Improving drug-drug interactions prediction with interpretability via meta-path-based information fusion.

Drug-drug interactions (DDIs) are compound effects when patients take two or more drugs at the same time, which may weaken the efficacy of drugs or cause unexpected side effects. Thus, accurately predicting DDIs is of great significance for the drug development and the drug safety surveillance. Although many methods have been proposed for the task, the biological knowledge related to DDIs is not fully utilized and the complex semantics among drug-related biological entities are not effectively captured in existing methods, leading to suboptimal performance. Moreover, the lack of interpretability for the predicted results also limits the wide application of existing methods for DDIs prediction. In this study, we propose a novel framework for predicting DDIs with interpretability. Specifically, we construct a heterogeneous information network (HIN) by explicitly utilizing the biological knowledge related to the procedure of inducing DDIs. To capture the complex semantics in HIN, a meta-path-based information fusion mechanism is proposed to learn high-quality representations of drugs. In addition, an attention mechanism is designed to combine semantic information obtained from meta-paths with different lengths to obtain final representations of drugs for DDIs prediction. Comprehensive experiments are conducted on 2410 approved drugs, and the results of predictive performance comparison show that our proposed framework outperforms selected representative baselines on the task of DDIs prediction. The results of ablation study and cold-start scenario indicate that the meta-path-based information fusion mechanism red is beneficial for capturing the complex semantics among drug-related biological entities. Moreover, the results of case study demonstrate that the designed attention mechanism is able to provide partial interpretability for the predicted DDIs. Therefore, the proposed method will be a feasible solution to the task of predicting DDIs.

Rosavin thwarts amyloid-ß-induced macromolecular damages and neurotoxicity, exhibiting anti-Alzheimer's disease activity in Wister rat model.

Lately, interest surrounding the utilization of plant-derived compounds as a viable beneficial approach for treating Alzheimer's disease (AD) has significantly increased. This study aimed to assess the defensive properties of rosavin against Alzheimer's disease induced by amyloid-ß, utilizing experimental models. We found that rosavin exhibited anti-aggregation and disaggregation properties, suggesting its potential to prevent the gathering of Aß-aggregates. In vitro experiments revealed that rosavin effectively mitigated the neurotoxicity induced by Aß in Neuro-2a cells, showcasing its protective potential. Rosavin significantly improved the Aß-induced cognitive deficits in Wistar rats, particularly in spatial memory. Which the pathophysiology of AD includes oxidative damage, which negatively impacts biological macromolecules. Triggers the apoptotic process, causing macromolecular destruction. Interestingly, rosavin attenuated Aß-induced macromolecular damages, thereby preserving neuronal integrity. Furthermore, the activation of antioxidative defense enzymes by rosavin inhibited oxidative damage. The positive outcomes associated with rosavin were primarily attributed to its capacity to enhance acetylcholine-mediated effects. Finally, rosavin has the potential to alleviate Aß-induced neurotoxicity and macromolecular damages, ultimately resulting in enhanced memorial and reasoning function in Wistar rats, offering promising prospects for the treatment of AD.

Microstructure and Nanomechanical Properties of Single Trabecular Bone in Different Regions of Osteonecrosis of the Femoral Head.

This study aimed to compare the microstructure and nanomechanical properties of single trabecular bone in different regions of osteonecrosis of the femoral head. Osteonecrotic femoral heads were taken from 20 patients undergoing total hip arthroplasties between 2011 and 2014. Following incision, resin was embedded and polished, and divided into four regions according to the type of pathologic change; i.e., subchondral bone, and necrotic, sclerotic, and healthy regions. Indents from a single trabecular bone of each region were randomly selected to undergo nanoindentation. The results are (1) The elastic modulus and degree of hardness were significantly elevated in the sclerotic region, but there were no differences in necrotic and subchondral bone regions compared with healthy regions. (2) The elastic modulus and hardness of the single trabecular bone were significantly greater in central versus edge regions (for all regions). The conclusions are (1) The mechanical properties of single bone trabeculae were not markedly altered in the necrotic region. (2) The elastic modulus and degree of hardness increased significantly between the edge and central regions, regardless of whether the bone was normal or osteonecrotic.

[The Significance of Analysis of Soil from the Surface of Hetao Plain, Inner Mongolia with Near Infrared Spectra].

