Nomogram Utilizing ABVS Radiomics and Clinical Factors for Predicting ≤ 3 Positive Axillary Lymph Nodes in HR+ /HER2- Breast Cancer with 1-2 Positive Sentinel Nodes.

BACKGROUND: In HR+ /HER2- breast cancer patients with ≤ 3 positive axillary lymph nodes (ALNs), genomic tests can streamline chemotherapy decisions. Current studies, centered on tumor metrics, miss broader patient insights. Automated Breast Volume Scanning (ABVS) provides advanced 3D imaging, and its potential synergy with radiomics for ALN evaluation is untapped. OBJECTIVE: This study sought to combine ABVS radiomics and clinical characteristics in a nomogram to predict ≤ 3 positive ALNs in HR+ /HER2- breast cancer patients with 1-2 positive sentinel lymph nodes (SLNs), guiding clinicians in genetic test candidate selection. METHODS: We enrolled 511 early-stage breast cancer patients: 362 from A Hospital for training and 149 from B Hospital for validation. Using LASSO logistic regression, primary features were identified. A clinical-radiomics nomogram was developed to predict the likelihood of ≤ 3 positive ALNs in HR+ /HER2- patients with 1-2 positive SLNs. We assessed the discriminative capability of the nomogram using the ROC curve. The model's calibration was confirmed through a calibration curve, while its fit was evaluated using the Hosmer-Lemeshow (HL) test. To determine the clinical net benefits, we employed the Decision Curve Analysis (DCA). RESULTS: In the training group, 81.2% patients had ≤ 3 metastatic ALNs, and 83.2% in the validation group. We developed a clinical-radiomics nomogram by analyzing clinical characteristics and rad-scores. Factors like positive SLNs (OR=0.077), absence of negative SLNs (OR=11.138), lymphovascular invasion (OR=0.248), and rad-score (OR=0.003) significantly correlated with ≤ 3 positive ALNs. The clinical-radiomics nomogram, with an AUC of 0.910 in training and 0.882 in validation, outperformed the rad-score-free clinical nomogram (AUCs of 0.796 and 0.782). Calibration curves and the HL test (P values 0.688 and 0.691) confirmed its robustness. DCA showed the clinical-radiomics nomogram provided superior net benefits in predicting ALN burden across specific threshold probabilities. CONCLUSION: We developed a clinical-radiomics nomogram that integrated radiomics from ABVS images and clinical data to predict the presence of ≤ 3 positive ALNs in HR+ /HER2- patients with 1-2 positive SLNs, aiding oncologists in identifying candidates for genomic tests, bypassing ALND. In the era of precision medicine, combining genomic tests with SLN biopsy refines both surgical and systemic patient treatments.

Polyethylenimine Triggers Dll4 Degradation to Regulate Angiogenesis In Vitro.

The Dll4-Notch signaling pathway plays a crucial role in the regulation of angiogenesis and is a promising therapeutic target for diseases associated with abnormal angiogenesis, such as cancer and ophthalmic diseases. Here, we find that polyethylenimine (PEI), a cationic polymer widely used as nucleic acid transfection reagents, can target the Notch ligand Dll4. By immunostaining and immunoblotting, we demonstrate that PEI significantly induces the clearance of cell-surface Dll4 and facilitates its degradation through the lysosomal pathway. As a result, the activation of Notch signaling in endothelial cells is effectively inhibited by PEI, as evidenced by the observed decrease in the generation of the activated form of Notch and expression of Notch target genes Hes1 and Hey1. Furthermore, through blocking Dll4-mediated Notch signaling, PEI treatment enhances angiogenesis in vitro. Together, our study reveals a novel biological effect of PEI and establishes a foundation for the development of a Dll4-targeted biomaterial for the treatment of angiogenesis-related disease.

Integration of scRNA and bulk RNA-sequence to construct the 5-gene molecular prognostic model based on the heterogeneity of thyroid carcinoma endothelial cell.

