AMPK-a key factor in crosstalk between tumor cell energy metabolism and immune microenvironment?

Immunotherapy has now garnered significant attention as an essential component in cancer therapy during this new era. However, due to immune tolerance, immunosuppressive environment, tumor heterogeneity, immune escape, and other factors, the efficacy of tumor immunotherapy has been limited with its application to very small population size. Energy metabolism not only affects tumor progression but also plays a crucial role in immune escape. Tumor cells are more metabolically active and need more energy and nutrients to maintain their growth, which causes the surrounding immune cells to lack glucose, oxygen, and other nutrients, with the result of decreased immune cell activity and increased immunosuppressive cells. On the other hand, immune cells need to utilize multiple metabolic pathways, for instance, cellular respiration, and oxidative phosphorylation pathways to maintain their activity and normal function. Studies have shown that there is a significant difference in the energy expenditure of immune cells in the resting and activated states. Notably, competitive uptake of glucose is the main cause of impaired T cell function. Conversely, glutamine competition often affects the activation of most immune cells and the transformation of CD4+T cells into inflammatory subtypes. Excessive metabolite lactate often impairs the function of NK cells. Furthermore, the metabolite PGE2 also often inhibits the immune response by inhibiting Th1 differentiation, B cell function, and T cell activation. Additionally, the transformation of tumor-suppressive M1 macrophages into cancer-promoting M2 macrophages is influenced by energy metabolism. Therefore, energy metabolism is a vital factor and component involved in the reconstruction of the tumor immune microenvironment. Noteworthy and vital is that not only does the metabolic program of tumor cells affect the antigen presentation and recognition of immune cells, but also the metabolic program of immune cells affects their own functions, ultimately leading to changes in tumor immune function. Metabolic intervention can not only improve the response of immune cells to tumors, but also increase the immunogenicity of tumors, thereby expanding the population who benefit from immunotherapy. Consequently, identifying metabolic crosstalk molecules that link tumor energy metabolism and immune microenvironment would be a promising anti-tumor immune strategy. AMPK (AMP-activated protein kinase) is a ubiquitous serine/threonine kinase in eukaryotes, serving as the central regulator of metabolic pathways. The sequential activation of AMPK and its associated signaling cascades profoundly impacts the dynamic alterations in tumor cell bioenergetics. By modulating energy metabolism and inflammatory responses, AMPK exerts significant influence on tumor cell development, while also playing a pivotal role in tumor immunotherapy by regulating immune cell activity and function. Furthermore, AMPK-mediated inflammatory response facilitates the recruitment of immune cells to the tumor microenvironment (TIME), thereby impeding tumorigenesis, progression, and metastasis. AMPK, as the link between cell energy homeostasis, tumor bioenergetics, and anti-tumor immunity, will have a significant impact on the treatment and management of oncology patients. That being summarized, the main objective of this review is to pinpoint the efficacy of tumor immunotherapy by regulating the energy metabolism of the tumor immune microenvironment and to provide guidance for the development of new immunotherapy strategies.

A combination of logical judging circuit and water-resistant ultrathin film PEDOT: PSS electrode for noninvasive ECG measurement.

Heart disease-related deaths have increased in recent decades, with most patients dying of sudden cardiac arrest. In such instances, the effect of regular electrocardiogram (ECG) measurements is minimal. Therefore, long-term ECG monitoring has become increasingly important. In this paper, we report a non-adhesive high accuracy ECG monitoring system that can be used in various scenarios without interfering with daily activities. The ECG ultra-thin film electrode is made by water-resistant material based on poly(3,4-ethylenedioxythiophene) poly(4-styrenesulfonate) (PEDOT: PSS) electrode doped with ethylene glycol (EG) and xylitol, to improve the noise signal caused by sweat. The optimal ratio of the three ingredients of PEDOT: PSS/xylitol/EG was determined experimentally to accommodate the ECG monitoring. By using the proposed selectively closed multi-channel single-lead logic circuit, the noise of ECG signal received from the proposed film electrode can be successfully reduced during broad-area electrode measurements, thus to improve ECG measurement accuracy.

