The treatment efficacy of bone tissue engineering strategy for repairing segmental bone defects under diabetic condition.

Background: Diabetes mellitus is a systematic disease which exert detrimental effect on bone tissue. The repair and reconstruction of bone defects in diabetic patients still remain a major clinical challenge. This study aims to investigate the potential of bone tissue engineering approach to improve bone regeneration under diabetic condition. Methods: In the present study, decalcified bone matrix (DBM) scaffolds were seeded with allogenic fetal bone marrow-derived mesenchymal stem cells (BMSCs) and cultured in osteogenic induction medium to fabricate BMSC/DBM constructs. Then the BMSC/DBM constructs were implanted in both subcutaneous pouches and large femoral bone defects in diabetic (BMSC/DBM in DM group) and non-diabetic rats (BMSC/DBM in non-DM group), cell-free DBM scaffolds were implanted in diabetic rats to serve as the control group (DBM in DM group). X-ray, micro-CT and histological analyses were carried out to evaluate the bone regenerative potential of BMSC/DBM constructs under diabetic condition. Results: In the rat subcutaneous implantation model, quantitative micro-CT analysis demonstrated that BMSC/DBM in DM group showed impaired bone regeneration activity compared with the BMSC/DBM in non-DM group (bone volume: 46 ± 4.4 mm3 vs 58.9 ± 7.15 mm3, *p < 0.05). In the rat femoral defect model, X-ray examination demonstrated that bone union was delayed in BMSC/DBM in DM group compared with BMSC/DBM in non-DM group. However, quantitative micro-CT analysis showed that after 6 months of implantation, there was no significant difference in bone volume and bone density between the BMSC/DBM in DM group (199 ± 63 mm3 and 593 ± 65 mg HA/ccm) and the BMSC/DBM in non-DM group (211 ± 39 mm3 and 608 ± 53 mg HA/ccm). Our data suggested that BMSC/DBM constructs could repair large bone defects in diabetic rats, but with delayed healing process compared with non-diabetic rats. Conclusion: Our study suggest that biomaterial sacffolds seeded with allogenic fetal BMSCs represent a promising strategy to induce and improve bone regeneration under diabetic condition.

The role and mechanism of engineered nanovesicles derived from hair follicle mesenchymal stem cells in the treatment of UVB-induced skin photoaging.

BACKGROUND: Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) are effective in the treatment of skin photoaging; however, their low yield and functional decline with passage progression limit their clinical application. Cell-derived nanovesicles (CNVs) are potential alternatives that can address the limitations of EVs derived from MSCs and are conducive to clinical transformations. Hair follicle mesenchymal stem cells (HFMSCs), a type of MSCs, have demonstrated the function of repairing skin tissues; nevertheless, the efficacy of CNVs from HFMSCs (HFMSC-CNVs) in the treatment of skin photoaging remains unclear. Therefore, ultraviolet radiation B (UVB)-induced photoaging nude mice and human dermal fibroblasts (HDFs) were used as experimental models to investigate the therapeutic effects of HFMSC-CNVs in photoaging models. METHODS: HFMSC-CNVs were successfully prepared using the mechanical extrusion method. UVB-induced nude mice and HDFs were used as experimental models of photoaging. Multiple approaches, including hematoxylin-eosin and Masson staining, immunohistochemistry, immunofluorescence, detection of reactive oxygen species (ROS), flow cytometry, western blotting, and other experimental methods, were combined to investigate the possible effects and mechanisms of HFMSC-CNVs in the treatment of skin photoaging. RESULTS: In the nude mouse model of skin photoaging, treatment with HFMSC-CNVs reduced UVB-induced skin wrinkles (p < 0.05) and subcutaneous capillary dilation, alleviated epidermis thickening (p < 0.001), and dermal thinning (p < 0.001). Furthermore, HFMSC-CNVs upregulated proliferating cell nuclear antigen (PCNA) expression (p < 0.05) and decreased the levels of ROS, ß-galactosidase (ß-Gal), and CD86 (p < 0.01). In vitro experiments, treatment with HFMSC-CNVs enhanced the cellular activity of UVB-exposed HDFs (p < 0.05), and reduced ROS levels and the percentage of senescent cells (p < 0.001), and alleviated cell cycle arrest (p < 0.001). HFMSC-CNVs upregulated the expression of Collagen I (Col I), SMAD2/3, transforming growth factor beta (TGF-ß), catalase (CAT), glutathione peroxidase-1 (GPX-1), and superoxide dismutase-1 (SOD-1) (p < 0.05) and downregulated the expression of cycle suppressor protein (p53), cell cycle suppressor protein (p21), and matrix metalloproteinase 3 (MMP3) (p < 0.05). CONCLUSION: Conclusively, the anti-photoaging properties of HFMSC-CNVs were confirmed both in vivo and in vitro. HFMSC-CNVs exert anti-photoaging effects by alleviating cell cycle arrest, decreasing cellular senescence and macrophage infiltration, promoting cell proliferation and extracellular matrix (ECM) production, and reducing oxidative stress by increasing the activity of antioxidant enzymes.

