Polysaccharide of Asparagus cochinchinensis (Lour.) Merr regulates macrophage immune response and epigenetic memory through TLR4-JNK/p38/ERK signaling pathway and histone modification.

BACKGROUND: Innate immune memory of macrophages is closely linked to histone modifications. While various studies have demonstrated that the polysaccharide of Asparagus cochinchinensis (Lour.) Merr (ACMP), extracted through alcohol-alkali extraction, enhances macrophages' non-specific immune function; no literature currently addresses whether ACMP's regulatory effect is related to innate immune memory and histone modification. PURPOSE: This study aims to investigate if ACMP induces innate immune memory emergence in macrophages via pattern recognition receptor (PRR). STUDY DESIGN: After co-incubating different doses of ACMP with RAW264.7 cells and BMDM cells, we observed changes in signaling pathways related to PRR and assessed the presence of innate immune memory phenomenon in the cells. METHODS: We observed the morphological characteristics of the ACMP using a scanning electron microscope, infrared spectrum, and HPLC pre-column derivatization method. We used q-PCR, Western blot, RNA-seq, and CUT&Tag-seq methods to examine ACMP's regulation of macrophage immune response and innate immune memory and explored its specific mechanism. RESULTS: ACMP, primarily composed of Man, GlcN, Rha, Fuc, GalA, Xyl, Glc, Gal, Ara, and, exhibited a molar ratio of each monosaccharide (1.41: 0.35: 0.49: 0.18: 1.00: 97.12: 0.36: 3.58: 1.14). ACMP regulated immunological function in macrophages through the TLR4-MAPK-JNK/p38/ERK pathway. ACMP induced elevated levels of chromosomal H3K4me1, enhancing TNF-α, IL-1ß, and other genes' responsiveness, allowing macrophages to develop innate immune memory to ACMP stimulation. CONCLUSION: This study first time demonstrates that ACMP regulates immunological function through the TLR4-MAPK-JNK/ERK/p38 signaling pathway, distinct from prior reports. ACMP induces innate immune memory in macrophages in response to its immune stimulation by promoting increased H3K4me1 on chromosomes. This mechanism may be crucial in how plant polysaccharides regulate macrophages and the body's immune function.

Ganoderma lucidum spore oil synergistically enhances the function of cyclophosphamide in the prevention of breast cancer metastasis.

BACKGROUND: Ganoderma lucidum ( G . lucidum ) is a traditional Chinese herbal medicine that has shown potential as an alternative adjuvant therapy for cancer patients. However, the mechanisms and adjuvant therapeutic effects of G . lucidum in cancer treatment remain unclear. METHODS: In this work, G . lucidum spore oil (GanoOil), a newly developed oily G . lucidum spore extract was used to investigate the mechanisms and adjuvant therapeutic effects of GanoOil in conjunction with the chemotherapeutic drug cyclophosphamide (CTX) for preventing breast cancer metastasis. RESULTS: In the model of lung metastasis, orally administered GanoOil increased the population of CD8 + T cells and interleukin (IL)-6 cytokine levels in mouse blood, whereas also enhancing the activity of natural killer cells in the spleen. Furthermore, the combination of GanoOil and CTX effectively suppressed the lung metastasis of circulating breast cancer cells, alleviated CTX-induced weight loss, and reduced the ratio of lung and spleen weight to body weight in mice. Moreover, high concentrations of GanoOil exhibited no significant toxicity or side effects in both in vitro and in vivo experiments. CONCLUSION: In conclusion, GanoOil is a safe drug that can enhance immune activity in mice to achieve therapeutic effects on cancer, and can also synergistically inhibit tumor metastasis with CTX.

[Progress in antitumor activity of diterpenoid alkaloids in plants of Aconitum].

Small-molecule compounds with rich sources have diverse structures and activities. The active ingredients in traditional Chinese medicine(TCM) provide new sources for the discovery of new antitumor drugs. Aconitum plants as Chinese medicinal plants have the effects of dispelling wind, removing dampness, warming meridian, and relieving pain. They are mainly used to treat inflammation, pain, rheumatism, and tumors, improve heart function, and dilate blood vessels in clinical practice. Diterpenoid alkaloids are the main active components of Aconitum plants, including C20-, C19-, C18-diterpenoid alkaloids and bis-diterpenoid alkaloids. Stu-dies have demonstrated that diterpenoid alkaloids can effectively treat lung cancer, liver cancer, breast cancer, colon cancer and other cancers. Diterpenoid alkaloids are considered as the most promising natural compounds against cancers. In this review, we summarized the chemical structures and antitumor activities of C20-, C19-, C18-diterpenoid alkaloids and bis-diterpenoid alkaloids extracted from plants of Aconitum, aiming to provide reference for further development of diterpenoid alkaloids from Aconitum as antitumor drugs.

