ABSTRACT
BACKGROUND: The emergence of the global problem of multi-drug resistant bacteria (MDR) is closely related to the improper use of antibiotics, which gives birth to an urgent need for antimicrobial innovation in the medical and health field. Silver nanoparticles (AgNPs) show significant antibacterial potential because of their unique physical and chemical properties. By accurately regulating the morphology, size and surface properties of AgNPs, the antibacterial properties of AgNPs can be effectively enhanced and become a next generation antibacterial material with great development potential. OBJECTIVE: The detection of the inhibitory effect of AgNPs on MDR provides more possibilities for the research and development of new antimicrobial agents. METHODS: Promote the formation of AgNPs by redox reaction; determine the minimum inhibitory concentration (MIC) of AgNPs to bacteria by broth microdilution method; evaluate the killing efficacy of AgNPs against multi-drug-resistant bacteria by plate counting; evaluate the inhibitory effect of AgNPs on biofilm construction by crystal violet staining; study the drug resistance of bacteria by gradually increasing the concentration of AgNPs; and detect the toxicity of AgNPs to cells by CCK-8 method. RESULTS: AgNPs has a significant bactericidal effect on a variety of drug-resistant bacteria. After exposure to AgNPs solution for 12 hours, the number of E. coli decreased sharply, and S. aureus was basically eliminated after 16 hours. In particular, AgNPs showed stronger inhibition against Gram-negative bacteria. In addition, AgNPs can effectively hinder the formation of bacterial biofilm, and its inhibitory effect increases with the increase of AgNPs solution concentration. When AgNPs is used for a long time, the development of bacterial resistance to it is slow. From the point of view of safety, AgNPs has no harmful effects on organisms and has biosafety. CONCLUSION: AgNPs can inhibit MDR, and the bacteriostatic ability of Gram-negative bacteria is higher than that of Gram-positive bacteria. It can also inhibit the formation of bacterial biofilm, avoid drug resistance and reduce cytotoxicity.
ABSTRACT
The Drosophila melanogaster MD-RR strain contains an Rdl mutation (A301S) resulting in resistance to several insecticide classes viz. phenyl pyrazoles (e.g., fipronil), cyclodienes (e.g., dieldrin), and chlorinated aliphatic hydrocarbons (e.g., lindane). Fitness costs are commonly observed with resistant insect populations as side effects of the genetic change conferring the resistant phenotype. Because of fitness costs, reversion from the resistant to susceptible genotype and phenotype is common. However, the Rdl genotype in D. melanogaster appears to allow the flies to maintain the resistant genotype/phenotype without selective pressure and with minimal fitness costs. We provide evidence that compensation for the Rdl mutation influences the cholinergic system, where an increase in acetylcholinesterase gene expression and enzyme activity results in neurophysiological changes and cross resistance to a carbamate insecticide (propoxur oral resistance ratio (RR) of 63) and an organophosphate insecticide (dichlorvos oral RR of 7). Such cross resistance was not previously reported with the initial collection and testing of this strain. In addition to acetylcholinesterase, the Rdl mutation influences the expression of the muscarinic acetylcholine receptor subtype-B, resulting in resistance to non-selective muscarinic compounds (pilocarpine and atropine). Collectively, these results indicate that the Rdl mutation (A301S) at GABA-gated ionophore complex influences the physiology of the cholinergic system, leading to resistance to established insecticide classes. Additionally, this mutation may impact the effectiveness of insecticides targeting novel sites, like muscarinic receptors.