Viral infection dynamics with immune chemokines and CTL mobility modulated by the infected cell density.

We study a viral infection model incorporating both cell-to-cell infection and immune chemokines. Based on experimental results in the literature, we make a standing assumption that the cytotoxic T lymphocytes (CTL) will move toward the location with more infected cells, while the diffusion rate of CTL is a decreasing function of the density of infected cells. We first establish the global existence and ultimate boundedness of the solution via a priori energy estimates. We then define the basic reproduction number of viral infection R 0 and prove (by the uniform persistence theory, Lyapunov function technique and LaSalle invariance principle) that the infection-free steady state E 0 is globally asymptotically stable if R 0 < 1 . When R 0 > 1 , then E 0 becomes unstable, and another basic reproduction number of CTL response R 1 becomes the dynamic threshold in the sense that if R 1 < 1 , then the CTL-inactivated steady state E 1 is globally asymptotically stable; and if R 1 > 1 , then the immune response is uniform persistent and, under an additional technical condition the CTL-activated steady state E 2 is globally asymptotically stable. To establish the global stability results, we need to prove point dissipativity, obtain uniform persistence, construct suitable Lyapunov functions, and apply the LaSalle invariance principle.

Cell-free fat extract promotes axon regeneration and retinal ganglion cells survival in traumatic optic neuropathy.

Injuries to axons within the central nervous system (CNS) pose a substantial clinical challenge due to their limited regenerative capacity. This study investigates the therapeutic potential of Cell-free fat extract (CEFFE) in CNS injury. CEFFE was injected intravitreally after the optic nerve was crushed. Two weeks post-injury, quantification of regenerated axons and survival rates of retinal ganglion cells (RGCs) were performed. Subsequently, comprehensive gene ontology (GO) an-notation elucidated the cellular origins and functional attributes of CEFFE components. Molecular mechanisms underlying CEFFE's therapeutic effects were explored through Western blotting (WB). Additionally, levels of inflammatory factors within CEFFE were determined using enzyme-linked immunosorbent assay (ELISA), and histological staining of microglia was conducted to assess its impact on neuroinflammation. CEFFE demonstrated a significant capacity to promote axon re-generation and enhance RGCs survival. GO annotation revealed the involvement of 146 proteins within CEFFE in axonogenesis and neurogenesis. WB analysis unveiled the multifaceted pathways through which CEFFE exerts its therapeutic effects. Elevated levels of inflammatory factors were detected through ELISA, and CEFFE exhibited a modulatory effect on microglial activation in the retinal tissue following optic nerve crush (ONC). The present study highlights the therapeutic promise of CEFFE in the management of CNS injuries, exemplified by its ability to foster axon regeneration and improve RGCs survival.

Interface Investigation on SiGe/Si Multilayer Structures: Influence of Different Epitaxial Process Conditions.

