Programmable DNA Scaffolds Enable Orthogonal Engineering of Cell Membrane-Based Nanovesicles for Therapeutic Development.

Cell membrane-based nanovesicles (CMNVs) play pivotal roles in biomolecular transportation in living organisms and appear as attractive bioinformed nanomaterials for theranostic applications. However, the current surface-engineering technologies are limited in flexibility and orthogonality, making it challenging to simultaneously display multiple different ligands on the CMNV surface in a precisely controlled manner. Here, we developed a DNA scaffold-programmed approach to orthogonally engineer CMNVs with versatile ligands. The designed DNA scaffolds can rapidly anchor onto the CMNV surface, and their unique sequences and hybridized properties enable independent control of the loading of multiple different types of biomolecules on the CMNVs. As a result, the orthogonal engineering of CMNVs with a renal targeted peptide and a therapeutic protein at controlled ratios demonstrated an enhanced renal targeting and repair potential in vivo. This study highlights that a DNA scaffold-programmed platform can provide a potent means for orthogonal and flexible surface engineering of CMNVs for diverse therapeutic purposes.

Injectable Multifunctional Composite Hydrogel as a Combination Therapy for Preventing Postsurgical Adhesion.

Postsurgical adhesion (PA) is a common and serious postoperative complication that affects millions of patients worldwide. However, current commercial barrier materials are insufficient to inhibit diverse pathological factors during PA formation, and thus, highly bioactive materials are needed. Here, this work designs an injectable multifunctional composite hydrogel that can serve as a combination therapy for preventing PA. In brief, this work reveals that multiple pathological events, such as chronic inflammatory and fibrotic processes, contribute to adhesion formation in vivo, and such processes can not be attenuated by barrier material (e.g., hydrogel) alone treatments. To solve this limitation, this work designs a composite hydrogel made of the cationic self-assembling peptide KLD2R and TGF-ß receptor inhibitor (TGF-ßRi)-loaded mesenchymal stem cell-derived nanovesicles (MSC-NVs). The resulting composite hydrogel displays multiple functions, including physical separation of the injured tissue areas, antibacterial effects, and local delivery and sustained release of anti-inflammatory MSC-NVs and antifibrotic TGF-ßRi. As a result, this composite hydrogel effectively inhibited local inflammation, fibrosis and adhesion formation in vivo. Moreover, the hydrogel also exhibits good biocompatibility and biodegradability in vivo. Together, the results highlight that this "all-in-one" composite hydrogel strategy may provide insights into designing advanced therapies for many types of tissue injury.

Bimodal DNA self-origami material with nucleic acid function enhancement.

BACKGROUND: The design of DNA materials with specific nanostructures for biomedical tissue engineering applications remains a challenge. High-dimensional DNA nanomaterials are difficult to prepare and are unstable; moreover, their synthesis relies on heavy metal ions. Herein, we developed a bimodal DNA self-origami material with good biocompatibility and differing functions using a simple synthesis method. We simulated and characterized this material using a combination of oxDNA, freeze-fracture electron microscopy, and atomic force microscopy. Subsequently, we optimized the synthesis procedure to fix the morphology of this material. RESULTS: Using molecular dynamics simulation, we found that the bimodal DNA self-origami material exhibited properties of spontaneous stretching and curling and could be fixed in a single morphology via synthesis control. The application of different functional nucleic acids enabled the achievement of various biological functions, and the performance of functional nucleic acids was significantly enhanced in the material. Consequently, leveraging the various functional nucleic acids enhanced by this material will facilitate the attainment of diverse biological functions. CONCLUSION: The developed design can comprehensively reveal the morphology and dynamics of DNA materials. We thus report a novel strategy for the construction of high-dimensional DNA materials and the application of functional nucleic acid-enhancing materials.

Apoptotic extracellular vesicles derived from hypoxia-preconditioned mesenchymal stem cells within a modified gelatine hydrogel promote osteochondral regeneration by enhancing stem cell activity and regulating immunity.