Subject(s)
Acetylcholinesterase , Chloride Channels , Drosophila Proteins , Drosophila melanogaster , Insecticide Resistance , Receptors, GABA-A , Animals , Acetylcholinesterase/genetics , Acetylcholinesterase/metabolism , Chloride Channels/genetics , Chloride Channels/metabolism , Drosophila melanogaster/genetics , Drosophila melanogaster/drug effects , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Insecticide Resistance/genetics , Insecticides , Mutation , Receptors, GABA-A/genetics , Receptors, GABA-A/metabolism , Receptors, Muscarinic/genetics , Receptors, Muscarinic/metabolismABSTRACT
The spectral emission of laser-induced plasma in water has a broadband continuum containing ultraviolet light, which can be used as a novel light source for the degradation of organic compounds. We studied the degradation process of the organic dye Rhodamine B (RhB) using plasma light source excited by the "Laser + Fe" mode. Spectral analysis and reaction kinetics modelling were used to study the degradation mechanism. The degradation process using this light source could be divided into two stages. The initial stage was mainly photocatalytic degradation, where ultraviolet light broke the chemical bond of RhB, and then RhB was degraded by the strong oxidising ability of ·OH. As the iron and hydrogen ion concentrations increased, the synergistic effect of photocatalysis and the Fenton reaction further enhanced the degradation rate in the later stage. The plasma excited by the "Laser + Fe" mode achieved photodegradation by effectively enhancing the ultraviolet wavelength ratio of the emission spectrum and triggered the Fenton reaction to achieve rapid organic matter degradation. Our findings indicate that the participation of the Fenton reaction can increase the degradation rate by approximately 10 times. Besides, the impact of pH on degradation efficiency demonstrates that both acidic and alkaline environments have better degradation effects than neutral conditions; this is because acidic environments can enhance the Fenton reaction, while alkaline environments can provide more ·OH.
ABSTRACT
Optical systems with extended depth of field (EDOF) are crucial for observation and measurement applications, where achieving compactness and a substantial depth of field (DOF) presents a considerable challenge with conventional optical elements. In this paper, we propose an innovative solution for the miniaturization of EDOF imaging systems by introducing an ultra-thin annular folded lens (AFL). To validate the practical feasibility of the theory, we design an annular four-folded lens with an effective focal length of 80.91 mm and a total thickness of only 8.50 mm. Simulation results show that the proposed folded lens has a DOF of 380.55 m. We further developed an AFL-based test system exhibiting a resolution of 0.11 mrad across a wide wavelength range of 486-656 nm. Additionally, we present experimental results from a miniature compact prototype, which further highlights the promising potential of folded lenses for long-range EDOF imaging.
ABSTRACT
Liver fibrosis has become a serious public health problem that can develop into liver cirrhosis and hepatocellular carcinoma and even lead to death. Cannabidiol (CBD), which is an abundant nonpsychoactive component in the cannabis plant, exerts cytoprotective effects in many diseases and under pathological conditions. In our previous studies, CBD significantly attenuated liver injury induced by chronic and binge alcohol in a mouse model and oxidative bursts in human neutrophils. However, the effects of CBD on liver fibrosis and the underlying mechanisms still need to be further explored. A mouse liver fibrosis model was induced by carbon tetrachloride (CCl4) for 10 weeks and used to explore the protective properties of CBD and related molecular mechanisms. After the injection protocol, serum samples and livers were used for molecular biology, biochemical and pathological analyses. The results showed that CBD could effectively improve liver function and reduce liver damage and liver fibrosis progression in mice; the expression levels of transaminase and fibrotic markers were reduced, and histopathological characteristics were improved. Moreover, CBD inhibited the levels of inflammatory cytokines and reduced the protein expression levels of p-NF-κB, NF-κB, p-IκBα, p-p38 MAPK, and COX-2 but increased the expression level of PPAR-α. We found that CBD-mediated protection involves inhibiting NF-κB and activating PPAR-α. In conclusion, these results suggest that the hepatoprotective effects of CBD may be due to suppressing the inflammatory response in CCl4-induced mice and that the NF-κB and PPAR-α signaling pathways might be involved in this process.
