Yinxieling decoction ameliorates psoriasis by regulating the differentiation and functions of Langerhans cells via the TGF-ß1/PU.1/IL-23 signal axis.

Langerhans cells (LCs) play a critical role in skin immune responses and the development of psoriasis. Yinxieling (YXL) is a representative Chinese herbal medicine for the treatment of psoriasis in South China. It was found to improve psoriasis without obvious side effects in the clinic. Here we attempted to clarify whether and how YXL regulates the differentiation and functions of LCs in Imiquimod (IMQ)-induced psoriasis in vivo and induced LCs in vitro. The Psoriasis Area Severity Index (PASI) score was used to evaluate the efficacy of YXL for IMQ-induced psoriasis-like mice. Flow cytometry was utilized to analyze the effects of YXL, to regulate the differentiation, migration, maturation, and antigen presentation of LCs. The results show that YXL significantly alleviated skin inflammation, as reduced in PASI score and classic psoriasis characteristics in pathological sections. Although there was no effect on the proportion of total DCs in the skin-draining lymph nodes, the expression of epidermal LCs and its transcription factor PU.1 were both markedly inhibited. LCs were also prevented from migrating from epidermal to skin-draining lymph nodes and mature. In addition, the number of LCs carrying antigens in the epidermis increased, which suggested that YXL could effectively prevent LCs from presenting antigens. In vitro, YXL had a significant impact on inhibiting the differentiation of LCs. Further data showed that YXL decreased the relative expression of transforming growth factor-ß (TGFß) messenger RNA (mRNA) and interleukin-23 (IL-23) mRNAs. Thus, YXL alleviates psoriasis by regulating differentiation, migration, maturation, and antigen presentation via the TGFß/PU.1/IL-23 signal axis.

FTO promotes the progression of retinoblastoma through YTHDF2-dependent N6-methyladenosine modification in E2F3.

Early treatment of retinoblastoma (RB) has significantly improved clinical outcomes. N6-methyladenosine (m6A) methylation is crucial for cancer progression. Thus, we investigated the role of FTO-dependent demethylation in RB and its underlying mechanisms. The biological behavior of RB cells was analyzed using cell counting kit-8, colony formation analysis, transwell assay, flow cytometry, and western blot analysis. m6A modification was evaluated using methylated RNA immunoprecipitation and dual-luciferase reporter assays, and E2F3 stability was assessed using Actinomycin D. The roles of FTO and E2F3 were also elucidated in vivo. These results indicated that FTO was highly expressed in RB cells with low m6A levels. FTO knockdown inhibited RB cell growth, migration, invasion, and epithelial-mesenchymal transition and arrested the cell cycle at the G0/G1 phase. Mechanistically, FTO interference promoted m6A methylation of E2F3, which was recognized by YTHDF2, thereby reducing mRNA stability. E2F3 overexpression partially rescued the effects of FTO knockdown on biological behavior. Moreover, FTO knockdown reduced tumor weight, tumor volume, ki67 expression, and tumor cell infiltration by mediating E2F3. Taken together, FTO silencing inhibited the malignant processes of RB by suppressing E2F3 in an m6A-YTHD2-dependent manner. These findings suggest that FTO is a novel therapeutic target for RB.

The Connection between High Myopia Patients and MiR-708a or MiR-148 Expression Levels in Aqueous Studies of Visual Acuity.

Myopia goes far beyond the inconvenience it brings. It is a prevailing and vision-threatening eye disease, especially in Asia. Aberrantly expressed miR-708a and miR-148 are critical for accurate diagnosis, good prognosis, and precise response prediction of myopia. In this paper, we aim to examine the potential contributions of miR-708a, miR-148a, and PAX6 to high myopia (HM). First, aqueous samples were taken from 25 exclusively HM eyes and 25 exclusively cataract eyes. For next-generation sequencing and bioinformatics analysis, RNA from sample 30one was used. Twenty more samples were used for RT-qPCR. 341 miRNAs in total were found in HM eyes; 249 mature miRNAs and 17 new miRNAs showed differential expression. The expression of hsa-miR-127-3p, hsa-let-7i-5p, and hsa-miR-98-5p was identified using RT-qPCR. MiR-708a and miR-148, which may be linked to the development of myopia and serve as possible biomarkers, are notably highly expressed in atrial tissues of HM patients. Our findings may help deepen the understanding of the mechanisms behind the high expression of miR-708a and miR-148 in atrial tissues of patients with HM.

