DNA methylation regulates TREM1 expression to modulate immune responses and drive progression in colorectal neuroendocrine neoplasm as a potential therapeutic target.

Background: Colorectal neuroendocrine neoplasms (CrNENs) are rare malignancies with limited therapeutic options and poorly understood molecular mechanisms. The roles of genetic, epigenetic, and immune factors in CrNEN progression remain largely unknown.

Methods: We employed an integrative multi-omics approach combining two-sample Mendelian randomization, Bayesian colocalization, methylation quantitative trait loci (mQTLs), cis-expression QTLs (cis-eQTLs), protein QTLs (pQTLs), summary data-based Mendelian randomization, mediation analyses, immunohistochemistry validation, and pan-cancer validation using TCGA and GTEx data, including DNA methylation profiling using the SMART, UALCAN, UCSC Xena and MethSurv platforms to provide integrative insights into potential epigenetic regulation in oncogenesis.

Toward a Species Search Engine: KISSE Offers a Rigorous Statistical Framework for Bone Collagen Tandem Mass Spectrometry Data.

DNA and bone collagen are two key sources of resilient molecular markers used to identify species from their remains. Collagen is more stable than DNA, and thus it is preferred for ancient and degraded samples. Current mass spectrometry-based collagen sequencing approaches are empirical and lack a rigorous statistical framework.

Impact of serum TRAb level changes on the efficacy of I therapy in Graves' disease: a decision tree prediction model.

Objectives: This study aims to evaluate the relationship between changes in thyroid stimulating hormone receptor antibody (TRAb) levels before and after treatment and the efficacy of radioactive iodine therapy (RAI) for Graves' disease (GD). Additionally, a decision tree model was developed to predict treatment outcomes based on variations in serum TRAb levels.

Methods: A total of 728 patients were evaluated to investigate the association between TRAb level fluctuations and RAI treatment efficacy.

Effect of Benzyl Isothiocyanate on Anaplastic Thyroid Cancer Evaluated by Network Pharmacology Combined with Experiments.

Benzyl isothiocyanate (BITC), a natural compound abundant in cruciferous vegetables, plays an important role in the chemoprevention of various human malignancies. However, the mechanism by which BITC inhibits tumor cell growth is not fully understood. This study combined network pharmacology, molecular docking, cellular experiments, and mouse tumor models to predict and validate the targets and mechanisms of BITC in the treatment of anaplastic thyroid carcinoma (ATC).

Selective Therapeutic Potential of a H2O2-Inducible DNA Interstrand Cross-linker in Anaplastic Thyroid Carcinoma.

We aimed to investigate hydrogen peroxide-inducible DNA interstrand cross-link (HP-ICL) as a targeted therapy for anaplastic thyroid cancer (ATC) due to its higher H2O2 content than normal cells. In vitro analysis included fluorescence microscopy for H2O2 levels and exposure of ATC cells to various HP-ICL concentrations followed by assessment of cell viability, apoptosis, cell cycle, and DNA damage using methyl thiazolyl tetrazolium (MTT), flow cytometry, and a γH2AX assay. Protein levels related to apoptosis and the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway were measured by Western blotting.

Utility of F-FDG PET/CT metabolic parameters on post-transplant lymphoproliferative disorder diagnosis.

Objective: Using F-FDG PET/CT metabolic parameters to differentiate post-transplant lymphoproliferative disorder (PTLD) and reactive lymphoid hyperplasia (RLH), and PTLD subtypes.

Methods: F-FDG PET/CT and clinical data from 63 PTLD cases and 19 RLH cases were retrospectively collected. According to the 2017 WHO classification, PTLD was categorized into four subtypes: nondestructive (ND-PTLD), polymorphic (P-PTLD), monomorphic (M-PTLD), and classic Hodgkin.

Shikonin inhibits the growth of anaplastic thyroid carcinoma cells by promoting ferroptosis and inhibiting glycolysis.

Anaplastic thyroid carcinoma is one of the highly fatal cancers and poses a serious threat to human health. Ferroptosis has been widely studied and proved to have an important role in tumor suppression, providing new avenues for cancer therapy; glutathione peroxidase 4(GPX4) and selenoprotein thioredoxin reductase(TXNRD1) are important regulatory targets in ferroptosis.Warburg effect is one of the important energy sources for cancer hypermetabolism, and pyruvate kinase isoenzyme 2 (PKM2) is a key metabolism enzyme that is important in this effect.

Precision-engineered PROTACs minimize off-tissue effects in cancer therapy.