The technology of near infrared spectrum, marked by its convenience and effectiveness, which has been applied extensively in lithological analysis, is suitable for component analysis of regional geology, due to its superiority in analyzing numerous samples in a relatively short time. Since different mineral molecule peaks will show different characters when being analyzed in the near infrared spectrum, we can acquire the information about the mineral composition, water content, mineral crystallinity and etc. In this passage, the soil from the surface of Hetao Plain has been analyzed, and in this case, we can obtain the information about the mineral composition, water content, mineral crystallinity and etc. Referring the features of local environment and climate, we could surmise the source of the minerals in soil and the environment where they formed. The result not only consummates the geological characterization of Hetao area, but also has great significance revealing mechanism of soil-formation in Hetao area. The result shows that the soil from surface of Hetao Plain is mainly composed by altered minerals, such as kaolinite, smectite, ledikite, muscovite etc, and is presumed to be from acidic rock mass of the Yinshan mountains. The passage also indicates that the Yinshan mountains have great impact on the formation of the soil on Hetao Plain in the aspect of climate, for example, though the climate of inner Mongolia is continental arid climate, enough rainfall and the substantial differences in mean annual precipitation ensure the relatively moist environment in this area, and make the sediments altered adequately, proposing new aspects about exploring the mechanism of the soil-formation in Hetao area.

Fabrication and in vitro evaluation of an articular cartilage extracellular matrix-hydroxyapatite bilayered scaffold with low permeability for interface tissue engineering.

BACKGROUND: Osteochondral interface regeneration is challenging for functional and integrated cartilage repair. Various layered scaffolds have been used to reconstruct the complex interface, yet the influence of the permeability of the layered structure on cartilage defect healing remains largely unknown. METHODS: We designed and fabricated a novel bilayered scaffold using articular cartilage extracellular matrix (ACECM) and hydroxyapatite (HAp), involving a porous, oriented upper layer and a dense, mineralised lower layer. By optimising the HAp/ACECM ratio, differing pore sizes and porosities were obtained simultaneously in the two layers. To evaluate the effects of permeability on cell behaviour, rabbit chondrocytes were seeded. RESULTS: Morphological observations demonstrated that a gradual interfacial region was formed with pore sizes varying from 128.2 ± 20.3 to 21.2 ± 3.1 µm. The permeability of the bilayered scaffold decreased with increasing compressive strain and HAp content. Mechanical tests indicated that the interface was stable to bearing compressive and shear loads. Accordingly, the optimum HAp/ACECM ratio (7 w/v%) in the layer to mimic native calcified cartilage was found. Chondrocytes could not penetrate the interface and resided only in the upper layer, where they showed high cellularity and abundant matrix deposition. CONCLUSIONS: Our findings suggest that a bilayered scaffold with low permeability, rather than complete isolation, represents a promising candidate for osteochondral interface tissue engineering.

[XRD, FTIR and XPS analysis of oxidized particles from Dongshengmiao pyrite-polymetallic sulfide deposit, inner Mongolia].

In the present paper, characteristics of material compositions, phase structures, surface element states, and transformation mechanism of oxidized particles from Dongshengmiao pyrite-polymetallic sulfide deposit were studied using modern analytical testing technology including XRD, FTIR and XPS. The results show that the samples consist of gypsum, calcite, quartz, muscovite, goethite, organic matter, etc. Primary ore in deep oxidation zone mainly under went such processes as oxidization, hydrolysis, dehydration and carbonation. Compared to the surface oxidation zone of arid and extremely arid regions in the northwestern China, the oxidation process and oxidizing condition of the deep oxidation zone were less complex. New mineral type was also not found, and extensively developed sulfate minerals were rare to be seen. The research results can not only be applied to mineral identification of oxidized particles from this type of ore deposit but also play an important role in ore exploration, mining, mineral processing, etc.

Delivery, maternal and neonatal outcomes in nulliparous women with gestational diabetes undergoing epidural labour analgesia: a propensity score-matched analysis.

