Pharmacogenomic analysis in adrenocortical carcinoma reveals genetic features associated with mitotane sensitivity and potential therapeutics.

Background: Adrenocortical carcinoma (ACC) is an aggressive endocrine malignancy with limited therapeutic options. Treating advanced ACC with mitotane, the cornerstone therapy, remains challenging, thus underscoring the significance to predict mitotane response prior to treatment and seek other effective therapeutic strategies. Objective: We aimed to determine the efficacy of mitotane via an in vitro assay using patient-derived ACC cells (PDCs), identify molecular biomarkers associated with mitotane response and preliminarily explore potential agents for ACC. Methods: In vitro mitotane sensitivity testing was performed in 17 PDCs and high-throughput screening against 40 compounds was conducted in 8 PDCs. Genetic features were evaluated in 9 samples using exomic and transcriptomic sequencing. Results: PDCs exhibited variable sensitivity to mitotane treatment. The median cell viability inhibition rate was 48.4% (IQR: 39.3-59.3%) and -1.2% (IQR: -26.4-22.1%) in responders (n=8) and non-responders (n=9), respectively. Median IC50 and AUC were remarkably lower in responders (IC50: 53.4 µM vs 74.7 µM, P<0.0001; AUC: 158.0 vs 213.5, P<0.0001). Genomic analysis revealed CTNNB1 somatic alterations were only found in responders (3/5) while ZNRF3 alterations only in non-responders (3/4). Transcriptomic profiling found pathways associated with lipid metabolism were upregulated in responder tumors whilst CYP27A1 and ABCA1 expression were positively correlated to in vitro mitotane sensitivity. Furthermore, pharmacologic analysis identified that compounds including disulfiram, niclosamide and bortezomib exhibited efficacy against PDCs. Conclusion: ACC PDCs could be useful for testing drug response, drug repurposing and guiding personalized therapies. Our results suggested response to mitotane might be associated with the dependency on lipid metabolism. CYP27A1 and ABCA1 expression could be predictive markers for mitotane response, and disulfiram, niclosamide and bortezomib could be potential therapeutics, both warranting further investigation.

Association between premature vascular smooth muscle cells senescence and vascular inflammation in Takayasu's arteritis.

OBJECTIVES: Arterial wall inflammation and remodelling are the characteristic features of Takayasu's arteritis (TAK). It has been proposed that vascular smooth muscle cells (VSMCs) are the main targeted cells of inflammatory damage and participate in arterial remodelling in TAK. Whether VSMCs are actively involved in arterial wall inflammation has not been elucidated. Studies have shown that cellular senescence in tissue is closely related to local inflammation persistence. We aimed to investigate whether VSMCs senescence contributes to vascular inflammation and the prosenescent factors in TAK. METHODS: VSMCs senescence and senescence-associated secretory phenotype were detected by histological examination, bulk RNA-Seq and single-cell RNA-seq conducted on vascular surgery samples of TAK patients. The key prosenescent factors and the downstream signalling pathway were investigated in a series of in vitro and ex vivo experiments. RESULTS: Histological findings, primary cell culture and transcriptomic analyses demonstrated that VSMCs of TAK patients had the features of premature senescence and contributed substantially to vascular inflammation by upregulating the expression of senescence-associated inflammatory cytokines. IL-6 was found to be the critical cytokine that drove VSMCs senescence and senescence-associated mitochondrial dysfunction in TAK. Mechanistically, IL-6-induced non-canonical mitochondrial localisation of phosphorylated STAT3 (Tyr705) prevented mitofusin 2 (MFN2) from proteasomal degradation, and subsequently promoted senescence-associated mitochondrial dysfunction and VSMCs senescence. Mitochondrial STAT3 or MFN2 inhibition ameliorated VSMCs senescence in ex vivo cultured arteries of TAK patients. CONCLUSIONS: VSMCs present features of cellular senescence and are actively involved in vascular inflammation in TAK. Vascular IL-6-mitochondrial STAT3-MFN2 signalling is an important driver of VSMCs senescence.

Treatment of malignant airway obstruction with Y-shape sigma stent loaded with I125 seeds installed via rigid bronchoscopy.