Structured lipids produced from palm-olein oil by interesterification: A controllable lipase-catalyzed approach in a solvent-free system.

Palm olein (POL) was modified by enzymatic interesterification with different degrees of acyl migration in a solvent-free packed bed reactor. The fatty acid and acylglycerol composition, isomer content, thermodynamic behavior, and relationship between crystal polymorphism, solid fat content (SFC), crystal microstructure, and texture before and after modification were studied. We found that the increase in sn-2 saturation interesterification was not only due to the generated tripalmitin (PPP) but also caused by acyl migration, and the SFC profiles were changed accordingly. The emergence of high melting point acylglycerols was an important factor accelerating the crystallization rate, further shortening the crystallization induction time, leading to the formation of large crystal spherulites, thereby reducing the hardness. The transformation from the ß' to the ß form occurred during post-hardening during storage. The isomer content also affected the physicochemical properties of the modified POL.

Sophora subprostrate polysaccharide regulates histone acetylation to inhibit inflammation in PCV2-infected murine splenic lymphocytes in vitro and in vivo.

Porcine circovirus type 2 (PCV2) has caused large economic losses in the swine industry worldwide; therefore, research on relevant therapeutic medicines is still urgently needed. To define the relationship between histone acetylation and inflammation induced by PCV2, we investigated whether traditional Chinese medicinal polysaccharides could alleviate viral infection by regulating histone acetylation. In this study, Sophora subprostrate polysaccharide (SSP)-treated PCV2-infected murine splenic lymphocytes in vitro and murine spleen in vivo were used to explore the regulatory effects of SSP on inflammation and histone acetylation caused by PCV2. SSP at different concentrations significantly reduced the secretion levels of the proinflammatory cytokines TNF-α and IL-6, the activity of COX-2, the mRNA expression levels of TNF-α, IL-6, iNOS and COX-2 and the protein expression levels of iNOS and COX-2 but promoted the secretion and mRNA expression levels of IL-10. Furthermore, the different concentrations of SSP significantly regulated the activity of histone acetylase (HAT) and the mRNA expression of HAT1, increased the activity of histone deacetylase (HDAC) and the mRNA expression of HDAC1 and reduced the protein expression levels of Ac-H3 and Ac-H4. Overall, SSP inhibited inflammation in PCV2-infected murine splenic lymphocytes by regulating histone acetylation in vitro and in vivo, thus playing an important role in PCV2 infection.

Enzymatic Interesterification of Palm Stearin and Palm Olein Blend Catalyzed by sn-1,3-Specific Lipase: Interesterification Degree, Acyl Migration, and Physical Properties.

Acyl migration of fatty acid at sn-2 is often observed alongside enzymatic interesterification (EIE), causing the loss of lipase selectivity toward the acyl group at sn-1,3. In this study, an oil blend consisting of palm stearin (PST) and palm olein (POL) was interesterified via a chemical interesterification (CIE) and enzymatic method using a packed bed reactor. Characterization in terms of the triacylglycerol (TAG) compositions, sn-2 fatty acid distributions, and solid fat content profiles was performed. In comparison to that of CIE fats, EIE fats showed different modification effects on the solid fat content. Under similar reaction conditions, different interesterification degrees (IDs) were obtained according to the various blend ratios. Using the same mass ratio of substrates (POL/PST of 9:1), the EIE reaction time and temperature affected the ID and the change in the fatty acyl group at the sn-2 position. Under the reaction time of 46 min, an ID of 94.41% was acquired, while at 80 °C, the degree of acyl migration at sn-2 was 92.87%. EIE with high acyl migration exhibited a lower crystallization rate than that of EIE with low acyl migration. However, the effect of acyl migration on crystal polymorphism and oxidative stability was insignificant. Outcomes from this study are meaningful for the establishment of a theoretical basis for a controlled positional-specific EIE that is catalyzed by sn-1,3-specific lipase.

Modified Jian-pi-yang-zheng decoction inhibits gastric cancer progression via the macrophage immune checkpoint PI3Kγ.

