BACKGROUND Colorectal cancer(CRC) is one of the main causes of cancer-related deaths in China and around the world. Advanced CRC(ACRC) patients suffer from a low cure rate though treated with targeted therapies. The r...BACKGROUND Colorectal cancer(CRC) is one of the main causes of cancer-related deaths in China and around the world. Advanced CRC(ACRC) patients suffer from a low cure rate though treated with targeted therapies. The response rate is about 50% to chemotherapy and cetuximab, a monoclonal antibody targeting epidermal growth factor receptor(EGFR) and used for ACRC with wild-type KRAS. It is important to identify more predictors of cetuximab efficacy to further improve precise treatment. Autophagy, showing a key role in the cancer progression, is influenced by the EGFR pathway. Whether autophagy can predict cetuximab efficacy in ACRC is an interesting topic.AIM To investigate the effect of autophagy on the efficacy of cetuximab in colon cancer cells and ACRC patients with wild-type KRAS.METHODS ACRC patients treated with cetuximab plus chemotherapy, with detailed data and tumor tissue, at Sun Yat-sen University Cancer Center from January 1, 2005,to October 1, 2015, were studied. Expression of autophagy-related proteins[Beclin1, microtubule-associated protein 1 A/B-light chain 3(LC3), and 4 Ebinding protein 1(4 E-BP1)] was examined by Western blot in CRC cells and by immunohistochemistry in cancerous and normal tissues. The effect of autophagy on cetuximab-treated cancer cells was confirmed by MTT assay. The associations between Beclin1, LC3, and 4 E-BP1 expression in tumor tissue and the efficacy of cetuximab-based therapy were analyzed.RESULTS In CACO-2 cells exposed to cetuximab, LC3 and 4 E-BP1 were upregulated, and P62 was downregulated. Autophagosome formation was observed, and autophagy increased the efficacy of cetuximab. In 68 ACRC patients,immunohistochemistry showed that Beclin1 levels were significantly correlated with those of LC3(0.657, P < 0.001) and 4 E-BP1(0.211, P = 0.042) in ACRC tissues.LC3 was significantly overexpressed in tumor tissues compared to normal tissues(P < 0.001). In 45 patients with wild-type KRAS, the expression levels of these three proteins were not related to progression-free survival; however, the expression levels of Beclin1(P = 0.010) and 4 E-BP1(P = 0.005), pathological grade(P = 0.002), and T stage(P = 0.004) were independent prognostic factors for overall survival(OS).CONCLUSION The effect of cetuximab on colon cancer cells might be improved by autophagy.LC3 is overexpressed in tumor tissues, and Beclin1 and 4 E-BP1 could be significant predictors of OS in ACRC patients treated with cetuximab.展开更多
We induced human placenta-derived mesenchymal stem cells （hPMSCs） to differentiate into neural cells by adding chemical reagents, despite the fact that toxic chemicals induce cell shrinkage or cytoskeletal formation...We induced human placenta-derived mesenchymal stem cells （hPMSCs） to differentiate into neural cells by adding chemical reagents, despite the fact that toxic chemicals induce cell shrinkage or cytoskeletal formation, which does not represent a proper cell differentiation process. The present study established a co-culture system with hPMSCs and neural cells and analyzed the influence of neural cells on hPMSC differentiation in a co-culture system, hPMSCs were isolated and purified from human full-term placenta using collagenase digestion. Fetal neural cells were co-cultured with hPMSCs for 48 hours using the Transwell co-culture system, hPMSCs co-cultured with neural cells exhibited a slender morphology with a filament. After 96 hours, hPMSCs expressed neuron-specific enolase, which suggested that co-culture of hPMSCs and neural cells induced neural differentiation of hPMSCs.展开更多
A series of zinc silylamido complexes based upon NNO tridentate enolic Schiff base framework have been synthesized and characterized. These complexes were tested for the ring opening polymerization of lactide and e-ca...A series of zinc silylamido complexes based upon NNO tridentate enolic Schiff base framework have been synthesized and characterized. These complexes were tested for the ring opening polymerization of lactide and e-caprolactone, exhibiting notably high activity at ambient temperature, The influence of imine bridge length and substituents of diketone over the course of polymerization was investigated in details. Remarkably, 4a was confirmed to be a rare example of exceedingly active and robust zinc catalysts, achieving major transformation of lactide under extremely low loading （0.025 mol%） within 18 rain. The influence of various monomers as well as the polymerization mechanism have also been discussed.展开更多
Background Myocardial infarction （MI） has likely contributed to the increased prevalence of heart failure （HF）. As a result of re- duced cardiac function, splanchnic blood flow decreases, causing ischemia in villi...Background Myocardial infarction （MI） has likely contributed to the increased prevalence of heart failure （HF）. As a result of re- duced cardiac function, splanchnic blood flow decreases, causing ischemia in villi and damage to the intestinal barrier. The induction of heme oxygenase-1 （HO-1） could prevent, or lessen the effects of stress and inflammation. Thus, the effect and mechanism thereof of HO-1 on the intestines of rats with HF was investigated. Methods Male Wistar rats with heart failure through ligation of the left coronary artery were identified with an left ventricular ejection fraction of 〈 45% through echocardiography and then divided into various experimental groups based on the type of peritoneal injection they received [MI： saline; MI ＋ Cobalt protoporphyrin （CoPP）： CoPP solution; and MI ＋ Tin mesoporphyrin IX dichloride （SnMP）： SnMP solution]. The control group was comprised of rats without coronary ligation. Echocardiogra- phy was performed before ligation for a baseline and eight weeks after ligation in order to evaluate the cardiac function of the rats. The bac- terial translocation （BT） incidence, mesenteric microcirculation, amount of endotoxins in the vein serum, ileum levels of HO- 1, carbon oxide （CO）, nitric oxide （NO）, intedeuldn （IL）-10, turnour necrosis factor-et （TNF-ct）, and the ileum morphology were determined eight weeks after the operation. Results The rats receiving MI ＋ CoPP injections exhibited a recovery in cardiac function, an amelioration of mesenteric microcirculation and change in morphology, a lower BT incidence, a reduction in serum and ileac NO and TNF-ct levels, and an elevation in ileac HO-1, CO, and interleukin-10 （[L-10） levels compared to the MI group （P 〈 0.05）. The rats that received the MI ＋ SnMP injections exhibited results inverse to the MI （P 〈 0.05） group. Conclusions HO-1 exerted a protective effect on the intestines of rats with HF by inhibiting the inflammation and amelioration of microcirculation through the CO pathway. This protective effect could be independent from the recovery of cardiac function.展开更多
