We investigated whether co-expression of Neurog1 and Atoh1 in common neurosensory precursors could explain the loss of hair cells in Neurog1 null mice. Analysis of terminal mitosis, using BrdU, supports previous findings regarding timing of exit from cell cycle. Specifically, we show that cell cycle exit occurs in spiral sensory neurons in a base-to-apex progression followed by cell
Background
How exosomal microRNAs (miRNAs) derived from macrophages contribute to the development of drug resistance in the context of the hypoxic tumor microenvironment in epithelial ovarian cancer (EOC) remains poorly understood.
Methods
The miRNA levels were detected by qRT-PCR. Protein levels of HIF-1α, CD163 and PTEN-PI3K/AKT pathway were assessed by Western blot (WB) and Immunohistochemistry (IHC). Exosomes were isolated, and then confirmed by Transmission electron microscopy (TEM), Nanoparticle Tracking Analysis (NTA) and WB. Internalization of macrophages-secreted exosomes in EOC cells was detected by Confocal microscope. Subsequently, Dual-luciferase reporter assay verified PTEN was the target of miR-223. Gain- and loss-of-function experiments, rescue experiments, and SKOV3 xenograft models were performed to uncover the underlying mechanisms of miR-223 and PTEN-PI3K/AKT pathway, as well as the exosomal miR-223 in inducing multidrug resistance in vitro and in vivo.
Results
Here, we showed hypoxic EOC cells triggered macrophages recruitment and induced macrophages into a tumor-associated macrophage (TAM)-like phenotype; exosomes derived from hypoxic macrophages enhanced the malignant phenotype of EOC cells, miR-223 was enriched in exosomes released from macrophages under hypoxia, which could be transferred to the co-cultivated EOC cells, accompanied by enhanced drug resistant of EOC cells. Besides, results from a functional assay revealed that exosomal miR-223 derived from macrophages promoted the drug resistance of EOC cells via the PTEN-PI3K/AKT pathway both in vivo and in vitro. Furthermore, patients with high HIF-1a expression had statistically higher CD163+ cell infiltration and intertumoral levels of miR-223. Finally, circulating exosomal miR-223 levels were closely related to the recurrence of EOC.
Conclusions
These data indicate a unique role of exosomal miR-223 in the cross-talk between macrophages and EOC cells in chemotherapy resistance, through a novel exosomal miR-223/PTEN-PI3K/AKT signaling pathway.
Electronic supplementary material
The online version of this article (10.1186/s13046-019-1095-1) contains supplementary material, which is available to authorized users.
Our findings demonstrated that LncRNA SNHG4 promoted tumour growth by sponging miR-224-3p and represented a poor prognostic factor in patients with osteosarcoma.
Gastric cancer (GC) is one of the most common malignant tumors worldwide. Emerging evidence has shown that abnormal microRNAs (miRNAs) expression is involved in tumorigenesis. MiR-329 was previously reported to act as a tumor suppressor or oncogene in some types of cancer. However, its function in gastric cancer (GC) is unclear. Here, we found that miR-329 was down-regulated in GC compared with adjacent controls. Enforced expression of miR-329 inhibited proliferation, migration and invasion of gastric cancer cells in vitro. We identified T lymphoma invasion and metastasis 1 (TIAM1) gene as potential target of miR-329. MiR-329 levels inversely correlated with TIAM1 expression in GC. Importantly, TIAM1 rescued the miR-329-mediated inhibition of cell invasion and proliferation. Finally, reintroduction of miR-329 significantly inhibited tumor formation of GC in the xenograft mice. Our findings suggest that miR-329 is a tumor suppressor and potential therapeutic target of GC
The elderly are at high risk of contracting respiratory infectious diseases, including COVID-19 infection. The recent pandemic has the potential to cause significant physical and mental damage in older adults. Similarly to other mind-body exercises in Traditional Chinese medicine, Qigong features regulation of breath rhythm and pattern, body movement and posture, and meditation. Given these traits, Qigong has the potential to play a role in the prevention, treatment, and rehabilitation of respiratory infections, such as COVID-19. Potential mechanisms of action include stress reduction, emotion regulation, strengthening of respiratory muscles, reduction of inflammation, and enhanced immune function. Three forms of Qigong; abdominal breathing, Ba Duan Jin and Liu Zi Jue, all of which are gentle, smooth, and simple for the elderly to practice, are recommended in this context.
