Epigenetic silencing schlafen-11 sensitizes esophageal cancer to ATM inhibitor.

BACKGROUND: Targeting DNA damage response (DDR) pathway is a cutting-edge strategy. It has been reported that Schlafen-11 (SLFN11) contributes to increase chemosensitivity by participating in DDR. However, the detailed mechanism is unclear. AIM: To investigate the role of SLFN11 in DDR and the application of synthetic lethal in esophageal cancer with SLFN11 defects. METHODS: To reach the purpose, eight esophageal squamous carcinoma cell lines, 142 esophageal dysplasia (ED) and 1007 primary esophageal squamous cell carcinoma (ESCC) samples and various techniques were utilized, including methylation-specific polymerase chain reaction, CRISPR/Cas9 technique, Western blot, colony formation assay, and xenograft mouse model. RESULTS: Methylation of SLFN11 was exhibited in 9.15% of (13/142) ED and 25.62% of primary (258/1007) ESCC cases, and its expression was regulated by promoter region methylation. SLFN11 methylation was significantly associated with tumor differentiation and tumor size (both P < 0.05). However, no significant associations were observed between promoter region methylation and age, gender, smoking, alcohol consumption, TNM stage, or lymph node metastasis. Utilizing DNA damaged model induced by low dose cisplatin, SLFN11 was found to activate non-homologous end-joining and ATR/CHK1 signaling pathways, while inhibiting the ATM/CHK2 signaling pathway. Epigenetic silencing of SLFN11 was found to sensitize the ESCC cells to ATM inhibitor (AZD0156), both in vitro and in vivo. CONCLUSION: SLFN11 is frequently methylated in human ESCC. Methylation of SLFN11 is sensitive marker of ATM inhibitor in ESCC.

UCHL5 promotes hepatocellular carcinoma progression by promoting glycolysis through activating Wnt/ß-catenin pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is highly malignant with a dismal prognosis, although the available therapies are insufficient. No efficient ubiquitinase has been identified as a therapeutic target for HCC despite the complicating role that of proteins ubiquitination plays in the malignant development of HCC. METHODS: The expression of ubiquitin carboxyl terminal hydrolase L5 (UCHL5) in HCC tumor tissue and adjacent normal tissue was determined using the cancer genome atlas (TCGA) database and was validated using real-time quantitative polymerase chain reaction (RT-qRCR), Western blot and immunohistochemistry (IHC), and the relation of UCHL5 with patient clinical prognosis was explored. The expression of UCHL5 was knocked down and validated, and the effect of UCHL5 on the biological course of HCC was explored using cellular assays. To clarify the molecular mechanism of action of UCHL5 affecting HCC, expression studies of Adenosine triphosphate adenosine triphosphate (ATP), extracellular acidification (ECAR), and glycolysis-related enzymes were performed. The effects of UCHL5 on ß-catenin ubiquitination and Wnt signaling pathways were explored in depth and validated using cellular functionalities. Validation was also performed in vivo. RESULTS: In the course of this investigation, we discovered that UCHL5 was strongly expressed in HCC at both cellular and tissue levels. The prognosis of patients with high UCHL5 expression is considerably worse than that of those with low UCHL5 expression. UCHL5 has been shown to increase the degree of glycolysis in HCC cells with the impact of stimulating the proliferation and metastasis of HCC cells in both in vivo and in vitro. UCHL5 downregulates its degree of ubiquitination by binding to ß-catenin, which activates the Wnt/ß-catenin pathway and accelerates HCC cell glycolysis. Thereby promoting the growth of the HCC. CONCLUSIONS: In summary, we have demonstrated for the first time that UCHL5 is a target of HCC and promotes the progression of hepatocellular carcinoma by promoting glycolysis through the activation of the Wnt/ß-catenin pathway. UCHL5 may thus serve as a novel prognostic marker and therapeutic target for the treatment of HCC.

Breaking the Tumor Chronic Inflammation Balance with a Programmable Release and Multi-Stimulation Engineering Scaffold for Potent Immunotherapy.