Over the past decade,nanoparticle-based therapeutic modalities have become promising strategies in cancer therapy.Selective delivery of anticancer drugs to the lesion sites is critical for elimination of the tumor and...Over the past decade,nanoparticle-based therapeutic modalities have become promising strategies in cancer therapy.Selective delivery of anticancer drugs to the lesion sites is critical for elimination of the tumor and an improved prognosis.Innovative design and advanced biointerface engineering have promoted the development of various nanocarriers for optimized drug delivery.Keeping in mind the biological framework of the tumormicroenvironment,biomembrane-camouflaged nanoplatforms have been a research focus,reflecting their superiority in cancer targeting.In this review,we summarize the development of various biomimetic cell membrane-camouflaged nanoplatforms for cancertargeted drug delivery,which are classified according to the membranes fromdifferent cells.The challenges and opportunities of the advanced biointerface engineering drug delivery nanosystems in cancer therapy are discussed.展开更多
The functional properties of endogenous Schwann cells(SCs)during nerve repair are dynamic.Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the r...The functional properties of endogenous Schwann cells(SCs)during nerve repair are dynamic.Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the repair of damaged nerves.Previous studies showed that miR-221-3p promotes the proliferation and migration of SCs,and miR-338-3p promotes the myelination of SCs.In this study,we established rat models of sciatic nerve injury by bridging the transected sciatic nerve with a silicone tube.We injected a miR-221 lentiviral vector system together with a doxycycline-inducible Tet-On miR-338 lentiviral vector system into the cavity of nerve conduits of nerve stumps to sequentially regulate the biological function of endogenous SCs at different stages of nerve regeneration.We found that the biological function of SCs was sequentially regulated,the diameter and density of myelinated axons were increased,the expression levels of NF200 and myelin basic protein were increased,and the function of injured peripheral nerve was improved using this system.miRNA Target Prediction Database prediction,Nanopore whole transcriptome sequencing,quantitative PCR,and dual luciferase reporter gene assay results predicted and verified Cdkn1b and Nrp1 as target genes of miR-221-3p and miR-338-3p,respectively,and their regulatory effects on SCs were confirmed in vitro.In conclusion,here we established a new method to enhance nerve regeneration through sequential regulation of biological functions of endogenous SCs,which establishes a new concept and model for the treatment of peripheral nerve injury.The findings from this study will provide direct guiding significance for clinical treatment of sciatic nerve injury.展开更多
Hyperkalemia,usually associated with predisposing chronic diseases as heart failure(HF),severe kidney disease or diabetes mellitus(DM),[1]is defined as an elevation of potassium concentration more than 5.5 mmol/L,[2].
White spot lesions （WSLs）, due to enamel demineralization, occur frequently in orthodontic treatment. We recently developed a novel rechargeable dental composite containing nanoparticles of amorphous calcium phospha...White spot lesions （WSLs）, due to enamel demineralization, occur frequently in orthodontic treatment. We recently developed a novel rechargeable dental composite containing nanoparticles of amorphous calcium phosphate （NACP） with long-term calcium （Ca） and phosphate （P） ion release and caries-inhibiting capability. The objectives of this study were to develop the first NACP- rechargeable orthodontic cement and investigate the effects of recharge duration and frequency on the efficacy of ion re-release. The rechargeable cement consisted of pyromellitic glycerol dimethacrylate （PMGDM） and ethoxylated bisphenol A dimethacrylate （EBPADMA）. NACP was mixed into the resin at 40% by mass. Specimens were tested for orthodontic bracket shear bond strength （SBS） to enamel, Ca and P ion initial release, recharge and re-release. The new orthodontic cement exhibited an SBS similar to commercial orthodontic cement without CaP release （P〉 0.1）. Specimens after one recharge treatment （e.g., 1 min immersion in recharge solution repeating three times in one day, referred to as ＂1 min 3 times＂） exhibited a substantial and continuous re-release of Ca and P ions for 14 days without further recharge. The ion re-release did not decrease with increasing the number of recharge/re-release cycles （P〉 0.1）. The ion re-release concentrations at 14 days versus various recharge treatments were as follows： 1 min 3 times〉3 min 2 times〉 1 min 2 times〉6 min 1 time〉3 min 1 time〉 1 min 1 time. In conclusion, although previous studies have shown that NACP nanocomposite remineralized tooth lesions and inhibited caries, the present study developed the first orthodontic cement with Ca and P ion recharge and long-term release capability. This NACP-rechargeable orthodontic cement is a promising therapy to inhibit enamel demineralization and WSLs around orthodontic brackets.展开更多
Dentin hypersensitivity(DH)associated with dentinal tubule exposure is one of the most common causes of toothache with a rapid onset and short duration.Medication,filling repair,laser irradiation,crown therapy,and des...Dentin hypersensitivity(DH)associated with dentinal tubule exposure is one of the most common causes of toothache with a rapid onset and short duration.Medication,filling repair,laser irradiation,crown therapy,and desensitizing toothpaste are standard clinical treatment strategies,but unsatisfactory treatment modalities are marked by long-term administration,poor dentinal tubule closure,microleakage,and the development of secondary caries.To improve the treatment efficiency of DH,numerous organic or inorganic biomaterials have been developed to relieve toothache and reverse the instability of desensitization.Biomaterials are expected to participate in dental remineralization to achieve desensitization.This review discusses various biomaterials for DH therapy based on different desensitization mechanisms,including dentinal tubule closure and dental nerve blockade,and presents a perspective on the underlying future of dentin regeneration medicine for DH therapy.展开更多
