Human serum-derived exosomes modulate macrophage inflammation to promote VCAM1-mediated angiogenesis and bone regeneration.

During exogenous bone-graft-mediated bone defect repair, macrophage inflammation dictates angiogenesis and bone regeneration. Exosomes from different human cells have shown macrophage immunomodulation-mediated bone regeneration potential. However, the effect of human serum-derived exosomes (serum-Exo) on macrophage immunomodulation-mediated angiogenesis during bone defect repair has not been investigated yet. In this study, we explored the effects of serum-Exo on macrophage inflammation regulation-mediated angiogenesis during bone defect repair and preliminarily elucidated the mechanism. Healthy serum-Exo was isolated by ultracentrifugation. The effect of serum-Exo on LPS-induced M1 macrophage inflammation was analysed in vitro. The conditioned medium of serum-Exo-treated LPS-induced M1 macrophage (serum-Exo-treated M1 macrophage-CM) was used to culture human umbilical vein endothelial cells (HUVEC), and the effect on angiogenesis was analysed by western blot, qRT-PCR, etc. mRNA-sequencing of HUVECs was performed to identify deferentially expressed genes. Finally, the rat mandibular defect model was established and treated with Bio-Oss and Bio-Oss + Exo. The effect of the Bio-Oss + Exo combination on mandibular bone regeneration was observed by micro-computed tomography (micro-CT), haematoxylin and eosin (HE) staining, Masson staining, and immunohistochemical staining. Serum-Exo promoted the proliferation of RAW264.7 macrophages and reduced the expression of M1-related genes such as IL-6, IL-1ß, iNOS, and CD86. Serum-Exo-treated M1 macrophage-CM induced the proliferation, migration, and angiogenic differentiation of HUVEC, as well as the expression of H-type blood vessel markers CD31 and endomucin (EMCN), compared with M1 macrophage-CM. Moreover, higher expression of vascular endothelial adhesion factor 1 (VCAM1) in HUVEC cultured with serum-Exo-treated M1 macrophage-CM compared with M1 macrophages-CM. Inhibition of VCAM1 signalling abrogated the pro-angiogenic effect of serum-Exo-treated M1 macrophage-CM on HUVEC. Local administration of serum-Exo during mandibular bone defect repair reduced the number of M1 macrophages and promoted angiogenesis and osteogenesis. Collectively, our results demonstrate the macrophage inflammation regulation-mediated pro-angiogenic potential of serum-Exo during bone defect repair possibly via upregulation of VCAM1 signalling in HUVEC.

Dkk-1-TNF-α crosstalk regulates MC3T3E1 pre-osteoblast proliferation and differentiation under mechanical stress through the ERK signaling pathway.

The study aims to explore the role of the ERK signaling pathway in the crosstalk between Dkk-1 and TNF-α in MC3T3E1 pre-osteoblasts under cyclic tensile/compressive stress. A forced four-point bending system was used to apply cyclic uniaxial tensile/compressive strain (2000 µ, 0.5 Hz) to MC3T3E1 cells. Dkk-1 and TNF-α expression were upregulated in MC3T3E1 cells under compressive strain. Cell proliferation, the cell cycle, osteogenesis-related gene (Wnt5a, Runx2, Osterix) expression, ß-catenin expression, and the p-ERK/ERK ratio were significantly enhanced, whereas apoptosis, the RANKL/OPG ratio, and TNF-α expression were significantly attenuated, by Dkk-1 silencing. Dkk-1 expression increased and the effects of Dkk-1 silencing were reversed when exogenous TNF-α was added. Mechanically, TNF-α crosstalked with Dkk-1 through ERK signaling in MC3T3E1 cells. ERK signaling blockade impaired Dkk-1-induced TNF-α expression and TNF-α-mediated Dkk-1 expression. Dkk-1 and TNF-α crosstalked, partially through ERK signaling, in MC3T3E1 cells under compressive/tensile strain, synergistically modulating various biological behaviors of the cells. These findings not only provide mechanical insight into the cellular events and molecular regulation of orthodontic tooth movement (OTM), but also aid the development of novel strategies to accelerate OTM.

Highly Sensitive Temperature-Pressure Bimodal Aerogel with Stimulus Discriminability for Human Physiological Monitoring.

