Iron is one of the necessary metal elements in the human body.There are numerous factors that control the balance of iron metabolism,and its storage and transportation mechanisms are intricate.As one of the most energ...Iron is one of the necessary metal elements in the human body.There are numerous factors that control the balance of iron metabolism,and its storage and transportation mechanisms are intricate.As one of the most energyintensive tissues in the body,the retina is susceptible to iron imbalance.The occurrence of iron overload in the retina leads to the generation of a significant quantity of reactive oxygen species.This will aggravate local oxidative stress and inflammatory reactions and even lead to ferroptosis,eventually resulting in retinal dysfunction.The blood-retinaretinal barrier is eventually harmed by oxidative stress and elevated inflammation,which are characteristics of retinal vascular disorders.The pathophysiology of retinal vascular disorders may be significantly influenced by iron.Recently,iron-chelating agents have been found to have antioxidative and anti-inflammatory actions in addition to iron chelating.Therefore,iron neutralization is considered to be a new and potentially useful therapeutic strategy.This article reviews the iron overload in retinal vascular diseases and discusses the therapeutic potential of iron-chelating agents.展开更多
Rice bran residue possessed a steady lipase activity((26.68 ± 3.69)%)after its endogenous lipase was extracted continuously by phosphate buffer solution(PBS)for 24 h. T herefore, the aim of this research was to e...Rice bran residue possessed a steady lipase activity((26.68 ± 3.69)%)after its endogenous lipase was extracted continuously by phosphate buffer solution(PBS)for 24 h. T herefore, the aim of this research was to explore whether there exist any bound lipases in rice bran(Oryza sativa). Three physical treatments(grinding, homogenizing and ultrasound crush)and 6 enzymatic treatments(cellulase, hemicellulase, pectinase, complex cellulase, glucoamylase and α-amylase)were applied to rice bran in order to investigate this bound lipase. The relative catalytic activities of extraction supernatant and residue for pectinase group were(437.63 ± 22.54)% and(159.26 ± 2.12)%, respectively, which were significantly higher(P < 0.05)than other groups. This phenomenon demonstrated that lipase was the most likely to combine with pectin. Molecular simulation proved that pectin could combine with two rice bran lipases(lipase 315 and lipase 308)and cover the catalytic centers so as to prevent the lipases from encountering the substrate and inhibiting their catalytic activities. During combination, pectin could make the lipases more compact and reduce the solvent accessible surface area of lipases, which would make the lipases inactive to molecular interaction. In summary, part of rice bran lipase was proved to exist in bound form and combined with the pectin.展开更多
BACKGROUND The carcinogenesis of stomach adenocarcinoma(STAD)involves many different molecules and multiple pathways,including the NOTCH signaling pathway.As a key factor that functions as a critical link in the NOTCH...BACKGROUND The carcinogenesis of stomach adenocarcinoma(STAD)involves many different molecules and multiple pathways,including the NOTCH signaling pathway.As a key factor that functions as a critical link in the NOTCH pathway,mind bomb 1(MIB1)is upregulated in various tumors and has been reported to promote cell metastasis and invasion.However,studies on the role of MIB1 in STAD are limited.Here,we evaluated the prognostic value of MIB1 in STAD and its association with immune infiltration and copy number variation.AIM To elucidate the relationship between MIB1 gene and gastric cancer(GC)and provide a new idea for the treatment of GC.METHODS We identified mutations in the MIB1 gene by searching the cBioPortal database and then analyzed their relationship with the overall survival rate and diseasefree survival rate using the Kaplan-Meier method.The Cancer Genome Atlas(TCGA)database provided transcript levels for MIB1 in STADs and normal tissues.As a method of distinguishing the STAD tissues from adjacent normal tissues,a receiver operating characteristic(ROC)curve was generated.Kaplan-Meier plotter was used to determine the effect of MIB1 expression on survival.Based on the LinkedOmics database,we were able to identify the coexpressed genes of the MIB1 gene,the top 50 positively correlated genes,and the top 50 negatively correlated genes.STRING was used to construct protein-protein interaction networks related to the MIB1 gene.An analysis of functional enrichment was carried out using the R package“Cluster Profiler”.The relationships between mRNA expression of MIB1 and immune infiltrates were assessed by Tumor IMmune Estimation Resource(TIMER)and the“GSVA package”in R.RESULTS According to the cBioPortal database,the MIB1 mutation rate in 287 patients in the TCGA dataset was approximately 6%.Kaplan-Meier survival analysis showed that patients with STAD in the mutated group had a worse prognosis than those in the unmutated group(P=0.0156).There was a significant upregulation of MIB1 expression in STAD tissues compared to adjacent normal tissues.A high T stage was associated with increased MIB1 mRNA expression.The ROC curve analysis revealed 59.4%sensitivity and 85.6%specificity of MIB1 for differentiating STAD tissues from adjacent normal tissues at a truncation level of 2.248.Kaplan-Meier plotter indicated that patients with higher MIB1 levels had a worse prognosis than those with lower levels(26.4 mo vs 56.2 mo,P=0.0330).A correlation analysis demonstrated an association between immune infiltrates and MIB1 mRNA expression.CONCLUSION Upregulation of MIB1 expression is significantly associated with poor survival rate and immune infiltration in gastric adenocarcinoma.MIB1 may be a biomarker for the poor prognosis of STAD patients and a potential immunotherapeutic target.展开更多
BACKGROUND Colorectal cancer(CRC)is a common life-threatening disease that often requires surgical intervention,such as laparoscopic radical resection.However,despite successful surgeries,some patients experience dise...BACKGROUND Colorectal cancer(CRC)is a common life-threatening disease that often requires surgical intervention,such as laparoscopic radical resection.However,despite successful surgeries,some patients experience disease relapse.Identifying the risk factors for CRC relapse can help guide clinical interventions and improve patient outcomes.AIM To determine the risk factors that may lead to CRC relapse after laparoscopic radical resection.METHODS We performed a retrospective analysis using the baseline data of 140 patients with CRC admitted to our hospital between January 2018 and January 2020.All included participants were followed up until death or for 3 years.The baseline data and laboratory indicators were compared between the patients who experienced relapse and those who did not experienced relapse.RESULTS Among the 140 patients with CRC,30 experienced relapse within 3 years after laparoscopic radical resection and 110 did not experience relapse.The relapse group had a higher frequency of rectal tumors with low differentiation and lymphatic vessel invasion than that of the non-relapse group.The expression of serum markers and the prognostic nutritional index were lower,whereas the neutrophil-to-lymphocyte ratio,expression of cytokeratin 19 fragment antigen 21-1,vascular endothelial growth factor,and Chitinase-3-like protein 1 were significantly higher in the relapse group than those in the non-relapse group.The groups did not differ significantly based on other parameters.Logistic regression analysis revealed that all the above significantly altered factors were independent risk factors for CRC relapse.CONCLUSION We identified multiple risk factors for CRC relapse following surgery,which can be considered for the clinical monitoring of patients to reduce disease recurrence and improve patient survival.展开更多
