Cardioprotective effect of Chinese herbal medicine for anthracycline-induced cardiotoxicity in cancer patients: A meta-analysis of prospective studies.

BACKGROUND: To assess the benefits and harmful effects of Chinese herbal medicine (CHM) formulations in preventing anthracyclines (ANT)-induced cardiotoxicity. METHOD: The Cochrane Library, Pubmed and EMBASE databases were electronically searched for relevant randomized controlled trials (RCTs) published till December 2021 in English or Chinese-language, in addition to manual searches through the reference lists of the selected papers, and the Chinese Conference Papers Database. Data was extracted by 2 investigators independently. RESULT: Seventeen RCTs reporting 11 different CHMs were included in this meta-analysis. The use of CHM reduced the occurrence of clinical heart failure (RR 0.48, 95% CI 0.39 to 0.60, P < .01) compared to the control group. Data on subclinical heart failure in terms of LVEF values showed that CHM reduced the occurrence of subclinical heart failure (RR 0.47, 95% CI 0.35 to 0.62, P < .01) as well. CONCLUSION: CHM is an effective and safe cardioprotective intervention that can potentially prevent ANT-induced cardiotoxicity. However, due to the insufficient quality of the included trials, our results should be interpreted with cautious.

Relationship between Acute Mastitis and Constitution of Traditional Chinese Medicine in Chinese Breastfeeding Mothers.

OBJECTIVE: The purpose of this study was to explore the relationship between acute mastitis and the constitution of traditional Chinese medicine (TCM) and the potential risk factors of acute mastitis in Chinese breastfeeding mothers. METHOD: A retrospective study on infant feeding practices was conducted in the Breast Surgery Department of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between February 2017 and March 2018. A total of 184 women with acute mastitis and 201 women without mastitis of childbearing age were included in this study. All participants filled a baseline questionnaire on demographic characteristics, previous deliveries, and mastitis history and other possible risk factors; data were collected by face-to-face interview. Logistic regression analysis was conducted to ascertain pertinent risk factors affecting the incidence of acute mastitis. The biased constitution of TCM of participants was identified through questionnaires surveyed with the TCM constitution table (ZYYXH/T157-2009). The relationship between acute mastitis and the constitution of TCM was assessed. RESULTS: The protective factors included regular nipple cleansing and cesarean section. The risk factors were nipple infection, Primipara, improper diet, emotional stimuli, postpartum colostrum overdue for more than 72 h, breastfeeding more than 7 times each day, and late primiparity age. Forty-five percent of acute mastitis occurred within 8 weeks after postpartum, and the most common biased constitution of TCM at this period was Qi-Deficiency Constitution (QDC) and Qi-Stagnation Constitution (QSC). Another peak was 25-48 weeks after delivery, accounting for 18%, and the most common biased constitution of TCM was QSC and QDC. More participants were or were prone to be classified as Balanced Constitution (BC) in the control group than the case group (88.5% vs 29.6%), while QDC was the most common constitution of TCM in the case group. The logistic regression analysis further proved that BC was the protective factor of acute mastitis while QDC was a risk factor. CONCLUSIONS: The protective factors of acute mastitis were regular nipple cleansing and cesarean section. The risk factor was nipple infection. Among all the constitutions of TCM, BC was a protective factor, while QDC was a risk factor. For all breastfeeding mothers with various constitutions of TCM, regular nipple cleansing and breast vacuuming, a healthy lifestyle, and a positive mental state can keep mastitis away.

Platycodon grandiflorum Protects Against Anthracycline-Induced Cardiotoxicity in Early Breast Cancer Patients.

