AIM: To investigate the relationship between contrastenhanced ultrasound(CEUS),basic fibroblast growth factor(b FGF),endothelin-1(ET-1),and hepatocellular carcinoma(HCC) recurrence after ablation. METHODS: A total of ...AIM: To investigate the relationship between contrastenhanced ultrasound(CEUS),basic fibroblast growth factor(b FGF),endothelin-1(ET-1),and hepatocellular carcinoma(HCC) recurrence after ablation. METHODS: A total of 51 HCC patients(38 males and 13 females) who received radiofrequency ablation in our hospital from June 2012 to July 2014 were enrolled in this study. The patients were divided into two groups: recurrence group and non-recurrence group. Routine abdominal examination was first performed in the horizontal position. Then the patients underwent CEUS and immunohistochemical staining before receiving radiofrequency ablation. All patients were followed-up every three months for one year.The results of CEUS and serum tumor marker levels were evaluated and combined together to estimate HCC recurrence and metastasis. Patients were divided into two groups: recurrence group and non-recurrence group. Quantitative parameters of CEUS and tumor expression levels of b FGF and ET-1 were compared between the two groups,respectively. Binary logistic regression analysis was used to analyze the relationship between CEUS quantitative parameters,expression levels of ET-1 and b FGF,and HCC recurrence after ablation. RESULTS: Based on the quantitative parameters of CEUS before patients received radiofrequency ablation,the levels of tumor rise time(t RT),tumor time to peak(t TTP),tumor peak intensity(t PI) and tumorparenchymal peak intensity(t-p PI) in the recurrence group were significantly lower than those in the nonrecurrence group(16.6 ± 6.1 vs 23.2 ± 7.0,P = 0.000; 41.2 ± 10.2 vs 59.6 ± 14.2,P = 0.000; 23.8 ± 6.7 vs 31.4 ± 6.4,P = 0.000; 7.1 ± 3.4 vs 14.6 ± 7.4,P = 0.000; respectively). The expression levels of b FGF in the recurrence group were significantly higher than those in the non-recurrence group(P < 0.05). Levels of t TTP showed a significant inverse correlation with the level of b FGF in tumors(r =-0.312,P = 0.037). The Binary logistic regression analysis results revealed that the levels of t RT,t TTP,t PI and the level of b FGF were associated with HCC recurrence after radiofrequency ablation(P < 0.05). CONCLUSION: CEUS is a noninvasive and effective method for evaluating the angiogenesis of HCC,and predicting its recurrence and prognosis.展开更多
Objective: To investigate the role and potential mechanism of CXCR4 in promoting targeted homing of bone marrow mesenchymal stem cells(BMSCs) with ultrasound-exposed microbubbles(UM) pretreatment. Methods: Third gener...Objective: To investigate the role and potential mechanism of CXCR4 in promoting targeted homing of bone marrow mesenchymal stem cells(BMSCs) with ultrasound-exposed microbubbles(UM) pretreatment. Methods: Third generation BMSCs were divided into four groups control group, ultrasound(US) group, UM group and ultrasound-exposed microbubbles plus catalase group. RT-PCR and western blot were performed to determine the levels of CXCR4 m RNA transcription and protein expression, respectively. Third generation BMSCs were labeled with Fluo-α/AM and divided into three groups: control group, US group and UM group, and flurorescence intensities in the cells were observed immediately, 5 min and 15 min after intervention underflurorescence microscope. The calcium iron levels in the cells were analyzed. BMSCs were divided into i ve group: group A without calcium in the medium, group B, group C, group D and group E containing calcium chloride with concentration of l mol, 2 mol, 4mol, anti-calciurn-sensing receptor antibody, respectively. RT-PCR and western blot were performed to determine the levels of CXCR4 m RNA transcription and proteins expression of the third generation BMSCs of each group, respectively. Results: The levels of CXCR4 m RNA transcription and protein expression between US group and control group had no statistically signii cant dif erence(P>0.05) shown by RT-PCR and western blot; the transcription level in the UM group was signii cantly higher than that in US group and control group(P<0.05); and in the ultrasound-exposed microbubbles plus catalase group, the transcription level was much lower than that in UM group. Fluorescence intensify in the cells of US group had no signii cant dif erence compared with that in the cells of the control group(P>0.05), which in the cells of UM group was signii cantly higher than that in the cells of both US group and control group(P<0.05). Compared to group A, expressions of CXCR4 of group B to D were signii cantly increased in concentration-dependent manner showed by RT-PCR and western blot(P< 0.05). Compared to group C, expressions of CXCR4 of group E were signii cantly decreased(P< 0.05). Conclusions: UM can promote the inl ux of calcium in BMSCs and increase m RNA transcription and protein expression of CXCR4. The latter may partly be caused by influx of calcium.展开更多
Primary liver cancer and liver metastases are among the most frequent malignancies worldwide,with an increasing number of new cases and deaths every year.Traditional surgery is only suitable for a limited proportion o...Primary liver cancer and liver metastases are among the most frequent malignancies worldwide,with an increasing number of new cases and deaths every year.Traditional surgery is only suitable for a limited proportion of patients and imaging-guided percutaneous thermal ablation has achieved optimistic results for management of hepatic malignancy.This synopsis outlines the first clinical practice guidelines for ultrasoundguided percutaneous microwave ablation therapy for hepatic malignancy,which was created by a joint task force of the Society of Chinese Interventional Ultrasound.The guidelines aim at standardizing the microwave ablation procedure and therapeutic efficacy assessment,as well as proposing the criteria for the treatment candidates.展开更多
Ultrasound can be used not only in examination, but also in therapy, especially in the therapy of cancer. Sonodynamic therapy is an experimental cancer therapy method which uses ultrasound to enhance the cytotoxic eff...Ultrasound can be used not only in examination, but also in therapy, especially in the therapy of cancer. Sonodynamic therapy is an experimental cancer therapy method which uses ultrasound to enhance the cytotoxic effects of agents known as sonosensitizers. It has been tested in vitro and in vivo. The ultrasound could penetrate the tissue and cell under some of conditions which directly changes cell membrane permeability, thereby allowing the delivery of exogenous molecules into the cells in some degree. Ultrasound could inhibit the proliferation or induce the apoptosis of cancer cells in vitro or in vivo. Recent researches indicated low-frequency and low-intensity ultrasound could induce cell apoptosis, which could be strengthened by sonodynamic sensitivity, microbubbles, chemotherapeutic drugs and so on. Most kinds of ultrasound suppressed the proliferation of cancer cells through inducing the apoptosis of cancer cells. The mechanism of apoptosis is not clear. In this review, we will focus on and discuss the mechanisms of the induction of cancer cell apoptosis by ultrasound.展开更多