AIM: To evaluate the efficacy of telomerase activity assay and peritoneal lavage cytology (PLC) examination in peritoneal lavage fluid for the prediction of peritoneal metastasis in gastric cancer patients, and to exp...AIM: To evaluate the efficacy of telomerase activity assay and peritoneal lavage cytology (PLC) examination in peritoneal lavage fluid for the prediction of peritoneal metastasis in gastric cancer patients, and to explore the relationship between telomerase activity and proliferating cell nuclear antigen expression. METHODS: Telomeric repeated amplification protocol (TRAP)-enzyme-linked immunosorbent assay (ELISA) was performed to measure the telomerase activity in 60 patients with gastric cancer and 50 with peptic ulcer. PLC analysis of the 60 patients with gastric cancer was used for comparison. The proliferating cell nuclear antigen (PCNA) in gastric carcinoma was immunohistochemically examined. RESULTS: The telomerase activity and PLC positive rate in peritoneal lavage fluid from patients with gastric cancer was 41.7/ (25/60), and 25.0/ (15/60), respectively. The positive rate of telomerase activity was significantly higher than that of PLC in the group of pT4 (15/16 vs 9/16, P < 0.05), P1-3 (13/13 vs 9/13, P < 0.05) and diffuse type (22/42 vs 13/42, P < 0.05). The patients with positive telomerase activity, peritoneal metastasis, and serosal invasion had signifi cantly higher levels of average PCNA proliferation index (PI), (55.00 ± 6.59 vs 27.43 ± 7.72, 57.26 ± 10.18 vs 29.15 ± 8.31, and 49.82 ± 6.74 vs 24.65 ± 7.33, respectively, P < 0.05).CONCLUSION: The TRAP assay for telomerase activity is a useful adjunct for cytologic method in the diagnosis of peritoneal micrometastasis and well related to higher proliferating activity of gastric cancer. The results of this study also suggest a promising future therapeutic strategy for treating peritoneal dissemination based on telomerase inhibition.展开更多
BACKGROUND Cervical cancer is the fourth commonest malignancy in women around the world.It represents the second most commonly diagnosed cancer in South East Asian women,and an important cancer death cause in women of...BACKGROUND Cervical cancer is the fourth commonest malignancy in women around the world.It represents the second most commonly diagnosed cancer in South East Asian women,and an important cancer death cause in women of developing nations.Data collected in 2018 revealed 5690000 cervical cancer cases worldwide,85%of which occurred in developing countries.AIM To assess self-perceived burden(SPB)and related influencing factors in cervical cancer patients undergoing radiotherapy.METHODS Patients were prospectively included by convenient sampling at The Fifth Affiliated Hospital of Sun Yat-Sen University,China between March 2018 and March 2019.The survey was completed using a self-designed general information questionnaire,the SPB scale for cancer patients,and the self-care self-efficacy scale,Strategies Used by People to Promote Health,which were delivered to patients with cervical cancer undergoing radiotherapy.Measurement data are expressed as the mean±SD.Enumeration data are expressed as frequencies or percentages.Caregivers were the spouse,offspring,and other in 46.4,40.9,and 12.7%,respectively,and the majority were male(59.1%).As for pathological type,90 and 20 cases had squamous and adenocarcinoma/adenosquamous carcinomas,respectively.Stage IV disease was found in 12(10.9%)patients.RESULTS A total of 115 questionnaires were released,and five patients were excluded for too long evaluation time(n=2)and the inability to confirm the questionnaire contents(n=3).Finally,a total of 110 questionnaires were collected.They were aged 31-79 years,with the 40-59 age group being most represented(65.4%of all cases).Most patients were married(91.8%)and an overwhelming number had no religion(92.7%).Total SPB score was 43.13±16.65.SPB was associated with the place of residence,monthly family income,payment method,transfer status,the presence of radiotherapy complications,and the presence of pain(P<0.05).The SPB and self-care self-efficacy were negatively correlated(P<0.01).In multivariate analysis,self-care self-efficacy,place of residence,monthly family income,payment method,degree of radiation dermatitis,and radiation proctitis were influencing factors of SPB(P<0.05).CONCLUSION Patients with cervical cancer undergoing radiotherapy often have SPB.Self-care self-efficacy scale,place of residence,monthly family income,payment method,and radiation dermatitis and proctitis are factors independently influencing SPB.展开更多
Objective:We aim to investigate radiomic imaging features extracted in computed tomography(CT)images to differentiate invasive pulmonary adenocarcinomas(IPAs)from non-IPAs appearing as part-solid ground-glass nodules(...Objective:We aim to investigate radiomic imaging features extracted in computed tomography(CT)images to differentiate invasive pulmonary adenocarcinomas(IPAs)from non-IPAs appearing as part-solid ground-glass nodules(GGNs),and to incorporate significant radiomic features with other clinically-assessed features to develop a diagnostic nomogram model for IPAs.Methods:This retrospective study was performed,with Institutional Review Board approval,on 88 patients with a total of 100 part-solid nodules(56 IPAs and 44 non-IPAs)that were surgically confirmed between February 2014and November 2016 in the First Affiliated Hospital of China Medical University.Quantitative radiomic features were computed automatically on 3D nodule volume segmented from arterial-phase contrast-enhanced CT images.A set of regular risk factors and visually-assessed qualitative CT imaging features were compared with the radiomic features using logistic regression analysis.Three diagnostic models,i.e.,a basis model using the clinical factors and qualitative CT features,a radiomics model using significant radiomic features,and a nomogram model combining all significant features,were built and compared in terms of receiver operating characteristic(ROC)curves.Decision curve analysis was performed for the nomogram model to explore its potential clinical benefit.Results:In addition to three visually-assessed qualitative imaging features,another three quantitative features selected from hundreds of radiomic features were found to be significantly(all P<0.05)associated with IPAs.The diagnostic nomogram model showed a significantly higher performance[area under the ROC curve(AUC)=0.903]in differentiating IPAs from non-IPAs than either the basis model(AUC=0.853,P=0.0009)or the radiomics model(AUC=0.769,P<0.0001).Decision curve analysis indicates a potential benefit of using such a nomogram model in clinical diagnosis.Conclusions:Quantitative radiomic features provide additional information over clinically-assessed qualitative features for differentiating IPAs from non-IPAs appearing as GGNs,and a diagnostic nomogram model including all these significant features may be clinically useful in preoperative strategy planning.展开更多