Tumor-associated chronic inflammation severely restricts the efficacy of immunotherapy in cold tumors. Here, a programmable release hydrogel-based engineering scaffold with multi-stimulation and reactive oxygen species (ROS)-response (PHOENIX) is demonstrated to break the chronic inflammatory balance in cold tumors to induce potent immunity. PHOENIX can undergo programmable release of resiquimod and anti-OX40 under ROS. Resiquimod is first released, leading to antigen-presenting cell maturation and the transformation of myeloid-derived suppressor cells and M2 macrophages into an antitumor immune phenotype. Subsequently, anti-OX40 is transported into the tumor microenvironment, leading to effector T-cell activation and inhibition of Treg function. PHOENIX consequently breaks the chronic inflammation in the tumor microenvironment and leads to a potent immune response. In mice bearing subcutaneous triple-negative breast cancer and metastasis models, PHOENIX effectively inhibited 80% and 60% of tumor growth, respectively. Moreover, PHOENIX protected 100% of the mice against TNBC tumor rechallenge by electing a robust long-term antigen-specific immune response. An excellent inhibition and prolonged survival in PHOENIX-treated mice with colorectal cancer and melanoma is also observed. This work presents a potent therapeutic scaffold to improve immunotherapy efficiency, representing a generalizable and facile regimen for cold tumors.

Analysis of the causes of primary revision after unicompartmental knee arthroplasty: A case series.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) has great advantages in the treatment of unicompartmental knee osteoarthritis, but its revision rate is higher than that of total knee arthroplasty. AIM: To summarize and analyse the causes of revision after UKA. METHODS: This is a retrospective case series study in which the reasons for the first revision after UKA are summarized. We analysed the clinical symptoms, medical histories, laboratory test results, imaging examination results and treatment processes of the patients who underwent revision and summarized the reasons for primary revision after UKA. RESULTS: A total of 13 patients, including 3 males and 10 females, underwent revision surgery after UKA. The average age of the included patients was 67.62 years. The prosthesis was used for 3 d to 72 months. The main reasons for revision after UKA were improper suturing of the surgical opening (1 patient), osteophytes (2 patients), intra-articular loose bodies (2 patients), tibial prosthesis loosening (2 patients), rheumatoid arthritis (1 patient), gasket dislocation (3 patients), anterior cruciate ligament injury (1 patient), and medial collateral ligament injury with residual bone cement (1 patient). CONCLUSION: The causes of primary revision after UKA were gasket dislocation, osteophytes, intra-articular loose bodies and tibial prosthesis loosening. Avoidance of these factors may greatly reduce the rate of revision after UKA, improve patient satisfaction and reduce medical burden.

Biomechanical response of decompression alone in lower grade lumbar degenerative spondylolisthesis--A finite element analysis.

BACKGROUND: Previous studies have demonstrated the clinical efficacy of decompression alone in lower-grade spondylolisthesis. A higher rate of surgical revision and a lower rate of back pain relief was also observed. However, there is a lack of relevant biomechanical evidence after decompression alone for lower-grade spondylolisthesis. PURPOSE: Evaluating the biomechanical characteristics of total laminectomy, hemilaminectomy, and facetectomy for lower-grade spondylolisthesis by analyzing the range of motion (ROM), intradiscal pressure (IDP), annulus fibrosus stress (AFS), facet joints contact force (FJCF), and isthmus stress (IS). METHODS: Firstly, we utilized finite element tools to develop a normal lumbar model and subsequently constructed a spondylolisthesis model based on the normal model. We then performed total laminectomy, hemilaminectomy, and one-third facetectomy in the normal model and spondylolisthesis model, respectively. Finally, we analyzed parameters, such as ROM, IDP, AFS, FJCF, and IS, for all the models under the same concentrate force and moment. RESULTS: The intact spondylolisthesis model showed a significant increase in the relative parameters, including ROM, AFS, FJCF, and IS, compared to the intact normal lumbar model. Hemilaminectomy and one-third facetectomy in both spondylolisthesis and normal lumbar models did not result in an obvious change in ROM, IDP, AFS, FJCF, and IS compared to the pre-operative state. Moreover, there was no significant difference in the degree of parameter changes between the spondylolisthesis and normal lumbar models after undergoing the same surgical procedures. However, total laminectomy significantly increased ROM, AFS, and IS and decreased the FJCF in both normal lumbar models and spondylolisthesis models. CONCLUSION: Hemilaminectomy and one-third facetectomy did not have a significant impact on the segment stability of lower-grade spondylolisthesis; however, patients with LDS undergoing hemilaminectomy and one-third facetectomy may experience higher isthmus stress on the surgical side during rotation. In addition, total laminectomy changes the biomechanics in both normal lumbar models and spondylolisthesis models.

