Fitzpatrickfrom1174
ficant potential to be used as putative drugs.
we identified a novel ferroptosis-related gene signature for prognostic prediction in glioma patients and revealed the relationship between ferroptosis-related genes and immune checkpoint molecules.
we identified a novel ferroptosis-related gene signature for prognostic prediction in glioma patients and revealed the relationship between ferroptosis-related genes and immune checkpoint molecules.The volumes of a cell [cell volume (CV)] and its organelles are adjusted by osmoregulatory processes. During pinocytosis, extracellular fluid volume equivalent to its CV is incorporated within an hour and membrane area equivalent to the cell's surface within 30 min. Since neither fluid uptake nor membrane consumption leads to swelling or shrinkage, cells must be equipped with potent volume regulatory mechanisms. Normally, cells respond to outwardly or inwardly directed osmotic gradients by a volume decrease and increase, respectively, i.e., they shrink or swell but then try to recover their CV. However, when a cell death (CD) pathway is triggered, CV persistently decreases in isotonic conditions in apoptosis and it increases in necrosis. One type of CD associated with cell swelling is due to a dysfunctional pinocytosis. Methuosis, a non-apoptotic CD phenotype, occurs when cells accumulate too much fluid by macropinocytosis. In contrast to functional pinocytosis, in methuosis, macropinosomes neither recycle nosicular membrane, phosphoinositides, monomeric G proteins and their targets, as well as the submembranous cytoskeleton. Our aim is to highlight important cellular mechanisms, components, and processes that may lead to methuotic CD upon their derangement.[This corrects the article DOI 10.3389/fcell.2020.600926.].
High myopia with alopecia areata in the occipital region has been observed in patients with Knobloch syndrome caused by
mutations. This study investigated other possible genetic causes of high myopia in patients with alopecia areata in the cranial midline.
Six patients with early onset high myopia and alopecia areata in the cranial midline were recruited. Targeted high-throughput sequencing was performed on the proband's DNA to detect potential pathogenic variants. Cosegregation analysis was performed for available family members. Minigene assay and RNA Sequencing were used to validate the abnormality of possible splicing change and gross deletion. Ophthalmological and neuroimaging examinations were performed.
Eight novel and one known loss-of-function mutants were detected in all six patients, including a gross deletion detected by RNA sequencing. Four
mutants in three patients with scalp leisure in the occipital region; and five
mutations in three patients with scalp leisure in the parietal region. Further assessments indicated that patients with
mutations had Knobloch syndrome, and the patients with
mutations had Poretti-Boltshauser syndrome.
Our study found that early onset high myopia with midline alopecia areata could be caused not only by mutations of the
gene but also by mutations in the
gene. To our knowledge, we are the first to observe scalp defects in patients with
mutations. High myopia with alopecia areata in the cranial midline could be treated as an early diagnostic clue for ophthalmologists to consider the two kinds of rare diseases.
Our study found that early onset high myopia with midline alopecia areata could be caused not only by mutations of the COL18A1 gene but also by mutations in the LAMA1 gene. To our knowledge, we are the first to observe scalp defects in patients with LAMA1 mutations. High myopia with alopecia areata in the cranial midline could be treated as an early diagnostic clue for ophthalmologists to consider the two kinds of rare diseases.In vitro differentiation or expansion of stem and progenitor cells under chemical stimulation or genetic manipulation is used for understanding the molecular mechanisms of cell differentiation and self-renewal. However, concerns around the cell identity of in vitro-cultured cells exist. Bioinformatics methods, which rely heavily on signatures of cell types, have been developed to estimate cell types in bulk samples. The Tabula Muris Senis project provides an important basis for the comprehensive identification of signatures for different cell types. Here, we identified 46 cell type-specific (CTS) gene clusters for 83 mouse cell types. We conducted Gene Ontology term enrichment analysis on the gene clusters and revealed the specific functions of the relevant cell types. Next, we proposed a simple method, named CTSFinder, to identify different cell types between bulk RNA-Seq samples using the 46 CTS gene clusters. We applied CTSFinder on bulk RNA-Seq data from 17 organs and from developing mouse liver over different stages. We successfully identified the specific cell types between organs and captured the dynamics of different cell types during liver development. We applied CTSFinder with bulk RNA-Seq data from a growth factor-induced neural progenitor cell culture system and identified the dynamics of brain immune cells and nonimmune cells during the long-time cell culture. We also applied CTSFinder with bulk RNA-Seq data from reprogramming induced pluripotent stem cells and identified the stage when those cells were massively induced. Finally, we applied CTSFinder with bulk RNA-Seq data from in vivo and in vitro developing mouse retina and captured the dynamics of different cell types in the two development systems. The CTS gene clusters and CTSFinder method could thus serve as promising toolkits for assessing the cell identity of in vitro culture systems.Tumor growth and metastasis are responsible for breast cancer-related mortality. Andrographolide (Andro) is a traditional anti-inflammatory drug used in the clinic that inhibits NF-κB activation. selleck inhibitor Recently, Andro has been found in the treatment of various cancers. Andro inhibits breast cell proliferation and invasion and induces apoptosis via activating various signaling pathways. Therefore, the underlying mechanisms with regard to the antitumor effects of Andro still need to be further confirmed. Herein, a MMTV-PyMT spontaneous luminal-like breast cancer lung metastatic transgenic tumor model was employed to estimate the antitumor effects of Andro on breast cancer in vivo. Andro significantly inhibited tumor growth and metastasis in MMTV-PyMT mice and suppressed the cell proliferation, migration, and invasion of MCF-7 breast cancer cells in vitro. Meanwhile, Andro significantly inhibited the expression of NF-κB, and the downregulated NF-κB reduced miR-21-5p expression. In addition, miR-21-5p dramatically inhibited the target gene expression of programmed cell death protein 4 (PDCD4).