Effect of 460 nm blue light PBM on human MeWo melanoma cells.

Photobiomodulation (PBM) using 460 nm blue light has been shown to have an inhibitory effect on skin cancer cells. In this study, we used a continuous LED light source with a wavelength of 460 nm and designed various combinations of power density (ranging from 6.4 to 25.6 mW) and dose (ranging from 0.96 to 30.72 J/cm2) to conduct treatment experiments on MeWo cells to investigate the effects of blue light on MeWo melanoma cells. We are focusing on cell viability, cytotoxicity, mitochondrial function, oxidative stress, and apoptosis. We found that blue light inhibits these melanoma cells through oxidative stress and DNA damage, and this inhibition intensifies at higher irradiance levels. Although the cells initially attempt to resist the stress induced by the treatment, they eventually undergo apoptosis over time. These findings contribute to understanding melanoma's molecular response to blue light PBM, lay the groundwork for future clinical applications.

Construction and verification of atopic dermatitis diagnostic model based on pyroptosis related biological markers using machine learning methods.

OBJECTIVE: The aim of this study was to construct a model used for the accurate diagnosis of Atopic dermatitis (AD) using pyroptosis related biological markers (PRBMs) through the methods of machine learning. METHOD: The pyroptosis related genes (PRGs) were acquired from molecular signatures database (MSigDB). The chip data of GSE120721, GSE6012, GSE32924, and GSE153007 were downloaded from gene expression omnibus (GEO) database. The data of GSE120721 and GSE6012 were combined as the training group, while the others were served as the testing groups. Subsequently, the expression of PRGs was extracted from the training group and differentially expressed analysis was conducted. CIBERSORT algorithm calculated the immune cells infiltration and differentially expressed analysis was conducted. Consistent cluster analysis divided AD patients into different modules according to the expression levels of PRGs. Then, weighted correlation network analysis (WGCNA) screened the key module. For the key module, we used Random forest (RF), support vector machines (SVM), Extreme Gradient Boosting (XGB), and generalized linear model (GLM) to construct diagnostic models. For the five PRBMs with the highest model importance, we built a nomogram. Finally, the results of the model were validated using GSE32924, and GSE153007 datasets. RESULTS: Nine PRGs were significant differences in normal humans and AD patients. Immune cells infiltration showed that the activated CD4+ memory T cells and Dendritic cells (DCs) were significantly higher in AD patients than normal humans, while the activated natural killer (NK) cells and the resting mast cells were significantly lower in AD patients than normal humans. Consistent cluster analysis divided the expressing matrix into 2 modules. Subsequently, WGCNA analysis showed that the turquoise module had a significant difference and high correlation coefficient. Then, the machine model was constructed and the results showed that the XGB model was the optimal model. The nomogram was constructed by using HDAC1, GPALPP1, LGALS3, SLC29A1, and RWDD3 five PRBMs. Finally, the datasets GSE32924 and GSE153007 verified the reliability of this result. CONCLUSIONS: The XGB model based on five PRBMs can be used for the accurate diagnosis of AD patients.

Reversible Recognition-Based Boronic Acid Probes for Glucose Detection in Live Cells and Zebrafish.

Glucose, a critical source of energy, directly determines the homeostasis of the human body. However, due to the lack of robust imaging probes, the mechanism underlying the changes of glucose homeostasis in the human body remains unclear. Herein, diboronic acid probes with good biocompatibility and high sensitivity were synthesized based on an ortho-aminomethylphenylboronic acid probe, phenyl(di)boronic acid (PDBA). Significantly, by introducing the water-solubilizing group -CN directly opposite the boronic acid group and -COOCH3 or -COOH groups to the ß site of the anthracene in PDBA, we obtained the water-soluble probe Mc-CDBA with sensitive response (F/F0 = 47.8, detection limit (LOD) = 1.37 µM) and Ca-CDBA with the highest affinity for glucose (Ka = 4.5 × 103 M-1). On this basis, Mc-CDBA was used to identify glucose heterogeneity between normal and tumor cells. Finally, Mc-CDBA and Ca-CDBA were used for imaging glucose in zebrafish. Our research provides a new strategy for designing efficient boronic acid glucose probes and powerful new tools for the evaluation of glucose-related diseases.

A near-infrared, colorimetric and ratiometric fluorescent sensor with high sensitivity to hydrogen peroxide and viscosity for solutions detection and imaging living cells.

