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1.
J Med Chem ; 67(13): 11053-11068, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38952152

ABSTRACT

Metastable binding sites (MBS) have been observed in a multitude of molecular dynamics simulations and can be considered low affinity allosteric binding sites (ABS) that function as stepping stones as the ligand moves toward the orthosteric binding site (OBS). Herein, we show that MBS can be utilized as ABS in ligand design, resulting in ligands with improved binding kinetics. Four homobivalent bitopic ligands (1-4) were designed by molecular docking of (S)-alprenolol ((S)-ALP) in the cocrystal structure of the ß2 adrenergic receptor (ß2AR) bound to the antagonist ALP. Ligand 4 displayed a potency and affinity similar to (S)-ALP, but with a >4-fold increase in residence time. The proposed binding mode was confirmed by X-ray crystallography of ligand 4 in complex with the ß2AR. This ligand design principle can find applications beyond the ß2AR and G protein-coupled receptors (GPCRs) as a general approach for improving the pharmacological profile of orthosteric ligands by targeting the OBS and an MBS simultaneously.


Subject(s)
Molecular Docking Simulation , Receptors, Adrenergic, beta-2 , Receptors, Adrenergic, beta-2/metabolism , Receptors, Adrenergic, beta-2/chemistry , Ligands , Humans , Binding Sites , Crystallography, X-Ray , Alprenolol/chemistry , Alprenolol/pharmacology , Alprenolol/metabolism , Adrenergic beta-2 Receptor Antagonists/chemistry , Adrenergic beta-2 Receptor Antagonists/pharmacology , Adrenergic beta-2 Receptor Antagonists/metabolism , Molecular Dynamics Simulation , Drug Design
2.
Front Public Health ; 12: 1410722, 2024.
Article in English | MEDLINE | ID: mdl-38952739

ABSTRACT

Radiological science and nuclear technology have made great strides in the twenty-first century, with wide-ranging applications in various fields, including energy, medicine, and industry. However, those developments have been accompanied by the inherent risks of exposure to nuclear radiation, which is a source of concern owing to its potentially adverse effects on human health and safety and which is of particular relevance to medical personnel who may be exposed to certain cancers associated with low-dose radiation in their working environment. While medical radiation workers have seen a decrease in their occupational exposure since the 1950s thanks to improved measures for radiation protection, a concerning lack of understanding and awareness persists among medical professionals regarding these potential hazards and the required safety precautions. This issue is further compounded by insufficient capabilities in emergency response. This highlights the urgent need to strengthen radiation safety education and training to ensure the well-being of medical staff who play a critical role in radiological and nuclear emergencies. This review examines the health hazards of nuclear radiation to healthcare workers and the awareness and willingness and education of healthcare workers on radiation protection, calling for improved training programs and emergency response skills to mitigate the risks of radiation exposure in the occupational environment, providing a catalyst for future enhancement of radiation safety protocols and fostering of a culture of safety in the medical community.


Subject(s)
Health Personnel , Occupational Exposure , Radiation Protection , Humans , Occupational Exposure/prevention & control , Radioactive Hazard Release , Radiation Injuries/prevention & control , Health Knowledge, Attitudes, Practice , Awareness
3.
Front Immunol ; 15: 1400177, 2024.
Article in English | MEDLINE | ID: mdl-38953027

