To investigate the effects of particle size, mPEG molecular weight, coating density and zeta potential of monomethoxyl poly(ethylene glycol)-poly(lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles on their transportation across the rat nasal mucosa, mPEG-PLGA-NPs with different mPEG molecular weights (M(r) 1 000, 2 000) and coating density (0, 5%, 10%, 15%) and chitosan coated PLGA-NP, which loaded coumarin-6 as fluorescent marker, were prepared with the nanoprecipitation method and emulsion-solvent evaporation method, and determine their particle size, zeta potential, the efficiency of fluorescent labeling, in vitro leakage rate and the stability with the lysozyme were determined. The effects of physical and chemical properties on the transmucosal transport of the fluorescent nanoparticles were investigated by confocal laser scanning microscopy (CLSM). The result showed that the size of nanoparticles prepared with nanoprecipitation method varied between 120 and 200 nm; the size of nanoparticles prepared with emulsion-solvent evaporation method varied between 420 and 450 nm. Nanoparticles dispersed uniformly; the zeta potential of PLGA-NPs was negative; mPEG-PLGA-NPs was close to neutral; chitosan coated PLGA-NPs was positive; and the efficiency of fluorescent labeling were higher than 80%. In vitro leak was less than 5% within 4 h and nanoparticles were basically stable with lysozyme. The CLSM results show that the transportation efficiency of mPEG-PLGA-NPs with a high PEG coating density and high mPEG molecular weight was significantly higher than that of uncoated PLGA nanoparticles and also that of chitosan coated PLGA-NPs (P < 0.05). The hydrophilcity, zeta potential and particle size of nanoparticles play important roles on the efficiency of mPEG-PLGA nanoparticles to transport across the rat nasal mucosa.

The present study is to establish Caco-2/HT29-MTX co-cultured cells and investigate the transport capability of PLGA nanoparticles with different surface chemical properties across Caco-2/HT29-MTX co-cultured cells. PLGA-NPs, mPEG-PLGA-NPs and chitosan coated PLGA-NPs were prepared by nanoprecipitation method using poly(lactic-co-glycolic acid) as carrier material with surface modified by methoxy poly(ethylene glycol) and chitosan. The particle size and zeta potential of nanoparticles were measured by dynamic light scattering. Coumarin 6 was used as a fluorescent marker in the transport of nanoparticles investigated by confocal laser scanning microscopy. The transport of furanodiene (FDE) loaded nanoparticles was quantitively determined by high performance liquid chromatography. Colchicine and nocodazole were used in the transport study to explore the involved endocytosis mechanisms of nanoparticles. Distribution of the tight junction proteins ZO-1 was also analyzed by immunofluorescence staining. The results showed that the nanoparticles dispersed uniformly. The zeta potential of PLGA-NPs was negative, the mPEG-PLGA-NPs was close to neutral and the CS-PLGA-NPs was positive. The entrapment efficiency of FDE in all nanoparticles was higher than 75%. The transport capability of mPEG-PLGA-NPs across Caco-2/HT29-MTX co-cultured cells was higher than that of PLGA-NPs and CS-PLGA-NPs. Colchicine and nocodazole could significantly decrease the transport amount of nanoparticles. mPEG-PLGA-NPs could obviously reduce the distribution of ZO-1 protein than PLGA-NPs and CS-PLGA-NPs. The transport mechanism of PLGA-NPs and mPEG-PLGA-NPs were indicated to be a combination of endocytosis and paracellular way, while CS-PLGA-NPs mainly relied on the endocytosis way. PEG coating could shield the surface charge and enhance the hydrophilicity of PLGA nanoparticles, which leads mPEG-PLGA-NPs to possess higher anti-adhesion activity. As a result, mPEG-PLGA-NPs could penetrate the mucus layer rapidly and transport across Caco-2/HT29-MTX co-cultured cells.

Objective To assess the antiangiogenic role of recombinant human endostatin combined with chemoradiotherapy and the capacity,and to explore the early tumor response as measured by comparing the change of MRI perfusion parameter.Methods From May 2012 to March 2013,22 locally advanced nasopharyngeal carcinoma patients who received recombinant human endostatin combined with chemoradiotherapy following induction chemotherapy,were included in the prospective study group.The other 25 patients,who received chemoradiotherapy following induction chemotherapy alone in the same period,were included in the control group.The perfusion parameters including blood volume(BV),blood flux(BF),mean transit time (MTT) were obtained by carrying out MR perfusion scanning at 3 time points:before induction chemotherapy,after induction chemotherapy,the end of concurrent chemoradiotherapy.Results Compared with before induction chemotherapy,the perfusion parameters including BV and BF obviously decreased in the study group (F =3.05,3.85,P ＜ 0.05).The parameter of MTT had no obviously change in the study group(P ＞0.05).In the control group,the change of BV,BF and MTT of nasopharyngeal lesions area during the treatment showed no significant difference (P ＞ 0.05).To make comparison between the two groups,at the end of concurrent chemoradiotherapy,BF of nasopharyngeal lesions area in the study group was 0.72 ± 0.56 and 1.92 ± 1.26 in the control group,the former showing significantly declined results (t =-3.056,P =0.012).Conclusions Recombinant human endostatin might be a good indicator of local tumor microvascular changes and the treatment-related toxicity could be tolerated.Magnetic resonance perfusion imaging maybe assessed the capacity of anti-angiogenesis therapy to induce early tumor response.Clinical trial registration Chinese clinical trial registry,ChiCRTONRC-12002394.