Predicting the Efficacy of Repeated Shockwave Lithotripsy for Treating Patients with Upper Urinary Tract Calculi Using an Artificial Neural Network Model.

PURPOSE: To establish a prediction model for repeated shockwave lithotripsy (SWL) efficacy to help choose an appropriate treatment plan for patients with a single failed lithotripsy, reducing their treatment burden. PATIENTS AND METHODS: The clinical records and imaging data of 304 patients who underwent repeat SWL for upper urinary tract calculi (UUTC) at the Urology Centre of Shiyan People's Hospital between April 2019 and April 2023 were retrospectively collected. This dataset was divided into training (N = 217; 146 males [67.3%] and 71 females [32.7%]) and validation (N = 87; 66 males [75.9%] and 21 females [24.1%]) sets. The overall predictive accuracy of the models was calculated separately for the training and validation.  Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curve (AUC) was calculated. The normalized importance of each independent variable (derived from the one-way analyses) in the input layer of the artificial neural network (ANN) model for the dependent variable (success or failure in repeat SWL) in the output layer was plotted as a bar chart. RESULTS: This study included 304 patients, of whom 154 (50.7%) underwent successful repeat SWL. Predictive models were constructed in the training set and assessed in the validation set. Fourteen influencing factors were selected as input variables to build an ANN model: age, alcohol, body mass index, sex, hydronephrosis, hematuria, mean stone density (MSD), skin-to-stone distance (SSD), stone heterogeneity index (SHI), stone volume (SV), stone retention time, smoking, stone location, and urinary irritation symptom. The model's AUC was 0.852 (95% confidence interval (CI): 0.8-0.9), and its predictive accuracy for stone clearance in the validation group was 83.3%. The order of importance of the independent variables was MSD > SV > SSD > stone retention time > SHI. CONCLUSION: Establishing an ANN model for repeated SWL of UUTC is crucial for optimizing patient care. This model will be pivotal in providing accurate treatment plans for patients with an initial unsuccessful SWL treatment. Moreover, it can significantly enhance the success rate of subsequent SWL treatments, ultimately alleviating patients' treatment burden.

[Technical Status and Development Trend of Medical Electron Linear Accelerators].

More than 70% of tumor patients require radiotherapy. Medical electron linear accelerators are important high-end radiotherapy equipment for tumor radiotherapy. With the application of artificial intelligence technology in medical electron linear accelerator, radiotherapy has evolved from ordinary radiotherapy to today's intelligent radiotherapy. This study introduces the development history, working principles and system composition of medical electron linear accelerators. It outlines the key technologies for improving the performance of medical linear electron accelerators, including beam control, multi-leaf collimator, guiding technology and dose evaluation. It also looks forward to the development trend of major radiotherapy technologies, such as biological guided radiotherapy, FLASH radiotherapy and intelligent radiotherapy, which provides references for the development of medical electron linear accelerators.

[Retracted] miR­660­5p is associated with cell migration, invasion, proliferation and apoptosis in renal cell carcinoma.

Following the publication of the above article, the authors contacted the Editorial Office to explain that a couple of errors concerning data handling/labelling had been made, firstly during the preparation of the representative images in Fig. 3B, resulting in the wrong image being selected for the data panel showing the ACHN cells treated with 'Inhibitor NC' at 0 h experiment, and secondly in Fig. 5A, resulting in the wrong image being selected for the data panel showing the ACHN cells treated with 'Inhibitor NC' experiment. The authors requested that a corrigendum be published to take account of the errors that were made during the preparation of this figure. Subsequently, an independent investigation of the published data was undertaken by the Editorial Office, which revealed that the 'Inhibitor' data panel in Fig. 6A and the 'Mimic NC' data panel in Fig. 6B were also overlapping, such that these data were likely to have been derived from the same original source, even though these data panels were intended to have shown the results from differently performed experiments. The Editor of Molecular Medicine Reports has considered the authors' request to publish a corrigendum, but given the number of overlapping data panels that have been identified and the number of figures that would be in need of correction, the Editor has decided to decline the authors' request to publish a corrigendum on account of an overall lack of confidence in the presented data, and instead has determined that the paper should be retracted. Upon receiving this news from the Editor, the authors accepted the Editor's decision. The Editor apologizes to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 17: 2051­2060, 2018; DOI: 10.3892/mmr.2017.8052].

