Intrinsic Molecular Mechanisms Research Articles

Lycium barbarum Ameliorates Oral Mucositis via HIF and TNF Pathways: A Network Pharmacology Approach.

Oral mucositis is the most common and troublesome complication for cancer patients receiving radiotherapy or chemotherapy. Recent research has shown that Lycium barbarum, an important economic crop widely grown in China, has epithelial protective effects in several other organs. However, it is unknown whether or not Lycium barbarum can exert a beneficial effect on oral mucositis. Network pharmacology has been suggested to be applied in "multi-component-multi-target" functional food studies. The purpose of this study is to evaluate the effect of Lycium barbarum on oral mucositis through network pharmacology, molecular docking and experimental validation. To explore the biological effects and molecular mechanisms of Lycium barbarum in the treatment of oral mucositis through network pharmacology and molecular docking combined with experimental validation. Based on network pharmacology methods, we collected the active components and related targets of Lycium barbarum from public databases, as well as the targets related to oral mucositis. We mapped protein- protein interaction (PPI) networks, performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment, and constructed a 'components-disease-targets' network and 'components- pathways-targets' network using Cytoscape to further analyse the intrinsic molecular mechanisms of Lycium barbarum against oral mucositis. The affinity and stability predictions were performed using molecular docking strategies, and experiments were conducted to demonstrate the biological effects and possible mechanisms of Lycium barbarum against oral mucositis. A network was established between 49 components and 61 OM targets. The main active compounds were quercetin, beta-carotene, palmatine, and cyanin. The predicted core targets were IL-6, RELA, TP53, TNF, IL10, CTNNB1, AKT1, CDKN1A, HIF1A and MYC. The enrichment analysis predicted that the therapeutic effect was mainly through the regulation of inflammation, apoptosis, and hypoxia response with the involvement of TNF and HIF pathways. Molecular docking results showed that key components bind well to the core targets. In both chemically and radiation-induced OM models, Lycium barbarum significantly promoted healing and reduced inflammation. The experimental verification showed Lycium barbarum targeted the key genes (IL-6, RELA, TP53, TNF, IL10, CTNNB1, AKT1, CDKN1A, HIF1A, and MYC) through regulating the HIF and TNF signaling pathways, which were validated using the RT-qPCR, immunofluorescence staining and western blotting assays. In conclusion, the present study systematically demonstrated the possible therapeutic effects and mechanisms of Lycium barbarum on oral mucositis through network pharmacology analysis and experimental validation. The results showed that Lycium barbarum could promote healing and reduce the inflammatory response through TNF and HIF signaling pathways.

WDR68 stimulates cellular proliferation via activating ribosome biogenesis in 293T cells

WDR68, a conserved WD40 repeat-containing protein, interacts with E1A and is involved in the E1A-induced cell proliferation and oncogenic transformation, but the intrinsic molecular mechanisms of this process remain to be elucidated. Here, we demonstrate that WDR68 promotes the proliferation of 293T cells by interacting with a series of ribosome biogenesis-regulating proteins. Gene Set Enrichment Analysis (GSEA) of RNA-seq data also revealed that the ribosome biogenesis-associated gene signatures could be the most significantly enriched in the WDR68 expression groups. In accordance, 293T cells are more sensitive to the ribosome biogenesis inhibitors than 293 cells. Taken together, our results indicated that WDR68 could promote cell proliferation through the activation of ribosome biogenesis in the 293T cell context. This provides new insights into the understanding of the function of WDR68 and the molecular characterisation of 293T tool cells.

Bacillus B2 promotes root growth and enhances phosphorus absorption in apple rootstocks by affecting MhMYB15.

