Ojeok-san enhances platinum sensitivity in ovarian cancer by regulating adipocyte paracrine IGF1 secretion

Platinum is a commonly used drug for ovarian cancer (OvCa) treatment, but drug resistance limits its clinical application. This study intended to delineate the effects of adipocytes on platinum resistance in OvCa. OvCa cells were maintained in the adipocyte-conditioned medium. Cell viability and apoptosis were detected by CCK-8 and flow cytometry, separately. Proliferation and apoptosis-related protein expression were assayed by western blot. The IC50 values of cisplatin and carboplatin were determined using CCK-8. IGF1 secretion and expression were assayed via ELISA and western blot, respectively. A xenograft model was established, and pathological changes were detected by H&E staining. Proliferation and apoptosis-associated protein expression was assessed via IHC. Adipocytes promoted the viability and repressed cell apoptosis in OvCa, as well as enhancing platinum resistance, while the addition of IGF-1 R inhibitor reversed the effects of adipocytes on proliferation, apoptosis, and drug resistance of OvCa cells. Treatment with different concentrations of Ojeok-san (OJS) inhibited the adipocyte-induced platinum resistance in OvCa cells by suppressing IGF1. The combined treatment of OJS and cisplatin significantly inhibited tumour growth in vivo with good mouse tolerance. In summary, OJS inhibited OvCa proliferation and platinum resistance by suppressing adipocyte paracrine IGF1 secretion.</p

Additional file 1 of Genome-wide analysis of the metallothionein gene family in cassava reveals its role in response to physiological stress through the regulation of reactive oxygen species

Supplementary Material

Identification of key immune cell-related genes involved in tumorigenesis and prognosis of cervical squamous cell carcinoma

The infiltration of immune cells can significantly affect the prognosis and immune therapy of patients with cervical squamous cell carcinoma (CSCC). This study aimed to explore key immune cell-related genes in the tumorigenesis and prognosis of CSCC. The module significantly related to immunity was screened by weighted gene co-expression network analysis (WGCNA) and ESTIMATE analysis, followed by correlation analysis with clinical traits. Key candidate genes were intersected with the protein–protein interaction (PPI) network genes for immune-related genes. The relationship between immune cell infiltration and key genes was analyzed. Tumor immune dysfunction and exclusion (TIDE) and immunophenoscore (IPS) predicted the response to immunotherapy in CSCC patients. Clinically, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry were manipulated for analyzing the changes in mRNA and protein expression of key genes in cancer. Western blot was conducted to assess the correlation between key genes and immune infiltration. The brown module was notably associated with the immune microenvironment of CSCC, from which three immune-related key genes (TYROBP, CCL5, and HLA-DRA) were obtained. High expression of these genes was significantly positively associated with the infiltration abundance of T cells, B cells, and other immune cells. High expression levels of three key genes were confirmed in para-cancer tissue and correlated with the abundance of immune cells. The high-expression group of key genes was more sensitive to immunotherapy. We provide a theoretical basis for searching for potential targets for effective treatment and diagnosis of CSCC and provide new ideas for developing novel immunotherapy strategies.</p

Multimodal Plasmonic Assay of Copper(II) Ion via Stimuli-Responsive State Transformation of Silver Molecular Nanoparticles

Molecular nanoparticles (MNPs) have gained increased attention recently due to their unique structures and properties. However, their applications remain largely unexplored. Herein, we present an Ag MNPs-based multimodal plasmonic assay. This assay relied on changes in optical properties due to stimuli-responsive state trans-formation from MNPs to plasmonic nanoparticles (PNPs). As a proof-of-concept, naked-eye colorimetric assay, spectrophotometric assay and “turn-on” Raman assay of Cu²⁺ were developed. The feasibility of this approach for real-world applications was demonstrated with the determination of Cu²⁺ in human serum. This multimodal plasmonic assay exhibited several significant advantages, including selectivity, sensitivity, label-free nature, and multimodal capability. Because of these merits, Ag MNPs could be promising nanosensors for wide important applications such as diagnostics and environmental analysis

Two-Photon and Deep-Red Emission Ratiometric Fluorescent Probe with a Large Emission Shift and Signal Ratios for Sulfur Dioxide: Ultrafast Response and Applications in Living Cells, Brain Tissues, and Zebrafishes

Sulfur dioxide (SO₂) is a dangerous environmental pollutant. Excessive intake of it may cause some respiratory diseases and even lung cancer. The development of effective methods for detection of SO₂ is of great importance for the environment and physiology. Herein, we have designed and synthesized a novel two-photon (TP) and deep-red emission ratiometric fluorescent probe (<b>CP</b>) for detection of SO₂. Notably, the novel probe <b>CP</b> exhibited ultrafast response to SO₂ in less than 5 s and displayed a great emission shift (195 nm) and a large emission signal ratio variation (enhancement from 0.1347 to 100.14). In addition, the unique probe was successfully employed for imaging SO₂ not only in the mitochondria of living cells but also in brain tissues and zebrafishes

Malonylome Analysis Reveals the Involvement of Lysine Malonylation in Metabolism and Photosynthesis in Cyanobacteria