Jian-pi-yang-zheng Decoction (JPYZ) is a traditional Chinese medicine that is used for the treatment of advanced gastric cancer, and it shows good efficacy in patients. A previous study indicated that JPYZ inhibited the progression of gastric cancer via the regulation of tumor-associated macrophages (TAMs), but the underlying molecular target of JPYZ regulation of TAMs has not been determined. The present study used modified-JPYZ (mJPYZ) to extend our investigation of gastric cancer. Our results showed that mJPYZ inhibited gastric cancer progression in vivo and in vitro. We found that mJPYZ decreased the activity of PI3-kinase γ (PI3Kγ) in TAMs, reduced the anti-inflammatory factor IL-10 and increased the expression of pro-inflammatory cytokines, such as TNF-α and IL-1ß, which ultimately promoted the conversion of TAMs from M2 to M1. Our findings also indicated that mJPYZ inhibited the growth and metastasis of gastric cancer by alleviating the unfavorable differentiation of TAMs via the PI3Kγ signaling cascades. In conclusion, the present findings indicated that mJPYZ inhibited gastric cancer cell EMT via PI3Kγ-dependent TAM reprogramming, which eventually suppressed gastric cancer growth and metastasis. Our study provides an underlying mechanism of a Chinese medicine in the treatment of gastric cancer via PI3Kγ in macrophages.

Characterization of enzymatically interesterified palm oil-based fats and its potential application as cocoa butter substitute.

Cocoa butter substitutes (CBS) used for chocolate preparation was produced using a mixture of palm kernel oil (PKO) and enzymatically interesterified fats. The interesterified fats consisted of palm olein (POL), fully hydrogenated palm oil (FHPO) and PKO that were catalyzed using Lipozyme TL IM at 65 °C in a solvent-free packed bed reactor. An interesterification degree of 97.10% was obtained using feed flow rate of 70 mL/min and the interesterified fats showed steep solid fat content (SFC) curve characteristics with low SFC at high temperature. In the binary system, PKO and the interesterified fats showed good compatibility at 5-10 °C, while eutectic effects were observed at 15-35 °C. CBS produced from PKO and the interesterified fats in a mass ratio of 4:6 (CBS-46) and 3:7 (CBS-37) had crystals formed prominently in the ß' form. Without the need of a tempering process, chocolate made using CBS-46 as the base oil exhibited the desired properties in terms of hardness and fracturability.

The Effects of Astragalus Polysaccharide on Bone Marrow-Derived Mesenchymal Stem Cell Proliferation and Morphology Induced by A549 Lung Cancer Cells.

BACKGROUND The tumor microenvironment in lung cancer plays an important role in tumor progression and metastasis. Bone marrow-derived mesenchymal stem cells (MSCs) co-cultured with A549 lung cancer cells show changes in morphology, increase cell proliferation, and cell migration. This study aimed to investigate the effects of Astragalus polysaccharide (APS), a traditional Chinese herbal medicine, on the changes induced in bone marrow-derived MSCs by A549 lung cancer cells in vitro. MATERIAL AND METHODS Bone marrow-derived MSCs were co-cultured with A549 cells (Co-BMSCs). Co-cultured bone marrow-derived MSCs and A549 cells treated with 50 µg/ml of APS (Co-BMSCs + APS) were compared with untreated Co-BMSCs. Cell proliferation was measured using the cell counting kit-8 (CCK-8) assay. Flow cytometry evaluated the cell cycle. Microarray assays for mRNA expression and Western blot for protein expression were used. RESULTS Compared with untreated Co-BMSCs, APS treatment of Co-BMSCs improved cell morphology, reduced cell proliferation, and inhibited cell cycle arrest. The mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-kappaB) pathway, TP53, caspase-3, acetylated H4K5, acetylated H4K8, and acetylated H3K9 were involved in the regulatory process. CONCLUSIONS APS treatment reduced cell proliferation and morphological changes in bone marrow-derived MSCs that were co-cultured with A549 lung cancer cells in vitro.

Interesterification of rice bran wax and palm olein catalyzed by lipase: Crystallization behaviours and characterization.