Due to the chelation of phosphorus in the soil, it becomes unavailable for plant growth and development. The mechanisms by which phosphorus-solubilizing bacteria activate immobilized phosphorus to promote the growth and development of woody plants, as well as the intrinsic molecular mechanisms, are not clear. Through the analysis of microbial communities in the rhizosphere 16S V3-V4 and a homologous gene encoding microbial alkaline phosphomonoesterase (phoD) in phosphate-efficient (PE) and phosphate-inefficient apple rootstocks, it was found that PE significantly enriched beneficial rhizobacteria. The best phosphorus-solubilizing bacteria, Bacillus sp. strain 7DB1 (B2), was isolated, purified, and identified from the rhizosphere soil of PE rootstocks. Incubatingwith Bacillus B2 into the rhizosphere of apple rootstocks significantly increased the soluble phosphorus and flavonoid content in the rhizosphere soil. Simultaneously, this process stimulates the root development of the rootstocks and enhances plant phosphorus uptake. After root transcriptome sequencing, candidate transcription factor MhMYB15, responsive to Bacillus B2, was identified through heatmap and co-expression network analysis. Yeast one-hybrid, electrophoretic mobility shift assay, and LUC assay confirmed that MhMYB15 can directly bind to the promoter regions of downstream functional genes, including chalcone synthase MhCHS2 and phosphate transporter MhPHT1;15. Transgenic experiments with MhMYB15 revealed that RNAi-MhMYB15 silenced lines failed to induce an increase in flavonoid content and phosphorus levels in the roots under the treatment of Bacillus B2, and plant growth was slower than the control. In conclusion, MhMYB15 actively responds to Bacillus B2, regulating the accumulation of flavonoids and the uptake of phosphorus, thereby influencing plant growth and development.

Epitope-Shared Hapten Enhancing Antibody Polyreactivity for Simultaneous Immunochromatography of Oxyphenisatin Adulterants.

Given the significant threat posed by oxyphenisatin adulterants (OPHs) in weight-loss foods, simultaneous analysis of the OPHs is necessary. Herein, four novel haptens based on the general epitope shared among the OPHs were raised by computer-aided chemical modeling prediction, with the expectation of eliciting antibody responses targeting three of the OPHs. One obtained monoclonal antibody (mAb) showed maximal half-inhibitory concentration (IC50) of 0.40-12.11 ng/mL for OPHs. The key interaction forces responsible for the corecognition of the OPHs were revealed by the intrinsic molecular mechanism. The developed immunochromatography (ICA) indicated a detection capability for screening (CCβ) for OPHs estimated to be 5-600 ng/g in jelly, candy tablets, and oral liquid. Furthermore, the analysis of 15 real samples by our method showed a good correlation with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Our research not only presented a rapid approach for identifying OPHs adulteration but also proposed an effective hapten prediction strategy to enhance antibody polyreactivity.

Peroxidase in plant defense: Novel insights for cadmium accumulation in rice (Oryza sativa L.)

Phenylpropanoid biosynthesis plays crucial roles in the adaptation to cadmium (Cd) stress. Nevertheless, few reports have dabbled in physiological mechanisms of such super pathway regulating Cd accumulation in plants. Herein, by integrating transcriptomic, histological and molecular biology approaches, the present study dedicated to clarify molecular mechanism on how rice adapt to Cd stress via phenylpropanoid biosynthesis. Our analysis identified that the enhancement of phenylpropanoid biosynthesis was as a key response to Cd stress. Intriguingly, POD occupied a significant part in this process, with the number of POD related genes accounted for 26/29 of all upregulated genes in phenylpropanoid biosynthesis. We further used SHAM (salicylhydroxamic acid, the POD inhibitor) to validate that POD exhibited a negative correlation with the Cd accumulation in rice tissues, and proposed two intrinsic molecular mechanisms on POD in contributing to Cd detoxification. One strategy was that POD promoted the formation of lignin and CSs both in endodermis and exodermis for intercepting Cd influx. In detail, inhibited POD induced by external addition of SHAM decreased the content of lignin by 50.98–66.65 % and delayed percentage of the DTIP-CS to root length by 39.17–104.51 %. The other strategy was expression of transporter genes involved in Cd uptake, including OsIRT1, OsIRT2, OsZIP1 and OsZIP, negatively regulated by POD. In a word, our findings firstly draws a direct link between POD activity and the Cd accumulation, which is imperative for the breeding of rice with low-Cd-accumulating capacity in the future.

Chemical interplay between gut microbiota and epigenetics: Implications in circadian biology.