OBJECTIVE: This study aimed to retrospectively analyse the influence of epidural labour analgesia (ELA) on delivery and maternal and neonatal outcomes in nulliparous women with gestational diabetes mellitus (GDM) using propensity score-matched analysis. DESIGN: Retrospective cohort analysis. SETTING: Primary care practices in a teaching hospital from March 2018 to October 2021. PARTICIPANTS: A total of 816 delivery records of nulliparous women with GDM were collected and retrospectively analysed. INTERVENTIONS: ELA and non-ELA (NELA) cohorts were assessed. MAIN OUTCOME MEASURE: The primary outcome assessed was delivery type (spontaneous, assisted vaginal or caesarean). The secondary outcomes assessed included labour duration and maternal and neonatal outcomes. RESULTS: A total of 137 propensity score-matched pairs of ELA and NELA patients were analysed. ELA was associated with a decreased rate of caesarean section (18.3% vs 46.0% in the ELA vs NELA cohort, respectively; p<0.05) and an increased occurrence of assisted vaginal delivery (35.8% vs 12.4% in the ELA vs NELA cohort, respectively; p<0.05). The duration of the first and total stages of labour was prolonged, the occurrence of postpartum fever increased, and the duration of hospital stay was shortened in those receiving ELA (all p<0.05). Additionally, neonatal birth weight, plasma glucose levels and neonatal macrosomia occurrence increased, while neonatal intensive care unit admissions and neonatal hypoglycaemia decreased in the ELA versus the NELA group (all p<0.05). With respect to other maternal and neonatal outcomes, both cohorts were similar. CONCLUSIONS: The use of ELA decreases the rate of caesarean section and improves maternal and neonatal outcomes in nulliparous women with GDM. TRIAL REGISTRATION NUMBER: ChiCTR-2000033091.

A Biocompatible Self-Powered Piezoelectric Poly(vinyl alcohol)-Based Hydrogel for Diabetic Wound Repair.

Acute and chronic wounds, caused by trauma, tumors, diabetic foot ulcers, etc., are usually difficult to heal, while applying exogenous electrical stimulation to enhance the endogenous electric field in the wound has been proven to significantly accelerate wound healing. However, traditional electrical stimulation devices require an additional external power supply, making them poor in portability and comfort. In this work, a self-powered piezoelectric poly(vinyl alcohol) (PVA)/polyvinylidene fluoride (PVDF) composite hydrogel is constructed by establishing a distinctive preparation process of freezing/thawing-solvent replacement-annealing-swelling. The hydrogen bonding in the hydrogel is remarkably enhanced by the annealing-swelling process, which is stronger between PVA/PVDF molecules than that between PVA molecules, promoting transformation of the α-phase into the electroactive ß-phase PVDF and facilitating formation of a much more crystalline structure with high cross-linking density. Hence, an obvious piezoelectric response with high piezoelectric coefficient and electrical signal output with superior stability and sensitivity and excellent mechanical strength and stretchability was achieved for hydrogels. PVA/PVDF composite hydrogels with good cytocompatibility significantly promote proliferation, migration, and secretion of extracellular matrix proteins and growth factors of fibroblasts, possibly through activating the AKT and ERK1/2 signaling pathways. In a wound model of diabetic rats, piezoelectric hydrogels could not only rapidly attract wound exudate and maintain the wet environment of the wound bed but also convert the mechanical energy generated by rats' physical activities into electrical energy, so as to provide local piezoelectric stimulation to the wound bed evenly and symmetrically in real time. Such an effect significantly promotes re-epithelialization and collagen deposition and increases angiogenesis and secretion of growth factors in wound tissue. Besides, it regulates the macrophage phenotype from the M1 subtype (pro-inflammatory subtype) to the M2 subtype (anti-inflammatory subtype) and reduces the expression levels of inflammatory factors, thus accelerating wound healing. The development of such a novel piezoelectric hydrogel provides new therapeutic strategies for chronic wound healing.

A risk prediction model of post-stroke cognitive impairment based on magnetic resonance spectroscopy imaging.