Rice bran wax (RBW) is a traditional plant based natural wax and an increasingly popular component in textiles, fruit coatings and cosmetics. Properties of RBW can be modified by acyglycerols, and the resulting products can possess features with great potential in different applications. In this study, RBW was interesterified with palm olein (POL) catalyzed by Lipozyme TL IM, and the effects of RBW on the crystallization rate, solid fat content (SFC) and thermodynamic properties were investigated. The crystallization rates of RBW-based enzymatically interesterified (EIE) products were significantly higher than both the starting mixture and fully hydrogenated rapeseed oil (FHRSO). The EIE RBW-based samples were predominantly crystallized in ß' form, and presented a much smoother SFC profile as compared to physically blended raw materials. The SFC values were significantly decreased, conversely increased, and remained constant, and at 10 °C, 20-30 °C, and 35-40 °C as the wax ester and acylglycerols compositions changes. Overall, RBW-based samples after EIE showed an increased hardness and good surface properties, which make it a potential plastic fats substitute.

The Evaluation of Animal Models in the Development of Anticancer Agents: From Preclinical to Clinical Tests.

BACKGROUND: One of the main reasons for most of the anticancer drugs to fail in the late preclinical testing and early clinical trials is the differences in drug effects observed from animals and patients, and the challenge has been to find a balance to reduce the inherent differences from species. OBJECTIVE: Predicting safe starting doses and dosing schedules for human clinical trials is the main purpose of toxicological studies of anticancer drugs. METHODS: Relevant information and data were assimilated from manuscripts, congress publications, and online sources. RESULTS: We systematically overview the cons and pros of animal models and briefed the ways to determine human clinical starting doses derived from animal toxicological studies for anticancer drugs. CONCLUSION: This information helps smart select the suitable predictive model for anti-cancer drugs with the different mechanisms and emphasized the pharmaceutical challenges behind and ahead.

Sorafenib in combination with gemcitabine plus cisplatin chemotherapy in metastatic renal collecting duct carcinoma: A prospective, multicentre, single-arm, phase 2 study.

BACKGROUND: Collecting duct carcinoma (CDC) is a rare type of renal cancer with a poor prognosis. As there are no standard guidelines for the management of metastatic CDC (mCDC), we evaluated the efficacy and safety of combined therapies of sorafenib, gemcitabine, plus cisplatin in patients with mCDC. MATERIALS AND METHODS: A prospective, multicentre, single-arm, open-label, phase 2 trial (ClinicalTrials.gov identifier NCT01762150) that enrolled 26 mCDC patients with no prior systemic chemotherapy. Patients were treated with sorafenib (400 mg orally, twice daily) combined with chemotherapy (gemcitabine 1000 mg/m2, intravenously for 30-60 min on days 1 and 8, plus cisplatin 25 mg/m2, intravenously on days 1-3, repeated every 28 days for 4 cycles), until disease progression, unacceptable toxicity, or study discontinuation for any other reason. The primary end-points were progression-free survival (PFS) and 6-month PFS rate. RESULTS: The 6-month PFS rate was 65%, and the median PFS was 8.8 months (95% confidence interval [CI]: 6.7-10.9) with a median overall survival of about 12.5 months (95% CI: 9.6-15.4). The objective response rate was 30.8%, and the disease control rate was 84.6%. The treatment was generally well tolerated. Major grade 3/4 toxicities included leucopenia (26.9%), thrombocytopenia (23.1%), anaemia (11.5%) and palmar-plantar erythrodysesthesia (7.7%). CONCLUSIONS: Though the combination of sorafenib and chemotherapy demonstrated a similar outcome as that of the previously reported regimens in patients with mCDC, this combination may be a suitable option for patients who have low Eastern Cooperative Oncology Group performance status or less metastatic sites.

A low trans margarine fat analog to beef tallow for healthier formulations: Optimization of enzymatic interesterification using soybean oil and fully hydrogenated palm oil.

The health hazard of tallow and partial hydrogenated oils is well known in margarine productions. For this, food manufactures are urged to develop novel alternatives for healthier margarine formulations. The highest interesterification degree acquired with lipase Lipozyme 435 standing out from other catalysts (solid acid, sodium hydroxide and methoxide) was applied to produce low trans margarine fat analogs to beef tallow (BT) with the blend of soybean oil (SO) and fully hydrogenated palm oil (FHPO) in a mass ratio of 4:3. Reaction parameters like enzyme dosage (4.2 wt%), temperature (95 °C) and time (245 min) were optimized using the Box-Behnken design. Regarding fatty acid profiles, triacylglycerol species, solid fat content, polymorphism, melting and crystallization behaviors, the resulting interesterified oil was characterized in comparison with BT, FHPO and the SO-FHPO blend so as to prove its potential in formulating low trans fat margarines because of desirable physicochemical properties and polymorphs.