Background:Extensive studies have confirmed the efficacy of taxanes in combination with anthracycline-based chemotherapy on breast cancer.However,few studies have assessed the efficacy of weekly taxane-anthracycline r...Background:Extensive studies have confirmed the efficacy of taxanes in combination with anthracycline-based chemotherapy on breast cancer.However,few studies have assessed the efficacy of weekly taxane-anthracycline regimens on locally advanced breast cancer.This study was to compare the efficacy and safety of a weekly taxaneanthracycline regimen with those of tri-weekly anthracycline-based regimen in patients with locally advanced breast cancer.Methods:Patients with locally advanced breast cancer were randomized to receive 4-6 cycles of neoadjuvant chemotherapy with tri-weekly 5-fluorouracil-epirubicin-cyclophosphamide(FEC) regimen or weekly paclitaxel-epirubicin(PE) regimen.The primary endpoint was the pathologic complete response(pCR) rate.Other endpoints included the clinical tumor response,breast-conserving surgery rate,and adverse events.Results:Between March 2010 and September 2013,293 patients were randomized to the FEC(n=151) and PE(n=142) arms.The overall clinical response rate was significantly higher in the PE arm than in the FEC arm(76.06%vs.59.95%,P=0.001).Consistently,the post-chemotherapy pathologic T and N stages were significantly lower in the PE arm than in the FEC arm(P<0.001).However,the pCR rate was similar in the two arms(10.61%vs.12.31%,P=0.665).Overall,36(27.27%) patients in the FEC arm and 6(35.28%) in the PE arm were qualified for breast-conserving surgery.Most adverse events were comparable in both arms,with more severe neutropenia in the PE arm than in the FEC arm(11.97%vs.5.96%,P=0.031).Conclusions:In patients with locally advanced breast cancer,weekly PE was not superior to FEC in terms of pCR.However,weekly PE has a higher response rate and superior down-staging effects.On this account,the PE regimen may be considered an alternative option for locally advanced breast cancer.Long-term follow-up data are needed to confirm the efficacy of this regimen on locally advanced breast cancer.Trial registration Chinese clinical trial registry,ChiCTR-TRC-10001043,September 21。展开更多
High content of citric acid in red raspberry juice leads to poor sensory experience. This study developed a feasible method to degrade citric acid in red raspberry juice using a novel characterized Issatchenkia terric...High content of citric acid in red raspberry juice leads to poor sensory experience. This study developed a feasible method to degrade citric acid in red raspberry juice using a novel characterized Issatchenkia terricola WJL-G4 isolated from red raspberry fruits. I. terricola WJL-G4 exhibited a potent capability of reducing the citric acid contents from(22.8 ± 0.08) g/L to(6.2 ± 0.02) g/L within 36 h fermentation, then completely depleted after 48 h. Furthermore, the contents of phenolic compound, including neochlorogenic acid, p-coumaric acid, raspberry ketone, and rutin significantly increased after 36 h fermentation. Fermentation increased total flavonoid contents in red raspberry juice, compared to that in control group. Volatile profiles exhibited to be enriched after fermentation, which contributed to the improvement of the juice taste. Our findings showed that I. terricola WJL-G4 can be applied in deacidification, enrichment of flavonoid compounds and volatile profiles in fermented red raspberry juice..展开更多
The thermal structure of the continental subduction zone can be deduced from high-pressure and ultra-high-pressure rock samples or numerical simulation.However,petrological data indicate that the temperature of subduc...The thermal structure of the continental subduction zone can be deduced from high-pressure and ultra-high-pressure rock samples or numerical simulation.However,petrological data indicate that the temperature of subducted continental plates is generally higher than that derived from numerical simulation.In this paper,a two-dimensional kinematic model is used to study the thermal structure of continental subduction zones,with or without a preceding oceanic slab.The results show that the removal of the preceding oceanic slab can effectively increase the slab surface temperature of the continental subduction zone in the early stage of subduction.This can sufficiently explain the difference between the cold thermal structure obtained from previous modeling results and the hot thermal structure obtained from rock sample data.展开更多
To The Editor I want to congratulate Dr.Tan and colleagues for their article entitled'Weekly taxane-anthracycline combination regimen versus tri-weekly anthracycline-based regimen for the treatment of locally adva...To The Editor I want to congratulate Dr.Tan and colleagues for their article entitled'Weekly taxane-anthracycline combination regimen versus tri-weekly anthracycline-based regimen for the treatment of locally advanced breast cancer:a randomized controlled trial'[1].The pathologic complete response(pCR)rate was similar in the two arms(10.61%vs.12.31%,P=0.665).However,the展开更多
[Objectives] The aim was to study the contact activity of combination use of garlic,onion and stone calamus extracts on Helicoverpa armigera and their co-toxicity coefficient( CTC) and mixture ratio. [Methods] Leaf di...[Objectives] The aim was to study the contact activity of combination use of garlic,onion and stone calamus extracts on Helicoverpa armigera and their co-toxicity coefficient( CTC) and mixture ratio. [Methods] Leaf dipping method was used to study the contact activity of the three kinds of plant extracts against H. armigera. Based on this,the co-toxicity coefficient of the compound of the three kinds of extracts was determined. Orthogonal test was used to explore the optimal mixture ratio of the three kinds of extract for combination use. [Results]The extracts of garlic,onion and stone calamus had good inhibition and contract activity on H. armigera larvae. The LC50 values of the three kinds of plant extracts against H. armigera were 175. 0,217. 0 and 79. 2 mg/L,respectively. When the mixture ratios of stone calamus to garlic,and stone calamus to onion were both 2:1,the extract showed a synergistic effect( CTC > 120); when the mixture ratios of stone calamus to garlic,and stone calamus to onion were 1:1 and 1:2,respectively,the extracts showed an additive effect( 80 < CTC < 120); and then garlic extract and onion extract were mixed according to the ratio of 1:1,the additive effect was slight( CTC < 90). Among the three kinds of extracts,the extract of stone calamus showed the strongest contact activity,followed by that of garlic. The results of co-toxicity coefficient determination and orthogonal test showed that the contact activity of combination use of the three kinds of extracts was stronger than that of the single extract overall. When the extracts of garlic,onion and stone calamus were mixed according to the ratio of 2:3:1( mass concentration ratio),the contact activity of the compound against H. armigera reached 95. 3%. [Conclusions]The study results provide a scientific basis and theoretical reference for the development of new plant-derived pesticides based on the pharmacodynamics of garlic,onion and stone calamus.展开更多