Subject(s)
Cannabidiol , Carbon Tetrachloride , Liver Cirrhosis , NF-kappa B , PPAR alpha , Animals , Cannabidiol/pharmacology , Cannabidiol/therapeutic use , NF-kappa B/metabolism , PPAR alpha/metabolism , Liver Cirrhosis/drug therapy , Liver Cirrhosis/pathology , Liver Cirrhosis/chemically induced , Liver Cirrhosis/metabolism , Mice , Carbon Tetrachloride/toxicity , Male , Signal Transduction/drug effects , Disease Models, Animal , Mice, Inbred C57BL , Liver/pathology , Liver/drug effects , Liver/metabolismABSTRACT
Coactivator-associated arginine methyltransferase 1 (CARM1), pivotal for catalyzing arginine methylation of histone and non-histone proteins, plays a crucial role in developing various cancers. CARM1 was initially recognized as a transcriptional coregulator by orchestrating chromatin remodeling, transcription regulation, mRNA splicing and stability. This diverse functionality contributes to the recruitment of transcription factors that foster malignancies. Going beyond its established involvement in transcriptional control, CARM1-mediated methylation influences a spectrum of biological processes, including the cell cycle, metabolism, autophagy, redox homeostasis, and inflammation. By manipulating these physiological functions, CARM1 becomes essential in critical processes such as tumorigenesis, metastasis, and therapeutic resistance. Consequently, it emerges as a viable target for therapeutic intervention and a possible biomarker for medication response in specific cancer types. This review provides a comprehensive exploration of the various physiological functions of CARM1 in the context of cancer. Furthermore, we discuss potential CARM1-targeting pharmaceutical interventions for cancer therapy.
ABSTRACT
Bursaphelenchus xylophilus (Steiner&Buhrer) Nickle is a global quarantine pest that causes devastating mortality in pine species. The rapid and uncontrollable parasitic spread of this organism results in substantial economic losses to pine forests annually. In this study, we used the MaxEnt model and GIS software ArcGIS10.8 to predict the distribution of B. xylophilus based on collected distribution points and 19 environmental variables (with a correlation coefficient of|R| > 0.8) for the contemporary period (1970-2000), 2041-2060 (2050s), 2061-2080 (2070s), and 2081-2100 (2090s) under four shared socioeconomic pathways (SSPs). We conducted a comprehensive analysis of the key environmental factors affecting the geographical distribution of B. xylophilus and suitable distribution areas. Our results indicate that in current prediction maps B. xylophilus had potential suitable habitats in all continents except Antarctica, with East Asia being the region with the most highly suitable areas and the most serious epidemic area currently. Precipitation of the warmest quarter, temperature seasonality, precipitation of the wettest month, and maximum temperature of the warmest month were identified as key environmental variables that determine the distribution of B. xylophilus. Under future climatic conditions, the potential geographic distribution of B. xylophilus will expand relative to current conditions. In particular, under the SSP5-8.5 scenario in 2081-2100, suitable areas will expand to higher latitudes, and there will be significant changes in suitable areas in Europe, East Asia, and North America. These findings are crucial for future prevention and control management and monitoring.
Subject(s)
Pinus , Xylophilus , Ecosystem , Forests , Temperature , Asia, Eastern , Pinus/parasitologyABSTRACT
Litsea coreana Levl. var. sinensis (Allen) Yang et P. H. Huang is a popular ethnic herb and beverage plant known for its high flavonoid content, which has been linked to a variety of pharmacological benefits and crucial health-promoting impacts in humans. The progress in understanding the molecular mechanisms of flavonoid accumulation in this plant has been hindered due to the deficiency of genomic and transcriptomic resources. We utilized a combination of Illumina and Oxford Nanopore Technology (ONT) sequencing to generate a de novo hybrid transcriptome assembly. In total, 126,977 unigenes were characterized, out of which 107,977 were successfully annotated in seven public databases. Within the annotated unigenes, 3,781 were categorized into 58 transcription factor families. Furthermore, we investigated the presence of four valuable flavonoids-quercetin-3-O-ß-D-galactoside, quercetin-3-O-ß-D-glucoside, kaempferol-3-O-ß-D-galactoside, and kaempferol-3-O-ß-D-glucoside in 98 samples, using high-performance liquid chromatography. A weighted gene co-expression network analysis identified two co-expression modules, MEpink and MEturquoise, that showed strong positive correlation with flavonoid content. Within these modules, four transcription factor genes (R2R3-MYB, NAC, WD40, and ARF) and four key enzyme-encoding genes (CHI, F3H, PAL, and C4H) emerged as potential hub genes. Among them, the R2R3-MYB (LcsMYB123) as a homologous gene to AtMYB123/TT2, was speculated to play a significant role in flavonol biosynthesis based on phylogenetic analysis. Our findings provided a theoretical foundation for further research into the molecular mechanisms of flavonoid biosynthesis. Additionally, The hybrid transcriptome sequences will serve as a valuable molecular resource for the transcriptional annotation of L. coreana var. sinensis, which will contribute to the improvement of high-flavonoid materials.