Multimodal sensor with high sensitivity, accurate sensing resolution, and stimuli discriminability is very desirable for human physiological state monitoring. A dual-sensing aerogel is fabricated with independent pyro-piezoresistive behavior by leveraging MXene and semicrystalline polymer to assemble shrinkable nanochannel structures inside multilevel cellular walls of aerogel for discriminable temperature and pressure sensing. The shrinkable nanochannels, controlled by the melt flow-triggered volume change of semicrystalline polymer, act as thermoresponsive conductive channels to endow the pyroresistive aerogel with negative temperature coefficient of resistance of -10.0% °C-1 and high accuracy within 0.2 °C in human physiological temperature range of 30-40 °C. The flexible cellular walls, working as pressure-responsive conductive channels, enable the piezoresistive aerogel to exhibit a pressure sensitivity up to 777 kPa-1 with a detectable pressure limit of 0.05 Pa. The pyro-piezoresistive aerogel can detect the temperature-dependent characteristics of pulse pressure waveforms from artery vessels under different human body temperature states.

B7-H1 Promotes the Functional Effect of Human Gingiva-Derived Mesenchymal Stem Cells on Collagen-Induced Arthritis Murine Model.

Recent studies found that mesenchymal stem cells (MSCs), by virtue of their tissue recovery and immunoregulatory properties, have shown a broad prospect for applications in various autoimmune and degenerative diseases. Although the potential therapeutic use of MSCs is considerable, studies and clinical treatment efficacy are preliminary due to the heterogeneity of MSCs. Herein, based on RNA-sequencing (RNA-seq) and single cell sequence properties, we demonstrated that B7-H1 plays an important role in the immunosuppressive function of human gingiva-derived mesenchymal stem cells (GMSCs) in a collagen-induced arthritis murine model that is dependent on STAT3 signaling. Our data offer convincing evidence that B7-H1 expression by GMSCs helps to identify a new subpopulation of MSCs with a greater immunosuppressive property. The approach provides a unique and additional strategy for stem cells-based therapies of autoimmune and other inflammatory diseases.

CD39 Produced from Human GMSCs Regulates the Balance of Osteoclasts and Osteoblasts through the Wnt/ß-Catenin Pathway in Osteoporosis.

Osteoporosis is a disease in which the density and quality of bone are reduced, causing bones to become weak and so brittle that a fall or even mild stresses can cause a fracture. Current drug treatment consists mainly of antiresorptive agents that are unable to stimulate new bone formation. Our recent studies have defined a critical role of gingiva-derived mesenchymal stem cells (GMSCs) in attenuating autoimmune arthritis through inhibition of osteoclast formation and activities, but it remains to be ruled out whether the administration of GMSCs to patients with osteoporosis could also regulate osteoblasts and eventually affect bone formation and protection. With the use of an ovariectomized mouse model, we here demonstrated that adoptive transfer of GMSCs regulated the balance of osteoclasts and osteoblasts, eventually contributing to dynamic bone formation. Validation by RNA sequencing (RNA-seq), single-cell sequencing, revealed a unique population of CD39+ GMSC that plays an important role in promoting bone formation. We further demonstrated that CD39 produced from GMSC exerted its osteogenic capacity through the Wnt/ß-catenin pathway. Our results not only establish a previously unidentified role and mechanism of GMSC for bone promotion but also a potential therapeutic target for management of patients with osteoporosis and other bone loss conditions.

Electrochemical cleavage of aryl ethers promoted by sodium borohydride.

The NaBH4 (or TBABH4)-promoted electrochemically reductive cleavage of aryl C-O bonds in diaryl ethers to produce phenols and arenes with high yields and excellent selectivities at room temperature was reported. Air- and water-tolerable, this process also works on the cleavage of aryl alkyl and benzyl ethers. The application to break the ß-O-4, α-O-4, and 4-O-5 lignin model compounds is also illustrated, which highlights the advance toward the goal of lignin conversion.

Impacts of microplastic contamination on the rheology properties of sediments in a eutrophic shallow lake.