Objective To investigate the impacts of fire needling combined with Huoxue Huayu Decoction on disease severity,skin barrier function and hemorheology in patients with psoriasis vulgaris of blood stasis syndrome.Methods A total of 120 patients with psoriasis vulgaris of blood stasis syn-drome treated in our hospital were randomly divided into traditional Chinese medicine group(60 ca-ses)and combined group(60 cases)according to the random number table method.The TCM syn-drome scores,severity[Psoriasis Area and Severity Index(PASI)score],hemorheology(whole blood low shear viscosity and high shear viscosity,plasma viscosity),skin barrier function(transepi-dermal moisture loss,stratum corneum water content and sebum content),quality of life[Dermatology Life Quality Index(DLQI)score]and clinical healing effect were compared.Results Compared with before treatment,the scores of TCM syndromes such as hypertrophic infiltration of skin lesions,skin lesion color,pruritus,and skin dryness,PASI score,whole blood low shear viscosity,whole blood high shear viscosity,plasma viscosity,transepidermal water loss and DLQI score in both groups were decreased after treatment,and the degree of reduction in the combined group was more significant than that in the traditional Chinese medicine group(P＜0.05).Compared with before treatment,the wa-ter content and sebum content of the stratum corneum in both groups increased after treatment,and the combined group was higher than the traditional Chinese medicine group(P＜0.05).The total effective rate of the combined group was 93.33％,which was higher than 78.33％of the traditional Chinese medicine group(P＜0.05).Conclusion Fire needling combined with Huoxue Huayu Decoction for psoriasis vulgaris of blood stasis syndrome can usefully ameliorate the clinical symptoms and skin barrier function,regulate blood rheologyindexes,and enhance the quality of life.

Objective To investigate the impacts of fire needling combined with Huoxue Huayu Decoction on disease severity,skin barrier function and hemorheology in patients with psoriasis vulgaris of blood stasis syndrome.Methods A total of 120 patients with psoriasis vulgaris of blood stasis syn-drome treated in our hospital were randomly divided into traditional Chinese medicine group(60 ca-ses)and combined group(60 cases)according to the random number table method.The TCM syn-drome scores,severity[Psoriasis Area and Severity Index(PASI)score],hemorheology(whole blood low shear viscosity and high shear viscosity,plasma viscosity),skin barrier function(transepi-dermal moisture loss,stratum corneum water content and sebum content),quality of life[Dermatology Life Quality Index(DLQI)score]and clinical healing effect were compared.Results Compared with before treatment,the scores of TCM syndromes such as hypertrophic infiltration of skin lesions,skin lesion color,pruritus,and skin dryness,PASI score,whole blood low shear viscosity,whole blood high shear viscosity,plasma viscosity,transepidermal water loss and DLQI score in both groups were decreased after treatment,and the degree of reduction in the combined group was more significant than that in the traditional Chinese medicine group(P＜0.05).Compared with before treatment,the wa-ter content and sebum content of the stratum corneum in both groups increased after treatment,and the combined group was higher than the traditional Chinese medicine group(P＜0.05).The total effective rate of the combined group was 93.33％,which was higher than 78.33％of the traditional Chinese medicine group(P＜0.05).Conclusion Fire needling combined with Huoxue Huayu Decoction for psoriasis vulgaris of blood stasis syndrome can usefully ameliorate the clinical symptoms and skin barrier function,regulate blood rheologyindexes,and enhance the quality of life.