Vanillic acid attenuates H2O2-induced injury in H9c2 cells by regulating mitophagy via the PINK1/Parkin/Mfn2 signaling pathway.

Vanillic acid, a phenolic compound mainly obtained from the foot of Picrorhiza scrophulariiflora Pennell, has been demonstrated to possess a cardiovascular-protective effect in previous studies. However, there is lack of research on vanillic acid protecting cardiomyocytes from oxidative stress injury by mediating mitophagy. In the present study, oxidative stress injury in the H9c2 cell line was induced by H2O2. Our results confirmed that vanillic acid mitigated apoptosis and injury triggered by oxidative stress, evidenced by the decline in production of reactive oxygen species and malondialdehyde and level of lactate dehydrogenase and the increase of superoxide dismutase and glutathione. The use of vanillic acid could also improve the polarization of mitochondrial membrane potential and decrease the cellular calcium level. After treatment by vanillic acid, impaired autophagy flux and mitophagy were improved, and the length of mitochondria was restored. Vanillic acid increased the expression of PINK1, Parkin, Mfn2, and the ratio of LC3-II/LC3-I and decreased the expression of p62. But, under the intervention of mitophagy inhibitor 3-MA, vanillic acid could not change the expression of PINK1/Parkin/Mfn2 and downstream genes to affect cell autophagy, mitophagy, and mitochondrial function. Our findings suggested that vanillic acid activated mitophagy to improve mitochondrial function, in which the PINK1/Parkin/Mfn2 pathway could be the potential regulatory mechanism.

Toll-like receptor 3 gene regulates cataract-related mechanisms via the Jagged-1/Notch signaling pathway.

Epithelial-melancholy transition (EMT) is the main cause of organ fibrosis and a common pathogenetic mechanism in most cataracts. This study aimed to explore the molecular mechanism of Toll-like receptor (TLR)-3 in the occurrence and development of post-cataract EMT and to provide new ideas for the prevention and treatment of posterior capsule opacification (PCO). In the presence or absence of TLR3, the human lens epithelial cell (LEC) line, SRA01/04, was treated with the transforming growth factor (TGF)-ß2. Cell counting kit-8 (CCK-8) and Transwell assays were used to analyze the cell proliferation, migration, and invasion. The expression levels of proteins and RNAs were detected by western blotting and quantitative polymerase chain reaction (qPCR) experiments. Functional gain and loss studies showed that TLR3 regulates the proliferation, migration, and invasion of LECs and EMT induced by TGF-ß2. Moreover, TLR3 regulates the expression of Jagged-1, Notch-1, and Notch-3 These findings indicate that TLR3 prevents the progression of lens fibrosis by targeting the Jagged-1/Notch signaling pathway to regulate the proliferation, migration, and invasion of LECs, and TGF-ß2-induced EMT. Therefore, the TLR3-Jagged-1/Notch signaling axis may be a potential therapeutic target for the treatment of fibrotic cataracts.

A newly nitrobenzoxadiazole (NBD)-fused reversible fluorescence probe for pH monitoring and application in bioimaging.

pH plays an essential role in virtually all biological processes, which thus needs to be tightly regulated. Especially small changes in pH value in biological systems will affect the normal metabolic functions of animals and plants. Therefore, it is very important to accurately track changes in pH in biological systems. Herein, we rationally fabricated a new molecular pH probe (NBD-pbz) based on conjugation of the 2-Piperazin-1-yl-1,3-benzothiazole (pbz) and 7-nitro-1,2,3-benzoxadiazole (NBD) building blocks. The following test on NBD-pbz revealed that it can offer a sensitive and selective tracking of pH changes from 3.2 to 7.6 with pKa 5.51, and not only in eukaryotic cells (especially the imaging of ocular tumor cell OCM-1) and zebrafish but also in mung bean sprouts via fluorometric turn on response and an intramolecular charge transfer (ICT) based working mechanism strategy. Therefore, this NBD-pbz probe not only replenishes the current repertory of molecular pH probes but also extends the application of pH probes to monitor pH variation in the plant kingdom, which will undoubtedly arouse greater research interest in the field.