Metal-Plastic Hybrid Additive Manufacturing to Realize Small-Scale Self-Propelled Catalytic Engines.

Microengines driven by catalytic decomposition of a fuel have been an interesting research area recently due to their diverse applications, such as environmental monitoring and drug delivery. Literature reports a number of studies on this topic where researchers have made various attempts to manufacture such microengines. Some such methods are deposition of catalytic metal layers on sacrificial photoresists, electrochemical deposition of metal layers on polymeric structures, or 3D printing of structures followed by multi-step loading of structures with catalysts. These methods, even though proven to be effective, are tedious, time-consuming, and expensive. To address these issues, herein we report a 3D printing technique to realize microengines in a simple, rapid, and inexpensive single-step process. The printing of various shapes of microengines is achieved using digital light processing printing of a catalyst resin, where Pd(II) acts as a catalyst resin. The proposed integrated molding process can achieve cost-effective preparation of high-efficiency microengines. We demonstrate the locomotion of these microengines in 30% (w/w) H2O2 through the decomposition of H2O2 to generate oxygen to facilitate the self-propelled locomotion. The study characterizes the microengine based on several factors, such as the role of H2O2, Pd, shape, and design of the microengine, to get a full picture of the self-locomotion of microengines. The study shows that the developed method is feasible to manufacture microengines in a simple, rapid, and inexpensive manner to be suitable for numerous applications such as environmental monitoring, remediation, drug delivery, diagnosis, etc., through the modification of the catalyst resin and fuel, as desired.

Molecular mechanism underlying epithelial-mesenchymal transformation and cisplatin resistance in esophageal squamous cell carcinoma.

Esophageal cancer (EC) occupies the seventh spot of the most prevalent malignancy cancer ailments worldwide and the sixth leading cause of cancer-related death. Esophageal squamous cell carcinoma (ESCC) is also the most predominant histological subtype of EC, and cisplatin (DDP) is commonly used as a first-line chemotherapeutic drug for the late advanced stages of the disease. However, the emergence of drug resistance during clinical treatment possesses a significant challenge to the therapeutic success and patient outcomes. Collectively, the epithelial-mesenchymal transformation (EMT) is a process in which transcription factors are induced to regulate the expression of epithelial and stromal markers to promote the differentiation of epithelial cells into stromal cells. Recent studies have demonstrated a close association between EMT and chemotherapy resistance in tumor cells, with concrete evidence of reciprocal reinforcement. Therefore, in this review, we elucidate the molecular mechanism underlying ESCC, shed light on the mechanisms driving DDP resistance, and provide insights into the intricate interplay between EMT and ESCC. We have aimed to provide some new hypotheses and perspectives that may address-inform future therapeutic strategies for ESCC treatment.

The 3'­untranslated region of XB130 regulates its mRNA stability and translational efficiency in non­small cell lung cancer cells.

Silencing XB130 inhibits cell proliferation and epithelial-mesenchymal transition in non-small cell lung cancer (NSCLC), suggesting that downregulating XB130 expression may impede NSCLC progression. However, the molecular mechanism underlying the regulation of XB130 expression remains unclear. In the present study, the role of the 3'-untranslated region (3'-UTR) in the regulation of XB130 expression was investigated. Recombinant psiCHECK-2 vectors with wild-type, truncated, or mutant XB130 3'-UTR were constructed, and the effects of these insertions on reporter gene expression were examined using a dual-luciferase reporter assay and reverse transcription-quantitative PCR. Additionally, candidate proteins that regulated XB130 expression by binding to critical regions of the XB130 3'-UTR were screened for using an RNA pull-down assay, followed by mass spectrometry and western blotting. The results revealed that insertion of the entire XB130 3'-UTR (1,218 bp) enhanced reporter gene expression. Positive regulatory elements were primarily found in nucleotides 113-989 of the 3'-UTR, while negative regulatory elements were found in the 1-112 and 990-1,218 regions of the 3'-UTR. Deletion analyses identified nucleotides 113-230 and 503-660 of the 3'-UTR as two major fragments that likely promote XB130 expression by increasing mRNA stability and translation rate. Additionally, a U-rich element in the 970-1,053 region of the 3'-UTR was identified as a negative regulatory element that inhibited XB130 expression by suppressing translation. Furthermore, seven candidate proteins that potentially regulated XB130 expression by binding to the 113-230, 503-660, and 970-1,053 regions of the 3'-UTR were identified, shedding light on the regulatory mechanism of XB130 expression. Collectively, these results suggested that complex sequence integrations in the mRNA 3'-UTR variably affected XB130 expression in NSCLC cells.