Proteolysis-targeting chimeras (PROTACs) offer a groundbreaking approach to selectively degrade disease-related proteins by utilizing the ubiquitin-proteasome system. While this strategy shows great potential in preclinical and clinical settings, off-tissue effects remain a major challenge, leading to toxicity in healthy tissues. This review explores recent advancements aimed at improving PROTAC specificity, including tumor-specific ligand-directed PROTACs, pro-PROTACs activated in tumor environments, and E3 ligase overexpression strategies.

One-Pot Time-Induced Proteome Integral Solubility Alteration Assay for Automated and Sensitive Drug-Target Identification.

The proteome integral solubility alteration (PISA) assay is widely used for identifying drug targets, but it is labor-intensive and time-consuming and requires a substantial amount of biological sample. Aiming at enabling automation and greatly reducing the sample amount, we developed one-pot time-induced (OPTI)-PISA. Here, we demonstrate OPTI-PISA performance on identifying targets of multiple drugs in cell lysate and scaling down the sample amount to sub-microgram levels, making the PISA method suitable for NanoProteomics.

MFP-YOLO: a multi-scale feature perception network for CT bone metastasis detection.

Bone metastasis is one of the most common forms of metastasis in the late stages of malignancy. The early detection of bone metastases can help clinicians develop appropriate treatment plans. CT images are essential for diagnosing and assessing bone metastases in clinical practice.

Study on the mechanism of 17-Hydroxy-jolkinolide B on anaplastic thyroid cancer cell.

Background: Anaplastic thyroid cancer (ATC) has a dismal prognosis, and the optimal treatment has not yet been confirmed. Euphorbia fischeriana Steud has been proven to exhibit pharmacological properties, including various antitumor effects, that can be used to treat numerous diseases and has been used to treat cancer. 17-Hydroxy-jolkinolide B (17-HJB) is one of the major diterpenoids produced from plants, but little research has investigated how it affects cancer.

Redox-Inducible Radiomimetic Photosensitizers Selectively Suppress Cancer Cell Proliferation by Damaging DNA through Radical Cation Chemistry.

Radiotherapy leverages ionizing radiation to kill cancer cells through direct and indirect effects, and direct effects are considered to play an equal or greater role. Several photosensitizers have been developed to mimic the direct effects of radiotherapy, generating radical cations in DNA models, but none has been applied in cellular studies. Here, we design a radiomimetic photosensitizer, producing DNA radical cations in cells for the first time.

Prognostic Value and Immune Landscapes of Four Types of RNA Modification Writer-Related LncRNAs Signature in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is the predominant pathological subtype of non-small cell lung cancer (NSCLC). The four primary forms of RNA adenosine modifications, N6-methyladenosine (mA), N1-methyladenosine (mA), alternative polyadenylation (APA) and adenosine-to-inosine (A-to-I) RNA editing, play a critical role in tumor progression. However, the clinical significance of RNA modification writer-related long non-coding RNAs (lncRNAs) in LUAD remains unclear.

Gel-Assisted Proteome Position Integral Shift Assay Returns Molecular Weight to Shotgun Proteomics and Identifies Caspase 3 Substrates.

Here, we present a high-throughput virtual top-down proteomics approach that restores the molecular weight (MW) information in shotgun proteomics and demonstrates its utility in studying proteolytic events in programmed cell death. With gel-assisted proteome position integral shift (GAPPIS), we quantified over 7000 proteins in staurosporine-induced apoptotic HeLa cells and identified 84 proteins exhibiting in a statistically significant manner at least two of the following features: (i) a negative MW shift; (ii) an elevated ratio in a pair of a semitryptic and tryptic peptide, (iii) a negative shift in the standard deviation of MW estimated for different peptides, and (iv) a negative shift in skewness of the same data. Of these proteins, 58 molecules were previously unreported caspase 3 substrates.

Selective anti-tumor activity of glutathione-responsive abasic site trapping agent in anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive thyroid cancer with poor prognosis. Killing cancer cells by inducing DNA damage or blockage of DNA repair is a promising strategy for chemotherapy. It is reported that aldehyde-reactive alkoxyamines can capture the AP sites, one of the most common DNA lesions, and inhibit apurinic/apyrimidinic endonuclease 1(APE1)-mediated base excision repair (BER), leading to cell death.

Targeting miR-31 represses tumourigenesis and dedifferentiation of BRAF-associated thyroid carcinoma.

Background: BRAF is the most common genetic mutation in differentiated thyroid cancer (DTC) occurring in 60% of patients and drives malignant tumour cell phenotypes including proliferation, metastasis and immune-escape. BRAF-mutated papillary thyroid cancer (PTC) also displays greatly reduced expression of thyroid differentiation markers, thus tendency to radioactive iodine (RAI) refractory and poor prognosis. Therefore, understanding the molecular mechanisms and main oncogenic events underlying BRAF will guide future therapy development.