SiGe/Si multilayer is the core structure of the active area of gate-all-around field-effect transistors and semiconductor quantum computing devices. In this paper, high-quality SiGe/Si multilayers have been grown by a reduced-pressure chemical vapor deposition system. The effects of temperature, pressure, interface processing (dichlorosilane (SiH2Cl2, DCS) and hydrogen chloride (HCl)) on improving the transition thickness of SiGe to Si interfaces were investigated. The interface quality was characterized by transmission electron microscopy/atomic force microscopy/high-resolution X-ray diffraction methods. It was observed that limiting the migration of Ge atoms in the interface was critical for optimizing a sharp interface, and the addition of DCS was found to decrease the interface transition thickness. The change of the interfacial transition layer is not significant in the short treatment time of HCl. When the processing time of HCl is increased, the internal interface is optimized to a certain extent but the corresponding film thickness is also reduced. This study provides technical support for the acquisition of an abrupt interface and will have a very favorable influence on the performance improvement of miniaturized devices in the future.

Dynamic optimal allocation of medical resources: a case study of face masks during the first COVID-19 epidemic wave in the United States.

In this paper, we propose a two-group SIR epidemic model to simulate the outcome of the stay-at-home policy and the imposed face mask policy during the first COVID-19 epidemic wave in the United States. Then, we use a dynamic optimal control approach (with the objective of minimizing total deaths) to find the optimal dynamical distribution of face masks between healthcare workers and the general public. It is not surprising that all face masks should be solely reserved for healthcare workers if the supply is short. However, when the supply is indeed sufficient, our numerical study indicates that the general public should share a large portion of face masks at the beginning of the epidemic wave to dramatically reduce the death toll. This interesting result partially contradicts the guideline advised by the US Surgeon General and the Centers for Disease Control and Prevention (CDC) in March 2020. The optimality of this sounding CDC guideline highly depends on the supply level of face masks, which changes frequently; hence, it should be adjusted according to the supply of face masks.

The importance of quarantine: modelling the COVID-19 testing process.

We incorporate the disease state and testing state into the formulation of a COVID-19 epidemic model. For this model, the basic reproduction number is identified and its dependence on model parameters related to the testing process and isolation efficacy is discussed. The relations between the basic reproduction number, the final epidemic and peak sizes, and the model parameters are further explored numerically. We find that fast test reporting does not always benefit the control of the COVID-19 epidemic if good quarantine while awaiting test results is implemented. Moreover, the final epidemic and peak sizes do not always increase along with the basic reproduction number. Under some circumstances, lowering the basic reproduction number increases the final epidemic and peak sizes. Our findings suggest that properly implementing isolation for individuals who are waiting for their testing results would lower the basic reproduction number as well as the final epidemic and peak sizes.

Graphene Oxide/Gelatin Nanofibrous Scaffolds Loaded with N-Acetyl Cysteine for Promoting Wound Healing.

Purpose: We aimed to develop an antioxidant dressing material with pro-angiogenic potential that could promote wound healing. Gelatin (Gel) was selected to improve the biocompatibility of the scaffolds, while graphene oxide (GO) was added to enhance their mechanical property. The loaded N-Acetyl cysteine (NAC) was performing the effect of scavenging reactive oxygen species (ROS) at the wound site. Materials and Methods: The physicochemical and mechanical properties, NAC releases, and biocompatibility of the NAC-GO-Gel scaffolds were evaluated in vitro. The regeneration capability of the scaffolds was systemically investigated in vivo using the excisional wound-splinting model in mice. Results: The NAC-GO-Gel scaffold had a stronger mechanical property and sustainer NAC release ability than the single Gel scaffold, which resulted in a better capacity for cell proliferation and migration. Mice wound-splinting models revealed that the NAC-GO-Gel scaffold effectively accelerated wound healing, promoted re-epithelialization, enhanced neovascularization, and reduced scar formation. Conclusion: The NAC-GO-Gel scaffold not only promotes wound healing but also reduces scar formation, showing a great potential application for the repair of skin defects.

Viral dynamics with immune responses: effects of distributed delays and Filippov antiretroviral therapy.

