Advances in the differentiation of pluripotent stem cells into vascular cells

Blood vessels constitute a closed pipe system distributed throughout the body,transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys.Changes in blood vessels are related to many disorders like stroke,myocardial infarction,aneurysm,and diabetes,which are important causes of death worldwide.Translational research for new appro-aches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems.Although mice or rats have been widely used,applying data from animal studies to human-specific vascular physiology and pathology is difficult.The rise of induced pluripotent stem cells(iPSCs)provides a reliable in vitro resource for disease modeling,regenerative medicine,and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells.This review summarizes the latest progress from the establishment of iPSCs,the strategies for differentiating iPSCs into vascular cells,and the in vivo trans-plantation of these vascular derivatives.It also introduces the application of these technologies in disease modeling,drug screening,and regenerative medicine.Additionally,the application of high-tech tools,such as omics analysis and high-throughput sequencing,in this field is reviewed.

Armarium facilitating angina management post myocardial infarction concomitant with coronavirus disease 2019

The outbreak and spread of coronavirus disease 2019(COVID-19)are not only a disaster of people’s life and health over the world,[1–3]but also the challenge for medical practitioner in clinical management.Owing to many diagnostic instruments are not suitable or convenient to use any more in contagious ward considering the risk of cross infections,such as traditional stethoscope or electrocardiogram(ECG).In this scenarios,wireless and digital equipment are optimal choices for epidemic management in order to exert rapid diagnosis and disease evaluation.Herein,we reported a case of the patient suffering both COVID-19 and myocardial infarction,for which the tele-ECG and wireless stethoscope facilitated the accurate diagnosis and instant management.

Phenotypic and functional comparison of rat enteric neural crest-derived cells during fetal and earlypostnatal stages

In our previous study,we showed that with increasing time in culture,the growth characteristics of enteric neural crest-derived cells(ENCCs)change,and that the proliferation,migration and neural differentiation potential of these cells in vitro notably diminish.However,there are no studies on the developmental differences in these characteristics between fetal and early-postnatal stages in vitro or in vivo.In this study,we isolated fetal(embryonic day 14.5)and postnatal(postnatal day 2)ENCCs from the intestines of rats.Fetal ENCCs had greater maximum cross-sectional area of the neurospheres,stronger migration ability,and reduced apoptosis,compared with postnatal ENCCs.However,fetal and postnatal ENCCs had a similar differentiation ability.Fetal and postnatal ENCCs both survived after transplant into a rat model of Hirschsprung’s disease.In these rats with Hirschsprung’s disease,the number of ganglionic cells in the myenteric plexus was higher and the distal intestinal pressure change was greater in animals treated with fetal ENCCs compared with those treated with postnatal ENCCs.These findings suggest that,compared with postnatal ENCCs,fetal ENCCs exhibit higher survival and proliferation and migration abilities,and are therefore a more appropriate seed cell for the treatment of Hirschsprung’s disease.This study was approved by the Animal Ethics Committee of the Second Affiliated Hospital of Xi’an Jiaotong University(approval No.2016086)on March 3,2016.

Responses of phospholipase D and lipoxygenase to mechanical wounding in postharvest cucumber fruits

This study was to investigate the responses of phospholipase D(PLD) and lipoxygenase(LOX) to mechanical wounding in postharvest cucumber(Cucumis sativus L.cv.Biyu-2) fruits.Membrane-associated Ca2+ content,activities and gene expression of PLD and LOX,and contents of phosphatidylcholine(PC),phosphatidylinositol(PI),and phosphatidic acid(PA) were determined in cucumber fruits following mechanical wounding.Results show that PLD and LOX activities increased with the PLD and LOX mRNAs which are upregulated upon wounding,while membrane-associated Ca2+ content decreased.Accompanying with the increase of PLD and LOX activities,accumulation of PA and losses of PC and PI were observed in all fruits,but there were differences of degrees between wounded and control fruits.Results suggest that PLD and LOX might be the main hydrolytic enzymes of phospholipids in postharvest cucumber fruits participating in the mechanical wounding injury.The activation of PLD and LOX might be the result of gene expression,which could be stimulated by the Ca2+ flowing from the membrane to the cytoplasm upon receiving the wounding signals.