Circadian rhythms are intrinsic molecular mechanisms that synchronize biological functions with the day/night cycle. The mammalian gut is colonized by a myriad of microbes, collectively named the gut microbiota. The microbiota impacts host physiology via metabolites and structural components. A key mechanism is the modulation of host epigenetic pathways, especially histone modifications. An increasing number of studies indicate the role of the microbiota in regulating host circadian rhythms. However, the mechanisms remain largely unknown. Here, we summarize studies on microbial regulation of host circadian rhythms and epigenetic pathways, highlight recent findings on how the microbiota employs host epigenetic machinery to regulate circadian rhythms, and discuss its impacts on host physiology, particularly immune and metabolic functions. We further describe current challenges and resources that could facilitate research on microbiota-epigenetic-circadian rhythm interactions to advance our knowledge of circadian disorders and possible therapeutic avenues.

Investigating the Effects of Perampanel on Autophagy-mediated Regulation of GluA2 and PSD95 in Epilepsy.

Epilepsy is a chronic neurological disorder characterized by recurrent seizures. Despite various treatment approaches, a significant number of patients continue to experience uncontrolled seizures, leading to refractory epilepsy. The emergence of novel anti-epileptic drugs, such as perampanel (PER), has provided promising options for effective epilepsy treatment. However, the specific mechanisms underlying the therapeutic effects of PER remain unclear. This study aimed to investigate the intrinsic molecular regulatory mechanisms involved in the downregulation of GluA2, a key subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, following epileptic seizures. Primary mouse hippocampal neurons were cultured and subjected to an epilepsy cell model. The expression levels of GluA2 and autophagy-related proteins were assessed using Western blotting and real-time fluorescent quantitative PCR. Immunofluorescence and immunohistochemistry techniques were employed to investigate the nuclear translocation of CREB-regulated transcriptional coactivator 1 (CRTC1). Additionally, status epilepticus animal models were established to further validate the findings. The epilepsy cell model exhibited a significant decrease in GluA2 expression, accompanied by elevated levels of autophagy-related proteins. Immunofluorescence analysis revealed the nuclear translocation of CRTC1, which correlated with the expression of autophagy-related genes. Treatment with an autophagy inhibitor reversed the decreased expression of GluA2 in the epilepsy cell model. Furthermore, the calcium/calmodulin-dependent protein phosphatase inhibitor FK506 and CaN overexpression affected the dephosphorylation and nuclear translocation of CRTC1, consequently influencing GluA2 expression. Animal model results further supported the involvement of these molecular mechanisms in epilepsy. Our findings suggest that the downregulation of GluA2 following epileptic seizures involves the activation of autophagy and the regulation of CRTC1 nuclear translocation. These intrinsic molecular regulatory mechanisms provide potential targets for developing novel therapeutic strategies to alleviate refractory epilepsy and preserve cognitive functions in patients.

A double inducible cell ablation system for eliminating senescent astrocytes via apoptosis.

Cell senescence stands as a principal risk factor for various neurodegenerative diseases, with astrocytic senescence emerging as a potentially pivotal player in the pathogenesis of aging and neurodegenerative disorders. Clearing senescent astrocytes holds promise as a potential therapeutic approach for senescence-related diseases. In this study, we designed and constructed two plasmids aimed at inducing apoptosis in senescent astrocytes. This was achieved through the ligation of FKBP (FK506-binding protein) and FRB (FKBP and FKBP rapamycin binding domain) and the formation of caspase8 dimers, thereby achieving the purpose of eliminating senescent astrocytes. The developed vector system demonstrates a specifically capability to induce apoptosis in aging astrocytes, offering a targeted approach to eliminate these cells. The utilization of the double -inducible suicide gene system provides a versatile tool forstimulating cell apoptosis and inhibiting cellular senescence. This system proves valuable in exploring the intrinsic roles and molecular mechanisms of senescent cells in the occurrence and development of aging-related diseases. Ultimately, it offers a potential avenue for developing an efficient treatment system for such conditions.

Molecular mechanisms of circular RNA in breast cancer: a narrative review.