ABSTRACT

Background: Chimeric antigen receptor T (CAR-T) cell therapies have achieved remarkable success in the treatment of hematological tumors. However, given the distinct features of solid tumors, particularly heterogeneity, metabolic aggressiveness, and fewer immune cells in tumor microenvironment (TME), the practical utility of CAR-T cells for solid tumors remains as a challenging issue. Meanwhile, although anti-PD-1 monoclonal antibody (mAb) has shown clinical efficacy, most mAbs also show limited clinical benefits for solid tumors due mainly to the issues associated with the lack of immune cells in TME. Thus, the infiltration of targeted immunological active cells into TME could generate synergistic efficacy for mAbs. Methods: We present a combinational strategy for solid tumor treatment, which combines armored-T cells to express Fc-gamma receptor I (FcγRI) fragment on the surfaces for targeting various tumors with therapeutically useful mAbs. Choosing CD20 and HER-2 as the targets, we characterized the in vitro and in vivo efficacy and latent mechanism of the combination drug by using flow cytometry, ELISA and other methods. Results: The combination and preprocessing of armored T-cells with corresponding antibody of Rituximab and Pertuzumab exerted profound anti-tumor effects, which is demonstrated to be mediated by synergistically produced antibody-dependent cellular cytotoxicity (ADCC) effects. Meanwhile, mAb was able to carry armored-T cell by preprocessing for the infiltration to TME in cell derived xenograft (CDX) model. Conclusions: This combination strategy showed a significant increase of safety profiles from the reduction of antibody doses. More importantly, the present strategy could be a versatile tool for a broad spectrum of cancer treatment, with a simple pairing of engineered T cells and a conventional antibody.


Subject(s)
Neoplasms , Receptors, IgG , T-Lymphocytes , Tumor Microenvironment , Receptors, IgG/immunology , Receptors, IgG/metabolism , Humans , Animals , Mice , Neoplasms/immunology , Neoplasms/therapy , Neoplasms/drug therapy , T-Lymphocytes/immunology , Tumor Microenvironment/immunology , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal/immunology , Cell Line, Tumor , Xenograft Model Antitumor Assays , Immunotherapy, Adoptive/methods , Receptor, ErbB-2/immunology , Receptor, ErbB-2/antagonists & inhibitors , Antineoplastic Agents, Immunological/pharmacology , Antineoplastic Agents, Immunological/therapeutic use , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/genetics , Female , Antigens, CD20/immunology
4.
Front Nutr ; 11: 1351067, 2024.
Article in English | MEDLINE | ID: mdl-38835962

ABSTRACT

Objective: Existing studies have reported sustained changes in the cortical structure of rats due to coffee-related factors, which are speculated to occur in the human body. However, there is a lack of research on this topic. Additionally, previous observational studies have found the impact of diseases on cortical structure and the potential therapeutic effects of coffee on these diseases. Our aim was to study the causal effects of coffee-related factors on the human brain using SNPs (single nucleotide polymorphisms). We will connect these discovered causal effects to the impact of diseases on the brain. Through triangulating evidence, we will reveal the potential active areas of coffee in preventing diseases. Methods: We utilized GWAS data from multiple cohorts and their databases, selecting instrumental variables for genetic prediction of coffee intake and plasma levels of caffeine and its direct metabolites. We applied these instrumental variables to individual data on cortical thickness and surface area, as well as hippocampal volume, from the ENIGMA and CHARGE consortium for Mendelian randomization analysis (MR). Triangular evidence was obtained by integrating existing evidence through a specified retrieval strategy, calculating the overlap between coffee's effects on brain regions and disease-related brain regions to identify potential regions of action. Results: The MR analysis yielded 93 positive results for 9 exposures, among which theobromine, a metabolite in the caffeine pathway, was found to be associated with increased hippocampal volume. For cortical structure, theobromine in the caffeine pathway was associated with a decrease in total surface area, while theobromine and caffeine in the pathway were associated with an increase in total thickness. The overlap rate of triangular evidence showed no difference in both overall and subgroup analyses, indicating a high overlap between the effects of coffee on brain regions and disease. Conclusions: From predicted outcomes from causal effects, coffee intake-related factors may have lasting effects on cortical structure. Additionally, theobromine and theophylline have the greatest impact on certain brain gyri, rather than caffeine. Triangulation evidence indicates that disease and coffee intake-related factors act on the same cortical regions, suggesting the presence of potential shared or antagonistic pathways.

