Impact of neoadjuvant chemotherapy on perioperative immune function in breast cancer patients: a propensity score-matched retrospective study.

To evaluate the impact of neoadjuvant chemotherapy on perioperative immune function in breast cancer patients, focusing on CD3+, CD4+, CD8+, and natural killer (NK) cells, as well as the CD4+/CD8+ ratio. We retrospectively reviewed medical records of breast cancer patients who underwent surgery with or without neoadjuvant chemotherapy at our medical center from January 2020 to December 2022. Patients were matched 1:1 based on propensity scores. Immune cell proportions and the CD4+/CD8+ ratio were compared on preoperative day one and postoperative days one and seven. Among matched patients, immune cell proportions and the CD4+/CD8+ ratio did not significantly differ between those who received neoadjuvant chemotherapy and those who did not at any of the three time points. Similar results were observed in chemotherapy-sensitive patients compared to the entire group of patients who did not receive neoadjuvant chemotherapy. However, chemotherapy-insensitive patients had significantly lower proportions of CD4+ and NK cells, as well as a lower CD4+/CD8+ ratio, at all three time points compared to patients who did not receive neoadjuvant chemotherapy. Neoadjuvant chemotherapy may impair immune function in chemotherapy-insensitive patients, but not in those who are sensitive to the treatment.

Mendelian randomization analyses reveal no genetic causal effects of major adipokines on systemic lupus erythematosus.

Epidemiological studies have shown that the levels of serum adipokine such as leptin and resistin are associated with the risk of developing systemic lupus erythematosus (SLE). Nevertheless, whether either leptin or resistin has causal impacts on the risk of SLE is still unknown. In this study, two-sample univariable MR analyses and multivariable MR analysis were performed to explore the causal relationships between adipokines and SLE. Additionally, the potential causal effects of SLE on major adipokines were evaluated using reverse MR analyses. The results of inverse-variance weighted (IVW), weighted median, weighted mode and MR‒Egger methods concordantly supported that major adipokines have no causal effects on the risk of SLE. In the multivariable MR IVW analysis with leptin and resistin as covariates, neither leptin (odds ratio (OR) = 3.093, P = 0.067) nor resistin (OR = 0.477, P = 0.311) was identified as an independent risk factor for SLE, which is in line with the univariable MR results. In conclusion, our analyses revealed no evidence to support that these three major adipokines are risk factors for SLE.

Effects of combined microplastic and cadmium pollution on sorghum growth, Cd accumulation, and rhizosphere microbial functions.

The interaction between microplastics (MPs) and cadmium (Cd) poses a threat to agricultural soil environments, and their effects on plant growth and rhizosphere microbial community functions are not yet clear. In this study, energy sorghum was used as a test plant to investigate the effects of two types of MPs, polystyrene (PS) and polyethylene (PE), at different particle sizes (13 µm, 550 µm) and concentrations (0.1%, 1% w/w), and Cd, as well as their interactions, on the growth of sorghum in a soil-cultivation pot experiment. The results showed that the combined effects of MP and Cd pollution on the dry weight and Cd accumulation rate in sorghum varied depending on the type, concentration, and particle size of the MPs, with an overall trend of increasing stress from combined pollution with increasing Cd content and accumulation. High-throughput sequencing analysis revealed that combined MP and Cd pollution increased bacterial diversity, and the most significant increase was observed in the abundance-based coverage estimator (ACE), Shannon, and Sobs indices in the 13 µm 1% PS+Cd treatment group. Metagenomic analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways revealed that 19 groups of metabolic pathways, including microbial metabolism and methane metabolism, differed significantly under combined MP and Cd pollution. Hierarchical clustering results indicated that Cd treatment and combined MP and Cd treatment affected the abundances of sorghum rhizosphere soil nitrogen (N) and phosphorus (P) cycling genes and that the type of MP present was an important factor affecting N and P cycling genes. The results of this study provide a basis for exploring the toxic effects of combined MP and Cd pollution and for conducting soil environmental risk assessments.

Microemulsion-Assisted Self-Assembly of Indium Porphyrin Photosensitizers with Enhanced Photodynamic Therapy.