Microplastic (MP) contamination is a growing global concern, with lake sediments serving as a significant sink for MP due to both anthropogenic and natural activities. Given the increasing evidence of MP accumulation in sediments, it was crucial to assess their influence on sediment erosion resistance, which directly affected sediment resuspension. To fill this gap, this study focused on the effect of MP on the sediments rheological properties. After 60-day experiments, it was found that MP addition into sediments reduced sediment viscosity, yield stress, and flow point shear stress. Meanwhile, MPs also significantly altered sediment properties and extracellular polymer composition. MP addition reduced extracellular polymeric substances production and cation exchange capacity, which then worked together and led to a weak sediment structure. Seemingly, MPs changed fluid sediment characteristics and caused stronger fluidity under less shear force. Consequently, the accumulation of MP might facilitate the resuspension of sediments under smaller wind and wave disturbances. This study provided novel insights into the direct impact of MPs on sediment physical properties using rheology, thereby enhancing our understanding of the environmental behavior of MPs in lake ecosystems.

Nanoplastics enhance the denitrification process and microbial interaction network in wetland soils.

With the widespread presence of plastic waste in ecosystems, it is imperative to understand the response of natural processes to micro- and nanoplastic pollution pressures. However, the effects of nanoplastics on biogeochemical cycles are still overlooked and controversial. This study investigated the effects of three particle sizes (100 µm, 7 µm, and 80 nm) of polystyrene (PS) micro/nanoplastics (0.08 % of mass concentration) on denitrification processes and nirS/nirK denitrifying bacterial communities in wetland soils. The results indicated that PS nanoplastics were found to significantly enhance denitrification rates from 21.30 to 54.73 µmol N2·h-1·kg-1, increasing by 1.57 times compared to the control. Exposure to nanoplastics caused shifts in the composition and structure of the nirS-type denitrifier community. LEfSe analysis, random forest, and Mantel tests revealed that nirS denitrifying bacteria, especially Sideroxydans, played a pivotal role in driving denitrification rates (Mantel's R = 0.24, p = 0.002), likely due to the faster release of organic substrates from nanoplastics. Microbial co-occurrence networks demonstrated that nanoplastic amendments fostered a denser denitrifier network and led to shifts in keystone species. Sideroxydans appeared more likely to cooperate with other bacteria, such as Burkholderiales, to complete denitrification processes. This study suggests that nanoplastics are a potentially stronger driver of denitrification than microplastics, providing insight into the impact of plastic pollutants on biogeochemical cycling in natural wetland ecosystems. Given the widespread distribution of wetlands, the potential increase in gaseous nitrogen emissions due to nanoplastics pollution warrants attention.

Gingival-derived mesenchymal stem cells alleviate allergic asthma inflammation via HGF in animal models.

Allergic asthma is a chronic non-communicable disease characterized by lung tissue inflammation. Current treatments can alleviate the clinical symptoms to some extent, but there is still no cure. Recently, the transplantation of mesenchymal stem cells (MSCs) has emerged as a potential approach for treating allergic asthma. Gingival-derived mesenchymal stem cells (GMSCs), a type of MSC recently studied, have shown significant therapeutic effects in various experimental models of autoimmune diseases. However, their application in allergic diseases has yet to be fully elucidated. In this study, using an OVA-induced allergic asthma model, we demonstrated that GMSCs decrease CD11b+CD11c+ proinflammatory dendritic cells (DCs), reduce Th2 cells differentiation, and thus effectively diminish eosinophils infiltration. We also identified that the core functional factor, hepatocyte growth factor (HGF) secreted by GMSCs, mediated its effects in relieving airway inflammation. Taken together, our findings indicate GMSCs as a potential therapy for allergic asthma and other related diseases.

Infusion of GMSCs relieves autoimmune arthritis by suppressing the externalization of neutrophil extracellular traps via PGE2-PKA-ERK axis.