As a recently validated reversible post translational modification, lysine malonylation regulates diverse cellular processes from bacteria to mammals, but its existence and function in photosynthetic organisms remain unknown. Cyanobacteria are the most ancient group of photosynthetic prokaryotes and contribute about 50% of the total primary production on Earth. Previously, we reported the lysine acetylome in the model cyanobacterium <i>Synechocystis</i> sp. PCC 6803 (<i>Synechocystis</i>). Here we performed the first proteomic survey of lysine malonylation in <i>Synechocystis</i> using highly accurate tandem mass spectrometry in combination with affinity purification. We identified 598 lysine malonylation sites on 339 proteins with high confidence in total. A bioinformatic analysis suggested that these malonylated proteins may play various functions and were distributed in diverse subcellular compartments. Among them, many malonylated proteins were involved in cellular metabolism. The functional significance of lysine malonylation in the metabolic enzyme activity of phosphoglycerate kinase (PGK) was determined by site-specific mutagenesis and biochemical studies. Interestingly, 27 proteins involved in photosynthesis were found to be malonylated for the first time, suggesting that lysine malonylation may be involved in photosynthesis. Thus our results provide the first lysine malonylome in a photosynthetic organism and suggest a previously unexplored role of lysine malonylation in the regulation of metabolic processes and photosynthesis in <i>Synechocystis</i> as well as in other photosynthetic organisms

Precision Imprinting of Glycopeptides for Facile Preparation of Glycan-Specific Artificial Antibodies

Antibodies specific to glycans are essential in many areas for many important fields, including disease diagnostics, therapeutics, and fundamental researches. However, due to their low immunogenicity and poor availability, glycans pose serious challenges to antibody development. Although molecular imprinting has developed into important methodology for creating antibody mimics with low cost and better stability, glycan-specific molecularly imprinted polymers (MIPs) still remain rather rare. Herein, we report a new strategy, precision imprinting with alternative templates, for the facile preparation of glycan-specific MIPs. Glycopeptides with desirable peptide length immobilized on a boronate affinity substrate were first prepared as alternative templates through <i>in situ</i> dual enzymatic digestion. A thinlayer was then produced to cover the glycans to an appropriate thickness through precision imprinting. With glycoproteins containing only N-glycans as well as both N- and O-glycans as glycan source, this approach was proved to be widely applicable and efficient. The strategy is particularly significant for the recognition of O-glycans, because enzymes that can release O-glycans from O-linked glycoproteins are lacking. The MIPs exhibited excellent glycan specificity. Specific extraction of glycopeptides and glycoproteins containing certain glycans from complex samples was demonstrated. This strategy opened a new avenue for the facile preparation of glycan-specific MIPs, facilitating glycan-related applications and research

Hybrid Approach Combining Boronate Affinity Magnetic Nanoparticles and Capillary Electrophoresis for Efficient Selection of Glycoprotein-Binding Aptamers

Capillary electrophoresis (CE) and magnetic beads have been widely used for the selection of aptamers owing to their efficient separation ability. However, these methods alone are associated with some apparent drawbacks. CE suffers from small injection volumes and thereby only a limited amount of aptamer can be collected at each round. While the magnetic beads approach is often associated with tedious procedure and nonspecific binding. Herein we present a hybrid approach that combines the above two classical aptamer selection methods to overcome the drawbacks associated with these methods alone. In this hybrid method, one single round selection by boronate affinity magnetic nanoparticles (BA-MNPs) was first performed and then followed by a CE selection of a few rounds. The BA-MNPs-based selection eliminated nonbinding sequences, enriching effective sequences in the nucleic acid library. While the CE selection, which was carried out in free solutions, eliminated steric hindrance effects in subsequent selection. Two typical glycoproteins, Ribonuclease B (RNase B) and alkaline phosphatase (ALP), were used as targets. This hybrid method allowed for efficient selection of glycoprotein-binding aptamers within 4 rounds (1 round of BA-MNPs-based selection and 3 rounds of CE selection) and the dissociation constants reached 10^–8 M level. The hybrid selection approach exhibited several significant advantages, including speed, affinity, specificity, and avoiding negative selection. Using one of the selected ALP-binding aptamers as an affinity ligand, feasibility for real application of the selected aptamers was demonstrated through constructing an improved enzyme activity assay

Molecularly Imprinted Polymer-Based Plasmonic Immunosandwich Assay for Fast and Ultrasensitive Determination of Trace Glycoproteins in Complex Samples

Glycoproteins play significant roles in many biological processes. Assays of glycoproteins have significant biological importance and clinical values, for which immunoassay has been the workhorse tool. However, immunoassay suffers from some disadvantages, such as poor availability of high-specificity antibodies and limited stability of biological reagents. Herein, we present an antibody-free and enzyme-free approach, called molecularly imprinted polymer (MIP)-based plasmonic immunosandwich assay (PISA), for fast and ultrasensitive detection of trace glycoproteins in complex samples. A gold-based boronate affinity MIP array was used to specifically extract the target glycoprotein from complex samples. After washing away unwanted species, the captured glycoprotein was labeled with boronate affinity silver-based Raman nanotags. Thus, sandwich-like complexes were formed on the array. Upon being shined with a laser beam, the gold-based array generated a surface plasmon wave, which significantly enhanced the surface-enhanced Raman scattering (SERS) signal of the silver-based Raman nanotags. The MIP ensured the specificity of the assay, while the plasmonic detection provided ultrahigh sensitivity. Erythropoietin (EPO), a glycoprotein hormone that controls erythropoiesis or red blood cell production, was employed as a test glycoprotein in this study. Specific detection of EPO in solution down to 2.9 × 10^–14 M was achieved. Using a novel strategy to accommodate the method of standard addition to a logarithmic dose–response relationship, EPO in human urine was quantitatively determined by this approach. The analysis time required only 30 min in total. This approach holds promising application prospects in many areas, such as biochemical research, clinical diagnosis, and antidoping analysis