Designing and constructing supramolecular photosensitizer nanosystems with highly efficient photodynamic therapy (PDT) is vital in the nanomedical field. Despite recent advances in forming well-defined superstructures, the relationship between molecular arrangement in nanostructures and photodynamic properties has rarely been involved, which is crucial for developing stable photosensitizers for highly efficient PDT. In this work, through a microemulsion-assisted self-assembly approach, indium porphyrin (InTPP) was used to fabricate a series of morphology-controlled self-assemblies, including nanorods, nanospheres, nanoplates, and nanoparticles. They possessed structure-dependent 1O2 generation efficiency. Compared with the other three nanostructures, InTPP nanorods featuring strong π-π stacking, J-aggregation, and high crystallinity proved to be much more efficient at singlet oxygen (1O2) production. Also, theoretical modeling and photophysical experiments verified that the intermolecular π-π stacking in the nanorods could cause a decreased singlet-triplet energy gap (ΔEST) compared with the monomer. This played a key role in enhancing intersystem crossing and facilitating 1O2 generation. Both in vitro and in vivo experiments demonstrated that the InTPP nanorods could trigger cell apoptosis and tumor ablation upon laser irradiation (635 nm, 0.1 W/cm2) and exhibited negligible dark toxicity and high phototoxicity. Thus, the supramolecular self-assembly strategy provides an avenue for designing high-performance photosensitizer nanosystems for photodynamic therapy and beyond.

Polystyrene microplastics enhance oxidative dissolution but suppress the aquatic acute toxicity of a commercial cadmium yellow pigment under simulated irradiation.

Commercial cadmium yellow (CdS) pigment widely coexist with microplastics (MPs) in surface water, thus it is important to understand how MPs affect CdS pigment stability and toxicity under irradiation. Herein, the dissolution of CdS pigment (krelease = 0.118 h-1) under irradiation was visibly increased to 0.144 h-1 by polystyrene (PS) MPs, due to reactive species generation such as 1O2, •OH and 3PS* , while O2•- was unimportant to this process. The O2, humic acid, photoaging status of PS MPs could promote PS MPs-related CdS pigment dissolution rate by modifying reactive species generation. However, the CO32-, PO43- and alkaline condition significantly decreased the dissolution rate to 0.091, 0.053 and 0.094 h-1, respectively, through modifying free Cd2+ stability. Comparably, PS MPs-related CdS pigment dissolution was relatively slow in natural water samples (krelease = 0.075 h-1). PS MPs at environmental concentration can also promote CdS pigment dissolution and Cd2+ release, but suppress acute toxicity of CdS pigment to zebrafish larvae as increasing 10 h survival from 65% to 85% by adsorbing the Cd2+ and decreasing Cd2+ bioavailability. This study emphasized the environmental risks and human safety of CdS pigment should be carefully evaluated in the presence of PS MPs in aquatic environments.

Surgical techniques to prevent delayed gastric emptying after pancreaticoduodenectomy.

BACKGROUND: Delayed gastric emptying (DGE) is one of the most common complications after pancreaticoduodenectomy (PD). DGE represents impaired gastric motility without significant mechanical obstruction and is associated with an increased length of hospital stay, increased healthcare costs, and a high readmission rate. We reviewed published studies on various technical modifications to reduce the incidence of DGE. DATA SOURCES: Studies were identified by searching PubMed for relevant articles published up to December 2022. The following search terms were used: "pancreaticoduodenectomy", "pancreaticojejunostomy", "pancreaticogastrostomy", "gastric emptying", "gastroparesis" and "postoperative complications". The search was limited to English publications. Additional articles were identified by a manual search of references from key articles. RESULTS: In recent years, various surgical procedures and techniques have been explored to reduce the incidence of DGE. Pyloric resection, Billroth II reconstruction, Braun's enteroenterostomy, and antecolic reconstruction may be associated with a decreased incidence of DGE, but more high-powered studies are needed in the future. Neither laparoscopic nor robotic surgery has demonstrated superiority in preventing DGE, and the use of staplers is controversial regarding whether they can reduce the incidence of DGE. CONCLUSIONS: Despite many innovations in surgical techniques, there is no surgical procedure that is superior to others to reduce DGE. Further larger prospective randomized studies are needed.

Development and validation of two redox-related genes associated with prognosis and immune microenvironment in endometrial carcinoma.

