BACKGROUND Bilateral internal mammary arteries(BIMAs)as the most advanced surgical option for coronary artery bypass grafting(CABG)are usually recommended for younger patients without traditional risk factors.This stu...BACKGROUND Bilateral internal mammary arteries(BIMAs)as the most advanced surgical option for coronary artery bypass grafting(CABG)are usually recommended for younger patients without traditional risk factors.This study compares outcomes in propensity score-matched patients aged over 70 years who received BIMAs versus those who received a single internal mammary artery(SIMA).METHODS From 2013 to 2024,8123 patients underwent primary CABG for multivessel coronary artery disease at our institution.BIMA grafting was performed in 1233 patients(15.17%),with in situ BIMA grafting in 290 patients(3.57%).For in situ BIMA group,the right internal mammary artery was used to revascularize the right coronary artery,while the left internal mammary artery was utilized for the left anterior descending artery.BIMA patients aged over 70 years(n=79)were compared with SIMA patients(n=79)using propensity score matching.Primary outcome was all-cause mortality at 30 days and 8 years.Secondary outcomes included length of hospital stay,incidence of postoperative major adverse cardiovascular and cerebrovascular events,sternal wound infection and the need for subsequent percutaneous revascularization.RESULTS There was no difference in immediate postoperative primary and secondary outcomes.Mean follow-up was 8.3±1.0 years with an 8-year freedom from death of 67.08%±1.1%in the BIMA group versus 58.22%±0.9%in the SIMA group(P<0.05).CONCLUSIONS BIMAs as in situ grafts can be successfully used in CABG for patients aged 70 years and older.Consequently,the refined techniques for constructing internal mammary artery grafts used in this study challenge traditionally accepted limitations regarding the use of BIMAs.展开更多
Mammary stem cells(MaSCs),endowed with self-renewal and multilineage differentiation capabilities,are crucial for mammary gland development,function,and disease initiation.Recent advances in MaSCs biology research enc...Mammary stem cells(MaSCs),endowed with self-renewal and multilineage differentiation capabilities,are crucial for mammary gland development,function,and disease initiation.Recent advances in MaSCs biology research encompass molecular marker identification,regulatory pathway dissection,and microenvironmental crosstalk.This review synthesizes key progress and remaining challenges in MaSC research.Molecular profiling advances have identified key markers recently,such as Procr,DII1,Bcl11b,and PD-L1.Central to their regulatory logic are evolutionarily conserved pathways,including Wnt,Notch,Hedgehog,and Hippo,which exhibit context-dependent thresholds to balance self-renewal and differentiation.Beyond intrinsic signaling,the dynamic interplay between MaSCs and their microenvironment,such as luminalderived Wnt4,macrophage-mediated TNF-α signaling,and adrenergic inputs from sympathetic nerves,spatially orchestrates stem cell behavior.In addition,this review also discusses the roles of breast cancer stem cells(BCSCs) in tumorigenesis and therapeutic resistance,focusing on the molecular mechanisms underlying MaSC transformation into BCSCs.Despite progress,challenges remain:human MaSCs functional assays lack standardization,pathway inhibitors risk off-target effects,and delivery systems lack precision.Emerging tools like spatial multi-omics,organoids,and biomimetic scaffolds address these gaps.By integrating MaSCs and BCSCs biology,this review links mechanisms to breast cancer and outlines strategies to target malignancy to accelerate clinical translation.展开更多
Background Lactate is a classical byproduct of glucose metabolism,and the main lactate production pathway depends on glycolysis.Lactate stabilized HIF1αby inhibiting PHD activity,leading to hypoxic stress response an...Background Lactate is a classical byproduct of glucose metabolism,and the main lactate production pathway depends on glycolysis.Lactate stabilized HIF1αby inhibiting PHD activity,leading to hypoxic stress response and exacerbating glycolysis in multiple tissues.However,the redox induction mechanism of lactate in mammary gland has not been understood yet.Herein,we describe a lactate-responsive HIF1α/circadian control mechanism in oxidative stress in the mammary glands of dairy cows.Results The in vivo study showed that dairy cows with high lactate concentrations are associated with reduced milk yield and more ROS accumulation in mammary gland.Western blot results in MAC-T cells showed positive correlation between lactate concentrations,expression of HIF1αand oxidative stress indicators,but not circadian core components.To test how lactate-mediated HIF1αdysfunction leads to cell protection process,we investigated altered expression of circadian core related genes following HIF1αstabilization.We found that stabilized HIF1αby lactate inhibited stimulated expression of circadian core components due to the similarity of HRE and E-box transcription elements.Furthermore,we found that lactate treatment strengthened the binding of HIF1αwith BMAL1,HMOX1 and FOXO3 in MAC-T cells.Moreover,HIF1αknockdown altered expression of circadian rhythm related genes and reduced oxidative stress state.Conclusion In summary,our study highlights the central role of competitive transcriptional element occupancy in lactate-mediated oxidative stress of mammary gland,which is caused by HIF1αstabilization and circadian rhythm dysfunction.Our findings introduce a novel nutritional strategy with potential applications in dairy farming for optimizing milk production and maintaining mammary gland health.展开更多
A lactating dairy cow mammary epithelial cell(DCMEC)model is useful for studying milk synthesis and lactation in the dairy cow mammary gland.However,the cells can only maintain their original characteristics for a lim...A lactating dairy cow mammary epithelial cell(DCMEC)model is useful for studying milk synthesis and lactation in the dairy cow mammary gland.However,the cells can only maintain their original characteristics for a limited period in vitro.Thus,the proliferative capacity and lactation pattern of subcultured DCMECs need to be characterized.In the present study,subcultured DCMECs appeared to proliferate without changes in morphology or growth pattern up to the 12th passage.Subculturing had no obvious effect on the lactation capacity of the subcultured DCMEC up to the 10th passage in vitro.These results indicated that the DCMEC line could be subpassaged up to 10 times and still maintain its original milk synthesis characteristics.Moreover,DCMECs were frozen using different methods,and the method of placing the vials in the foam box was determined after cryopreservation with the best adherence of 91.2%.This method was recommended for long-term cryopreservation for DCMECs.展开更多