Prognostic Role of Neutrophil to Lymphocyte Ratio in Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis.

This meta-analysis assessed the use of the neutrophil-to-lymphocyte ratio (NLR) as a means of early detection of contrast-induced nephropathy (CIN) following diagnostic or therapeutic procedures. We used Web of Science, PubMed, and Scopus to conduct a systematic search. There was no limitation regarding language or date of publication. We reported standardized mean difference (SMD) with a 95% confidence interval (CI). Due to high heterogeneity, a random-effects model was used, and the Newcastle-Ottawa scale was used for quality assessment. Thirty-one articles were included in the analysis. Patients in the CIN group had elevated levels of NLR compared with those in the non-CIN group (SMD = 0.78, 95% CI = 0.52-1.04, P < .001). Similar results were observed in either prospective (SMD = 1.03, 95% CI = 0.13-1.93, P = .02) or retrospective studies (SMD = 0.70, 95% CI = 0.45-0.96, P < .001). The pooled sensitivity of NLR was 74.02% (95% CI = 66.54%-81.02%), and the pooled specificity was 60.58% (95% CI = 53.94%-66.84%). NLR shows potential as a cost-effective biomarker for predicting CIN associated with contrast-involved treatments. This could help implement timely interventions to mitigate CIN and improve outcomes.

Self-supporting noncovalent Choline Alginate/Tannic acid/Ag antibacterial films for strawberry preservation.

Packaging materials with peculiar antibacterial properties can shield off and inhibit microorganism proliferation, thus achieving packaging goals such as fresh-keeping, good hygiene, and biosafety. Especially, antibacterial films made of biocompatible substances have received wide attentions, which could effectively extend the shelf life, enhance food security, and guarantee economic benefits. Herein, a self-supporting hybrid antibacterial film was prepared based on non-covalently linked choline hydroxide (ChOH) and alginic acid (HAlg). Then tannic acid (TA) and silver ions were added to improve the mechanical and antimicrobial properties of this hybrid film. The rich hydroxyl groups from TA not only form multiple hydrogen bonds with ChAlg, but can also in situ reduce silver ions to silver nanoparticles, which were confirmed with various characterizations. In addition, the quantitative antibacterial test proved that the antibacterial rate was significantly improved after adding silver ions, reaching >60 %. In an actual storage test, we found that choline cation (Ch+) captured in antibacterial film by electrostatic interaction could achieve sustained release, i.e. sustainable bacteriostasis, and keep strawberries fresh for 48 h at room temperature. This work offers a new strategy for preparing antibacterial films via non-covalent weak interactions, explored an alternative antibacterial film for food packaging applications.

Resveratrol Ameliorates Retinal Ischemia-Reperfusion Injury by Modulating the NLRP3 Inflammasome and Keap1/Nrf2/HO-1 Signaling Pathway.

Glaucoma, as an ischemia-reperfusion (I/R) injury disease, leading irreversible blindness through the loss of retinal ganglion cells (RGCs), mediated by various pathways. Resveratrol (Res) is a polyphenolic compound that exerts protective effects against I/R injury in many tissues. This article aimed to expound the underlying mechanisms through which Res protects RGCs and reduces visual dysfunction in vivo. An experimental glaucoma model was created using 6-8-week wild-type male C57BL/6J mice. Res was injected intraperitoneally for 5 days. The mice were then grouped according to the number of days after surgery and whether Res treatment was administered. We applied the Brn3a-labeled immunofluorescence staining and flash electroretinography (ERG) to assess the survival of RGCs and visual function. The expression of components of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, the interleukin-1-beta (IL-1ß), and vital indicators of kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme-oxygenase 1 (HO-1) pathway at the protein and RNA levels were detected respectively. The survival of RGCs was reduced after surgery compared to controls, whereas Res application rescued RGCs and improved visual dysfunction. In conclusion, our results discovered that Res administration showed neuroprotective effects through inhibition of the NLRP3 inflammasome pathway and activation of Keap1/Nrf2/HO-1 pathway. Thus, we further elucidated the potential of Res in glaucoma therapy.