HnRNPAB is an independent prognostic factor in non­small cell lung cancer and is involved in cell proliferation and metastasis.

Heterogeneous nuclear ribonucleoprotein A/B (hnRNPAB) is an RNA binding protein that is closely associated with the biological function and metabolism of RNA, which is involved in the malignant transformation of various tumor cells. However, the role and mechanisms of hnRNPAB in non-small cell lung cancer (NSCLC) are still unclear. In the present study, the expression levels of hnRNPAB in NSCLC and normal tissues were analyzed using the human protein atlas database and UALCAN database. The clinical significance of hnRNPAB was assayed using the data of NSCLC cases from The Cancer Genome Atlas database. Subsequently, two stable NSCLC cell lines with hnRNPAB knockdown were constructed and the effects of hnRNPAB silencing on cell viability, migration, invasion and epithelial-mesenchymal transition (EMT) were identified. Genes associated with hnRNPAB expression in NSCLC were screened using the Linked Omics database and verified by quantitative real-time PCR (RT-qPCR). The database analysis indicated that hnRNPAB was mainly expressed in the nucleus of NSCLC cells. Compared with the normal tissues, hnRNPAB expression was overexpressed in NSCLC tissues and was closely associated with the overall survival, sex, tumor-node-metastases classification, and poor prognosis of patients with lung adenocarcinoma. Functionally, knockdown of hnRNPAB inhibited the proliferation, migration, invasion and EMT of NSCLC cells and arrested the cell cycle at G1 phase. Mechanistically, the bioinformatics analysis and RT-qPCR verification demonstrated that hnRNPAB knockdown led to a significant expression change of genes associated with tumorigenesis. In conclusion, the present study indicated that hnRNPAB played an important role in the malignant transformation of NSCLC, supporting the significance of hnRNPAB as a novel potential therapeutic target for the early diagnosis and prognosis of NSCLC.

Good or bad: Paradox of plasminogen activator inhibitor 1 (PAI-1) in digestive system tumors.

The fibrinolytic system is involved in many physiological functions, among which the important members can interact with each other, either synergistically or antagonistically to participate in the pathogenesis of many diseases. Plasminogen activator inhibitor 1 (PAI-1) acts as a crucial element of the fibrinolytic system and functions in an anti-fibrinolytic manner in the normal coagulation process. It inhibits plasminogen activator, and affects the relationship between cells and extracellular matrix. PAI-1 not only involved in blood diseases, inflammation, obesity and metabolic syndrome but also in tumor pathology. Especially PAI-1 plays a different role in different digestive tumors as an oncogene or cancer suppressor, even a dual role for the same cancer. We term this phenomenon "PAI-1 paradox". PAI-1 is acknowledged to have both uPA-dependent and -independent effects, and its different actions can result in both beneficial and adverse consequences. Therefore, this review will elaborate on PAI-1 structure, the dual value of PAI-1 in different digestive system tumors, gene polymorphisms, the uPA-dependent and -independent mechanisms of regulatory networks, and the drugs targeted by PAI-1 to deepen the comprehensive understanding of PAI-1 in digestive system tumors.

New Metal-Plastic Hybrid Additive Manufacturing for Precise Fabrication of Arbitrary Metal Patterns on External and Even Internal Surfaces of 3D Plastic Structures.