Background In perinatal dairy cows,ketosis is a prevalent metabolic disorder that lowers milk output and per-formance.Mitochondrial dysfunction and chronic inflammation in mammary tissue are linked to elevated blood k...Background In perinatal dairy cows,ketosis is a prevalent metabolic disorder that lowers milk output and per-formance.Mitochondrial dysfunction and chronic inflammation in mammary tissue are linked to elevated blood ketone levels,particularlyβ-hydroxybutyrate(BHB).Recent research has linked cytosolic mitochondrial DNA(mtDNA)with chronic aseptic inflammation by activating the cGAS-STING pathway during metabolic disorders,while autophagy activation effectively reverses this process.However,whether it is involved in mammary gland damage during ketosis is poorly understood.Therefore,this study aimed to explore the underlying mechanisms of mtDNA-induced inflammation under BHB stress and evaluate the potential therapeutic strategy of autophagy activation in mitigating this damage.Results Our study found an increased cytoplasmic mtDNA abundance in mammary gland tissues of dairy cows with ketosis and bovine mammary epithelial cell line(MAC-T)subjected to BHB stress.Further investigations revealed the activation of the cGAS-STING pathway and inflammatory response,indicated by elevated levels of cGAS and STING,along with increased phosphorylation levels of TBK1,P65,and IκB,and higher transcript levels of pro-inflammatory factors(IL-1B,IL-6,and TNF-α)in both in vivo and in vitro experiments.Notably,STING inhibition via si-STING transfection reversed BHB-induced inflammation.Additionally,autophagy activation appeared to protect against BHB stress by facilitating the removal of cytoplasmic mtDNA and preventing cGAS-STING pathway-mediated inflammation.Conclusions The findings illustrate that elevated BHB levels lead to the release of cytoplasmic mtDNA,which in turn activates the cGAS-STING pathway and triggers an inflammatory response in the mammary glands during hyper-ketonemia.Conversely,autophagy activation has been shown to alleviate this process by promoting cytoplasmic mtDNA degradation.展开更多
Background Ferroptosis is characterized by increased production of reactive oxygen species(ROS)and membrane lipid peroxidation that can exacerbate inflammatory damage.Extracellular vesicles(EVs)isolated from bovine mi...Background Ferroptosis is characterized by increased production of reactive oxygen species(ROS)and membrane lipid peroxidation that can exacerbate inflammatory damage.Extracellular vesicles(EVs)isolated from bovine milk have many biological functions,including antioxidant properties.However,the role of EVs on Klebsiella pneumoniaeinduced ferroptosis and oxidative stress in bovine mammary epithelial cells(bMECs)and murine mammary tissue is unclear.In this study,EVs were isolated from bovine colostrum,mature milk and clinical mastitis milk(defined as C-EVs,M-EVs and CM-EVs,respectively)and assessed by transmission electron microscopy,Western blot and transcriptome sequencing.Effects of EVs on K.pneumoniae-induced ferroptosis and oxidative stress in bMECs were evaluated with immunofluorescence and Western blot.Results In bMECs,infection with K.pneumoniae induced oxidative stress,decreasing protein expression of Nrf2,Keap1 and HO-1 plus SOD activity,and increasing ROS concentrations.However,protein expression of GPX4,ACSL4 and S100A4 in bMECs,all factors that regulate ferroptosis,was downregulated by K.pneumoniae.Furthermore,this bacterium compromised tight junctions in murine mammary tissue,with low expression of ZO-1 and Occludin,whereas protein expression of Nrf2 and GPX4 was also decreased in mammary tissue.Adding C-EVs,M-EVs or CMEVs reduced oxidative stress and ferroptosis in K.pneumoniae-infected bMECs in vitro and murine mammary tissues in vivo.Conclusion In conclusion,all 3 sources of milk-derived EVs alleviated oxidative stress and ferroptosis in K.pneumoniae-infected bMECs and mammary tissues.展开更多
Background Although several cell culture systems have been developed to investigate the function of the mam-mary gland in dairy livestock,they have potential limitations,such as the loss of alveolar structure or genet...Background Although several cell culture systems have been developed to investigate the function of the mam-mary gland in dairy livestock,they have potential limitations,such as the loss of alveolar structure or genetic and phe-notypic differences from their native counterparts.Overcoming these challenges is crucial for lactation research.Development of protocols to establish lactating organoid of livestock represents a promising goal for the future.In this study,we developed a protocol to establish a culture system for mammary organoids in dairy goats to model the mammary gland development and lactation process.Results The organoids cultured within an extracellular matrix gel maintained a bilayer structure that closely resem-bled the native architecture of mammary tissue.The expansion of mammary organoids was significantly promoted by growth factors containing epidermal growth factor and fibroblast growth factor 2 whereas the proliferative index of the organoids was significantly inhibited by the treatment with WNT inhibitors.Upon stimulation with a lactogenic medium containing prolactin,the mammary organoids exhibited efficient lactation,characterized by the accumu-lation of lipid droplets in the lumen space.The lactation could be sustained for more than 3 weeks.Importantly,the expression patterns of genes related to fatty acid synthesis and milk proteins in lactating organoids closely mirrored those observed in mammary tissues.These observations were confirmed by data from proteomic analysis that the bulk of milk proteins was produced in the lactating organoids.Conclusion This study is the first to establish a mammary organoid culture system modeling the mammary gland development and lactation process in ruminants.The efficient induction of lactation in ruminant mammary organoids holds promises for advancing the field of cell-based milk bio-manufacture in the food industry.展开更多
BACKGROUND Internal mammary(IM)lymphadenopathies in breast cancer indicate a worse prognosis than axillary metastases,yet they are rarely assessed.Accurate staging is essential for treatment planning.Robotic biopsy of...BACKGROUND Internal mammary(IM)lymphadenopathies in breast cancer indicate a worse prognosis than axillary metastases,yet they are rarely assessed.Accurate staging is essential for treatment planning.Robotic biopsy offers a promising alternative to video-assisted thoracic surgery for precise histological sampling.This article outlines a systematic robot-assisted dissection approach to enhance staging accuracy and optimize breast cancer management.CASE SUMMARY At our institution,robotic lymphadenectomy of the IM chain was performed in 5 patients between July 2020 and December 2024.Patients were positioned in a 30°semi-supine position with a roll under the shoulder to elevate the chest.The camera port was inserted in the fifth intercostal space along the mid-axillary line,allowing a 0°,12 mm robotic camera to inspect the chest cavity;CO_(2) insufflation(8 L/minute,8-10 mmHg)facilitated lung collapse and pneumo-mediastinum formation for improved dissection.Under direct vision,two additional operative ports were placed:One in the third intercostal space(anterior axillary line)and another in the fifth intercostal space(3-4 cm lateral to the parasternal line).The mean operative time was 118 minutes,with a median hospital stay of two days.No major complications occurred.Histology confirmed breast carcinoma metas tases in three patients,while two had benign disease.CONCLUSION Robotic biopsy of IM lymph nodes is safe,feasible,and provides key information on breast cancer management,with very rare contraindications.展开更多