5.
Int Immunopharmacol ; 138: 112558, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38941666

ABSTRACT

BACKGROUND: This study aims to analyze the efficacy and safety of neoadjuvant programmed cell death-1 (PD-1) blockade plus chemotherapy in real-world applications. Additionally, we report survival outcomes with a median follow-up of 40.1 months. METHODS: From January 2018 to October 2022, we retrospectively recruited patients with esophageal squamous cell carcinoma (ESCC) who underwent surgery after receiving PD-1 blockade (immunotherapy) plus chemotherapy at Jiangsu Cancer Hospital. RESULTS: A total of 132 eligible ESCC patients were included, and R0 resection was achieved in 131 cases (99.2 %). A complete pathological response rate (ypT0N0) was observed in 32 patients (24.2 %), and the objective response rate was 59.1 %. The most common grade 3-4 treatment-related adverse events (TRAEs) were leukopenia (18.2 %) and neutropenia (15.9 %). Three cases (2.3 %) of grade 3 immune-related AEs were observed, including increased ALT (0.8 %), rash (0.8 %), and encephalitis (0.8 %). The 1-year disease-free survival (DFS) and overall survival (OS) rates were 68.2 % and 89.4 %, respectively, and the 2-year DFS and OS rates were 55.1 % and 78.6 %, respectively. The pathological responses of 103 cases (94.5 % of 109) of the index lymph node (ILN) were categorized as the worst regression subgroup. In these cases, using the pathological response of the ILN to indicate the status of other lymph nodes would not result to a missed therapeutic lymph node dissection. CONCLUSIONS: Neoadjuvant immunotherapy plus chemotherapy is safe and effective for ESCC, with observable survival benefits. The pathological response of the ILN after neoadjuvant therapy may have important value in guiding therapeutic lymph node dissection.

7.
Anticancer Drugs ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38940933

ABSTRACT

Liver cancer is a prevalent malignant tumor globally. The newly approved first-line drug, donafenib, is a novel oral small molecule multi-tyrosine kinase inhibitor that has significant antitumor effects on liver cancer. This study aims to investigate the antitumor effects of donafenib on liver cancer and to explore its potential mechanisms. Donafenib significantly inhibited the viability of Huh-7 and HCCLM3 cells, inhibited malignant cell proliferation, and promoted cell apoptosis, as demonstrated by CCK-8, EdU, and Calcein/PI (propidium iodide) staining experiments. The results of DNA damage detection experiments and western blot analysis indicate that donafenib caused considerable DNA damage in liver cancer cells. The analysis of poly (ADP-ribose) polymerase 1 (PARP1) in liver cancer patients using online bioinformatics data websites such as TIMER2.0, GEPIA, UALCAN, cBioPortal, Kaplan-Meier Plotter, and HPA revealed a high expression of PARP1, which is associated with poor prognosis. Molecular docking and western blot analysis demonstrated that donafenib can directly target and downregulate the protein expression of PARP1, a DNA damage repair protein, thereby promoting DNA damage in liver cancer cells. Western blot and immunofluorescence detection showed that the group treated with donafenib combined with PARP1 inhibitor had significantly higher expression of γ-H2AX and 8-OHdG compared to the groups treated with donafenib or PARP1 inhibitors alone, the combined treatment suppresses the expression of the antiapoptotic protein Bcl2 and enhances the protein expression level of the proapoptotic protein Bcl-2-associated X protein (BAX). These data suggest that the combination of donafenib and a PARP1 inhibitor results in more significant DNA damage in cells and promotes cell apoptosis. Thus, the combination of donafenib and PARP1 inhibitors has the potential to be a treatment option for liver cancer.