Objective: To explore the clinical value of a risk prediction model of post-stroke cognitive impairment (PSCI) based on proton magnetic resonance spectroscopy (1H-MRS).Methods:A retrospective analysis was conducted on 376 stroke patients hospitalized between March 2016 and March 2019. Their relevant clinical baseline data were collected at admission. After the patients' condition was stabilized, 1H-MRS was performed to detect the related indices of the bilateral prefrontal lobe, thalamus, basal ganglia, hippocampus, precuneus, and angular gyrus. Within 12 months of the onset of stroke, cognitive impairment tests were performed monthly. Based on score results, stroke patients were divided into two groups: PSCI and post-stroke non-PSCI (N-PSCI). Thirty-four characteristic parameters of baseline and imaging data were extracted from the PSCI and N-PSCI groups. The least absolute shrinkage and selection operator (LASSO) regression was used for optimal feature selection, and a nomogram prediction model was established. The predictive ability of the model was validated by a calibration plot and the area under the curve (AUC) of the receiver operating characteristic curve.Results: Six risk factors were identified from clinical baseline data and MRS indices based on screening by LASSO dimensionality reduction. The consistency test of the correction curve showed that the prediction probability of the PSCI nomogram had good correlation with actual diagnosis. The AUCs of internal and external validation were 0.8935 and 0.8523, respectively.Discussion: A PSCI risk prediction model based on MRS serves to assist clinicians in estimating the risk of cognitive impairment after stroke.

Exploring the inhibitory effects of liquiritigenin against tau fibrillation and related neurotoxicity as a model of preventive care in Alzheimer's disease.

Aggregation of tau protein into the form of insoluble amyloid fibrils is linked with Alzheimer's disease. The identification of potential small molecules that can inhibit tau protein from undergoing aggregation has received a great deal of interest, recently. In the present study, the possible inhibitory effects of liquiritigenin as a member of chiral flavanone family on tau amyloid fibrils formation and their resulting neurotoxicity were assessed by different biophysical and cellular assays. The inhibitory effect of the liquiritigenin against tau amyloid formation was investigated using thioflavin T (ThT) and 1-Anilino-8-naphthalene sulfonate (ANS) fluorescence spectroscopy, Congo red (CR) binding assays, transmission electron microscopy (TEM) analysis, and circular dichroism (CD) spectroscopy. Neurotoxicity assays were also performed against neuron-like cells (SH-SY5Y) using 3-(4,5-Dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) reduction, reactive oxygen species (ROS), catalase (CAT) and caspase-3 activity measurements. We found that liquiritigenin served as an efficient inhibitor of tau amyloid fibrils formation through prevention of structural transition in tau structure, exposure of hydrophobic patches and their associated neurotoxicity mediated by decrease in the production of ROS and caspase-3 activity and elevation of CAT activity. These data may finally find applications in the development of promising inhibitors against amyloid fibril formation and treatment of Alzheimer's disease.

Evaluation of heptelidic acid as a potential inhibitor for tau aggregation-induced Alzheimer's disease and associated neurotoxicity.

Tau is a major component of protein plaques in tauopathies, especially Alzheimer's disease (AD). The purpose of the present study is to explore the inhibitory effects of heptelidic acid as a bioactive compound from fungus T. koningii on tau fibrillization and associated neurotoxicity. The influences of various concentrations of heptelidic acid on tau fibrillization and underlying neurotoxicity were explored by assessment of the biophysical (ThT/Nile red fluorescence, CR absorbance, CD, and TEM) and cellular (MTT, LDH, and caspase-3) assays. It was shown that heptelidic acid inhibited tau fibrillization in a concentration-dependent manner. On the other hand, cellular assays indicated that the viability, LDH release, and caspase-3 activity were regulated when neurons were exposed to tau samples co-incubated with heptelidic acid. In conclusion, it may be indicated that heptelidic acid inhibited tau fibrillization which was accompanied by formation of amorphous aggregated species of tau with much less neurotoxicity than tau amyloid alone. Thus, heptelidic acid can be considered as a potential candidate in preventive care studies to inhibit the formation of tau plaques as neurotoxic species.

Syringic acid demonstrates promising protective effect against tau fibrillization and cytotoxicity through regulation of endoplasmic reticulum stress-mediated pathway as a prelude to Alzheimer's disease.