Objective:This study primarily focuses on analyzing the inductive effects of emotional disturbances on the malignant transformation process of mammary gland epithelial cells.Methods:A total of 42 patients with maligna...Objective:This study primarily focuses on analyzing the inductive effects of emotional disturbances on the malignant transformation process of mammary gland epithelial cells.Methods:A total of 42 patients with malignant transformation of mammary gland epithelial cells(breast cancer,observation group)and 42 patients without malignant transformation of mammary gland epithelial cells(non-breast tumors,control group)were selected as research subjects.The earliest consultation time was January 2022,and the latest was January 2024.The extent of psychological stress impact on these patients was compared.Results:Compared with the control group,the observation group experienced a higher frequency and intensity(LEU value)of adverse life events,with P<0.05.The intensity of adverse life events in the observation group,except for mild events,was significantly higher than that in the control group(P<0.05).In terms of the content distribution of adverse life events,the proportion of marital and family problems in the observation group was significantly higher than that in the control group(P<0.05).The negative coping score and positive coping score in the observation group were significantly different from those in the control group(P<0.05).Regarding social support,the objective support score in the observation group was higher than that in the control group(P<0.05).Conclusion:During the malignant transformation process of mammary gland epithelial cells,long-term emotional disturbances have a significant impact,indicating a close relationship between psychological stress and the occurrence of breast cancer.展开更多
[ Objective] To investigate the feasibility of the primary culture of bovine mammary epithelial cells in biochemical incubator. [ Method] In vitro, bovine mammary epithelial cells were isolated and cultured by the tis...[ Objective] To investigate the feasibility of the primary culture of bovine mammary epithelial cells in biochemical incubator. [ Method] In vitro, bovine mammary epithelial cells were isolated and cultured by the tissue explant method in order to investigate the optimal culture conditions. The morphology observation and identification of the cultured cells were performed by inverted microscope observation, Giemsa staining and cytokeratin immunohistochemistry. [ Result] Observed with inverted microscope, most of the bovine mammary epithelial cells were polygonal and displayed typical slabstone-like appearance. As it can be seen from cell staining results, the cell body was big and the nucleus was stained dark blue and was round or oval in shape, with clearly visible nucleoli, generally 2 -4 nucleoli. The tissue-specific expression of cytokeratin 14 and cytokeratin 18 genes in mammary epithelial cells was identified by cytokeratin immunohistochemistry. [ Conclusion] Primary bovine mammary epithelial cells were successfully cultured in biochemical incubator.展开更多
MicroRNAs （miRNAs） are endogenous -22 nucleofide-long noncoding RNAs. In this study, to investigate miRNA expression profiles and their functions in mammary gland development, we have used microarray as well as qRT-...MicroRNAs （miRNAs） are endogenous -22 nucleofide-long noncoding RNAs. In this study, to investigate miRNA expression profiles and their functions in mammary gland development, we have used microarray as well as qRT-PCR, to analyze the miRNA expression changes along the murine mammary cycle during pregnancy, particularly on transition from pregnancy to lactation. It shows that every developmental stage of the mammary gland has its own mjRNA expression pattern. Compared with virgin and involution, some miRNAs such as miR-138 and miR-431 are downregulated, whereas, some miRNAs such as miR-133 and miR-133a-133b are upregulated during pregnancy and lactation. These results indicate that miRNAs are functionally involved in mammary gland development.展开更多
Objective To evaluate the outcome of off-pump coronary artery bypass grafting(OPCABG)using a bilateral internal mammary artery(BIMA)Y configuration graft to achieve total arterial myocardial revascularization.Methods ...Objective To evaluate the outcome of off-pump coronary artery bypass grafting(OPCABG)using a bilateral internal mammary artery(BIMA)Y configuration graft to achieve total arterial myocardial revascularization.Methods From October 2002 to December 2008,208 patients(196 males and 12 females)underwent OPCABG using a BIMA Y configuration graft.The average age of the patients was 56.5±11.3 years,with an age range of 33-78 years.A total of 167(80.2%)cases had triple-vessel disease.Left main stem disease was found in 33(15.9%)cases,and double-vessel disease was found in 8(3.9%)cases.The semi-skeletonization technique was used to harvest the two internal mammary arteries(IMAs),and then the free right internal mammary artery was connected end-to-side to the left internal mammary artery(LIMA)in situ to complete the Y configuration graft.Off-pump and sequential anastomosis methods were used to perform coronary artery bypass surgery in all patients.Graft patency was assessed intm-operatively with the HT311 transit time flowmeter.Results A total of 728 distal anastomoses were performed in 208 patients,with the average being 3.5±1.3 per person.No one died or experienced recurrent angina within 30 days after the operation.Conclusions OPCABG using the BIMA Y graft was safe and effective to achieve total arterial revascularization.This method avoids surgical operation on the ascending aorta and other incisions.展开更多
Objective： To study the effect of Runing II （a Chinese herbal preparation for mammary cancer） on the growth and metastasis of transplanted tumor of mammary cancer MA-891-bearing TA2 mice and its mechanism. Methods...Objective： To study the effect of Runing II （a Chinese herbal preparation for mammary cancer） on the growth and metastasis of transplanted tumor of mammary cancer MA-891-bearing TA2 mice and its mechanism. Methods： The model of mammary cancer MA-891 cell strain transplanted tumor of TA2 mice with lung metastasis were developed to observe the effect of Runing II on the growth and metastasis of the transplanted tumor. The immunohistochemical method and image analysis were adopted to detect the levels of vascular endothelial growth factor （VEGF）, vascular endothelial growth factor receptor （VEGFR）, and micro-vessel count （MVC） and micro-vessel area （MVA）. Results： In the Runing II group, the tumor weight inhibition rate and the lung metastasis inhibition rate were 37.3% and 65.4% respectively, the tumor growth and lung metastasis were obviously inhibited; And the levels of VEGF and VEGFR, MVC and MVA were significantly decreased as compared with those in the tumor-bearing control group （P〈0.05）. Conclusion： The Chinese herbal preparation Running II can inhibit the metastasis of tumor through inhibiting the angiogenesis, and the mechanism is possibly related with down-regulation of VEGF and VEGFR expression.展开更多
[Objective] The aim of this study was to optimize conditions of exogenous gene mediated by liposome to transfect yak mammary epithelial cells in Vitro.[Method] Yak mammary epithelial cells were isolated and cultivated...[Objective] The aim of this study was to optimize conditions of exogenous gene mediated by liposome to transfect yak mammary epithelial cells in Vitro.[Method] Yak mammary epithelial cells were isolated and cultivated in Vitro by the methods of collagenase digestion and tissue adhesion.The expression of cytokeratin in yak mammary epithelial cell was detected by immunocytochemistry technique.With green fluorescence protein as the report gene,yak mammary epithelial cells were transfected with exogenous gene m...展开更多
The vectors carrying the genes coding for the proteins of interest are of unpredictable efficiency in transgenic animals. The expression vector of mammary gland (pINGG) containing GCSF genomic DNA was injected into m...The vectors carrying the genes coding for the proteins of interest are of unpredictable efficiency in transgenic animals. The expression vector of mammary gland (pINGG) containing GCSF genomic DNA was injected into mouse mammary gland, and expression was detected in the milk of mice. The result showed that mammary gland injection method could provide a convenient transient system to confirm vector validity.展开更多