Anti-proliferation effects of ethanolic extracts from Sophora moorcroftiana seeds on human hepatocarcinoma HepG2 cell line.

Previous studies have shown that the ethanolic extracts from Sophora moorcroftiana seeds (ee-Sms) have in vitro anticancer properties. The anti-proliferation effects of ee-Sms on HepG2 cells were assessed by MTT assay and cell cycle analysis. Total cell proteins were separated by two-dimensional electrophoresis (2-DE), and protein spots with more than two-fold difference were analysed by MALDI-TOF/TOF-MS. MTT assay showed that the anti-proliferation of ee-Sms demonstrates dose- and time dependently. HepG2 cells were treated with ee-Sms at 1.30 mg/mL for 48 h induced cell cycle arrest in S phase. The differentially-expressed proteins were involved in DNA repair, cell proliferation, cell metabolism and immunoreaction. This study sheds new insights into the molecular mechanisms underlying the anti-proliferation properties of ee-Sms in HepG2 cells.

Protective effect of curcumin on TNBS-induced intestinal inflammation is mediated through the JAK/STAT pathway.

BACKGROUND: Curcumin displays a protective role in rat models of intestinal inflammation. However, the mechanism of how curcumin affects on intestinal inflammation is less known. The purpose of the current study is to explore the signal pathway in which the curcumin protecting rat from intestinal inflammation. METHODS: The intestinal inflammation rat models were made by TNBS treatment. Curcumin was added to their diet 5 days before the TNBS instillation. After that, body weight change, score of macroscopic assessment of disease activity and microscopic scoring were utilized to analyse the severity of the induced inflammation. In addition, the level of pro-inflammatory cytokines and anti-inflammatory were detected to determine the effect of curcumin on intestinal inflammation. The JAK/STAT pathway of pro-inflammation response was also evaluated. Finally, the impact of curcumin on apoptosis in intestinal inflammation was assessed by TUNEL staining. RESULTS: Rats pretreated with curcumin significantly reversed the decrease of body weight and increase of colon weight derived from TNBS-induced colitis. Histological improvement was observed in response to curcumin. In addition, curcumin attenuated TNBS-induced secretion of pro-inflammatory cytokines and M1/M2 ratio, while stimulated the secretion of anti-inflammatory cytokines. The inhibition of pro-inflammation response was mediated by SOCS-1, which could efficiently suppress JAK/STAT pathways. Furthermore, curcumin efficiently suppressed the TNBS-induced apoptosis, and reduced the accumulation of cytochrome C in cytosol. CONCLUSION: The anti-inflammatory effect of curcumin is realized by enhancing SOCS-1 expression and inhibiting JAK/STAT pathways. Curcumin also plays an anti-apoptotic role in TNBS-induced intestinal inflammation. We propose that curcumin may have therapeutic implications for human intestinal inflammation.

Prognostic analysis of Chinese patients with metastasis renal cell cancer receiving sorafenib: results from a multicenter long-term follow-up retrospective study.

The effects of sorafenib for Chinese patients with metastatic renal cell cancer (mRCC) were evaluated to figure out the relationship between clinical variables and prognosis. The data were analyzed retrospectively from six comprehensive cancer centers in Northeast China. All cases were diagnosed as mRCC histopathologically without exception. Patients were taken 400 mg sorafenib orally twice daily until progression of disease or intolerable toxic reaction occurred. Overall survival (OS), progression-free survival (PFS), and the influence of clinical variables on survival were appointed as main outcome measures. Clinical data were analyzed using SPSS statistical software. P<0.05 was considered as statistically significant. A total of 131 patients were available for survival analysis. The median follow-up periods were 16.9 months, and the median OS and PFS were 16.1 months and 10.5 months, respectively. Univariate analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), metastatic sites, and previous therapy were significantly associated with OS, whereas PFS was merely associated with ECOG PS and previous therapy. The multivariate analysis suggested that ECOG PS, metastatic sites, and previous therapy were the independent prognostic factors for OS, and ECOG PS and previous therapy as the independent prognostic factors for PFS. In the subgroup analysis for patients with visceral metastasis, the prognosis of patients with lung metastasis alone was better than those cases with liver metastasis alone or multiple organs metastasis. In our study, sorafenib shows a higher curative activity for patients with mRCC in Northeast China. ECOG PS, metastatic lesions, and previous therapy may be important parameters for OS and PFS prediction. Lung metastases alone may be a more sensitive indicator for sorafenib than other organ metastases.