Objective:To discuss the relationship of ultrasonic shear wave velocity (SWV) with oncogene and tumor suppressor gene expression in primary liver cancer lesions as well as angiogenesis factor contents.Methods:100 pati...Objective:To discuss the relationship of ultrasonic shear wave velocity (SWV) with oncogene and tumor suppressor gene expression in primary liver cancer lesions as well as angiogenesis factor contents.Methods:100 patients with primary liver cancer who underwent surgical treatment in our hospital between March 2014 and September 2016 were collected as observation group, and 50 healthy subjects who received physical examination in our hospital during the same period were collected as normal control group. The ultrasonic SWV levels of two groups of subjects were measured before the operation, and the observation groups were further divided into high SWV group and low SWV group, 50 cases in each group. Intraoperative tumor tissue samples were kept and fluorescence quantitative PCR was used to determine the mRNA expression of oncogenes and tumor suppressor genes. Enzyme-linked immunosorbent assay was used to determine serum contents of angiogenesis factors in observation group before operation.Results:Hepatic ultrasonic SWV level in observation group was significantly higher than that in normal control group;proto-oncogene CK, Ki67, Gly-3, Survivin and Pokemon mRNA expression in tumor tissue of high SWV group were higher than those of low SWV group while tumor suppressor genes Tg737, p16, p27, PTEN and runx3 mRNA expression were lower than those of low SWV group;serum angiogenesis factors VEGF, MMP-9 and IGF-1R contents were higher than those in low SWV group. Conclusion: The hepatic ultrasonic SWV level increases in patients with primary liver cancer, and the SWV level is directly correlated with oncogene and tumor suppressor gene expression as well as angiogenesis factor contents.展开更多
This case report describes a foreign body retained in the liver long after perihepatic gauze packing. A 64-year-old female patient had suffered a rib fracture and liver rupture during a traffic accident in 1973. She d...This case report describes a foreign body retained in the liver long after perihepatic gauze packing. A 64-year-old female patient had suffered a rib fracture and liver rupture during a traffic accident in 1973. She discovered a mass in her right hypochondrium. Her hepatic ultrasonography showed a round mass (20.3 cm × 17.3 cm × 16.0 cm in size) with fluid echogenicity in the right lobe of her liver, and a hepatic cystic-solid mass (19.7 cm × 18.5 cm × 15.6 cm in size) was identified in an abdominal computerized tomography scan. Several pieces of gauze were extracted, and brown pus from the hepatic mass was suctioned during her exploratory laparotomy. Histology documented gauze remnants with necrotic material inclusions and fibrotic capsules. To our knowledge, this patient's case represents the longest time for which a foreign body has been retained in the liver. In addition, we conducted a comprehensive literature review of foreign bodies retained in the liver. Foreign bodies may be introduced into the liver via penetrating trauma, surgical procedures or the ingestion of foreign bodies (which then migrate from the gut). Thus, they can be classified into the following three categories: penetrating, medical and migrated foreign bodies. The details of the case are thoroughly described.展开更多
Two cases of prostatic neuroendocrine carcinoma(PNEC) imaged by computed tomography(CT) and magnetic resonance imaging(MRI), and literature review are presented. Early enhanced CT, MRI, especially diffusionweighted im...Two cases of prostatic neuroendocrine carcinoma(PNEC) imaged by computed tomography(CT) and magnetic resonance imaging(MRI), and literature review are presented. Early enhanced CT, MRI, especially diffusionweighted image were emphasized, the complementary roles of ultrasound, CT, MRI, clinical and laboratory characteristic's features in achieving accurate diagnosis were valued in the preoperative diagnosis of PNEC.展开更多
Calcium phosphate cements （CPCs） are frequently used to repair bone defects. Since their discovery in the 1980s, extensive research has been conducted to improve their properties, and emerging evidence supports thei...Calcium phosphate cements （CPCs） are frequently used to repair bone defects. Since their discovery in the 1980s, extensive research has been conducted to improve their properties, and emerging evidence supports their increased application in bone tissue engineering. Much effort has been made to enhance the biological performance of CPCs, including their biocompatibility, osteoconductivity, osteoinductivity, biodegradability, bioactivity, and interactions with cells. This review article focuses on the major recent developments in CPCs, including 3D printing, injectability, stem cell delivery, growth factor and drug delivery, and pre- vascularization of CPC scaffolds via co-culture and tri-culture techniques to enhance angiogenesis and osteogenesis.展开更多
Uric acid is an important, naturally occurring serum antioxidant. The present study investigates the use of uric acid for promoting proliferation and neuronal differentiation of mesenchymal stem cells derived from hum...Uric acid is an important, naturally occurring serum antioxidant. The present study investigates the use of uric acid for promoting proliferation and neuronal differentiation of mesenchymal stem cells derived from human placenta tissue. Human placenta-derived mesenchymal stem cells were pre-induced in the presence of either 0, 0.2, 0.4 or 0.8 mM uric acid in combination with 1 mM β-mercaptoethanol for 24 hours, followed by exposure to identical uric acid concentrations and 5 mM β-mercaptoethanol for 6 and 10 hours. Cells developed a neuronal-like morphology, with formation of interconnected process extensions, typical of neural cells. Immunocytochemistry and immunofluorescence staining showed neuron specific enolase positive cells were present in each group except the control group. A greater number of neuron specific enolase positive cells were observed in 0.8 mM uric acid in combination with 5 mM β-mercaptoethanol at 10 hours. After 24 hours of induction, Nissl bodies were detected in the cytoplasm of all differentiated cell groups except the control group and Nissl body numbers were greatest in human placenta-derived mesenchymal stem cells grown in the presence of 0.8 mM uric acid and 5 mM β-mercaptoethanol. These results suggest uric acid accelerates differentiation of human placenta-derived mesenchymal stem cells into neuronal-like cells in a time-and concentration-dependent manner.展开更多