Background Environmental heat stress(HS)can have detrimental effects on milk production by compromising the mammary function.Mammary plasma flow(MPF)plays a crucial role in nutrient supply and uptake in the mam-mary g...Background Environmental heat stress(HS)can have detrimental effects on milk production by compromising the mammary function.Mammary plasma flow(MPF)plays a crucial role in nutrient supply and uptake in the mam-mary gland.In this experiment,we investigated the physiological and metabolic changes in high-yielding cows exposed to different degrees of HS:no HS with thermal-humidity index(THI)below 68(No-HS),mild HS(Mild-HS,68≤THI≤79),and moderate HS(Mod-HS,79<THI≤88)in their natural environment.Our study focused on the changes in blood oxygen supply and mammary glucose uptake and utilization.Results Compared with No-HS,the MPF of dairy cows was greater(P<0.01)under Mild-HS,but was lower(P<0.01)in cows under Mod-HS.Oxygen supply and consumption exhibited similar changes to the MPF under different HS,with no difference in ratio of oxygen consumption to supply(P=0.46).The mammary arterio-vein differences in glucose concentration were lower(P<0.05)under Mild-and Mod-HS than under no HS.Glucose supply and flow were significantly increased(P<0.01)under Mild-HS but significantly decreased(P<0.01)under Mod-HS compared to No-HS.Glucose uptake(P<0.01)and clearance rates(P<0.01)were significantly reduced under Mod-HS compared to those under No-HS and Mild-HS.Under Mild-HS,there was a significant decrease(P<0.01)in the ratio of lac-tose yield to mammary glucose supply compared to that under No-HS and Mod-HS,with no difference(P=0.53)in the ratio of lactose yield to uptaken glucose among different HS situations.Conclusions Degrees of HS exert different influences on mammary metabolism,mainly by altering MPF in dairy cows.The output from this study may help us to develop strategies to mitigate the impact of different degrees of HS on milk production.展开更多
[Objective]The aim of this study was to explore the technical system of induced expression in vitro of goat mammary gland epithelial cell,and evaluate expression efficiency of mammary gland specific vector and foreign...[Objective]The aim of this study was to explore the technical system of induced expression in vitro of goat mammary gland epithelial cell,and evaluate expression efficiency of mammary gland specific vector and foreign protein at the cell level.[Method]Goat mammary gland epithelial cell transfected by human lactoferrin gene was inducted by culturing in DMEM/F12 medium supplemented with 5 mg/L insulin,5 mg/L prolactin and 1 mg/L hydrocortisone.Supernatant was collected per 6 hours and concentrated.Expression situation of foreign protein were detected by SDS-PAGE and Western blotting.[Result]There was target protein expression in the induced culture medium,which molecular weight was about 42 kD.[Conclusion]The method used in this study can induce goat mammary gland epithelial cell to express foreign gene,it lays a foundation for researching heterologous expression of foreign gene and producing mammary gland bioreactor.展开更多
We present a case of a 71-year-old woman suffering from mammary Paget,s disease and having a 10-years history of an irregular, widespread erosion accompanied by itching and burning on the skin of her left chest, exten...We present a case of a 71-year-old woman suffering from mammary Paget,s disease and having a 10-years history of an irregular, widespread erosion accompanied by itching and burning on the skin of her left chest, extending to the breast. The erosion had steadily enlarged and had become increasingly tender. The nipple and areola of the left breast disappeared and could not be recognized. No abnormality of the right nipple, areola, and covering skin and no supernumerary nipple were seen. Mammography and ultrasonography could not be performed because of severe pain and erosive wetness. Histopathology of a surgical biopsy specimen showed epidermal infiltration by large, round, clear atypical cells scattered individually or in small clusters and distributed horizontally throughout the epidermis. The cytoplasm of these large cells was pale and vacuolated and was equivalent to that in nipple cells in Paget,s disease, and a diagnosis of mammary Paget,s disease was made. We performed total mastectomy of the left breast with wide excision of the Paget lesion of the left chest and axillary lymph node sampling. Histological examination of the specimen showed typical distribution of Paget,s cells;however no ductal carcinoma in situ was found in the mammary ducts and invasive growth was not recognized beyond the basal membrane of the lesion. From this evidences, we established a diagnosis of large, irregulaly shaped unusual mammary Paget,s disease, not of breast cancer origin, covering the left breast, areola, and nipple.展开更多
The effects of Aspirin on tumor chemoprevention and inhibition have been debated and researched in recent years and its effects on colorectal cancer are quite clear.For breast cancer,however,conclusions are inconsiste...The effects of Aspirin on tumor chemoprevention and inhibition have been debated and researched in recent years and its effects on colorectal cancer are quite clear.For breast cancer,however,conclusions are inconsistent and the anti-tumor mechanism of Aspirin is not clear yet.In our study,we used DMBA-induced mammary gland carcinogenesis model to assess the chemoprevention effect of Aspirin on mammary precancerous lesions.After SD rats were treated with Aspirin,the total numbers of precancerous lesion in experimental groups were 16（40 mg/kg Aspirin） and 13（20 mg/kg Aspirin）,while the number in control group was 35.In vitro,we found that Aspirin inhibited cell proliferation in human breast cancer cell line MCF-7 by SRB assay with no apparent cytotoxity under the doses of 10,8,6,4 and 2 mM,the inhibitory rates were 86.96%,54.56%,24.83%,14.24% and 4.49%,respectively.In mechanism research,the results of gene microarray assay demonstrated that 4 mM and 2 mM Aspirin were effective in changing gene expression profile in MCF-7 cells.The expression of cell cycle regulator,cyclin A,was significantly down-regulated under the same doses,while the down-regulation of Cdk2 was only remarkable at 4 mM.Our findings reveal that Aspirin is effective in tumor inhibition during initial phase in rats.In MCF-7 cells,Aspirin reduces cell proliferation without significant cytotoxity and its possible mechanism involves altering tumor-related gene expression and regulating cell cycle process.展开更多