There are several studies reporting that different plant-based metabolites are potential inhibitors of protein amyloid fibrillation. As chemical features of metabolites can regulate protein aggregation process, in the present in vitro investigation, tau protein was selected as a model of Alzheimer's disease to elaborate the inhibitory effect of syringic acid (SA) on its assembly and associated neurotoxicity in aggregation conditions. Extrinsic fluorescence, Congo red adsorption, and CD spectroscopic studies, TEM, size-exclusion chromatography, and MALDI-TOF mass spectrometry analysis along with MTT and qRT-PCR assays were performed to assess the inhibitory effects of SA against tau aggregation and neurotoxicity. It was shown that SA has the tendency to control the aggregation of the tau proteins through modulating the amyloid kinetic parameters, exposure of hydrophobic residues, and structural changes. Moreover, the structures formed in the presence of SA recovered the viability of neuron-like cells (SH-SY5Y) through regulation of endoplasmic reticulum stress signaling pathway by downregulation of ATF-6, caspase-8 and caspase-3 mRNA. In conclusion, it can be suggested that SA may be used as a potential small molecule in the development of therapeutic platforms against Alzheimer's disease.

Diffusion of neutral solutes within human osteoarthritic cartilage: Effect of loading patterns.

OBJECTIVE: Variation of the solute diffusion within articular cartilage is an important feature of osteoarthritis (OA) progression. For in vitro study of monitoring of the diffusion process, it is essential to simulate physiological conditions as much as possible. Our objective was to investigate the effects of loading patterns on diffusion processes of neutral solutes within osteoarthritic cartilage. METHODS: Osteochondral plugs were harvested from human tibial plateaus and separated into three OA stages according to modified Mankin scoring system. The samples were subjected to static or cyclic compression using a carefully designed loading device. Contrast-enhanced micro-computed tomography (CEµCT) was applied to acquire image sequences while the cartilage was being compressed. The apparent diffusion maps and diffusion coefficients were analysed, as well as histological and stereological assessments of the plugs. RESULTS: The diffusion of neutral solutes was significantly affected by the loading patterns. For OA cartilage with early and middle stages, cyclic loading accelerated contrast agent infiltration compared with static loading. However, for late-stage OA samples, no acceleration of diffusion was observed in the first 2 â€‹h because of the insufficient resilience of compressed cartilage. The accumulation of neutral solutes in an upward invasive fissure also suggested that solutes could penetrate into the fissure under cyclic loading. CONCLUSIONS: To our knowledge, this is the first study to combine the cyclic compression and CEµCT scanning in the diffusion testing of human OA cartilage. This loading pattern could simulate the physiological conditions and reduce the time to reach solute equilibrium within cartilage. The diffusion data may contribute to joint drug-injection therapies for early OA. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The combination of cyclic loading and CEµCT scanning enabled diffusion analysis of osteoarthritic cartilage under different compressions. A comprehensive evaluation of OA cartilage and subchondral bone may benefit from this technique. The diffusion data provide theoretical support and reference for intra-articular injection of drugs.

AAV-Anti-miR-214 Prevents Collapse of the Femoral Head in Osteonecrosis by Regulating Osteoblast and Osteoclast Activities.

Osteonecrosis of the femoral head, an intractable but common disease that eventually triggers collapse of the femoral head, is characterized by increased osteoclast activity and markedly decreased osteoblast activity in the necrotic region of the femoral head. MicroRNA (miRNA)-214 (miR-214) may play important roles in vertebrate skeletal development by inhibiting osteoblast function by targeting activating transcription factor 4 (ATF4) and promoting osteoclast function via phosphatase and tensin homolog (PTEN). This study revealed significantly increased levels of miR-214 in necrotic regions, with commensurate changes in the numbers of its target cells (both osteoblasts and osteoclasts). To investigate whether targeting miR-214 could prevent femoral head collapse, we constructed an adeno-associated virus (AAV)-associated anti-miR-214 (AAV-anti-miR-214) and evaluated its function in vivo. AAV-anti-miR-214 promoted osteoblast activity and diminished osteoclast activity, effectively preventing collapse of the femoral head in a rat model of osteonecrosis.

Analysis of early stage osteonecrosis of the human femoral head and the mechanism of femoral head collapse.