Due to its unique structure, articular cartilage has limited abilities to undergo self-repair after injury. Additionally, the repair of articular cartilage after injury has always been a difficult problem in the field of sports medicine. Previous studies have shown that the therapeutic use of mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) has great potential for promoting cartilage repair. Recent studies have demonstrated that most transplanted stem cells undergo apoptosis in vivo, and the apoptotic EVs (ApoEVs) that are subsequently generated play crucial roles in tissue repair. Additionally, MSCs are known to exist under low-oxygen conditions in the physiological environment, and these hypoxic conditions can alter the functional and secretory properties of MSCs as well as their secretomes. This study aimed to investigate whether ApoEVs that are isolated from adipose-derived MSCs cultured under hypoxic conditions (hypoxic apoptotic EVs [H-ApoEVs]) exert greater effects on cartilage repair than those that are isolated from cells cultured under normoxic conditions. Through in vitro cell proliferation and migration experiments, we demonstrated that H-ApoEVs exerted enhanced effects on stem cell proliferation, stem cell migration, and bone marrow derived macrophages (BMDMs) M2 polarization compared to ApoEVs. Furthermore, we utilized a modified gelatine matrix/3D-printed extracellular matrix (ECM) scaffold complex as a carrier to deliver H-ApoEVs into the joint cavity, thus establishing a cartilage regeneration system. The 3D-printed ECM scaffold provided mechanical support and created a microenvironment that was conducive to cartilage regeneration, and the H-ApoEVs further enhanced the regenerative capacity of endogenous stem cells and the immunomodulatory microenvironment of the joint cavity; thus, this approach significantly promoted cartilage repair. In conclusion, this study confirmed that a ApoEVs delivery system based on a modified gelatine matrix/3D-printed ECM scaffold together with hypoxic preconditioning enhances the functionality of stem cell-derived ApoEVs and represents a promising approach for promoting cartilage regeneration.

Association between sleep patterns and galectin-3 in a Chinese community population.

BACKGROUND: Irregular sleep patterns have been associated with inflammation. Galectin-3, a novel biomarker, plays an important role in inflammation. We investigated the relationship between sleep patterns and galectin-3 in a Chinese population. METHODS: A total of 1,058 participants from the Shenzhen-Hong Kong United Network on Cardiovascular Disease study were included in the analysis. Age and sex-adjusted linear regression models were employed to investigate the relationship between galectin-3 level and traditional metabolic biomarkers. Logistic regression models were used to estimate the association among sleep disturbance, nighttime sleep duration, and daytime napping duration and elevated galectin-3, with elevated galectin-3 defined as galectin-3 level > 65.1 ng/ml. RESULTS: Of study participants, the mean age was 45.3 years and 54.3% were women. Waist circumference, natural logarithm (ln)-transformed triglyceride, and ln-transformed high sensitivity C-reactive protein were positively associated with galectin-3 level (age and sex-adjusted standardized ß [95% confidence interval (CI)], 0.12 [0.04, 0.21], 0.11 [0.05, 0.17], and 0.08 [0.02, 0.14], respectively). Sleep disturbance was associated with elevated galectin-3 (odds ratio [95% CI], 1.68 [1.05, 2.68], compared to those without sleep disturbance) after adjusting for traditional metabolic biomarkers. No interaction was observed between galectin-3 and age, sex, obesity, hypertension, and diabetes on sleep disturbance. No association was found between nighttime sleep duration or daytime napping duration and elevated galectin-3. CONCLUSIONS: Our study provides evidence of a significant association between sleep disturbance and elevated galectin-3 level, independent of traditional metabolic biomarkers. Screening and interventions on galectin-3 could assist in preventing sleep disturbance-induced inflammatory disease.

Hydrophilic nanofibers with aligned topography modulate macrophage-mediated host responses via the NLRP3 inflammasome.