Subject(s)
Litsea , Transcriptome , Humans , Litsea/genetics , Litsea/metabolism , Quercetin , Phylogeny , Gene Expression Profiling , Flavonoids/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Gene Expression Regulation, PlantABSTRACT
Rare genetic diseases, often referred to as orphan diseases due to their low prevalence and limited treatment options, have long posed significant challenges to our medical system. In recent years, Messenger RNA (mRNA) therapy has emerged as a highly promising treatment approach for various diseases caused by genetic mutations. Chemically modified mRNA is introduced into cells using carriers like lipid-based nanoparticles (LNPs), producing functional proteins that compensate for genetic deficiencies. Given the advantages of precise dosing, biocompatibility, transient expression, and minimal risk of genomic integration, mRNA therapies can safely and effectively correct genetic defects in rare diseases and improve symptoms. Currently, dozens of mRNA drugs targeting rare diseases are undergoing clinical trials. This comprehensive review summarizes the progress of mRNA therapy in treating rare genetic diseases. It introduces the development, molecular design, and delivery systems of mRNA therapy, highlighting their research progress in rare genetic diseases based on protein replacement and gene editing. The review also summarizes research progress in various rare disease models and clinical trials. Additionally, it discusses the challenges and future prospects of mRNA therapy. Researchers are encouraged to join this field and collaborate to advance the clinical translation of mRNA therapy, bringing hope to patients with rare genetic diseases.
Subject(s)
Genetic Therapy , RNA, Messenger , Rare Diseases , Humans , Rare Diseases/therapy , Rare Diseases/genetics , RNA, Messenger/administration & dosage , RNA, Messenger/genetics , Animals , Genetic Therapy/methods , Genetic Diseases, Inborn/therapy , Genetic Diseases, Inborn/genetics , Nanoparticles , Gene Editing/methodsABSTRACT
Hepatitis B is a major global challenge, but there is a lack of epidemiological research on hepatitis B incidence from a change point perspective. This study aimed to fill this gap by identifying significant change points and trends in hepatitis time series in Xinjiang, China. The datasets were obtained from the Xinjiang Information System for Disease Control and Prevention. The Mann-Kendall-Sneyers (MKS) test was used to detect change points and trend changes on the hepatitis B time series of 14 regions in Xinjiang, and the effectiveness of this method was validated by comparing it with the binary segmentation (BS) and segment regression (SR) methods. Based on the results of change point analysis, the prevention and control policies and measures of hepatitis in Xinjiang were discussed. The results showed that 8 regions (57.1%) with at least one change fell within the 95% confidence interval (CI) in all 14 regions by the MKS test, where five regions (Turpan (TP), Hami (HM), Bayingolin (BG), Kyzylsu Kirgiz (KK), Altai (AT)) were identified at one change point, two change points existed for two regions (Aksu (AK), Hotan (HT)) and three change points was detected in 1 region (Bortala (BT)). Most of the change points occurred at both ends of the sequence. More change points indicated an upward trend in the front half of the sequence, while in the latter half, many change points indicated a downward trend prominently. Finally, in comparing the results of the three change point tests, the MKS test showed a 61.5% agreement (8/13) with the BS and SR.