Clinical,Neuroimaging,and Pathological Analyses of 13 Chinese Leigh Syndrome Patients with Mitochondrial DNA Mutations

Background: Leigh syndrome(LS) is a rare disease caused by mitochondrial defects and has high phenotypic and genotypic heterogeneity.We analyzed the clinical symptoms, neuroimaging, muscular histopathology, and genotypes of 13 Chinese LS patients with mitochondrial DNA(mtDNA) mutations.Methods: Mutations in mtDNA were identified by targeted sequencing. The brain imaging features on magnetic resonance imaging(MRI)were analyzed. The levels of lactate in fasting blood and cerebrospinal fluid(CSF) were routinely tested. The levels of urinary organic acids, plasma amino acids, and acylcarnitines were examined with gas chromatography–mass spectrometry and tandem mass spectrometry.The histopathological traits of skeletal muscles were analyzed under microscope.Results: Among 13 patients, mutations of MT?NDs(n = 8) and MT?ATP6(n = 4) genes were most common. Strabismus(8/13), muscle weakness(8/13), and ataxia(5/13) were also common, especially for the patients with late?onset age after 2 years old. However, respiratory distress was common in patients with early?onset age before 2 years old. The most frequently affected brain area in these patients was the brain stem(12/13), particularly the dorsal part of midbrain, followed by basal ganglia(6/13), thalamus(6/13), cerebellum(5/13),and supratentorial white matter(2/13). Besides, the elevated lactate levels in CSF(6/6) were more common than those in serum(7/13).However, the analysis of abnormal plasma amino acid and urinary organic acid showed limited results(0/3 and 1/4, respectively). Muscular histopathology showed mitochondrial myopathy in the three late?onset patients but not in the early?onset ones.Conclusions: Noninvasive genetic screening is recommended for mtDNA mutations in MT?NDs and MT?ATP6 genes in patients with ophthalmoplegia, muscle weakness, ataxia, and respiratory disorder. Furthermore, the lactate detection in CSF and the brain MRI scanning are suggested as the diagnosis methods for LS patients with mtDNA mutations.

Late-onset mitochondrial disease in a patient with MELAS and mitochondrial DNA T14487C mutation

To the Editor: Mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS) is one of the most common multisystem mitochondrial disorders with broad clinical manifestations.[1] It is usually caused by point mutations in the mitochondrial MT-TL1 gene, which accounts for approximately 80% of mutations in individuals with MELAS syndrome.[2] Pathogenic mitochondrial DNA (mtDNA) mutations were first described in 1980[3] and m.l4487T>C is a known pathogenic mtDNA mutation,[4] which has been reported in patients with Leigh syndrome, optic neuropathy, ptosis, dystonia, and encephalomyopathy. We herein report a patient with late-onset MELAS syndrome with the m.l4487T>C mutation for the first time.

A Dynamic Programming Algorithm for the κ-Haplotyping Problem

The Minimum Fragments Removal （MFR） problem is one of the haplotyping problems： given a set of fragments, remove the minimum number of fragments so that the resulting fragments can be partitioned into k classes of non-conflicting subsets. In this paper, we formulate the κ-MFR problem as an integer linear programming problem, and develop a dynamic programming approach to solve the κ-MFR problem for both the gapless and gap eases.

Activated mTOR signaling pathway in myofibers with inherited metabolic defect might be an evidence for mTOR inhibition therapies

Background:Abnormally activated mechanistic target of rapamycin(mTOR)pathway has been reported in several model animals with inherited metabolic myopathies(IMMs).However,the profiles of mTOR pathway in skeletal muscles from patients are still unknown.This study aimed to analyze the activity of mTOR pathway in IMMs muscles.Methods:We collected muscle samples from 25 patients with mitochondrial myopathy(MM),lipid storage disease(LSD)or Pompe disease(PD).To evaluate the activity of mTOR pathway in muscle specimens,phosphorylation of S6 ribosomal protein(p-S6)and p70S6 kinase(p-p70S6K)were analyzed by Western blotting and immunohistochemistry.Results:Western blotting results showed that p-p70S6K/p70S6K in muscles from LSD and MM was up-regulated when compared with normal controls(NC)(NC vs.LSD,U=2.000,P=0.024;NC vs.MM:U=6.000,P=0.043).Likewise,p-S6/S6 was also upregulated in muscles from all three subgroups of IMMs(NC vs.LSD,U=0.000,P=0.006;NC vs.PD,[7=0.000,P=0.006;NC vs.MM,U=1.000,P=0.007).Immunohistochemical study revealed that p-S6 was mainly expressed in fibers with metabolic defect.In MM muscles,most p-S6 positive fibers showed cytochrome C oxidase(COX)deficiency(U=5.000,P=0.001).In LSD and PD muscles,p-S6 was mainly overexpressed in fibers with intramuscular vacuoles containing lipid droplets(17=0.000,P=0.002)or basophilic materials(U=0.000,P=0.002).Conclusion:The mTOR pathway might be activated in myofibers with various metabolic defects,which might provide evidence for mTOR inhibition therapy in human IMMs.

Reply to “Phenotypic and Genotypic Peculiarities in Chinese Patients with Leigh Syndrome”

To the Editor: We really appreciate the readers5 interest and comments about our article, and to have the opportunity to make an explanation[1].