INTRODUCTION: Rheumatoid arthritis (RA) is a systemic autoimmune disease with limited treatment success, characterized by chronic inflammation and progressive cartilage and bone destruction. Accumulating evidence has shown that neutrophil extracellular traps (NETs) released by activated neutrophils are important for initiating and perpetuating synovial inflammation and thereby could be a promising therapeutic target for RA. K/B × N serum transfer-induced arthritis (STIA) is a rapidly developed joint inflammatory model that somehow mimics the inflammatory response in patients with RA. Human gingival-derived mesenchymal stem cells (GMSCs) have been previously shown to possess immunosuppressive effects in arthritis and humanized animal models. However, it is unknown whether GMSCs can manage neutrophils in autoimmune arthritis. OBJECTIVES: To evaluate whether infusion of GMSCs can alleviate RA by regulating neutrophils and NETs formation. If this is so, we will explore the underlying mechanism(s) in an animal model of inflammatory arthritis. METHODS: The effects of GMSCs on RA were assessed by comparing the symptoms of the K/B × N serum transfer-induced arthritis (STIA) model administered either with GMSCs or with control cells. Phenotypes examined included clinical scores, rear ankle thickness, paw swelling, inflammation, synovial cell proliferation, and immune cell frequency. The regulation of GMSCs on NETs was examined through immunofluorescence and immunoblotting in GMSCs-infused STIA mice and in an in vitro co-culture system of neutrophils with GMSCs. The molecular mechanism(s) by which GMSCs regulate NETs was explored both in vitro and in vivo by silencing experiments. RESULTS: We found in this study that adoptive transfer of GMSCs into STIA mice significantly ameliorated experimental arthritis and reduced neutrophil infiltration and NET formation. In vitro studies also showed that GMSCs inhibited the generation of NETs in neutrophils. Subsequent investigations revealed that GMSCs secreted prostaglandin E2 (PGE2) to activate protein kinase A (PKA), which ultimately inhibited the downstream extracellular signal-regulated kinase (ERK) pathway that is essential for NET formation. CONCLUSION: Our results demonstrate that infusion of GMSCs can ameliorate inflammatory arthritis mainly by suppressing NET formation via the PGE2-PKA-ERK signaling pathway. These findings further support the notion that the manipulation of GMSCs is a promising stem cell-based therapy for patients with RA and other autoimmune and inflammatory diseases.

miRNA-148a-containing GMSC-derived EVs modulate Treg/Th17 balance via IKKB/NF-κB pathway and treat a rheumatoid arthritis model.

Mesenchymal stem cells (MSCs) have demonstrated potent immunomodulatory properties that have shown promise in the treatment of autoimmune diseases, including rheumatoid arthritis (RA). However, the inherent heterogeneity of MSCs triggered conflicting therapeutic outcomes, raising safety concerns and limiting their clinical application. This study aimed to investigate the potential of extracellular vesicles derived from human gingival mesenchymal stem cells (GMSC-EVs) as a therapeutic strategy for RA. Through in vivo experiments using an experimental RA model, our results demonstrate that GMSC-EVs selectively homed to inflamed joints and recovered Treg and Th17 cell balance, resulting in the reduction of arthritis progression. Our investigations also uncovered miR-148a-3p as a critical contributor to the Treg/Th17 balance modulation via IKKB/NF-κB signaling orchestrated by GMSC-EVs, which was subsequently validated in a model of human xenograft versus host disease (xGvHD). Furthermore, we successfully developed a humanized animal model by utilizing synovial fibroblasts obtained from patients with RA (RASFs). We found that GMSC-EVs impeded the invasiveness of RASFs and minimized cartilage destruction, indicating their potential therapeutic efficacy in the context of patients with RA. Overall, the unique characteristics - including reduced immunogenicity, simplified administration, and inherent ability to target inflamed tissues - position GMSC-EVs as a viable alternative for RA and other autoimmune diseases.

Calibration of discrete element parameters for simulating wheat crushing.

The mechanical properties of wheat grains were measured and analyzed using discrete element software, which provided crucial data for their processing in a mill. The foundational Hertz-Mindlin model was used as a theoretical framework to evaluate the accumulation angle of wheat grains. The Plackett-Burman, steepest ascent, and Box-Behnken methods were utilized in a series of experiments, with the accumulation angle serving as the dependent variable. Targeting the actual angle of repose in the response surface, the optimal parameters were derived using the regression equations. These included a static-friction coefficient of 0.3 between individual wheat grains, rolling-friction coefficient of 0.04 for wheat-wheat interactions, static-friction coefficient of 0.554 for wheat-tooth roller interactions, collision recovery coefficient of 0.5 for wheat-wheat collisions, collision recovery coefficient of 0.45 for wheat-tooth roller collisions, and rolling-friction coefficient of 0.05 for wheat-roller interactions. Relying on the bonding contact model of Hertz-Mindlin, virtual uniaxial compression tests were conducted to calibrate the wheat grain bonding parameters. A regression equation for the critical load was subsequently generated using the critical load of the wheat grain bonding model as the response variable. The optimal parameters were calculated and incorporated into the EDEM model for computation, which resulted in a relative error of 1.6% between the calculated and observed values, confirming the accuracy and feasibility of the calibration method, suggesting that the calibrated parameters were accurate.