In recent studies, the tumourigenesis and development of endometrial carcinoma (EC) have been correlated significantly with redox. We aimed to develop and validate a redox-related prognostic model of patients with EC to predict the prognosis and the efficacy of immunotherapy. We downloaded gene expression profiles and clinical information of patients with EC from the Cancer Genome Atlas (TCGA) and the Gene Ontology (GO) dataset. We identified two key differentially expressed redox genes (CYBA and SMPD3) by univariate Cox regression and utilised them to calculate the risk score of all samples. Based on the median of risk scores, we composed low-and high-risk groups and performed correlation analysis with immune cell infiltration and immune checkpoints. Finally, we constructed a nomogram of the prognostic model based on clinical factors and the risk score. We verified the predictive performance using receiver operating characteristic (ROC) and calibration curves. CYBA and SMPD3 were significantly related to the prognosis of patients with EC and used to construct a risk model. There were significant differences in survival, immune cell infiltration and immune checkpoints between the low-and high-risk groups. The nomogram developed with clinical indicators and the risk scores was effective in predicting the prognosis of patients with EC. In this study, a prognostic model constructed based on two redox-related genes (CYBA and SMPD3) were proved to be independent prognostic factors of EC and associated with tumour immune microenvironment. The redox signature genes have the potential to predict the prognosis and the immunotherapy efficacy of patients with EC.

Construction of coaxial liquid centrifugal platform for the extraction of active ingredients from natural products.

In the classical natural product extraction and separation process, it is tedious and requires large amounts of reagents and time. In this study, an efficient coaxial liquid centrifugal oil-water-oil triple-liquid-phase system with a simple structure and convenient operation was successfully constructed and used to extract flavonoids from Platycladi Cacumen. The results showed that the coaxial liquid centrifugal platform constructed in this study had good stability and 6 ml was the minimum volume of the middle phase for 1000 rpm to stabilize the system. Besides, it was easy to repeat the operation: the relative standard deviations of the extraction yields of flavonoids and sugar in six parallel operations were all less than 10%. Moreover, it was only one-tenth of the time required for this method as traditional liquid-liquid extraction while reducing the use of volatile organic reagents. Finally, the new method was more selective than the traditional method for the extraction of flavonoids. Therefore, this study provides a possibility for the coaxial liquid centrifugal platform to be used in multi-liquid phase systems to achieve the simultaneous extraction of different parts of natural products by different liquid phases. It is expected to provide a reliable reference for further expansion of small-scale experimental operations to industrial production.

[Corrigendum] High glucose and high insulin conditions promote MCF­7 cell proliferation and invasion by upregulating IRS1 and activating the Ras/Raf/ERK pathway.

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that, in the wound­healing assays portrayed in Fig. 2A on p. 6692, in the 0 h row, the 'NG + LI' and 'HG + HI' panels contained overlapping data, such that they appeared to have been derived from the same original source. After having examined their original data, the authors have realized that this figure was inadvertently assembled incorrectly. The corrected version of Fig. 2. showing the correct data for the 'HG + HI' panel, is shown on the next page. Note that this error did not significantly affect the results or the conclusions reported in this paper, and all the authors agree with the publication of this Corrigendum. Furthermore, the authors apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 6690­6696, 2017; DOI: 10.3892/mmr.2017.7420].

[Corrigendum] Thymoquinone inhibits epithelial­mesenchymal transition in prostate cancer cells by negatively regulating the TGF­ß/Smad2/3 signaling pathway.

After the publication of the article, an interested reader drew to the authors' attention that the Du145 'Control' migration panel in Fig. 2C appeared to overlap with the Du145 'Control' invasion panel in Fig. 5A; furthermore, two of the Du145 panels in Fig. 5A also appeared to overlap. The authors have consulted their original data, and realize that these figures were inadvertently assembled incorrectly. The corrected versions of Figs. 2 and 5, incorporating the correct data for the Du145 'Control' panel in Fig. 2C, and the TQ­/TGF­ß OE­ invasion and migration panels, and the TQ+/TGF­ß OE+ migration panel, in Fig. 5A, are shown on the next page. These further corrections do not grossly affect the results or the conclusions reported in this work. The authors all agree to this Corrigendum, and are grateful to the Editor of Oncology Reports for granting them the opportunity to correct the errors that were made during the assembly of these figures. Lastly, the authors apologize to the readership for any inconvenience these errors may have caused. [Oncology Reports 38: 3592­3598, 2017; DOI: 10.3892/or.2017.6012].

Tropomyosin 2 exerts anti-tumor effects in lung adenocarcinoma and is a novel prognostic biomarker.

BACKGROUND: Tropomyosin 2 (TPM2), a member of the actin filament binding protein family, plays distinct roles in the progression of different cancer types. Until now, there has been no study reporting TPM2 expression nor its function in lung adenocarcinoma (LUAD). METHODS: In the present study, we examined the expression profile of TPM2 by immunohistochemistry (IHC). The clinical significance of TPM2 was assessed by univariate and multivariate analyses. Function of TPM2 in LUAD was evaluated by knockdown and overexpression strategies in three LUAD cell lines, followed by proliferation and invasion assays. Xenografts were conducted in nude mice to further validate the tumor-related role of TPM2. RESULTS: Our results showed that TPM2 was downregulated in LUAD specimens and the low expression of TPM2 was associated with poor outcomes of LUAD patients. Overexpressing TPM2 inhibited cell proliferation and invasion of LUAD cell lines, while silencing TPM2 exerted the opposite effects. The effects of TPM2 in LUAD were further confirmed by xenograft assays. CONCLUSIONS: Our results indicated that TPM2 exerted an anti-oncogenic role in LUAD via inhibiting tumor progression, thus providing a novel direction for the prognostic prediction and disease treatment.

Clinical Data-CT Radiomics-Based Model for Predicting Prognosis of Patients with Gastrointestinal Pancreatic Neuroendocrine Neoplasms (GP-NENs).

Purpose: Based on computerized tomography (CT) radiomics and clinical data, a model was established to predict the prognosis of patients with gastrointestinal pancreatic neuroendocrine neoplasms (GP-NENs). Methods: In the data collection, the clinical imaging and survival follow-up data of 225 GP-NENs patients admitted to Xiangyang No.1 People's Hospital and Jiangsu Province Hospital of Chinese Medicine from August 2015 to February 2021 were collected. According to the follow-up results, they were divided into the nonrecurrent group (n = 108) and the recurrent group (n = 117), based on which a training set and a test set were established at a ratio of 7/3. In the training set, a variety of models were established with significant clinical and imaging data (P < 0.05) to predict the prognosis of GP-NENs patients, and then these models were verified in the test set. Results: Our newly developed combined prediction model had high predictive efficacy. Univariate analysis showed that Radscore 1/2/3, age, Ki-67 index, tumor pathological type, tumor primary site, and TNM stage were risk factors for the prognosis of GP-NENs patients (all P < 0.05). The area under the receiver operating characteristic (ROC) curves (AUC) of the combined model was significantly higher [AUC:0.824, 95% CI 0.0342 (0.751-0.883)] than that of the clinical data model [AUC:0.786, 95% CI 0.0384(0.709-0.851)] and the radiomics model [AUC:0.712, 95% CI 0.0426(0.631-0.785)]. The decision curve also confirmed that the combined model had a higher clinical net benefit. The same results were achieved in the test set. Conclusion: The prognosis of patients with GP-NENs is generally poor. The combined model based on clinical data and CT radiomics can help to early predict the prognosis of patients with GP-NENs, and then necessary interventions could be provided to improve the survival rate and quality of life of patients.

Identification of Key Genes in Severe Burns by Using Weighted Gene Coexpression Network Analysis.

The aims of this work were to explore the use of weighted gene coexpression network analysis (WGCNA) for identifying the key genes in severe burns and to provide a reference for finding therapeutic targets for burn wounds. The GSE8056 dataset was selected from the gene expression database of the US National Center for Biotechnology Information for analysis, and a WGCNA network was constructed to screen differentially expressed genes (DEGs). Gene Ontology and pathway enrichment of DGEs were analyzed, and protein interaction network was constructed. A burn mouse model was constructed, and the burn tissue was taken to identify the expression levels of differentially expressed genes. The results showed that the optimal soft threshold for constructing the WGCNA network was 9. 10 coexpressed gene modules were identified, among which the green, brown, and gray modules had the largest number of burn-related genes. The DEGs were mainly related to immune cell activation, inflammatory response, and immune response, and they were enriched in PD-1/PD-L1, Toll-like receptor, p53, and nuclear factor-kappa B (NF-κB) signaling pathways. 5 DEGs were screened and identified, namely, Jun protooncogene (JUN), signal transducer and activator of transcription 1 (STAT1), BCL2 apoptosis regulator (Bcl2), matrix metallopeptidase 9 (MMP9), and Toll-like receptor 2 (TLR2). Compared with skin tissue of normal mouse, the messenger ribose nucleic acid (mRNA) and protein expression levels (PEL) of STAT1 and Bcl2 in burn tissue were greatly decreased, while those of JUN, MMP9, and TLR2 were increased obviously (p < 0.05). In conclusion, STAT1, Bcl2, JUN, MMP9, and TLR2 can be potential biological targets for the treatment of severe burn wounds.