We explored the mechanism of early stage osteonecrotic femoral head collapse by analyzing and comparing different regions in human osteonecrotic femoral head samples. Eight osteonecrotic femoral heads (ARCO II-III) were obtained from patients undergoing total hip arthroplasty. Bone structure was observed and evaluated by micro-computed tomography (CT) scans and pathology. Osteoblast and osteoclast activities were detected by tartrate-resistant acid phosphatase, alkaline phosphatase, and immunofluorescent staining. Some trabeculae had microfractures in the subchondral bone and necrotic region, which had lower bone mineral density, as well as trabecular thickness and number, but greater osteoclast activity. A sclerotic band had already appeared in certain samples which had greater trabecular thickness and number, bone mineral density, and osteoblast activity. The appearance of the femoral head did not change significantly in the early stage of osteonecrosis of the femoral head. However, osteoblast and osteoclast activities had already changed in different regions of the osteonecrotic femoral head, which may lead to eventual collapse of the femoral head. Therefore, osteonecrosis of the femoral head must be treated during the early stage. In addition, osteoblast activity should be promoted and osteoclast activity inhibited as early as possible to prevent collapse of an osteonecrotic femoral head.

Functional tissue-engineered microtissue derived from cartilage extracellular matrix for articular cartilage regeneration.

We developed a promising cell carrier prepared from articular cartilage slices, designated cartilage extracellular matrix (ECM)-derived particles (CEDPs), through processes involving physical pulverization, size screening, and chemical decellularization. Rabbit articular chondrocytes (ACs) or adipose-derived stem cells (ASCs) rapidly attached to the surface of the CEDPs and proliferated with high cell viability under microgravity (MG) condition in a rotary cell culture system (RCCS) or static condition. Gene profiling results demonstrated that ACs expanded on CEDPs exhibited significantly enhanced chondrogenic phenotypes compared with monolayer culture, and that ASCs differentiated into a chondrogenic phenotype without the use of exogenous growth factors. Moreover, MG culture conditions in a RCCS bioreactor were superior to static culture conditions in terms of maintaining the chondrogenic phenotype of ACs and inducing ACS chondrogenesis. With prolonged expansion, functional microtissue aggregates of AC- or ASC-laden CEDPs were formed. Further, AC- or ASC-based microtissues were directly implanted in vivo to repair articular osteochondral defects in a rabbit model. Histological results, biomechanical evaluations, and radiographic assessments indicated that AC- and ASC-based microtissues displayed equal levels of superior hyaline cartilage repair, whereas the other two treatment groups, in which osteochondral defects were treated with CEDPs alone or fibrin glue, exhibited primarily fibrous tissue repair. These findings provide an alternative method for cell culture and stem cell differentiation and a promising strategy for constructing tissue-engineered cartilage microtissues for cartilage regeneration. STATEMENT OF SIGNIFICANCE: Despite the remarkable progress in cartilage tissue engineering, cartilage repair still remains elusive. In the present study, we developed a cell carrier, namely cartilage extracellular matrix-derived particles (CEDPs), for cell proliferation of articular chondrocytes (ACs) and adipose-derived stem cells (ASCs), which improved the maintenance of chondrogenic phenotype of ACs, and induced chondrogenesis of ASCs. Moreover, the functional microtissue aggregates of AC- or ASC-laden CEDPs induced equal levels of superior hyaline cartilage repair in a rabbit model. Therefore, our study demonstrated an alternative method for chondrocyte culture and stem cell differentiation, and a promising strategy for constructing tissue-engineered cartilage microtissues for in vivo articular cartilage repair and regeneration.

Fabrication of nanofibrous microcarriers mimicking extracellular matrix for functional microtissue formation and cartilage regeneration.

Cartilage has rather limited capacities for self-repair and regeneration. To repair complexly shaped cartilage tissue defects, we propose the application of microtissues fabricated from bone marrow-derived mesenchymal stem cells (BMSCs) cultured in natural bionic nanofibrous microcarriers (NF-MCs). The NF-MCs were structurally and functionally designed to mimic natural extracellular matrix (ECM) by crosslinking dialdehyde bacterial cellulose (DBC) with DL-allo-hydroxylysine (DHYL) and complexing chitosan (CS) with DHYL through electrostatic interactions. The orthogonal design allows for fine tuning of fiber diameter, pore size, porosity, mechanical properties, and biodegradation rate of the NF-MC. BMSCs cultured in NF-MCs showed improved proliferation compared with those cultured in chitosan microcarriers (CS-MCs). After three-week culture under microgravity conditions, functional cartilage microtissues were generated. When implanted into a knee articular cartilage defect in mice, the microtissue showed superior in vivo cartilage repair as characterized by cell tracking, histology, micro CT image, and gait analysis. Versatile in natural biopolymer design and biomimetic in nanofibrous component embedded in macroporous microcarriers, these injectable NC-MCs demonstrate to be effective carriers for cell proliferation and differentiation. Furthermore, the functional microtissues also show their prospect in repair of cartilage tissue, and suggest their potential for other tissues in general.