Breast cancer is presently the most prevalent cancer and the leading cause of cancer-related deaths in women worldwide. Circular RNA (circRNA) is a class of closed circRNAs lacking a 5'-end cap structure and a 3'-end polyA tail, which is highly stable and widely involved in a variety of pathophysiological processes such as cell proliferation, differentiation, and apoptosis. In recent years, accumulating studies have shown that circRNAs play an important role in the development and prognosis of breast cancer, but there are fewer literature reviews on their intrinsic molecular mechanisms which is the aim of this study. This review synthesizes the findings of literature retrieved from searches of PubMed and Google Scholar databases, hand searches, and authoritative texts. Citations mainly originate from the past 3 years. The articles need to describe the role of circRNA in breast cancer; no language restrictions were imposed. This review summarizes the latest relevant literature and systematically reviews the four main mechanisms of circRNA in breast cancer from the perspective of circRNA function. At the same time, we describe the formation mechanism, characterization, and biological functions of circRNAs. We reviewed the status of actual knowledge about circRNA biogenesis and functions and summarized novel findings regarding the molecular mechanism of circRNA in breast cancer. Meanwhile, this review explores the possibility of circRNAs for becoming new biodiagnostic indicators and therapeutic targets in breast cancer.

A Comparison of Watermelon Flesh Texture across Different Ploidy Levels Using Histology and Cell Wall Measurements

Watermelon fruits of different ploidy levels exhibit significant variations in texture. This study aimed to investigate the primary factors that influence texture differences. To achieve this, we conducted an investigation into the differences in fruit texture development using homozygous autogamous diploid (2×) lines and their autotriploid (3×) and autotetraploid (4×) lines ‘Yixuan’. The study investigated fruit development, flesh texture profile analysis (TPA), flesh cell wall polysaccharide content, and flesh cell microstructure analysis in 2×, 3×, and 4× watermelon fruits. The study found that as watermelon fruits matured, several characteristics increased, including fruit weight, TSS (total soluble solids) content, rind hardness, flesh cell size, and cell wall polysaccharide contents such as crude fiber, cellulose, hemicellulose, lignin, and protopectin. In contrast, the flesh texture parameters and soluble pectin content of the flesh cell wall decreased over time. Significant differences in fruit flesh texture and flesh cell structure were observed among fruits of different ploidy levels at the 32 DAP. Specifically, the 2× fruits displayed considerably lower rind hardness, reduced flesh texture (Hardness, Fracturability, Chewiness, Gumminess), and cell density compared to the 3× and 4× fruits. Additionally, the 2× fruits had larger cell sizes than the 3× and 4× fruits. However, there were no significant differences observed in the flesh cell wall polysaccharide contents across various ploidy levels. These findings suggest that the variation in texture among watermelon fruits of different ploidy levels can be attributed to the size and arrangement of the flesh cells. This research provides a foundation for the further exploration of the intrinsic regulatory factors and molecular mechanisms contributing to texture variation in polyploid watermelon fruits.

Recent Advances in the Specialized Metabolites Mediating Resistance to Insect Pests and Pathogens in Tea Plants (Camellia sinensis).

Tea is the second most popular nonalcoholic beverage consumed in the world, made from the buds and young leaves of the tea plants (Camellia sinensis). Tea trees, perennial evergreen plants, contain abundant specialized metabolites and suffer from severe herbivore and pathogen attacks in nature. Thus, there has been considerable attention focusing on investigating the precise function of specialized metabolites in plant resistance against pests and diseases. In this review, firstly, the responses of specialized metabolites (including phytohormones, volatile compounds, flavonoids, caffeine, and L-theanine) to different attacks by pests and pathogens were compared. Secondly, research progress on the defensive functions and action modes of specialized metabolites, along with the intrinsic molecular mechanisms in tea plants, was summarized. Finally, the critical questions about specialized metabolites were proposed for better future research on phytohormone-dependent biosynthesis, the characteristics of defense responses to different stresses, and molecular mechanisms. This review provides an update on the biological functions of specialized metabolites of tea plants in defense against two pests and two pathogens.