[Retracted] Oncogenic miR-23a-5p is associated with cellular function in RCC.

Following the publication of this article, a concerned reader drew to the Editor's attention that, for the invasion and migration assay data shown in Fig. 4 on p. 2314, three pairs of data panels were overlapping, such that data which were intended to show the results from differently performed experiments were obtained from a smaller number of original sources. Moreover, after having conducted an internal investigation, the Editorial Office also observed that some of the flow cytometric data shown in Fig. 6 were duplicated in Fig. 7. Considering the number of overlapping data panels that have been identified in this published paper, the Editor of Molecular Medicine Reports has concluded that the article should be retracted from the publication on account of a lack of confidence in the integrity of the data. Upon contacting the authors about this matter, they accepted the decision to retract this paper. The Editor apologizes to the readership for any inconvenience caused, and thanks the interested reader for drawing this matter to our attention. [Molecular Medicine Reports 16: 2309-2317, 2017; DOI: 10.3892/mmr.2017.6829].

Adsorption Properties of Dissolved Gas Molecules in Transformer Oil on the ReSe2 Monolayer: A DFT Study.

Based on density functional theory, the adsorption behavior of seven typical dissolved gas molecules (CO, CO2, H2, CH4, C2H2, C2H4, and C2H6) and H2O molecule on the ReSe2 monolayer was systematically investigated. The interactions between the ReSe2 monolayer and eight gas molecules were investigated by calculating the adsorption energies, charge transfer, density of states (DOS), and deformation charge density (DCD) for eight different adsorption systems. The gas sensitivity of the ReSe2 monolayer toward these gases was studied using frontier molecular orbital theory and work function analysis. The results demonstrate that compared to other gas molecules, the ReSe2 monolayer exhibits a stronger interaction with CO with an adsorption energy of -1.49 eV. It also displays excellent sensitivity and selectivity toward CO making it a promising candidate for CO gas sensing applications. We aspire that this research will offer theoretical guidance for the development of ReSe2-based gas sensors and contribute to state monitoring technology in oil-immersed power equipment.

[Corrigendum] Identification of lncRNA EGOT as a tumor suppressor in renal cell carcinoma.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, concerrning the Transwell cell migration and invasion assay data shown in Fig. 6A and B for the 786­O cell line on p. 7206, the pcDNA3.1­EGOT 'Migration' and 'Invasion' (a­1 and b­1) data panels appeared to contain overlapping sections of data, such that they were potentially derived from the same original source, where these panels were intended to show the results from differently performed experiments. The authors have re­examined their original data, and realize that the 'Invasion' (b­1) panel in Fig. 6B was inadvertently chosen incorrectly. The revised version of Fig. 6, now featuring the correct data for the 'Invasion' experiment (B1 in the replacement figure) in Fig. 6B, is shown on the next page. Note that this error did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused.[Molecular Medicine Reports 16: 7072­7079, 2017; DOI: 10.3892/mmr.2017.7470].

Identification and validation of an immunotherapeutic signature for colon cancer based on the regulatory patterns of ferroptosis and their association with the tumor microenvironment.