PURPOSE: To summarize and analyze the safety and efficacy of a Y-shape Sigma stent loaded with I125 in patients with inoperable malignant main airway obstruction. METHODS: This study was approved by the Institutional Ethics Committee, and a written informed consent was obtained from each participant. A Y-shape Sigma stent loaded with I125 was placed under vision from rigid bronchoscopy. The primary endpoint was alleviation of symptoms and improvement of Karnofsky Performance Status (KPS) score, and the secondary endpoint was complications and technical success. RESULTS: From November 2018 through June 2023, total 33 patients with malignant airway obstruction were palliatively treated by installing Y-shape Sigma stents loaded with I125. The airway lumen was immediately restored and the average airway opening significantly increased to 70 ± 9.4% after the procedure from baseline 30.2 ± 10.5% (p < 0.05). Average KPS score was improved from baseline 30.0 ± 10.0 to 70.0 ± 10.0 (p < 0.05) as well as PaO2 from baseline 50.1 ± 15.4 mmHg to 89.3 ± 8.6 mmHg (p < 0.05). The technical success rate of placing the stent in this study was 73%, and adverse events or complications including bleeding, I125 loss, and airway infection occurred during or after the procedure. CONCLUSION: Placement of Y-shape Sigma stents under vision from rigid bronchoscopy in the patients with malignant airway obstruction is feasible and it immediately alleviates dyspnea and significantly improves quality of life.

Population-based BRCA germline mutation screening in the Han Chinese identifies individuals at risk of BRCA mutation-related cancer: experience from a clinical diagnostic center from greater Shanghai area.

BACKGROUND: Deleterious BRCA1/2 (BRCA) mutation raises the risk for BRCA mutation-related malignancies, including breast, ovarian, prostate, and pancreatic cancer. Germline variation of BRCA exhibits substantial ethnical diversity. However, there is limited research on the Chinese Han population, constraining the development of strategies for BRCA mutation screening in this large ethnic group. METHODS: We profile the BRCA mutational spectrum, including single nucleotide variation, insertion/deletion, and large genomic rearrangements in 2,080 apparently healthy Chinese Han individuals and 522 patients with BRCA mutation-related cancer, to determine the BRCA genetic background of the Chinese Han population, especially of the East Han. Incident cancer events were monitored in 1,005 participants from the healthy group, comprising 11 BRCA pathogenic/likely pathogenic (PLP) variant carriers and 994 PLP-free individuals, including 3 LGR carriers. RESULTS: Healthy Chinese Han individuals demonstrated a distinct BRCA mutational spectrum compared to cancer patients, with a 0.53% (1 in 189) prevalence of pathogenic/likely pathogenic (PLP) variant, alongside a 3 in 2,080 occurrence of LGR. BRCA1 c. 5470_5477del demonstrated high prevalence (0.44%) in the North Han Chinese and penetrance for breast cancer. None of the 3 LGR carriers developed cancer during the follow-up. We calculated a relative risk of 135.55 (95% CI 25.07 to 732.88) for the development of BRCA mutation-related cancers in the BRCA PLP variant carriers (mean age 42.91 years, median follow-up 10 months) compared to PLP-free individuals (mean age 48.47 years, median follow-up 16 months). CONCLUSION: The unique BRCA mutational profile in the Chinese Han highlights the potential for standardized population-based BRCA variant screening to enhance BRCA mutation-related cancer prevention and treatment.

Customizable Porphyrin Platform Enables Folate Receptor PET Imaging Using Copper-64.

Folate receptors including folate receptor α (FRα) are overexpressed in up to 90% of ovarian cancers. Ovarian cancers overexpressing FRα often exhibit high degrees of drug resistance and poor outcomes. A porphyrin chassis has been developed that is readily customizable according to the desired targeting properties. Thus, compound O5 includes a free base porphyrin, two water-solubilizing groups that project above and below the macrocycle plane, and a folate targeting moiety. Compound O5 was synthesized (>95% purity) and exhibited aqueous solubility of at least 0.48 mM (1 mg/mL). Radiolabeling of O5 with 64Cu in HEPES buffer at 37 °C gave a molar activity of 1000 µCi/µg (88 MBq/nmol). [64Cu]Cu-O5 was stable in human serum for 24 h. Cell uptake studies showed 535 ± 12% bound/mg [64Cu]Cu-O5 in FRα-positive IGROV1 cells when incubated at 0.04 nM. Subcellular fractionation showed that most radioactivity was associated with the cytoplasmic (39.4 ± 2.7%) and chromatin-bound nuclear (53.0 ± 4.2%) fractions. In mice bearing IGROV1 xenografts, PET imaging studies showed clear tumor uptake of [64Cu]Cu-O5 from 1 to 24 h post injection with a low degree of liver uptake. The tumor standardized uptake value at 24 h post injection was 0.34 ± 0.16 versus 0.06 ± 0.07 in the blocking group. In summary, [64Cu]Cu-O5 was synthesized at high molar activity, was stable in serum, exhibited high binding to FRα-overexpressing cells with high nuclear translocation, and gave uptake that was clearly visible in mouse tumor xenografts.