Background: Anthracycline-based chemotherapy is an effective treatment used for early-stage breast cancer patients. However, anthracycline use is limited due to its cardiotoxic effects. Recent studies have shown that Platycodon grandiflorum (PG) protects the heart from anthracycline-induced cardiotoxicity. However, no randomized, placebo-controlled clinical trial has been performed to investigate the clinical use of PG to prevent anthracycline-induced cardiotoxicity. This study aimed to evaluate the cardioprotective effects and safety of PG in early breast cancer patients receiving anthracycline-based chemotherapy. Methods: A total of 125 early breast cancer patients receiving anthracycline-based chemotherapy were enrolled and randomized into a PG group or placebo group in a 1:1 ratio. Results: Only 2 (3.1%) participants in the placebo group and 1 (1.6%) participant in the PG group experienced NYHA (New York Heart Association) class III or IV heart failure. There were no significant differences observed between the 2 groups. However, compared with the placebo group, patients in the PG group showed a lower incidence of subclinical heart failure (21.9% vs 8.2%, respectively, P = .033), as well as lower cardiac troponin T levels (48.4% vs 31.1%, respectively, P = .002). Importantly, there were no differences observed in the antitumor effects of anthracycline between the 2 groups (disease-free survival: hazards ratio = 1.09, 95% confidence interval = 0.45-2.62, P = .84; overall survival: hazards ratio = 1.46, 95% confidence interval = 0.33-6.43, P = .62). Conclusion: PG prevents anthracycline-induced acute and chronic cardiac injury in early-stage breast cancer patients without compromising the antitumor effects of chemotherapy.

Cardioprotective effect of Platycodon grandiflorum in patients with early breast cancer receiving anthracycline-based chemotherapy: study protocol for a randomized controlled trial.

BACKGROUND: Anthracyclines, alone or in combination with other drugs, are among the most effective chemotherapeutic agents to treat breast cancer both in the adjuvant and neoadjuvant setting. Unfortunately, anthracycline-associated dose-dependent cardiotoxicity is a limiting factor in clinical use. Extensive efforts have been devoted to identifying strategies to prevent anthracycline-induced cardiotoxicity. However, most cardioprotective agents have shown little effect in clinical trials. Herbal medicines are pure, natural substances that have been used for centuries in many countries, including China. This trial aims to evaluate the cardioprotective effects and safety of Platycodon grandiflorum granules compared to placebo granules in patients with early breast cancer receiving anthracycline-based chemotherapy. METHOD/DESIGN: This study is a single-center, double-blinded, randomized, placebo-controlled, parallel-group trial. A total of 120 patients will be randomly allocated in a 1:1 ratio to receive either P. grandiflorum granules or placebo granules twice daily for 12 weeks. The primary outcome is heart failure (either clinical or subclinical). The secondary outcomes include all-cause mortality, cardiac death, electrocardiogram (ECG) findings, left ventricular diastolic function, longitudinal systolic strain and velocities measured by tissue Doppler imaging, cardiac biomarkers, such as troponin I (TnI), brain natriuretic peptide (BNP), and creatine kinase isoenzymes (CK-MB). Assessments will be performed at baseline (before randomization) and 3, 6, 9, 12, 16, and 20 weeks after randomization. DISCUSSION: This will be the first clinical trial to evaluate the cardioprotective effects and safety of P. grandiflorum in patients with early breast cancer receiving anthracycline-based chemotherapy. We are also performing this trial to assess the feasibility of a larger-scale clinical trial in the future. TRAIL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-16009256 . Registered on 23 September 2016.

Mg2+ mimicry in the promotion of group I ribozyme activities by aminoglycoside antibiotics.

Aminoglycoside antibiotics inhibit several types of ribozymes, including group I introns, by displacing critical Mg2+ ions. However, they stimulate activity of the small hairpin ribozyme. We show here that aminoglycosides promote self-splicing of the Cr.psbA2 group I intron at subthreshold Mg2+ concentrations. Neomycin is the most effective of the aminoglycosides tested; it stimulates splicing of Cr.psbA2 at micromolar concentrations, and, in this respect, is >100-fold more effective than spermidine. At optimal Mg2+ for Cr.psbA2 splicing, these drugs, especially kanamycin B and tobramycin, promote GTP attack at the 3' splice-site. Kinetic analysis suggests that this is due to an alternatively folded state of the ribozyme that is induced, or stabilized, by aminoglycosides. A similar effect is observed at high Mg2+ concentrations. Comparing the effects of structurally related aminoglycosides indicates that splicing promotion is more sensitive to drug structure than misfolding and occurs at lower drug concentrations. These data show that aminoglycosides can promote biochemical activities of a large ribozyme by acting as a Mg2+ mimic. The results also underscore the functional diversity of group I introns in nature.