Dendrimeric anticancer prodrugs for targeted delivery of ursolic acid to folate receptor-expressing cancer cells: synthesis and biological evaluation.

The anticancer efficacy of ursolic acid (UA) was limited by poor water solubility, non-specific tumor distribution, and low bioavailability. To overcome this problem, polyamidoamine (PAMAM) conjugated with UA and folic acid (FA) as novel dendrimeric prodrugs were designed and successfully synthesized by a concise one-pot synthetic approach. Both FA and UA were covalently conjugated to the surface of PAMAM through acid-labile ester bonds and the covalently linked UA could be hydrolysed either in acidic (pH 5.4) or in neutral (pH 7.4) PBS solution. The cellular uptake study indicated that the presence of FA enhanced uptake of the dendrimeric prodrugs in folate receptor (FR) over-expressing Hela cells. The enhanced cellular uptake could be due to the electrostatic absorptive endocytosis and FR-mediated endocytosis. In contrast, for HepG2 cells, a FR-negative cell line, FA conjugation on the surface of the dendrimer showed no effect on the cellular uptake. In MTT assay and cell cycle analysis, FA-modified dendrimeric prodrugs showed significantly enhanced toxicity than non-FA-modified ones in Hela cells. These results suggested that FA-modified dendrimeric UA prodrugs have the potential for targeted delivery of UA into cancer cells to improve its anti-tumor efficacy.

Two new neuroprotective phenolic compounds from Gastrodia elata.

Two new phenolic compounds 4-(4'-hydroxybenzyl) phenyl glucoside (gastrodin B, 1) and 1'-hydroxymethyl-phenyl 4-hydroxy-3-(4″-hydroxybenzyl) benzyl ether (gastrol B, 2) were isolated from the rhizomes of Gastrodia elata. Their structures were elucidated on the basis of spectroscopic data and chemical reaction. All compounds exhibited potent neuroprotective activity against H2O2-induced PC12 cell damage.

[Preventive effect of low-dose carvedilol combined with candesartan on the cardiotoxicity of anthracycline drugs in the adjuvant chemotherapy of breast cancer].

OBJECTIVE: To investigate the effect of low-dose carvedilol combined with candesartan in the prevention of acute and chronic cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer. METHODS: Forty patients were randomly divided into two groups: the experimental group with chemotherapy plus low-dose carvedilol combined with candesartan (20 cases) and control group with chemotherapy alone (20 cases). The same chemotherapy was given to the two groups. All the 40 patients had no contraindication for carvedilol and candesartan. Patients of the experimental group received low-dose carvedilol from 2.5 mg orally twice a day at first cycle to 5 mg twice a day gradually if no side reactions, and candesartan 2.5 mg orally once a day. Electrocardiogram, ultrasonic cardiogram, arrhythmia, troponin and non-hematologic toxicity were recorded and compared after the second, forth and sixth cycle of chemotherapy. Each cycle included 21 days. RESULTS: LVEF was decreased along with the prolongation of chemotherapy in the experimental group and control group. LVEDD and LVESD showed no significant changes in the experimental group, but gradually increased in the control group. After four and six cycles of chemotherapy, LVEF were (57.00 ± 5.13)% and (45.95 ± 3.68)%, respectively, in the control group, significantly lower than that of (67.00 ± 5.13)% and (57.50 ± 2.57)%, respectively, in the experimental group (P < 0.05). After six cycles of chemotherapy, LVEDD and LVESD were (50.00 ± 10.48) mm and (35.01 ± 2.99) mm, respectively, in the control group, significantly higher than those before chemotherapy (P < 0.05) and experimental group (P < 0.001). The rate of ST segment and T wave abnormalities was 80.0% in the control group after six cycles of chemotherapy, significantly higher than that of 25.0% after four cycles of chemotherapy (P = 0.001) and 10.0% after two cycles of chemotherapy (P < 0.001). The reduction of QRS voltage, arrhythmia and abnormal troponin were 55.0%, 45.0% and 45.0%, respectively, in the control group, significantly higher than those in the experimental group (20.0%, P < 0.05), (10.0%, P = 0.010) and (10.0%, P < 0.05), respectively. The rate of abnormal expression of troponin was 45.0% in the control group, significantly higher than the 10.0% in the experimental group (P < 0.05). CONCLUSIONS: The use of low-dose carvedilol combined with candesartan can reduce the acute and chronic cardiotoxicity of anthracycline drugs, and with tolerable toxicities. This may provide a new approach to prevent cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer.