Notes

An introduction to your Japanese Irregular Exotropia Multicenter Study through the Mandarin chinese Association for Child fluid warmers Ophthalmology and also Strabismus.
The present results expanded the mutational spectrum of the BSCL2 gene in the Chinese population and suggested that introns 2 and 3 of BSCL2 are prone to recombination. Thus, exon 3 deletion should be considered for patients with CGL2 when only one BSCL2 variant is detected through WES.The Nemo‑like kinase (NLK), a conserved serine/threonine kinase, plays a critical role in the regulation of a variety of transcription factors, with important roles in determining cell fate. Although recent studies have demonstrated decreased expression patterns of NLK in various types of human cancer, the functional mechanism of NLK in cancer development has not been elucidated. Here, in the present study overexpression of NLK was found to inhibit the growth and migration of the non‑small cell lung cancer A549 cell line. NLK was subsequently found to interact with 14‑3‑3ζ (also known as YWHAZ), which is responsible for E‑cadherin silencing during epithelial‑mesenchymal transition (EMT). Furthermore, NLK overexpression was able to restore the expression of E‑cadherin inhibited by 14‑3‑3ζ. Notably, NLK interacts with 14‑3‑3ζ and prevents its dimerization, which is essential for 14‑3‑3ζ stability and function. By fusing two copies of the 14‑3‑3ζ gene, via a Gly‑rich linker, a non‑dissociable dimer of 14‑3‑3ζ was formed. It was found that NLK was unable to restore the expression of E‑cadherin inhibited by the overexpression of the fused dimer of 14‑3‑3ζ. In addition, the increased ability of migration induced by the overexpression of fused 14‑3‑3ζ dimer could not be altered by NLK overexpression. The results from the present study indicate that NLK is a negative regulator of 14‑3‑3ζ and plays a tumor suppressive role in the inhibition of cancer cell migration.MicroRNA (miRNA/miR)‑21‑5p has been proposed as an oncogenic miRNA in human tumors; however, the exact role of miR‑21‑5p has not been fully determined in endometrial cancer. SRY‑box 17 (SOX17) is associated with endometrial cancer development and progression; however, the regulatory mechanisms underlying SOX17 expression in endometrial cancer remain unclear. In the present study, tumor samples were collected from 160 postmenopausal women with endometrial cancer. All tumor samples were examined for miR‑21‑5p expression by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The results demonstrated that miR‑21‑5p expression was associated with shorter overall survival. In addition, overexpression of miR‑21‑5p promoted epithelial to mesenchymal transition (EMT), whereas silencing miR‑21‑5p reversed EMT in endometrial cancer cell lines. Using RT‑qPCR and western blotting, it was revealed that overexpressing miR‑21‑5p significantly inhibited SOX17 protein expression in endometrial cancer cell lines. Furthermore, as determined by luciferase reporter assay, ectopic expression of miR‑21‑5p inhibited the activity of the SOX17 mRNA 3'‑untranslated region (3'UTR), whereas silencing miR‑21‑5p promoted the activity of the SOX17 mRNA 3'UTR in endometrial cancer cell lines. Overexpression of SOX17 promoted mesenchymal to epithelial transition, whereas silencing SOX17 induced EMT in endometrial cancer cell lines. In addition, tumor SOX17 expression was associated with better overall survival. Therefore, it may be concluded that miR‑21‑5p promotes EMT by targeting SOX17 in human endometrial cancer.Emerging evidence suggests that long non‑coding RNAs (lncRNAs) play pivotal roles in cancer progression, including in intrahepatic cholangiocarcinoma (IHCC). The overexpression of lncRNA ZEB1 antisense 1 (ZEB1‑AS1) has been discovered in several types of cancer; however, the clinical significance and functional role of ZEB1‑AS1 in IHCC have not yet been determined. In the present study, ZEB1‑AS1 was found to be upregulated in IHCC cell lines and tissues. A high ZEB1‑AS1 expression was associated with clinical progression and a poor survival of patients with IHCC, and was identified as an independent risk factor for a poor prognosis. Nimodipine cell line In addition, ZEB1‑AS1 promoted the proliferation and metastasis of IHCC cells both in vitro and in vivo. ZEB1‑AS1 was demonstrated to increase the expression of ZEB1 by sponging miR‑200a and to thereby accelerate epithelial‑mesenchymal transition (EMT). On the whole, the findings of the present study demonstrate that ZEB1‑AS1 promotes proliferation and metastasis in IHCC, and induces EMT through the miR‑200a/ZEB1 signaling pathway. ZEB1‑AS1 may thus be a promising prognostic biomarker and essential therapeutic target for IHCC.Non‑small cell lung carcinoma (NSCLC) accounts for 85% of all lung cancers and the five‑year survival rate is ~1% in the late stage. Circular RNAs (circRNAs) were reported to be involved in the progression of diverse human cancers. However, the role of circ‑ACACA in NSCLC progression remains elusive. Quantitative polymerase chain reaction was conducted to detect the expression levels of circ‑ACACA and microRNA (miR)‑1183 in NSCLC tissues and cells. A Cell Counting Kit‑8 assay and transwell assay were employed to check proliferation and migration, respectively. Metabolic alternations in NSCLC cells were monitored by the Seahorse XFe96 analyzer. The protein levels of cellular myelocytomatosis, matrix metallopeptidase 9, glucose transporter 1, phosphatase and tensin homolog, phosphoinositide 3‑kinases (PI3K), phosphorylated PI3K (p‑PI3K), protein kinase B (PKB) and p‑PKB in samples were measured by western blotting. The interaction between circ‑ACACA and miR‑1183 was predicted by circular RNA Interactome, which was verified by dual‑luciferase reporter assay, RNA immunoprecipitation assay and RNA pull‑down assay. Xenograft tumor model was established to investigate the biological roles of circ‑ACACA in vivo. The level of circ‑ACACA was markedly upregulated in NSCLC tissues and cells, which was contrary to the expression of miR‑1183. Knockdown of circ‑ACACA inhibited proliferation and migration of NSCLC cells and also reduced the glycolysis rate. In addition, miR‑1183 was a target of circ‑ACACA and its downregulation reversed circ‑ACACA silencing‑mediated inhibitory impact on NSCLC progression. Further studies indicated that circ‑ACACA regulated the PI3K/PKB pathway through interacting with miR‑1183 and downregulation of circ‑ACACA suppressed tumor growth. Knockdown of circ‑ACACA impeded NSCLC progression by sponging miR‑1183 and inactivating the PI3K/PKB signaling pathway.Congenital talipes equinovarus (CTEV) is a common birth defect with an unclear genetic pathogenesis that results from both genetic and environmental factors. The present study aimed to identify novel variants in patients with CTEV using whole‑exome sequencing (WES) and to investigate the genetic factors responsible for the development of CTEV.A cohort of nine neonates/infants with suspected CTEV was recruited. Subsequently, sequential tests, including chromosome karyotyping and WES, were performed for each of the participants. Familial validation was performed using Sanger sequencing and low‑coverage copy‑number variation (CNV) sequencing. A novel CNV containing the mediator complex subunit 13L gene at 12q24.21‑q24.23 was detected by WES and further investigated by CNVseq. Additionally, a novel de novo missense variation, transforming growth factor‑β receptor 2 c.1280T>C, was identified by WES and further investigated by Sanger sequencing. The two identified variations were hypothesized to be causative genetic factors for the development of CTEV in the two cases the variations were identified in. In the present study, two pathogenic variations (one CNV and one single‑base variation) were detected in two Chinese families with CTEV. The results of the present study may aid in investigating the molecular basis of CTEV; however, further investigation is required.It is commonly known that the specific function of a given ATPase associated with diverse cellular activities protein (i.e., a member of the AAA superfamily of proteins) depends primarily on its subcellular location. The microtubule‑severing protein fidgetin (Fign) possesses a nuclear localization signal (NLS) that facilitates its translocation to the nucleus, where its assembly is finalized; here, Fign contributes to the regulation of microtubule configuration by cutting and trimming microtubule polymers. In the present study, Fign was found to be a nuclear protein, whose N‑terminal sequence (SSLKRKAFYM; residues 314‑323) acts as an NLS. Following substitution (KR to NN; 317‑318) or deletion (NT; 314‑323) mutations within the NLS, Fign, which is predominantly expressed in the nucleus, was found to reside in the cytoplasm of transfected cells. Furthermore, Fign was found to have an essential role in microtubule severing by preferentially targeting highly‑tyrosinated microtubules (tyr‑MTs). Mutation of the Fign NLS did not affect its microtubule‑severing function or the cleavage of tyr‑MTs, but did affect the cellular distribution of the Fign protein itself. Taken altogether, an NLS for Fign was identified, and it was demonstrated that the basic amino acids K317 and R318 are necessary for regulating its entry into the nucleus, whereas an increase in Fign in the cytosol due to mutations of the NLS did not affect its cleavage function.Total saponins extracted from Dioscorea collettii (TSD), extracts of the Chinese herb Dioscorea, are thought to exhibit therapeutic benefit in gouty arthritis. However, its exact mechanism remains unclear. The current study aimed to elucidate the underlying mechanisms by investigating the effects of TSD on the inflammation induced by monosodium urate (MSU) crystals in THP‑1 macrophages. The viability of THP‑1 macrophages was examined using the MTT assay and the levels of inflammatory cytokines, including interleukin (IL)‑1β, IL‑18 and tumor necrosis factor (TNF)‑α, released by the cells were quantitatively measured using ELISA kits. The results revealed that the protein level of cluster of differentiation 11b increased in THP‑1 cells treated with 100 ng/ml phorbol ester, suggesting that monocytic THP‑1 cells were successfully differentiated into macrophages. TSD decreased the levels of inflammatory cytokines, including TNF‑α, IL‑18 and IL‑1β, secreted by THP‑1 macrophages. As the release of IL‑1β and IL‑18 is dependent on the NLR family pyrin domain containing 3 (NALP3) inflammasome and caspase‑1, the current study investigated the effect of TSD on the aforementioned proteins. The results revealed that TSD decreased the protein levels of NALP3 and apoptosis‑associated speck‑like, which serve important roles in the assembly of the NALP3 inflammasome. Furthermore, NALP3 inflammasome‑related proteins were also decreased by TSD in rotenone induced THP‑1 macrophages, TSD inhibited the activation of caspase‑1 and rotenone‑induced NALP3 inflammasome activation in THP‑1 macrophages. The results obtained in the current study revealed that TSD attenuated MSU crystal‑induced inflammation by inhibiting rotenone‑induced activation of the NALP3 inflammasome and caspase‑1, suggesting that these two proteins may be novel targets for the treatment of gouty arthritis.
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