Contrast-Enhanced Ultrasound-Magnetic Resonance Imaging Radiomics Based Model for Predicting the Biochemical Recurrence of Prostate Cancer: A Feasibility Study.

Objective: This study was aimed at developing a model for predicting postoperative biochemical recurrence of prostate cancer (PCa) using clinical data-CEUS-MRI radiomics and at verifying its clinical effectiveness. Methods: The clinical imaging data of 159 patients pathologically confirmed with PCa and who underwent radical prostatectomy in Xiangyang No. 1 People's Hospital and Jiangsu Hospital of Chinese Medicine from March 2016 to December 2020 were retrospectively analyzed. According to the 2-5-year follow-up results, the patients were divided into the biochemical recurrence (BCR) group (n = 59) and the control group (n = 100). The training set and test set were established in the proportion of 7/3; 4 prediction models were established based on the clinical imaging data. In training set, the area under the curve (AUC) and decision curve analysis (DCA) by R was conducted to compare the efficiency of 4 prediction models, and then, external validation was performed using the test set. Finally, a nomogram tool for predicting BCR was developed. Results: Univariate regression analysis confirmed that the SmallAreaHighGrayLevelEmphasis, RunVariance, Contrast, tumor diameter, clinical T stage, lymph node metastasis, distant metastasis, Gleason score, preoperative PSA, treatment method, CEUS-peak intensity (PI), time to peak (TTP), arrival time (AT), and elastography grade were the influencing factors for predicting BCR. In the training set, the AUC of combinatorial model demonstrated the highest efficiency in predicting BCR [AUC: 0.914 (OR 0.0305, 95% CI: 0.854-0.974)] vs. the general clinical data model, the CEUS model, and the MRI radiomics model. The DCA confirmed the largest net benefits of the combinatorial model. The test set validation gave consistent results. The nomogram tool has been well applied clinically. Conclusion: The previous clinical and imaging data alone did not perform well for predicting BCR. Our combinatorial model firstly using clinical data-CEUS-MRI radiomics provided an opportunity for clinical screening of BCR and help improve its prognosis.

Association between tea consumption and semen quality among 1385 healthy Chinese men.

Information on the association between tea drinking and semen quality is limited. Little is reported on whether tea drinking is benefit to sperm quality. This cross-sectional and longitudinal study was conducted between April 2017 and July 2018. Participants were healthy men who were screened as potential sperm donors recruited at the Hubei Province Human Sperm Bank of China. A structured questionnaires containing sociodemographic information, daily habits, sperm collection-related information was completed for each participant at interview. Repeated semen samples were taken to examine the sperm parameters, including sperm volume, sperm concentration, sperm count, progressive motility, and total motility. A total of 1385 men with 6466 sperm samples were included in this study. Two groups were compared: tea drinking men (389, 28.1%) and non-tea drinking men (996, 71.9%). Compared with subjects who never drink tea, the analyses showed that sperm concentration and total sperm count were higher in tea-consuming subjects. A 10-year period or more duration of tea drinking significantly increased semen concentrations by 16.27% (P < 0.05). Sperm concentration was increased in subjects with a frequency of tea drinking of 3 days or more per week (P < 0.05) or, among men who were occasional alcohol drinkers, when tea concentration was weak (P < 0.05). No evidence of trend effects (P for trend > 0.05) or interaction effects (P for interaction > 0.05) between tea consumption and sperm quality, respectively. Our findings provide evidence that tea drinking may improve male reproductive health. Long-term, frequent, weak tea drinking tends to increase sperm quality among men with low BMI or health-related behaviors like smoking or alcohol intake.

Perilipin 5 protects against oxygen-glucose deprivation/reoxygenation-elicited neuronal damage by inhibiting oxidative stress and inflammatory injury via the Akt-GSK-3ß-Nrf2 pathway.