Subject(s)
Hepatitis B , Humans , Time Factors , China/epidemiology , Hepatitis B/diagnosis , Hepatitis B/epidemiology , IncidenceABSTRACT
BACKGROUND/PURPOSE: Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba (R. crenulate), a famous and characteristic Tibetan medicine, has been demonstrated to exert an outstanding brain protection role in the treatment of high-altitude hypoxia disease. However, the metabolic effects of R. crenulate on high-altitude hypoxic brain injury (HHBI) are still incompletely understood. Herein, the anti-hypoxic effect and associated mechanisms of R. crenulate were explored through both in vivo and in vitro experiments. STUDY DESIGN/METHODS: The mice model of HHBI was established using an animal hypobaric and hypoxic chamber. R. crenulate extract (RCE, 0.5, 1.0 and 2.0 g/kg) and salidroside (Sal, 25, 50 and 100 mg/kg) was given by gavage for 7 days. Pathological changes and neuronal apoptosis of mice hippocampus and cortex were evaluated using H&E and TUNEL staining, respectively. The effects of RCE and Sal on the permeability of blood brain barrier (BBB) were detected by Evans blue staining and NIR-II fluorescence imaging. Meanwhile, the ultrastructural BBB and cerebrovascular damages were observed using a transmission electron microscope (TEM). The levels of tight junction proteins Claudin-1, ZO-1 and occludin were detected by immunofluorescence. Additionally, the metabolites in mice serum and brain were determined using UHPLC-MS and MALDI-MSI analysis. The cell viability of Sal on hypoxic HT22 cells induced by CoCl2 was investigated by cell counting kit-8. The contents of LDH, MDA, SOD, GSH-PX and SDH were detected by using commercial biochemical kits. Meanwhile, intracellular ROS, Ca2+ and mitochondrial membrane potential were determined by corresponding specific labeled probes. The intracellular metabolites of HT22 cells were performed by the targeted metabolomics analysis of the Q300 kit. The cell apoptosis and necrosis were examined by YO-PRO-1/PI, Annexin V/PI and TUNEL staining. In addition, mitochondrial morphology was tested by Mito-tracker red with confocal microscopy and TEM. Real-time ATP production, oxygen consumption rate, and proton efflux rate were measured using a Seahorse analyzer. Subsequently, MCU, OPA1, p-Drp1ser616, p-AMPKα, p-AMPKß and Sirt1 were determined by immunofluorescent and western blot analyses. RESULTS: The results demonstrated that R. crenulate and Sal exert anti-hypoxic brain protection from inhibiting neuronal apoptosis, maintaining BBB integrity, increasing tight junction protein Claudin-1, ZO-1 and occludin and improving mitochondrial morphology and function. Mechanistically, R. crenulate and Sal alleviated HHBI by enhancing the tricarboxylic acid cycle to meet the demand of energy of brain. Additionally, experiments in vitro confirmed that Sal could ameliorate the apoptosis of HT22 cells, improve mitochondrial morphology and energy metabolism by enhancing mitochondrial respiration and glycolysis. Meanwhile, Sal-mediated MCU inhibited the activation of Drp1 and enhanced the expression of OPA1 to maintain mitochondrial homeostasis, as well as activation of AMPK and Sirt1 to enhance ATP production. CONCLUSION: Collectively, the findings suggested that RCE and Sal may afford a protective intervention in HHBI through maintaining BBB integrity and improving energy metabolism via balancing MCU-mediated mitochondrial homeostasis by activating the AMPK/Sirt1 signaling pathway.
Subject(s)
Blood-Brain Barrier , Energy Metabolism , Plant Extracts , Rhodiola , Animals , Rhodiola/chemistry , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Mice , Plant Extracts/pharmacology , Energy Metabolism/drug effects , Male , Apoptosis/drug effects , Glucosides/pharmacology , Disease Models, Animal , Phenols/pharmacology , Brain Injuries/drug therapy , Brain Injuries/metabolism , Cell Line , Mitochondria/drug effects , Mitochondria/metabolism , Altitude Sickness/drug therapy , Altitude Sickness/metabolism , Hypoxia/drug therapyABSTRACT
A design method of the computational flat diffractive computational flat diffractive optical system is presented to simplify the optical system structure and achieve high image quality. The aberration expression of the flat diffractive optical element (FDOE) is derived, and then computational imaging methods are used to eliminate the influence of off-axis aberration on image quality, so the field of view is expanded. Based on theoretical analysis, the FDOE is designed, and the field of view has been expanded from 2° to 5°. The results show that the detail resolution of the edge field of view is enhanced after restoration, and the modulation transfer function (MTF) of different subareas calculated using the slanted-edge method improved by an average of 0.17. The diffraction efficiency of the FDOE is greater than 95.75%. This method realizes the miniaturization and lightweight of the optical system, and provides new ideas for the integration of optical systems.