Successful biomaterial implantation requires appropriate immune responses. Macrophages are key mediators involved in this process. Currently, exploitation of the intrinsic properties of biomaterials to modulate macrophages and immune responses is appealing. In this study, we prepared hydrophilic nanofibers with an aligned topography by incorporating polyethylene glycol and polycaprolactone using axial electrospinning. We investigated the effect of the nanofibers on macrophage behavior and the underlying mechanisms. With the increase of hydrophilicity of aligned nanofibers, the inflammatory gene expression of macrophages adhering to them was downregulated, and M2 polarization was induced. We further presented clear evidence that the inflammasome NOD-like receptor thermal protein domain associated protein 3 (NLRP3) was the cellular sensor by which macrophages sense the biomaterials, and it acted as a regulator of the macrophage-mediated response to foreign bodies and implant integration. In vivo, we showed that the fibers shaped the implant-related immune microenvironment and ameliorated peritendinous adhesions. In conclusion, our study demonstrated that hydrophilic aligned nanofibers exhibited better biocompatibility and immunological properties.

Impact of healthy lifestyles on risk of hypertension in the Chinese population: finding from SHUN-CVD study.

INTRODUCTION: Lifestyle factors are known to play a role in the development of hypertension. We aimed to study the relationship between lifestyle and hypertension in a Chinese population. METHODS: This study involved 3,329 participants (1,463 men and 1,866 women) aged 18-96 years in the Shenzhen-Hong Kong United Network on Cardiovascular Disease. A healthy lifestyle score was derived from 5 factors: no smoking, no alcohol consumption, active physical activity, normal body mass index, and a healthy diet. Multiple logistic regression was used to investigate the relationship between lifestyle score and hypertension. The influence of each lifestyle component on hypertension was also assessed. RESULTS: In the overall population, 950 (28.5%) participants had hypertension. The risk of hypertension decreased with increasing healthy lifestyle scores. Compared with participants with the lowest score (score: 0), the multivariable odds ratios (ORs) and corresponding 95% confidence intervals for participants with scores 3, 4, and 5 were 0.65 (0.41-1.01), 0.62 (0.40-0.97), and 0.37 (0.22-0.61), respectively (P for trend <0.001). After adjusting for age, sex, and diabetes, the score was associated with hypertension risk (P for trend = 0.005). Compared with a lifestyle score of 0, the adjusted OR for hypertension for participants with a score of 5 was 0.46 (0.26-0.80). CONCLUSIONS: The risk of hypertension is inversely related to the healthy lifestyle score. This reinforces the need to address lifestyle to reduce the risk of hypertension.

Self-Templating-Oriented Manipulation of Ultrafine Pt3 Cu Alloyed Nanoparticles into Asymmetric Porous Bowl-Shaped Configuration for High-Efficiency Methanol Electrooxidation.

The precise and comprehensive manipulation of the component, size, and geometric nano-architecture of platinum-based electrocatalysts into porous and hollow structure can effectively impart the catalysts with substantially improved electrochemical performance, yet remain formidably challenging. Herein, a straightforward fabrication of porous platinum-copper alloyed nanobowls (abbreviated as Pt3 Cu NBs hereafter) assembled by ultrafine nanoparticles (≈2.9 nm) via a one-pot hydrothermal approach with the assistance of a structure-directing agent of N,N'-methylenebisacrylamide (MBAA) is reported. The involvement of MBAA plays a decisive role in the formation of Pt-MBAA complex solid nanospheres, which serve as the self-sacrificial reactive template for the deposition/growth of Pt3 Cu nanoparticles and the eventual formation of the asymmetric open-shelled nanobowls. Benefitting from the 3D sufficient accessibility of exterior/interior surfaces, high atom-utilization efficiency, and PtCu bimetallic alloy synergy, the self-supported Pt3 Cu NBs demonstrate remarkably enhanced activity, better anti-poisoning capability, and reinforced robustness for the methanol oxidation reaction (MOR) as compared with the commercial Pt black benchmark, exhibiting great application promises in practical fuel cell systems. It is envisaged that the innovative self-templated synthetic strategy outlined here may provide a perspective to design a range of porous bowl-shaped high-performance nanocatalysts.

Subjective health status: an easily available, independent, robust and significant predictive factor at the prometaphase of vaccination programs for the vaccination behavior of Chinese adults.

