Potato Resistant Starch Type 1 Promotes Obesity Linked with Modified Gut Microbiota in High-Fat Diet-Fed Mice.

Obesity has become a major disease that endangers human health. Studies have shown that dietary interventions can reduce the prevalence of obesity and diabetes. Resistant starch (RS) exerts anti-obesity effects, alleviates metabolic syndrome, and maintains intestinal health. However, different RS types have different physical and chemical properties. Current research on RS has focused mainly on RS types 2, 3, and 4, with few studies on RS1. Therefore, this study aimed to investigate the effect of RS1 on obesity and gut microbiota structure in mice. In this study, we investigated the effect of potato RS type 1 (PRS1) on obesity and inflammation. Mouse weights, as well as their food intake, blood glucose, and lipid indexes, were assessed, and inflammatory factors were measured in the blood and tissues of the mice. We also analyzed the expression levels of related genes using PCR, with 16S rRNA sequencing used to study intestinal microbiota changes in the mice. Finally, the level of short-chain fatty acids was determined. The results indicated that PRS1 promoted host obesity and weight gain and increased blood glucose and inflammatory cytokine levels by altering the gut microbiota structure.

Bioinspired nanovesicles released from injectable hydrogels facilitate diabetic wound healing by regulating macrophage polarization and endothelial cell dysfunction.

Wound healing is one of the major global health concerns in diabetic patients. Overactivation of proinflammatory M1 macrophages could lead to delayed wound healing in diabetes. 4-octyl itaconate (4OI), a derivative of the metabolite itaconate, has aroused growing interest recently on account of its excellent anti-inflammatory properties. Cell membrane coating is widely regarded as a novel biomimetic strategy to deliver drugs and inherit properties derived from source cells for biomedical applications. Herein, we fused induced pluripotent stem cell-derived endothelial cell (iEC) membrane together with M1 type macrophage membrane to construct a hybrid membrane (iEC-M) camouflaged 4OI nanovesicles (4OI@iEC-M). Furthermore, bioinspired nanovesicles 4OI@iEC-M are incorporated into the injectable, multifunctional gelatin methacryloyl hydrogels for diabetic wound repair and regeneration. In our study, bioinspired nanovesicles could achieve dual-targeted deliver of 4OI into both M1 macrophages and endothelial cells, thereby promoting macrophage polarization and protecting endothelial cells. With the synergistically anti-inflammatory and immunoregulative effects, the bioinspired nanovesicles-loaded hydrogels could facilitate neovascularization and exhibit superior diabetic wound repair and regeneration. Taken together, this study might provide a novel strategy to facilitate diabetic wound healing, thereby reducing limb amputation and mortality of diabetes.

Population pharmacokinetics of tacrolimus in Chinese adult liver transplant patients.

Tacrolimus is widely used in organ transplantation to prevent rejection. However, the narrow therapeutic window and the large inter-and intra-individual variability in the pharmacokinetics (PK) of tacrolimus make it difficult for individualization of dosing. This study aimed at developing a population pharmacokinetic model for estimating the oral clearance of tacrolimus in Chinese liver transplant patients, and identifying factors that contribute to the PK variability of tacrolimus. Data of 151 liver transplant patients who received tacrolimus were analyzed in this study. The population PK model was analyzed and the covariates including population demographic and biochemical characteristics, drug combination, and genetic polymorphism were explored using non-linear mixed-effects modeling approach. A single-compartment population PK model was developed, and the final model was CL/F = (14.6-2.38 × cytochrome P450 (CYP) 3A5-3.72 × WZC+1.04 × (POD/9)+2.48 × COR) × Exp(ηi ), where CYP3A5 was 1 for CYP3A5*3/*3, Wuzhi Capsule (WZC) was 1 when patients took tacrolimus combined with WZC, otherwise it was 0, corticosteroids (COR) was 1 when patients take tacrolimus combined with COR, otherwise, it was 0, POD was the post-operative day. Visual inspection and bootstrap indicated that the final model was stable and robust. In this study, we developed the first tacrolimus population PK model in Chinese adult liver transplant patients. We first determined the influence of WZC on tacrolimus in these people, which could provide useful PK information for the drug combination of tacrolimus and WZC. We also revealed the influence of genetic polymorphism of CYP3A5, POD, and a combination of COR on tacrolimus PK. Therefore, these significant factors should be taken into consideration in optimizing dosage regimens.

