Transferrin improved the generation of cardiomyocyte from human pluripotent stem cells for myocardial infarction repair.

Human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) hold great promise for the repair of the injured heart, but optimal cell production in a fully chemically defined and cost-effective system is essential for the efficacy and safety of cell transplantation therapies. In this study, we provided a simple and efficient strategy for cardiac differentiation from hPSCs and performed functional evaluation in a rat model of myocardial infarction. Using a chemically defined medium including four components, recombinant human albumin, ascorbic acid, human transferrin, and RPMI 1640, we developed a manageable and cost-effective protocol for robust generation of CMs from hPSCs. Interestingly, the addition of transferrin helped hPSCs to transit from TeSR-E8 medium to the simple cardiac differentiation medium and successfully initiated mesoderm differentiation without significant cell death. The CM generation efficiency was up to 85% based on cTnT expression. We performed transcriptome profiling from differentiation day 0 to 35, and characterized interesting dynamic change of cardiac genes. CMs derived from transferrin-supplemented simple medium have similar transcriptome and the maturation level compared to those generated in B27 minus insulin medium as well as their in vivo counterparts. Importantly, after transplantation, hPSC-derived CMs survived in the infarcted rat heart, significantly improved the physiological function and reduced fibrosis. Our study offers an easy-to-use and cost-effective method for cardiac differentiation and facilitates the translational application of hPSC-derived CMs for heart repair.

Evaluation of Germline Genetic Testing Criteria in a Hospital-Based Series of Women With Breast Cancer.

PURPOSE: To determine the sensitivity and specificity of genetic testing criteria for the detection of germline pathogenic variants in women with breast cancer. MATERIALS AND METHODS: Women with breast cancer enrolled in a breast cancer registry at a tertiary cancer center between 2000 and 2016 were evaluated for germline pathogenic variants in 9 breast cancer predisposition genes (ATM, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53). The performance of the National Comprehensive Cancer Network (NCCN) hereditary cancer testing criteria was evaluated relative to testing of all women as recommended by the American Society of Breast Surgeons. RESULTS: Of 3,907 women, 1,872 (47.9%) meeting NCCN criteria were more likely to carry a pathogenic variant in 9 predisposition genes compared with women not meeting criteria (9.0% v 3.5%; P < .001). Of those not meeting criteria (n = 2,035), 14 (0.7%) had pathogenic variants in BRCA1 or BRCA2. The sensitivity of NCCN criteria was 70% for 9 predisposition genes and 87% for BRCA1 and BRCA2, with a specificity of 53%. Expansion of the NCCN criteria to include all women diagnosed with breast cancer at ≤ 65 years of age achieved > 90% sensitivity for the 9 predisposition genes and > 98% sensitivity for BRCA1 and BRCA2. CONCLUSION: A substantial proportion of women with breast cancer carrying germline pathogenic variants in predisposition genes do not qualify for testing by NCCN criteria. Expansion of NCCN criteria to include all women diagnosed at ≤ 65 years of age improves the sensitivity of the selection criteria without requiring testing of all women with breast cancer.

Tenuigenin ameliorates learning and memory impairments induced by ovariectomy.

Estrogen deficiency is associated with cognitive impairment. Hormone replacement therapy (HRT) has proven to be effective in preventing and reversing the memory and learning deficiencies. However, conventional estrogenic treatment could increase the risks of breast cancer and venous thromboembolism. Tenuigenin (TEN) is putatively believed as the active component extracted from a Chinese herb Polygala tenuifolia root. Although TEN has been shown to enhance learning and memory in healthy mice, it remains unknown whether or not TEN could ameliorate learning and memory impairments. In the present study, mice were divided into four groups: sham-operated (sham), ovariectomized (OVX), OVX+estradiol benzoate (EB) and OVX+TEN groups. Step-through passive avoidance and Y-maze tests were used to assess learning and memory abilities, and the number of nitric oxide synthase (NOS) positive neurons and the synaptic measurement of hippocampal CA1 area were examined. The results showed that TEN was given orally to OVX mice, leading to the improvement of learning and memory in step-through passive avoidance and Y-maze tests. TEN could reduce the loss of NOS positive neurons and prevent the synaptic morphological changes induced by ovariectomy. Our results suggest that TEN may exert a potential therapeutic value for menopause cognitive dysfunction.

Colon may provide new therapeutic targets for treatment of chronic kidney disease with Chinese medicine / 中国结合医学杂志

Chronic kidney disease (CKD) has become a worldwide health and social problem. Retarding its progression to end-stage renal disease is beneficial both to the patients and the healthcare system. Plenty of clinical trials have indicated that enema with Chinese medicine could effectively prevent chronic renal failure, and was widely used in the clinical practice. However, studies on mechanism were still nearly blank, which may prevent further improvement of therapeutic efficacy. Recent studies had discovered that colon was an important organ where uremic toxins were generated. The uremic toxins involved could not only promote CKD progression, but also was closely correlated with CKD mortality. Reducing production and promoting excretion of toxins were confirmed to reduce renal tubule interstitial fibrosis and delay renal progression. On the basis of the theory of gut-kidney axis above, we had conducted pilot clinical researches to evaluate the effect of enema with Chinese medicine on the intestinal flora, gut barrier, enterogenous uremic toxins and renal protection. The preliminary results revealed that rheum enema through colon could accelerate intestinal dynamics, improve intestinal barrier function, regulate intestinal flora and reduce production and absorption of intestine-derived uremic toxins such as indoxyl sulfate, which may reduce renal fibrosis and delay renal progression. Further studies could provide more evidence for colon as a new therapeutic target for the treatment of CKD with Chinese medicine.