BACKGROUND: The World Health Organization (WHO) proposed COVID-19 vaccination as an emergent and important method to end the COVID-19 pandemic. Since China started vaccination programs in December 2020, vaccination has spread to provinces and municipalities nationwide. Previous research has focused on people's vaccination willingness and its influencing factors but has not examined vaccination behavior. We examine the effectiveness of psychosocial factors in predicting vaccination behavior. METHODS: A cross-sectional online survey was performed among Chinese adults on 8 May and 4 June 2021. The statistical analysis of the data included univariate analysis, receiver operator characteristics (ROC) analysis and ordinal multiclassification logistic regression model analysis. RESULTS: Of the 1300 respondents, 761 (58.5%) were vaccinated. Univariate analysis showed that a high education level and good subjective health status were protective factors for vaccination behavior, while suffering from chronic diseases was a risk factor. ROC analysis showed that subjective health status (AUC = 0.625, 95% CI: 0.594-0.656, P < 0.001) was the best predictor of vaccination behavior. Logistic regression analysis with subjective health status as a dependent variable indicated that older age, female sex, depression, neurasthenia, obsession, hypochondriasis and chronic disease were significant risk factors, while positive coping tendencies were a significant protective factor. CONCLUSION: Our study found a simple and effective marker, subjective health status, that can predict vaccination behavior. This finding can guide future epidemic prevention work.

Hydrogel composite scaffolds achieve recruitment and chondrogenesis in cartilage tissue engineering applications.

BACKGROUND: The regeneration and repair of articular cartilage remains a major challenge for clinicians and scientists due to the poor intrinsic healing of this tissue. Since cartilage injuries are often clinically irregular, tissue-engineered scaffolds that can be easily molded to fill cartilage defects of any shape that fit tightly into the host cartilage are needed. METHOD: In this study, bone marrow mesenchymal stem cell (BMSC) affinity peptide sequence PFSSTKT (PFS)-modified chondrocyte extracellular matrix (ECM) particles combined with GelMA hydrogel were constructed. RESULTS: In vitro experiments showed that the pore size and porosity of the solid-supported composite scaffolds were appropriate and that the scaffolds provided a three-dimensional microenvironment supporting cell adhesion, proliferation and chondrogenic differentiation. In vitro experiments also showed that GelMA/ECM-PFS could regulate the migration of rabbit BMSCs. Two weeks after implantation in vivo, the GelMA/ECM-PFS functional scaffold system promoted the recruitment of endogenous mesenchymal stem cells from the defect site. GelMA/ECM-PFS achieved successful hyaline cartilage repair in rabbits in vivo, while the control treatment mostly resulted in fibrous tissue repair. CONCLUSION: This combination of endogenous cell recruitment and chondrogenesis is an ideal strategy for repairing irregular cartilage defects.

Application of Maillard Reaction Products Derived Only from Enzymatically Hydrolyzed Sesame Meal to Enhance the Flavor and Oxidative Stability of Sesame Oil.

The low-temperature roasting of sesame oil has become increasingly popular because of its nutritional benefits; however, the flavor is reduced. In order to improve the quality of sesame oil without exogenous addition, sesame meal was hydrolyzed and further used to prepare Maillard reaction products (MRPs) while protease hydrolysis (PH) and glucoamylase-protease hydrolysis (GPH) were used, and their respective Maillard products (PHM and GPHM) were added in the oils for reducing sugar and total sugar content determination, free amino acid determination, and color and descriptive sensory analysis, as well as electronic nose, SPME-GC-MS, odor activity value, and oxidative stability analyses. Results showed that the MRPs could be produced using the enzymatically hydrolyzed sesame meal without exogenous addition, and the oil flavor blended with GPHM (GPHM-SO) was significantly (p < 0.05) improved with the best sensory quality. The composition of pyrazines (119.35 µg/mL), furans (13.95 µg/mL), and sulfur substances (6.25 µg/mL) contributed positively to sensory properties in GPHM-SO, and 2,5-dimethylpyrazine, 2,6-dimethylpyrazine, and 2,3-dimethylpyrazine were characterized as the key flavor compounds with odor activity values of 7.01, 14.80, and 31.38, respectively. Furthermore, the oxidative stability of the oil was significantly improved with the addition of MRPs, and the shelf life of GPHM-SO was predicted to be extended by 1.9 times more than that of the crude oil based on the accelerated oxidation fitting analysis. In general, the MRPs derived only from sesame meal can enhance the flavor and oxidative stability of sesame oil and can be applied in the oil industry.