Effect of hepar-protecting Wuzhi capsule on pharmacokinetics and dose-effect character of tacrolimus in healthy volunteers.

Wuzhi capsule (WZC), a preparation of Fructus Schisandra sphenanthera extract, has been used widely for the treatment of viral and drug-induced hepatitis in China. This study aimed to determine the pharmacokinetic parameters of tacrolimus (TAC) when co-administered with WZC and the dose-effect of WZC on tacrolimus in healthy volunteers. The effect of an increased dosage of WZC (1, 2, 6, and 8 capsules once daily) on the relative oral exposure of tacrolimus was assessed to explore the dose-response relationship between WZC and tacrolimus using bioanalysis, pharmacokinetic, and genotypical analyses. The influence of CYP3A5 and MDR1 genetic polymorphisms on the WZC dose was elucidated by maintaining the Ctrough of tacrolimus in Chinese healthy volunteers. When co-administered with WZC, the Tmax of tacrolimus was increased significantly while the apparent oral clearance was decreased. The plasma tacrolimus level in volunteers with high CYP3A5 expression was much lower than that in those with mutant CYP3A5. However, polymorphisms of MDR1 exon26 C3435T, exon21 G2677T/A, and exon12 C1236T were not associated with plasma tacrolimus levels. Our findings provide important information on interactions between modern medications and herbal products, thus facilitating a better usage of tacrolimus in patients receiving WZC.

Two new xanthones, a new lignin, and twenty phenolic compounds from Smilax china and their NO production inhibitory activities.

Two new xanthones smilone A (1), smilone B (2), and a new lignin smilgnin A (3) were isolated from the rhizomes of Smilax china L., together with three known xanthones (4-6), four lignins (7-10), two flavones (11, 12), two stilbenoids (13, 14), and ten organic phenoloids (15-24). Of them, compounds 4-6 were isolated from the genus Smilax for the first time. The structures of 1-24 were elucidated by the extensive analysis of spectral data and compared with the literature. All compounds were evaluated for their inhibitory effects against LPS-induced NO production in RAW264.7 macrophages. Among them, compound 24 exhibited significant inhibitory activity against NO production (IC50 = 1.26 µM), while compounds 3, 6, and 7 showed weak activities at the concentration of 50 µM.[Formula: see text].

Prognostic and diagnostic significance of circRNAs expression in lung cancer.

Circular RNAs (circRNAs) have spurred considerable interest in numerous tumors. We aimed to investigate the clinical, prognostic, and diagnostic roles of circRNAs in human lung cancer. We systematically searched PubMed, Web of Science, EMBASE, Scopus, CBM, and the Cochrane Library databases up to July 24, 2018. Eligible studies about the relationship between circRNAs expression and clinical, prognostic, and diagnostic outcomes in patients with lung cancer were in our study. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were to investigate clinical parameters, and hazard ratios (HRs) and 95% CIs to estimate overall survival (OS). A total of 23 relevant studies were eligible, with 15 on clinicopathological features, 14 on prognosis, and six on diagnosis. For clinical features, high expression of oncogenic circRNAs was remarkably related to poor clinical parameters. Whereas, the results of tumor-suppressor circRNAs were the complete opposite. For the prognostic roles, oncogenic circRNAs had an unfavorable impact on overall survival (OS: HR = 3.24, 95% Cl: 2.70-3.77), and elevated level of tumor-suppressor circRNAs was correlated with longer survival (OS: HR = 0.57, 95% Cl: 0.43-0.70). For the diagnostic values, the pooled result showed an area under the curve (AUC) of 0.86, with 77% sensitivity and 81% specificity in distinguishing patients with lung cancer from healthy ones. The above results suggested that circRNAs have the potential to be novel indicators for prognostic and diagnostic evaluation of patients with lung cancer.