Thyroid cancer (TC) is a kind of cancer with high heterogeneity, which leads to significant difference in prognosis. The prognostic molecular processes are not well understood. Cancer cells and tumor microenvironment (TME) cells jointly determine the heterogeneity. However, quite a little attention was paid to cells in the TME in the past years. In this study, we not only reveal that endothelial cells (ECs) are strongly associated with the progress of papillary thyroid cancer (PTC) using single-cell RNA-seq (scRNA-seq) data downloaded from Gene Expression Omnibus (GEO) and WGCNA, but also screen 5 crucial genes of ECs: CLDN5, ABCG2, NOTCH4, PLAT, and TMEM47. Furthermore, the 5-gene molecular prognostic model is constructed, which can predict how well a patient will do on PD-L1 blockade immunotherapy for TC and evaluate prognosis. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrates that PLAT is decreased in TC and the increase of PLAT can restrain the migratory capacity of TC cells. Meanwhile, in TC cells, PLAT suppresses VEGFa/VEGFR2-mediated human umbilical vascular endothelial cell (HUVEC) proliferation and tube formation. Totally, we construct the 5-gene molecular prognostic model from the perspective of EC and provide a new idea for immunotherapy of TC.

Identification of cryptic balanced translocations in couples with unexplained recurrent pregnancy loss based upon embryonic PGT-A results.

PURPOSE: The goal of this study is to determine whether any balanced translocation (BT) had been missed by previous karyotyping in patients with unexplained recurrent pregnancy loss (uRPL). METHODS: This case series included 48 uRPL-affected couples with normal karyotypes. The embryos from these couples have all undergone preimplantation testing for aneuploidies (PGT-A). Based on the PGT-A's results, 48 couples could be categorized into two groups: 17 couples whose multiple embryos were detected with similar structural variations (SVs, segmental/complete) and 31 couples without such findings but who did not develop any euploid embryo despite at least three high-quality blastocysts being tested. The peripheral blood sample of each partner was then collected for mate-pair sequencing (MPseq) to determine whether any of them were BT carriers. RESULTS: MPseq analyses identified 13 BTs in the 17 couples whose multiple embryos had similar SVs detected (13/17, 76.47%) and three BTs in the 31 couples without euploid embryo obtained (3/31, 9.7%). Among the 16 MPseq-identified BTs, six were missed due to the limited resolution of G-banding karyotyping analysis, and the rest were mostly owing to the similar banding patterns and/or comparable sizes shared by the two segments exchanged. CONCLUSION: A normal karyotype does not eliminate the possibility of carrying BT for couples with uRPL. The use of PGT-A allows us to perceive the "carrier couples" missed by karyotyping analysis, providing an increased risk of finding cryptic BTs if similar SVs are always detected on two chromosomes among multiple embryos. Nonetheless, certain carriers with translocated segments of sub-resolution may still go unnoticed.

[Protective effect of Liujing Toutong Tablets on rats with permanent cerebral ischemia via NF-κB signaling pathway].