8.
Eur J Histochem ; 68(3)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38934084

ABSTRACT

Artificial light can affect eyeball development and increase myopia rate. Matrix metalloproteinase 2 (MMP-2) degrades the extracellular matrix, and induces its remodeling, while tissue inhibitor of matrix MMP-2 (TIMP-2) inhibits active MMP-2. The present study aimed to look into how refractive development and the expression of MMP-2 and TIMP-2 in the guinea pigs' remodeled sclerae are affected by artificial light with varying spectral compositions. Three weeks old guinea pigs were randomly assigned to groups exposed to five different types of light: natural light, LED light with a low color temperature, three full spectrum artificial lights, i.e. E light (continuous spectrum in the range of ~390-780 nm), G light (a blue peak at 450 nm and a small valley 480 nm) and F light (continuous spectrum and wavelength of 400 nm below filtered). A-scan ultrasonography was used to measure the axial lengths of their eyes, every two weeks throughout the experiment. Following twelve weeks of exposure to light, the sclerae were observed by optical and transmission electron microscopy. Immunohistochemistry, Western blot and RT-qPCR were used to detect the MMP-2 and TIMP-2 protein and mRNA expression levels in the sclerae. After four, six, eight, ten, and twelve weeks of illumination, the guinea pigs in the LED and G light groups had axial lengths that were considerably longer than the animals in the natural light group while the guinea pigs in the E and F light groups had considerably shorter axial lengths than those in the LED group. Following twelve weeks of exposure to light, the expression of the scleral MMP-2 protein and mRNA were, from low to high, N group, E group, F group, G group, LED group; however, the expression of the scleral TIMP-2 protein and mRNA were, from high to low, N group, E group, F group, G group, LED group. The comparison between groups was statistically significant (p<0.01). Continuous, peaks-free or valleys-free artificial light with full-spectrum preserves remodeling of scleral extracellular matrix in guinea pigs by downregulating MMP-2 and upregulating TIMP-2, controlling eye axis elongation, and inhibiting the onset and progression of myopia.


Subject(s)
Matrix Metalloproteinase 2 , Sclera , Tissue Inhibitor of Metalloproteinase-2 , Animals , Guinea Pigs , Matrix Metalloproteinase 2/metabolism , Tissue Inhibitor of Metalloproteinase-2/metabolism , Tissue Inhibitor of Metalloproteinase-2/genetics , Sclera/metabolism , Light , Myopia/metabolism , Refraction, Ocular
9.
J Exp Clin Cancer Res ; 43(1): 154, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822363

ABSTRACT

BACKGROUND: RNA modifications of transfer RNAs (tRNAs) are critical for tRNA function. Growing evidence has revealed that tRNA modifications are related to various disease processes, including malignant tumors. However, the biological functions of methyltransferase-like 1 (METTL1)-regulated m7G tRNA modifications in breast cancer (BC) remain largely obscure. METHODS: The biological role of METTL1 in BC progression were examined by cellular loss- and gain-of-function tests and xenograft models both in vitro and in vivo. To investigate the change of m7G tRNA modification and mRNA translation efficiency in BC, m7G-methylated tRNA immunoprecipitation sequencing (m7G tRNA MeRIP-seq), Ribosome profiling sequencing (Ribo-seq), and polysome-associated mRNA sequencing were performed. Rescue assays were conducted to decipher the underlying molecular mechanisms. RESULTS: The tRNA m7G methyltransferase complex components METTL1 and WD repeat domain 4 (WDR4) were down-regulated in BC tissues at both the mRNA and protein levels. Functionally, METTL1 inhibited BC cell proliferation, and cell cycle progression, relying on its enzymatic activity. Mechanistically, METTL1 increased m7G levels of 19 tRNAs to modulate the translation of growth arrest and DNA damage 45 alpha (GADD45A) and retinoblastoma protein 1 (RB1) in a codon-dependent manner associated with m7G. Furthermore, in vivo experiments showed that overexpression of METTL1 enhanced the anti-tumor effectiveness of abemaciclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor. CONCLUSION: Our study uncovered the crucial tumor-suppressive role of METTL1-mediated tRNA m7G modification in BC by promoting the translation of GADD45A and RB1 mRNAs, selectively blocking the G2/M phase of the cell cycle. These findings also provided a promising strategy for improving the therapeutic benefits of CDK4/6 inhibitors in the treatment of BC patients.