BACKGROUND: Perilipin 5 (Plin5) acts as a pivotal mediator of oxidative stress and inflammation and is associated with the progression of relevant diseases. Cerebral ischemic stroke is a severe pathological condition that involves excess oxidative stress and inflammation. However, whether Plin5 plays a role in the progression of cerebral ischemic stroke remains unaddressed. This work focused on the investigation of Plin5 in oxygen-glucose deprivation/reoxygenation (OGD/R)-injured neurons, an in vitro model for studying cerebral ischemic stroke. METHODS: The primary neuronal cells were isolated from the hippocampus of newborn mice. Neurons were subjected to OGD/R treatment to establish an in vitro model for studying cerebral ischemic stroke. Neurons were infected with recombinant adenovirus expressing Plin5 to upregulate Plin5 expression. The mRNA levels were measured by real-time quantitative PCR (RT-qPCR). Protein levels were determined by immunoblotting. Cell viability was assessed via cell counting kit-8 (CCK-8) assay. Cell apoptosis was evaluated via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Annexin V-Allophycocyanin/7-Amino Actinomycin D (Annexin V-APC/7-AAD) apoptotic assays. Oxidative stress was monitored by dichlorofluorescein diacetate (DCFH-DA) probe. Inflammatory cytokine release was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: A decreased level of Plin5 was observed in neurons challenged with OGD/R. Plin5 overexpression remarkably subdued OGD/R-elicited apoptosis, oxidative stress and proinflammatory response. Plin5 overexpression led to an enhancement of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway associated with regulation of the Akt-glycogen synthase kinase-3ß (GSK-3ß). The blocking of Akt was able to reverse the enhancing effect of Plin5 on Nrf2 activation. The restraining of Akt or silencing of Nrf2 diminished the protective effects of Plin5 in OGD/R-injured neurons. CONCLUSIONS: Plin5 confers neuroprotection for neurons against OGD/R damage via effects on the Nrf2-Akt-GSK-3ß pathway. This work indicates a possible role of Plin5 in cerebral ischemic stroke and the up-regulation of Plin5 is a sort of survival strategy for neurons suffering from ischemic injury.

High efficacy of alectinib in a patient with advanced lung adenocarcinoma with 2 rare ALK fusion sites: a case report.

Anaplastic lymphoma kinase (ALK) fusions have been identified in approximately 5% of non-small cell lung cancer (NSCLC) cases. ALK-tyrosine kinase inhibitors (TKIs) are the standard first-line treatment for patients with ALK-positive (ALK+) advanced NSCLC. Along with widespread use of next-generation sequencing (NGS) for the molecular diagnosis of lung cancer, an increasing number of ALK fusion partners are being reported, with the majority being effective for ALK-TKIs. Here, we present the case of a 42-year-old female with no smoking history who was diagnosed with stage IVB lung adenocarcinoma. Two rare ALK fusions were detected simultaneously by NGS in this patient: latent transforming growth factor beta-binding protein 1 (LTBP1)-ALK and huntingtin-interacting protein 1 (HIP1)-ALK. HIP1-ALK fusion was also detected by further RNA sequencing, but LTBP1-ALK failed to give a positive signal. The patient received alectinib as first-line therapy and consequently achieved a good response. Progression-free survival (PFS) was more than 19 months, and the treatment with alectinib is ongoing currently. During treatment, clinical symptoms disappeared and no significant adverse events occurred. This is the first case report describing a patient with an NSCLC tumor harboring 2 rare ALK fusions who responded to alectinib. Our report enriches the knowledge of ALK fusion sites and provides an effective clinical basis for the screening of sensitive fusions.

TRPM2-AS promotes paclitaxel resistance in prostate cancer by regulating FOXK1 via sponging miR-497-5p.