UV-aging of microplastics increases proximal ARG donor-recipient adsorption and leaching of chemicals that synergistically enhance antibiotic resistance propagation.

Despite growing attention to environmental pollution by microplastics (MP), the effects of MP aging on bacterial horizontal gene transfer (HGT) have not been systematically investigated. Here, we used UV-aged polystyrene microplastics (PS-MPs) to investigate how aging affects antibiotic resistance genes (ARGs) transfer efficiency from various ARG vectors to recipient bacteria. The adsorption capacity of MP20 (20-day UV-aged PS-MPs) towards E. coli (harboring plasmid-borne blaTEM-1), plasmid pET29 (harboring blaNDM-1) and phage lambda (carrying the aphA1 ARG) increased by 6.6-, 5.2- and 8.3-fold, respectively, relative to pristine PS-MPs (MP0), due to increased specific surface area and affinity for these ARG vectors. Moreover, MP20 released more organic compounds (TOC 1.6 mg/g-MP20, versus 0.2 mg/g-MP0 in 4 h) -possibly depolymerization byproducts (verified by GC-MS), which induced intracellular ROS generation, increased cell permeability and upregulated HGT associated genes. Accordingly, MP20 enhanced ARG transfer frequency from E. coli, plasmid pET29 and phage lambda (relative to MP0) by 1.3-, 4.7- and 3.5-fold, respectively. The Bliss independence model infers that higher bacterial adsorption and exposure to chemicals released during MP aging synergistically enhanced ARG transfer. This underscores the need to assess the significance of this overlooked phenomenon to the environmental dissemination of antibiotic resistance and other HGT processes.

Evaluating how lodging affects maize yield estimation based on UAV observations.

Timely and accurate pre-harvest estimates of maize yield are vital for agricultural management. Although many remote sensing approaches have been developed to estimate maize yields, few have been tested under lodging conditions. Thus, the feasibility of existing approaches under lodging conditions and the influence of lodging on maize yield estimates both remain unclear. To address this situation, this study develops a lodging index to quantify the degree of lodging. The index is based on RGB and multispectral images obtained from a low-altitude unmanned aerial vehicle and proves to be an important predictor variable in a random forest regression (RFR) model for accurately estimating maize yield after lodging. The results show that (1) the lodging index accurately describes the degree of lodging of each maize plot, (2) the yield-estimation model that incorporates the lodging index provides slightly more accurate yield estimates than without the lodging index at three important growth stages of maize (tasseling, milking, denting), and (3) the RFR model with lodging index applied at the denting (R5) stage yields the best performance of the three growth stages, with R2 = 0.859, a root mean square error (RMSE) of 1086.412 kg/ha, and a relative RMSE of 13.1%. This study thus provides valuable insight into the precise estimation of crop yield and demonstra\tes that incorporating a lodging stress-related variable into the model leads to accurate and robust estimates of crop grain yield.

Association between anxiety, depression, and bowel air bubbles at colonoscopy: a prospective observational study.

BACKGROUND: Psychological illness could affect the gut transmission. However, few studies have reported on the association between anxiety and depression and bowel preparation failure at colonoscopy. Bowel air bubbles have become an indispensable index to evaluate intestinal cleanliness. The aim of the present study was to investigate whether anxiety and depression are associated with the bowel air bubbles. METHODS: The present study was a prospective observational study of patients who underwent colonoscopy in our hospital. Participants received the standard bowel preparation guidance, including split-dose polyethylene glycol and a low-fiber diet 1 day before colonoscopy. The primary outcome was degree of the bowel air bubble, measured by bubble scores. Univariate and multivariate logistic regression analyses were used to verify the association between anxiety and depression and bowel air bubbles. RESULTS: A total of 304 patients were enrolled in the present study between July 2019 and January 2020; 302 of these had complete data. The mean age was 48.74±11.73 years. Fifty six of 302 patients had anxiety. Age between 45 and 60 years [odds ratio (OR): 2.09, 95% confidence interval (CI): 1.13-3.87], age >60 years (OR: 1.99, 95% CI: 1.01-3.95), and anxiety (OR: 3.85, 95% CI: 2.12-6.97) were identified as risk factors for bowel air bubbles. A bachelor degree and above (OR: 0.27, 95% CI: 0.07-0.97) were identified as protective factors for bowel air bubbles. CONCLUSIONS: Anxiety is an independent risk factor of bowel air bubbles in colonoscopy diagnosis. Medical professionals should be mindful of this prior to performing colonoscopy.