In this paper, we propose a general viral infection model to incorporate two infection modes (virus-to-cell mode and cell-to-cell mode), the CTL immune response, and the distributed intracellular delays during the processes of viral infection, viral production, and CTLs recruitment. We investigate the existence, the uniqueness, and the global stability of three equilibria: infection-free equilibrium [Formula: see text], immune-inactivated equilibrium [Formula: see text] and immune-activated equilibrium [Formula: see text], respectively. We prove that the viral dynamics are determined by two threshold parameters: the basic reproduction number for infection [Formula: see text] and the basic reproduction number for immune response [Formula: see text]. We also numerically explore the viral dynamics beyond stability. We use bifurcation diagrams to show that increasing the delay in CTL immune cell recruitment can induce a switch in viral load from a stable constant level to sustained oscillations, and then back to a stable equilibrium. We also compare the contributions of the two infection modes to the total infection level and identify the key parameters that would affect the percentages of virus-to-cell infection and cell-to-cell infection. Finally, we explore how Filippov control can be applied in antiretroviral therapy to reduce the viral loads.

Electrospun flexible magnesium-doped silica bioactive glass nanofiber membranes with anti-inflammatory and pro-angiogenic effects for infected wounds.

Antibacterial, anti-inflammatory, and pro-angiogenic properties are prerequisites for dressing materials that accelerate the healing process of infected wounds. Herein, we report a magnesium-doped silica bioactive glass (SiO2/MgO) nanofiber membrane prepared by electrospinning. Our results demonstrate that this SiO2/MgO nanofiber membrane has good flexibility and hydrophilicity, which give it intimate contact with wound beds. In vitro assessments illustrate its good cytocompatibility and bioactivity that contribute to its robust cell proliferation and angiogenesis. It shows capacity in modulating the cellular inflammatory response of murine macrophages. In addition, in vitro assays prove its good antibacterial activity against both Gram-positive and Gram-negative strains. In a full-thickness skin defect inoculated with Staphylococcus aureus in mice, it effectively inhibits bacterial infection. Both gene expression and histological/immunohistochemical analyses confirmed the down-regulated pro-inflammatory factors, up-regulated anti-inflammatory factors, and enhanced angiogenesis. Taken together, these desirable properties work in concert to contribute to the rapid healing of infected wounds and make it a good candidate for wound dressing materials.

A New Class of Weighted CUSUM Statistics.

A change point is a location or time at which observations or data obey two different models: before and after. In real problems, we may know some prior information about the location of the change point, say at the right or left tail of the sequence. How does one incorporate the prior information into the current cumulative sum (CUSUM) statistics? We propose a new class of weighted CUSUM statistics with three different types of quadratic weights accounting for different prior positions of the change points. One interpretation of the weights is the mean duration in a random walk. Under the normal model with known variance, the exact distributions of these statistics are explicitly expressed in terms of eigenvalues. Theoretical results about the explicit difference of the distributions are valuable. The expansions of asymptotic distributions are compared with the expansion of the limit distributions of the Cramér-von Mises statistic and the Anderson and Darling statistic. We provide some extensions from independent normal responses to more interesting models, such as graphical models, the mixture of normals, Poisson, and weakly dependent models. Simulations suggest that the proposed test statistics have better power than the graph-based statistics. We illustrate their application to a detection problem with video data.

Diagnostic and predictive values of serum metabolic profiles in sudden sensorineural hearing loss patients.

Sudden sensorineural hearing loss (SSNHL) is an otologic emergency, and metabolic disturbance is involved in its pathogenesis. This study recruited 20 SSNHL patients and 20 healthy controls (HCs) and collected their serum samples. Serum metabolites were detected by liquid chromatography-mass spectrometry, and metabolic profiles were analyzed. All patients were followed up for 3 months and categorized into recovery and non-recovery groups. The distinctive metabolites were assessed between two groups, and their predictive values for hearing recovery were evaluated. Analysis results revealed that SSNHL patients exhibited significantly characteristic metabolite signatures compared to HCs. The top 10 differential metabolites were further analyzed, and most of them showed potential diagnostic values based on receiver operator characteristic (ROC) curves. Finally, 14 SSNHL patients were divided into the recovery group, and six patients were included in the non-recovery group. Twelve distinctive metabolites were observed between the two groups, and ROC curves demonstrated that N4-acetylcytidine, p-phenylenediamine, sphingosine, glycero-3-phosphocholine, and nonadecanoic acid presented good predictabilities in the hearing recovery. Multivariate analysis results demonstrated that serum N4-Acetylcytidine, sphingosine and nonadecanoic acid levels were associated with hearing recovery in SSNHL patients. Our results identified that SSNHL patients exhibited distinctive serum metabolomics signatures, and several serum biomarkers were proved to be potential in predicting hearing recovery. The discriminative metabolites might contribute to illustrating the mechanisms of SSNHL and provide possible clues for its treatments.