Skin is the largest organ of the human body and a possible source of stem cells for research and cell-based therapy. We have isolated a population of mesenchymal stem cell-like pluripotent cells from human epidermis, ...Skin is the largest organ of the human body and a possible source of stem cells for research and cell-based therapy. We have isolated a population of mesenchymal stem cell-like pluripotent cells from human epidermis, termed human (h) EMSCPCs. This preliminary study tested if these hEMSCPCs can be induced to differentiate into neural-like cells. Human EMSCPCs were first cultured for four to seven days in a serum-free neural stem cell (NSC) medium for pre-induction. During pre-induction, hEMSCPCs coalesced into dense spheres that resembled neural rosettes. In the presence of a conditioned differentiation medium, pre-induced cells took on the morphological characteristics of neural cells, including slender projections with inflated or claw-like ends that contacted the soma or projections of other cells as revealed by confocal microscopy. Moreover, these differentiating cells expressed the neural-specific markers β-III tubulin, MAP2, GFAP, and synapsin I as evidenced by immunocytochemistry. Both pre-induced hEMSCPCs and uninduced hEMSCPCs were labeled with CM-DiI and transplanted into the vitreous cavities of nude mice. Transplanted cells were examined four weeks later in frozen eyeball sections by immunofluorescence staining, which demonstrated superior retinal migration and neural differentiation of pre-induced cells. Our study is the first to demonstrate that hEMSCPCs possess the capacity to differentiate into neural-like cells, suggesting potential uses for the treatment of retinal diseases such as age-related macular degeneration.展开更多
Environmental effects of nano remediation engineering of arsenic(As)pollution need to be considered.In this study,the roles of Fe_(2)O_(3)and TiO_(2)nanoparticles(NPs)on the microbial mediated As mobilization from As ...Environmental effects of nano remediation engineering of arsenic(As)pollution need to be considered.In this study,the roles of Fe_(2)O_(3)and TiO_(2)nanoparticles(NPs)on the microbial mediated As mobilization from As contaminated soil were investigated.The addition of Fe_(2)O_(3)and TiO_(2)NPs restrained As(V)release,and stimulated As(Ⅲ)release.As(V)concentration decreased by 94% and 93% after Fe_(2)O_(3)addition,and decreased by 89% and 45% after Ti O_(2)addition compared to the Biotic and Biotic+Acetate(amended with sodium acetate)controls,respectively.The maximum values of As(Ⅲ)were 20.5 and 27.1μg/L at 48 d after Fe_(2)O_(3)and TiO_(2)NPs addition,respectively,and were higher than that in Biotic+Acetate control(12.9μg/L).The released As co-precipitated with Fe in soils in the presence of Fe_(2)O_(3)NPs,but adsorbed on TiO_(2)NPs in the presence of TiO_(2)NPs.Moreover,the addition of NPs amended with sodium acetate as the electron donor clearly promoted As(V)reduction induced by microbes.The NPs addition changed the relative abundance of soil bacterial community,while Proteobacteria(42.8%-70.4%),Planctomycetes(2.6%-14.3%),and Firmicutes(3.5%-25.4%)were the dominant microorganisms in soils.Several potential As/Fe reducing bacteria were related to Pseudomonas,Geobacter,Desulfuromonas,and Thiobacillus.The addition of Fe_(2)O_(3)and TiO_(2)NPs induced to the decrease of arr A gene.The results indicated that the addition of NPs had a negative impact on soil microbial population in a long term.The findings offer a relatively comprehensive assessment of Fe_(2)O_(3)and TiO_(2)NPs effects on As mobilization and soil bacterial communities.展开更多
Oral squamous cell carcinoma(OSCC)is known as one of the most malignant tumors with high recurrence and fatality rate.The poor tumor-targeting ability of traditional chemotherapeutic drugs has been a grand challenge f...Oral squamous cell carcinoma(OSCC)is known as one of the most malignant tumors with high recurrence and fatality rate.The poor tumor-targeting ability of traditional chemotherapeutic drugs has been a grand challenge for anti-OSCC therapy.Beyond that,a large quantity of tumor associated macrophages in OSCC tissues further diminish the anti-tumor effects of these drugs.Therefore,we produced a therapeutic nano drug delivery system(FA-PEG-PLA-JQ1)through encapsulating JQ1[a small-molecule inhibitor of bromodomain containing protein 4(BRD4)]into the folic acid(FA)-modified nanoparticle(PEG-PLA),which could prolong the half-life of JQ1 and target the tumor tissues.And then,JQ1 released from this nanoparticle could prevent OSCC growth inducing tumor cell apoptosis,inhibiting tumor angiogenesis and the polarization of M2 type macrophages.In conclusion,our date demonstrated the therapeutic benefits of FA-PEG-PLA-JQ1 against OSCC in vivo or in vitro,which could be a novel treatment strategy for OSCC in coming days.展开更多
Human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC)has been the most challenging subtype of BC,consisting of 20%of BC with an apparent correlation with poor prognosis.Despite that pyrotinib,a new...Human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC)has been the most challenging subtype of BC,consisting of 20%of BC with an apparent correlation with poor prognosis.Despite that pyrotinib,a new HER2 inhibitor,has led to dramatic improvements in prognosis,the efficacy of pyrotinib monotherapy remains largely restricted due to its acquired resistance.Therefore,identifying a new potential antitumor drug in combination with pyrotinib to amplify therapeutic efficacy is a pressing necessity.Here,we reported a novel combination of pyrotinib with chrysin and explored its antitumor efficacy and the underlying mechanism in HER2-positive BC.We determined that pyrotinib combined with chrysin yielded a potent synergistic effect to induce more evident cell cycle arrest,inhibit the proliferation of BT-474 and SK-BR-3 BC cells,and repress in vivo tumor growth in xenograft mice models.This may be attributed to enhanced autophagy induced by endoplasmic reticulum stress.Furthermore,the combined treatment of pyrotinib and chrysin induced ubiquitination and glucose-6-phosphate dehydrogenase(G6PD)degradation by upregulating zinc finger and BTB/POZ domain-containing family protein 16(ZBTB16)in tumorigenesis of BC.Mechanistically,we identified that miR-16-5p was a potential upstream regulator of ZBTB16,and it showed a significant inverse correlation with ZBTB16.Inhibition of miR-16-5p overexpression by restoring ZBTB16 significantly potentiated the overall antitumor efficacy of pyrotinib combined with chrysin against HER2-positive BC.Together,these findings demonstrate that the combined treatment of pyrotinib and chrysin enhances autophagy in HER2-positive BC through an unrecognized miR-16-5p/ZBTB16/G6PD axis.展开更多
基金Supported by Luzhou Municipal People’s Government and Southwest Medical University(No.2021LZXNYD-J03)Science and Technology Department of Sichuan Province Project(No.2022YFS0611).