Constructing precise metal patterns on complex three-dimensional (3D) plastic parts allows the fabrication of functional devices for advanced applications. However, it is currently expensive and requires complex processes. This study demonstrates a process for the fabrication of 3D metal-plastic composite structures with arbitrarily complex shapes. A light-cured resin is modified to prepare the active precursor allowing subsequent electroless plating (ELP). A multimaterial digital light processing 3D printer was newly developed to fabricate the parts containing regions made of either standard resin or active precursor nested within each other. Selective 3D ELP processing of such parts provided various metal-plastic composite parts having complicated hollow structures with specific topological relationships with the resolution of 40 µm. Using this technique, 3D devices that cannot be manufactured by traditional methods are possible, and metal patterns can be produced inside plastic parts as a means of further miniaturizing electronics. The proposed method can also generate metal coatings exhibiting improved adhesion of metal to substrate. Finally, several sensors composed of different functional materials and specific metal patterns were designed and fabricated. The present results demonstrate the viability of the proposed method and suggest potential applications in the fields of 3D electronics, wearable devices, and sensors.

Epithelial-Mesenchymal Transition Gene Signature Is Associated with Neoadjuvant Chemoradiotherapy Resistance and Prognosis of Esophageal Squamous Cell Carcinoma.

Background: Neoadjuvant chemoradiotherapy (neo-CRT) in combination with surgery increases survival compared to surgery alone, as indicated by the esophageal squamous cell carcinoma (ESCC) treatment recommendations. However, the benefits of neo-CRT are diverse among patients. Consequently, the development of new biomarkers that correlate with neo-CRT might be important for the treatment of ESCC. Methods: The differentially expressed genes (DEG) between responsive and resistant samples from the GSE45670 dataset were obtained. On the TCGA dataset, survival analysis was performed to identify prognosis-related-EMT-genes. For EMT score model construction, lasso regression analysis in the TCGA cohort was used to identify the genes. In the TCGA-ESCC cohort, age, stage, and EMT score were used to construct a nomogram. Results: In total, 10 prognosis-related-EMT-genes were obtained. These 10 genes consisted of 6 risky genes and 4 protective genes. Based on the lasso analysis and univariate Cox regression, an EMT score model consisting of 7 genes (CLEC18A, PIR, KCNN4, MST1R, CAPG, ALDH5A1, and COX7B) was identified. ESCC patients with a high EMT score have a worse prognosis. These genes were differentially expressed between responsive and resistant patients and had a high accuracy for distinguishing resistant and responsive patients. Conclusions: The identified genes have the potential to function as molecular biomarkers for predicting ESCC patients' resistance to neo-CRT. This research may aid in the elucidation of the molecular processes driving resistance and the identification of targets for improving the prognosis for ESCC.

The effects of wrist position and radioulnar wrist compression on median nerve longitudinal mobility.

BACKGROUND: Carpal tunnel syndrome is an entrapment neuropathy at the wrist characterized by compromised median nerve mobility. The purpose of this study was to investigate the effect of wrist position on median nerve longitudinal mobility in healthy subjects and the effect of radioulnar wrist compression on the median nerve mobility under non-neutral wrist positions. METHODS: Dynamic B mode ultrasound images captured longitudinal median nerve motion in the carpal tunnel in 10 healthy subjects at wrist neutral position, 30-degree flexion, and 30-degree extension. In each position, RWC of 0, 5, 10, and 15 N were applied. One-way repeated measure analysis of variance (ANOVA), Post-hoc Tukey's tests, and the Friedman Test were used to show the significant differences of median nerve longitudinal mobility at different wrist positions and force conditions. FINDINGS: Median nerve longitudinal mobility was found to be significantly influenced by wrist position (P < 0.05). The mobility under wrist neutral position was 3.02 mm/s, 38% higher than under wrist flexion (2.18 ± 0.60 mm/s), and 32% higher than under wrist extension (2.29 ± 0.43 mm/s). The impaired median nerve mobility was significantly restored under 10 N radioulnar wrist compression (P < 0.05), by 34.4% under wrist flexion (3.03 ± 0.85 mm/s), and 38.9% under wrist extension (3.07 ± 0.79 mm/s). INTERPRETATION: Non-neutral wrist positions compromise median nerve longitudinal mobility, but moderate radioulnar compressive forces are beneficial in the recovery of median nerve longitudinal mobility, and may help to prevent symptoms associated with carpal tunnel syndrome.

Association between eight hypermethylation-related genes and gastric cancer: a systematic review and meta-analysis.