High-resolution mass spectrometry-based non-targeted metabolomics reveals toxicity of naphthalene on tall fescue and intrinsic molecular mechanisms

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous at relatively high concentrations by atmospheric deposition, and they are threatening to the environment. In this study, the toxicity of naphthalene on tall fescue and its potential responding mechanism was first studied by integrating approaches. Tall fescue seedlings were exposed to 0, 20, and 100 mg L−1 naphthalene in a hydroponic environment for 9 days, and toxic effects were observed by the studies of general physiological studies, chlorophyll fluorescence, and root morphology. Additionally, Ultra Performance Liquid Chromatography - Electrospray Ionization - High-Resolution Mass Spectrometry (UPLC-ESI-HRMS) was used to depict metabolic profiles of tall fescue under different exposure durations of naphthalene, and the intrinsic molecular mechanism of tall fescue resistance to abiotic stresses. Tall fescue shoots were more sensitive to the toxicity of naphthalene than roots. Low-level exposure to naphthalene inhibited the electron transport from the oxygen-evolving complex (OEC) to D1 protein in tall fescue shoots but induced the growth of roots. Naphthalene induced metabolic change of tall fescue roots in 12 h, and tall fescue roots maintained the level of sphingolipids after long-term exposure to naphthalene, which may play important roles in plant resistance to abiotic stresses.

Dietary creatine promotes creatine reserves, protein deposition, and myofiber hyperplasia in muscle of juvenile largemouth bass (Micropterus salmoides)

Creatine can increase muscle mass, enhance performance, prevent disease-induced muscle atrophy, and improve overall cellular energy. This study investigated the effects of creatine as a feed additive on muscle growth and intrinsic molecular regulation mechanism in largemouth bass (Micropterus salmoides). Seven diets supplemented with different concentrations of creatine (0%, 0.1%, 0.25%, 0.5%, 1%, 2%, and 4%) were fed to juvenile largemouth bass (4.5–5.1 g) for eight weeks. Dietary creatine significantly increased body weight and body length, and reduced feed conversion ratio. High-performance liquid chromatography analysis revealed that dietary creatine addition notably increased creatine and phosphocreatine levels by 19.94% and 16.54% in the muscle of largemouth bass, respectively. Histological observation showed that dietary creatine significantly increased the total muscle fiber number and decreased the mean muscle fiber diameter. The Western blot results indicated that creatine ingestion significantly increased the protein level of MyoD1 in the muscle and promoted muscle fiber hyperplasia. In addition, dietary creatine also contributed to mTOR-S6K/4EBP1-mediated protein synthesis by maintaining AMPKα Thr172 dephosphorylation and AKT Thr308 phosphorylation. Moreover, the protein levels of the muscle-specific E3 ligases Atrogin1 and Murf1 responsible for ubiquitination degradation exhibited no significant change after feeding with creatine in largemouth bass. Overall, our data showed that creatine as a feed additive increased creatine and phosphocreatine contents, thus promoting muscle protein deposition and myofiber hyperplasia, eventually elevating growth performance and feed utilization efficiency in juvenile largemouth bass. The regression analysis of weight gain rate, specific growth rate, and feed conversion ratio determined 0.46%–0.54% creatine concentration range as optimal supplementation concentration for the culture of juvenile largemouth bass.

Abstract B109: Reinforcing risk prediction for intraductal papillary mucinous neoplasms of the pancreas with AI-optimized nucleotide-to-amino acid analyses