Considering to the importance of hydrogen peroxide (H2O2) in a number of pathological processes and fluorescence sensor as a powerful tool for imaging and therapy of H2O2-related diseases, herein, a near-infrared fluorescent sensor for colorimetric and ratiometric detecting H2O2 and viscosity, named NCR, was constructed and reported. Its long emission wavelength (670 nm) avoids the interference of biological autofluorescence. When NCR interacted with 10 equiv. of H2O2, colorimetric characteristic provides a clear naked eye recognition (colourless turned to green under UV light and light purple turned to colorless under visible light). In addition, NCR shows high sensitivity to viscosity with or without the addition of H2O2. It was also found alkaline environment contribute to enhance fluorescence response to H2O2. A suitable water-octanol partition coefficient (logP, 0.521 ± 0.003) and low cytotoxicity displayed that NCR is very favorable to image living cells. Furthermore, exogenous and endogenous H2O2 was detected successfully by NCR in living Hela cells. These studies indicate that NCR has great potential to develop as a practical tool for monitoring H2O2 level in biological process.

High-Frequency Ultrasound and Shear Wave Elastography in Quantitative Differential Diagnosis of High-Risk and Low-Risk Basal Cell Carcinomas.

OBJECTIVES: The purpose of this study was to investigate the value of high-frequency ultrasound and shear wave elastography (SWE) in quantitative differential diagnosis of high-risk and low-risk basal cell carcinomas (BCCs). METHODS: A total of 52 BCCs confirmed by surgical pathology were studied. Taking pathologic subtypes as reference, all the cases were classified as high-risk BCCs or low-risk BCCs. High-frequency ultrasound parameters and SWE parameters recorded preoperatively were retrospectively analyzed. The differences of two groups were compared. RESULTS: There were 12 high-risk BCCs and 40 low-risk BCCs. The maximum infiltration depth (MID) and average Young's modulus (Eave ) of high-risk BCCs were 5.76 ± 2.56 mm and 31.61 ± 12.36 kPa, whereas of low-risk BCCs were 4.29 ± 1.77 mm and 20.04 ± 4.74 kPa, respectively, P < .05. The area under the receiver operator characteristic curve of MID and Eave were 0.714 and 0.811, P > .05. Taking 5.5 mm of MID and 24.45 kPa of Eave as the threshold for the diagnosis of high-risk BCCs, the sensitivity, specificity, and accuracy were 58.3%, 82.5%, 76.9% and 75.0%, 82.5%, 80.8%, P > .05. CONCLUSIONS: The MID and Eave of the lesion can be used to determine the recurrence risk of BCCs and provide a reference for the development of individualized treatment plans.

Spinal neurofibromatosis with NF1 mutation in a classic neurofibromatosis type 1 family: A case report and literature review.

BACKGROUND: Spinal neurofibromatosis (SNF) is a related form of Neurofibromatosis type 1 (NF1) with a low incidence. Here, we report a SNF patient with NF1 (OMIM *613113) mutation in a classic NF1 family to enrich the case data. METHODS: We presented the clinical data of a 27-year-old female suffered from SNF. Two NF1 individuals (the mother and the brother) in the patient's family were also described. In the SNF patient, tumors in cervical were removed by surgical operation after the spinal MRI evaluation. Hematoxylin-eosin staining and immunohistochemistry were performed to better characterize the excised tumors. NF1 exons of the patient and her NF1 families were further sequenced by the next-generation sequencing technology. RESULTS: The patient developed irregular café-au-lait macules, multi-subcutaneous nodules, recurrent numbness, and weakness of both lower extremities. Multiple neurofibromas were found in the whole spine by spinal MRI. Tumor-like cells and hyperplasia of ganglion cells were found in the excised tissue by H&E staining and immunohistochemistry, respectively. One-year follow-up on the SNF patient showed that after the surgery lower limb pain, numbness and convulsion were completely relieved. A common germ-line pathogenic mutation (NM_000267.3:c.1721 + 3A>G) was found in both the SNF patient and her classic NF1 families. CONCLUSION: A case of SNF with classic NF1 mutation in a classic NF1 family was identified for the first time, indicating that SNF may share the same gene mutation with NF1, while the different manifestation of NF1 and SNF may be related to gene modification.

LRRC8A potentiates temozolomide sensitivity in glioma cells via activating mitochondria-dependent apoptotic pathway.