Milk is synthesized by mammary epithelial cells of lactating mammals. The synthetic capacity of the mammary gland depends largely on the number and efficiency of functional mammary epithelial cells. Structural develop...Milk is synthesized by mammary epithelial cells of lactating mammals. The synthetic capacity of the mammary gland depends largely on the number and efficiency of functional mammary epithelial cells. Structural development of the mammary gland occurs during fetal growth, prepubertal and post-pubertal periods, pregnancy, and lactation under the control of various hormones （particularly estrogen, growth hormone, insulin-like growth factor-I, progesterone, placental lactogen, and prolactin） in a species- and stage-dependent manner. Milk is essential for the growth, development, and health of neonates. Amino acids （AA）, present in both free and peptide-bound forms, are the most abundant organic nutrients in the milk of farm animals. Uptake of AA from the arterial blood of the lactating dam is the ultimate source of proteins （primarily 13-casein and a-lactalbumin） and bioactive nitrogenous metabolites in milk. Results of recent studies indicate extensive catabolism of branched-chain AA （leucine, isoleucine and valine） and arginine to synthesize glutamate, glutamine, alanine, aspartate, asparagine, proline, and polyamines. The formation of polypeptides from AA is regulated not only by hormones （e.g., prolactin, insulin and glucocorticoids） and the rate of blood flow across the lactating mammary gland, but also by concentrations of AA, lipids, glucose, vitamins and minerals in the maternal plasma, as well as the activation of the mechanistic （mammalian） target rapamycin signaling by certain AA （e.g., arginine, branched-chain AA, and glutamine）. Knowledge of AA utilization （including metabolism） by mammary epithelial cells will enhance our fundamental understanding of lactation biology and has important implications for improving the efficiency of livestock production worldwide.展开更多
文摘BACKGROUND Bilateral internal mammary arteries(BIMAs)as the most advanced surgical option for coronary artery bypass grafting(CABG)are usually recommended for younger patients without traditional risk factors.This study compares outcomes in propensity score-matched patients aged over 70 years who received BIMAs versus those who received a single internal mammary artery(SIMA).METHODS From 2013 to 2024,8123 patients underwent primary CABG for multivessel coronary artery disease at our institution.BIMA grafting was performed in 1233 patients(15.17%),with in situ BIMA grafting in 290 patients(3.57%).For in situ BIMA group,the right internal mammary artery was used to revascularize the right coronary artery,while the left internal mammary artery was utilized for the left anterior descending artery.BIMA patients aged over 70 years(n=79)were compared with SIMA patients(n=79)using propensity score matching.Primary outcome was all-cause mortality at 30 days and 8 years.Secondary outcomes included length of hospital stay,incidence of postoperative major adverse cardiovascular and cerebrovascular events,sternal wound infection and the need for subsequent percutaneous revascularization.RESULTS There was no difference in immediate postoperative primary and secondary outcomes.Mean follow-up was 8.3±1.0 years with an 8-year freedom from death of 67.08%±1.1%in the BIMA group versus 58.22%±0.9%in the SIMA group(P<0.05).CONCLUSIONS BIMAs as in situ grafts can be successfully used in CABG for patients aged 70 years and older.Consequently,the refined techniques for constructing internal mammary artery grafts used in this study challenge traditionally accepted limitations regarding the use of BIMAs.
基金supported by the National Natural Science Foundation of China(32270837 and 32470849 to C.C.32400661 to M.Z.)the Key Research Project of Hangzhou Institute for Advanced Study(B04006C023001 to C.C.).
文摘Mammary stem cells(MaSCs),endowed with self-renewal and multilineage differentiation capabilities,are crucial for mammary gland development,function,and disease initiation.Recent advances in MaSCs biology research encompass molecular marker identification,regulatory pathway dissection,and microenvironmental crosstalk.This review synthesizes key progress and remaining challenges in MaSC research.Molecular profiling advances have identified key markers recently,such as Procr,DII1,Bcl11b,and PD-L1.Central to their regulatory logic are evolutionarily conserved pathways,including Wnt,Notch,Hedgehog,and Hippo,which exhibit context-dependent thresholds to balance self-renewal and differentiation.Beyond intrinsic signaling,the dynamic interplay between MaSCs and their microenvironment,such as luminalderived Wnt4,macrophage-mediated TNF-α signaling,and adrenergic inputs from sympathetic nerves,spatially orchestrates stem cell behavior.In addition,this review also discusses the roles of breast cancer stem cells(BCSCs) in tumorigenesis and therapeutic resistance,focusing on the molecular mechanisms underlying MaSC transformation into BCSCs.Despite progress,challenges remain:human MaSCs functional assays lack standardization,pathway inhibitors risk off-target effects,and delivery systems lack precision.Emerging tools like spatial multi-omics,organoids,and biomimetic scaffolds address these gaps.By integrating MaSCs and BCSCs biology,this review links mechanisms to breast cancer and outlines strategies to target malignancy to accelerate clinical translation.
基金supported by National Nature Science Foundation of China(32102552 and 32172741).
文摘Background Lactate is a classical byproduct of glucose metabolism,and the main lactate production pathway depends on glycolysis.Lactate stabilized HIF1αby inhibiting PHD activity,leading to hypoxic stress response and exacerbating glycolysis in multiple tissues.However,the redox induction mechanism of lactate in mammary gland has not been understood yet.Herein,we describe a lactate-responsive HIF1α/circadian control mechanism in oxidative stress in the mammary glands of dairy cows.Results The in vivo study showed that dairy cows with high lactate concentrations are associated with reduced milk yield and more ROS accumulation in mammary gland.Western blot results in MAC-T cells showed positive correlation between lactate concentrations,expression of HIF1αand oxidative stress indicators,but not circadian core components.To test how lactate-mediated HIF1αdysfunction leads to cell protection process,we investigated altered expression of circadian core related genes following HIF1αstabilization.We found that stabilized HIF1αby lactate inhibited stimulated expression of circadian core components due to the similarity of HRE and E-box transcription elements.Furthermore,we found that lactate treatment strengthened the binding of HIF1αwith BMAL1,HMOX1 and FOXO3 in MAC-T cells.Moreover,HIF1αknockdown altered expression of circadian rhythm related genes and reduced oxidative stress state.Conclusion In summary,our study highlights the central role of competitive transcriptional element occupancy in lactate-mediated oxidative stress of mammary gland,which is caused by HIF1αstabilization and circadian rhythm dysfunction.Our findings introduce a novel nutritional strategy with potential applications in dairy farming for optimizing milk production and maintaining mammary gland health.
基金Supported by the National Natural Science Foundation of China(31601141)。
文摘A lactating dairy cow mammary epithelial cell(DCMEC)model is useful for studying milk synthesis and lactation in the dairy cow mammary gland.However,the cells can only maintain their original characteristics for a limited period in vitro.Thus,the proliferative capacity and lactation pattern of subcultured DCMECs need to be characterized.In the present study,subcultured DCMECs appeared to proliferate without changes in morphology or growth pattern up to the 12th passage.Subculturing had no obvious effect on the lactation capacity of the subcultured DCMEC up to the 10th passage in vitro.These results indicated that the DCMEC line could be subpassaged up to 10 times and still maintain its original milk synthesis characteristics.Moreover,DCMECs were frozen using different methods,and the method of placing the vials in the foam box was determined after cryopreservation with the best adherence of 91.2%.This method was recommended for long-term cryopreservation for DCMECs.
基金supported by the National Natural Science Foundation of China(32125038)the National Key R&B Program of China(2023YFD1801100)China Agriculture Research System(CARS-36).