Prognostic value of prognostic nutritional index and systemic immune-inflammation index in patients with osteosarcoma.

The aim of this study was to evaluate the relationship between prognostic nutritional index (PNI) and systemic immune-inflammation index (SII) and clinical features and prognosis of osteosarcoma patients. We retrospectively investigated 126 patients with surgery for osteosarcoma between 2012 and 2018 at our hospital. The preoperative PNI was calculated as albumin level (g/L) + 5 × total lymphocyte count (10 9 /L). The SII was defined as platelet × neutrophil/lymphocyte counts. The optimal cut-off values for PNI and SII were evaluated with receiver operating curve analysis. Clinical features and PNI and SII were tested with the χ 2 test. The effects of PNI and SII on overall survival (OS) was investigated by Kaplan-Meier method and Cox proportional hazards model. A low preoperative PNI was remarkably correlated with tumor size, Enneking stage, pathological fracture, local recurrence, metastasis, and neoadjuvant chemotherapy ( p < 0.05). Whereas, a high SII was significantly associated with tumor size, histological type, Enneking stage, and neoadjuvant chemotherapy ( p < 0.05). There was a significant negative relationship between the PNI and SII ( r = 0.384; p < 0.001). For univariate analyses, the results revealed that tumor size, local recurrence, metastasis, PNI, and SII were predictors of OS ( p < 0.05). In multivariate analyses, local recurrence ( p = 0.010), metastasis ( p < 0.001), PNI ( p < 0.001), and SII ( p = 0.029) as independent prognostic factors were significantly correlated with OS. This study suggested that PNI and SII could be important prognostic parameters for patients with osteosarcoma.

Association between GDF5 rs143383 genetic polymorphism and musculoskeletal degenerative diseases susceptibility: a meta-analysis.

BACKGROUND: Several studies have assessed the association between GDF5 rs143383 polymorphism and the susceptibility of musculoskeletal degenerative diseases, such as intervertebral disc degeneration (IDD) and osteoarthritis (OA), but the results are inconsistent. The aim of our study was to evaluate the association between them comprehensively. METHODS: A systematical search was conducted on PubMed, Scopus, Web of Science (WOS), Embase, and the Cochrane Library databases updated to April 20, 2018. Eligible studies about polymorphisms in GDF5 gene and risk of IDD or OA were included. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were utilized. RESULTS: Fifteen studies with a total of 5915 cases and 12,252 controls were finally included in our study. Meta-analysis of GDF5 rs143383 polymorphism was statistically associated with increased risk of musculoskeletal degenerative diseases under each genetic model (allele model: OR = 1.32, 95% CI 1.19-1.48, P = 0.000; homozygote model: OR = 1.80, 95%CI 1.49-2.16, P = 0.000; heterozygote model: OR = 1.37, 95%CI 1.21-1.55, P = 0.000; dominant model: OR = 1.56, 95%CI 1.39-1.75, P = 0.000; recessive model: OR = 1.39, 95%CI 1.20-1.60, P = 0.000). Stratified analyses based on disease type showed a significant association between the GDF5 rs143383 polymorphism and increased risk of IDD and OA under all genetic models studied. When stratified with ethnicity, pooled outcomes revealed that this polymorphism was significantly related with increased risk of musculoskeletal degenerative diseases in both Asian and Caucasian populations under all genetic models studied. CONCLUSIONS: The present study suggested that GDF5 rs143383 polymorphism was significantly associated with susceptibility to musculoskeletal degenerative diseases.

Beneficial effect of compound essential oil inhalation on central fatigue.