Fractional flow reserve(FFR)computed from computed tomography angiography(CTA),i.e.,FFRCT has been used in the clinic as a noninvasive parameter for functional assessment of coronary artery stenosis.It has also been s...Fractional flow reserve(FFR)computed from computed tomography angiography(CTA),i.e.,FFRCT has been used in the clinic as a noninvasive parameter for functional assessment of coronary artery stenosis.It has also been suggested to be used in the assessment of carotid artery stenosis.The wall thickness of the vessel is an important parameter when establishing a fluid-structure coupling model of carotid stenosis.This work studies the effect of the vessel wall thickness on hemodynamic parameters such as FFRCT in carotid stenosis.Models of carotid stenosis are established based on CTA image data using computer-aided design software.It is assumed that the vessel wall is a linear elastic and isotropic material,and the blood an incompressible Newtonian fluid.Under the pulsating flow condition,ANSYS Transient Structural and CFX are used to simulate the blood flow of fluid-structure coupling in the carotid stenosis model in order to obtain hemodynamic parameters and the corresponding FFRCT.The results show that when the elastic modulus of the vessel wall is fixed,FFRCT will decrease with the increase of the wall thickness.Similarly,FFRCT will decrease with the increase of the elastic modulus when the wall thickness is fixed.The difference in hemodynamic parameters such as FFRCT,however,is relatively small if the stiffness of the two models are close.The results demonstrate that the effect of the vessel wall thickness,especially for a model with small elastic modulus,should be taken into account in using FFRCT for functional assessment of carotid stenosis.Moreover,under the linear elasticity and isotropic material assumptions,the stiffness coefficient may replace the elastic modulus and wall thickness as a parameter reflecting material property of the vessel wall in the carotid stenosis model.展开更多
In order to improve the surgical treatment of the congenital heart disease patient with single ventricle defect,two axial flow blood pumps,one with diffuser and the other without diffuser,were designed and virtually i...In order to improve the surgical treatment of the congenital heart disease patient with single ventricle defect,two axial flow blood pumps,one with diffuser and the other without diffuser,were designed and virtually implanted into an idealized total cavopulmonary connection(TCPC)model to form two types of Pump-TCPC physiological structure.Computational fluid dynamics(CFD)simulationswere performed to analyze the variations of the hemodynamic characteristics,such as flow field,wall shear stress(WSS),oscillatory shear index(OSI),relative residence time(RRT),between the two Pump-TCPC models.Numerical results indicate that the Pump-TCPC with diffuser has better flow field stability,less damage on endothelial cell of vessel wall,and lower risk of vascular injury and thrombosis formation than that without diffuser.展开更多
Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer’s disease(AD).The mitochondrial contact site and cristae organizing system(MICOS)plays a pivotal role in shaping the inner mitochondrial...Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer’s disease(AD).The mitochondrial contact site and cristae organizing system(MICOS)plays a pivotal role in shaping the inner mitochondrial membrane,forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function.In the past decade,MICOS abnormalities have been extensively linked to AD pathogenesis.In particular,dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD,often in association with hallmark pathological features such as amyloid-b plaque accumulation,neurofibrillary tangle formation,and neuronal apoptosis.Furthermore,MICOS subunits interact with several etiologically relevant proteins,significantly influencing AD progression.The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD.Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment.In the present review,we introduce current understanding of MICOS structures and functions,highlight MICOS pathogenesis in AD,and summarize the available MICOS-targeting drugs potentially useful for AD.展开更多
A biomimetic electrical microenvironment is known to facilitate bone defect repair.Nevertheless,precise and non-invasive modulation of the in situ electrical microenvironment poses a formidable challenge.This study de...A biomimetic electrical microenvironment is known to facilitate bone defect repair.Nevertheless,precise and non-invasive modulation of the in situ electrical microenvironment poses a formidable challenge.This study develops a poly(vinylidene fluoride-trifluoroethylene)(P(VDF-TrFE))membrane with a precisely controlled porous structure.Ultrasonic stimulation is applied to induce acoustic-mechanic-electric(AcME)conversion and regulate the membrane’s surface potential to modulate the in situ electrical microenvironment.When the ultrasound frequency aligns with the membrane’s inherent frequency,maximal electrical energy conversion occurs via the resonance effect,which generates the highest possible surface potential.The maximal AcME conversion is achieved by a 12μm pore-sized P(VDF-TrFE)membrane with a resonance frequency of 40 kHz,resulting in the highest surface potential of-65.56 mV.Finite element modeling indicates that the deformation and stress of porous membranes are higher than that of non-porous membranes under the stimulation of ultrasound,yielding the highest surface potential.In vitro experiments and sequencing analysis show that the honeycomb sandwich-structured P(VDF-TrFE)membrane under the stimulation of the resonance ultrasound promoted osteogenic differentiation of rBMSCs through the PI3K-Akt signaling pathway.When the porous membranes are implanted to cover cranial defects,the bone defect repair is significantly enhanced under the stimulation of ultrasound compared with the non-porous membranes.This study establishes a new strategy for efficient AcME conversion on piezoelectric membranes and offers new insights into the applications of ultrasound-responsive piezoelectric materials for bone defect repair.展开更多
Cuprotosis,a new type of cell death,provides great opportunities for the treatment of oral squamous cell carcinoma,as nanocarriers of copper ions can induce cuprotosis and immunogenic death.Here,we studied an editor t...Cuprotosis,a new type of cell death,provides great opportunities for the treatment of oral squamous cell carcinoma,as nanocarriers of copper ions can induce cuprotosis and immunogenic death.Here,we studied an editor that enables production of a nanoparticle“storm”in oral squamous cell carcinoma,maximizing the toxic effect of these particles and reprogramming the tumor microenvironment;as a result,T cells and natural killer(NK)cells can infiltrate the tumor microenvironment to activate an antitumor immune response.On this basis,the editor can be combined with optical therapy to improve patient prognosis.In this study,the metal ratio was regulated in response to the nanocarrier of acid response type.Thus,in the presence of a specific copper ion content,the nanocarrier could change the permeability of the tumor cell membrane.Based on these results,the nanoparticles were cracked in an acidic environment and then released copper ions.Finally,the nanoparticles contributed to cuprotosis and immunogenic death.In addition,the editor could inhibit murine oral cancer 1(MOC1)tumors in C57BL/6 without toxicity.The rate of tumor growth inhibition was as high as approximately 80%.This strategy provides a new idea for immunotherapy.Moreover,it can improve the interaction between immunotherapy and the copper-induced death of oral squamous cell carcinoma.Above all,this study will provide a new opportunity for the effective treatment of oral squamous cell carcinoma.展开更多