文摘Iron is one of the necessary metal elements in the human body.There are numerous factors that control the balance of iron metabolism,and its storage and transportation mechanisms are intricate.As one of the most energyintensive tissues in the body,the retina is susceptible to iron imbalance.The occurrence of iron overload in the retina leads to the generation of a significant quantity of reactive oxygen species.This will aggravate local oxidative stress and inflammatory reactions and even lead to ferroptosis,eventually resulting in retinal dysfunction.The blood-retinaretinal barrier is eventually harmed by oxidative stress and elevated inflammation,which are characteristics of retinal vascular disorders.The pathophysiology of retinal vascular disorders may be significantly influenced by iron.Recently,iron-chelating agents have been found to have antioxidative and anti-inflammatory actions in addition to iron chelating.Therefore,iron neutralization is considered to be a new and potentially useful therapeutic strategy.This article reviews the iron overload in retinal vascular diseases and discusses the therapeutic potential of iron-chelating agents.
基金funded by the China Scholarship Council (202006820015)National Natural Science Foundation of China (31872890)State Key Laboratory of Food Science and Technology Free Orientation Project (SKLF-ZZB-201709)。
文摘Rice bran residue possessed a steady lipase activity((26.68 ± 3.69)%)after its endogenous lipase was extracted continuously by phosphate buffer solution(PBS)for 24 h. T herefore, the aim of this research was to explore whether there exist any bound lipases in rice bran(Oryza sativa). Three physical treatments(grinding, homogenizing and ultrasound crush)and 6 enzymatic treatments(cellulase, hemicellulase, pectinase, complex cellulase, glucoamylase and α-amylase)were applied to rice bran in order to investigate this bound lipase. The relative catalytic activities of extraction supernatant and residue for pectinase group were(437.63 ± 22.54)% and(159.26 ± 2.12)%, respectively, which were significantly higher(P < 0.05)than other groups. This phenomenon demonstrated that lipase was the most likely to combine with pectin. Molecular simulation proved that pectin could combine with two rice bran lipases(lipase 315 and lipase 308)and cover the catalytic centers so as to prevent the lipases from encountering the substrate and inhibiting their catalytic activities. During combination, pectin could make the lipases more compact and reduce the solvent accessible surface area of lipases, which would make the lipases inactive to molecular interaction. In summary, part of rice bran lipase was proved to exist in bound form and combined with the pectin.
基金Supported by the Science and Technology Program of Liaoning Province,No.2021-MS-040.
文摘BACKGROUND The carcinogenesis of stomach adenocarcinoma(STAD)involves many different molecules and multiple pathways,including the NOTCH signaling pathway.As a key factor that functions as a critical link in the NOTCH pathway,mind bomb 1(MIB1)is upregulated in various tumors and has been reported to promote cell metastasis and invasion.However,studies on the role of MIB1 in STAD are limited.Here,we evaluated the prognostic value of MIB1 in STAD and its association with immune infiltration and copy number variation.AIM To elucidate the relationship between MIB1 gene and gastric cancer(GC)and provide a new idea for the treatment of GC.METHODS We identified mutations in the MIB1 gene by searching the cBioPortal database and then analyzed their relationship with the overall survival rate and diseasefree survival rate using the Kaplan-Meier method.The Cancer Genome Atlas(TCGA)database provided transcript levels for MIB1 in STADs and normal tissues.As a method of distinguishing the STAD tissues from adjacent normal tissues,a receiver operating characteristic(ROC)curve was generated.Kaplan-Meier plotter was used to determine the effect of MIB1 expression on survival.Based on the LinkedOmics database,we were able to identify the coexpressed genes of the MIB1 gene,the top 50 positively correlated genes,and the top 50 negatively correlated genes.STRING was used to construct protein-protein interaction networks related to the MIB1 gene.An analysis of functional enrichment was carried out using the R package“Cluster Profiler”.The relationships between mRNA expression of MIB1 and immune infiltrates were assessed by Tumor IMmune Estimation Resource(TIMER)and the“GSVA package”in R.RESULTS According to the cBioPortal database,the MIB1 mutation rate in 287 patients in the TCGA dataset was approximately 6%.Kaplan-Meier survival analysis showed that patients with STAD in the mutated group had a worse prognosis than those in the unmutated group(P=0.0156).There was a significant upregulation of MIB1 expression in STAD tissues compared to adjacent normal tissues.A high T stage was associated with increased MIB1 mRNA expression.The ROC curve analysis revealed 59.4%sensitivity and 85.6%specificity of MIB1 for differentiating STAD tissues from adjacent normal tissues at a truncation level of 2.248.Kaplan-Meier plotter indicated that patients with higher MIB1 levels had a worse prognosis than those with lower levels(26.4 mo vs 56.2 mo,P=0.0330).A correlation analysis demonstrated an association between immune infiltrates and MIB1 mRNA expression.CONCLUSION Upregulation of MIB1 expression is significantly associated with poor survival rate and immune infiltration in gastric adenocarcinoma.MIB1 may be a biomarker for the poor prognosis of STAD patients and a potential immunotherapeutic target.
文摘BACKGROUND Colorectal cancer(CRC)is a common life-threatening disease that often requires surgical intervention,such as laparoscopic radical resection.However,despite successful surgeries,some patients experience disease relapse.Identifying the risk factors for CRC relapse can help guide clinical interventions and improve patient outcomes.AIM To determine the risk factors that may lead to CRC relapse after laparoscopic radical resection.METHODS We performed a retrospective analysis using the baseline data of 140 patients with CRC admitted to our hospital between January 2018 and January 2020.All included participants were followed up until death or for 3 years.The baseline data and laboratory indicators were compared between the patients who experienced relapse and those who did not experienced relapse.RESULTS Among the 140 patients with CRC,30 experienced relapse within 3 years after laparoscopic radical resection and 110 did not experience relapse.The relapse group had a higher frequency of rectal tumors with low differentiation and lymphatic vessel invasion than that of the non-relapse group.The expression of serum markers and the prognostic nutritional index were lower,whereas the neutrophil-to-lymphocyte ratio,expression of cytokeratin 19 fragment antigen 21-1,vascular endothelial growth factor,and Chitinase-3-like protein 1 were significantly higher in the relapse group than those in the non-relapse group.The groups did not differ significantly based on other parameters.Logistic regression analysis revealed that all the above significantly altered factors were independent risk factors for CRC relapse.CONCLUSION We identified multiple risk factors for CRC relapse following surgery,which can be considered for the clinical monitoring of patients to reduce disease recurrence and improve patient survival.