Objective:To observe the protective effect of breviscapineon mice with cisplatin-induced nephrotoxicity.Methods:Mice were given a single injection of cisplalin(8 mg/kg,up.);then,breviscapine was given to mice at 25 mg...Objective:To observe the protective effect of breviscapineon mice with cisplatin-induced nephrotoxicity.Methods:Mice were given a single injection of cisplalin(8 mg/kg,up.);then,breviscapine was given to mice at 25 mg/kg and 50 mg/kg doses,respectively,once a day for seven days.Renal tissue structure was observed after animals were sacrificed.Blood urea nitrogen(BUN),serum creatinine(Scr),lipid peroxide(MDA) and superoxide dismutase(SOD) serum levels were detected;and MDA,glutathione peroxidase,and SOD levels in the renal cortex were detected.Results:Compared with the blank control group(BCG),the kidney pathological damage of mice in the model control group(MCG) was more severe.After applying different doses of breviscapine,different degrees of renal injury improvement appeared.Compared with the BCG,the serum levels of Scr and BUN in the MCG increased to(89.92±6.78) μmoL/L and(15.32±4.53) mmoL/L.The differences were statistical significant(P<0.01).Compared with the MCG,the serum levels of Scr and BUN in the Bre low-dose groups and Bre high-dose groups decreased significantly(P<0.05).Compared with the BCG,the MDA levels in serum and in the renal cortex in the MCG significantly increased,while the SOD levels significantly decreased.Both the differences were statistically significant(P<0.01).In the Bre low-dose groups and Bre high-dose groups,MDA levels in serum and in the renal cortex significantly decreased,while SOD and glutathione peroxidase levels in the renal cortex significantly increased,compared with the MCG;and the differences were statistically significant(P<0.05).Conclusions:Breviscapine can reduce cisplatin induced renal toxicity in mice and it's possible through inhibition of renal tubule cell lipid peroxidation and reduces the nephrotoxicity of cisplatin.展开更多
Diagnostic ultrasound is a useful and noninvasive method in clinical medicine. Although due to its qualitative, sub- jective and experience-based nature, ultrasound image interpretation can be influenced by image cond...Diagnostic ultrasound is a useful and noninvasive method in clinical medicine. Although due to its qualitative, sub- jective and experience-based nature, ultrasound image interpretation can be influenced by image conditions such as scanning frequency and machine settings. In this paper, a novel method is proposed to extract the liver features using the joint features of fractal dimension and the entropies of texture edge co-occurrence matrix based on ultrasound images, which is not sensitive to changes in emission frequency and gain. Then, Fisher linear classifier and support vector machine are employed to test a group of 99 in-vivo liver fibrosis images from 18 patients, as well as other 273 liver images from 18 normal human volunteers.展开更多
Objective To investigate the diagnostic value of miniprobe ultrasonography (MPS) in the protruding lesions of esophagus. Methods Sixty-two patients with protruding lesions of esophagus were examined with MPS. Results ...Objective To investigate the diagnostic value of miniprobe ultrasonography (MPS) in the protruding lesions of esophagus. Methods Sixty-two patients with protruding lesions of esophagus were examined with MPS. Results The MPS examination showed diseases of esophageal polyp, inflammatory protruding, esophageal leiomyoma, esophageal leiomyosarcoma, esophageal venous aneurysm, esophageal lipoma, esophageal cyst, esophageal carcinoma, and extra esophageal compression including aorta compression, lung tumor compression and spina compression. Fourteen patients were verified by surgical operations and pathological examinations, resulting in 92.86% (13/14) diagnosis accuracy rate. Forty-eight cases had results of gastroscope examination consistent with that of MPS. Twelve cases had results of CT and MRI examination consistent with that of MPS. Follow-up was completed on 22 patients. Conclusion Besides imaging the esophageal layer, MPS can precisely locate the histological layer of the esophageal protruding lesions and predict their characters. This indicates its value in the diagnosis and differential diagnosis of the protruding lesions of esophagus. Furthermore, the miniature probe used in MPS examination can pass the structured esophagus, enabling wider application of the examination.展开更多
AIM: To evaluate the utility of liver reserve function by acoustic radiation force impulse(ARFI) imaging in patients with liver tumors. METHODS: Seventy-six patients with liver tumors were enrolled in this study. Seru...AIM: To evaluate the utility of liver reserve function by acoustic radiation force impulse(ARFI) imaging in patients with liver tumors. METHODS: Seventy-six patients with liver tumors were enrolled in this study. Serum biochemical indexes, such as aminotransferase(ALT), aspartate aminotransferase(AST), serum albumin(ALB), total bilirubin(T-Bil), and other indicators were observed. Liver stiffness(LS) was measured by ARFI imaging, measurements were repeated 10 times, and the average value of the results was taken as the final LS value. Indocyanine green(ICG) retention was performed, and ICG-K and ICG-R15 were recorded. Child-Pugh(CP) scores were carried out based on patient's preoperative biochemical tests and physical condition. Correlations among CP scores,ICG-R15, ICG-K and LS values were observed and analyzed using either the Pearson correlation coefficient or the Spearman rank correlation coefficient. KruskalWallis test was used to compare LS values of CP scores, and the receiver-operator characteristic(ROC) curve was used to analyze liver reserve function assessment accuracy. RESULTS: LS in the ICG-R15 10%-20% group was significantly higher than in the ICG-R15 < 10% group; and the difference was statistically significant(2.19 ± 0.27 vs 1.59 ± 0.32, P < 0.01). LS in the ICG-R15 > 20% group was significantly higher than in the ICG-R15 < 10% group; and the difference was statistically significant(2.92 ± 0.29 vs 1.59 ± 0.32, P < 0.01). The LS value in patients with CP class A was lower than in patients with CP class B(1.57 ± 0.34 vs 1.86 ± 0.27, P < 0.05), while the LS value in patients with CP class B was lower than in patients with CP class C(1.86 ± 0.27 vs 2.47 ± 0.33, P < 0.01). LS was positively correlated with ICG-R15(r = 0.617, P < 0.01) and CP score(r = 0.772, P < 0.01). Meanwhile, LS was negatively correlated with ICG-K(r =-0.673, P < 0.01). AST, ALT and T-Bil were positively correlated with LS, while ALB was negatively correlated with LS(P < 0.05). The ROC curve revealed that the when the LS value was 2.34 m/s, the Youden index was at its highest point, sensitivity was 69.2% and specificity was 92.1%. CONCLUSION: For patients with liver tumors, ARFI imaging is a useful tool for assessing liver reserve function.展开更多
Cancer stem cells(CSCs) are a small subset of cells in cancers that are thought to initiate tumorous transformation and promote metastasis, recurrence, and resistance to treatment. Growing evidence has revealed the ex...Cancer stem cells(CSCs) are a small subset of cells in cancers that are thought to initiate tumorous transformation and promote metastasis, recurrence, and resistance to treatment. Growing evidence has revealed the existence of CSCs in various types of cancers and suggested that CSCs differentiate into diverse lineage cells that contribute to tumor progression. We may be able to overcome the limitations of cancer treatment with a comprehensive understanding of the biological features and mechanisms underlying therapeutic resistance in CSCs. This review provides an overview of the properties, biomarkers, and mechanisms of resistance shown by CSCs. Recent findings on metabolic features, especially fatty acid metabolism and ferroptosis in CSCs, are highlighted, along with promising targeting strategies. Targeting CSCs is a potential treatment plan to conquer cancer and prevent resistance and relapse in cancer treatment.展开更多