Cell-free fat extract protects septic lethality via restraining NLRP3 inflammasome activation.

BACKGROUND: Sepsis is a dysregulated host response to infection with high mortality and current management cannot reach optimal remission. Previous studies have shown that cell-free fat extract (CEFFE) is a kind of bioactive extraction from adipose tissues and exhibits a potent anti-inflammatory effect on wound healing and inflammatory diseases. However, the potential role of CEFFE in sepsis remains unclear. METHODS: CEFFE was extracted from healthy donors and was intraperitoneally injected into septic mice. The septic mice models were constructed using lipopolysaccharide (LPS), E. coli, and cecal ligation and puncture (CLP). The survival of septic mice was detected for 96 h and Kaplan-Meier analysis was used to analyze the differences of survival rates. Lung tissues that were collected from septic mice were subjected to HE staining to evaluate the extent of lung injury, and the mice serum was obtained for inflammasome-related cytokines detection. Moreover, peritoneal macrophages were extracted from C57 mice and treated with CEFFE and/or inflammasome activators. The level of IL-1ß, IL-18, IL-6, and TNF-α was detected by ELISA, and the activation of NLRP3 were evaluated by Western Blot. Total mtDNA and mitochondrial permeability transition pore were determined to explore the mitochondrial dysfunction in the activation of NLRP3 inflammasome with or without CEFEE. Coimmunoprecipitation (Co-IP) assays were performed to confirm the mechanism of NLRP3 activation induced by CEFFE. RESULTS: CEFFE significantly improved the survival of sepsis mice and alleviate sepsis-induced lung injury. Moreover, CEFFE significantly decreased the level of inflammasome-cytokines (IL-1ß and IL-18) but not the pro-inflammatory cytokines such as IL-6 and TNF-α. Moreover, CEFFE markedly suppressed the canonical activation of NLRP3 inflammasome without affecting inflammasomes NLRC4 and AIM2. Additionally, the non-canonical activation of NLRP3 inflammasome was significantly inhibited by CEFFE. CEFFE treatment attenuated the mtDNA outflow and the increase of mitochondrial permeability induced by both canonical and non-canonical pathway of NLRP3 inflammasome activation. The results of Co-IP assays revealed that CEFFE remarkably attenuated the oligomerization of ASC and inhibited the association between NLRP3 and ASC. CONCLUSION: Our study revealed that CEFFE could significantly alleviate sepsis-related injuries possibly by suppressing NLRP3 inflammasome activation. CEFFE was a promising approach for sepsis treatment.

Solving the initial value problem of ordinary differential equations by Lie group based neural network method.

To combine a feedforward neural network (FNN) and Lie group (symmetry) theory of differential equations (DEs), an alternative artificial NN approach is proposed to solve the initial value problems (IVPs) of ordinary DEs (ODEs). Introducing the Lie group expressions of the solution, the trial solution of ODEs is split into two parts. The first part is a solution of other ODEs with initial values of original IVP. This is easily solved using the Lie group and known symbolic or numerical methods without any network parameters (weights and biases). The second part consists of an FNN with adjustable parameters. This is trained using the error back propagation method by minimizing an error (loss) function and updating the parameters. The method significantly reduces the number of the trainable parameters and can more quickly and accurately learn the real solution, compared to the existing similar methods. The numerical method is applied to several cases, including physical oscillation problems. The results have been graphically represented, and some conclusions have been made.