Subject(s)
Breast Neoplasms , Methyltransferases , RNA, Transfer , Humans , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Mice , Animals , Methyltransferases/metabolism , Methyltransferases/genetics , RNA, Transfer/genetics , RNA, Transfer/metabolism , Methylation , Cell Line, Tumor , Cell Proliferation , Carcinogenesis/genetics , Cell Cycle Checkpoints , Protein Biosynthesis , Xenograft Model Antitumor Assays , Mice, Nude
10.
Angew Chem Int Ed Engl ; 63(30): e202405313, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-38738593

ABSTRACT

Three-dimensional covalent organic frameworks (3D COFs), recognized for their tailorable structures and accessible active sites, offer a promising platform for developing advanced photocatalysts. However, the difficulty in the synthesis and functionalization of 3D COFs hinders their further development. In this study, we present a series of 3D-bcu-COFs with 8 connected porphyrin units linked by linear linkers through imine bonds as a versatile platform for photocatalyst design. The photoresponse of 3D-bcu-COFs was initially modulated by functionalizing linear linkers with benzo-thiadiazole or benzo-selenadiazole groups. Furthermore, taking advantage of the well-exposed porphyrin and imine sites in 3D-bcu-COFs, their photocatalytic activity was optimized by stepwise protonation of imine bonds and porphyrin centers. The dual protonated COF with benzo-selenadiazole groups exhibited enhanced charge separation, leading to an increased photocatalytic H2O2 production under visible light. This enhancement demonstrates the combined benefits of linker functionalization and stepwise protonation on photocatalytic efficiency.

11.
Sci Rep ; 14(1): 12384, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811601

ABSTRACT

Compared with conventional soils, such as sand and clay, little knowledge on the coefficient of lateral earth pressure at-rest (K0) has been established for loess in the current literature. This paper presents an experimental investigation on K0 of compacted loess and the associated impacts on undrained shear behaviour. By adopting a K0 consolidation module in the triaxial system, the K0 stress state for loess samples was achieved through a unique feedback control. During the K0 consolidation, the deviatoric stress (q) increases progressively with the premise that the volumetric strain (εv) of the sample equals to the axial strain (εa). The results show that the K0 value of compacted loess is in a range of 0.28 to 0.53, which is dependent on the packing density and the clay content. A distinguishable decrease of K0 was found in the course of K0 consolidation for the loosely compacted loess sample, whereas a similar trend was not observed in the dense sample. In the undrained shear stage, all loess specimens revealed contractive response in the stress path (q-p') diagram, which can be quantified by a modified collapsibility index (Ic). The index is consistently higher for the K0 consolidated loess samples than for the isotropic ones. The experimental results indicate a strong impact of the initial stress state on the shear behaviour of compacted loess.

12.
ChemMedChem ; 19(14): e202400111, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38622787

ABSTRACT

Abnormally localized nucleic acids (NAs) are considered as pathogen associated molecular patterns (PAMPs) in innate immunity. They are recognized by NAs-specific pattern recognition receptors (PRRs), leading to the activation of associated signaling pathways and subsequent production of type I interferons (IFNs) and pro-inflammatory cytokines, which further trigger the adaptive immunity. Notably, NAs-mediated innate immune activation is highly dependent on the conformation changes, especially the aggregation of PRRs. Evidence indicates that the characteristics of NAs including their length, concentration and even spatial structure play essential roles in inducing the aggregation of PRRs. Therefore, nucleic acid materials (NAMs) with high valency of NAs and high-order structures hold great potential for activating innate and adaptive immunity, making them promising candidates for cancer immunotherapy. In recent years, a variety of NAMs have been developed and have demonstrated significant efficacy in achieving satisfactory anti-tumor immunity in multiple mouse models, exhibiting huge potential for clinical application in cancer treatment. This review aims to discuss the mechanisms of NAMs-mediated innate immune response, and summarize their applications in cancer immunotherapy.