Purpose:To screen potential tumor antigens for melanoma vaccine development and identify different immune subtypes.Methods:Transcriptional data(HTSEQ-FPKM)and clinical information of a 472 Melanoma cohort GDC TCGA Mel...Purpose:To screen potential tumor antigens for melanoma vaccine development and identify different immune subtypes.Methods:Transcriptional data(HTSEQ-FPKM)and clinical information of a 472 Melanoma cohort GDC TCGA Melanoma(SKCM)were downloaded from the UCSC XENA website(http://xena.ucsc.edu/).Subsequently,transcriptome data and clinical information of 210 melanoma cohort GSE65904 were downloaded from Gene Expression Omnibus(GEO),a large global public database.All the transcriptome expression data matrices were log2 transformed for subsequent analysis.GEPIA,TIMER,and IMMPORT databases are also used for analysis.Cell function experiments were performed to validate the role of the IDO1 gene in melanoma cell line A375.Results:Our study provides potential tumor antigens for vaccine development in melanoma patients:GZMB,GBP4,CD79A,APOBEC3F,IDO1,JCHAIN,LAG3,PLA2G2D,XCL2.In addition,we divide melanoma patients into two immune subtypes that have significant differences in tumor immunity and may have different responses to vaccination.In view of the unclear role of IDO1 in melanoma,we selected IDO1 for cell assay validation.Cell function assay showed that IDO1 was significantly overexpressed in the melanoma A375 cell line.After IDO1 knockdown,the activity,invasion,migration and healing ability of A375 cell lines were significantly decreased.Conclusion:Our study could provide a reference for the development of vaccines for melanoma patients.展开更多
The ability of 3D ultrasound volume contrast imaging in C-plane （VCI-C） in the assessment of female levator hiatus was analyzed in eighty normal nullipaxas. Interoperator variability in levator hiatus measurements w...The ability of 3D ultrasound volume contrast imaging in C-plane （VCI-C） in the assessment of female levator hiatus was analyzed in eighty normal nullipaxas. Interoperator variability in levator hiatus measurements was analyzed. The comparison of the axial image of magnetic resonance imaging （MRI） and C-plane image of volume contrast imaging （VCI） in thirty normal nulliparas was also done. It shows that VCI-C can clearly demonstrate the structure and accurately quantitates the size of the levator hiatus. It is reliable, convenient and without contraindication in assessment of female levator hiatus. The technology opens up entirely new modality for assessing female pelvic floor.展开更多
Osteoarthritis(OA)is the main cause of disability in the elderly.Effective intervention in the early and middle stage of osteoarthritis can greatly prevent or slow down the development of the disease,and reduce the pr...Osteoarthritis(OA)is the main cause of disability in the elderly.Effective intervention in the early and middle stage of osteoarthritis can greatly prevent or slow down the development of the disease,and reduce the probability of joint replacement.However,there is to date no effective intervention for early and middle-stage OA.OA microenvironment mainly destroys the balance of oxidative stress,extracellular matrix synthesis and degradation of chondrocytes under the joint action of biological and mechanical factors.Herein,hollow Prussian blue nanozymes(HPBzymes)were designed via a modified hydrothermal template-free method.The aim of this study was to investigate the effects of HPBzymes on chondrocytes and the progression of OA.The intrinsic bioactivities of HPBzymes were excavated in vitro and in vivo,remodeling microenvironment for significantly protecting chondrocytes and delaying the progression of traumatic OA by inhibiting reactive oxygen species(ROS)and Rac1/nuclear factor kappa-B(NF-κB)signaling in a rat model.HPBzyme significantly diminished interleukin(IL)-1β-stimulated inflammation,extracellular matrix degradation,and apoptosis of human chondrocytes.HPBzyme attenuated the expression of Rac1 and the ROS levels and prevented the release and nuclear translocation of NF-κB.Deeply digging the intrinsic bioactivities of nanozyme with single component to remodel microenvironment is an effective strategy for ROS-associated chronic diseases.This study reveals that excavating the bioactivities of nanomedicine deserves attention for diagnosis and treatment of severe diseases.展开更多
Fibrotic remodeling is an adverse consequence of immune response-driven phenotypic modulation of cardiac cells following myocardial infarction(Ml).MicroRNA-146b(miR-146b)is an active regulator of immunomodulation,but ...Fibrotic remodeling is an adverse consequence of immune response-driven phenotypic modulation of cardiac cells following myocardial infarction(Ml).MicroRNA-146b(miR-146b)is an active regulator of immunomodulation,but its function in the cardiac inflammatory cascade and its clinical implication in fibrotic remodeling following Ml remain largely unknown.Herein,miR-146b-5p was found to be upregulated in the infarcted myocardium of mice and the serum of myocardial ischemia patients.Gain-and loss-of-function experiments demonstrated that miR-146b-5p was a hypoxia-induced regulator that governed the pro-fibrotic phenotype transition of cardiac cells.Overexpression of miR-146b-5p activated fibroblast proliferation,migration,and fibroblast-to-myofibroblast transition,impaired endothelial cell function and stress survival,and disturbed macrophage paracrine signaling.Interestingly,the opposite effects were observed when miR-146b-5p expression was inhibited.Luciferase assays and rescue studies demonstrated that the miR-146b-5p target genes mediating the above phenotypic modulations included interleukin 1 receptor associated kinase 1(IRAKI)and carcinoembryonic antigen related cell adhesion molecule 1(CEACAM1).Local delivery of a miR-146b-5p antagomir significantly reduced fibrosis and cell death,and upregulated capillary and reparative macrophages in the infarcted myocardium to restore cardiac remodeling and function in both mouse and porcine Ml models.Local inhibition of miR-146b-5p may represent a novel therapeutic approach to treat cardiac fibrotic remodeling and dysfunction following Ml.展开更多
Vascular regeneration and patency maintenance,without anticoagulant administration,represent key developmental trends to enhance small-diameter vascular grafts(SDVG)performance.In vivo engineered autologous biotubes h...Vascular regeneration and patency maintenance,without anticoagulant administration,represent key developmental trends to enhance small-diameter vascular grafts(SDVG)performance.In vivo engineered autologous biotubes have emerged as SDVG candidates with pro-regenerative properties.However,mechanical failure coupled with thrombus formation hinder translational prospects of biotubes as SDVGs.Previously fabricated poly(ε-caprolactone)skeleton-reinforced biotubes(PBs)circumvented mechanical issues and achieved vascular regeneration,but orally administered anticoagulants were required.Here,highly efficient and biocompatible functional modifications were introduced to living cells on PB lumens.The 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(DMPE)-PEG-conjugated anti-coagulant bivalirudin(DPB)and DMPE-PEG-conjugated endothelial progenitor cell(EPC)-binding TPS-peptide(DPT)modifications possessed functionality conducive to promoting vascular graft patency.Co-modification of DPB and DPT swiftly attained luminal saturation without influencing cell viability.DPB repellent of non-specific proteins,DPB inhibition of thrombus formation,and DPB protection against functional masking of DPT’s EPC-capture by blood components,which promoted patency and rapid endothelialization in rat and canine artery implantation models without anticoagulant administration.This strategy offers a safe,facile,and fast technical approach to convey additional functionalization to living cells within tissue-engineered constructs.展开更多