文摘BACKGROUND Colorectal cancer(CRC) is one of the main causes of cancer-related deaths in China and around the world. Advanced CRC(ACRC) patients suffer from a low cure rate though treated with targeted therapies. The response rate is about 50% to chemotherapy and cetuximab, a monoclonal antibody targeting epidermal growth factor receptor(EGFR) and used for ACRC with wild-type KRAS. It is important to identify more predictors of cetuximab efficacy to further improve precise treatment. Autophagy, showing a key role in the cancer progression, is influenced by the EGFR pathway. Whether autophagy can predict cetuximab efficacy in ACRC is an interesting topic.AIM To investigate the effect of autophagy on the efficacy of cetuximab in colon cancer cells and ACRC patients with wild-type KRAS.METHODS ACRC patients treated with cetuximab plus chemotherapy, with detailed data and tumor tissue, at Sun Yat-sen University Cancer Center from January 1, 2005,to October 1, 2015, were studied. Expression of autophagy-related proteins[Beclin1, microtubule-associated protein 1 A/B-light chain 3(LC3), and 4 Ebinding protein 1(4 E-BP1)] was examined by Western blot in CRC cells and by immunohistochemistry in cancerous and normal tissues. The effect of autophagy on cetuximab-treated cancer cells was confirmed by MTT assay. The associations between Beclin1, LC3, and 4 E-BP1 expression in tumor tissue and the efficacy of cetuximab-based therapy were analyzed.RESULTS In CACO-2 cells exposed to cetuximab, LC3 and 4 E-BP1 were upregulated, and P62 was downregulated. Autophagosome formation was observed, and autophagy increased the efficacy of cetuximab. In 68 ACRC patients,immunohistochemistry showed that Beclin1 levels were significantly correlated with those of LC3(0.657, P < 0.001) and 4 E-BP1(0.211, P = 0.042) in ACRC tissues.LC3 was significantly overexpressed in tumor tissues compared to normal tissues(P < 0.001). In 45 patients with wild-type KRAS, the expression levels of these three proteins were not related to progression-free survival; however, the expression levels of Beclin1(P = 0.010) and 4 E-BP1(P = 0.005), pathological grade(P = 0.002), and T stage(P = 0.004) were independent prognostic factors for overall survival(OS).CONCLUSION The effect of cetuximab on colon cancer cells might be improved by autophagy.LC3 is overexpressed in tumor tissues, and Beclin1 and 4 E-BP1 could be significant predictors of OS in ACRC patients treated with cetuximab.
文摘We induced human placenta-derived mesenchymal stem cells （hPMSCs） to differentiate into neural cells by adding chemical reagents, despite the fact that toxic chemicals induce cell shrinkage or cytoskeletal formation, which does not represent a proper cell differentiation process. The present study established a co-culture system with hPMSCs and neural cells and analyzed the influence of neural cells on hPMSC differentiation in a co-culture system, hPMSCs were isolated and purified from human full-term placenta using collagenase digestion. Fetal neural cells were co-cultured with hPMSCs for 48 hours using the Transwell co-culture system, hPMSCs co-cultured with neural cells exhibited a slender morphology with a filament. After 96 hours, hPMSCs expressed neuron-specific enolase, which suggested that co-culture of hPMSCs and neural cells induced neural differentiation of hPMSCs.
基金financially supported by the National Natural Science Foundation of China(Nos.21574124,51503203 and51233004)
文摘A series of zinc silylamido complexes based upon NNO tridentate enolic Schiff base framework have been synthesized and characterized. These complexes were tested for the ring opening polymerization of lactide and e-caprolactone, exhibiting notably high activity at ambient temperature, The influence of imine bridge length and substituents of diketone over the course of polymerization was investigated in details. Remarkably, 4a was confirmed to be a rare example of exceedingly active and robust zinc catalysts, achieving major transformation of lactide under extremely low loading （0.025 mol%） within 18 rain. The influence of various monomers as well as the polymerization mechanism have also been discussed.
文摘Background Myocardial infarction （MI） has likely contributed to the increased prevalence of heart failure （HF）. As a result of re- duced cardiac function, splanchnic blood flow decreases, causing ischemia in villi and damage to the intestinal barrier. The induction of heme oxygenase-1 （HO-1） could prevent, or lessen the effects of stress and inflammation. Thus, the effect and mechanism thereof of HO-1 on the intestines of rats with HF was investigated. Methods Male Wistar rats with heart failure through ligation of the left coronary artery were identified with an left ventricular ejection fraction of 〈 45% through echocardiography and then divided into various experimental groups based on the type of peritoneal injection they received [MI： saline; MI ＋ Cobalt protoporphyrin （CoPP）： CoPP solution; and MI ＋ Tin mesoporphyrin IX dichloride （SnMP）： SnMP solution]. The control group was comprised of rats without coronary ligation. Echocardiogra- phy was performed before ligation for a baseline and eight weeks after ligation in order to evaluate the cardiac function of the rats. The bac- terial translocation （BT） incidence, mesenteric microcirculation, amount of endotoxins in the vein serum, ileum levels of HO- 1, carbon oxide （CO）, nitric oxide （NO）, intedeuldn （IL）-10, turnour necrosis factor-et （TNF-ct）, and the ileum morphology were determined eight weeks after the operation. Results The rats receiving MI ＋ CoPP injections exhibited a recovery in cardiac function, an amelioration of mesenteric microcirculation and change in morphology, a lower BT incidence, a reduction in serum and ileac NO and TNF-ct levels, and an elevation in ileac HO-1, CO, and interleukin-10 （[L-10） levels compared to the MI group （P 〈 0.05）. The rats that received the MI ＋ SnMP injections exhibited results inverse to the MI （P 〈 0.05） group. Conclusions HO-1 exerted a protective effect on the intestines of rats with HF by inhibiting the inflammation and amelioration of microcirculation through the CO pathway. This protective effect could be independent from the recovery of cardiac function.
基金Financially supported by the National Natural Science Foundation of China(Grant Nos.51973216,51873207,51803006,51673190,51603204,51673187,and 51520105004)the Science and Technology Development Program of Jilin Province(Grant Nos.20190201068JC,20170101102JC,and 20160414047GH)+2 种基金the Medical and Health Program of Jilin Province(Grant No.20190304047YY)the Youth Talents Promotion Project of Jilin Province(Grant No.181909)and the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.2019005).