ABSTRACT
Cannabidiol (CBD) is an extract of natural cannabinoids that has therapeutic implications for a variety of ailments, such as neurological diseases, cardiomyopathy, and diabetes, due to its strong anti-inflammatory and oxidative stress properties. Our purpose was to reveal the possible underlying mechanisms and effect of CBD on the glucose oxidase (GO)-induced activation of HSC-T6 and LX-2 cells. The results showed that CBD effectively inhibited the proliferation and activation of HSC-T6 and LX-2 cells, and reduced the production of profibrotic factors to different degrees. CBD disrupted the NOX4 signalling pathway in activated HSC-T6 and LX-2 cells, reduced ROS and MDA levels, and increased SOD and GSH levels, thereby stabilizing the oxidative imbalance. CBD significantly inhibited the phosphorylation and degradation of NF-κB and IκBα, and decreased the release of TNF-α, IL-1ß and IL-6. Moreover, CBD and an NF-κB-specific inhibitor (CAPE) effectively inhibited the expression of α-SMA, COL I, TNF-α and IL-1ß to promote collagen metabolism and inhibit the inflammatory response. Overall, CBD inhibited HSCs activation through a and the mechanism involving the inhibition of NOX4 and NF-κB-dependent ROS regulation, thereby reducing inflammation and ameliorating oxidative imbalances.
Subject(s)
Cannabidiol , NF-kappa B , Humans , NF-kappa B/metabolism , Hepatic Stellate Cells , Cannabidiol/pharmacology , Cannabidiol/metabolism , Tumor Necrosis Factor-alpha/metabolism , Reactive Oxygen Species/metabolism , Liver Cirrhosis/metabolism , NADPH Oxidase 4/metabolismABSTRACT
Osteoporosis, a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture, has led to a high risk of fatal osteoporotic fractures worldwide. Accumulating evidence has revealed that sexual dimorphism is a notable feature of osteoporosis, with sex-specific differences in epidemiology and pathogenesis. Specifically, females are more susceptible than males to osteoporosis, while males are more prone to disability or death from the disease. To date, sex chromosome abnormalities and steroid hormones have been proven to contribute greatly to sexual dimorphism in osteoporosis by regulating the functions of bone cells. Understanding the sex-specific differences in osteoporosis and its related complications is essential for improving treatment strategies tailored to women and men. This literature review focuses on the mechanisms underlying sexual dimorphism in osteoporosis, mainly in a population of aging patients, chronic glucocorticoid administration, and diabetes. Moreover, we highlight the implications of sexual dimorphism for developing therapeutics and preventive strategies and screening approaches tailored to women and men. Additionally, the challenges in translating bench research to bedside treatments and future directions to overcome these obstacles will be discussed.
Subject(s)
Bone Diseases, Metabolic , Osteoporosis , Osteoporotic Fractures , Male , Humans , Female , Sex Characteristics , Bone Density , Osteoporosis/epidemiology , Osteoporotic Fractures/complications , Bone Diseases, Metabolic/complicationsABSTRACT
Inflammation-associated diseases encompass a range of infectious diseases and non-infectious inflammatory diseases, which continuously pose one of the most serious threats to human health, attributed to factors such as the emergence of new pathogens, increasing drug resistance, changes in living environments and lifestyles, and the aging population. Despite rapid advancements in mechanistic research and drug development for these diseases, current treatments often have limited efficacy and notable side effects, necessitating the development of more effective and targeted anti-inflammatory therapies. In recent years, the rapid development of nanotechnology has provided crucial technological support for the prevention, treatment, and detection of inflammation-associated diseases. Various types of nanoparticles (NPs) play significant roles, serving as vaccine vehicles to enhance immunogenicity and as drug carriers to improve targeting and bioavailability. NPs can also directly combat pathogens and inflammation. In addition, nanotechnology has facilitated the development of biosensors for pathogen detection and imaging techniques for inflammatory diseases. This review categorizes and characterizes different types of NPs, summarizes their applications in the prevention, treatment, and detection of infectious and inflammatory diseases. It also discusses the challenges associated with clinical translation in this field and explores the latest developments and prospects. In conclusion, nanotechnology opens up new possibilities for the comprehensive management of infectious and inflammatory diseases.