Mitochondria-targeted sonodynamic therapy(SDT)is a promising strategy to inhibit tumor growth and activate the anti-tumor immune responses.Identifying the mechanisms underlying mitochondria-targeted SDT,further optimi...Mitochondria-targeted sonodynamic therapy(SDT)is a promising strategy to inhibit tumor growth and activate the anti-tumor immune responses.Identifying the mechanisms underlying mitochondria-targeted SDT,further optimizing its efficacy,developing novel sonosensitizer carriers with good biocompatibility pose major challenges to the clinical practice of SDT.In this study,we investigated the mechanisms of mitochondria-targeted SDT and demonstrated that it suppressed the mitochondrial electron transport chain(ETC)in pancreatic cancer cells through RNA-sequencing analysis.Based on these findings,we constructed the functional lipid droplets(LDs)(CPI-613/IR780@LDs),which combined mitochondria-targeted SDT with the tricarboxylic acid(TCA)cycle inhibitor CPI-613.CPI-613/IR780@LDs synergistically inhibited the TCA cycle and the ETC of mitochondrial aerobic respiration to reduce oxygen consumption and increase reactive oxygen species(ROS)generation at the tumor site,thus enhancing the efficacy of SDT in hypoxic pancreatic cancer.Moreover,the combination of mitochondria-targeted SDT and anti-PD-1 antibody exhibited excellent tumor inhibition and activated anti-tumor immune responses by increasing tumorinfiltrating CD8+T cells and reducing regulatory T cells,synergistically arresting the growth of both primary and metastatic pancreatic tumors.Meanwhile,lipid droplets are cell-derived biological carriers with natural mitochondrial targeting ability and can achieve efficient hydrophobic drug loading through active phagocytosis.Therefore,the functional lipid droplet-based SDT combined with anti-PD-1 antibody holds great potential in the clinical treatment of hypoxic pancreatic cancer.展开更多
Background The incidence and mortality rate of pancreatic cancer have increased dramatically in China over recent decades. Focused ultrasound （FU） has been somewhat successful in treating pancreatic cancer. The purp...Background The incidence and mortality rate of pancreatic cancer have increased dramatically in China over recent decades. Focused ultrasound （FU） has been somewhat successful in treating pancreatic cancer. The purpose of this study was to investigate apoptosis in pancreatic cancer cells induced by FU. Methods Suspension of human pancreatic carcinoma cell line PaTu 8988t was radiated by FU, using five doses with different radiation parameters and patterns, including one blank control. Temperature increase of the cell suspension was monitored. Cell apoptosis and death after FU radiation was observed using fluorescence microscopy and was tested by flow cytometer at 3, 6, 12, 24, and 48 hours after ultrasound radiation. Results The maximum cell suspension temperatures following five radiation doses were 28℃, （42.20±2.17）℃, （50.80±0.84）℃, （55.80±2.17）℃, and （65.20±3.11）℃; differences between the doses were statistically significant （P 〈0.05）. The apoptosis rate peaked at 24 hours after radiation, at （0.56±0.15）%, （1.28±0.16）%, （1.84±0.29）%, （5.74±1.15）%, and （2.00±0.84）% for the five doses; differences between the doses were statistically significant （P 〈0.05）. Between doses 1--4, cell apoptosis rates increased as the Tmax increased, in dose 5, as the Tmax was above 60℃, the apoptosis rate decreased. Conclusion Sub-threshold thermal exposures of FU radiation with a continuous radiation pattern could result in higher percentage of apoptosed cells.展开更多
The overexpression of heat shock proteins(HSPs)in tumor cells can activate inherent defense mechanisms during hyperthermia-based treatments,inducing thermoresistance and thus diminishing the treatment efficacy.Here,we...The overexpression of heat shock proteins(HSPs)in tumor cells can activate inherent defense mechanisms during hyperthermia-based treatments,inducing thermoresistance and thus diminishing the treatment efficacy.Here,we report a distinct“non-inhibitor involvement”strategy to address this issue through engineering a calcium-based nanocatalyst(G/A@CaCO_(3)-PEG).The constructed nanocatalyst consists of calcium carbonate(CaCO_(3))-supported glucose oxidase(GOD)and 2D antimonene quantum dots(AQDs),with further surface modification by lipid bilayers and polyethylene glycol(PEG).The engineered G/A@CaCO_(3)-PEG nanocatalyst features prolonged blood circulation,which is stable at neutral pH but rapidly degrades under mildly acidic tumor microenvironment,resulting in rapid release of drug cargo in the tumor microenvironment.The integrated GOD effectively catalyzes the depletion of glucose for reducing the supplies of adenosine triphosphate(ATP)and subsequent down-regulation of HSP expression.This effect then augments the therapeutic efficacy of photothermal hyperthermia induced by 2D AQDs upon irradiation with near-infrared light as assisted by reversing the cancer cells’thermoresistance.Consequently,synergistic antineoplastic effects can be achieved via low-temperature photothermal therapy.Systematic in vitro and in vivo evaluations have demonstrated that G/A@CaCO_(3)-PEG nanocatalysts feature potent antitumor activity with a high tumor-inhibition rate(83.92%).This work thus paves an effective way for augmenting the hyperthermia-based tumor treatments via restriction of the ATP supply.展开更多
Inoperable liver tumors are often treated by thermal ablation that destroys the tumor in situ and spares the adjacent hepatic tissue.Thermal–physical treatment has many advantages,but treatment by freezing or heating...Inoperable liver tumors are often treated by thermal ablation that destroys the tumor in situ and spares the adjacent hepatic tissue.Thermal–physical treatment has many advantages,but treatment by freezing or heating alone has some limitations.By taking the advantages and disadvantages of cryosurgery and thermotherapy into consideration,a new thermal technique that combines cryosurgery and radio frequency ablation has been proposed,thereby overcoming the disadvantages of each treatment strategy and improving therapeutic outcomes.This new approach remains to be systematically studied in the liver;therefore,this study was performed to estimate survival after alternated cooling and heating ablation therapy in a VX2 rabbit liver tumor model.Sixteen days after VX2 carcinoma implantation into the rabbit liver,tumors were treated with alternated cooling and heating ablation therapy.Rabbits were monitored for 6 months after treatment and assessed with ultrasound(US)and computed tomography at 1,7,14,and 30 days posttreatment.Untreated tumor-bearing animals served as the control group.Our results show that alternate freezing and heating ablation therapy resulted in a good recovery of VX2 rabbits.Compared with the control group,treated rabbits lived significantly longer(P\0.05),with 70%of treated animals surviving to 196 days posttreatment without metastasis or recurrence,while none of the controls did so.There was no local recurrence in the treatment group.All rabbits in the control group developed metastasis,while metastasis was only observed in 30% of treated rabbits.These results suggest that alternate cooling and heating ablation therapy can prolong the survival time of rabbits with VX2 liver tumors and is an effective method for tumor therapy.Furthermore,we also showed in this model that contrast enhanced US is a valid follow-up approach to assess treatment effectiveness.展开更多