Subject(s)
Immunity, Innate , Immunotherapy , Neoplasms , Nucleic Acids , Immunity, Innate/drug effects , Humans , Neoplasms/immunology , Neoplasms/drug therapy , Neoplasms/therapy , Nucleic Acids/chemistry , Nucleic Acids/pharmacology , Animals
13.
Sci Rep ; 14(1): 9126, 2024 Apr 21.
Article in English | MEDLINE | ID: mdl-38644392

ABSTRACT

This study takes environmental factors and individual factors as variables to explore the deep internal mechanism of the impact of a comprehensive environment on higher education physical education (PE) teachers' job burnout. Little research has been done on how environmental factors affect the internal mechanism of college and university PE teachers' job burnout through individual factors (e.g., professional pressure and teaching efficacy). In this study, the participants were 231 PE teachers from seven comprehensive universities, and four questionnaires were administered to measure the participants' job burnout, perceived overall environment, teaching efficacy, and occupational stress. Research has found that environmental factors have a significant negative impact on occupational stress, and occupational stress plays an important mediating role between environment and occupational burnout. Research has shown that differences in external environments lead to varying levels of personal stress among college physical education teachers, which in turn affects their level of occupational burnout. The study concludes that a good social, working, and living environment helps to reduce the work pressure on PE teachers, improves their sense of teaching efficacy, and inhibits the occurrence of teachers' job burnout.

14.
Molecules ; 29(8)2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38675553

ABSTRACT

In traditional Chinese medicine, Aurantii Fructus Immatures (AFIs) have been utilized for more than 2000 years. The proportions of different fruit parts are crucial for evaluating AFI quality in China. However, the basis for this statement's substance is unclear. Differences in quality are intimately correlated with a plant's metabolite composition. On the basis of a widely targeted metabolome, this study intended to investigate the metabolite composition and evaluate the antioxidant capacity of the peel and pulp of an AFI. Metabolites were identified and quantified by UHPLC-QqQ-MS. To assess their antioxidant ability, DPPH and ABTS assays were carried out. There were 1327 chemical compounds identified by UHPLC-QqQ-MS. After screening the differential metabolites using a multivariate statistical analysis, it was found that there were 695 significant differences in the metabolites between the peel and the pulp. Among them, it was discovered that the content of active ingredients in the peel group was higher than that in the pulp group. Furthermore, the aqueous extracts from the peel showed stronger antioxidant capacities than those from the pulp. The metabolites and antioxidant capacities were significantly different between the peel and the pulp. This study of different fruit parts might provide a guide for AFI quality assessments.


Subject(s)
Antioxidants , Fruit , Metabolomics , Antioxidants/metabolism , Fruit/chemistry , Fruit/metabolism , Metabolomics/methods , Chromatography, High Pressure Liquid , Citrus/chemistry , Citrus/metabolism , Metabolome , Plant Extracts/chemistry , Plant Extracts/pharmacology
15.
Front Oncol ; 14: 1358750, 2024.
Article in English | MEDLINE | ID: mdl-38646440

ABSTRACT

The tumor microenvironment is a complex ecosystem where various cellular and molecular interactions shape the course of cancer progression. Macrophage colony-stimulating factor (M-CSF) plays a pivotal role in this context. This study delves into the biological properties and functions of M-CSF in regulating tumor-associated macrophages (TAMs) and its role in modulating host immune responses. Through the specific binding to its receptor colony-stimulating factor 1 receptor (CSF-1R), M-CSF orchestrates a cascade of downstream signaling pathways to modulate macrophage activation, polarization, and proliferation. Furthermore, M-CSF extends its influence to other immune cell populations, including dendritic cells. Notably, the heightened expression of M-CSF within the tumor microenvironment is often associated with dismal patient prognoses. Therefore, a comprehensive investigation into the roles of M-CSF in tumor growth advances our comprehension of tumor development mechanisms and unveils promising novel strategies and approaches for cancer treatment.