The integrated landscape of ferroptosis regulatory patterns and their association with colon microenvironment have been demonstrated in recent studies. However, the ferroptosis-related immunotherapeutic signature for colon cancer (CC) remains unclear. We comprehensively evaluated 1623 CC samples, identified patterns of ferroptosis modification based on ferroptosis-associated genes, and systematically correlated these patterns with tumor microenvironment (TME) cell infiltration characteristics. In addition, the ferroptosis-regulated gene score (FRG-score) was constructed to quantify the pattern of ferroptosis alterations in individual tumors. Three distinct patterns of ferroptosis modification were identified, including antioxidant defense, iron toxicity, and lipid peroxidation. The characteristics of TME cell infiltration under these three patterns were highly consistent with the three immune phenotypes of tumors, including immune-inflamed, immune-excluded and immune-desert phenotypes. We also demonstrated that evaluation of ferroptosis regulatory patterns within individual tumors can predict tumor inflammatory status, tumor subtype, TME stromal activity, genetic variation, and clinical outcome. Immunotherapy cohorts confirmed that patients with low FRG-scores showed remarkable therapeutic and clinical benefits. Furthermore, the hub gene apolipoprotein L6 (APOL6), a drug-sensitive target associated with cancer cell ferroptosis, was identified through our proposed novel key gene screening process and validated in CC cell lines and scRNA-seq.

Global research status and frontiers on autophagy in hepatocellular carcinoma: a comprehensive bibliometric and visualized analysis.

BACKGROUND: An extensive body of research has explored the role of autophagy in hepatocellular carcinoma (HCC), revealing its critical involvement in the disease's pathogenesis, progression, and therapeutic targeting. However, there is a discernible deficit in quantitative, analytical studies concerning autophagy in the context of HCC. Accordingly, this investigation endeavored to meticulously assess the evolution of autophagy research, employing bibliometric citation analysis to offer a comprehensive evaluation of the findings in this field. METHODS: The authors conducted a literature search on 2 August 2023, to extract relevant publications spanning from 2013 to 2022, indexed in the Science Citation Index-Expanded (SCIE) of the Web of Science Core Collection (WOSCC). Subsequently, the authors performed a bibliometric assessment of the compiled documents using visualization tools such as CiteSpace and VOSviewer. RESULTS: The search yielded 734 publications penned by 4699 authors, encompassing contributions from 41 countries and 909 institutions, disseminated across 272 journals, and comprising 26 295 co-cited references from 2667 journals. Notably, China led in publication volume with 264 articles (amounting to 35.9%) and exhibited the most robust collaboration with the United States. The mechanisms underlying autophagy's influence on the emergence and advancement of HCC, as well as the implicated proteins and genes, have garnered significant attention. In recent years, investigations of targeting autophagy and the resistance to sorafenib have surfaced as pivotal themes and emerging frontiers in this domain. CONCLUSIONS: This study rigorously collated and distilled the prevailing research narratives and novel insights on autophagy in HCC. The resultant synthesis provides a substantive foundation for medical professionals and researchers, as well as pivotal implications for future investigative endeavors in this arena.

Curcumin suppresses metastasis of triple-negative breast cancer cells by modulating EMT signaling pathways: An integrated study of bioinformatics analysis.

This study aimed to use bioinformatics approaches for predicting the anticancer mechanisms of curcumin on triple-negative breast cancer (TNBC) and to verify these predictions through in vitro experiments. Initially, the Cell Counting Kit-8 (CCK8) assay was employed to rigorously investigate the influence of curcumin on the proliferative capacity of TNBC cells. Subsequently, flow cytometry was employed to meticulously assess the impact of curcumin on cellular apoptosis and the cell cycle regulation. Transwell assays were employed to meticulously evaluate the effect of curcumin on the motility of TNBC cells. RNA sequencing was conducted, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of differentially expressed genes, aiming to elucidate the potential anticancer mechanisms underlying curcumin's effects. To thoroughly elucidate the interactions among multiple proteins, we constructed a protein-protein interaction (PPI) network. Finally, the expression levels of several key proteins, including fibronectin, mTOR, ß-Catenin, p-Akt, Akt, N-Cadherin, p-S6, and S6, were assessed using the western blot. The CCK8 assay results showed that curcumin significantly inhibited the proliferation of Hs578T and MDA-MB-231 cells. Flow cytometry results showed that curcumin induced apoptosis in these cells and arrested the cell cycle at the G2/M phase. Additionally, Transwell assay results showed that curcumin effectively reduced the motility of Hs578T and MDA-MB-231 cells. Enrichment analysis of RNA sequencing data showed that the mechanism of action of curcumin was significantly associated with signaling pathways such as pathways in cancer, focal adhesion, and PI3K-Akt signaling pathways. Subsequently, we constructed a protein-protein interaction network to elucidate the interactions among multiple proteins. Finally, Western blotting analysis showed that curcumin significantly decreased the expression levels of key proteins including Fibronectin, mTOR, ß-Catenin, p-Akt, Akt, N-Cadherin, p-S6, and S6. Curcumin exhibits its therapeutic potential in TNBC by modulating multiple signaling pathways. It may inhibit the epithelial-mesenchymal transition process by downregulating the expression of proteins involved in the mTOR and PI3K-Akt signaling pathways, thereby suppressing the motility of TNBC cells. These findings provide experimental evidence for considering curcumin as a potential therapeutic strategy in the treatment of TNBC.