This study investigated the neuroprotective effects and underlying mechanism of Liujing Toutong Tablets(LJTT) on a rat model of permanent middle cerebral artery occlusion(pMCAO). The pMCAO model was established using the suture method. Eighty-four male SPF-grade SD rats were randomly divided into a sham operation group, a model group, a nimodipine group(0.020 g·kg~(-1)), and high-, medium-, and low-dose LJTT groups(2.8, 1.4, and 0.7 g·kg~(-1)). The Longa score, adhesive removal test and laser speckle contrast imaging technique were used to evaluate the degree of neurological functional impairment and changes in local cerebral blood flow. The survival and mortality of rats in each group were recorded daily. After seven days of continuous administration following the model induction, the rats in each group were euthanized, and brain tissue and blood samples were collected for corresponding parameter measurements. Nissl staining was used to examine pathological changes in brain tissue neurons. The levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-1ß, vascular endothelial growth factor(VEGF), calcitonin gene-related peptide(CGRP), beta-endorphin(ß-EP), and endogenous nitric oxide(NO) in rat serum were measured using specific assay kits. The entropy weight method was used to analyze the weights of various indicators. The protein expression levels of nuclear factor kappa-B(NF-κB), inhibitor kappaB alpha(IκBα), phosphorylated IκBα(p-IκBα), and phosphorylated inhibitor of NF-κB kinase alpha(p-IKKα) in brain tissue were determined using Western blot. Immunohistochemistry was used to detect the protein expression of chemokine-like factor 1(CKLF1) and C-C chemokine receptor 5(CCR5) in rat brain tissue. Compared with the sham operation group, the model group showed significantly higher neurological functional impairment scores, prolonged adhesive removal time, decreased cerebral blood flow, increased neuronal damage, reduced survival rate, significantly increased levels of TNF-α, IL-1ß, IL-6, CGRP, and NO in serum, significantly decreased levels of VEGF and ß-EP, significantly increased expression levels of NF-κB p65, p-IκBα/IκBα, and p-IKKα in rat brain tissue, and significantly upregulated protein expression of CKLF1 and CCR5. Compared with the model group, the high-dose LJTT group significantly improved the neurological functional score of pMCAO rats after oral administration for 7 days. LJTT at all doses significantly reduced adhesive removal time and restored cerebral blood flow. The high-and medium-dose LJTT groups significantly improved neuronal damage. The LJTT groups at all doses showed reduced levels of TNF-α, IL-1ß, IL-6, CGRP, and NO in rat serum, increased VEGF and ß-EP levels, and significantly decreased expression levels of NF-κB p65, p-IκBα/IκBα, p-IKKα, and CCR5 protein in rat brain tissue. The entropy weight analysis revealed that CGRP and ß-EP were significantly affected during the model induction, and LJTT exhibited a strong effect in reducing the release of inflammatory factors such as TNF-α and IL-1ß. LJTT may exert a neuroprotective effect on rats with permanent cerebral ischemia by reducing neuroinflammatory damage, and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the regulation of the CKLF1/CCR5 axis. Additionally, LJTT may exert certain analgesic effects by reducing CGRP and NO levels and increasing ß-EP levels.

A Weakly Supervised Learning Method for Cell Detection and Tracking Using Incomplete Initial Annotations.

The automatic detection of cells in microscopy image sequences is a significant task in biomedical research. However, routine microscopy images with cells, which are taken during the process whereby constant division and differentiation occur, are notoriously difficult to detect due to changes in their appearance and number. Recently, convolutional neural network (CNN)-based methods have made significant progress in cell detection and tracking. However, these approaches require many manually annotated data for fully supervised training, which is time-consuming and often requires professional researchers. To alleviate such tiresome and labor-intensive costs, we propose a novel weakly supervised learning cell detection and tracking framework that trains the deep neural network using incomplete initial labels. Our approach uses incomplete cell markers obtained from fluorescent images for initial training on the Induced Pluripotent Stem (iPS) cell dataset, which is rarely studied for cell detection and tracking. During training, the incomplete initial labels were updated iteratively by combining detection and tracking results to obtain a model with better robustness. Our method was evaluated using two fields of the iPS cell dataset, along with the cell detection accuracy (DET) evaluation metric from the Cell Tracking Challenge (CTC) initiative, and it achieved 0.862 and 0.924 DET, respectively. The transferability of the developed model was tested using the public dataset FluoN2DH-GOWT1, which was taken from CTC; this contains two datasets with reference annotations. We randomly removed parts of the annotations in each labeled data to simulate the initial annotations on the public dataset. After training the model on the two datasets, with labels that comprise 10% cell markers, the DET improved from 0.130 to 0.903 and 0.116 to 0.877. When trained with labels that comprise 60% cell markers, the performance was better than the model trained using the supervised learning method. This outcome indicates that the model's performance improved as the quality of the labels used for training increased.

Analysis of the impact of high-speed rail on the spatio-temporal distribution of residential population and industrial structure.