Abstract Intraductal papillary mucinous neoplasms (IPMNs) often precede invasive pancreatic ductal adenocarcinoma, with each IPMN tumor carrying a 10-25% risk of progressing to cancer within 10 years of detection. The objective of this work is to employ AI-augmented analyses of single mutations occurring at specific tri-nucleotide sequences or codons and identify markers associated with the progression of cysts to pancreatic cancer. Despite being precursors of pancreatic cancer there is a lack of validated intervention targets for precision prevention for IPMNs. Currently cancer prevention for patients with IPMN is centered on surgery using a risk-tailored approach; the clinical ability to stratify risk of cancer progression of individual IPMN tumors is poor and essentially no effective non-surgical interventions exist. To advance the precision cancer prevention for IPMNs we develop an intelligent, machine learning (ML) derived framework addressing the challenge of IPMN stratification from samples with limited data space, e.g., somatic mutations. Our study incorporates the text-based statistical and ML analyses of the mutational profiles of patients’ genomes followed by an integration of codon sequence derived mutational features for biomarkers validation. Given the potential of genome spatial organization to understand mutagenesis and genomic instability, we also map the DNA sequence information onto the local spatial genome organization to elucidate intrinsic features and molecular mechanisms that potentially lead to mutations. Results of this study show that information extracted from mutational profiles with the proposed methods significantly improves performance of the ML models in stratification of IPMNs and biomarker identification. We also present how utilization of these ML tools for mutational data, spatial genome organization, and functional analyses from tumor samples, can aid understanding of the underlying mechanisms of mutations in IPMNs and pancreatic cancer. Citation Format: Nam Nguyen, Jamie K. Teer, Margaret A. Park, Patricia McDonald, Jason B. Fleming, Jennifer B. Permuth, Kwang-Cheng Chen, Aleksandra Karolak. Reinforcing risk prediction for intraductal papillary mucinous neoplasms of the pancreas with AI-optimized nucleotide-to-amino acid analyses [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B109.

Sputum proteomics in lung disorders.

Lung diseases affect pulmonary and respiratory function and are caused by bacterial viral and fungal infection as well as environmental factors. Unfortunately, symptom overlap between various pulmonary diseases often prevents clear differentiation and uncertain diagnosis. Accordingly, identification of specific markers of inflammatory activity in early disease stage could potential unveil the intrinsic molecular mechanisms of the underlying pathology. Proteomic studies aimed at understanding the genetic/environmental contributions to the development and progression of lung diseases represent a promising approach for diagnosis and treatment. The fluid phase of sputum represents a rich protein source and is frequently used in these studies. This chapter addresses causes of lung disorders, sputum composition, collection and processing as well as the clinical significance and challenges associated with the presence of interfering factors. Basics of proteomics and mass spectrometry are also described, together with the analytical approaches to investigate the sputum proteome. Finally, we explore the application of sputum proteomics in severe lung disorders including COVID-19 infection, chronic obstructive pulmonary disease, asthma, cystic fibrosis, lung cancer and tuberculosis.

Single-cell insights into epithelial morphogenesis in the neonatal mouse uterus.

The uterus is vital for successful reproduction in mammals, and two different types of epithelia (luminal and glandular) are essential for embryo implantation and pregnancy establishment. However, the essential cellular and molecular factors and pathways governing postnatal epithelium maturation, determination, and differentiation in developing uterus are yet to be elucidated. Here, the epithelium of the neonatal mouse uterus was isolated and subjected to single-cell transcriptome (scRNA-seq) analysis. Both the undifferentiated epithelium and determined luminal epithelium were heterogeneous and contained several different cell clusters based on single-cell transcription profiles. Substantial gene expression differences were evident as the epithelium matured and differentiated between postnatal days 1 to 15. Two new glandular epithelium-expressed genes (Gas6 and Cited4) were identified and validated by in situ hybridization. Trajectory analyses provided a framework for understanding epithelium maturation, lineage bifurcation, and differentiation. A candidate set of transcription factors and gene regulatory networks were identified that potentially direct epithelium lineage specification and morphogenesis. This atlas provides a foundation important to discover intrinsic cellular and molecular mechanisms directing uterine epithelium morphogenesis during a critical window of postnatal development.

A Role of Multi-Omics Technologies in Sheep and Goat Meats: Progress and Way Ahead.

Sheep and goat meats are increasingly popular worldwide due to their superior nutritional properties and distinctive flavor profiles. In recent decades, substantial progress in meat science has facilitated in-depth examinations of ovine and caprine muscle development during the antemortem phase, as well as post-mortem changes influencing meat attributes. To elucidate the intrinsic molecular mechanisms and identify potential biomarkers associated with meat quality, the methodologies employed have evolved from traditional physicochemical parameters (such as color, tenderness, water holding capacity, flavor, and pH) to some cutting-edge omics technologies, including transcriptomics, proteomics, and metabolomics approaches. This review provides a comprehensive analysis of multi-omics techniques and their applications in unraveling sheep and goat meat quality attributes. In addition, the challenges and future perspectives associated with implementing multi-omics technologies in this area of study are discussed. Multi-omics tools can contribute to deciphering the molecular mechanism responsible for the altered the meat quality of sheep and goats across transcriptomic, proteomic, and metabolomic dimensions. The application of multi-omics technologies holds great potential in exploring and identifying biomarkers for meat quality and quality control, thereby promoting the optimization of production processes in the sheep and goat meat industry.