The management of chronic wounds in diabetes remains challenging due to the complexity of impaired wound healing,delayed healing,susceptibility to infection,and elevated risk of reopening,highlighting the need for eff...The management of chronic wounds in diabetes remains challenging due to the complexity of impaired wound healing,delayed healing,susceptibility to infection,and elevated risk of reopening,highlighting the need for effective chronic wound management with innovative approaches such as multifunctional hydrogels.Here,we have produced HA-DA@rhCol hydrogels consisting of dopamine-modified hyaluronic acid and recombinant human collagen type-III(rhCol)by oxidative coupling of the catechol group using the H_(2)O_(2)/HRP catalytic system.The post-reactive hydrogel has a good porous structure,swelling rate,reasonable degradation,rheological and mechanical properties,and the catechol group and dopamine impart to the hydrogel tissue adhesiveness,antioxidant capacity,and excellent photothermal effects leading to superior in vitro antimicrobial activity.In addition,the ability of rhCol to confer hydrogels to promote angiogenesis and wound repair has also been investigated.Cytotoxicity and hemolysis tests demonstrated the good biocompatibility of the hydrogel.Wound closure,collagen deposition and immunohistochemical examination confirmed the ability of the hydrogel to promote diabetic wound healing.In summary,the adhesive hemostatic antioxidative hydrogel with rhCol to promote wound healing in diabetic rat is an excellent chronic wound dressing.展开更多
文摘AIM: To investigate the relationship between contrastenhanced ultrasound(CEUS),basic fibroblast growth factor(b FGF),endothelin-1(ET-1),and hepatocellular carcinoma(HCC) recurrence after ablation. METHODS: A total of 51 HCC patients(38 males and 13 females) who received radiofrequency ablation in our hospital from June 2012 to July 2014 were enrolled in this study. The patients were divided into two groups: recurrence group and non-recurrence group. Routine abdominal examination was first performed in the horizontal position. Then the patients underwent CEUS and immunohistochemical staining before receiving radiofrequency ablation. All patients were followed-up every three months for one year.The results of CEUS and serum tumor marker levels were evaluated and combined together to estimate HCC recurrence and metastasis. Patients were divided into two groups: recurrence group and non-recurrence group. Quantitative parameters of CEUS and tumor expression levels of b FGF and ET-1 were compared between the two groups,respectively. Binary logistic regression analysis was used to analyze the relationship between CEUS quantitative parameters,expression levels of ET-1 and b FGF,and HCC recurrence after ablation. RESULTS: Based on the quantitative parameters of CEUS before patients received radiofrequency ablation,the levels of tumor rise time(t RT),tumor time to peak(t TTP),tumor peak intensity(t PI) and tumorparenchymal peak intensity(t-p PI) in the recurrence group were significantly lower than those in the nonrecurrence group(16.6 ± 6.1 vs 23.2 ± 7.0,P = 0.000; 41.2 ± 10.2 vs 59.6 ± 14.2,P = 0.000; 23.8 ± 6.7 vs 31.4 ± 6.4,P = 0.000; 7.1 ± 3.4 vs 14.6 ± 7.4,P = 0.000; respectively). The expression levels of b FGF in the recurrence group were significantly higher than those in the non-recurrence group(P < 0.05). Levels of t TTP showed a significant inverse correlation with the level of b FGF in tumors(r =-0.312,P = 0.037). The Binary logistic regression analysis results revealed that the levels of t RT,t TTP,t PI and the level of b FGF were associated with HCC recurrence after radiofrequency ablation(P < 0.05). CONCLUSION: CEUS is a noninvasive and effective method for evaluating the angiogenesis of HCC,and predicting its recurrence and prognosis.
文摘Objective: To investigate the role and potential mechanism of CXCR4 in promoting targeted homing of bone marrow mesenchymal stem cells(BMSCs) with ultrasound-exposed microbubbles(UM) pretreatment. Methods: Third generation BMSCs were divided into four groups control group, ultrasound(US) group, UM group and ultrasound-exposed microbubbles plus catalase group. RT-PCR and western blot were performed to determine the levels of CXCR4 m RNA transcription and protein expression, respectively. Third generation BMSCs were labeled with Fluo-α/AM and divided into three groups: control group, US group and UM group, and flurorescence intensities in the cells were observed immediately, 5 min and 15 min after intervention underflurorescence microscope. The calcium iron levels in the cells were analyzed. BMSCs were divided into i ve group: group A without calcium in the medium, group B, group C, group D and group E containing calcium chloride with concentration of l mol, 2 mol, 4mol, anti-calciurn-sensing receptor antibody, respectively. RT-PCR and western blot were performed to determine the levels of CXCR4 m RNA transcription and proteins expression of the third generation BMSCs of each group, respectively. Results: The levels of CXCR4 m RNA transcription and protein expression between US group and control group had no statistically signii cant dif erence(P>0.05) shown by RT-PCR and western blot; the transcription level in the UM group was signii cantly higher than that in US group and control group(P<0.05); and in the ultrasound-exposed microbubbles plus catalase group, the transcription level was much lower than that in UM group. Fluorescence intensify in the cells of US group had no signii cant dif erence compared with that in the cells of the control group(P>0.05), which in the cells of UM group was signii cantly higher than that in the cells of both US group and control group(P<0.05). Compared to group A, expressions of CXCR4 of group B to D were signii cantly increased in concentration-dependent manner showed by RT-PCR and western blot(P< 0.05). Compared to group C, expressions of CXCR4 of group E were signii cantly decreased(P< 0.05). Conclusions: UM can promote the inl ux of calcium in BMSCs and increase m RNA transcription and protein expression of CXCR4. The latter may partly be caused by influx of calcium.
文摘Primary liver cancer and liver metastases are among the most frequent malignancies worldwide,with an increasing number of new cases and deaths every year.Traditional surgery is only suitable for a limited proportion of patients and imaging-guided percutaneous thermal ablation has achieved optimistic results for management of hepatic malignancy.This synopsis outlines the first clinical practice guidelines for ultrasoundguided percutaneous microwave ablation therapy for hepatic malignancy,which was created by a joint task force of the Society of Chinese Interventional Ultrasound.The guidelines aim at standardizing the microwave ablation procedure and therapeutic efficacy assessment,as well as proposing the criteria for the treatment candidates.
基金supported by the Major Infrastructure Projects of Shanghai Science and Technology (No. 10JC1412600)
文摘Ultrasound can be used not only in examination, but also in therapy, especially in the therapy of cancer. Sonodynamic therapy is an experimental cancer therapy method which uses ultrasound to enhance the cytotoxic effects of agents known as sonosensitizers. It has been tested in vitro and in vivo. The ultrasound could penetrate the tissue and cell under some of conditions which directly changes cell membrane permeability, thereby allowing the delivery of exogenous molecules into the cells in some degree. Ultrasound could inhibit the proliferation or induce the apoptosis of cancer cells in vitro or in vivo. Recent researches indicated low-frequency and low-intensity ultrasound could induce cell apoptosis, which could be strengthened by sonodynamic sensitivity, microbubbles, chemotherapeutic drugs and so on. Most kinds of ultrasound suppressed the proliferation of cancer cells through inducing the apoptosis of cancer cells. The mechanism of apoptosis is not clear. In this review, we will focus on and discuss the mechanisms of the induction of cancer cell apoptosis by ultrasound.