The effect of early oral feeding after esophagectomy on the incidence of anastomotic leakage: an updated review.

OBJECTIVE: Early oral feeding (EOF) is considered to be an important component of enhanced recovery after surgery (ERAS), but raises the concern of increased risk of anastomotic leakage (AL) in patients receiving esophagectomy. This review aimed to elucidate the correlation of EOF and the incidence of AL after esophageal resection. METHODS: We searched PubMed, Web of Science, Scopus, Cochrane Library and Google Scholar from their inception to February 2020 for published articles that compared AL after EOF (oral feeding initiated within postoperative day [POD] 3) vs. conventional feeding regimen (nil-by-mouth with enteral tube nutrition support, until oral feeding since POD 4 and beyond) following esophagectomy. RESULTS: A total of 11 full articles were included in this review, including 5 registered randomized controlled trials (RCTs) and 6 observational studies that compared EOF with conventional care after esophagectomy. Meta-analysis was not possible due to significant heterogeneity, bias, and small sample sizes. Among the 11 included studies, 9 (including the 5 RCTs) showed that EOF did not increase AL rate, whereas the other 2 retrospective studies indicated that delayed oral feeding resulted in fewer AL. CONCLUSIONS: EOF after esophagectomy probably does not increase the incidence of AL, and it is a promising strategy in line with the essence of ERAS. However, more and better evidence from high-quality RCTs are still needed.

Human gingival tissue-derived MSC suppress osteoclastogenesis and bone erosion via CD39-adenosine signal pathway in autoimmune arthritis.

BACKGROUND: Bone destruction is one of many severe complications that occurs in patients with rheumatoid arthritis (RA) and current therapies are unable to cure this manifestation. This study here aims to determine whether GMSC can directly inhibit osteoclast formation and eventually attenuate osteoclastogenesis and bone erosion in an inflammatory milieu. METHOD: GMSC were co-cultured with osteoclast precursors with or without CD39 inhibitor, CD73 inhibitor or adenosine receptors inhibitors pretreatment and osteoclast formation were evaluated in vitro. 2×10^6 GMSC per mouse were transferred to CIA mice and pathology scores, the frequency of osteoclasts, bone erosion in joints were assessed in vivo. FINDING: GMSC but not control cells, markedly suppressed human or mice osteoclastogenesis in vitro. GMSC treatment also resulted in a dramatically decreased level of NF-κB p65/p50 in osteoclasts in vitro. Infusion of GMSC to CIA significantly attenuated the severity of arthritis, pathology scores, frequency of osteoclasts, particularly bone erosion, as well as a decreased expression of RANKL in synovial tissues in vivo. Blockade of CD39/CD73 or adenosine receptors has significantly abrogated the suppressive ability of GMSC in vitro and therapeutic effect of GMSC on bone erosion during CIA in vivo. INTERPRETATION: GMSC inhibit osteoclast formation in vitro and in vivo partially via CD39-CD73-adenosine signals. Manipulation of GMSC may have a therapeutic implication on rheumatoid arthritis and other bone erosion related diseases. FUND: This study was supported by grants from the National Key R&D Program of China (2017YFA0105801 to F.H); the Zhujiang Innovative and Entrepreneurial Talent Team Award of Guangdong Province (2016 ZT 06S 252 to F·H) and National Institutes of Health (R01 AR059103, R61 AR073409 and NIH Star Award to S.G.Z).

Preparation of cefquinome sulfate cationic proliposome and evaluation of its efficacy on Staphylococcus aureus biofilm.