Background: Although multiple gene promoter hypermethylation has been associated with gastric carcinogenesis, data on their specific relationship remains scant. We aimed to investigate the correlation between the status of multiple gene promoter methylation and gastric cancer (GC). Methods: We searched PubMed, EMBASE, CNKI, Wanfang, Cqvip and Cochrane Library up to May 2021. We systematically assessed the association between methylation status of the CpG islands and the risk of GC. We compared the incidence of DNA methylation between tumor and non-tumor tissues, and evaluated the clinicopathological significance of the DNA methylation in gastric carcinoma. The data was presented by an odds ratio (OR) with an accompanying 95% confidence interval (CI). We then generated forest plots calculated by fixed-effects or random-effects model. Results: This study enrolled a total of 201 studies (140 papers). Our analysis showed a higher frequency of methylation of the CpG islands in GC tissues compared to non-neoplastic tissues. Besides, the data demonstrated that polygene's aberrant promoter methylation might be linked to the initial development and progression of GC. Discussion: The genes with altered DNA methylation might serve as epigenetic biomarkers, providing a promising molecular diagnostic and prognostic tool for human GC. However, our findings need further evaluation in large randomized controlled trials.

Serum gamma-glutamyl transpeptidase-to-platelet ratio (GPR) can predict the prognosis of hepatocellular carcinoma: a meta-analysis and systematic review.

Background: The relationship between serum gamma-glutamyl transpeptidase-to-platelet ratio (GPR) before treatment and the prognosis of patients with hepatocellular carcinoma (HCC) is unclear. Here, we review and summarize existing data and try to determine the predictive value of GPR in the treatment of HCC. Methods: We searched Web of Science, PubMed, Embase and China national knowledge infrastructure (CNKI) for clinical trials investigating GPR and HCC in participants with and without HCC. We developed the inclusion criteria based on the principle of population-intervention-result-control-study design. Studies that do not meet the standards were excluded. Studies were subjected to quality assessments using the Cochrane Risk of Bias Tool for cluster-randomized control trials. Sensitivity, statistical, heterogeneity, and publication bias analyses on STATA version 16.1 (STATA 2020). Results: The pooled data from 7 studies of 1,952 patients showed that the specificity of GPR for predicting the prognosis of HCC was 0.67 (95% CI: 0.61-0.73), and the sensitivity was 0.62 (95% CI: 0.57-0.67). The Fagan chart prediction shows that the patient's GPR indicates the prognostic effect of HCC. The positive predictive value is 32%, which is significantly higher than before. The ROC curve is used to analyze the effectiveness of GPR in predicting the prognosis of HCC, and the area under the curve (AUC) is 0.69 (0.65-0.73). There is no publication bias in this study (The Deek funnel chart, P=0.48). Discussion: Our results are similar to those of most previous studies, and meta-analysis showed that GPR has well sensitivity, accuracy, and prognostic value in HCC.

Photodynamic Therapy in Combination with Chemotherapy, Targeted, and Immunotherapy As a Successful Therapeutic Approach for Advanced Gastric Adenocarcinoma: A Case Report and Literature Review.

Objective: To explore the efficacy of photodynamic therapy combined with chemotherapy, targeted therapy, and immunotherapy in poorly differentiated gastric adenocarcinoma (GAC). Background: Advanced GAC has high malignancy and mortality rate. To date, no study has applied photodynamic treatment (PDT) combined with chemo-, targeted, and immunotherapy to treat this cancer. Patient and methods: Clinical data of a patient diagnosed with poorly differentiated GAC admitted to the department of oncology of the Lanzhou University Second Hospital were retrospectively analyzed. The patient underwent four PDT procedures combined with chemo-, targeted, and immunotherapy. Results: A 72-year-old male patient received combination therapy of PDT. This treatment resolved the cancerous tissues and levels of tumor markers. There was no recurrence and metastasis during a 7-month follow-up. Conclusions: Combination therapy of PDT can effectively treat tumors and may be a method suitable for elderly patients with advanced GAC.

3D-printed swab with cover for precision diagnosis.