Circ-FAT1 Up-Regulates FOSL2 Expression by Sponging miR-619-5p to Facilitate Colorectal Cancer Progression.

Circular RNA FAT atypical cadherin 1 (circ-FAT1) has been reported to play roles in colorectal cancer (CRC) development. Here, the purpose of this study was to investigate the function and mechanism of circ-FAT1 in CRC tumorigenesis and its potential value in the clinic. Levels of genes and proteins were examined by quantitative real-time polymerase chain reaction and Western blot. In vitro assays were conducted using cell counting kit-8 assay, 5-Ethynyl-2'-deoxyuridine assay, flow cytometry, transwell assay, and tube formation assay, respectively. The target relationship between miR-619-5p and circ-FAT1 or FOS-like antigen 2 (FOSL2) was verified by dual-luciferase reporter and RNA immunoprecipitation assays. In vivo assay was performed using a mouse subcutaneous xenograft model. Circ-FAT1 and FOSL2 were highly expressed in CRC tissues and cells. Functionally, knockdown of circ-FAT1 or FOSL2 suppressed CRC cell apoptosis, migration, invasion, and angiogenesis, but induced cell apoptosis in vitro. Mechanistically, circ-FAT1 acted as a sponge for miR-619-5p to up-regulate the expression of FOSL2, which was confirmed to be a target of miR-619-5p. A series of rescue experiments demonstrated that miR-619-5p inhibition or FOSL2 overexpression reversed the inhibitory action of circ-FAT1 silencing on CRC cell malignant phenotypes mentioned above. Pre-clinically, lentivirus-mediated circ-FAT1 knockdown inhibited the tumorigenesis of CRC xenografts in nude mice via regulating miR-619-5p and FOSL2. Circ-FAT1 knockdown repressed FOSL2 expression by sponging miR-619-5p to suppress CRC tumorigenesis, providing a potential approach for CRC therapeutics.

Exosomes Derived by SIRT1-Overexpressing Bone Marrow Mesenchymal Stem Cells Improve Pubococcygeus Muscle Injury in Rats.

BACKGROUND AND OBJECTIVES: To evaluate the effect of exosomes (Exos) derived from silent mating type information regulation 2 homolog 1 (SIRT1)-overexpressing human bone marrow mesenchymal stem cells (BMSCs) on the recovery of pubococcygeus muscle Injury. METHODS AND RESULTS: Exos isolated from SIRT1-overexpressing BMSCs (SIRT1/exos) were injected into a vaginal dilation-induced rat model of Stress urinary incontinence (SUI). The efficacy of Exos treatment on SUI was evaluated by determining the values of urodynamic parameters. The proliferation and differentiation of satellite cells (SCs) were examined by CCK-8 assay, Western blotting, and immunofluorescence staining. The mRNA and protein expression of molecules related to SC differentiation were detected by RT-qPCR and Western blotting, respectively. Treatment with SIRT1/exos significantly improved the values of abdominal leak point pressure (ALPP), maximum bladder volume (MBV), and estimated marginal mean in rats of SUI. Exposure of SIRT1/exos enhanced the proliferation, differentiation, and activation of SCs. Moreover, SIRT1/exos exhibited their positive effect on BMSCs by activating the ERK signaling. CONCLUSIONS: Our findings demonstrated that SIRT1/exos meliorated pubococcygeus muscle injury in rats by promoting ERK pathway, which may provide a novel cell-free therapeutic strategy for SUI.

Threshold dynamics of a nonlocal and delayed cholera model in a spatially heterogeneous environment.

A nonlocal and delayed cholera model with two transmission mechanisms in a spatially heterogeneous environment is derived. We introduce two basic reproduction numbers, one is for the bacterium in the environment and the other is for the cholera disease in the host population. If the basic reproduction number for the cholera bacterium in the environment is strictly less than one and the basic reproduction number of infection is no more than one, we prove globally asymptotically stability of the infection-free steady state. Otherwise, the infection will persist and there exists at least one endemic steady state. For the special homogeneous case, the endemic steady state is actually unique and globally asymptotically stable. Under some conditions, the basic reproduction number of infection is strictly decreasing with respect to the diffusion coefficients of cholera bacteria and infectious hosts. When these conditions are violated, numerical simulation suggests that spatial diffusion may not only spread the infection from high-risk region to low-risk region, but also increase the infection level in high-risk region.