Heparin promotes the growth of human embryonic stem cells in a defined serum-free medium.

A major limitation in developing applications for the use of human embryonic stem cells (HESCs) is our lack of knowledge of their responses to specific cues that control self-renewal, differentiation, and lineage selection. HESCs are most commonly maintained on inactivated mouse embryonic fibroblast feeders in medium supplemented with FCS, or proprietary replacements such as knockout serum-replacement together with FGF-2. These undefined culture conditions hamper analysis of the mechanisms that control HESC behavior. We have now developed a defined serum-free medium, hESF9, for the culture of HESCs on a type I-collagen substrate without feeders. In contrast to other reported media for the culture of HESCs, this medium has a lower osmolarity (292 mosmol/liter), l-ascorbic acid-2-phosphate (0.1 microg/ml), and heparin. Insulin, transferrin, albumin conjugated with oleic acid, and FGF-2 (10 ng/ml) were the only protein components. Further, we found that HESCs would proliferate in the absence of exogenous FGF-2 if heparin was also present. However, their growth was enhanced by the addition of FGF-2 up to 10 ng/ml although higher concentrations were deleterious in the presence of heparin.

[Clinical observation on effect of modified huanglian wendan decoction in treating diabetic asymptomatic myocardial ischemia].

OBJECTIVE: To investigate the clinical efficacy of modified huanglian wendan decoction (MHWD) on diabetic asymptomatic myocardial ischemia. METHODS: Ninety patients were randomly divided into two groups. The control group (n=30) was given Xinkang tablet (XKT) at a dose of 20 mg, twice a day. The treated group (n=35) was given MHWD besides XKT as that given to the control group. The treatment course for both groups was 1 month. Indexes, including blood glucose, glycosylated hemoglobin, blood lipids, myocardial zymogram, hemorheologic parameters, urinary albumin, routine examination of blood and urine, function of liver and kidney, as well as 24h dynamic electrocardiogram and electrocardiogram exercise test were measured in the two groups before and after treatment. RESULTS: The total clinical effective rate in the treated group and the control group was 88.33% and 56.67% respectively (P < 0.05), showing significant difference between them. The frequency of ischemia attacking, paroxysmal cumulative time, motion related incidence were lower in the treated group after treatment than those in the control group. Besides, in the treated group after treatment, the level of blood lipids and hemorheologic parameters were significantly improved (P < 0.05 or P < 0.01), hematocrit was unchanged and triglyceride, red blood cell agglutination index and erythrocyte deformability index were obviously different to those in the control group (P < 0.05). While in the control group after treatment, except the improving of whole blood viscosity (P < 0.05), no significant change was found in the other indices. CONCLUSION: MHWD has effects in improving myocardial ischemia, bettering hemorheologic condition and reducing blood lipids.

Clinical observation on effect of modified huanglian wendan decoction in treating diabetic asymptomatic myocardial ischemia / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the clinical efficacy of modified huanglian wendan decoction (MHWD) on diabetic asymptomatic myocardial ischemia.</p><p><b>METHODS</b>Ninety patients were randomly divided into two groups. The control group (n=30) was given Xinkang tablet (XKT) at a dose of 20 mg, twice a day. The treated group (n=35) was given MHWD besides XKT as that given to the control group. The treatment course for both groups was 1 month. Indexes, including blood glucose, glycosylated hemoglobin, blood lipids, myocardial zymogram, hemorheologic parameters, urinary albumin, routine examination of blood and urine, function of liver and kidney, as well as 24h dynamic electrocardiogram and electrocardiogram exercise test were measured in the two groups before and after treatment.</p><p><b>RESULTS</b>The total clinical effective rate in the treated group and the control group was 88.33% and 56.67% respectively (P < 0.05), showing significant difference between them. The frequency of ischemia attacking, paroxysmal cumulative time, motion related incidence were lower in the treated group after treatment than those in the control group. Besides, in the treated group after treatment, the level of blood lipids and hemorheologic parameters were significantly improved (P < 0.05 or P < 0.01), hematocrit was unchanged and triglyceride, red blood cell agglutination index and erythrocyte deformability index were obviously different to those in the control group (P < 0.05). While in the control group after treatment, except the improving of whole blood viscosity (P < 0.05), no significant change was found in the other indices.</p><p><b>CONCLUSION</b>MHWD has effects in improving myocardial ischemia, bettering hemorheologic condition and reducing blood lipids.</p>