The collection capacity of common nasopharyngeal swabs and irregularities of medical personnel limit the accuracy of PCR testing. This study describes a newly designed 3D-printed swab that is combined with a 3D-printed cover to prevent the extraction of undesired nasal secretions. This swab improved the accuracy of PCR test results. The results of a series of experiments showed that, because of the mucus extraction effect, 3D-printed swabs can replace ordinary cotton swabs. The crisis of the worldwide medical supply shortage can be ameliorated to a certain extent by applying 3D printing technology.

A comprehensive study of celastrol metabolism in vivo and in vitro using ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry.

Celastrol has attracted great attention owing to its anti-arthritis, antioxidant, and anticancer activities. Nevertheless, its metabolism in vivo (rats) and in vitro (rat liver microsomes and intestinal flora) has not been comprehensively characterized. In this study, ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry was used as a rapid and sensitive approach for studying the metabolism of celastrol in vivo and in vitro. A total of 43 metabolites were identified and characterized. These include 26 metabolites in vivo, and 28 metabolites in vitro (nine metabolites in rat liver microsomes and 24 metabolites in rat intestinal flora). Additionally, the celastrol-biotransformation capacity of the intestinal tract was confirmed to exceed that of the liver. Furthermore, the metabolic profile of celastrol is summarised. The information obtained from this study may provide a basis for understanding the pharmacological mechanisms of celastrol and will be beneficial for clinical applications.

Electro-spray deposited TiO2 bilayer films and their recyclable photocatalytic self-cleaning strategy.

Recyclable titanium dioxide (TiO2)-based photocatalytic self-cleaning films (SCFs) having a bilayer structure were prepared and assessed. These SCFs comprised two layers of fibers fabricated using an electrospinning process. The self-cleaning layer was made of acrylonitrile-butadiene-styrene (ABS) fibers with embedded TiO2 while the substrate layer was composed of fibers made by simultaneously electrospinning poly (vinyl alcohol) (PVA) and ABS. This substrate improved the mechanical strength of the SCF and provided greater adhesion due to the presence of the PVA. The experimental results showed that the hydrophobicity (as assessed by the water contact angle), photocatalytic properties and self-cleaning efficiency of the SCF were all enhanced with increasing TiO2 content in the ABS/TiO2 fibers. In addition, the introduction of the substrate layer allowed the SCFs to be applied to various surfaces and then peeled off when desired. The ABS fibers effectively improved the strength of the overall film, while deterioration of the ABS upon exposure to UV light was alleviated by the addition of TiO2. These SCFs can potentially be recycled after use in various environments, and therefore have applications in the fields of environmental protection and medical science.

The Role of N6-Methyladenosine Methylation in the Progression of Endometrial Cancer.

Purpose: N6-methyladenosine (m6A) methylation was the most abundant internal modification on messenger RNAs in eukaryotes. This study intended to explore the role of m6A methylation in endometrial cancer (EC). Materials and Methods: The m6A-sequencing data "GSE93911" of human EC were downloaded from Gene Expression Omnibus database. Hisat2 software and MACS2 were used to perform the alignment of reads and m6A methylation peak calling, and the peaks were annotated using Chipseeker. Then, differential m6A methylation peaks between normal and tumor samples were analyzed, followed by the functional enrichment analysis of the differentially methylated genes in promoter and 3' untranslated region (UTR) using Clusterprofiler. Based on the 450K methylated chip data, gene expression and clinical data in The Cancer Genome Atlas, the differentially methylated genes were verified, followed by Cox univariate/multivariate regression analysis and survival analysis. Finally, a risk prognosis model was constructed. Results: The m6A peak number was decreased in EC. The distribution of m6A peaks was highly enriched near transcriptional start site, in promoter, UTR, intron and exon, followed by distal intergenic. A total of 581 differentially methylated genes (361 hyper- and 220 hypomethylated genes) were identified in promoter and UTR regions that were enriched in insulin resistance (IR) and extracellular matrix (ECM). A total of 181 genes with significant differential expressions and differential methylation site in EC were selected. Of which, 31 genes were correlated with survival, and an 11-gene risk prognosis model was identified, including GDF7, BNC2, SLC8A1, B4GALNT3, DHCR24, ESRP1, HOXB9, IGSF9, KIAA1324, MSnX1, and PHGDH. Conclusion: The m6A methylation regulated EC progression by targeting the genes related to IR and ECM. A 11-gene risk prognosis model was identified to predict survival of patients with EC.