An updated meta-analysis of the asporin gene D-repeat in knee osteoarthritis: effects of gender and ethnicity.

BACKGROUND: Knee osteoarthritis (KOA) is the most prevalent form of knee joint disease and characterized by the progressive degeneration of articular cartilage. Although pathology of KOA remains unknown, genetic factors are considered to be the major cause. Asporin is a group of biologically active components of extracellular matrix (ECM) in articular cartilage, and asporin gene (ASPN) D-repeat polymorphism was reported to be associated with KOA. Thus, our meta-analysis is aimed at investigation of the association between asporin D-repeat polymorphism and susceptibility of KOA. METHODS: We gathered data from MEDLINE, Embase, OVID, and ScienceDirect to search relevant published epidemiological studies through April 2017. Compared with previous studies, our meta-analysis is the first study to investigate the association of ASPN D15, D16, and D17 alleles and KOA susceptibility by ethnic- and sex-stratified subgroup analysis. RESULTS: We found no significant association between D15 allele and susceptibility to KOA (OR = 1.05, 95% CI 0.95-1.17) in overall population. The same results were observed in the analysis of D16 (OR = 1.01, 95% CI 0.80-1.28) and D17 alleles (OR = 1.28, 95% CI 0.91-1.80). The ethnic- and sex-subgroup analyses did not alter the ORs. However, significant association was detected in the sensitivity analysis of D17 in overall population (OR = 1.05, 95% CI 0.95-1.17) and Asian population (OR = 1.78, 95% CI 1.02-3.11, P < 0.05). CONCLUSION: Our results indicated that D-repeat polymorphism of ASPN may not play a major role in susceptibility of KOA in ethnic- and sex-specific analysis. Because of the limitations of the present meta-analysis, firm conclusions could not be drawn based on the current evidence, and further studies are required to detect genuine role of ASPN.

Acupotomy versus sodium hyaluronate for treatment of knee osteoarthritis in rabbits.

OBJECTIVE: To investigate the possible advantages of acupotomy over sodium hyaluronate injection for the treatment of knee osteoarthritis (KOA). METHODS: Twenty rabbits were divided randomly into four groups (n = 5 in each): a control group, model group, acupotomy group, and sodium hyaluronate injection group. The model, acupotomy, and sodium hyaluronate groups underwent anterior cruciate ligament transection plus partial medial meniscectomy. Sodium hyaluronate injection and acupotomy were administered to the respective groups from weeks 5 to 8, and samples of the tibial plateau and medial condyle of the femur were collected in week 9. Vascular endothelial growth factor (VEGF) expression was assessed in cartilage and subchondral bone by immunohistochemical staining. RESULTS: Articular cartilage degeneration was less pronounced in the acupotomy compared with the model and sodium hyaluronate groups. VEGF expression levels in cartilage and subchondral bone were increased in the model group compared with the control group (P < 0.01), and acupotomy had a more pronounced therapeutic effect than sodium hyaluronate injection (P < 0.01). CONCLUSION: Acupotomy and sodium hyaluronate injection may both reduce degeneration in the cartilage and subchondral bone in KOA based on the results from a rabbit model, but acupotomy improved the histopathology and reduced the VEGF content more effectively than sodium hyaluronate injection, probably by reducing venous stasis and intraosseous pressure. Acupotomy may improve KOA by lowering VEGF.

Past, present, and future of microcarrier-based tissue engineering.

The top issue in tissue engineering is how to obtain more seed cells quickly and to preserve their characteristic morphology during in vitro expansion culture of cells. Microcarriers can help to amplify cell numbers and maintain the appropriate phenotype for tissue repair and restoration of function. In addition, microtissue with cell microcarriers can be used to repair diseased tissues or organs. This review introduces the materials used for, and classification of, microcarriers and the improvements in, and potential applications of, microtissues with cell microcarriers in tissue engineering.