BACKGROUNDS: Although the physical and mental enhancement effect of essential oils have been proved, the beneficial effect of essential oil in central fatigue remains unclear. In this study, we extracted essential oils from nine aromatic plants to make a compound essential oil, and detected the therapeutic effect of central fatigue by daily aerial diffusion. METHODS: Thirty-three rats were randomly and equally divided into control group, chronic sleep deprivation group, and compound essential oil inhalation group. Central fatigue was generated by chronic sleep deprivation. RESULTS: After 21-day various interferences, it is found that the sleep deprivation rats showed an evident decrease in physical endurance, negative emotion, and cognitive dysfunction compared with the control group, and the group that treated with the compound essential oil behaved significantly better than central fatigue group. CONCLUSION: We concluded that this formula of essential oils could alleviate central fatigue on rats, and our study provides a new direction of application of aromatic therapy, which could be expanded to insomnia, depression and other healthy issue in the further research.

Identification of Alkaloids from Corydalis yanhusuo W. T. Wang as Dopamine D1 Receptor Antagonists by Using CRE-Luciferase Reporter Gene Assay.

Corydalis yanhusuo W. T. Wang (C. yanhusuo) has been traditionally used for drug addiction and pain relief in China. In our previous study, we showed that the extract of C. yanhusuo blocks dopamine receptors, demonstrating that its pharmacological activities are mostly due to the antagonistic effects of some of its components at dopamine receptors. As part of our ongoing project on C. yanhusuo, the aim of the present study is to establish a high-throughput and low-cost screening assay system and test the abilities of the isolated alkaloids from C. yanhusuo to inhibit dopamine-induced dopamine D1 receptor activity. By using our established cyclic adenosine monophosphate (cAMP)-response element (CRE)-luciferase reporter gene assay system, we identified eight alkaloids from C. yanhusuo with D1 receptor antagonistic activities. We next validated the activities of these compounds using fluorometric imaging plate reader (FLIPR) assay by measuring the intracellular Ca2+ change. Six out of eight compounds, including tetrahydropalmatine, corydaline, 13-methyldehydrocorydalmine, dehydrocorybubine, dehydrocorydaline, and columbamine, can be confirmed for their inhibitory activities. The dopamine-receptor-antagonistic effects of four compounds, including 13-methyldehydrocorydalmine, dehydrocorydaline, columbamine, and corydaline, are reported for the first time. The present study provides an important pharmacological basis to support the traditional use of C. yanhusuo in China.

Anti-Inflammatory Activities of Compounds Isolated from the Rhizome of Anemarrhena asphodeloides.

Fifteen unreported compounds in Anemarrhena asphodeloides, iriflophene (3), hostaplantagineoside C (7), tuberoside G (8), spicatoside B (9), platycodin D (14), platycoside A (15), platycodin D2 (16), polygalacin D2 (17), platycodin D3 (18), isovitexin (20), vitexin (21), 3,4-dihydroxyallylbenzene-3-O-α-l-rhamnopyranosyl(1→6)-ß-d-glucopyranoside (22), iryptophan (24), adenosine (25), α-d-Glucose monoallyl ether (26), together with eleven known compounds (1, 2, 4⁻6, 10⁻13, 19 and 23), were isolated from the rhizomes of Anemarrhena asphodeloides. The chemical structures of these compounds were characterized using HRMS and NMR. The anti-inflammatory activities of the compounds were evaluated by investigating their ability to inhibit LPS-induced NO production in N9 microglial cells. Timosaponin BIII (TBIII) and trans-hinokiresinol (t-HL) exhibited significant inhibitory effects on the NO production in a dose-dependent manner with IC50 values of 11.91 and 39.08 µM, respectively. Immunoblotting demonstrated that TBIII and t-HL suppressed NO production by inhibiting the expressions of iNOS in LPS-stimulated N9 microglial cells. Further results revealed that pretreatment of N9 microglial cells with TBIII and t-HL attenuated the LPS-induced expression tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) at mRNAs and protein levels. Moreover, the activation of nuclear factor-κB (NF-κB) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways were inhibited by TBIII and t-HL, respectively. Our findings indicate that the therapeutic implication of TBIII and t-HL for neurogenerative disease associated with neuroinflammation.