Complement C5 activation promotes type 2 diabetic kidney disease via activating STAT3 pathway and disrupting the gut-kidney axis.

Diabetic kidney disease (DKD) is a severe DM complication. While complement C5 up-regulation and gut dysbiosis are found in T2DM, their roles in DKD are unclear. Here, we investigated the effect of C5 on the gut microbiota during DKD development. Renal C5a/C5a receptor (C5aR) expression changes were measured in T2DM patients and db/db mice. Db/db mice were treated with a C5aR antagonist (C5aRA), and renal function, gut microbiota and renal genome changes were analysed. The effects of C5a and short-chain fatty acids (SCFAs) on the signal transducer and activator of transcription 3 (STAT3) pathway were examined in vitro. C5a was up-regulated in glomerular endothelial cells (GECs) of T2DM patients and db/db mice. Although glucose and lipid metabolism were unchanged, C5aR blockade alleviated renal dysfunction, ECM deposition, macrophage infiltration and proinflammatory factor expression in db/db mice. C5aRA partly reversed the declines in gut microbiota diversity and abundance and gut SCFA levels in db/db mice. C5aRA down-regulated the expression of many immune response-related genes, such as STAT3, in db/db mouse kidneys. C5aRA and SCFAs suppressed C5a-induced STAT3 activation in human renal glomerular endothelial cells (HRGECs). Based on our results, C5 hyperactivation promotes DKD by activating STAT3 in GECs and impairing the gut-kidney axis, suggesting that this hyperactivation is a potential target for the treatment of DKD.

Indispensable role of mitochondria in maintaining the therapeutic potential of curcumin in acute kidney injury.

Acute kidney injury (AKI) is a serious disease for which effective therapeutic agents are required. The capacity of curcumin (CUR) to resolve renal inflammation/oxidative stress and mitochondrial damage has been reported, but crosstalk between these effects and the consequence of this crosstalk remain elusive. In this study, a hypoxia/reoxygenation (H/R)-induced renal tubular epithelial cell (TEC) injury model and an ischaemia/reperfusion (I/R)-induced mouse AKI model were treated with CUR with or without mitochondrial inhibitors (rotenone and FCCP) or siRNA targeting mitochondrial transcription factor A (TFAM). Changes in mitochondrial function, inflammation, the antioxidant system and related pathways were analysed. In vitro, CUR suppressed NFκB activation and cytokine production and induced NRF2/HO-1 signalling in TECs under H/R conditions. CUR treatment also reduced mitochondrial ROS (mtROS) and mitochondrial fragmentation and enhanced mitochondrial biogenesis, TCA cycle activity and ATP synthesis in damaged TECs. However, the anti-inflammatory and antioxidant effects of CUR in damaged TECs were markedly abolished upon mitochondrial disruption. In vivo, CUR treatment improved renal function and antioxidant protein (NRF2 and SOD2) expression and reduced oxidative stress (8-OHdG), tubular apoptosis/death, cytokine release/macrophage infiltration and mitochondrial damage in the kidneys of AKI mice. In vitro, the anti-inflammatory and antioxidant effects of CUR in damaged kidneys were impaired when mitochondrial function was disrupted. These results suggest mitochondrial damage is a driving factor of renal inflammation and redox imbalance. The therapeutic capacity of CUR in kidneys with AKI is primarily dependent on mitochondrial mechanisms; thus, CUR is a potential therapy for various diseases characterized by mitochondrial damage.

Repair of articular cartilage defect using adipose-derived stem cell-loaded scaffold derived from native cartilage extracellular matrix.