Identification of clinically relevant subsets CD39+PD-1+CD8+ T cells and CD39+ regulatory T cells in intrahepatic cholangiocarcinoma using single-cell CyTOF.

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy with limited treatment options and a dismal prognosis. The tumor immune microenvironment (TIME) is crucial for iCCA progression, yet its comprehensive characterization remains incomplete. This study utilized mass cytometry by time of flight (CyTOF) to comprehensively analyze immune cell populations in fresh iCCA tumor samples and adjacent peritumor liver tissues. Notably, NK cell percentages significantly decreased in iCCA lesions compared to peritumor liver tissues. Conversely, an enrichment of immunosuppressive CD39+Foxp3+CD4+ regulatory T cells (CD39+T-regs) and exhausted-like CD8+T cells (with pronounced CD39 and PD-1 expression) within TIME was identified and confirmed by multiplex immunofluorescence staining in an independent patient cohort (n = 140). Crucially, tumor-infiltrating CD39+T-regs and CD39+PD-1+CD8+T cells emerged as independent prognostic indicators associated with an unfavorable prognosis in iCCA. These findings unveil the intricate immune landscape within iCCA, offering valuable insights for disease management and novel cancer immunotherapies.

Evaluating the association between effort-reward imbalance and suboptimal health status among hospital nurses: a cross-sectional study.

OBJECTIVES: Occupational stress is a common complaint in nurses, who perceived more sense of effort-reward imbalance (ERI). Suboptimal health status (SHS) is a state between health and disease. However, the correlation between ERI and SHS is unclear. Therefore, the aim of this study was to examine the prevalence of SHS and ERI and evaluate the relationship between ERI and SHS in clinical nurses by a cross-sectional study. MATERIAL AND METHODS: The current cross-sectional study was conducted through an online survey at Dongping People's Hospital in China. A total of 633 completed surveys were received. Effort-reward imbalance was measured by subscales of the ERI questionnaire. SHS was measured by the Suboptimal Health Status Questionnaire - 25 (SHSQ-25). The relationship between ERI and SHS in nurses was subsequently assessed by Spearman's correlation coefficient and logistic regression model. RESULTS: The mean age of the optimal health status (OHS) group (M±SD 26.3±7.3 years) was younger than the SHS group (M±SD 30.3±6.9 years). The prevalence of SHS was 54.5% (345/633). Female nurses aged ≥30 years, a junior college or university graduate educational level, smokers, and nurses without regular exercise were at a higher risk of SHS. In Spearman's correlation analysis, ERI reflected by the effort-reward ratio was correlated with SHSQ-25 score (r = 0.662, p < 0.001). In logistic regression, ERI was strongly associated with SHS after potential confounding factors adjusting (OR 27.924, 95% CI 22.845-34.132). CONCLUSIONS: The prevalence of SHS was significantly high in clinical nurses. Administrators should pay more attention to health status of female nurses aged ≥30 years, with a junior college or bachelor's degree, smoking, and without regular exercise to reduce the SHS and ERI. Int J Occup Med Environ Health. 2024;37(2):166-75.

Mesenchymal Stem Cell-Derived Exosomes Promote Recovery of The Facial Nerve Injury through Regulating Macrophage M1 and M2 Polarization by Targeting the P38 MAPK/NF-Κb Pathway.