Intrinsic Molecular Mechanisms of Transformation between Isomeric Intermediates Formed at Different Stages of Cysteine-Xylose Maillard Reaction Model through Dehydration.

2-Threityl-thiazolidine-4-carboxylic acid (TTCA) and Amadori rearrangement product (ARP), the isomeric intermediates derived from the cysteine-xylose (Cys-Xyl) Maillard reaction model, possessed the ability to produce similar flavor profile during the thermal process, but the flavor formation or browning rate of heated TTCA was significantly lower than that of ARP. Macroscopically, the yield of TTCA reached the maximum when the moisture content of the reaction system just dropped to nearly 0% during the thermal reaction-vacuum dehydration process. During the subsequent dynamic intramolecular dehydration process, the reaction remained at an early stage of the Maillard reaction, and TTCA was the main intermediate. Thereinto, the water activity of the samples decreased with the increased dehydration time. From a molecular perspective, the dissipation of free water promoted the conversion of combined water to immobilized water and free water, increasing the intramolecular dehydration. Instantaneous high-temperature dehydration during the spray drying process revealed a higher efficiency than the thermal reaction-vacuum dehydration process, which facilitated the specific conversion of substrates to intermediates (TTCA, ARP). The loss of free water and immobilized water was a key driving force for the direct formation of TTCA/ARP, regulating the formation stages of MRIs. The increase of the inlet air temperature could alter the ratio of TTCA and ARP at the equilibrium state.

Covalent conjugation with quercetin mitigates allergenicity of the bee pollen allergen Bra c p in a murine model

Profilin family members are highly conserved food allergens that can cause widespread cross-allergic reactions. Our previous research has demonstrated that the covalent conjunction with quercetin can disrupt the conformational epitopes of a profilin allergen, Bra c p. In this study, we further investigated the intrinsic molecular mechanisms using molecular dynamics simulations. Moreover, the allergenic potential of Bra c p and its conjugate with quercetin was assessed in BALB/c mice. The results showed that continuous interaction with quercetin increased the molecular motion of Bra c p, causing changes to its α-helices and exposing hydrophobic residues which altered antigenic epitopes. Additionally, mice treated with Bra c p-quercetin conjugate showed reduced allergic reactions compared to those treated with Bra c p alone by regulating purine metabolism, calcium signaling, and CD4+CD25+ Tregs proportion. Quercetin conjugation decreases the allergenicity of Bra c p, providing a scientific foundation for reducing the profilin allergens in food.

Unraveling the dangerous duet between cancer cell plasticity and drug resistance

AbstractCancer cell plasticity is the ability of tumor cells to switch phenotypes and is one of the predominant requisites of cancer cells capable of undergoing metastasis. Cancer cell plasticity is also recognized as one of the major contributors to intratumoral heterogeneity, a critical factor underlying the progression of malignant tumors, which is known to modify tumor response and induce resistance against various modes of therapy, thus posing a barrier to efficient cancer management. Cancer cell plasticity is acquired by the subversion of cell signaling pathways like mitogen‐activated protein kinase pathway, phosphoinositide‐3‐kinase, signal transducer and activator of transcription 3, Wnt, Hedgehog and Notch as well as cellular programs such as epithelial to mesenchymal transition and phenotypic plasticity. This complex phenomenon has been studied in many cancer types like pancreatic cancer, colon cancer and breast cancer. This review will explore the current understanding we have in breast cancer on the intrinsic molecular mechanisms of cancer cell plasticity and the resistance to various types of cancer therapy that arise as a result of plasticity. We conclude by exploring the potential novel therapies that specifically target the pathways leading to plasticity and can be leveraged to treat patients living with the disease.