Regulation of Exosomes in the Pathogenesis of Breast Cancer

Extracellular vesicles (EVs) are a heterogeneous group of endogenous nanoscale vesicles that are secreted by various cell types. Based on their biogenesis and size distribution, EVs can be broadly classified as exosomes and microvesicles. Exosomes are enveloped by lipid bilayers with a size of 30–150 nm in diameter, which contain diverse biomolecules, including lipids, proteins and nucleic acids. Exosomes transport their bioactive cargoes from original cells to recipient cells, thus play crucial roles in mediating intercellular communication. Breast cancer is the most common malignancy among women and remains a major health problem worldwide, diagnostic strategies and therapies aimed at breast cancer are still limited. Growing evidence shows that exosomes are involved in the pathogenesis of breast cancer, including tumorigenesis, invasion and metastasis. Here, we provide a straightforward overview of exosomes and highlight the role of exosomes in the pathogenesis of breast cancer, moreover, we discuss the potential application of exosomes as biomarkers and therapeutic tools in breast cancer diagnostics and therapeutics

A Correlation Study between Two Adjacent Same-Meridian Acupoints after Laser-Needle Acupuncture with Optical Coherence Tomography and Diffuse Reflectance Spectra

This study is to investigate the correlations among Sanjian (LI3), Hegu (LI4), and Yangxi (LI5) acupoints and their corresponding nonacupoints on the Yangming Large Intestine Meridian of Hand before and after laser irradiation using optical coherence tomography (OCT) and diffuse reflectance spectra. The experiment was conducted on 10 healthy people. A 658 nm laser with 50 mW output power was used for irradiating LI4, LI5 acupoints and their corresponding nonacupoints. As to LI4 acupoint with laser irradiation for duration of 15 or 45 minutes, the OCT backscattered light intensities of LI4 and LI5 acupoints increased significantly, and the reflectance intensities (RIs) of the LI3, LI4, and LI5 acupoints decreased significantly. As to LI5 acupoint with laser irradiation for duration of 15 or 45 minutes, the changes of OCT backscattered light intensities of the corresponding irradiated acupoint and LI4 acupoint increased significantly, and the RIs decreased significantly. However, the OCT backscattered light intensities and RIs for their nonacupoints were almost not changed. The results show that an association exists between two adjacent same-meridian acupoints on the same meridian after laser-needle acupuncture to some extent

Profiling analysis of long non-coding RNAs in early postnatal mouse hearts

Mammalian cardiomyocytes undergo a critical hyperplastic-to-hypertrophic growth transition at early postnatal age, which is important in establishing normal physiological function of postnatal hearts. In the current study, we intended to explore the role of long non-coding (lnc) RNAs in this transitional stage. We analyzed lncRNA expression profiles in mouse hearts at postnatal day (P) 1, P7 and P28 via microarray. We identified 1,146 differentially expressed lncRNAs with more than 2.0-fold change when compared the expression profiles of P1 to P7, P1 to P28, and P7 to P28. The neighboring genes of these differentially expressed lncRNAs were mainly involved in DNA replication-associated biological processes. We were particularly interested in one novel cardiac-enriched lncRNA, ENSMUST00000117266, whose expression was dramatically down-regulated from P1 to P28 and was also sensitive to hypoxia, paraquat, and myocardial infarction. Knockdown ENSMUST00000117266 led to a significant increase of neonatal mouse cardiomyocytes in G0/G1 phase and reduction in G2/M phase, suggesting that ENSMUST00000117266 is involved in regulating cardiomyocyte proliferative activity and is likely associated with hyperplastic-to-hypertrophic growth transition. In conclusion, our data have identified a large group of lncRNAs presented in the early postnatal mouse heart. Some of these lncRNAs may have important functions in cardiac hyperplastic-to-hypertrophic growth transition

Attenuation of epigenetic regulator SMARCA4 and ERK-ETS signaling suppresses aging-related dopaminergic degeneration

How complex interactions of genetic, environmental factors and aging jointly contribute to dopaminergic degeneration in Parkinson's disease (PD) is largely unclear. Here, we applied frequent gene co‐expression analysis on human patient substantia nigra‐specific microarray datasets to identify potential novel disease‐related genes. In vivo Drosophila studies validated two of 32 candidate genes, a chromatin‐remodeling factor SMARCA4 and a biliverdin reductase BLVRA. Inhibition of SMARCA4 was able to prevent aging‐dependent dopaminergic degeneration not only caused by overexpression of BLVRA but also in four most common Drosophila PD models. Furthermore, down‐regulation of SMARCA4 specifically in the dopaminergic neurons prevented shortening of life span caused by α‐synuclein and LRRK2. Mechanistically, aberrant SMARCA4 and BLVRA converged on elevated ERK‐ETS activity, attenuation of which by either genetic or pharmacological manipulation effectively suppressed dopaminergic degeneration in Drosophila in vivo. Down‐regulation of SMARCA4 or drug inhibition of MEK/ERK also mitigated mitochondrial defects in PINK1 (a PD‐associated gene)‐deficient human cells. Our findings underscore the important role of epigenetic regulators and implicate a common signaling axis for therapeutic intervention in normal aging and a broad range of age‐related disorders including PD

Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke

BackgroundDual antiplatelet treatment has been shown to reduce recurrence of stroke compared to aspirin alone when initiated early after an acute stroke. The effect of clopidogrel and aspirin versus aspirin alone within 72 hours of acute cerebral ischemia from atherosclerosis has not been well studied.MethodsWe conducted a randomized, double-blind, placebo-controlled, 2-by-2 factorial trial in patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause, not receiving thrombolysis or thrombectomy in 222 hospitals in China. Patients were randomly assigned within 72 hours after symptom onset in a 1:1 ratio, to receive clopidogrel (300mg on day 1, 75mg daily on days 2-90) and aspirin (100-300mg on day1, 100mg daily on days 2-21), or clopidogrel placebo and aspirin (100-300mg on day1, 100mg daily on days 2-90). There was no interaction between this component of the factorial trial design trial and a second part that tested immediate vs delayed stain treatment and is reported separately. The primary efficacy outcome was a new stroke, and the primary safety outcome was moderate-to-severe bleeding, both within 90 days.ResultsA total of 6100 patients were enrolled, 3050 assigned to each trial group. The qualifying event for enrollment was TIA in 13%. Approximately 13% of patients were assigned to a treatment group within 24 hours and 87% were assigned between 24 and 72 hours of onset of stroke. A new stroke occurred in 222 (7.3%) in the clopidogrel-aspirin group, and 279 (9.2%) in the aspirin group (hazard ratio, 0.79; 95% confidence interval [CI], 0.66-0.94; P=0.008). Moderate-to-severe bleeding occurred in 27 (0.9%) and 13 patients (0.4%), respectively (hazard ratio, 2.08; 95% CI, 1.07-4.04, P=0.03).ConclusionsAmong patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, combined clopidogrel-aspirin initiated within 72 hours of onset was superior to aspirin alone in reducing the risk of new stroke at 90 days but was associated with a low but increased risk of moderate-to-severe bleeding

Advances in Multidisciplinary Treatment of Rectal Cancer

To summarize the advances in the multidisciplinary treatment of rectal cancer and to analyze the existing problems and development prospects. The full text database retrieval system of MEDLINE and the periodicals of CHKD were searched. The words “rectal cancer, diagnosis, surgery, chemotherapy, radiotherapy, targeted therapy, analysis” were used as key words for retrieval of literature concerning the values and clinical significance of rectal cancer multidisciplinary treatment from January, 2000 to December, 2007. Thirty papers were selected, of which 26 were used in analysis at last. Accurate preoperative staging of rectal cancer is a key factor in the multidisciplinary and comprehensive treatment of patients. A new therapy which is combined with radical operation can reduce the rate of local recurrence, prolong survival time, and particularly, promote the rate of sphincter preservation. Radical surgery combined with adjuvant therapy is still recognized as standard treatment modality for the patients with rectal cancer in stage II-III. Total removal of resectable metastases followed by prompt standard adjuvant therapy may extend survival time. The introduction of new chemical drugs, drugs of targeting therapy, and a regimen of combination therapy may improve outcomes in treatment for rectal cancer patients. A treatment standard for rectal cancer patients needs to be actively pursued. Compared with colon cancer patients, there has not been sufficient evidence to confi rm that the total survival rate of rectal cancer patients a t er multidisciplinary and comprehensive treatments has been improved; therefore, it needs to be further studied

Action Sites and Clinical Application of HIF-1α Inhibitors

Hypoxia-inducible factor-1α (HIF-1α) is widely distributed in human cells, and it can form different signaling pathways with various upstream and downstream proteins, mediate hypoxia signals, regulate cells to produce a series of compensatory responses to hypoxia, and play an important role in the physiological and pathological processes of the body, so it is a focus of biomedical research. In recent years, various types of HIF-1α inhibitors have been designed and synthesized and are expected to become a new class of drugs for the treatment of diseases such as tumors, leukemia, diabetes, and ischemic diseases. This article mainly reviews the structure and functional regulation of HIF-1α, the modes of action of HIF-1α inhibitors, and the application of HIF-1α inhibitors during the treatment of diseases