文摘Over the past decade,nanoparticle-based therapeutic modalities have become promising strategies in cancer therapy.Selective delivery of anticancer drugs to the lesion sites is critical for elimination of the tumor and an improved prognosis.Innovative design and advanced biointerface engineering have promoted the development of various nanocarriers for optimized drug delivery.Keeping in mind the biological framework of the tumormicroenvironment,biomembrane-camouflaged nanoplatforms have been a research focus,reflecting their superiority in cancer targeting.In this review,we summarize the development of various biomimetic cell membrane-camouflaged nanoplatforms for cancertargeted drug delivery,which are classified according to the membranes fromdifferent cells.The challenges and opportunities of the advanced biointerface engineering drug delivery nanosystems in cancer therapy are discussed.
基金supported by the National Natural Science Foundation of China,No.81771351the National Key R&D Program of China,No.2017YFA0105802+1 种基金the Joint Research Fund Liaoning-Shenyang National Laboratory for Materials Science,No.2019JH3/30100022the National Science Foundation for Post-doctoral Scientists of China,No.2018M641732(all to QA and LLW)。
文摘The functional properties of endogenous Schwann cells(SCs)during nerve repair are dynamic.Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the repair of damaged nerves.Previous studies showed that miR-221-3p promotes the proliferation and migration of SCs,and miR-338-3p promotes the myelination of SCs.In this study,we established rat models of sciatic nerve injury by bridging the transected sciatic nerve with a silicone tube.We injected a miR-221 lentiviral vector system together with a doxycycline-inducible Tet-On miR-338 lentiviral vector system into the cavity of nerve conduits of nerve stumps to sequentially regulate the biological function of endogenous SCs at different stages of nerve regeneration.We found that the biological function of SCs was sequentially regulated,the diameter and density of myelinated axons were increased,the expression levels of NF200 and myelin basic protein were increased,and the function of injured peripheral nerve was improved using this system.miRNA Target Prediction Database prediction,Nanopore whole transcriptome sequencing,quantitative PCR,and dual luciferase reporter gene assay results predicted and verified Cdkn1b and Nrp1 as target genes of miR-221-3p and miR-338-3p,respectively,and their regulatory effects on SCs were confirmed in vitro.In conclusion,here we established a new method to enhance nerve regeneration through sequential regulation of biological functions of endogenous SCs,which establishes a new concept and model for the treatment of peripheral nerve injury.The findings from this study will provide direct guiding significance for clinical treatment of sciatic nerve injury.
基金supported by the Gansu Provincial Health Research Project (GSWSKY2020-01)。
文摘Hyperkalemia,usually associated with predisposing chronic diseases as heart failure(HF),severe kidney disease or diabetes mellitus(DM),[1]is defined as an elevation of potassium concentration more than 5.5 mmol/L,[2].
基金supported by NIH R01 DE17974(Hockin HK Xu)National Science Foundation of China 81200820(to Xian-Ju Xie),81400487(to Lin Wang)+1 种基金Beijing Nova Program xx2014B060(to Xian-Ju Xie)University of Maryland School of Dentistry bridging fund(to Hockin HK Xu)
文摘White spot lesions （WSLs）, due to enamel demineralization, occur frequently in orthodontic treatment. We recently developed a novel rechargeable dental composite containing nanoparticles of amorphous calcium phosphate （NACP） with long-term calcium （Ca） and phosphate （P） ion release and caries-inhibiting capability. The objectives of this study were to develop the first NACP- rechargeable orthodontic cement and investigate the effects of recharge duration and frequency on the efficacy of ion re-release. The rechargeable cement consisted of pyromellitic glycerol dimethacrylate （PMGDM） and ethoxylated bisphenol A dimethacrylate （EBPADMA）. NACP was mixed into the resin at 40% by mass. Specimens were tested for orthodontic bracket shear bond strength （SBS） to enamel, Ca and P ion initial release, recharge and re-release. The new orthodontic cement exhibited an SBS similar to commercial orthodontic cement without CaP release （P〉 0.1）. Specimens after one recharge treatment （e.g., 1 min immersion in recharge solution repeating three times in one day, referred to as ＂1 min 3 times＂） exhibited a substantial and continuous re-release of Ca and P ions for 14 days without further recharge. The ion re-release did not decrease with increasing the number of recharge/re-release cycles （P〉 0.1）. The ion re-release concentrations at 14 days versus various recharge treatments were as follows： 1 min 3 times〉3 min 2 times〉 1 min 2 times〉6 min 1 time〉3 min 1 time〉 1 min 1 time. In conclusion, although previous studies have shown that NACP nanocomposite remineralized tooth lesions and inhibited caries, the present study developed the first orthodontic cement with Ca and P ion recharge and long-term release capability. This NACP-rechargeable orthodontic cement is a promising therapy to inhibit enamel demineralization and WSLs around orthodontic brackets.
基金This work was financially supported by the Special Program for Medical and Health Professionals of Jilin Province(No.JLSWSRCZX2021-085)the Achievement Transformation Fund of the First Hospital of Jilin University(Nos.JDYYZH-2102055 and JDYYZH-2102013).
文摘Dentin hypersensitivity(DH)associated with dentinal tubule exposure is one of the most common causes of toothache with a rapid onset and short duration.Medication,filling repair,laser irradiation,crown therapy,and desensitizing toothpaste are standard clinical treatment strategies,but unsatisfactory treatment modalities are marked by long-term administration,poor dentinal tubule closure,microleakage,and the development of secondary caries.To improve the treatment efficiency of DH,numerous organic or inorganic biomaterials have been developed to relieve toothache and reverse the instability of desensitization.Biomaterials are expected to participate in dental remineralization to achieve desensitization.This review discusses various biomaterials for DH therapy based on different desensitization mechanisms,including dentinal tubule closure and dental nerve blockade,and presents a perspective on the underlying future of dentin regeneration medicine for DH therapy.
基金Natural Science Foundation of China No:81170108.
