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Study finds new targets for triple-negative breast cancer treatment

Posted by star on 2018-10-08 18:43:12
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    A new study analyzes the transcriptome characteristics of triple-negative breast cancer (TNBC) patients, and identifies and confirms the novel inhibitor Wwox protein of JAK2/STAT3 signaling in breast cancer, elucidating abnormal attenuation of Wwox and abnormal activation of JAK2/STAT3 Such a negative correlation is an important cause of the metastasis of highly malignant TNBC. The study of Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis is published online in Nature-Communication.

    In recent years, the incidence of breast cancer in China has continued to rise. TNBC is a type with a high degree of malignancy. Its invasiveness is extremely strong, the risk of distant metastasis is large, and the prognosis is extremely poor. At present, its treatment is relatively simple, mainly chemotherapy, and it is easy to relapse and metastasize. Endocrine therapy and molecular targeted therapy are ineffective against TNBC compared to other types of breast cancer.

    The researchers screened transcriptomic analysis of TNBC cells and normal breast cells to obtain abnormal expression of multiple signals in the IL6/JAK2/STAT3 pathway, demonstrating the high abnormal expression of IL6 in TNBC cells and the persistence of JAK2/STAT3 activation. Activation may be an important factor in the distal metastasis of TNBC. The study also found that SOCS3, the main inhibitor of JAK2/STAT3, was not inhibited in TNBC; the newly discovered fragile site gene Wwox persisted in the IL6/JAK2/STAT3 signaling pathway in breast cancer. Specific inhibition occurs during activation. The researchers demonstrated the inhibitory effect of Wwox on sustained phosphorylation of STAT3 signaling and sustained activa......

Removal of aging glial cells is expected to treat Alzheimer disease

Posted by star on 2018-10-07 23:19:45
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    In a new study, aging cells accumulate in their brains before cognitive loss in the mouse model of brain disease. By preventing the accumulation of these aging cells, they are able to reduce tau protein aggregation, neuronal death and memory loss. The relevant research results are published online in Nature, and the title of the paper is "Clearance of senescent glial cells preventing tau-dependent pathology and cognitive decline".

    It is known that senescent cells accumulate in sites associated with aging diseases (including osteoarthritis and atherosclerosis) and neurodegenerative diseases (including Alzheimer's disease and Parkinson's disease) as the natural age grows. In previous studies, we have found that clearing senescent cells from naturally aged mice prolongs their healthy lifespan.

    In this new study, the mouse model of Alzheimer's disease produces sticky, spider-like tau tangles in their neurons, and their genetically modified senescent cells can be eliminated. When senescent cells were removed, the researchers found that the diseased mice maintained the ability to form memory and eliminate signs of inflammation, did not produce neurofibrillary tangles, and maintained normal brain quality. They also reported that drug interventions that remove senescent cells can regulate the accumulation of tau.

    In addition, the research team was able to identify specific cell types that are senescent. When the brain tissue was observed under a microscope, they found two different types of brain cells called microglia and astrocytes to age. These cells are important proponents of neuronal health and signaling, so it makes sense that aging of any of these cells can have a negativ......

How to prevent heart attacks in patients with hypertension

Posted by star on 2018-09-29 19:36:57
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    A recent large, long-term study has shown that people with high blood pressure want to prevent heart attacks, while taking antihypertensive drugs and statins (drugs that help regulate cholesterol levels) may be the best option.

    This study was published on The Lancet Journal under the title "Long-term mortality after blood pressure-lowering and lipid-lowering treatment in patients with hypertension in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Legacy study: 16-year follow-up Results of a randomised factorial trial".

    In the new study, the researchers tracked 8,580 British subjects enrolled between 1998 and 2000, all of whom had high blood pressure.

    According to ASCOT data, hypertensive patients who took amlodipine and perindopril for 5.5 years had a 29% reduction in the likelihood of death from a stroke 10 years later than those who received traditional antihypertensive medication.

    Moreover, compared with patients taking placebo alone, statins were taken at a normal level (6.5 mM per liter) of hypertensive patients, and the risk of death from heart disease and stroke was reduced by 15% after 16 years.

    In addition, patients with “double high” were treated with antihypertensive therapy (amlodipine and perindopril) and conventional cholesterol-lowering therapy, and the likelihood of death from cardiovascular disease was reduced by 21% within 10 years.



Yeast repair gapped plasmids by homologous recombination

Posted by star on 2018-09-29 19:10:27
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    Additional information about HR was gained by transforming yeast cells with recombinant plasmids that have yeast genes but lack a yeast replicator sequence. Because the plasmids lack a yeast replicator, their yeast genes can only be maintained if they integrate into the yeast genome. Early experiments showed that plasmids integrated into the yeast genome by HR between the yeast gene on the plasmid and the homologous yeast gene in the chromosomal DNA.

    Terry Orr- Weaver, Jack Szostak, and Rodney Rothstein performed experiments with a yeast transforming plasmid that lacks a yeast replicator and is therefore incapable of autonomous replication. The yeast plasmid carried two yeast markers derived from different chromosomal genes. In some experiments, they used a restriction endonuclease to make one double-strand break in one of the two genes and in other experiments they used two restriction endonucleases to make two double-strand breaks in one of the genes, removing an internal sequence and creating a gap. Surprisingly, the broken plasmids transformed at much higher frequencies than the uncut plasmid. Ail of the transformants were the result, of integration of the plasmid into chromosomal DNA. The plasmid was integrated at the homologous gene sequence in the chromosome and, moreover, the gapped plasmid was repaired during the transformation and integration process. These experiments showed that double-strand breaks stimulate HR. This formed the basis for a new HR model.



The Holliday junction

Posted by star on 2018-09-27 19:25:41
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    Robin Holliday proposed a model for HR in meiosis. According to this model, recombination begins after DNA replication. An endonuclease is proposed to introduce a single nick into each duplex so that strands with the same orientation in each duplex are nicked at the same site. Next, symmetric exchange of single DNA strands between duplexes occurs to form what is called symmetric het eroduplex DNA. The crossed strand structure is an important intermediate and is called the Holliday junction. This structure has four-way symmetry and can move down the paired chromatids by a process called branch migration, forming more heteroduplex DNA. At some point, the Holliday Junction structure is cleaved to generate two separate nicked duplexes, a process known as resolution. Because the Holliday junction has four-way symmetry, it can be resolved in an east-west direction, giving noncrossover products, or in a north-south direction, giving crossover products. Mismatch repair of the heteroduplex DNA region can either restore the original genotype or change the genotype of one (e. g., A)to the other (e. g., a). This change gives a 1:3 (or 3:1) segregation and explains the association of gene conversion with crossovers in the flanking region.

    The Holliday model has several shortcomings. As described below, recombination is now known to begin at a double-strand break or single-strand gap in one DNA molecule. Furthermore, even though extensive efforts have been made to detect an endonuclease with the specificity required by the model, no such enzyme has been found in eukaryotes although much progress has been made in identifying biochemical resolution activities. Despite these shortcomings, the Holliday model has made an important contribution to our understanding of DNA recombination and several features of the model, including the heteroduplex DNA intermediate, branch migration, the Holliday junction, and resolution, remain an importa......

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