A Smart "Sense-and-Treat" Nanoplatform Based on Semiconducting Polymer Nanoparticles for Precise Photothermal-Photodynamic Combined Therapy.

Integrated theranostic nanoplatforms with biomarker recognition and photothermal- and photodynamic (PTT/PDT) therapy is in high demand but remains challenging. Herein, a "sense-and-treat" nanoplatform based on semiconducting polymer nanoparticles (SPNs) for ratiometric bioimaging of phospholipase D (PLD) activity and PTT/PDT combined therapy was proposed. Semiconducting polymer nanoparticles (PSBTBT NPs) serve not only as photothermal agents but also as fluorescent quenchers of Rhodamine B (Rhod B) through a PLD-cleavable linker. Chlorin e6 (Ce6) was used as a photodynamic agent and fluorescence reference. The obtained nanoplatform (PSBTBT-Ce6@Rhod NPs) showed high PDT efficiency and photothermal performance upon single laser irradiation. The PTT/PDT combined therapy achieved more efficient tumor inhibition results as compared with single treatments. In addition, the overexpressed biomarker PLD in tumor tissue will cleave Rhod, leading to the fluorescence recovery of Rhod B and thus allowing the activatable fluorescence imaging of tumor and targeted phototherapy.

The self-assembly of a hybrid photosensitizer for the synergistically enhanced photodynamic/photothermal therapy.

The simultaneous near-infrared (NIR)-absorbed photodynamic therapy (PDT)/photothermal therapy (PTT) has proved to be a promising approach to increase the antitumor efficiency due to their synergistic effect. Herein, a boron dipyrromethene (BODIPY)-based photosensitizer was designed and synthesized for the enhanced synergistic NIR-absorbed PDT/PTT therapy upon NIR light irradiation. In this strategy, a three-dimensional rigid polyhedral oligomeric silsesquioxane (POSS) block was introduced into the Br-BODIPY molecule to alleviate the aggregation of the photosensitizer. The POSS hybrid BODIPY (Br-BODIPY-POSS) was further functionalized with a biocompatible amphiphilic PEG via a facile thiol-ene "click" reaction, affording Br-BODIPY-POSS-PEG2000 (BBPP). BBPP can self-assemble into nanoparticles, which maintain a competitive photothermal conversion efficiency (ηBBPP = 30.2%) with its counterpart Br-BODIPY-PEG (BBP, ηBBP = 34.5%). Significantly, BBPP exhibited a relatively higher oxygen quantum yield (ΦBBPP = 0.405) than BBP (ΦBBP = 0.175). The in vitro and in vivo experiments showed that BBPP possessed negligible dark cytotoxicity and a better phototherapeutic outcome than BBP. The proof-of-concept of the POSS hybrid photosensitizer offers guidance for the construction of single-component and PDT/PTT-balanced NIR nanoagents to promote the cancer therapeutic efficacy in the future.

Members of the miR-30 family inhibit the epithelial-to-mesenchymal transition of non-small-cell lung cancer cells by suppressing XB130 expression levels.

MicroRNAs (miRs) are associated with cancer metastasis. Aberrant expression levels of members of the miR-30 family have been observed in non-small-cell lung cancer (NSCLC). However, the effects of miR-30 family members on the epithelial-to-mesenchymal transition (EMT) of NSCLC cells and the underlying molecular mechanisms have not yet been fully elucidated. The present study investigated the effects of miR-30 family members on EMT, migration and invasion of NSCLC cells and found that overexpression of these miRs inhibited EMT via decreasing the expression levels of N-cadherin, ß-catenin and SNAI1, along with weakened migration and invasion abilities. Then, XB130 was identified as a downstream target of the miR-30 family members. XB130-knockdown also inhibited EMT of NSCLC cells, whereas ectopic overexpression of XB130 partly rescued the suppressive effects of miR-30c and miR-30d on EMT. In conclusion, miR-30 family members inhibited EMT of NSCLC cells, partially via suppressing XB130 expression levels.