Facial nerve (FN) injury seriously affects human social viability and causes a heavy economic and social burden. Although mesenchymal stem cell-derived exosomes (MSC-Exos) promise therapeutic benefits for injury repair, there has been no evaluation of the impact of MSC-Exos administration on FN repair. Herein, we explore the function of MSC-Exos in the immunomodulation of macrophages and their effects in repairing FN injury. An ultracentrifugation technique was used to separate exosomes from the MSC supernatant. Administrating MSC-Exos to SD rats via local injection after FN injury promoted axon regeneration and myelination and alleviated local and systemic inflammation. MSC-Exos facilitated M2 polarization and reduced the M1-M2 polarization ratio. miRNA sequencing of MSC-Exos and previous literature showed that the MAPK/NF-κb pathway was a downstream target of macrophage polarization. We confirmed this hypothesis both in vivo and in vitro. Our findings show that MSC-Exos are a potential candidate for treating FN injury because they may have superior benefits for FN injury recovery and can decrease inflammation by controlling the heterogeneity of macrophages, which is regulated by the p38 MAPK/NF-κb pathway.

Discriminative Detection of Different Cigarette Brands Using a Fast-Response Electronic Nose.

Electronic noses are an artificial olfactory system that mimics the animal olfactory function. Currently, metal oxide semiconductor (MOS) gas sensors play a vital role in the development of high-performance electronic noses and have widespread applications across various fields. They are particularly valuable in ensuring food safety, monitoring air quality, and even detecting explosives for antiterrorism purposes. However, there is an increasing demand for electronic noses to exhibit faster response times in large-scale commercial applications. To address this challenge, we developed a novel MOS gas sensor with a porous ceramic substrate, specifically designed to facilitate rapid gas diffusion. The sensing performance of the sensor array was evaluated and the result showed that the T90 time of porous ceramic-assisted MOS sensor was significantly (57%) shorter than sensors with a normal substrate. Moreover, the electronic nose system had demonstrated remarkable capability in accurately distinguishing between five distinct types of hazardous gases, including VOCs as well as ammonia. Furthermore, a low-cost electronic system was developed and applied to cigarette brand identification; 2490 groups of data were collected for each individual test at only a cost of 20 s. By employing a machine learning algorithm to analyze the data, an accuracy higher than 95% was achieved (96.29% for K nearest neighbor and 96.32% for random forest). We found that our system can resolve the onset time of electronic nose measurement with enough precision, and it was expected that this special approach by using porous ceramic as an insulating substrate can provide a simple and reliable method to manufacture a fast-response electronic nose.

Triglyceride-glucose index, renal function and cardiovascular disease: a national cohort study.

BACKGROUND: The triglyceride-glucose (TyG) index is a predictor of cardiovascular diseases; however, to what extent the TyG index is associated with cardiovascular diseases through renal function is unclear. This study aimed to evaluate the complex association of the TyG index and renal function with cardiovascular diseases using a cohort design. METHODS: This study included participants from the China Health and Retirement Longitudinal Study (CHARLS) free of cardiovascular diseases at baseline. We performed adjusted regression analyses and mediation analyses using Cox models. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Renal function was defined by the estimated glomerular filtration rate (eGFR). RESULTS: A total of 6 496 participants were included in this study. The mean age of the participants was 59.6 ± 9.5 years, and 2996 (46.1%) were females. During a maximum follow-up of 7.0 years, 1 996 (30.7%) people developed cardiovascular diseases, including 1 541 (23.7%) cases of heart diseases and 651 (10.0%) cases of stroke. Both the TyG index and eGFR level were significantly associated with cardiovascular diseases. Compared with people with a lower TyG index (median level) and eGFR ≥ 60 ml/minute/1.73 m2, those with a higher TyG index and decreased eGFR had the highest risk of cardiovascular diseases (HR, 1.870; 95% CI 1.131-3.069). Decreased eGFR significantly mediated 29.6% of the associations between the TyG index and cardiovascular diseases. CONCLUSIONS: The combination of a higher TyG index and lower eGFR level was associated with the highest risk of cardiovascular diseases. Renal function could mediate the association between the TyG index and cardiovascular risk.

Exosomal miR-200c and miR-141 as cerebrospinal fluid biopsy biomarkers for the response to chemotherapy in primary central nervous system lymphoma.