The purpose of this study was to investigate the feasibility of adipose-derived stem cells (ADSCs) as the seed cells of cartilage tissue engineering. ADSCs were isolated from adipose tissue that was harvested under sterile conditions from the inguen fold of porcines and cultured in vitro. Acellular cartilage extracellular matrix (ACECM) scaffolds of pigs were then constructed. Moreover, inflammatory cells, as well as cellular and humoral immune responses, were detected using hematoxylin and eosin staining staining, immunohistochemical staining, and western blot analysis. The results showed that the cartilage complex constructed by ADSCs and ACECM through tissue engineering successfully repaired the cartilage defect of the pig knee joint. The in vivo repair experiment showed no significant difference between chondrocytes, ADSCs, and induced ADSCs, indicating that ADSCs do not require in vitro induction and have the potential for chondrogenic differentiation in the environment around the knee joint. In addition, pig-derived acellular cartilage scaffolds possess no obvious immune inflammatory response when used in xenotransplantation. ADSCs may serve as viable seed cells for cartilage tissue engineering.

Meta-analysis of dose selection for budesonide in the treatment of Chinese patients with AECOPD.

OBJECTIVE: To systematically observe the curative efficacy and safety of budesonide inhalation in the treatment of acute exacerbation of chronic obstructive pulmonary disease, and to find a suitable dose of aerosolized budesonide for Chinese patients. METHODS: The meta-analysis study was conducted at Wenjiang District People's Hospital, Chengdu City, Sichuan Province, China from May 2019 to August 2019 and comprised randomised controlled trials of glucocorticoids for acute exacerbation of chronic obstructive pulmonary disease on the databases of the China National Knowledge Infrastructure, Wanfang Medical Network, PubMed, Medline, Embase, Cochrane Library and Google Scholar. Data extraction and quality evaluation of the studies was done and meta-analysis was then performed using RevMan 5.3. RESULTS: There were 25 studies identified that comprised 1959 patients. When the budesonide dose was 6mg/d and the methylprednisolone dose was 40mg/d, no significant difference was found in partial pressure of carbon dioxide and oxygen post-treatment (p>0.05). When the nebulized budesonide dose was <6mg/d, methylprednisolone was more effective than budesonide (p<0.05), while >6mg/d was not significantly more effective (p>0.05). At 4mg/d, the difference in the dyspnoea score post-treatment was significant (p<0.05). No significant difference was found in dyspnoea scores after intravenous glucocorticoid treatment when the dose was greater than or equal to 4mg/d. In terms of adverse reactions, the response rate of blood glucose, blood pressure, excitement, insomnia and stomach discomfort in the intravenous group was higher than that in the nebulised group (p<0.05). Oropharyngeal discomfort in the nebulized group was higher than that the intravenous group (p<0.05). CONCLUSIONS: The optimal dose for the inhalation of budesonide in Chinese patients was between 4mg/d and 6mg/d. The adverse reactions of nebulised budesonide were lower than those of intravenous methylprednisolone.

Peritoneal M2 macrophage transplantation as a potential cell therapy for enhancing renal repair in acute kidney injury.

Acute kidney injury (AKI) is a clinical condition that is associated with high morbidity and mortality. Inflammation is reported to play a key role in AKI. Although the M2 macrophages exhibit antimicrobial and anti-inflammatory activities, their therapeutic potential has not been evaluated for AKI. This study aimed to investigate the protective effect of peritoneal M2 macrophage transplantation on AKI in mice. The macrophages were isolated from peritoneal dialysates of mice. The macrophages were induced to undergo M2 polarization using interleukin (IL)-4/IL-13. AKI was induced in mice by restoring the blood supply after bilateral renal artery occlusion for 30 minutes. The macrophages were injected into the renal cortex of mice. The changes in renal function, inflammation and tubular proliferation were measured. The M2 macrophages were co-cultured with the mouse primary proximal tubular epithelial cells (PTECs) under hypoxia/reoxygenation conditions in vitro. The PTEC apoptosis and proliferation were analysed. The peritoneal M2 macrophages effectively alleviated the renal injury and inflammatory response in mice with ischaemia-reperfusion injury (IRI) and promoted the PTEC proliferation in vivo and in vitro. These results indicated that the peritoneal M2 macrophages ameliorated AKI by decreasing inflammatory response and promoting PTEC proliferation. Hence, the peritoneal M2 macrophage transplantation can serve as a potential cell therapy for renal diseases.