基金supported by the National Natural Science Foundation of China(No.81401428)
文摘Objective:To observe the protective effect of breviscapineon mice with cisplatin-induced nephrotoxicity.Methods:Mice were given a single injection of cisplalin(8 mg/kg,up.);then,breviscapine was given to mice at 25 mg/kg and 50 mg/kg doses,respectively,once a day for seven days.Renal tissue structure was observed after animals were sacrificed.Blood urea nitrogen(BUN),serum creatinine(Scr),lipid peroxide(MDA) and superoxide dismutase(SOD) serum levels were detected;and MDA,glutathione peroxidase,and SOD levels in the renal cortex were detected.Results:Compared with the blank control group(BCG),the kidney pathological damage of mice in the model control group(MCG) was more severe.After applying different doses of breviscapine,different degrees of renal injury improvement appeared.Compared with the BCG,the serum levels of Scr and BUN in the MCG increased to(89.92±6.78) μmoL/L and(15.32±4.53) mmoL/L.The differences were statistical significant(P<0.01).Compared with the MCG,the serum levels of Scr and BUN in the Bre low-dose groups and Bre high-dose groups decreased significantly(P<0.05).Compared with the BCG,the MDA levels in serum and in the renal cortex in the MCG significantly increased,while the SOD levels significantly decreased.Both the differences were statistically significant(P<0.01).In the Bre low-dose groups and Bre high-dose groups,MDA levels in serum and in the renal cortex significantly decreased,while SOD and glutathione peroxidase levels in the renal cortex significantly increased,compared with the MCG;and the differences were statistically significant(P<0.05).Conclusions:Breviscapine can reduce cisplatin induced renal toxicity in mice and it's possible through inhibition of renal tubule cell lipid peroxidation and reduces the nephrotoxicity of cisplatin.
文摘Diagnostic ultrasound is a useful and noninvasive method in clinical medicine. Although due to its qualitative, sub- jective and experience-based nature, ultrasound image interpretation can be influenced by image conditions such as scanning frequency and machine settings. In this paper, a novel method is proposed to extract the liver features using the joint features of fractal dimension and the entropies of texture edge co-occurrence matrix based on ultrasound images, which is not sensitive to changes in emission frequency and gain. Then, Fisher linear classifier and support vector machine are employed to test a group of 99 in-vivo liver fibrosis images from 18 patients, as well as other 273 liver images from 18 normal human volunteers.
文摘Objective To investigate the diagnostic value of miniprobe ultrasonography (MPS) in the protruding lesions of esophagus. Methods Sixty-two patients with protruding lesions of esophagus were examined with MPS. Results The MPS examination showed diseases of esophageal polyp, inflammatory protruding, esophageal leiomyoma, esophageal leiomyosarcoma, esophageal venous aneurysm, esophageal lipoma, esophageal cyst, esophageal carcinoma, and extra esophageal compression including aorta compression, lung tumor compression and spina compression. Fourteen patients were verified by surgical operations and pathological examinations, resulting in 92.86% (13/14) diagnosis accuracy rate. Forty-eight cases had results of gastroscope examination consistent with that of MPS. Twelve cases had results of CT and MRI examination consistent with that of MPS. Follow-up was completed on 22 patients. Conclusion Besides imaging the esophageal layer, MPS can precisely locate the histological layer of the esophageal protruding lesions and predict their characters. This indicates its value in the diagnosis and differential diagnosis of the protruding lesions of esophagus. Furthermore, the miniature probe used in MPS examination can pass the structured esophagus, enabling wider application of the examination.
文摘AIM: To evaluate the utility of liver reserve function by acoustic radiation force impulse(ARFI) imaging in patients with liver tumors. METHODS: Seventy-six patients with liver tumors were enrolled in this study. Serum biochemical indexes, such as aminotransferase(ALT), aspartate aminotransferase(AST), serum albumin(ALB), total bilirubin(T-Bil), and other indicators were observed. Liver stiffness(LS) was measured by ARFI imaging, measurements were repeated 10 times, and the average value of the results was taken as the final LS value. Indocyanine green(ICG) retention was performed, and ICG-K and ICG-R15 were recorded. Child-Pugh(CP) scores were carried out based on patient's preoperative biochemical tests and physical condition. Correlations among CP scores,ICG-R15, ICG-K and LS values were observed and analyzed using either the Pearson correlation coefficient or the Spearman rank correlation coefficient. KruskalWallis test was used to compare LS values of CP scores, and the receiver-operator characteristic(ROC) curve was used to analyze liver reserve function assessment accuracy. RESULTS: LS in the ICG-R15 10%-20% group was significantly higher than in the ICG-R15 < 10% group; and the difference was statistically significant(2.19 ± 0.27 vs 1.59 ± 0.32, P < 0.01). LS in the ICG-R15 > 20% group was significantly higher than in the ICG-R15 < 10% group; and the difference was statistically significant(2.92 ± 0.29 vs 1.59 ± 0.32, P < 0.01). The LS value in patients with CP class A was lower than in patients with CP class B(1.57 ± 0.34 vs 1.86 ± 0.27, P < 0.05), while the LS value in patients with CP class B was lower than in patients with CP class C(1.86 ± 0.27 vs 2.47 ± 0.33, P < 0.01). LS was positively correlated with ICG-R15(r = 0.617, P < 0.01) and CP score(r = 0.772, P < 0.01). Meanwhile, LS was negatively correlated with ICG-K(r =-0.673, P < 0.01). AST, ALT and T-Bil were positively correlated with LS, while ALB was negatively correlated with LS(P < 0.05). The ROC curve revealed that the when the LS value was 2.34 m/s, the Youden index was at its highest point, sensitivity was 69.2% and specificity was 92.1%. CONCLUSION: For patients with liver tumors, ARFI imaging is a useful tool for assessing liver reserve function.
基金supported by the National Key Research and Development Program of China (Grant No.2023YFC3402100)the National Natural Science Foundation of China (Grant No.92259102)。
文摘Cancer stem cells(CSCs) are a small subset of cells in cancers that are thought to initiate tumorous transformation and promote metastasis, recurrence, and resistance to treatment. Growing evidence has revealed the existence of CSCs in various types of cancers and suggested that CSCs differentiate into diverse lineage cells that contribute to tumor progression. We may be able to overcome the limitations of cancer treatment with a comprehensive understanding of the biological features and mechanisms underlying therapeutic resistance in CSCs. This review provides an overview of the properties, biomarkers, and mechanisms of resistance shown by CSCs. Recent findings on metabolic features, especially fatty acid metabolism and ferroptosis in CSCs, are highlighted, along with promising targeting strategies. Targeting CSCs is a potential treatment plan to conquer cancer and prevent resistance and relapse in cancer treatment.
基金supported by the Top Talent Project of Jiangsu Provincial People’s Hospital(No.YNRCZN0310).
文摘Purpose:To screen potential tumor antigens for melanoma vaccine development and identify different immune subtypes.Methods:Transcriptional data(HTSEQ-FPKM)and clinical information of a 472 Melanoma cohort GDC TCGA Melanoma(SKCM)were downloaded from the UCSC XENA website(http://xena.ucsc.edu/).Subsequently,transcriptome data and clinical information of 210 melanoma cohort GSE65904 were downloaded from Gene Expression Omnibus(GEO),a large global public database.All the transcriptome expression data matrices were log2 transformed for subsequent analysis.GEPIA,TIMER,and IMMPORT databases are also used for analysis.Cell function experiments were performed to validate the role of the IDO1 gene in melanoma cell line A375.Results:Our study provides potential tumor antigens for vaccine development in melanoma patients:GZMB,GBP4,CD79A,APOBEC3F,IDO1,JCHAIN,LAG3,PLA2G2D,XCL2.In addition,we divide melanoma patients into two immune subtypes that have significant differences in tumor immunity and may have different responses to vaccination.In view of the unclear role of IDO1 in melanoma,we selected IDO1 for cell assay validation.Cell function assay showed that IDO1 was significantly overexpressed in the melanoma A375 cell line.After IDO1 knockdown,the activity,invasion,migration and healing ability of A375 cell lines were significantly decreased.Conclusion:Our study could provide a reference for the development of vaccines for melanoma patients.