Predictive value of bone turnover markers and thyroid indicators for bone metabolism in GD patients after treatment.

Purpose: To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively.

Methods: We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT and FT before and after treatment (FT-P/FT-A, FT-P/FT-A) on whether BTMs recovered.

Urinary volatile organic compound metabolites and COPD among US adults: mixture, interaction and mediation analysis.

Background: Volatile organic compounds (VOCs) encompass hundreds of high production volume chemicals and have been reported to be associated with adverse respiratory outcomes such as chronic obstructive pulmonary disease (COPD). However, research on the combined toxic effects of exposure to various VOCs on COPD is lacking. We aimed to assess the effect of VOC metabolite mixture on COPD risk in a large population sample.

Adding Color to Mass Spectra of Biopolymers: Charge Determination Analysis (CHARDA) Assigns Charge State to Every Ion Peak.

Traditionally, mass spectrometry (MS) output is the ion abundance plotted versus the ionic mass-to-charge ratio /. While employing only commercially available equipment, Charge Determination Analysis (CHARDA) adds a third dimension to MS, estimating for individual peaks their charge states starting from = 1 and color coding in / spectra. CHARDA combines the analysis of ion signal decay rates in the time-domain data (transients) in Fourier transform (FT) MS with the interrogation of mass defects (fractional mass) of biopolymers.

Prognostic factors for postoperative papillary thyroid cancer with unexplained elevated Tg: A retrospective study.

Objective: This study aimed to investigate the underlying reasons for unexplained elevated thyroglobulin (Tg) in postoperative papillary thyroid cancer (PTC) patients according to follow-up results post RAT and to explore the long-term clinical outcomes and prognostic factors associated with these patients.

Methods: From April 2016 to June 2019, a retrospective study was conducted on postoperative PTC patients who underwent RAT at our institution. Patients with preablative stimulated thyroglobulin (psTg) > 10 ng/mL but no structurally evident disease were enrolled.

Higher adjuvant radioactive iodine therapy dosage helps intermediate-risk papillary thyroid carcinoma patients achieve better therapeutic effect.

Objective: This retrospective study aims to evaluate the therapeutic effect of varying dosages of adjuvant radioactive iodine (RAI) therapy on intermediate-risk papillary thyroid carcinoma (PTC) patients.

Methods: This retrospective study involved a total of 427 intermediate-risk PTC patients, out of which 202 received a 3.7GBq dosage of RAI, and 225 received a 5.

Ultralight Ultrafast Enzymes.

Inorganic materials depleted of heavy stable isotopes are known to deviate strongly in some physicochemical properties from their isotopically natural counterparts. Here we explored for the first time the effect of simultaneous depletion of the heavy carbon, hydrogen, oxygen and nitrogen isotopes on the bacterium E. coli and the enzymes expressed in it.

Macrocyclic-Albumin Conjugates for Precise Delivery of Radionuclides and Anticancer Drugs to Tumors.

Precise delivery of radionuclides and anticancer drugs to tumor tissue is crucial to ensuring drug synergism and optimal therapeutic effects in radionuclide-based combination radio-chemotherapy. However, current codelivery vectors often rely on physical embedment/adsorption to load anticancer drugs, which lacks precise mechanisms for drug loading and release, resulting in unpredictable combination effects. Herein, a macrocyclic-albumin conjugate (MAC) that enables precise loading and controlled release of anticancer drugs is presented.

Tandem Mass Spectrometry de novo Sequencing of the Skin Defense Peptides of the Central Slovenian Agile Frog .

Peptides released on frogs' skin in a stress situation represent their only weapon against micro-organisms and predators. Every species and even population of frog possesses its own peptidome being appropriate for their habitat. Skin peptides are considered potential pharmaceuticals, while the whole peptidome may be treated as a taxonomic characteristic of each particular population.

Experimental study on changes in metabolic mechanism of papillary thyroid carcinoma complicated with Hashimoto's thyroiditis.

Background: Whether the mechanism of thyroid papillary carcinoma (PTC) is the same in patients with a Hashimoto's thyroiditis (HT) background as compared with patients with a normal background remains a highly debated and controversial issue. In this study, we aimed to analyze the differences and similarities of the metabolic mechanism of PTC in normal and HT background, and to explore the relationship between HT and PTC.

Methods: The ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF/MS) technology was used to analyze 61 PTC patient tissues (31 HT background and 30 normal tissue (NC) background).