Macrophage membrane-camouflaged biomimetic nanovesicles for targeted treatment of arthritis.

Arthritis has become the most common joint disease globally. Current attention has shifted towards preventing the disease and exploring pharmaceutical and surgical treatments for early-stage arthritis. M2 macrophages are known for their anti-inflammatory properties and their ability to support cartilage repair, offering relief from arthritis. Whereas, it remains a great challenge to promote the beneficial secretion of M2 macrophages to prevent the progression of arthritis. Therefore, it is warranted to investigate new strategies that could use the functions of M2 macrophages and enhance its therapeutic effects. This review aims to explore the macrophage cell membrane-coated biomimetic nanovesicles for targeted treatment of arthritis such as osteoarthritis (OA), rheumatoid arthritis (RA), and gouty arthritis (GA). Cell membrane-camouflaged biomimetic nanovesicle has attracted increasing attention, which successfully combine the advantages and properties of both cell membrane and delivered drug. We discuss the roles of macrophages in the pathophysiology and therapeutic targets of arthritis. Then, the common preparation strategies of macrophage membrane-coated nanovesicles are concluded. Moreover, we investigate the applications of macrophage cell membrane-camouflaged nanovesicles for arthritis, such as OA, RA, and GA. Taken together, macrophage cell membrane-camouflaged nanovesicles hold the tremendous prospect for biomedical applications in the targeted treatment of arthritis.

Replicating human characteristics: A promising animal model of central fatigue.

Central fatigue is a common pathological state characterized by psychological loss of drive, lack of appetite, drowsiness, and decreased psychic alertness. The mechanism underlying central fatigue is still unclear, and there is no widely accepted successful animal model that fully represents human characteristics. We aimed to construct a more clinically relevant and comprehensive animal model of central fatigue. In this study, we utilized the Modified Multiple Platform Method (MMPM) combined with alternate-day fasting (ADF) to create the animal model. The model group rats are placed on a stationary water environment platform for sleep deprivation at a fixed time each day, and they were subjected to ADF treatment. On non-fasting days, the rats were allowed unrestricted access to food. This process was sustained over a period of 21 days. We evaluated the model using behavioral assessments such as open field test, elevated plus maze test, tail suspension test, Morris water maze test, grip strength test, and forced swimming test, as well as serum biochemical laboratory indices. Additionally, we conducted pathological observations of the hippocampus and quadriceps muscle tissues, transmission electron microscope observation of mitochondrial ultrastructure, and assessment of mitochondrial energy metabolism and oxidative stress-related markers. The results revealed that the model rats displayed emotional anomalies resembling symptoms of depression and anxiety, decreased exploratory behavior, decline in learning and memory function, and signs of skeletal muscle fatigue, successfully replicating human features of negative emotions, cognitive decline, and physical fatigue. Pathological damage and mitochondrial ultrastructural alterations were observed in the hippocampus and quadriceps muscle tissues, accompanied by abnormal mitochondrial energy metabolism and oxidative stress in the form of decreased ATP and increased ROS levels. In conclusion, our ADF+MMPM model comprehensively replicated the features of human central fatigue and is a promising platform for preclinical research. Furthermore, the pivotal role of mitochondrial energy metabolism and oxidative stress damage in the occurrence of central fatigue in the hippocampus and skeletal muscle tissues was corroborated.

Spatiotemporal dynamics of bacterioplankton communities in the estuaries of two differently contaminated coastal areas: Composition, driving factors and ecological process.