Staphylococcus aureus (S. aureus) has the propensity to form biofilms, which eventually cause antibiotic resistance and treatment failure. Cefquinome sulfate (CS) is an animal-specific antibacterial agent for S. aureus infection. In this work, CS cationic proliposomes (CSCPs) were prepared by solid-dispersion method combined with effervescent hydration to eradicate bacterial biofilm and improve the antibacterial effect of the drug. CSCPs were readily dispersed in water, thereby forming CS cationic liposomes (CSCLs) as a white, uniform suspension. The CSCLs had an encapsulation efficiency (EE) of 63.21%, a drug loading of 4.04%, an average particle size of 201.5 nm, and a positive zeta-potential of 65.29 mV. In vitro release studies showed that CSCLs had good sustained-release behavior. The CS and CSCL minimal inhibitory concentration (MIC) of S. aureus type culture strain were 1 and 0.48 g/mL, respectively. The eradication effect of CS on bacterial biofilm (BBF) was relatively weak during culture in drug-containing medium for 8 h-24 h. However, the CSCL eradication effect on BBF increased gradually, and the clearance rate of CSCLs on BBF was about twice that of CS. The clearance rate reached 81.30% with 2.5 × MIC in 24 h. All these results indicated that CSCLs can significantly improve the eradication effect of cefquinome on biofilm to inhibit bacterial growth.

PLGA nanoparticles simultaneously loaded with vincristine sulfate and verapamil hydrochloride: systematic study of particle size and drug entrapment efficiency.

PLGA nanoparticles simultaneously loaded with vincristine sulfate (VCR) and verapamil hydrochloride (VRP) were prepared via combining O/W emulsion solvent evaporation and salting-out method. Ten independent processing parameters and two materials characteristics were assessed systematically to enhance the incorporation of the two hydrophilic low molecular weight drugs into PLGA nanoparticles and minimize nanoparticles size. Approaches investigated for the enhancement of drug entrapment efficiencies and the minimization of particle size included the influence of the molecular weight (MW) of PLGA and the lactide to glycolide (L:G) ratio of PLGA, PLGA concentration, the degrees of hydrolyzation and polymerization of PVA, PVA concentration, initial VCR and VRP content, acetone to dichloromethane volume ratio, aqueous phase pH, salt concentration of aqueous phase, aqueous to organic phase volume ratio, sonication time, sonication energy and removal rate of organic solvents. The nanoparticles produced by optimal formulation were submicron size (111.4+/-2.35nm, n=3) and of low polydispersity (0.062+/-0.023, n=3). Nanoparticles observed by transmission electron microscopy (TEM) showed extremely spherical shape. The entrapment efficiencies determined with high performance liquid chromatogram (HPLC) by ultracentrifuge method were 55.35+/-4.22% for VCR and 69.47+/-5.34% for VRP, respectively (n=3).

Vaginal delivery of carboplatin-loaded thermosensitive hydrogel to prevent local cervical cancer recurrence in mice.

Local tumor recurrence after cervical cancer surgery remains a clinical problem. Vaginal delivery of thermosensitive hydrogel may be suited to reduce tumor relapse rate with more efficacy and safety. A pilot study was carried out to evaluate the efficacy of carboplatin-loaded poloxamer hydrogel to prevent local recurrence of cervical cancer after surgery. In vivo vaginal retention evaluation of 27% poloxamer hydrogel in mice was proven to be a suitable vaginal drug delivery formulation due to its low gelation temperature. A mimic orthotopic cervical/vaginal cancer recurrence model after surgery was established by injecting murine cervical cancer cell line U14 into the vaginal submucosa to simulate the residual tumor cells infiltrated in the surgical site, followed by drug administration 24 h later to interfere with the formation/recurrence of the tumor. By infusing fluorescein sodium-loaded hydrogel into the vagina of mice, a maximized accumulation of fluorescein sodium (Flu) in the vagina was achieved and few signals were observed in other organs. When used in the prevention of the cervical cancer formation/recurrence in mice, the carboplatin-loaded poloxamer hydrogel exhibited great efficacy and systemic safety. In conclusion, thermosensitive hydrogel presents a simple, practical approach for the local drug delivery via vagina against cervical cancer recurrence.