using immunohistochemical methods and free radical detection kits. Western blot assay was employed to study the underlying mechanisms. RESULTS: After Taxol treatment (0.1 µM), the ischemic microtubule disruption score was reduced to 9.8 ± 1.9%. The study revealed that 0.1, 0.3, and 1 µM taxol reduced the level of ROS by 33, 46 and 51%, respectively (p < 0.05). In additional, 0.3 and 1 µM taxol dramatically increased the activity of mitochondrial electron transport chain complex I (99.11 ± 2.59, 103.49 ± 3.89) and mitochondrial electron transport chain complex III (877.82 ± 12.08; 907.42 ± 16.21; 914.73 ± 19.39, *p < 0.05). Additionally, phosphorylation levels of JNK1 were significantly increased in the taxol group. Furthermore, the expression level of HO-1 increased with taxol treatments, which could be inhibited by the specific inhibitor of JNK, SP600125. DISCUSSION AND CONCLUSION: Taxol stabilized microtubules and effectively reduced ROS levels during ischemia. It also preserved the activity of mitochondrial complexes I and III. Interestingly, taxol induced the expression of HO-1 via the JNK pathway in cardiac myocytes.

Reduction of connexin 37 expression by RNA interference decreases atherosclerotic plaque formation.

The aim of this study was to examine the effects of connexin 37 (Cx37) interference on atherosclerotic plaques. Lentiviruses expressing small interfering RNA (siRNA) of Cx37 were constructed, and were shown to significantly knockdown the mRNA and protein expression of Cx37 in vitro. Sixty pigs on a high­fat diet were randomly divided into three treatment groups of saline, mock or Cx37 siRNA, to induce plaque formation. The Cx37 lentiviral suspension was transfected into the abdominal aortic plaques of pigs. Plaque characteristics were detected by intravascular ultrasound and the expression of Cx37 mRNA was detected by semi­quantitative polymerase chain reaction. The expression of Cx37 protein was analyzed by western blot analysis. Two months after lentivirus transfection, Cx37 mRNA levels were decreased by 38% in the Cx37 siRNA group, by 60% in the mock­siRNA group and by 63% in the saline group (P<0.05). The mock group showed no significant changes in Cx37 expression as compared with the saline group. Cx37 protein expression was lower in the Cx37 siRNA­treated group as compared with the other groups (0.21±0.07 vs. 0.65±0.06 vs. 0.54±0.07). The percentage of plaque necrosis at 10 months (two months following RNAi) was decreased in the Cx37 siRNA group as compared with that at eight months, prior to RNAi (5.26±2.11 vs. 7.83±1.03%, P<0.05). In the mock­siRNA and saline groups, no differences (P=0.074, 0.061, respectively) were observed. In the Cx37 siRNA group, plaque volumes following 10 months decreased relative to those following eight months, prior to RNAi (21.03±6.24 vs. 31.23±10.23, P<0.01). By contrast, in the mock siRNA and saline groups, plaque volumes after 10 months were increased relative to those following eight months (38.54±13.56 vs. 32.12±11.21 mm3, 37.36±14.21 vs. 30.21±12.02 mm3, P=0.031, P=0.027). Atherosclerotic plaque formation was effectively decreased through the downregulation of Cx37 mRNA using Cx37 siRNA.