With the development of high-speed rail, the spatiotemporal distance among regions has been shortened. However, the research on the spatiotemporal distribution and correlation of resident population and industrial structure caused by the opening of high-speed railway is relatively few. This study is aimed to explore the impact of high-speed rail on resident population and industrial structure, as well as the spatiotemporal agglomeration and evolution trend. The spatial-temporal distribution of the resident population, industrial structure, and the influence of high-speed rail was studied using panel data from 31 Chinese provinces from 2006 to 2018 using spatial autocorrelation analysis, standard deviation ellipse method, and DID model. The experimental results indicate that: (1) The resident population shows a significant positive spatial autocorrelation, while the industrial structure is vice versa. (2) The resident population and industrial structure are primarily centralized in the eastern and central areas, showing a "northeast-southwest" spatial distribution pattern. (3) High-speed rail and the resident population are negatively correlated, and there is heterogeneity. Although there is an association between high-speed rail and industrial structure that is positive, there is also a clear regional variability. This study contributes to providing the corresponding theoretical support and basis for the high-speed rail line planning in different regions and the relevant departments to formulate effective economic policies.

Discovery of an OTUD3 inhibitor for the treatment of non-small cell lung cancer.

The ubiquitin-proteasome system (UPS) controls protein turnover, and its dysfunction contributes to human diseases including cancer. Deubiquitinating enzymes (DUBs) remove ubiquitin from proteins to maintain their stability. Inhibition of DUBs could induce the degradation of selected oncoproteins and has therefore become a potential therapeutic strategy for cancer. The deubiquitylase OTUD3 was reported to promote lung tumorigenesis by stabilizing oncoprotein GRP78, implying that inhibition of OTUD3 may be a therapeutic strategy for lung cancer. Here, we report a small-molecule inhibitor of OTUD3 (named OTUDin3) by computer-aided virtual screening and biological experimental verification. OTUDin3 exhibited pronounced antiproliferative and proapoptotic effects by inhibiting deubiquitinating activity of OTUD3 in non-small-cell lung cancer (NSCLC) cell lines. Moreover, OTUDin3 efficaciously inhibited growth of lung cancer xenografts in mice. In summary, our results support OTUDin3 as a potent inhibitor of OTUD3, the inhibition of which may be a promising therapeutic strategy for NSCLC.

The effect of parental carrier of de novo mutated vs. inherited balanced reciprocal translocation on the chance of euploid embryos.

OBJECTIVE: To evaluate whether the effect of de novo mutated balanced reciprocal translocation on the rate of euploid embryos varied from inherited balanced reciprocal translocation. DESIGN: A retrospective cohort study compared the percentage of euploid embryo and proportion of patients with at least 1 euploid embryo between de novo mutated balanced reciprocal translocation (i.e., the group of de novo mutated carriers) and inherited balanced reciprocal translocation (i.e., the group of inherited carriers). SETTING: An academic fertility center. PATIENT(S): A total of 413 couples with balanced reciprocal translocation (219 female carriers and 194 male carriers) who underwent their first cycle of preimplantation genetic testing for structural rearrangements were included. INTERVENTION(S): Carriers of balanced reciprocal translocation either de novo mutated or inherited. MAIN OUTCOME MEASURE(S): The percentage of euploid embryo and proportion of patients with at least 1 euploid embryo. RESULT(S): The carriers of the de novo mutated balanced reciprocal translocation had a lower percentage of euploid embryos (19.5% vs. 25.5%), and were less likely to have at least 1 euploid embryo (47.1% vs. 60.1%) compared with the carriers of the inherited balanced reciprocal translocation. In the male-carrier subgroup, the percentage of euploid embryos (16.7% vs. 26.7%) and proportion of patients with at least 1 euploid embryo (41.9% vs. 67.5%) were lower among the de novo mutated carriers than those among the inherited carriers. However, in the female-carrier subgroup, there was no statistically significant difference in the percentage of euploid embryos (22.4% vs. 24.4%) or the proportion of patients with at least 1 euploid embryo (52.3% vs. 53.7%) between the de novo mutated carriers and inherited carriers. CONCLUSION(S): The de novo mutated balanced reciprocal translocation was associated with a lower percentage of euploid embryos and lower chance of obtaining at least 1 euploid embryo than the inherited balanced reciprocal translocation.