Interconnected nickel
bicarbonate (Ni(HCO3)2) hollow spheres were
produced and exploited for the first time as an anode of lithium ion
batteries, delivering the 80th reversible capacity of 1442 mAh g–1 at a current rate of 100 mA g–1, which is 3.9 times the theoretical capacity of commercial anode
graphite. The time-dependent study suggested a self-sacrificial templating
formation mechanism that yielded intriguing interconnected hollow
structures. X-ray photoelectron spectroscopy measurements on cycled
electrodes indicated that both the deep oxidation of Ni2+ into Ni3+ and the reversible reactions in HCO3
– accounted for the ultrahigh capacity of Ni(HCO3)2 in comparison to its generally accepted theoretical
capacity of 297 mAh g–1. Morphological characterizations
revealed that the interconnected hollow structures enabled the enhanced
rate performance and cycling stability, compared to those of the solid
counterpart, because of their larger contact areas with electrolyte
and better buffering effect to accommodate the volume change.
MR imaging directly showed the normal cartilage in all 16 sacroiliac joints of the 8 volunteers. In the 24 patients with AS, cartilage abnormalities were observed in 42 sacroiliac joints. More diagnoses of sacroiliitis were made using MR and CT imaging than using radiography (P < 0.001). Therefore, low-field-strength MR can be useful in detecting early sacroiliitis in patients with AS. MR imaging was able to reveal early cartilage changes and bone marrow edema, which could not be found by either CT or radiography.
BackgroundOsteoporotic vertebral compression fracture (OVCF) is a common type of fracture, and percutaneous kyphoplasty (PKP) is an eligible solution to it. Previous studies have revealed that both the volume and filling pattern of bone cement correlate with the clinical outcomes after PKP procedure. However, the role of bone cement distribution remains to be illustrated.MethodsTo retrospectively evaluate the relationship between the bone cement distribution and the clinical outcomes of unilateral PKP, we enrolled 73 OVCF patients receiving unilateral PKP treatment. All the intervened vertebrae were classified into three groups based on the bone cement distribution observed on postoperative X-ray films. Preoperative and postoperative radiographic parameters including the vertebral height and kyphotic Cobb angle were recorded, and anterior vertebral height restoration rate (AVHRR) and Cobb angle correction (CR) were then calculated to assess the vertebral height reconstruction. Preoperative and postoperative Oswestry Disability Index (ODI) and visual analogue scale (VAS) were adopted by interviewing patients to assess the mobility improvement and pain relief. Demographic data, body mass index (BMI), lumbar bone mineral density (evaluated by BMD T-score) of each patient, bone cement volume (BV), and bone cement extravasation (BE) were also recorded. Between- and within-group comparisons and multivariable correlation analysis were carried out to analyze the data.ResultsVAS and ODI scores were both significantly improved in all of the enrolled cases with no significant differences between groups. Among the three groups, the average age, AVHRR, and BV were significantly different. Occurrence of BE was significantly different between two of the three groups. AVHRR was demonstrated to correlate negatively with preoperative anterior vertebral height ratio and positively with preoperative Cobb angle, CR, diffusion score, and ODI changes.ConclusionsBone cement distribution is a potential predictor to the reconstructive effects in unilateral PKP for OVCFs. Bone cement distribution is associated with AVHRR and BV, as well as the risk of BE occurrence. Greater bone cement distribution may indicate better vertebral restoration along with a higher BE risk.
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