文摘Background In perinatal dairy cows,ketosis is a prevalent metabolic disorder that lowers milk output and per-formance.Mitochondrial dysfunction and chronic inflammation in mammary tissue are linked to elevated blood ketone levels,particularlyβ-hydroxybutyrate(BHB).Recent research has linked cytosolic mitochondrial DNA(mtDNA)with chronic aseptic inflammation by activating the cGAS-STING pathway during metabolic disorders,while autophagy activation effectively reverses this process.However,whether it is involved in mammary gland damage during ketosis is poorly understood.Therefore,this study aimed to explore the underlying mechanisms of mtDNA-induced inflammation under BHB stress and evaluate the potential therapeutic strategy of autophagy activation in mitigating this damage.Results Our study found an increased cytoplasmic mtDNA abundance in mammary gland tissues of dairy cows with ketosis and bovine mammary epithelial cell line(MAC-T)subjected to BHB stress.Further investigations revealed the activation of the cGAS-STING pathway and inflammatory response,indicated by elevated levels of cGAS and STING,along with increased phosphorylation levels of TBK1,P65,and IκB,and higher transcript levels of pro-inflammatory factors(IL-1B,IL-6,and TNF-α)in both in vivo and in vitro experiments.Notably,STING inhibition via si-STING transfection reversed BHB-induced inflammation.Additionally,autophagy activation appeared to protect against BHB stress by facilitating the removal of cytoplasmic mtDNA and preventing cGAS-STING pathway-mediated inflammation.Conclusions The findings illustrate that elevated BHB levels lead to the release of cytoplasmic mtDNA,which in turn activates the cGAS-STING pathway and triggers an inflammatory response in the mammary glands during hyper-ketonemia.Conversely,autophagy activation has been shown to alleviate this process by promoting cytoplasmic mtDNA degradation.
基金supported by the National Natural Science Foundation of China(32273082 and U21A20262).
文摘Background Ferroptosis is characterized by increased production of reactive oxygen species(ROS)and membrane lipid peroxidation that can exacerbate inflammatory damage.Extracellular vesicles(EVs)isolated from bovine milk have many biological functions,including antioxidant properties.However,the role of EVs on Klebsiella pneumoniaeinduced ferroptosis and oxidative stress in bovine mammary epithelial cells(bMECs)and murine mammary tissue is unclear.In this study,EVs were isolated from bovine colostrum,mature milk and clinical mastitis milk(defined as C-EVs,M-EVs and CM-EVs,respectively)and assessed by transmission electron microscopy,Western blot and transcriptome sequencing.Effects of EVs on K.pneumoniae-induced ferroptosis and oxidative stress in bMECs were evaluated with immunofluorescence and Western blot.Results In bMECs,infection with K.pneumoniae induced oxidative stress,decreasing protein expression of Nrf2,Keap1 and HO-1 plus SOD activity,and increasing ROS concentrations.However,protein expression of GPX4,ACSL4 and S100A4 in bMECs,all factors that regulate ferroptosis,was downregulated by K.pneumoniae.Furthermore,this bacterium compromised tight junctions in murine mammary tissue,with low expression of ZO-1 and Occludin,whereas protein expression of Nrf2 and GPX4 was also decreased in mammary tissue.Adding C-EVs,M-EVs or CMEVs reduced oxidative stress and ferroptosis in K.pneumoniae-infected bMECs in vitro and murine mammary tissues in vivo.Conclusion In conclusion,all 3 sources of milk-derived EVs alleviated oxidative stress and ferroptosis in K.pneumoniae-infected bMECs and mammary tissues.
基金Innovation 2030-Biological Breeding-Major Projects(2022ZD04014)Key R&D Program of Zhejiang Province(2022C04017).
文摘Background Although several cell culture systems have been developed to investigate the function of the mam-mary gland in dairy livestock,they have potential limitations,such as the loss of alveolar structure or genetic and phe-notypic differences from their native counterparts.Overcoming these challenges is crucial for lactation research.Development of protocols to establish lactating organoid of livestock represents a promising goal for the future.In this study,we developed a protocol to establish a culture system for mammary organoids in dairy goats to model the mammary gland development and lactation process.Results The organoids cultured within an extracellular matrix gel maintained a bilayer structure that closely resem-bled the native architecture of mammary tissue.The expansion of mammary organoids was significantly promoted by growth factors containing epidermal growth factor and fibroblast growth factor 2 whereas the proliferative index of the organoids was significantly inhibited by the treatment with WNT inhibitors.Upon stimulation with a lactogenic medium containing prolactin,the mammary organoids exhibited efficient lactation,characterized by the accumu-lation of lipid droplets in the lumen space.The lactation could be sustained for more than 3 weeks.Importantly,the expression patterns of genes related to fatty acid synthesis and milk proteins in lactating organoids closely mirrored those observed in mammary tissues.These observations were confirmed by data from proteomic analysis that the bulk of milk proteins was produced in the lactating organoids.Conclusion This study is the first to establish a mammary organoid culture system modeling the mammary gland development and lactation process in ruminants.The efficient induction of lactation in ruminant mammary organoids holds promises for advancing the field of cell-based milk bio-manufacture in the food industry.
文摘BACKGROUND Internal mammary(IM)lymphadenopathies in breast cancer indicate a worse prognosis than axillary metastases,yet they are rarely assessed.Accurate staging is essential for treatment planning.Robotic biopsy offers a promising alternative to video-assisted thoracic surgery for precise histological sampling.This article outlines a systematic robot-assisted dissection approach to enhance staging accuracy and optimize breast cancer management.CASE SUMMARY At our institution,robotic lymphadenectomy of the IM chain was performed in 5 patients between July 2020 and December 2024.Patients were positioned in a 30°semi-supine position with a roll under the shoulder to elevate the chest.The camera port was inserted in the fifth intercostal space along the mid-axillary line,allowing a 0°,12 mm robotic camera to inspect the chest cavity;CO_(2) insufflation(8 L/minute,8-10 mmHg)facilitated lung collapse and pneumo-mediastinum formation for improved dissection.Under direct vision,two additional operative ports were placed:One in the third intercostal space(anterior axillary line)and another in the fifth intercostal space(3-4 cm lateral to the parasternal line).The mean operative time was 118 minutes,with a median hospital stay of two days.No major complications occurred.Histology confirmed breast carcinoma metas tases in three patients,while two had benign disease.CONCLUSION Robotic biopsy of IM lymph nodes is safe,feasible,and provides key information on breast cancer management,with very rare contraindications.