A rapid and visual detection assay for Clonorchis sinensis based on recombinase polymerase amplification and lateral flow dipstick.

BACKGROUND: Fish-borne zoonotic clonorchiasis, caused by Clonorchis sinensis, is an emerging public health problem in several countries with more than 15 million people infected globally. However, a lack of accurate point-of-care (POC) diagnostic tests in resource-limited areas is still a critical barrier to effective treatment and control of clonorchiasis. The development of the recombinase polymerase amplification(RPA) assay, a POC diagnostic test based on the amplification of pathogen DNA, has provided a new, simple and inexpensive tool for disease detection with high sensitivity and specificity. METHODS: A novel RPA method was developed based on specific primers and probes, and combined with the dipstick, to allow for the rapid and intuitive detection of C. sinensis through the amplification of the mitochondrial cytochrome c oxidase subunit 1 (COX1) gene. The lower limit of detection for the combined RPA/lateral flow dipstick (RPA-LFD) assay was evaluated using dilutions of the target DNA sequence. Cross-reactivity was evaluated using genomic DNA from 10 additional control parasites. Forty human clinical stool samples were tested to verify its performance. RESULTS: The evaluated primers designed from the C. sinensis COX1 region can be used to detect adult worms, metacercariae, and eggs at 39 °C within 20 min, and the results can be visually observed using the LFD. The detection limit of pathogen genomic DNA was as low as 10 fg, and the number of metacercaria(e) in fish and egg(s) in faeces were both as low as one. This improved the sensitivity of low-infection detection tremendously. The test is species-specific, and no other related control parasites were detected. In human stool samples with eggs per gram (EPG) > 50, the RPA-LFD assay was performed consistent with conventional Kato-Katz (KK) and PCR methods. CONCLUSION: The established RPA-LFD assay provides a powerful tool for the diagnosis and epidemiological survey of C. sinensis from human and animal samples, and has important implications for the effective control of clonorchiasis.

Circular forms of dedicator of cytokinesis 1 promotes breast cancer progression by derepressing never in mitosis related kinase 2 via sponging miR-128-3p.

The conjecture of breast cancer is uncertain because of its explosive growth and the complicated molecular mechanisms. Circular RNAs (circRNAs) are regulatory RNA sequences present in the genome and their regulatory mechanism involves the sponging of microRNAs (miRNAs). In this study, we explored the regulation between circular forms of dedicator of cytokinesis 1 (circDOCK1) (hsa_circ_0007142) and miR-128-3p, and its implication on the pathogenesis of breast cancer modulated by never in mitosis (NIMA) related kinase 2 (NEK2). We revealed an increase in circDOCK1 and NEK2 expression, and a decrease in miR-128-3p expression in breast cancer tissues and cell lines. Bioinformatics analysis and experimental validation indicated a positive correlation between circDOCK1 and NEK2 expression but a negative correlation was recorded between miR-128-3p and circDOCK1 or NEK2, respectively. Furthermore, inhibition of circDOCK1 expression was followed by an increase in miR-128-3p and a decrease in NEK2 levels in vitro and in vivo. The luciferase assay concluded that miR-128-3p was a direct target of circDOCK1 while NEK2 was the direct target of miR-128-3p. Furthermore, circDOCK1 inhibition hindered breast cancer development by repressing NEK2 and thus promoting the increased expression of miR-128-3p both in vitro and in vivo. We therefore conclude that circDOCK1 promotes breast cancer progression by targeting miR-128-3p-mediated downregulation of NEK2 and that the circDOCK1/hsa-miR-128-3p/NEK2 axis may be a novel therapeutic target for breast cancer treatment.