Objective To design and synthesize novel Hsp90 inhibitors with dual functions of synergistically enhancing the antifungal activity of fluconazole （FLC） against drug-resistant fungi and anti-tumor activity based on the Hsp90 inhibitor Ganetespib. Methods The previous research found that Ganetespib had a good synergistic anti-resistant fungal activity with FLC, with a fractional inhibitory concentration index （FICI） of 0.023 to 0.039. In this study, structural modifications were made to Ganetespib by replacing its indole ring with a phenyl ring containing different substituents to design and synthesize a series of new compounds. The in vitro synergistic anti-resistant fungal activity against C. albicans 0304103 in combination with FLC, anti-tumor activity （against HEL, HL60 and A549 cells）, and Hsp90α inhibition activity were determined to explore their structure-activity relationship and mechanism of action. Results The chemical structures of 19 new compounds were confirmed by ¹H NMR, ¹³C NMR and HRMS. Most of the compounds exhibited strong Hsp90α inhibitory activity, good synergistic activity against drug-resistant fungi in combination with FLC and anti-tumor activity. The substitution of electron-donating groups on the benzene ring was beneficial to enhancing the synergistic activity against drug-resistant fungi in combination with FLC. Among them, compounds F3 and F5 showed excellent synergistic activity against drug-resistant fungi in combination with FLC （FICI were both 0.047） and anti-tumor activity （IC₅₀ were 0.025 to 0.15 μmol/L and 0.021 to 0.23 μmol/L respectively）, and could down-regulate the expression levels of drug resistance genes and efflux pump genes in fungi, inhibit the formation of fungal biofilms, and arrest the cell cycle of HEL cells at G0/G1 phase. Conclusion The novel Hsp90 inhibitors such as F3 and F5 could both effectively exert the dual activities of synergizing with FLC to combat drug-resistant fungi and fight against tumors, which provided a new idea for the development of new drugs with dual functions of synergizing with FLC to combat drug-resistant fungi and fight against tumors.

The cardiovascular system plays a crucial role in the entire organism. It performs many important functions, such as providing organs and tissues with nutrients, hormones, delivering oxygen to cells, and maintaining physiological temperature. For a long time, accurately identifying the nonlinear and anisotropic mechanical properties of the vascular wall within the body has been regarded as a key challenge in cardiovascular biomechanics, as these properties are critical determinants of overall cardiac function. Currently, the roles of mechanical and tissue properties in cardiovascular diseases such as arterial aneurysms and atherosclerosis remain hot topics in both basic and clinical researches. This review aims to summarize the latest research advances in the field of cardiovascular biomechanics and mechanobiology in the year 2022. In terms of cardiovascular biomechanics, researchers focus on the structure, function, and pathophysiology of the cardiovascular system, and use experimental methods such as mechanical modeling to study these issues. These include studies about biomechanical properties of diseases such as atherosclerosis, arterial aneurysms, and myocardial infarction, as well as the development and testing of treatment methods based on dynamics of the cardiovascular system. In terms of mechanobiology, researchers explore mechanical properties of cardiovascular cells and extracellular matrix, including prediction of cell mechanical properties based on machine learning, studies of biological material mechanical properties, and the role of mechanical properties in cardiovascular cell phenotype changes. These research findings provide new ideas and methods for diagnosing and treating cardiovascular diseases and offer new insights into researches in biomechanics and mechanobiology fields.

Long non-coding RNA (lncRNA) Dnm3os plays a critical role in peritendinous fibrosis and pulmonary fibrosis, but its role in the process of cardiac fibrosis is still unclear. Therefore, we carried out study by using the myocardial fibrotic tissues obtained by thoracic aortic constriction (TAC) in an early study of our group, and the
Fibroblasts ; Fibrosis ; Humans ; Myocardium/pathology* ; RNA, Long Noncoding ; Signal Transduction ; Transforming Growth Factor beta1

Calnexin is a lectin-like molecular chaperone protein on the endoplasmic reticulum, mediating unfolded protein responses, the endoplasmic reticulum Ca homeostasis, and Ca signals conduction. In recent years, studies have found that calnexin plays a key role in the heart diseases. This study aims to explore the role of calnexin in the activation of cardiac fibroblasts. A transverse aortic constriction (TAC) mouse model was established to observe the activation of cardiac fibroblasts , and the cardiac fibroblasts activation model was established by transforming growth factor β1 (TGFβ1) stimulation. The adenovirus was respectively used to gene overexpression and silencing calnexin in cardiac fibroblasts to elucidate the relationship between calnexin and cardiac fibroblasts activation, as well as the possible underlying mechanism. We confirmed the establishment of TAC model by echocardiography, hematoxylin-eosin, Masson, and Sirius red staining, and detecting the expression of cardiac fibrosis markers in cardiac tissues. After TGFβ1 stimulation, markers of the activation of cardiac fibroblast, and proliferation and migration of cardiac fibroblast were detected by quantitative PCR, Western blot, EdU assay, and wound healing assay respectively. The results showed that the calnexin expression was reduced in both the TAC mice model and the activated cardiac fibroblasts. The overexpression of calnexin relieved cardiac fibroblasts activation, in contrast, the silencing of calnexin promoted cardiac fibroblasts activation. Furthermore, we found that the endoplasmic reticulum stress was activated during cardiac fibroblasts activation, and endoplasmic reticulum stress was relieved after overexpression of calnexin. Conversely, after the silencing of calnexin, endoplasmic reticulum stress was further aggravated, accompanying with the activation of cardiac fibroblasts. Our data suggest that the overexpression of calnexin may prevent cardiac fibroblasts against activation by alleviating endoplasmic reticulum stress.