基金Bayan Nur Science and Technology Plan Project(Project No.:K202148)。
文摘Objective:This study primarily focuses on analyzing the inductive effects of emotional disturbances on the malignant transformation process of mammary gland epithelial cells.Methods:A total of 42 patients with malignant transformation of mammary gland epithelial cells(breast cancer,observation group)and 42 patients without malignant transformation of mammary gland epithelial cells(non-breast tumors,control group)were selected as research subjects.The earliest consultation time was January 2022,and the latest was January 2024.The extent of psychological stress impact on these patients was compared.Results:Compared with the control group,the observation group experienced a higher frequency and intensity(LEU value)of adverse life events,with P<0.05.The intensity of adverse life events in the observation group,except for mild events,was significantly higher than that in the control group(P<0.05).In terms of the content distribution of adverse life events,the proportion of marital and family problems in the observation group was significantly higher than that in the control group(P<0.05).The negative coping score and positive coping score in the observation group were significantly different from those in the control group(P<0.05).Regarding social support,the objective support score in the observation group was higher than that in the control group(P<0.05).Conclusion:During the malignant transformation process of mammary gland epithelial cells,long-term emotional disturbances have a significant impact,indicating a close relationship between psychological stress and the occurrence of breast cancer.
基金Supported by Natural Science Foundation of Inner Mongolia Autono-mous Region (200711020407)China Agricultural University and Inner Mongolia Agricultural University Cooperation Projects~~
文摘[ Objective] To investigate the feasibility of the primary culture of bovine mammary epithelial cells in biochemical incubator. [ Method] In vitro, bovine mammary epithelial cells were isolated and cultured by the tissue explant method in order to investigate the optimal culture conditions. The morphology observation and identification of the cultured cells were performed by inverted microscope observation, Giemsa staining and cytokeratin immunohistochemistry. [ Result] Observed with inverted microscope, most of the bovine mammary epithelial cells were polygonal and displayed typical slabstone-like appearance. As it can be seen from cell staining results, the cell body was big and the nucleus was stained dark blue and was round or oval in shape, with clearly visible nucleoli, generally 2 -4 nucleoli. The tissue-specific expression of cytokeratin 14 and cytokeratin 18 genes in mammary epithelial cells was identified by cytokeratin immunohistochemistry. [ Conclusion] Primary bovine mammary epithelial cells were successfully cultured in biochemical incubator.
基金This work was supported by the Doctor Study Project of Heilongjiang Education in 2005.
文摘MicroRNAs （miRNAs） are endogenous -22 nucleofide-long noncoding RNAs. In this study, to investigate miRNA expression profiles and their functions in mammary gland development, we have used microarray as well as qRT-PCR, to analyze the miRNA expression changes along the murine mammary cycle during pregnancy, particularly on transition from pregnancy to lactation. It shows that every developmental stage of the mammary gland has its own mjRNA expression pattern. Compared with virgin and involution, some miRNAs such as miR-138 and miR-431 are downregulated, whereas, some miRNAs such as miR-133 and miR-133a-133b are upregulated during pregnancy and lactation. These results indicate that miRNAs are functionally involved in mammary gland development.
文摘Objective To evaluate the outcome of off-pump coronary artery bypass grafting(OPCABG)using a bilateral internal mammary artery(BIMA)Y configuration graft to achieve total arterial myocardial revascularization.Methods From October 2002 to December 2008,208 patients(196 males and 12 females)underwent OPCABG using a BIMA Y configuration graft.The average age of the patients was 56.5±11.3 years,with an age range of 33-78 years.A total of 167(80.2%)cases had triple-vessel disease.Left main stem disease was found in 33(15.9%)cases,and double-vessel disease was found in 8(3.9%)cases.The semi-skeletonization technique was used to harvest the two internal mammary arteries(IMAs),and then the free right internal mammary artery was connected end-to-side to the left internal mammary artery(LIMA)in situ to complete the Y configuration graft.Off-pump and sequential anastomosis methods were used to perform coronary artery bypass surgery in all patients.Graft patency was assessed intm-operatively with the HT311 transit time flowmeter.Results A total of 728 distal anastomoses were performed in 208 patients,with the average being 3.5±1.3 per person.No one died or experienced recurrent angina within 30 days after the operation.Conclusions OPCABG using the BIMA Y graft was safe and effective to achieve total arterial revascularization.This method avoids surgical operation on the ascending aorta and other incisions.
文摘Objective： To study the effect of Runing II （a Chinese herbal preparation for mammary cancer） on the growth and metastasis of transplanted tumor of mammary cancer MA-891-bearing TA2 mice and its mechanism. Methods： The model of mammary cancer MA-891 cell strain transplanted tumor of TA2 mice with lung metastasis were developed to observe the effect of Runing II on the growth and metastasis of the transplanted tumor. The immunohistochemical method and image analysis were adopted to detect the levels of vascular endothelial growth factor （VEGF）, vascular endothelial growth factor receptor （VEGFR）, and micro-vessel count （MVC） and micro-vessel area （MVA）. Results： In the Runing II group, the tumor weight inhibition rate and the lung metastasis inhibition rate were 37.3% and 65.4% respectively, the tumor growth and lung metastasis were obviously inhibited; And the levels of VEGF and VEGFR, MVC and MVA were significantly decreased as compared with those in the tumor-bearing control group （P〈0.05）. Conclusion： The Chinese herbal preparation Running II can inhibit the metastasis of tumor through inhibiting the angiogenesis, and the mechanism is possibly related with down-regulation of VEGF and VEGFR expression.
基金Supported by National Natural Science Foundation(30771550)~~
文摘[Objective] The aim of this study was to optimize conditions of exogenous gene mediated by liposome to transfect yak mammary epithelial cells in Vitro.[Method] Yak mammary epithelial cells were isolated and cultivated in Vitro by the methods of collagenase digestion and tissue adhesion.The expression of cytokeratin in yak mammary epithelial cell was detected by immunocytochemistry technique.With green fluorescence protein as the report gene,yak mammary epithelial cells were transfected with exogenous gene m...
文摘The vectors carrying the genes coding for the proteins of interest are of unpredictable efficiency in transgenic animals. The expression vector of mammary gland (pINGG) containing GCSF genomic DNA was injected into mouse mammary gland, and expression was detected in the milk of mice. The result showed that mammary gland injection method could provide a convenient transient system to confirm vector validity.