Straightforward smartphone assay for quantifying tannic acid in beverages based on colour change of Eu3+/polyethyleneimine complex.

Tannic acid (TA)-a natural product-is a polyphenol derivative that occurs in certain kinds of beverages. A large amount of TA could give rise to an unpleasant flavour and could negatively affect the human body by causing stomach irritation, abdominal pain, nausea, vomiting, and even death. Thus, the need exists for a simple TA detection procedure that meets specific criteria such as on-site analysis, portability, and affordability. Herein, we present a new TA assay, which is based on the fluorescent quenching effect of an efficient fluorophore, and which comprises a smartphone-integrated homemade reader system. The fluorescent polyethyleneimine-derivatised polymer (FP), a strong emitter at 510 nm, was synthesised with the aid of a facile sonication method. In the presence of Eu3+ ions, TA quenches the fluorescence of the FP via electrostatic interaction. A smartphone was used to capture an image of the FP undergoing fluorescence for conversion to RGB values. The blue channel was chosen for further analysis because it offered the highest R2-value compared to the red and green channels. We verified these results using a commercial spectrofluorometer and calculated the limit of detection of this assay as 87 nM and 20 nM for the homemade reader and spectrofluorometer, respectively. The detection range for TA with the proposed assay is 0.16-66.66 µM. The application of the proposed method to real beverage samples for TA detection demonstrates its analytical applicability.

Bifunctional Compounds as Molecular Degraders for Integrin-Facilitated Targeted Protein Degradation.

As effective ways to regulate protein levels, targeted protein degradation technologies have attracted great attention in recent years. Here, we established a novel integrin-facilitated lysosomal degradation (IFLD) strategy to degrade extracellular and cell membrane proteins using bifunctional compounds as molecular degraders. By conjugation of a target protein-binding ligand with an integrin-recognition ligand, the resulting molecular degrader proved to be highly efficient to induce the internalization and subsequent degradation of extracellular or cell membrane proteins in an integrin- and lysosome-dependent manner. As demonstrated in the development of BMS-L1-RGD, which is an efficient programmed death-ligand 1 (PD-L1) degrader validated both in vitro and in vivo, the IFLD strategy expands the toolbox for regulation of secreted and membrane-associated proteins and thus has great potential to be applied in chemical biology and drug discovery.

Thermally Treated Berberine-Loaded SA/PVA/PEO Electrospun Microfiber Membranes for Antibacterial Wound Dressings.

This study aimed to develop a safe and advanced antibacterial material of electrospun microfiber membranes (MFMs) for wound dressings. Combinations of several materials were investigated; thermal treatment and electrospinning techniques were used to form the best quality of MFMs to suit its end applications. By comparing the fiber morphology, diameter changes, and fracture strength, the suitable ratio of raw materials and thermal treatment were obtained before and after adding Trition X-100 as a surfactant for MFMs of sodium alginate/polyvinyl alcohol/polyethylene oxide (SA/PVA/PEO). The electrospinning solution was mixed with berberine as an antibacterial substance; meanwhile, calcium chloride (CaCl2) was used as the crosslinking agent. The antibacterial properties, water dissolution resistance, water content, and fracture strength were thoroughly investigated. The results showed that the antibacterial rates of MFMs with different mass fractions of berberine (0, 3, and 5 wt.%) to Escherichia coli (E. coli) were 14.7, 92.9, and 97.2%, respectively. The moisture content and fracture strength of MFMs containing 5 wt.% berberine were 72.0% and 7.8 MPa, respectively. In addition, the produced MFMs embodied great water dissolution resistance. Berberine-loaded SA/PVA/PEO MFMs could potentially serve as an antibacterial wound dressing substrate with low cost and small side effects.

Destabilization of TP53 by USP10 is essential for neonatal autophagy and survival.