基金the National Natural Science Foundation of China, No. 30370639
文摘AIM: To evaluate the efficacy of telomerase activity assay and peritoneal lavage cytology (PLC) examination in peritoneal lavage fluid for the prediction of peritoneal metastasis in gastric cancer patients, and to explore the relationship between telomerase activity and proliferating cell nuclear antigen expression. METHODS: Telomeric repeated amplification protocol (TRAP)-enzyme-linked immunosorbent assay (ELISA) was performed to measure the telomerase activity in 60 patients with gastric cancer and 50 with peptic ulcer. PLC analysis of the 60 patients with gastric cancer was used for comparison. The proliferating cell nuclear antigen (PCNA) in gastric carcinoma was immunohistochemically examined. RESULTS: The telomerase activity and PLC positive rate in peritoneal lavage fluid from patients with gastric cancer was 41.7/ (25/60), and 25.0/ (15/60), respectively. The positive rate of telomerase activity was significantly higher than that of PLC in the group of pT4 (15/16 vs 9/16, P < 0.05), P1-3 (13/13 vs 9/13, P < 0.05) and diffuse type (22/42 vs 13/42, P < 0.05). The patients with positive telomerase activity, peritoneal metastasis, and serosal invasion had signifi cantly higher levels of average PCNA proliferation index (PI), (55.00 ± 6.59 vs 27.43 ± 7.72, 57.26 ± 10.18 vs 29.15 ± 8.31, and 49.82 ± 6.74 vs 24.65 ± 7.33, respectively, P < 0.05).CONCLUSION: The TRAP assay for telomerase activity is a useful adjunct for cytologic method in the diagnosis of peritoneal micrometastasis and well related to higher proliferating activity of gastric cancer. The results of this study also suggest a promising future therapeutic strategy for treating peritoneal dissemination based on telomerase inhibition.
文摘BACKGROUND Cervical cancer is the fourth commonest malignancy in women around the world.It represents the second most commonly diagnosed cancer in South East Asian women,and an important cancer death cause in women of developing nations.Data collected in 2018 revealed 5690000 cervical cancer cases worldwide,85%of which occurred in developing countries.AIM To assess self-perceived burden(SPB)and related influencing factors in cervical cancer patients undergoing radiotherapy.METHODS Patients were prospectively included by convenient sampling at The Fifth Affiliated Hospital of Sun Yat-Sen University,China between March 2018 and March 2019.The survey was completed using a self-designed general information questionnaire,the SPB scale for cancer patients,and the self-care self-efficacy scale,Strategies Used by People to Promote Health,which were delivered to patients with cervical cancer undergoing radiotherapy.Measurement data are expressed as the mean±SD.Enumeration data are expressed as frequencies or percentages.Caregivers were the spouse,offspring,and other in 46.4,40.9,and 12.7%,respectively,and the majority were male(59.1%).As for pathological type,90 and 20 cases had squamous and adenocarcinoma/adenosquamous carcinomas,respectively.Stage IV disease was found in 12(10.9%)patients.RESULTS A total of 115 questionnaires were released,and five patients were excluded for too long evaluation time(n=2)and the inability to confirm the questionnaire contents(n=3).Finally,a total of 110 questionnaires were collected.They were aged 31-79 years,with the 40-59 age group being most represented(65.4%of all cases).Most patients were married(91.8%)and an overwhelming number had no religion(92.7%).Total SPB score was 43.13±16.65.SPB was associated with the place of residence,monthly family income,payment method,transfer status,the presence of radiotherapy complications,and the presence of pain(P<0.05).The SPB and self-care self-efficacy were negatively correlated(P<0.01).In multivariate analysis,self-care self-efficacy,place of residence,monthly family income,payment method,degree of radiation dermatitis,and radiation proctitis were influencing factors of SPB(P<0.05).CONCLUSION Patients with cervical cancer undergoing radiotherapy often have SPB.Self-care self-efficacy scale,place of residence,monthly family income,payment method,and radiation dermatitis and proctitis are factors independently influencing SPB.
基金supported by the National Natural Science Foundation of China (No. 81301222)the Special Research Grant for Non-profit Public Service (No. 201402013)the Science and Technology Department Project of Liaoning province (No. 2012020073-302)
文摘Objective:We aim to investigate radiomic imaging features extracted in computed tomography(CT)images to differentiate invasive pulmonary adenocarcinomas(IPAs)from non-IPAs appearing as part-solid ground-glass nodules(GGNs),and to incorporate significant radiomic features with other clinically-assessed features to develop a diagnostic nomogram model for IPAs.Methods:This retrospective study was performed,with Institutional Review Board approval,on 88 patients with a total of 100 part-solid nodules(56 IPAs and 44 non-IPAs)that were surgically confirmed between February 2014and November 2016 in the First Affiliated Hospital of China Medical University.Quantitative radiomic features were computed automatically on 3D nodule volume segmented from arterial-phase contrast-enhanced CT images.A set of regular risk factors and visually-assessed qualitative CT imaging features were compared with the radiomic features using logistic regression analysis.Three diagnostic models,i.e.,a basis model using the clinical factors and qualitative CT features,a radiomics model using significant radiomic features,and a nomogram model combining all significant features,were built and compared in terms of receiver operating characteristic(ROC)curves.Decision curve analysis was performed for the nomogram model to explore its potential clinical benefit.Results:In addition to three visually-assessed qualitative imaging features,another three quantitative features selected from hundreds of radiomic features were found to be significantly(all P<0.05)associated with IPAs.The diagnostic nomogram model showed a significantly higher performance[area under the ROC curve(AUC)=0.903]in differentiating IPAs from non-IPAs than either the basis model(AUC=0.853,P=0.0009)or the radiomics model(AUC=0.769,P<0.0001).Decision curve analysis indicates a potential benefit of using such a nomogram model in clinical diagnosis.Conclusions:Quantitative radiomic features provide additional information over clinically-assessed qualitative features for differentiating IPAs from non-IPAs appearing as GGNs,and a diagnostic nomogram model including all these significant features may be clinically useful in preoperative strategy planning.