Subject(s)
Communicable Diseases , Nanoparticles , Humans , Aged , Communicable Diseases/diagnosis , Communicable Diseases/drug therapy , Drug Carriers/therapeutic use , Nanoparticles/therapeutic use , Nanotechnology , Inflammation/drug therapyABSTRACT
Colorectal cancer (CRC) is a prevalent clinical malignancy of the gastrointestinal system, and its clinical drug resistance is the leading cause of poor prognosis. Mechanistically, CRC cells possess a specific oxidative stress defense mechanism composed of a significant number of endogenous antioxidants, such as glutathione, to combat the damage produced by drug-induced excessive reactive oxygen species (ROS). We report on a new anti-CRC nanoplatform, a multifunctional chemo-photothermal nanoplatform based on Camptothecin (CPT) and IR820, an indocyanine dye. The implementation of a GSH-triggered ferroptosis-integrated tumor chemo-photothermal nanoplatform successfully addressed the poor targeting ability of CPT and IR820 while exhibiting significant growth inhibitory effects on CRC cells. Mechanistically, to offset the oxidative stress created by the broken SeSe bonds, endogenous GSH was continuously depleted, which inactivated GPX4 to accumulate lipid peroxides and induce ferroptosis. Concurrently, exogenously administered linoleic acid was oxidized under photothermal conditions, resulting in an increase in LPO accumulation. With the breakdown of the oxidative stress defense system, chemotherapeutic efficacy could be effectively enhanced. In combination with photoacoustic imaging, the nanoplatform could eradicate solid tumors by means of ferroptosis-sensitized chemotherapy. This study indicates that chemotherapy involving a ferroptosis mechanism is a viable method for the treatment of CRC.
Subject(s)
Colorectal Neoplasms , Ferroptosis , Humans , Oxidative Stress , Glutathione , Colorectal Neoplasms/drug therapyABSTRACT
Recent progressions in immunotherapy have transformed cancer treatment, providing a promising strategy that activates the immune system of the patient to find and eliminate cancerous cells. Bispecific antibodies, which engage two separate antigens or one antigen with two distinct epitopes, are of tremendous concern in immunotherapy. The bi-targeting idea enabled by bispecific antibodies (BsAbs) is especially attractive from a medical standpoint since most diseases are complex, involving several receptors, ligands, and signaling pathways. Several research look into the processes in which BsAbs identify different cancer targets such angiogenesis, reproduction, metastasis, and immune regulation. By rerouting cells or altering other pathways, the bispecific proteins perform effector activities in addition to those of natural antibodies. This opens up a wide range of clinical applications and helps patients with resistant tumors respond better to medication. Yet, further study is necessary to identify the best conditions where to use these medications for treating tumor, their appropriate combination partners, and methods to reduce toxicity. In this review, we provide insights into the BsAb format classification based on their composition and symmetry, as well as the delivery mode, focus on the action mechanism of the molecule, and discuss the challenges and future perspectives in BsAb development.
Subject(s)
Antibodies, Bispecific , Neoplasms , Humans , Antibodies, Bispecific/therapeutic use , Immunotherapy/methods , Signal TransductionABSTRACT
Objective: Hepatitis B (HB) is a major global challenge, but there has been a lack of epidemiological studies on HB incidence in Xinjiang from a change-point perspective. This study aims to bridge this gap by identifying significant change points and trends. Method: The datasets were obtained from the Xinjiang Information System for Disease Control and Prevention. Change points were identified using binary segmentation for full datasets and a segmented regression model for five age groups. Results: The results showed four change points for the quarterly HB time series, with the period between the first change point (March 2007) and the second change point (March 2010) having the highest mean number of HB reports. In the subsequent segments, there was a clear downward trend in reported cases. The segmented regression model showed different numbers of change points for each age group, with the 30-50, 51-80, and 15-29 age groups having higher growth rates. Conclusion: Change point analysis has valuable applications in epidemiology. These findings provide important information for future epidemiological studies and early warning systems for HB.