BACKGROUND: To improve early diagnosis and chemotherapy efficacy monitoring in primary central nervous system lymphoma (PCNSL), cerebrospinal fluid (CSF) exosomal microRNA (miRNA) studies were performed. METHOD: Small RNA sequencing was performed to identify candidate exosomal miRNAs as CSF biopsy biomarkers from two patients with de novo PCNSL and two patients in remission after chemotherapy. miR-200c and miR-141 expression in CSF exosomes was further validated using relative quantitative real-time polymerase chain reaction in patients with PCNSL (n = 20), patients with other neurological diseases (n = 10), and normal subjects (n = 10). Receiver operating characteristic (ROC) curve analyses of miR-200c and miR-141 in the diagnosis and prediction of chemotherapy efficacy in PCNSL were performed in patients treated with methotrexate. Additionally, bioinformatics tools were utilized to predict the potential targets of miR-200c and miR-141. RESULTS: Exosomal miR-200c and miR-141 levels in CSF from patients with PCNSL were significantly lower than those in control subjects. Importantly, miR-200c and miR-141 were upregulated in patients with PCNSL after chemotherapy (P = 0.002). There was a significant correlation between the levels of miR-141 and IL-10 in CSF (P = 0.04). The combination of miR-200c and miR-141 yielded an area under the ROC curve of 0.761 for distinguishing PCNSL with sensitivity and specificity of 60.0% and 96.7%, respectively. The potential target genes of miR-200c and miR-141 in PCNSL included ATP1B3, DYNC1H1, MATR3, NUCKS1, ZNF638, NUDT4, RCN2, GNPDA1, ZBTB38, and DOLK. CONCLUSION: Collectively, miR-200c and miR-141 are likely to be upregulated in CSF exosomes after chemotherapy in patients with PCNSL, highlighting their potential as reliable liquid biopsy biomarkers for PCNSL diagnosis and chemotherapy efficacy monitoring.

Intraindividual difference in estimated GFR by creatinine and cystatin C, cognitive trajectories and motoric cognitive risk syndrome.

BACKGROUND: Intraindividual differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) can convey important clinical information regarding the health status. However, the clinical implications of these differences (eGFRdiff) for risk of cognitive decline and motoric cognitive risk syndrome (MCR) remains unclear. We aimed to investigate the longitudinal associations of eGFRdiff with cognitive trajectories and incident MCR. METHODS: Based on the China Health and Retirement Longitudinal Study, we identified two study sub-cohorts: one for cognitive trajectory follow-up (6423 participants; years:2011-2018) and another for incident MCR follow-up (2477 participants; years:2011-2015). The eGFRdiff was defined as eGFRcys minus eGFRcr. Adjusted ordinal and binary logistics regression models were separately used to assess the associations of eGFRdiff with cognitive trajectories and incident MCR. We also performed discordance analyses for eGFRdiff vs eGFRcys, eGFRcr or eGFR based on both creatinine and cystatin C (eGFRcys-cr). RESULTS: In the first sub-cohort, four distinct 7-year cognitive trajectories were identified. Each 1-SD higher eGFRdiff (value for eGFRcys minus eGFRcr) was associated with a lower risk of poorer cognitive trajectories (OR: 0.909, 95% CI: 0.877-0.942). In the second sub-cohort, 121 participants developed incident MCR after a 4-year follow-up. Each 1-SD higher eGFRdiff (value for eGFRcys minus eGFRcr) was linked with a 25.3% (95%CI: 16.6%-33.2%) decreased risk for MCR. The above associations persisted in individuals with normal kidney function. Additionally, the risk for cognitive decline and incident MCR was more strongly associated with eGFRcys than eGFRcr and eGFRcys-cr. For the discordance analyses, 'discordantly high eGFRdiff/low eGFR' group, but not 'discordantly low eGFRdiff/high eGFR', exhibited a significantly lower risk of poorer cognitive trajectories and MCR compared to the concordant group. CONCLUSIONS: A large negative difference between eGFRcys and eGFRcr (eGFRcys lower than eGFRcr) was associated with higher risk of cognitive decline and incident MCR. The eGFRdiff could capture additional valuable risk information beyond eGFRcys, eGFRcr, and eGFRcys-cr.

Computed Tomography-guided Percutaneous Lung Biopsy With Electromagnetic Navigation Compared With Conventional Approaches: An Open-label, Randomized Controlled Trial.