16.
Oral Oncol ; 152: 106798, 2024 May.
Article in English | MEDLINE | ID: mdl-38615583

ABSTRACT

Acquired radio-resistance is thought to be one of the main causes of recurrent metastasis after failure of nasopharyngeal carcinoma (NPC) radiotherapy, which may be related to X-ray-induced epithelial-mesenchymal transition (EMT) activation. The circadian clock gene, BMAL1, has been shown to correlate with the sensitivity of NPCs to radiotherapy, but the specific mechanism has not been reported. NPC cells were irradiated by conventional fractionation to generate radiotherapy-resistant cells. NPC cells with BMAL1 gene stabilization/overexpression and interference were obtained by lentiviral transfection. Western blotting, colony formation analysis, cell counting kit-8 assays, wound-healing tests, Transwell assays, flow cytometry, the EDU method, nuclear plasma separation experiments, HE staining, immunohistochemical staining and TUNEL staining were performed to explore the influence and molecular mechanism of the circadian clock gene, BMAL1, on NPC-acquired radio-resistance and EMT through in vitro and in vivo experiments. The results indicated that there was a gradual downregulation of BMAL1 gene protein expression during the routine dose induction of radio-resistance in NPC cells. EMT activation was present in the radiation-resistant cell line 5-8FR, and was accompanied by the significant enhancement of proliferation, migration and invasion. The BMAL1 gene significantly increased the radiosensitivity of the radiation-resistant cell line 5-8FR and reversed the acquired radio-resistance of NPCs, which was accomplished by inhibiting the TGF-ß1/Smads/Snail1 axis-mediated EMT.


Subject(s)
ARNTL Transcription Factors , Epithelial-Mesenchymal Transition , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Radiation Tolerance , Snail Family Transcription Factors , Transforming Growth Factor beta1 , Humans , Snail Family Transcription Factors/metabolism , ARNTL Transcription Factors/metabolism , ARNTL Transcription Factors/genetics , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/pathology , Transforming Growth Factor beta1/metabolism , Nasopharyngeal Neoplasms/metabolism , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/genetics , Cell Line, Tumor , Animals , Mice , Smad Proteins/metabolism , Mice, Nude , Circadian Clocks , Male
17.
Article in English | MEDLINE | ID: mdl-38432457

ABSTRACT

Male Japanese quails (Coturnix japonica) have been found to exhibit a three-phase metabolic change when subjected to prolonged fasting, during which basal thermogenesis is significantly reduced. A study had shown that there is a significant difference in the body temperature between male and female Japanese quails. However, whether female Japanese quails also show the same characteristic three-phase metabolic change during prolonged fasting and the underlying thermogenesis mechanisms associated with such changes are still unclear. In this study, female Japanese quails were subjected to prolonged starvation, and the body mass, basal metabolic rate (BMR), body temperature, mass of tissues and organs, body fat content, the state-4 respiration (S4R) and cytochrome c oxidase (CCO) activity in the muscle and liver of these birds were measured to determine the status of metabolic changes triggered by the starvation. In addition, the levels of glucose, triglyceride (TG) and uric acid, and thyroid hormones (T3 and T4) in the serum and the mRNA levels of myostatin (MSTN) and avian uncoupling protein (av-UCP) in the muscle were also measured. The results revealed the existence of a three-phase stage similar to that found in male Japanese quails undergoing prolonged starvation. Fasting resulted in significantly lower body mass, BMR, body temperature, tissues masses and most organs masses, as well as S4R and CCO activity in the muscle and liver. The mRNA level of av-UCP decreased during fasting, while that of MSTN increased but only during Phase I and II and decreased significantly during Phase III. Fasting also significantly lowered the T3 level and the ratio of T3/T4 in the serum. These results indicated that female Japanese quails showed an adaptive response in basal thermogenesis at multiple hierarchical levels, from organismal to biochemical, enzyme and cellular level, gene and endocrine levels and this integrated adjustment could be a part of the adaptation used by female quails to survive long-term fasting.