Thrombectomy for Stroke Caused by Cardiac Myxoma.

Large vessel occlusion stroke, caused by cardiac myxoma, is a rare and severe condition with poor neurological outcomes. Currently, there are no clear guidelines for treating patients with this condition. In our case, we describe a rare case of acute ischemic stroke caused by cardiac myxoma which was successfully treated with mechanical thrombectomy. At the end of a 6 months' follow-up, her National Institutes of Health Stroke Scale score (NIHSS) had significantly improved, from 20 to 3. This result is encouraging and suggests that mechanical thrombectomy may be a feasible therapy for large vessel occlusion stroke induced by cardiac myxoma emboli.

Mitochondrial ROS-induced lysosomal dysfunction impairs autophagic flux and contributes to M1 macrophage polarization in a diabetic condition.

Macrophage polarization toward the M1 phenotype and its subsequent inflammatory response have been implicated in the progression of diabetic complications. Despite adverse consequences of autophagy impairment on macrophage inflammation, the regulation of macrophage autophagy under hyperglycemic conditions is incompletely understood. Here, we report that the autophagy-lysosome system and mitochondrial function are impaired in streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-stimulated RAW 264.7 cells. Mitochondrial dysfunction promotes reactive oxygen species (ROS) production and blocks autophagic flux by impairing lysosome function in macrophages under hyperglycemic conditions. Conversely, inhibition of mitochondrial ROS by Mito-TEMPO prevents HG-induced M1 macrophage polarization, and its effect is offset by blocking autophagic flux. The role of mitochondrial ROS in lysosome dysfunction and M1 macrophage polarization is also demonstrated in mitochondrial complex I defective RAW 264.7 cells induced by silencing NADH:ubiquinone oxidoreductase subunit-S4 (Ndufs4). These findings prove that mitochondrial ROS plays a key role in promoting macrophage polarization to inflammatory phenotype by impairing autophagy-lysosome system, which might provide clue to a novel treatment for diabetic complications.

Co-culture systems-based strategies for articular cartilage tissue engineering.

Cartilage engineering facilitates repair and regeneration of damaged cartilage using engineered tissue that restores the functional properties of the impaired joint. The seed cells used most frequently in tissue engineering, are chondrocytes and mesenchymal stem cells. Seed cells activity plays a key role in the regeneration of functional cartilage tissue. However, seed cells undergo undesirable changes after in vitro processing procedures, such as degeneration of cartilage cells and induced hypertrophy of mesenchymal stem cells, which hinder cartilage tissue engineering. Compared to monoculture, which does not mimic the in vivo cellular environment, co-culture technology provides a more realistic microenvironment in terms of various physical, chemical, and biological factors. Co-culture technology is used in cartilage tissue engineering to overcome obstacles related to the degeneration of seed cells, and shows promise for cartilage regeneration and repair. In this review, we focus first on existing co-culture systems for cartilage tissue engineering and related fields, and discuss the conditions and mechanisms thereof. This is followed by methods for optimizing seed cell co-culture conditions to generate functional neo-cartilage tissue, which will lead to a new era in cartilage tissue engineering.

Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells: Characterization, Differentiation, and Applications in Cartilage Tissue Engineering.

Articular cartilage defects have very limited self-repair potential, and traditional bone marrow-stimulating therapy is not effective. Cartilage tissue engineering using bone marrow mesenchymal stem cells (BMSCs) and adipose tissue-derived mesenchymal stem cells (ADSCs) is considered an attractive treatment for cartilage lesions and osteoarthritis. However, studies proved that both BMSCs and ADSCs have their own advantages and shortcomings, including their sources, isolation methods, characterizations and differentiation potential. Understanding the properties and differences between ADSCs and BMSCs is important for clinical application in cartilage regeneration. This review provides an overview of BMSCs and ADSCs based on their characterization, isolation. Then, we summarized their differentiation potential in different experimental conditions. Finally, we discuss the applications of BMSCs and ADSCs in scaffold-free and scaffold-based cartilage tissue engineering. Based on different properties of BMSCs and ADSCs, and patient's physical condition, a more suitable therapeutic strategy can be selected.