Whole-exome sequencing explored mechanism of selpercatinib resistance in RET-rearranged lung adenocarcinoma transformation into small-cell lung cancer: a case report.

Small cell transformation was one mechanism by which EGFR-mutation NSCLC acquired resistance after tyrosine kinase inhibitors (TKIs) treatment. A few reports of small cell transformation occurred in other oncogene-driven lung cancers. We found the first case of transformation of a RET-rearranged lung adenocarcinoma to SCLC after selpercatinib, a novel highly selective RET TKIs. Whole-exome sequencing (WES) was used to explore alteration in gene expression in tumor tissue at initial diagnosis and after transformation into small cell carcinoma. We found that transformed into SCLC tumor tissue had inactivation of RB1 and TP53, with RET fusion was still present. In addition, the APOBEC family of cytidine deaminases appeared amplification. Although RET rearrangement still existed, using another RET TKIs was ineffective, and etoposide plus platinum might be an effective rescue treatment.

lncRNA MIR155HG Alleviates Depression-Like Behaviors in Mice by Regulating the miR-155/BDNF Axis.

Depression is one of most common psychiatric disorders, and the detailed molecular mechanism remains to be fully elucidated. Brain-derived neurotrophic factor (BDNF) is a critical neurotrophic factor that is decreased and closely involved in the development of depression. Noncoding RNAs are central regulators of cellular activities that modulate target genes. However, the roles of long noncoding RNA (lncRNA) MIR155HG and miRNA-155 (miR-155) in the pathophysiology of depression are unclear. In the present study, we aimed to explore the effects of lncRNA MIR155HG and miR-155 on the development of depression and uncover the underlying molecular mechanism. Real-time quantitative polymerase chain reaction was used to examine the expression of MIR155HG and miR-155. Western blotting was applied to measure the expression of BDNF. A luciferase reporter assay was utilized to determine the regulatory relationship between MIR155HG and miR-155. Our current work found that lncRNA MIR155HG and BDNF levels decreased while miR-155 levels increased in the hippocampal region of CUMS (chronic unpredictable mild stress) mice, a well-accepted mouse model of depression. Moreover, MIR155HG rescued while miR-155 exacerbated the depression-like behaviors of CUMS mice. Through bioinformatics analysis and luciferase reporter assays, we found that MIR155HG directly bound to and negatively modulated the expression of miR-155. Moreover, increased miR-155 was found to repress the expression of BDNF, a critical neurotrophic factor that has been reported to alleviate the depression-like behaviors of CUMS mice. Our present study revealed that lncRNA MIR155HG protected CUMS mice by regulating the miR-155/BDNF axis. Our study aimed to understand the pathophysiology of depression and provided potential therapeutic targets to diagnose and treat depression.

Di-2-ethylhexyl phthalate (DEHP) exposure induces sperm quality and functional defects in mice.

Di-2-ethylhexyl phthalate (DEHP) harms mammalian testis development, yet the specific mechanism of its effect on sperm quality and function is unclear. In this study, male mice were administrated DEHP (200 mg/kg/day) via intragastric (i.g.) injection for 35 days. The sperm quality and function of DEHP-exposed mice were evaluated. DEHP exposure reduced the relative testis weight and serum testosterone levels. In addition, sperm count and motility parameters decreased significantly, which led to reduced sperm fertility characterized by reduced acrosome reaction rate, sperm-egg binding capacity and blastocyte formation. DEHP exposure decreased anti-oxidant indicators and the expressions of Cat, Sod1, Prdx6 and Sirt1 in the testis. DEHP-exposure also resulted in decreased proliferating cell nuclear antigen (PCNA) expression in mice testis, as well as the dose-dependent inhibition of the proliferation of GC-1 and GC-2 cells. These phenotypes may be related to increased cell apoptosis characterized by BAX/BCL2 and P53 up-regulation. DEHP exposure resulted in the down-regulation of SIRT1 and p-AKT in mice testis and decreased levels of GC-1and GC-2 cells. DEHP co-incubation with sperm in vitro resulted in decreased tyrosine phosphorylation and progressive motility, as well as p-AKT expression in capacitated sperm. Differential sperm proteomics identified 495 differentially expressed proteins, including 257 proteins down-regulated in the DEHP-exposure group. Bioinformatics analysis showed that proteins involved in sperm-egg interaction and fertilization processes were significantly down-regulated. Pathway analysis demonstrated that the adhesion pathway was enriched in down-regulated proteins, while the pathway associated with ribosomes was enriched in up-regulated proteins. Conclusively, DEHP exposure impaired male fertility by affecting sperm quality and function, and a pathway mediating the DEHP-induced decline in sperm quality and function was identified. The study provides additional information for understanding the molecular mechanisms of DEHP exposure and its effects on male reproduction.

Protocadherin alpha 3 inhibits lung squamous cell carcinoma metastasis and epithelial-mesenchymal transition.