基金Financial support for the tumour response surveillance portion of this prospective randomized trial was provided by Pfizer(WS388465)Department of Science and Technology of Sichuan Province(2014SZ0190)
文摘Background:Extensive studies have confirmed the efficacy of taxanes in combination with anthracycline-based chemotherapy on breast cancer.However,few studies have assessed the efficacy of weekly taxane-anthracycline regimens on locally advanced breast cancer.This study was to compare the efficacy and safety of a weekly taxaneanthracycline regimen with those of tri-weekly anthracycline-based regimen in patients with locally advanced breast cancer.Methods:Patients with locally advanced breast cancer were randomized to receive 4-6 cycles of neoadjuvant chemotherapy with tri-weekly 5-fluorouracil-epirubicin-cyclophosphamide(FEC) regimen or weekly paclitaxel-epirubicin(PE) regimen.The primary endpoint was the pathologic complete response(pCR) rate.Other endpoints included the clinical tumor response,breast-conserving surgery rate,and adverse events.Results:Between March 2010 and September 2013,293 patients were randomized to the FEC(n=151) and PE(n=142) arms.The overall clinical response rate was significantly higher in the PE arm than in the FEC arm(76.06%vs.59.95%,P=0.001).Consistently,the post-chemotherapy pathologic T and N stages were significantly lower in the PE arm than in the FEC arm(P<0.001).However,the pCR rate was similar in the two arms(10.61%vs.12.31%,P=0.665).Overall,36(27.27%) patients in the FEC arm and 6(35.28%) in the PE arm were qualified for breast-conserving surgery.Most adverse events were comparable in both arms,with more severe neutropenia in the PE arm than in the FEC arm(11.97%vs.5.96%,P=0.031).Conclusions:In patients with locally advanced breast cancer,weekly PE was not superior to FEC in terms of pCR.However,weekly PE has a higher response rate and superior down-staging effects.On this account,the PE regimen may be considered an alternative option for locally advanced breast cancer.Long-term follow-up data are needed to confirm the efficacy of this regimen on locally advanced breast cancer.Trial registration Chinese clinical trial registry,ChiCTR-TRC-10001043,September 21。
基金supported by Heilongjiang Tongsheng Food Technology Co.Ltd.+1 种基金“the Fundamental Research Funds for the Central Universities”[grant number 2572018BA07 and 2572018CG02]“Applied Technology Research and Development Project of Harbin Science and Technology Bureau”[grant number 2017RAYXJ012]。
文摘High content of citric acid in red raspberry juice leads to poor sensory experience. This study developed a feasible method to degrade citric acid in red raspberry juice using a novel characterized Issatchenkia terricola WJL-G4 isolated from red raspberry fruits. I. terricola WJL-G4 exhibited a potent capability of reducing the citric acid contents from(22.8 ± 0.08) g/L to(6.2 ± 0.02) g/L within 36 h fermentation, then completely depleted after 48 h. Furthermore, the contents of phenolic compound, including neochlorogenic acid, p-coumaric acid, raspberry ketone, and rutin significantly increased after 36 h fermentation. Fermentation increased total flavonoid contents in red raspberry juice, compared to that in control group. Volatile profiles exhibited to be enriched after fermentation, which contributed to the improvement of the juice taste. Our findings showed that I. terricola WJL-G4 can be applied in deacidification, enrichment of flavonoid compounds and volatile profiles in fermented red raspberry juice..
基金supported by the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB 41000000)National Basic Research Program of China(Grant No.2015CB856106)National Natural Science Foundation of China(41774105,41820104004,41688103).
文摘The thermal structure of the continental subduction zone can be deduced from high-pressure and ultra-high-pressure rock samples or numerical simulation.However,petrological data indicate that the temperature of subducted continental plates is generally higher than that derived from numerical simulation.In this paper,a two-dimensional kinematic model is used to study the thermal structure of continental subduction zones,with or without a preceding oceanic slab.The results show that the removal of the preceding oceanic slab can effectively increase the slab surface temperature of the continental subduction zone in the early stage of subduction.This can sufficiently explain the difference between the cold thermal structure obtained from previous modeling results and the hot thermal structure obtained from rock sample data.
文摘To The Editor I want to congratulate Dr.Tan and colleagues for their article entitled'Weekly taxane-anthracycline combination regimen versus tri-weekly anthracycline-based regimen for the treatment of locally advanced breast cancer:a randomized controlled trial'[1].The pathologic complete response(pCR)rate was similar in the two arms(10.61%vs.12.31%,P=0.665).However,the
文摘[Objectives] The aim was to study the contact activity of combination use of garlic,onion and stone calamus extracts on Helicoverpa armigera and their co-toxicity coefficient( CTC) and mixture ratio. [Methods] Leaf dipping method was used to study the contact activity of the three kinds of plant extracts against H. armigera. Based on this,the co-toxicity coefficient of the compound of the three kinds of extracts was determined. Orthogonal test was used to explore the optimal mixture ratio of the three kinds of extract for combination use. [Results]The extracts of garlic,onion and stone calamus had good inhibition and contract activity on H. armigera larvae. The LC50 values of the three kinds of plant extracts against H. armigera were 175. 0,217. 0 and 79. 2 mg/L,respectively. When the mixture ratios of stone calamus to garlic,and stone calamus to onion were both 2:1,the extract showed a synergistic effect( CTC > 120); when the mixture ratios of stone calamus to garlic,and stone calamus to onion were 1:1 and 1:2,respectively,the extracts showed an additive effect( 80 < CTC < 120); and then garlic extract and onion extract were mixed according to the ratio of 1:1,the additive effect was slight( CTC < 90). Among the three kinds of extracts,the extract of stone calamus showed the strongest contact activity,followed by that of garlic. The results of co-toxicity coefficient determination and orthogonal test showed that the contact activity of combination use of the three kinds of extracts was stronger than that of the single extract overall. When the extracts of garlic,onion and stone calamus were mixed according to the ratio of 2:3:1( mass concentration ratio),the contact activity of the compound against H. armigera reached 95. 3%. [Conclusions]The study results provide a scientific basis and theoretical reference for the development of new plant-derived pesticides based on the pharmacodynamics of garlic,onion and stone calamus.