Subject(s)
Coturnix , Quail , Female , Male , Animals , Coturnix/metabolism , Quail/metabolism , Fasting/metabolism , Thermogenesis , RNA, Messenger/genetics
18.
Int J Mol Sci ; 25(5)2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38474274

ABSTRACT

Real-time quantitative PCR (qRT-PCR) is a pivotal technique for gene expression analysis. To ensure reliable and accurate results, the internal reference genes must exhibit stable expression across varied experimental conditions. Currently, no internal reference genes for Camellia impressinervis have been established. This study aimed to identify stable internal reference genes from eight candidates derived from different developmental stages of C. impressinervis flowers. We employed geNorm, NormFinder, and BestKeeper to evaluate the expression stability of these candidates, which was followed by a comprehensive stability analysis. The results indicated that CiTUB, a tubulin gene, exhibited the most stable expression among the eight reference gene candidates in the petals. Subsequently, CiTUB was utilized as an internal reference for the qRT-PCR analysis of six genes implicated in the petal pigment synthesis pathway of C. impressinervis. The qRT-PCR results were corroborated by transcriptome sequencing data, affirming the stability and suitability of CiTUB as a reference gene. This study marks the first identification of stable internal reference genes within the entire genome of C. impressinervis, establishing a foundation for future gene expression and functional studies. Identifying such stable reference genes is crucial for advancing molecular research on C. impressinervis.


Subject(s)
Camellia , Camellia/genetics , Gene Expression Profiling/methods , Transcriptome , Real-Time Polymerase Chain Reaction/methods , Flowers/genetics , Reference Standards
19.
Chin J Integr Med ; 30(5): 449-457, 2024 May.
Article in English | MEDLINE | ID: mdl-38488996

ABSTRACT

BACKGROUP: Currently, aromatherapy is being increasingly utilized in clinical practice, particularly in managing the side effects associated with radiotherapy and chemoradiotherapy. However, it remains to be established whether aromatherapy can effectively alleviate these symptoms. OBJECTIVE: To investigate the effects of aromatherapy on the physical and mental health of patients with cancer undergoing radiotherapy and chemotherapy. METHODS: Seven databases were researched from inception until September 29, 2023, including PubMed, Scopus, and Web of Science, Chinese National Knowledge Infrastructure, Wanfang database, China Biology Medicine disc and VIP Chinese Medical Journal Database. Review Manager version 5.3 was utilized for data analysis. The Cochrane Risk of Bias tool RoB2 was employed to evaluate the quality of the literature included in the study. Evidence quality rating was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach through the GRADEpro GDT online tool. RESULTS: Nineteen studies involving 1,541 patients were included. Aromatherapy can alleviate nausea [relative risk (RR)=0.64, 95% confidence interval (CI): 0.53 to 0.78, P<0.05, I2=46%; standardized mean difference (SMD)=-0.86, 95% CI: -1.21 to -0.51, P<0.05, I2=64%] and vomiting (RR=0.54, 95% CI: 0.42 to 0.69, P<0.05, I2=35%; SMD=-1.28, 95% CI: -1.52 to -1.03, P<0.05, I2=92%), improve sleep disorders [mean difference (MD)=-3.39, 95% CI: -3.95 to -2.84, P<0.05, I2=0%], relieve pain (SMD=-1.58, 95% CI: -1.96 to -1.21, P<0.05, I2=0%), mitigate fatigue (SMD=-1.28, 95% CI: -2.44 to -0.11, P<0.05, I2=93%) and enhance quality of life (SMD=0.50, 95% CI: 0.22 to 0.79, P<0.05, I2=0%) in cancer patients after radiotherapy and chemotherapy, but it may not have a significant effect on anxiety. The risk of bias was high in the included studies using the Cochrane Risk of Bias tool RoB2, and no studies were considered to be of high grade according to the GRADE system. CONCLUSIONS: Aromatherapy is an efficacious, safe and economic adjunctive therapy for cancer patients, which can mend the physical symptoms and mental health of cancer patients. However, more high-quality studies are needed to verify it. (PROSPERO registration No. CRD42023390171).


Subject(s)
Aromatherapy , Mental Health , Neoplasms , Humans , Aromatherapy/methods , Neoplasms/complications , Neoplasms/psychology , Neoplasms/radiotherapy , Neoplasms/therapy , Quality of Life , Radiotherapy/adverse effects
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