Selective expansion of renal cancer stem cells using microfluidic single-cell culture arrays for anticancer drug testing.

The suboptimal prognosis associated with drug therapy for renal cancer can be attributed to the presence of stem-cell-like renal cancer cells. However, the limited number of these cells prevents conventional drug screening assays from effectively assessing the response of renal cancer stem cells to anti-cancer agents. To address this issue, the present study employed microfluidic single-cell culture arrays to expand renal cancer stem cells by exploiting the anti-apoptosis and self-renewal properties of tumor stem cells. A microfluidic chip with 18 000 hydrophilic microwells was designed and fabricated to establish the single-cell culture array. Over a 7 day culture, the large-scale single-cell culture yielded a limited quantity of single-cell-derived tumorspheres. The sphere formation rates for Caki-1, 786-O, and ACHN cells were determined to be 8.74 ± 0.53%, 12.02 ± 1.43%, and 4.98 ± 1.68%, respectively. The expanded cells exhibited stemness characteristics, as indicated by immunofluorescence, flow cytometry, serial passaging, and in vitro differentiation assays. Additionally, the comparative transcriptomic analysis showed significant differences in the gene expression patterns of the expanded cells compared to the differentiated renal cancer cells. The drug testing indicated that renal cancer stem cells exhibited reduced sensitivity towards the tyrosine kinase inhibitors sorafenib and sunitinib, compared to differentiated renal cancer cells. This reduced sensitivity can be attributed to the elevated expression levels of tyrosine kinase in renal cancer stem cells. This present study provides evidence that the utilization of microfluidic single-cell culture arrays for selective cell expansion can facilitate drug testing of renal cancer stem cells.

Serine/threonine kinase 36 induced epithelial-mesenchymal transition promotes docetaxel resistance in prostate cancer.

To investigate the role and potential mechanism of serine/threonine kinase 36 (STK36) in docetaxel resistance-prostate cancer (PCa). The expression of STK36 in PCa and the correlation with clinicopathological characteristics of PCa patients were analyzed using the data from different databases and tissue microarrays. To investigate the role of STK36 on cell proliferation, invasion, and migration, STK36 was overexpressed and silenced in DU-145 and PC-3 cell lines. Cell counting kit-8 (CCK8) was used to test cell proliferation. Cell invasion and migration were detected by cell wound scratch assay and trans well, respectively. The expression profile of STK36, E-Cadherin, and Vimentin was analyzed by Western blot. Cell apoptosis was detected by the TUNEL assay. STK36 expression was upregulated in PCa tissue compared with adjacent benign PCa tissue; it was higher in patients with advanced stages compared with lower stages and was significantly correlated with decreased overall survival. Up-regulation of STK36 significantly promoted the proliferation, invasion, and migration of DU-145 and PC-3 cells and compensated for the suppression caused by docetaxel treatment in vitro. A striking apoptosis inhibition could be observed when dealing with docetaxel, although the apoptosis of DU-145 and PC-3 cells was not affected by the STK36 exclusive overexpression. Besides, E-Cadherin expression was restrained while the expression levels of vimentin were all enhanced. The knockdown of STK36 reversed the above process. STK36 up-regulation could accelerate the biological behavior and docetaxel resistance of PCa by epithelial-mesenchymal transition (EMT) activation. STK36 may be potentially used as a target in PCa resolvent with docetaxel.