BACKGROUND: Lung squamous cell carcinoma (LUSC) is associated with poor clinical prognosis and lacks available targeted therapy. Given that the major threat of cancer is metastasis, delineation of the molecular mechanism underlying it would help devise therapeutic strategies. OBJECTIVE: To investigate the functional role of protocadherin alpha 3 (PCDHA3) in LUSC, as well as investigate the underlying molecular mechanism. METHODS: Data for PCDHA3 expression and clinical information in The Cancer Genome Atlas (TCGA) were extracted and analyzed in the UALCAN platform. Expression levels of PCDHA3 in LUSC cell lines were analyzed via RT-PCR and western blot. Overexpression of PCDHA3 was conducted via plasmid transfection. CCK-8 and cell cycle assays were utilized to investigate effect of PCDHA3 on cell proliferation. Transwell assay was used to detect migration and invasion. The underlying mechanism was demonstrated via western blot analysis. RESULTS: Our data indicate that PCDHA3 was low expressed in three kinds of LUSC cell lines and best in H520 cells. Furthermore, overexpression of PCDHA3 could significantly impair LUSC cells proliferation, invasion and migration. Moreover, PCHDA3 repressed the biomarkers of mesenchymal (N-cadherin, fibronectin and vimentin) and increased expression of epithelial markers (E-cadherin and α-catenin). On the other hand, PCDHA3 overexpression partially blocked epithelial-mesenchymal transition. CONCLUSIONS: PCDHA3 suppressed the LUSC cells proliferation, invasion and migration via inhibiting the expression of EMT signatures, suggesting that PCDHA3 could serve as a valuable therapeutic target for LUSC therapy.

Circular RNA detection methods: A minireview.

Circular RNA (circRNA), a novel type of covalently closed RNA, is implicated in several developmental and metabolic disease processes. CircRNAs exhibit tissue-specific expression, and are stable, abundant, and highly conserved, making them ideal biomarkers for diagnosis and prognosis. Accurate profiling of circRNA, however, is a prerequisite for their clinical application. Traditional methods such as northern blotting, RT-qPCR, and microarray analysis provide useful but limited information. To address these issues, a number of novel assays have recently emerged, such as droplet digital PCR (ddPCR), isothermal exponential amplification, and rolling cycle amplification, which increase the sensitivity and specificity of circRNA detection. Herein, we summarize the advantages and limitations of the new detection methods and discuss the challenges as well as future directions.

Peroxidase Mimic Activities of Copper Selenide (CuSe) Nanoplates for Sensing H2O2 and L-Cysteine.

Compared with natural enzymes, artificial mimic enzymes have been widely studied for their high stability and cost effectiveness. In this study, CuSe nanoplates as a simulated enzyme which does not contain precious metals, has peroxidase activity. CuSe nanoplates were prepared and characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray energy dispersive spectrometer (EDS). Kinetic studies show that CuSe nanoplates exhibits a higher affinity for 3,3',5,5'-teramethylbenzidine (TMB) than horseradish peroxidase (HRP). The rapid colorimetric determination of H2O2 and L-cysteine were developed based on the catalytic efficiency. The linear range of detection for H2O2 is 5.0×10-6~8.0×10-5 M, and the detection limit is 2.9×10-6 M, while the relative standard error is less than 5%. In addition, L-cysteine was detected with a detection limit of 0.2×10-6 M. The good selectivity of the determination to H2O2 and L-cysteine in aqueous solution was also achieved. CuSe nanoplates as a simulated enzyme for sensor applications would be used in environmental monitoring and biomedical analysis.

[Color stability of ceromer of different thicknesses and resin adhesive materials of different types after accelerated aging].

OBJECTIVE: This study aims to investigate the color stability of ceromer with different thicknesses and different types of resin adhesive materials after accelerated aging and provide references for clinical application and selections. METHODS: Nine groups of experimental samples were used, and each group contained five samples. We made joint samples with ceromer having three different thicknesses (1.00, 0.75, 0.50 mm) combined with three different resin adhesive materials (RelyX Veneer, RelyX Unicem, Filtek Z350 Flow), respectively. All samples were placed into Xenon Lamp Aging Instrument to implement accelerated aging. Spectrophotometer was used to measure the lightness (L*), red green color value (a*), and blue yellow color value (b*) of all samples before and after accelerated aging. The change of lightness (ΔL), red green color value (Δa), blue yellow color value (Δb), and color variation (ΔE) were also calculated. We investigated the influence of ceromer veneer thicknesses and resin adhesive material types on color variation by two-factor analysis of variance. RESULTS: The thickness and type factors showed significant influence on ΔE values, and exhibited interactions (P < 0.05). The ΔE values of all experimental groups were lower than 3.3. After the accelerated aging process, all L*, a*, and b* values of the experimental groups decreased and the ΔL values were lower than 2.0. CONCLUSION: Ceromer veneer thickness and resin adhesive material types could affect the color stability of ceromer veneer and resin adhesive materials. The changes in lightness and color in ceromer veneer and resin adhesive materials are considered clinically acceptable after accelerated aging.

De novo acute megakaryoblastic leukemia with p210 BCR/ABL and t(1;16) translocation but not t(9;22) Ph chromosome.

Acute megakaryoblastic leukemia (AMKL) is a type of acute myeloid leukemia (AML), in which majority of the blasts are megakaryoblastic. De novo AMKL in adulthood is rare, and carries very poor prognosis. We here report a 45-year-old woman with de novo AMKL with BCR/ABL rearrangement and der(16)t(1;16)(q21;q23) translocation but negative for t(9;22) Ph chromosome. Upon induction chemotherapy consisting of homoharringtonine, cytarabine and daunorubicin, the patient achieved partial hematological remission. The patient was then switched to imatinib plus one cycle of CAG regimen (low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor), and achieved complete remission (CR). The disease recurred after 40 days and the patient eventually died of infection. To the best of our knowledge, this is the first report of de novo AMKL with p210 BCR/ABL and der(16)t(1;16)(q21;q23) translocation but not t(9;22) Ph chromosome.