文摘Objective:To discuss the relationship of ultrasonic shear wave velocity (SWV) with oncogene and tumor suppressor gene expression in primary liver cancer lesions as well as angiogenesis factor contents.Methods:100 patients with primary liver cancer who underwent surgical treatment in our hospital between March 2014 and September 2016 were collected as observation group, and 50 healthy subjects who received physical examination in our hospital during the same period were collected as normal control group. The ultrasonic SWV levels of two groups of subjects were measured before the operation, and the observation groups were further divided into high SWV group and low SWV group, 50 cases in each group. Intraoperative tumor tissue samples were kept and fluorescence quantitative PCR was used to determine the mRNA expression of oncogenes and tumor suppressor genes. Enzyme-linked immunosorbent assay was used to determine serum contents of angiogenesis factors in observation group before operation.Results:Hepatic ultrasonic SWV level in observation group was significantly higher than that in normal control group;proto-oncogene CK, Ki67, Gly-3, Survivin and Pokemon mRNA expression in tumor tissue of high SWV group were higher than those of low SWV group while tumor suppressor genes Tg737, p16, p27, PTEN and runx3 mRNA expression were lower than those of low SWV group;serum angiogenesis factors VEGF, MMP-9 and IGF-1R contents were higher than those in low SWV group. Conclusion: The hepatic ultrasonic SWV level increases in patients with primary liver cancer, and the SWV level is directly correlated with oncogene and tumor suppressor gene expression as well as angiogenesis factor contents.
基金Supported by Grants from the Technology Program of the Science Technology Department of Zhejiang Province, No.2011C37087the National Natural Science Foundation of China, No. 81000065
文摘This case report describes a foreign body retained in the liver long after perihepatic gauze packing. A 64-year-old female patient had suffered a rib fracture and liver rupture during a traffic accident in 1973. She discovered a mass in her right hypochondrium. Her hepatic ultrasonography showed a round mass (20.3 cm × 17.3 cm × 16.0 cm in size) with fluid echogenicity in the right lobe of her liver, and a hepatic cystic-solid mass (19.7 cm × 18.5 cm × 15.6 cm in size) was identified in an abdominal computerized tomography scan. Several pieces of gauze were extracted, and brown pus from the hepatic mass was suctioned during her exploratory laparotomy. Histology documented gauze remnants with necrotic material inclusions and fibrotic capsules. To our knowledge, this patient's case represents the longest time for which a foreign body has been retained in the liver. In addition, we conducted a comprehensive literature review of foreign bodies retained in the liver. Foreign bodies may be introduced into the liver via penetrating trauma, surgical procedures or the ingestion of foreign bodies (which then migrate from the gut). Thus, they can be classified into the following three categories: penetrating, medical and migrated foreign bodies. The details of the case are thoroughly described.
基金Supported by Zhejiang Medical Science and Technology Program funded projects,No.08B195
文摘Two cases of prostatic neuroendocrine carcinoma(PNEC) imaged by computed tomography(CT) and magnetic resonance imaging(MRI), and literature review are presented. Early enhanced CT, MRI, especially diffusionweighted image were emphasized, the complementary roles of ultrasound, CT, MRI, clinical and laboratory characteristic's features in achieving accurate diagnosis were valued in the preoperative diagnosis of PNEC.
基金supported by NIH R01 DE14190 and R21 DE22625(HX)the National Science Foundation of China 81401794(PW)and 81400487(LW)+2 种基金the Youth Fund of Science and Technology of Jilin Province 20150520043JH(LW)the China Postdoctoral Science Foundation 2015M581405(LW)the University of Maryland School of Dentistry bridge fund(HX)
文摘Calcium phosphate cements （CPCs） are frequently used to repair bone defects. Since their discovery in the 1980s, extensive research has been conducted to improve their properties, and emerging evidence supports their increased application in bone tissue engineering. Much effort has been made to enhance the biological performance of CPCs, including their biocompatibility, osteoconductivity, osteoinductivity, biodegradability, bioactivity, and interactions with cells. This review article focuses on the major recent developments in CPCs, including 3D printing, injectability, stem cell delivery, growth factor and drug delivery, and pre- vascularization of CPC scaffolds via co-culture and tri-culture techniques to enhance angiogenesis and osteogenesis.
文摘Uric acid is an important, naturally occurring serum antioxidant. The present study investigates the use of uric acid for promoting proliferation and neuronal differentiation of mesenchymal stem cells derived from human placenta tissue. Human placenta-derived mesenchymal stem cells were pre-induced in the presence of either 0, 0.2, 0.4 or 0.8 mM uric acid in combination with 1 mM β-mercaptoethanol for 24 hours, followed by exposure to identical uric acid concentrations and 5 mM β-mercaptoethanol for 6 and 10 hours. Cells developed a neuronal-like morphology, with formation of interconnected process extensions, typical of neural cells. Immunocytochemistry and immunofluorescence staining showed neuron specific enolase positive cells were present in each group except the control group. A greater number of neuron specific enolase positive cells were observed in 0.8 mM uric acid in combination with 5 mM β-mercaptoethanol at 10 hours. After 24 hours of induction, Nissl bodies were detected in the cytoplasm of all differentiated cell groups except the control group and Nissl body numbers were greatest in human placenta-derived mesenchymal stem cells grown in the presence of 0.8 mM uric acid and 5 mM β-mercaptoethanol. These results suggest uric acid accelerates differentiation of human placenta-derived mesenchymal stem cells into neuronal-like cells in a time-and concentration-dependent manner.
基金This study is funded by the national natural science foundation of China(Nos.81571128,11872152).
文摘Fractional flow reserve(FFR)computed from computed tomography angiography(CTA),i.e.,FFRCT has been used in the clinic as a noninvasive parameter for functional assessment of coronary artery stenosis.It has also been suggested to be used in the assessment of carotid artery stenosis.The wall thickness of the vessel is an important parameter when establishing a fluid-structure coupling model of carotid stenosis.This work studies the effect of the vessel wall thickness on hemodynamic parameters such as FFRCT in carotid stenosis.Models of carotid stenosis are established based on CTA image data using computer-aided design software.It is assumed that the vessel wall is a linear elastic and isotropic material,and the blood an incompressible Newtonian fluid.Under the pulsating flow condition,ANSYS Transient Structural and CFX are used to simulate the blood flow of fluid-structure coupling in the carotid stenosis model in order to obtain hemodynamic parameters and the corresponding FFRCT.The results show that when the elastic modulus of the vessel wall is fixed,FFRCT will decrease with the increase of the wall thickness.Similarly,FFRCT will decrease with the increase of the elastic modulus when the wall thickness is fixed.The difference in hemodynamic parameters such as FFRCT,however,is relatively small if the stiffness of the two models are close.The results demonstrate that the effect of the vessel wall thickness,especially for a model with small elastic modulus,should be taken into account in using FFRCT for functional assessment of carotid stenosis.Moreover,under the linear elasticity and isotropic material assumptions,the stiffness coefficient may replace the elastic modulus and wall thickness as a parameter reflecting material property of the vessel wall in the carotid stenosis model.