文摘Skin is the largest organ of the human body and a possible source of stem cells for research and cell-based therapy. We have isolated a population of mesenchymal stem cell-like pluripotent cells from human epidermis, termed human (h) EMSCPCs. This preliminary study tested if these hEMSCPCs can be induced to differentiate into neural-like cells. Human EMSCPCs were first cultured for four to seven days in a serum-free neural stem cell (NSC) medium for pre-induction. During pre-induction, hEMSCPCs coalesced into dense spheres that resembled neural rosettes. In the presence of a conditioned differentiation medium, pre-induced cells took on the morphological characteristics of neural cells, including slender projections with inflated or claw-like ends that contacted the soma or projections of other cells as revealed by confocal microscopy. Moreover, these differentiating cells expressed the neural-specific markers β-III tubulin, MAP2, GFAP, and synapsin I as evidenced by immunocytochemistry. Both pre-induced hEMSCPCs and uninduced hEMSCPCs were labeled with CM-DiI and transplanted into the vitreous cavities of nude mice. Transplanted cells were examined four weeks later in frozen eyeball sections by immunofluorescence staining, which demonstrated superior retinal migration and neural differentiation of pre-induced cells. Our study is the first to demonstrate that hEMSCPCs possess the capacity to differentiate into neural-like cells, suggesting potential uses for the treatment of retinal diseases such as age-related macular degeneration.
基金supported by the National Natural Science Foundation of China(No.41977283)the Qing Lan Project of Jiangsu Province of China。
文摘Environmental effects of nano remediation engineering of arsenic(As)pollution need to be considered.In this study,the roles of Fe_(2)O_(3)and TiO_(2)nanoparticles(NPs)on the microbial mediated As mobilization from As contaminated soil were investigated.The addition of Fe_(2)O_(3)and TiO_(2)NPs restrained As(V)release,and stimulated As(Ⅲ)release.As(V)concentration decreased by 94% and 93% after Fe_(2)O_(3)addition,and decreased by 89% and 45% after Ti O_(2)addition compared to the Biotic and Biotic+Acetate(amended with sodium acetate)controls,respectively.The maximum values of As(Ⅲ)were 20.5 and 27.1μg/L at 48 d after Fe_(2)O_(3)and TiO_(2)NPs addition,respectively,and were higher than that in Biotic+Acetate control(12.9μg/L).The released As co-precipitated with Fe in soils in the presence of Fe_(2)O_(3)NPs,but adsorbed on TiO_(2)NPs in the presence of TiO_(2)NPs.Moreover,the addition of NPs amended with sodium acetate as the electron donor clearly promoted As(V)reduction induced by microbes.The NPs addition changed the relative abundance of soil bacterial community,while Proteobacteria(42.8%-70.4%),Planctomycetes(2.6%-14.3%),and Firmicutes(3.5%-25.4%)were the dominant microorganisms in soils.Several potential As/Fe reducing bacteria were related to Pseudomonas,Geobacter,Desulfuromonas,and Thiobacillus.The addition of Fe_(2)O_(3)and TiO_(2)NPs induced to the decrease of arr A gene.The results indicated that the addition of NPs had a negative impact on soil microbial population in a long term.The findings offer a relatively comprehensive assessment of Fe_(2)O_(3)and TiO_(2)NPs effects on As mobilization and soil bacterial communities.
基金supported by the National Natural Science Foundation of China(Nos.32222046 and 82172630)the Key R&D Projects of the Science and Technology Department of Sichuan Province(No.2021YFS0235)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(Nos.ZYJC21022 and 2019HXFH017)。
文摘Oral squamous cell carcinoma(OSCC)is known as one of the most malignant tumors with high recurrence and fatality rate.The poor tumor-targeting ability of traditional chemotherapeutic drugs has been a grand challenge for anti-OSCC therapy.Beyond that,a large quantity of tumor associated macrophages in OSCC tissues further diminish the anti-tumor effects of these drugs.Therefore,we produced a therapeutic nano drug delivery system(FA-PEG-PLA-JQ1)through encapsulating JQ1[a small-molecule inhibitor of bromodomain containing protein 4(BRD4)]into the folic acid(FA)-modified nanoparticle(PEG-PLA),which could prolong the half-life of JQ1 and target the tumor tissues.And then,JQ1 released from this nanoparticle could prevent OSCC growth inducing tumor cell apoptosis,inhibiting tumor angiogenesis and the polarization of M2 type macrophages.In conclusion,our date demonstrated the therapeutic benefits of FA-PEG-PLA-JQ1 against OSCC in vivo or in vitro,which could be a novel treatment strategy for OSCC in coming days.
基金supported by the Sichuan Provincial Department of Science and Technology,International Cooperation in Science and Technology Innovation with Hong Kong,Macao,and Taiwan(2023YFH0095)1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC21035)+2 种基金Beijing Xislike Clinical Oncology Research Foundation(Y-HR2020MS-1031)Beijing Science and Technology Innovation Medical Development Foundation(KC2021-JF-0167-13)Key Research and Development Program of Xuzhou(KC20115)。
文摘Human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC)has been the most challenging subtype of BC,consisting of 20%of BC with an apparent correlation with poor prognosis.Despite that pyrotinib,a new HER2 inhibitor,has led to dramatic improvements in prognosis,the efficacy of pyrotinib monotherapy remains largely restricted due to its acquired resistance.Therefore,identifying a new potential antitumor drug in combination with pyrotinib to amplify therapeutic efficacy is a pressing necessity.Here,we reported a novel combination of pyrotinib with chrysin and explored its antitumor efficacy and the underlying mechanism in HER2-positive BC.We determined that pyrotinib combined with chrysin yielded a potent synergistic effect to induce more evident cell cycle arrest,inhibit the proliferation of BT-474 and SK-BR-3 BC cells,and repress in vivo tumor growth in xenograft mice models.This may be attributed to enhanced autophagy induced by endoplasmic reticulum stress.Furthermore,the combined treatment of pyrotinib and chrysin induced ubiquitination and glucose-6-phosphate dehydrogenase(G6PD)degradation by upregulating zinc finger and BTB/POZ domain-containing family protein 16(ZBTB16)in tumorigenesis of BC.Mechanistically,we identified that miR-16-5p was a potential upstream regulator of ZBTB16,and it showed a significant inverse correlation with ZBTB16.Inhibition of miR-16-5p overexpression by restoring ZBTB16 significantly potentiated the overall antitumor efficacy of pyrotinib combined with chrysin against HER2-positive BC.Together,these findings demonstrate that the combined treatment of pyrotinib and chrysin enhances autophagy in HER2-positive BC through an unrecognized miR-16-5p/ZBTB16/G6PD axis.