基金funded by grants from the National Nature Science Foundation(Grant Number 31930101U23A20231)。
文摘Background Environmental heat stress(HS)can have detrimental effects on milk production by compromising the mammary function.Mammary plasma flow(MPF)plays a crucial role in nutrient supply and uptake in the mam-mary gland.In this experiment,we investigated the physiological and metabolic changes in high-yielding cows exposed to different degrees of HS:no HS with thermal-humidity index(THI)below 68(No-HS),mild HS(Mild-HS,68≤THI≤79),and moderate HS(Mod-HS,79<THI≤88)in their natural environment.Our study focused on the changes in blood oxygen supply and mammary glucose uptake and utilization.Results Compared with No-HS,the MPF of dairy cows was greater(P<0.01)under Mild-HS,but was lower(P<0.01)in cows under Mod-HS.Oxygen supply and consumption exhibited similar changes to the MPF under different HS,with no difference in ratio of oxygen consumption to supply(P=0.46).The mammary arterio-vein differences in glucose concentration were lower(P<0.05)under Mild-and Mod-HS than under no HS.Glucose supply and flow were significantly increased(P<0.01)under Mild-HS but significantly decreased(P<0.01)under Mod-HS compared to No-HS.Glucose uptake(P<0.01)and clearance rates(P<0.01)were significantly reduced under Mod-HS compared to those under No-HS and Mild-HS.Under Mild-HS,there was a significant decrease(P<0.01)in the ratio of lac-tose yield to mammary glucose supply compared to that under No-HS and Mod-HS,with no difference(P=0.53)in the ratio of lactose yield to uptaken glucose among different HS situations.Conclusions Degrees of HS exert different influences on mammary metabolism,mainly by altering MPF in dairy cows.The output from this study may help us to develop strategies to mitigate the impact of different degrees of HS on milk production.
基金Supported by Doctoral Start Fund of Henan University of Science and Technology.
文摘[Objective]The aim of this study was to explore the technical system of induced expression in vitro of goat mammary gland epithelial cell,and evaluate expression efficiency of mammary gland specific vector and foreign protein at the cell level.[Method]Goat mammary gland epithelial cell transfected by human lactoferrin gene was inducted by culturing in DMEM/F12 medium supplemented with 5 mg/L insulin,5 mg/L prolactin and 1 mg/L hydrocortisone.Supernatant was collected per 6 hours and concentrated.Expression situation of foreign protein were detected by SDS-PAGE and Western blotting.[Result]There was target protein expression in the induced culture medium,which molecular weight was about 42 kD.[Conclusion]The method used in this study can induce goat mammary gland epithelial cell to express foreign gene,it lays a foundation for researching heterologous expression of foreign gene and producing mammary gland bioreactor.
文摘We present a case of a 71-year-old woman suffering from mammary Paget,s disease and having a 10-years history of an irregular, widespread erosion accompanied by itching and burning on the skin of her left chest, extending to the breast. The erosion had steadily enlarged and had become increasingly tender. The nipple and areola of the left breast disappeared and could not be recognized. No abnormality of the right nipple, areola, and covering skin and no supernumerary nipple were seen. Mammography and ultrasonography could not be performed because of severe pain and erosive wetness. Histopathology of a surgical biopsy specimen showed epidermal infiltration by large, round, clear atypical cells scattered individually or in small clusters and distributed horizontally throughout the epidermis. The cytoplasm of these large cells was pale and vacuolated and was equivalent to that in nipple cells in Paget,s disease, and a diagnosis of mammary Paget,s disease was made. We performed total mastectomy of the left breast with wide excision of the Paget lesion of the left chest and axillary lymph node sampling. Histological examination of the specimen showed typical distribution of Paget,s cells;however no ductal carcinoma in situ was found in the mammary ducts and invasive growth was not recognized beyond the basal membrane of the lesion. From this evidences, we established a diagnosis of large, irregulaly shaped unusual mammary Paget,s disease, not of breast cancer origin, covering the left breast, areola, and nipple.
基金The Comprehensive Center for Drug Discovery and Development,Peking University(Grant No.2009ZX09301-010)
文摘The effects of Aspirin on tumor chemoprevention and inhibition have been debated and researched in recent years and its effects on colorectal cancer are quite clear.For breast cancer,however,conclusions are inconsistent and the anti-tumor mechanism of Aspirin is not clear yet.In our study,we used DMBA-induced mammary gland carcinogenesis model to assess the chemoprevention effect of Aspirin on mammary precancerous lesions.After SD rats were treated with Aspirin,the total numbers of precancerous lesion in experimental groups were 16（40 mg/kg Aspirin） and 13（20 mg/kg Aspirin）,while the number in control group was 35.In vitro,we found that Aspirin inhibited cell proliferation in human breast cancer cell line MCF-7 by SRB assay with no apparent cytotoxity under the doses of 10,8,6,4 and 2 mM,the inhibitory rates were 86.96%,54.56%,24.83%,14.24% and 4.49%,respectively.In mechanism research,the results of gene microarray assay demonstrated that 4 mM and 2 mM Aspirin were effective in changing gene expression profile in MCF-7 cells.The expression of cell cycle regulator,cyclin A,was significantly down-regulated under the same doses,while the down-regulation of Cdk2 was only remarkable at 4 mM.Our findings reveal that Aspirin is effective in tumor inhibition during initial phase in rats.In MCF-7 cells,Aspirin reduces cell proliferation without significant cytotoxity and its possible mechanism involves altering tumor-related gene expression and regulating cell cycle process.
基金supported by Texas A&M Agri Life Research (H-8200)The Agriculture and Food Research Initiative Competitive Grant from the Animal Growth & Nutrient Utilization Program of the USDA National Institute of Food and Agriculture (2014-67015-21770)+4 种基金National Basic Research Program of China (2012CB126305)National Natural Science Foundation of China (31572412 and 31272450)the 111 Project (B16044)Natural Science Foundation of Hubei Province (2013CFA097 and 2013CFB325)Hubei Hundred Talent program
文摘Milk is synthesized by mammary epithelial cells of lactating mammals. The synthetic capacity of the mammary gland depends largely on the number and efficiency of functional mammary epithelial cells. Structural development of the mammary gland occurs during fetal growth, prepubertal and post-pubertal periods, pregnancy, and lactation under the control of various hormones （particularly estrogen, growth hormone, insulin-like growth factor-I, progesterone, placental lactogen, and prolactin） in a species- and stage-dependent manner. Milk is essential for the growth, development, and health of neonates. Amino acids （AA）, present in both free and peptide-bound forms, are the most abundant organic nutrients in the milk of farm animals. Uptake of AA from the arterial blood of the lactating dam is the ultimate source of proteins （primarily 13-casein and a-lactalbumin） and bioactive nitrogenous metabolites in milk. Results of recent studies indicate extensive catabolism of branched-chain AA （leucine, isoleucine and valine） and arginine to synthesize glutamate, glutamine, alanine, aspartate, asparagine, proline, and polyamines. The formation of polypeptides from AA is regulated not only by hormones （e.g., prolactin, insulin and glucocorticoids） and the rate of blood flow across the lactating mammary gland, but also by concentrations of AA, lipids, glucose, vitamins and minerals in the maternal plasma, as well as the activation of the mechanistic （mammalian） target rapamycin signaling by certain AA （e.g., arginine, branched-chain AA, and glutamine）. Knowledge of AA utilization （including metabolism） by mammary epithelial cells will enhance our fundamental understanding of lactation biology and has important implications for improving the efficiency of livestock production worldwide.