PURPOSE: The purpose of this study was to assess the efficiency and safety of computed tomography (CT)-guided percutaneous biopsy of lung lesions with electromagnetic (EM) navigation and compare them with those of conventional approaches. MATERIALS AND METHODS: Seventy-nine patients with lung or liver lesions who needed biopsies were enrolled in this trial. All patients were randomly assigned to the E group underwent CT-guided percutaneous biopsies with the EM navigation system or to the C group treated with conventional approaches. RESULTS: In total, 27 patients with lung lesions were assigned to the E group, and 20 patients were assigned to the C group. The diagnostic success rate was 92.6% and 95% in both groups, respectively (P>0.9999). The median number of needle repositions in the E group was less than that in the C group (2.0 vs. 2.5, P=0.03). The positioning success rate with 1 or 2 needle repositions for the E group was significantly higher than the C group (81.5% vs. 50%, P=0.03). The median accuracy of the puncture location in the E group was better than that in the C group (2.0 vs. 6.6 mm, P<0.0001). The total procedure time lengthened in the E group compared with the C group (30.5±1.6 vs. 18.3±1.7 min, P<0.0001), but the number of CT acquisitions was not significantly different (P=0.08). There was no significant difference in complication incidence between the 2 groups (P=0.44). CONCLUSION: The EM navigation system is an effective and safe auxiliary tool for CT-guided percutaneous lung biopsy, but lengthen the procedure time. TRIAL REGISTRATION: ChiCTR2100043361, registered February 9, 2021-retrospectively registered (http://www.medresman.org.cn/uc/project/projectedit.aspx?proj=7591).

Tungsten-based nanoparticles as contrast agents for liver tumor detection using dual-energy computed tomography.

Dual-energy computed tomography (DECT) is a commonly used imaging technique for detecting and diagnosing liver cancer. Currently, it is performed using clinically approved iodinated small molecule contrast agents (CAs). However, these iodinated CAs have several drawbacks, including sub-optimal contrast generation and contra-indication in patients with renal insufficiency. Herein, we synthesized tungsten-based CAs (i.e., WO3-x NPs) with excellent biocompatibility and investigated their effectiveness in DECT imaging. WO3-x NPs significantly enhanced the contrast between liver tumors and normal liver tissues as indicated by in vivo DECT imaging. Furthermore, WO3-x NPs exhibited excellent biocompatibility and minimal systemic toxicity. This study introduces a novel class of CAs for DECT and presents a promising method for accurate early diagnosis of liver tumors.

Detection of cell-type-enriched long noncoding RNAs in atherosclerosis using single-cell techniques: A brief review.

Cardiovascular diseases are the leading causes of mortality and morbidity worldwide. Atherosclerotic plaque underlies the predominant factors and is composed of various cell types, including structure cells, such as endothelial and smooth muscle cells, and immune cells, such as macrophages and T cells. Single-cell RNA sequencing (scRNA-seq) has been extensively applied to decipher these cellular heterogeneities to expand our understanding on the mechanisms of atherosclerosis (AS) and to facilitate identifying cell-type-specific long noncoding RNAs (LncRNAs). LncRNAs have been demonstrated to deeply regulate biological activities at the transcriptional and post-transcriptional levels. A group of well-documented functional lncRNAs in AS have been studied. In our review, we selectively described several lncRNAs involved in the critical process of AS. We highlighted four novel lncRNAs (lncRNA CARMN, LINC00607, PCAT19, LINC01235) detected in scRNA-seq datasets and their functions in AS. We also reviewed open web source and bioinformatic tools, as well as the latest methods to perform an in-depth study of lncRNAs. It is fundamental to annotate functional lncRNAs in the various biological activities of AS, as lncRNAs may represent promising targets in the future for treatment and diagnosis in clinical practice.

MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor.