Vitamin D growth inhibition of breast cancer cells: gene expression patterns assessed by cDNA microarray.

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the active metabolite of vitamin D, is a potent inhibitor of breast cancer cell growth. Although it is evident that 1,25(OH)2D3 inhibits growth of both estrogen receptor alpha-positive [ER alpha(+)] and -negative [ER alpha(-)] breast cancer cells, the cellular pathways contributing to these effects remain unclear. We studied the gene expression patterns in ER alpha(+) MCF-7 and ER alpha(-) MDA MB 231 human breast cancer cells following 1,25(OH)2D3 treatment, using cDNA expression arrays. Both cell lines showed a significant induction of the 1,25(OH)2D3-dependent 24-hydroxylase gene, a marker for the actions of 1,25(OH)2D3. In MCF-7 cells, 51 genes were up-regulated and 19 genes were down-regulated. The up-regulated genes encoded cell adhesion molecules, growth factors/modulators, steroid receptors/co-activators, cytokines, kinases and transcription factors. Of the up-regulated genes, 40% were implicated in cell cycle regulation and apoptosis and included cyclin G1 and cyclin I, p21-activated kinase-1 (PAK-1), p53, retinoblastoma like-2 [Rb2 (p130)], insulin-like growth factor binding protein-5 (IGFBP5) and caspases. Among the down-regulated genes were ER alpha, growth factors, cytokines and several kinases. Some of these results were confirmed by real-time PCR. In MDA MB 231 cells, 20 genes were up-regulated and 13 genes were down-regulated. Very few genes directly implicated in cell cycle regulation were up-regulated. The matrix metalloproteinases formed a major class of genes that were down-regulated in the MDA MB 231 cells. Seven genes were commonly up-regulated in both cell lines and these included transforming growth factor (TGFbeta2) and Rb2 (p130). In conclusion, the gene expression profiles of the two cell lines studied were different with a few overlapping genes suggesting that different cellular pathways might be regulated by 1,25(OH)2D3 to exert its growth inhibitory effects in ER alpha(+) and ER alpha(-) cells.

Reduction of autofluorescence on DNA microarrays and slide surfaces by treatment with sodium borohydride.

Microarray technology is currently being used extensively in functional genomics research and modern drug discovery and development. Henceforward, tremendous application potential for this technology exists in the fields of clinical diagnostics and prognostics, pathology, and toxicology for high-throughput analysis of "disease" gene expression. However, the major hurdle now in this technology is not the performance of the arrays but rather the efficient reproducibility of the hybridization signal intensity in a fluorescence-based analysis. The sensitivity of fluorescence detection on an array is to a large extent limited by the amount of background signal arising due to nonspecifically bound probes and fluorescence that is intrinsically associated with the chip substrate and/or the attached target DNA, the so-called autofluorescence. Here, we describe a simple and efficient method to reduce autofluorescence from undetermined sources on coated glass slides with and without DNA arrays. This sodium borohydride-mediated reduction process resulted in significantly lower and more even background fluorescence. This in turn extended the dynamic range of detection and reduced the average coefficient of variation of fluorescent signal ratios on DNA microarrays in addition to improving the detection of genes that are expressed at a low level.

Microfluidic devices for fluidic circulation and mixing improve hybridization signal intensity on DNA arrays.

Reactions of biomolecules with surface mounted materials on microscope slides are often limited by slow diffusion kinetics, especially in low volumes where diffusion is the only means of mixing. This is a particular problem for reactions where only small amounts of analyte are available and the required reaction volume limits the analyte concentration. A low volume microfluidic device consisting of two interconnected 9 mm x 37.5 mm reaction chambers was developed to allow mixing and closed loop fluidic circulation over most of the surface of a microscope slide. Fluid samples are moved from one reaction chamber to the other by the rotation of a magnetic stirring bar that is driven by a standard magnetic stirrer. We demonstrate that circulation and mixing of different reagents can be efficiently accomplished by this closed loop device with solutions varying in viscosity from 1 to 16.2 centipoise. We also show by example of a microarray hybridization that the reaction efficiency can be enhanced 2-5 fold through fluid mixing under conditions where diffusion is rate limiting. For comparison, similar results were achieved with a disposable commercial device that covers only half of the reaction area of the closed loop device.