基金the Scientific Research Project of Shanghai Municipal Health Bureau (No. 2008083)
文摘The ability of 3D ultrasound volume contrast imaging in C-plane （VCI-C） in the assessment of female levator hiatus was analyzed in eighty normal nullipaxas. Interoperator variability in levator hiatus measurements was analyzed. The comparison of the axial image of magnetic resonance imaging （MRI） and C-plane image of volume contrast imaging （VCI） in thirty normal nulliparas was also done. It shows that VCI-C can clearly demonstrate the structure and accurately quantitates the size of the levator hiatus. It is reliable, convenient and without contraindication in assessment of female levator hiatus. The technology opens up entirely new modality for assessing female pelvic floor.
基金supported by the National Natural Science Foundation of China(no.81801822)Shanghai S&T Major project(2018SHZDZX05)+3 种基金NSFC Key Projects of International Cooperation and Exchanges(81720108023)Shanghai Collaborative Innovation Center for Translational Medicine(no.TM201724)Natural Science Foundation of Shanghai(18ZR1429300)Interdisciplinary Program of Shanghai Jiao Tong University(no.YG2017QN20).
文摘Osteoarthritis(OA)is the main cause of disability in the elderly.Effective intervention in the early and middle stage of osteoarthritis can greatly prevent or slow down the development of the disease,and reduce the probability of joint replacement.However,there is to date no effective intervention for early and middle-stage OA.OA microenvironment mainly destroys the balance of oxidative stress,extracellular matrix synthesis and degradation of chondrocytes under the joint action of biological and mechanical factors.Herein,hollow Prussian blue nanozymes(HPBzymes)were designed via a modified hydrothermal template-free method.The aim of this study was to investigate the effects of HPBzymes on chondrocytes and the progression of OA.The intrinsic bioactivities of HPBzymes were excavated in vitro and in vivo,remodeling microenvironment for significantly protecting chondrocytes and delaying the progression of traumatic OA by inhibiting reactive oxygen species(ROS)and Rac1/nuclear factor kappa-B(NF-κB)signaling in a rat model.HPBzyme significantly diminished interleukin(IL)-1β-stimulated inflammation,extracellular matrix degradation,and apoptosis of human chondrocytes.HPBzyme attenuated the expression of Rac1 and the ROS levels and prevented the release and nuclear translocation of NF-κB.Deeply digging the intrinsic bioactivities of nanozyme with single component to remodel microenvironment is an effective strategy for ROS-associated chronic diseases.This study reveals that excavating the bioactivities of nanomedicine deserves attention for diagnosis and treatment of severe diseases.
文摘Fibrotic remodeling is an adverse consequence of immune response-driven phenotypic modulation of cardiac cells following myocardial infarction(Ml).MicroRNA-146b(miR-146b)is an active regulator of immunomodulation,but its function in the cardiac inflammatory cascade and its clinical implication in fibrotic remodeling following Ml remain largely unknown.Herein,miR-146b-5p was found to be upregulated in the infarcted myocardium of mice and the serum of myocardial ischemia patients.Gain-and loss-of-function experiments demonstrated that miR-146b-5p was a hypoxia-induced regulator that governed the pro-fibrotic phenotype transition of cardiac cells.Overexpression of miR-146b-5p activated fibroblast proliferation,migration,and fibroblast-to-myofibroblast transition,impaired endothelial cell function and stress survival,and disturbed macrophage paracrine signaling.Interestingly,the opposite effects were observed when miR-146b-5p expression was inhibited.Luciferase assays and rescue studies demonstrated that the miR-146b-5p target genes mediating the above phenotypic modulations included interleukin 1 receptor associated kinase 1(IRAKI)and carcinoembryonic antigen related cell adhesion molecule 1(CEACAM1).Local delivery of a miR-146b-5p antagomir significantly reduced fibrosis and cell death,and upregulated capillary and reparative macrophages in the infarcted myocardium to restore cardiac remodeling and function in both mouse and porcine Ml models.Local inhibition of miR-146b-5p may represent a novel therapeutic approach to treat cardiac fibrotic remodeling and dysfunction following Ml.
基金supported by the National Natural Science Foundation of China(NSFC)projects 81921004(D.K.),82127808(D.K.),32222043(K.W.),82250610231(A.C.M.)National Key R&D Program of China 2022YFA1105102(K.W.)+3 种基金Tianjin Natural Science Foundation 20JCYBJC01150(K.W.)Tianjin Natural Science Foundation 18JCZDJC37600(K.W.)NCC Fund NCC2020PY18(K.W.)Tianjin"Project+Team"Key Training Foundation XC202035(K.W.).
文摘Vascular regeneration and patency maintenance,without anticoagulant administration,represent key developmental trends to enhance small-diameter vascular grafts(SDVG)performance.In vivo engineered autologous biotubes have emerged as SDVG candidates with pro-regenerative properties.However,mechanical failure coupled with thrombus formation hinder translational prospects of biotubes as SDVGs.Previously fabricated poly(ε-caprolactone)skeleton-reinforced biotubes(PBs)circumvented mechanical issues and achieved vascular regeneration,but orally administered anticoagulants were required.Here,highly efficient and biocompatible functional modifications were introduced to living cells on PB lumens.The 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(DMPE)-PEG-conjugated anti-coagulant bivalirudin(DPB)and DMPE-PEG-conjugated endothelial progenitor cell(EPC)-binding TPS-peptide(DPT)modifications possessed functionality conducive to promoting vascular graft patency.Co-modification of DPB and DPT swiftly attained luminal saturation without influencing cell viability.DPB repellent of non-specific proteins,DPB inhibition of thrombus formation,and DPB protection against functional masking of DPT’s EPC-capture by blood components,which promoted patency and rapid endothelialization in rat and canine artery implantation models without anticoagulant administration.This strategy offers a safe,facile,and fast technical approach to convey additional functionalization to living cells within tissue-engineered constructs.
基金the financial support from the National Natural Science Foundation of China(Nos.32201138,82030048,and 82230069)the Key Research and Development Program of Zhejiang Province(No.2019C03077).