BACKGROUND: The Mitogen-activated protein kinase 1 (MAPK1) has both independent functions of phosphorylating histones as a kinase and directly binding the promoter regions of genes to regulate gene expression as a transcription factor. Previous studies have identified elevated expression of MAPK1 in human gastric cancer, which is associated with its role as a kinase, facilitating the migration and invasion of gastric cancer cells. However, how MAPK1 binds to its target genes as a transcription factor and whether it modulates related gene expressions in gastric cancer remains unclear. RESULTS: Here, we integrated biochemical assays (protein interactions and chromatin immunoprecipitation (ChIP)), cellular analysis assays (cell proliferation and migration), RNA sequencing, ChIP sequencing, and clinical analysis to investigate the potential genomic recognition patterns of MAPK1 in a human gastric adenocarcinoma cell-line (AGS) and to uncover its regulatory effect on gastric cancer progression. We confirmed that MAPK1 promotes AGS cells invasion and migration by regulating the target genes in different directions, up-regulating seven target genes (KRT13, KRT6A, KRT81, MYH15, STARD4, SYTL4, and TMEM267) and down-regulating one gene (FGG). Among them, five genes (FGG, MYH15, STARD4, SYTL4, and TMEM267) were first associated with cancer procession, while the other three (KRT81, KRT6A, and KRT13) have previously been confirmed to be related to cancer metastasis and migration. CONCLUSION: Our data showed that MAPK1 can bind to the promoter regions of these target genes to control their transcription as a bidirectional transcription factor, promoting AGS cell motility and invasion. Our research has expanded the understanding of the regulatory roles of MAPK1, enriched our knowledge of transcription factors, and provided novel candidates for cancer therapeutics.

Comparison of core needle biopsy and fine-needle aspiration methods in CT-guided percutaneous sampling of pancreatic tumors.

Aims: To compare the diagnostic efficacy and safety of CT-guided percutaneous core needle biopsy (CNB) and fine-needle aspiration (FNA) for pancreatic lesions. Methods and Material: A total of 176 patients with 176 pancreatic lesions who visited our hospital between January 2016 and March 2021 were retrospectively analyzed. They were divided into three groups: FNA group A (<1.5 cm between the lesion and great vessels necessitating FNA), FNA group B, and CNB (the latter two with ≥1.5 cm between the lesion and great vessels necessitating FNA). The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and postoperative. The statistical analysis was done using Statistical Package for the Social Sciences version 17.0. Results: One hundred and seventy six patient's specimens all met the requirements. There were no statistically significant differences in sensitivity, specificity, positive predictive value, negative predictive value, and accuracy between the CNB group and FNA group B, (P > 0.05). Thirteen samples submitted for genetic testing (5 in CNB group, 4 in each of the FNA groups A and B) all met the standards of next-generation sequencing gene detection. The main complications of these groups included abdominal pain, fever, and hyperamylasemia. Conclusions: CT-guided percutaneous FNA and CNB have similar diagnostic efficacy for pancreatic biopsy. Furthermore, FNA has a wide range of puncture indications and is very safe. Like CNB, the obtained tissue through FNA can be genetically tested to guide clinical treatment.

Diatom-derived mesoporous silica nanoparticles loaded with fucoidan for enhanced chemo-photodynamic therapy.

Combination therapy merges chemical photodynamic therapy (CPDT) to improve cancer treatment. It synergizes chemotherapy with photodynamic therapy (PDT), using photosensitizers to produce reactive oxygen species (ROS) when exposed to light, effectively killing drug-resistant cancer cells. It is not affected by drug resistance, making it an attractive option for combination with chemotherapy. In this study, the focus was on the design of a combination therapy of chemotherapy and PDT. They synthesized diatomaceous earth mesoporous silica nanoparticles (dMSN) containing lanthanide metal ions in a PDT composition. These nanoparticles can generate ROS under near-infrared light irradiation and have MRI and fluorescence imaging capabilities, confirming their phototherapeutic effect on HCT116 cancer cells at a 200 µg/mL concentration. Fucoidan, derived from brown algae, was used as the chemotherapy component. The fucoidan extracted from Sargassum oligocystum in Pingtung Haikou showed the highest anticancer activity, with cell viability of 57.4 % at 200 µg/mL on HCT116 cancer cells. For combination therapy, fucoidan was loaded into nanoparticles (dMSN-EuGd@fucoidan). Cell viability experiments revealed that at 200 µg/mL, the cell survival rate of dMSN-EuGd@Fucoidan on HCT116 cancer cells was 47.7 %. Combination therapy demonstrated superior anticancer efficacy compared to PDT or chemotherapy alone, successfully synthesizing nanoparticles for combined chemotherapy and photodynamic therapy.