Chloride (Cl-), a primary anion in the extracellular fluid, plays an important role in a variety of physiological and pathological processes, such as cell apoptosis and proliferation. However, the information about Cl- in cancer cell apoptosis and chemoresistance is poorly understood. In the present study, we found that temozolomide (TMZ) treatment led to a decrease in intracellular concentration of Cl- ([Cl-]i) in both U87 and TMZ-resistant U87/R glioma cells. The decrease in [Cl-]i was more noticeable in U87 cells than in U87/R cells. Moreover, the expression of LRRC8A was reduced in U87/R cells compared with U87 cells. LRRC8A downregulation inhibited TMZ, induced the decrease in [Cl-]i and abolished the difference of [Cl-]i between U87 cells and U87/R cells. Knockdown of LRRC8A using small interfering RNA attenuated TMZ-induced U87 cell growth inhibition and apoptosis, while overexpression of LRRC8A by adenoviral infection enhanced the effect of TMZ on U87 and U87/R cell viability and apoptosis. Furthermore, LRRC8A downregulation inhibited TMZ-induced mitochondria-dependent apoptosis, including elevated Bcl-2 expression, reduced Bax expression, cytochrome c release, and caspase nine and caspase three activation. On the contrary, upregulation of LRRC8A augmented the activation of mitochondria-dependent apoptotic pathway in U87 and U87/R cells. In conclusion, this study demonstrates that LRRC8A potentiates TMZ-induced glioma cell apoptosis via promoting mitochondria-dependent apoptosis, suggesting that LRRC8A can be represented as a novel target for drug resistance treatment in glioma cells.

The ultra-early protective effect of ulinastatin on rabbit acute lung injury induced by paraquat.

OBJECTIVE: To study ultra-early pathophysiological changes of rabbit acute lung injury (ALI) caused by paraquat (PQ) and discuss the ultra-early protective effect of ulinastatin on rabbit ALI due to PQ. METHODS: 30 New Zealand white rabbits were randomly divided into a control group, a paraquat group and an ulinastatin intervention group with 10 rabbits in each group. For paraquat group and intervention group a single dose of paraquat (35 mg/kg) was injected intraperitoneally to establish rabbit models of ALI. The control group was injected an equal volume of saline. The intervention group was treated with 100 Ku/kg ulinastatin immediately after the establishment of the ALI model. The respective experimental groups underwent 320-slice CT perfusion scan of pleural at 2h, 4h and 6h time point after modeling to get CTP (CT Perfusion) images and related parameters. 2 mL blood was collected in the marginal ear vein to determine the mass concentration of the vascular endothelial growth factor (VEGF). The animals were killed by air embolism after 6h and lung tissue was taken for pathology observation. RESULTS: The reginal blood flow (rBF) and reginal blood volume (rBV) of paraquat group at 2,4,6 h time point were significantly (P <0.05) lower than those of control group. The intervention group rBF and rBV at 2, 4 and 6 h time points were significantly higher (P <0.05) compared to paraquat group. The permeability surface (rPS) and VEGF mass concentration of paraquat group at 2,4,6 h time point were significantly higher than the control group (P <0.05), and the intervention group rPS and VEGF mass concentrations at 2,4,6h time point were significantly lower (P <0.05) than those of paraquat group. Pathological detection indicators of paraquat group (congestive capillary percentage, the number of red blood cells outside of capillaries, percentage of capillaries with basement membrane damage) were significantly higher (P <0.05) at 6h time point compared with the control group, while significantly lower (P <0.05) in intervention group than in paraquat groups. Pathological observation under light microscope showed in paraquat group obvious inflammatory cell infiltration, alveolar epithelial cell hyperplasia, widened alveolar septum, visible focal hemorrhage, visible acute and chronic inflammatory cell infiltration in bronchioles cavity; under electron microscopy alveolar epithelial cell degeneration and necrosis, vascular welling of the endothelial cells, basement membrane rupture, a lot of exudates in alveolar space. In the intervention group, the above the symptoms were mitigated. CONCLUSION: In the ultra-early stage of rabbit ALI induced by PQ, pulmonary vascular endothelial cell is damaged and serum VEGF mass concentration and pulmonary vascular permeability increase. Early ulinastatin intervention can reduce serum VEGF level and PQ-induced vascular permeability amplitude, indicating that ulinastatin has a protective effect on pulmonary vascular endothelial cells.