Seasonal variations of environmental parameters usually lead to considerable changes in microbial communities. Nevertheless, the specific response patterns of these communities in coastal areas subjected to different levels of contamination remain unclear. Our results revealed notable fluctuations in the bacterioplankton community both seasonally and spatially, with seasonal variations being particularly significant. The diversity and composition of bacterioplankton communities in the estuaries varied significantly across seasons and between seas. Some bacterial phyla that were highly abundant in the dry season (e.g., Patescibacteria and Epsilonbacteraeota) were almost absent in the wet season. Furthermore, the network analysis revealed that the bacterioplankton networks were more complex during the wet season than in the dry season. In the wet season, the estuarine bacterioplankton network in the Yellow Sea region was more complex and stable, while the opposite was true in the dry season. According to the neutral community model, stochastic processes played a more significant role in the formation of bacterioplankton communities during the wet season than during the dry season. Estuarine bacterioplankton communities in the Yellow Sea region were more affected by stochastic processes compared to those in the Bohai Sea. In summary, in the estuaries of two differently contaminated coastal areas, the seasonal increase in nutrient levels enhanced the deterministic processes and network complexity of the bacterioplankton communities.

Stem cell-based drug delivery strategy for skin regeneration and wound healing: potential clinical applications.

Stem cell-based therapy is widely accepted to be a promising strategy in tissue regenerative medicine. Nevertheless, there are several obstacles to applying stem cells in skin regeneration and wound healing, which includes determining the optimum source, the processing and administration methods of stem cells, and the survival and functions of stem cells in wound sites. Owing to the limitations of applying stem cells directly, this review aims to discuss several stem cell-based drug delivery strategies in skin regeneration and wound healing and their potential clinical applications. We introduced diverse types of stem cells and their roles in wound repair. Moreover, the stem cell-based drug delivery systems including stem cell membrane-coated nanoparticles, stem cell-derived extracellular vesicles, stem cell as drug carriers, scaffold-free stem cell sheets, and stem cell-laden scaffolds were further investigated in the field of skin regeneration and wound healing. More importantly, stem cell membrane-coating nanotechnology confers great advantages compared to other drug delivery systems in a broad field of biomedical contexts. Taken together, the stem cell-based drug delivery strategy holds great promise for treating skin regeneration and wound healing.

Overcoming T Cell Exhaustion in Tumor Microenvironment via Immune Checkpoint Modulation with Nano-Delivery Systems for Enhanced Immunotherapy.

Immune checkpoint blockade (ICB) therapy for tumors has arisen in growing interest. However, the low response rate of tumors to ICB is mainly attributed to the inhibitory infiltration of immune cells in the tumor microenvironment (TME). Despite the promising benefits of ICB, the therapeutic effects of antibodies are dependent on a high dose and long-term usage in the clinic, thereby leading to immune-related adverse effects. Accordingly, ICB combined with nano-delivery systems could be used to overcome T cell exhaustion, which reduces the side effects and the usage of antibodies with higher response rates in patients. In this review, the authors aim to overcome T cell exhaustion in TME via immune checkpoint modulation with nano-delivery systems for enhanced immunotherapy. Several strategies are summarized to combine ICB and nano-delivery systems to further enhance immunotherapy: a) expressing immune checkpoint on the surface of nano-delivery systems; b) loading immune checkpoint inhibitors into nano-delivery systems; c) loading gene-editing technology into nano-delivery systems; and d) nano-delivery systems mediated immune checkpoint modulation. Taken together, ICB combined with nano-delivery systems might be a promising strategy to overcome T cell exhaustion in TME for enhanced immunotherapy.

Macrophage membrane-coated nanovesicles for dual-targeted drug delivery to inhibit tumor and induce macrophage polarization.