文摘Mitochondria-targeted sonodynamic therapy(SDT)is a promising strategy to inhibit tumor growth and activate the anti-tumor immune responses.Identifying the mechanisms underlying mitochondria-targeted SDT,further optimizing its efficacy,developing novel sonosensitizer carriers with good biocompatibility pose major challenges to the clinical practice of SDT.In this study,we investigated the mechanisms of mitochondria-targeted SDT and demonstrated that it suppressed the mitochondrial electron transport chain(ETC)in pancreatic cancer cells through RNA-sequencing analysis.Based on these findings,we constructed the functional lipid droplets(LDs)(CPI-613/IR780@LDs),which combined mitochondria-targeted SDT with the tricarboxylic acid(TCA)cycle inhibitor CPI-613.CPI-613/IR780@LDs synergistically inhibited the TCA cycle and the ETC of mitochondrial aerobic respiration to reduce oxygen consumption and increase reactive oxygen species(ROS)generation at the tumor site,thus enhancing the efficacy of SDT in hypoxic pancreatic cancer.Moreover,the combination of mitochondria-targeted SDT and anti-PD-1 antibody exhibited excellent tumor inhibition and activated anti-tumor immune responses by increasing tumorinfiltrating CD8+T cells and reducing regulatory T cells,synergistically arresting the growth of both primary and metastatic pancreatic tumors.Meanwhile,lipid droplets are cell-derived biological carriers with natural mitochondrial targeting ability and can achieve efficient hydrophobic drug loading through active phagocytosis.Therefore,the functional lipid droplet-based SDT combined with anti-PD-1 antibody holds great potential in the clinical treatment of hypoxic pancreatic cancer.
文摘Background The incidence and mortality rate of pancreatic cancer have increased dramatically in China over recent decades. Focused ultrasound （FU） has been somewhat successful in treating pancreatic cancer. The purpose of this study was to investigate apoptosis in pancreatic cancer cells induced by FU. Methods Suspension of human pancreatic carcinoma cell line PaTu 8988t was radiated by FU, using five doses with different radiation parameters and patterns, including one blank control. Temperature increase of the cell suspension was monitored. Cell apoptosis and death after FU radiation was observed using fluorescence microscopy and was tested by flow cytometer at 3, 6, 12, 24, and 48 hours after ultrasound radiation. Results The maximum cell suspension temperatures following five radiation doses were 28℃, （42.20±2.17）℃, （50.80±0.84）℃, （55.80±2.17）℃, and （65.20±3.11）℃; differences between the doses were statistically significant （P 〈0.05）. The apoptosis rate peaked at 24 hours after radiation, at （0.56±0.15）%, （1.28±0.16）%, （1.84±0.29）%, （5.74±1.15）%, and （2.00±0.84）% for the five doses; differences between the doses were statistically significant （P 〈0.05）. Between doses 1--4, cell apoptosis rates increased as the Tmax increased, in dose 5, as the Tmax was above 60℃, the apoptosis rate decreased. Conclusion Sub-threshold thermal exposures of FU radiation with a continuous radiation pattern could result in higher percentage of apoptosed cells.
基金the financial support from the NSFC Key Projects of International Cooperation and Exchanges(Grant No.81720108023)National Key R&D Program of China(Grant No.2018YFC0115200)+2 种基金National Natural Science Foundation of China(Grant No.82001943)Translational medicine national science and technology infrastructure(Shanghai)open project fund(TMSK-2020-004)China Postdoctoral Science Foundation(2020M681331,2021T140458).
文摘The overexpression of heat shock proteins(HSPs)in tumor cells can activate inherent defense mechanisms during hyperthermia-based treatments,inducing thermoresistance and thus diminishing the treatment efficacy.Here,we report a distinct“non-inhibitor involvement”strategy to address this issue through engineering a calcium-based nanocatalyst(G/A@CaCO_(3)-PEG).The constructed nanocatalyst consists of calcium carbonate(CaCO_(3))-supported glucose oxidase(GOD)and 2D antimonene quantum dots(AQDs),with further surface modification by lipid bilayers and polyethylene glycol(PEG).The engineered G/A@CaCO_(3)-PEG nanocatalyst features prolonged blood circulation,which is stable at neutral pH but rapidly degrades under mildly acidic tumor microenvironment,resulting in rapid release of drug cargo in the tumor microenvironment.The integrated GOD effectively catalyzes the depletion of glucose for reducing the supplies of adenosine triphosphate(ATP)and subsequent down-regulation of HSP expression.This effect then augments the therapeutic efficacy of photothermal hyperthermia induced by 2D AQDs upon irradiation with near-infrared light as assisted by reversing the cancer cells’thermoresistance.Consequently,synergistic antineoplastic effects can be achieved via low-temperature photothermal therapy.Systematic in vitro and in vivo evaluations have demonstrated that G/A@CaCO_(3)-PEG nanocatalysts feature potent antitumor activity with a high tumor-inhibition rate(83.92%).This work thus paves an effective way for augmenting the hyperthermia-based tumor treatments via restriction of the ATP supply.
文摘Inoperable liver tumors are often treated by thermal ablation that destroys the tumor in situ and spares the adjacent hepatic tissue.Thermal–physical treatment has many advantages,but treatment by freezing or heating alone has some limitations.By taking the advantages and disadvantages of cryosurgery and thermotherapy into consideration,a new thermal technique that combines cryosurgery and radio frequency ablation has been proposed,thereby overcoming the disadvantages of each treatment strategy and improving therapeutic outcomes.This new approach remains to be systematically studied in the liver;therefore,this study was performed to estimate survival after alternated cooling and heating ablation therapy in a VX2 rabbit liver tumor model.Sixteen days after VX2 carcinoma implantation into the rabbit liver,tumors were treated with alternated cooling and heating ablation therapy.Rabbits were monitored for 6 months after treatment and assessed with ultrasound(US)and computed tomography at 1,7,14,and 30 days posttreatment.Untreated tumor-bearing animals served as the control group.Our results show that alternate freezing and heating ablation therapy resulted in a good recovery of VX2 rabbits.Compared with the control group,treated rabbits lived significantly longer(P\0.05),with 70%of treated animals surviving to 196 days posttreatment without metastasis or recurrence,while none of the controls did so.There was no local recurrence in the treatment group.All rabbits in the control group developed metastasis,while metastasis was only observed in 30% of treated rabbits.These results suggest that alternate cooling and heating ablation therapy can prolong the survival time of rabbits with VX2 liver tumors and is an effective method for tumor therapy.Furthermore,we also showed in this model that contrast enhanced US is a valid follow-up approach to assess treatment effectiveness.
基金supported by grants from National Natural Science Foundation of China No.82172206Zhejiang Provincial Medical and Healthy Science Foundation of China(No.2023RC183 and 2024KY110).
文摘The management of chronic wounds in diabetes remains challenging due to the complexity of impaired wound healing,delayed healing,susceptibility to infection,and elevated risk of reopening,highlighting the need for effective chronic wound management with innovative approaches such as multifunctional hydrogels.Here,we have produced HA-DA@rhCol hydrogels consisting of dopamine-modified hyaluronic acid and recombinant human collagen type-III(rhCol)by oxidative coupling of the catechol group using the H_(2)O_(2)/HRP catalytic system.The post-reactive hydrogel has a good porous structure,swelling rate,reasonable degradation,rheological and mechanical properties,and the catechol group and dopamine impart to the hydrogel tissue adhesiveness,antioxidant capacity,and excellent photothermal effects leading to superior in vitro antimicrobial activity.In addition,the ability of rhCol to confer hydrogels to promote angiogenesis and wound repair has also been investigated.Cytotoxicity and hemolysis tests demonstrated the good biocompatibility of the hydrogel.Wound closure,collagen deposition and immunohistochemical examination confirmed the ability of the hydrogel to promote diabetic wound healing.In summary,the adhesive hemostatic antioxidative hydrogel with rhCol to promote wound healing in diabetic rat is an excellent chronic wound dressing.