Chemoresistance seriously hinders the treatment efficiency of human cancers, including prostate cancer (PCa). Multiple long noncoding RNAs (lncRNAs) were involved in drug resistance in PCa. We aimed to explore the function of transient receptor potential cation channel subfamily M member 2 (TRPM2) antisense RNA (TRPM2-AS) in paclitaxel (PTX) resistance in PCa. Our results showed that TRPM2-AS was increased in PTX-resistant PCa cells. TRPM2-AS knockdown accelerated cell apoptosis and inhibited cell proliferation, migration, invasion, and PTX resistance in PTX-resistant PCa cells. MiR-497-5p was bound to TRPM2-AS and its inhibition reversed the effects of TRPM2-AS knockdown on cell progression and PTX resistance in PTX-resistant PCa cells. FOXK1 was identified as a target of miR-497-5p and FOXK1 overexpression showed similar effects on cell progression and PTX resistance with miR-497-5p inhibition in PTX-resistant PCa cells. In conclusion, TRPM2-AS knockdown suppressed cell progression and PTX resistance in PTX-resistant PCa cells by miR-497-5p/FOXK1 axis.

Circ_0001588 Upregulates ERBB4 to Promote Glioma Malignant Progression Through Sponging miR-1281.

Circular RNA (circRNA) plays a crucial part in glioma progression. However, the function of circ_0001588 in glioma development is still unknown. The study aims to reveal the role of circ_0001588 in glioma malignant progression and the inner molecular mechanism. The RNA expressions of circ_0001588, microRNA-1281 (miR-1281), and erb-b2 receptor tyrosine kinase 4 (ERBB4) were detected by qRT-PCR. Protein expression was checked by western blot analysis or immunohistochemistry assay. Cell proliferation was investigated by cell counting kit-8 and colony formation assays. Flow cytometry, transwell, and tube formation assays were used to detect cell apoptosis, cell migration, and invasion as well as angiogenesis, respectively. The binding relationship between miR-1281 and circ_0001588 or ERBB4 was identified by dual-luciferase reporter and RNA immunoprecipitation assays. Mouse model assay was performed to confirm the effect of circ_0001588 knockdown on tumor formation in vivo. Circ_0001588 and ERBB4 expressions were significantly upregulated, while miR-1281 was downregulated in glioma tissues and cells compared with control groups. Circ_0001588 expression was closely related to tumor size and WHO grade of glioma. Decreased expression of circ_0001588 in glioma cells led to significant decreases of cell proliferation, migration, invasion, and tube formation and an increase of cell apoptosis. Additionally, downregulation of miR-1281, a target miRNA of circ_0001588, rescued circ_0001588 knockdown-mediated effects. MiR-1281 also inhibited glioma malignant progression by targeting ERBB4. Importantly, circ_0001588 regulated ERBB4 expression by interacting with miR-1281. Furthermore, circ_0001588 depletion suppressed tumor formation in vivo. Circ_0001588 acted as an oncogene in glioma malignant progression by miR-1281/ERBB4 pathway, suggesting the potential of circ_0001588 as a therapeutic target for glioma.

Curcumin sensitizes carboplatin treatment in triple negative breast cancer through reactive oxygen species induced DNA repair pathway.

BACKGROUND: As patients with triple-negative breast cancer (TNBC) have a very weak response to hormone inhibition or anti-HER2 therapy, traditional chemotherapy is commonly used in these patients. Recently, carboplatin has been approved for the clinical treatment of TNBC. However, several patients exhibit resistance to carboplatin treatment. Therefore, strategies to enhance the antitumor effect of carboplatin need to be explored. In our study, we investigated the function of curcumin in increasing the response to carboplatin. METHODS AND RESULTS: MTT and colony formation assays were used to evaluate cell viability after carboplatin and curcumin treatment. In addition, we conducted flow cytometric and Western blot analyses to examine cellular apoptosis. Subsequently, molecular and biochemical experiments were used to explore the mechanism by which curcumin sensitized TNBC to carboplatin treatment. We demonstrated that different TNBC cells responded differently to carboplatin. Low-dose carboplatin killed CAL-51 cells but barely influenced CAL-51-R and MDA-MB-231 cells. To improve the sensitivity of resistant TNBC cells to carboplatin, combined treatment with curcumin was applied and was found to inhibit proliferation and induce apoptosis. Mechanistically, curcumin exerted its anticancer effect by increasing reactive oxygen species (ROS) production, which downregulated the DNA repair protein RAD51, leading to upregulation of γH2AX. As expected, ROS scavenger NAC reversed the inhibitory effect on growth and DNA repair pathway activity mediated by curcumin. CONCLUSION: Collectively, our data demonstrate that curcumin sensitizes TNBC to the anticancer effect of carboplatin by increasing ROS-induced DNA damage, thus providing an effective combination treatment strategy for TNBC.