Autophagy is essential for the maintenance of energy homeostasis and for survival during the neonatal starvation period. At birth, the trans-placental nutrient supply is suddenly interrupted, and neonates adapt to this adverse circumstance by activating autophagy. However, the mechanisms underlying the precise regulation of neonatal autophagy remain undefined. Here, we show that the destabilization of TP53 by the deubiquitylase ubiquitin-specific peptidase 10 (USP10) is essential for neonatal autophagy and survival. Usp10 deficiency results in decreased E3 ligase activity of MDM2 and accumulation of cytoplasmic TP53, which interferes with the conjugation of ATG12 and ATG5, the key autophagy-related genes, and ultimately inhibits autophagy in neonatal mice. Combined deletion of Tp53 and Usp10 recovers the nutrition supply and rescues the death phenotype of Usp10-deficient neonates. These findings reveal a role of the USP10-MDM2-TP53 axis in nutrient homeostasis and neonatal viability and provide insights into the long-perplexing mechanism by which cytoplasmic TP53 inhibits autophagy.

Function and therapeutic potential of transient receptor potential ankyrin 1 in fibrosis.

The transient receptor potential (TRP) protein superfamily is a special group of cation channels expressed in different cell types and signaling pathways. In this review, we focus on TRPA1 (transient receptor potential ankyrin 1), an ion channel in this family that exists in the cell membrane and shows a different function from other TRP channels. TRPA1 usually has a special activation effect that can induce cation ions, especially calcium ions, to flow into activated cells. In this paper, we review the role of TRPA1 in fibroblasts. To clarify the relationship between fibroblasts and TRPA1, we have also paid special attention to the interactions between TRPA1 and inflammatory factors leading to fibroblast activation. TRPA1 has different functions in the fibrosis process in different organs, and there have also been interesting discussions of the mechanism of TRPA1 in fibroblasts. Therefore, this review aims to describe the function of TRP channels in controlling fibrosis through fibroblasts in different organ inflammatory and immune-mediated diseases. We attempt to prove that TRPA1 is a target for fibrosis. In fact, some clinical trials have already proven that TRPA1 is a potential adjuvant therapy for treating fibrosis.

Docetaxel-resistant triple-negative breast cancer cell-derived exosomal lncRNA LINC00667 reduces the chemosensitivity of breast cancer cells to docetaxel via targeting miR-200b-3p/Bcl-2 axis.

Development of docetaxel (TXT) resistance is a major obstacle for triple-negative breast cancer (TNBC) treatment. Additionally, chemoresistant cell-derived exosomes were able to change the chemo-response of chemosensitive recipient cells via transportation of lncRNAs. It has been shown that lncRNA LINC00667 level was significantly elevated in breast cancer tissues. Therefore, we explored whether LINC00667 level is increased in TXT-resistant TNBC cell-derived exosomes. In addition, whether exosomal LINC00667 derived from TXT-resistant TNBC cell could affect TXT sensitivity in TXT-sensitive TNBC cells was investigated as well. In the present study, exosomes were isolated from the TXT-resistant TNBC cells and from TXT-sensitive TNBC cells. Next, the level of LINC00667 in the isolated exosomes was detected with RT-qPCR. We found that LINC00667 expression was obviously elevated in TXT-resistant TNBC cell-derived exosomes compared to that in TXT-sensitive TNBC cell-derived exosomes. In addition, LINC00667 could be transferred from TXT-resistant TNBC cells to TNBC cells via exosomes. Moreover, TXT-resistant TNBC cell secreted exosomal LINC00667 markedly reduced the sensitivity of TNBC cells to TXT via upregulation of Bcl-2. Meanwhile, downregulation of LINC00667 notably enhanced the sensitivity of TXT-resistant TNBC cells to TXT through downregulation of Bcl-2. Additionally, LINC00667 was considered to be a ceRNA to sponge miR-200b-3p, thereby elevating Bcl-2 expression. Collectively, TXT-resistant TNBC cell-derived exosomal LINC00667 could decrease the chemosensitivity of TNBC cells to TXT via regulating miR-200b-3p/Bcl-2 axis. These findings suggested that LINC00667 might serve as a promising target for enhancing sensitivity of TNBC cells to TXT therapy.