First known case of successful pressure ulcer treatment in a lung transplant patient with post-COVID-19 pneumonia.

Given the current COVID-19 crisis, multiple clinical manifestations and related complications of COVID-19 disease, especially in lung transplant patients following post-COVID-19 pneumonia, are a major challenge. Herein, we report the therapeutic course of the first reported case of sacrococcyx pressure ulcers (PU) in a 65-year-old male COVID-19 patient who underwent lung transplantation and developed a PU following surgery. We used a combination of regulated negative pressure-assisted wound therapy system (RNPT, six treatment courses, five days per treatment course), a skin tension-relief system (an intraoperative aid in minimising wounds caused by sacrococcygeal PUs) and a gluteus maximus myocutaneous flap to repair sacrococcygeal wounds. This successfully treated case provides a reference point for the treatment of similar cases.

Adipose-derived mesenchymal stem cells from obese mice prevent body weight gain and hyperglycemia.

Changes that occur to the stem cell microenvironment with disease are a major consideration that may affect the behavior and potential therapeutic efficacy of mesenchymal stem cells (MSCs). The purpose of this study is to evaluate the effects of adipose-derived MSCs (ADSCs) from obese mice with hyperglycemia on body weight and glucose homeostasis. After 10 weeks of high-fat diet, mice were injected with phosphate-buffered saline (PBS) and ADSCs derived from normal mice (N-ADSCs) or obese mice (O-ADSCs), respectively. Mice fed with standard rodent chow were injected with PBS and served as normal controls. Obese mice treated with O-ADSCs showed less body weight gain than those receiving PBS or N-ADSCs. The mice that received ADSCs, especially O-ADSCs, also showed improvement in obesity-related hyperglycemia. In particular, the inguinal fat was reduced in obese mice receiving O-ADSCs compared with other groups, probably caused by the increased lipolysis of inguinal fat. Moreover, ADSC infusion restored insulin receptor (INSR) expression in the muscle of obese mice. Differential expression of the CD90 surface marker was slightly increased, while monocyte chemoattractant protein 1 (MCP-1) was reduced in O-ADSCs compared to N-ADSCs. These data provide a theoretical basis that autologous ADSCs from obese individuals may be more effective for treating obesity and related hyperglycemia.

Silk fibroin/poly-(L-lactide-co-caprolactone) nanofiber scaffolds loaded with Huangbai Liniment to accelerate diabetic wound healing.

Diabetic infection is a long-term complication difficult to cure. The skin of diabetic patients is prone to damage, the healing is slow after the injury, and the wound occurs repeatedly. Therefore, there is an urgent need to develop an effective method for treating diabetes wounds. In this study, we used the electrospinning technique to load Huangbai Liniment (Compound Phellodendron Liquid, CPL) into Silk fibroin (SF) /poly-(L-lactide-co-caprolactone) (PLCL) to prepare the nanofiber membrane (SP/CPL) to treat the diabetic wound. The morphology and structure of the nanofibers were observed by scanning electron microscope (SEM). The SEM results indicate the smooth and bead free fibers and the diameter of the fiber decreased with increasing drug concentration. The release profile indicates the sustained release of the drug. Moreover, the drug-loaded nanofibers showed inhibitory effects for S.aureus and E.coli. Furthermore, in vitro cell culture studies showed the increased proliferation and adhesion of NIH-3T3 cells on the drug-containing nanofiber membrane. Animal experiments showed that the nanofiber membrane loaded with CPL increases the expression of the TGF-ß signaling pathway and collagen during wound healing, inhibits the expression of pro-inflammatory factors, and thus effectively promotes wound healing in diabetic mice. Therefore, the SP/CPL nanofiber scaffold with CPL loading is a potential candidate for diabetic wound dressings and tissue engineering.