Background: Immunosuppressive M2 macrophages in the tumor microenvironment (TME) can mediate the therapeutic resistance of tumors, and seriously affect the clinical efficacy and prognosis of tumor patients. This study aims to develop a novel drug delivery system for dual-targeting tumor and macrophages to inhibit tumor and induce macrophage polarization. Methods: The anti-tumor effects of methyltransferase like 14 (METTL14) were investigated both in vitro and in vivo. The underlying mechanisms of METTL14 regulating macrophages were also explored in this study. We further constructed the cyclic (Arg-Gly-Asp) (cRGD) peptide modified macrophage membrane-coated nanovesicles to co-deliver METTL14 and the TLR4 agonist. Results: We found that METTL14 significantly inhibits the growth of tumor in vitro. METTL14 might downregulate TICAM2 and inhibit the Toll-like receptor 4 (TLR4) pathway of macrophages, meanwhile, the combination of METTL14 and the TLR4 agonist could induce M1 polarization of macrophages. Macrophage membrane-coated nanovesicles are characterized by easy modification, drug loading, and dual-targeting tumor and macrophages, and cRGD modification can further enhance its targeting ability. It showed that the nanovesicles could improve the in vivo stability of METTL14, and dual-target tumor and macrophages to inhibit tumor and induce M1 polarization of macrophages. Conclusions: This study anticipates achieving the dual purposes of tumor inhibition and macrophage polarization, and providing a new therapeutic strategy for tumors.

LncRNA MEG3 promotes chemosensitivity of osteosarcoma by regulating antitumor immunity via miR-21-5p/p53 pathway and autophagy.

This study aimed to investigate the role of long non-coding RNA maternally expressed gene 3 (lncRNA MEG3) in chemosensitivity of osteosarcoma (OS), and to reveal the possible underlying mechanisms. In this study, we found that the expression of lncRNA MEG3 was significantly lower in OS tissues and cell lines. Furthermore, lncRNA MEG3 overexpression enhanced chemosensitivity of OS by inhibiting cell proliferation, migration, autophagy, and promoting antitumor immunity. LncRNA MEG3 functioned as miR-21-5 sponge to regulate p53 expression in OS. Mechanically, lncRNA MEG3 promoted OS chemosensitivity by regulating antitumor immunity via miR-21-5p/p53 pathway and autophagy. Collectively, this study provided the evidence that lncRNA MEG3 might be a promising therapeutic target for OS chemoresistance.

Biomimetic cell membrane-coated nanocarriers for targeted siRNA delivery in cancer therapy.

Small interfering RNA (siRNA) therapeutics for cancer are a focus of increasing research interest. However, the major obstacle to their clinical application is the targeted delivery of siRNA to cancer cells at desirable levels. Cell membrane-coated nanocarriers have the advantage of combining the properties of both cell membranes and nanoparticles (NPs). In this review, we highlight the most common RNAi therapeutics and the extracellular and intracellular barriers to siRNA delivery. Moreover, we discuss clinical applications of different cell membrane-coated nanocarriers for targeted siRNA delivery, including cancer cell membranes (CCMs), platelet membranes, erythrocyte membranes, stem cell membranes, exosome membranes, and hybrid membranes. Taken together, biomimetic cell membrane-coated nanotechnology is a promising strategy for targeted siRNA delivery for cancer treatment.

Dapagliflozin-Loaded Exosome Mimetics Facilitate Diabetic Wound Healing by HIF-1α-Mediated Enhancement of Angiogenesis.

Angiogenesis plays a critical role in diabetic wound healing. However, no effective strategies have been developed to target endothelial cells (ECs) to facilitate diabetic wound healing. Dapagliflozin (DA) as a sodium-glucose linked transporter 2 (SGLT2) inhibitor, may promote neovascularization in diabetic mice via HIF-1α-mediated enhancement of angiogenesis. Here, the bioinspired nanovesicles (NVs) prepared from induced pluripotent stem cells-derived ECs through an extrusion approach are reported, which can function as exosome mimetics to achieve targeted deliver of DA. Abundant membrane C-X-C motif chemokine receptor 4 conferred the EC-targeting ability of these NVs and the endothelial homology facilitated the accumulation in ECs. Furthermore, these DA-loaded induced pluripotent stem cells (iPSC)-EC NVs can facilitate angiogenesis and diabetic wound healing by HIF-1α/VEGFA pathway. Taken together, this study indicated that targeting ECs and regulating angiogenesis may be a promising strategy for the treatment of diabetic wound healing.