基金This work has been supported by the Natural Science Foundation of China(No.11872152).
文摘In order to improve the surgical treatment of the congenital heart disease patient with single ventricle defect,two axial flow blood pumps,one with diffuser and the other without diffuser,were designed and virtually implanted into an idealized total cavopulmonary connection(TCPC)model to form two types of Pump-TCPC physiological structure.Computational fluid dynamics(CFD)simulationswere performed to analyze the variations of the hemodynamic characteristics,such as flow field,wall shear stress(WSS),oscillatory shear index(OSI),relative residence time(RRT),between the two Pump-TCPC models.Numerical results indicate that the Pump-TCPC with diffuser has better flow field stability,less damage on endothelial cell of vessel wall,and lower risk of vascular injury and thrombosis formation than that without diffuser.
基金funded by the National Natural Science Foundation of China(No.81500858 to Xinwen Zhang,No.81700977 to Xu Yan)Natural Science Foundation of Liaoning Province(China)(No.2022-MS-231 to Xinwen Zhang)+1 种基金the Science and Technology Planning Project of Shenyang(China)(No.22-321-33-26 to Dehao Shang)Grants-in-Aid for Scientific Research(Japan)(No.22K09927 to Zhou Wu).
文摘Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer’s disease(AD).The mitochondrial contact site and cristae organizing system(MICOS)plays a pivotal role in shaping the inner mitochondrial membrane,forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function.In the past decade,MICOS abnormalities have been extensively linked to AD pathogenesis.In particular,dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD,often in association with hallmark pathological features such as amyloid-b plaque accumulation,neurofibrillary tangle formation,and neuronal apoptosis.Furthermore,MICOS subunits interact with several etiologically relevant proteins,significantly influencing AD progression.The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD.Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment.In the present review,we introduce current understanding of MICOS structures and functions,highlight MICOS pathogenesis in AD,and summarize the available MICOS-targeting drugs potentially useful for AD.
基金supported by the National Natural Science Foundation of China(Nos.82471029,U22A20314,and 81600905)the Peking University Medicine Fund of Fostering Young Scholars’Scentific&Technological Innovation supported by the Fundamental Research Funds for the Central Universities(No.BMU2018PY005)the National Key Research and Development Program of China(No.2018YFE0194400).
文摘A biomimetic electrical microenvironment is known to facilitate bone defect repair.Nevertheless,precise and non-invasive modulation of the in situ electrical microenvironment poses a formidable challenge.This study develops a poly(vinylidene fluoride-trifluoroethylene)(P(VDF-TrFE))membrane with a precisely controlled porous structure.Ultrasonic stimulation is applied to induce acoustic-mechanic-electric(AcME)conversion and regulate the membrane’s surface potential to modulate the in situ electrical microenvironment.When the ultrasound frequency aligns with the membrane’s inherent frequency,maximal electrical energy conversion occurs via the resonance effect,which generates the highest possible surface potential.The maximal AcME conversion is achieved by a 12μm pore-sized P(VDF-TrFE)membrane with a resonance frequency of 40 kHz,resulting in the highest surface potential of-65.56 mV.Finite element modeling indicates that the deformation and stress of porous membranes are higher than that of non-porous membranes under the stimulation of ultrasound,yielding the highest surface potential.In vitro experiments and sequencing analysis show that the honeycomb sandwich-structured P(VDF-TrFE)membrane under the stimulation of the resonance ultrasound promoted osteogenic differentiation of rBMSCs through the PI3K-Akt signaling pathway.When the porous membranes are implanted to cover cranial defects,the bone defect repair is significantly enhanced under the stimulation of ultrasound compared with the non-porous membranes.This study establishes a new strategy for efficient AcME conversion on piezoelectric membranes and offers new insights into the applications of ultrasound-responsive piezoelectric materials for bone defect repair.
基金the National Key Research and Development Program of China(No.2022YFC2403203-3)Jilin Province Department of Finance(No.jcsz2023481-13)+2 种基金the National Natural Science Foundation of China(Nos.51972003 and 52271127)the Intergovernmental International Co-operation Project of Beijing Municipal Science and Technology Commission(No.Z221100002722004)the 2023 Management Research Project(No.YS040223).
文摘Cuprotosis,a new type of cell death,provides great opportunities for the treatment of oral squamous cell carcinoma,as nanocarriers of copper ions can induce cuprotosis and immunogenic death.Here,we studied an editor that enables production of a nanoparticle“storm”in oral squamous cell carcinoma,maximizing the toxic effect of these particles and reprogramming the tumor microenvironment;as a result,T cells and natural killer(NK)cells can infiltrate the tumor microenvironment to activate an antitumor immune response.On this basis,the editor can be combined with optical therapy to improve patient prognosis.In this study,the metal ratio was regulated in response to the nanocarrier of acid response type.Thus,in the presence of a specific copper ion content,the nanocarrier could change the permeability of the tumor cell membrane.Based on these results,the nanoparticles were cracked in an acidic environment and then released copper ions.Finally,the nanoparticles contributed to cuprotosis and immunogenic death.In addition,the editor could inhibit murine oral cancer 1(MOC1)tumors in C57BL/6 without toxicity.The rate of tumor growth inhibition was as high as approximately 80%.This strategy provides a new idea for immunotherapy.Moreover,it can improve the interaction between immunotherapy and the copper-induced death of oral squamous cell carcinoma.Above all,this study will provide a new opportunity for the effective treatment of oral squamous cell carcinoma.
