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1.
J Sci Food Agric ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38843481

ABSTRACT

BACKGROUND: Lack of n-3 polyunsaturated fatty acids during the period of maternity drastically lowers the docosahexaenoic acid (DHA) level in the brain of offspring and studies have demonstrated that different molecular forms of DHA are beneficial to brain development. The aim of this study was to investigate the effect of short-term supplementation with DHA-enriched phosphatidylserine (PS) and phosphatidylcholine (PC) on DHA levels in the liver and brain of congenital n-3-deficient mice. RESULTS: Dietary supplementation with DHA significantly changed the fatty acid composition of various phospholipid molecules in the cerebral cortex and liver while DHA-enriched phospholipid was more effective than DHA triglyceride (TG) in increasing brain and liver DHA. Both DHA-PS and DHA-PC could effectively increase the DHA levels, but DHA in the PS form was superior to PC in the contribution of DHA content in the brain ether-linked PC (ePC) and liver lyso-phosphatidylcholine molecular species. DHA-PC showed more significant effects on the increase of DHA in liver TG, PC, ePC, phosphatidylethanolamine (PE) and PE plasmalogen (pPE) molecular species and decreasing the arachidonic acid level in liver PC plasmalogen, ePC, PE and pPE molecular species compared with DHA-PS. CONCLUSION: The effect of dietary interventions with different molecular forms of DHA for brain and liver lipid profiles is different, which may provide theoretical guidance for dietary supplementation of DHA for people. © 2024 Society of Chemical Industry.

2.
Foods ; 13(9)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38731757

ABSTRACT

The traditional fermentation process of soy sauce employs a hyperhaline model and has a long fermentation period. A hyperhaline model can improve fermentation speed, but easily leads to the contamination of miscellaneous bacteria and fermentation failure. In this study, after the conventional koji and moromi fermentation, the fermentation broth was pasteurized and diluted, and then inoculated with three selected microorganisms including Corynebacterium glutamicum, Corynebacterium ammoniagenes, and Lactiplantibacillus plantarum for secondary fermentation. During this ten-day fermentation, the pH, free amino acids, organic acids, nucleotide acids, fatty acids, and volatile compounds were analyzed. The fermentation group inoculated with C. glutamicum accumulated the high content of amino acid nitrogen of 0.92 g/100 mL and glutamic acid of 509.4 mg/100 mL. The C. ammoniagenes group and L. plantarum group were rich in nucleotide and organic acid, respectively. The fermentation group inoculated with three microorganisms exhibited the best sensory attributes, showing the potential to develop a suitable fermentation method. The brewing speed of the proposed process in this study was faster than that of the traditional method, and the umami substances could be significantly accumulated in this low-salt fermented model (7% w/v NaCl). This study provides a reference for the low-salt and rapid fermentation of seasoning.

3.
Anal Chim Acta ; 1308: 342667, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38740453

ABSTRACT

BACKGROUND: High-efficiency and highly reliable analysis of microRNAs (miRNAs) in bodily fluids highlights its significance to be extensively utilized as candidates for non-invasive "liquid biopsy" approaches. DNA biosensors based on strand displacement amplification (SDA) methods have been successfully designed to detect miRNAs given the efficiently amplified and recycled of the target sequences. However, the unpredictable DNA framework and heavy reliance on free diffusion or random reactant collisions in existing approaches lead to delayed reaction kinetics and inadequate amplification. Thus, it is crucial to create a modular probe with a controlled structure, high local concentration, and ease of synthesis. RESULTS: Inspired by the natural spatial-confinement effect based on a well-known streptavidin-biotin interaction, we constructed a protein-DNA hybrid, named protein-scaffolded DNA tetrads (PDT), which consists of four biotinylated Y-shaped DNA (Y-DNA) surrounding a streptavidin protein center via a streptavidin-biotin bridge. The streptavidin-biotin recognition system significantly increased the local concentration and intermolecular distance of the probes to achieve enhanced reaction efficiency and kinetics. The PDT-based assay starts with the target miRNA binding to Y-DNA, which disassembles the Y-DNA structures into three types of hairpin-shaped structures via self-primed strand displacement amplification (SPSDA) and generates remarkable fluorescence signal that is proportional to the miRNA concentration. Results demonstrated that PDT enabled a more efficient detection of miRNA-21 with a sensitivity of 1 fM. Moreover, it was proven reliable for the detection of clinical serum samples, suggesting great potential for advancing the development of rapid and robust signal amplification technologies for early diagnosis. SIGNIFICANCE: This simple yet robust system contributes to the early diagnosis of miR-21 with satisfactory sensitivity and specificity, and display a significantly improved nuclease resistance owing to their unique structure. The results suggested that the strategy is expected to provide a promising potential platform for tumor diagnosis, prognosis and therapy.


Subject(s)
Biotin , DNA , MicroRNAs , Nucleic Acid Amplification Techniques , Streptavidin , MicroRNAs/blood , Humans , Streptavidin/chemistry , DNA/chemistry , DNA/blood , Biotin/chemistry , Biosensing Techniques/methods , Limit of Detection
4.
Front Biosci (Landmark Ed) ; 29(5): 182, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38812309

ABSTRACT

Choline participates in three major metabolic pathways: oxidation, phosphorylation, and acetylation. Through oxidation, choline is converted to betaine and contributes to methyl metabolism and epigenetic regulation. Through phosphorylation, choline participates in phospholipid metabolism, and serves as the precursor of phosphocholine, phosphatidylcholine, glycerophosphocholine, and other essential compounds, thereby modulating lipid metabolism and transport. Through acetylation, choline is transformed into acetylcholine in cholinergic neurons, playing a vital role in neurotransmission. Moreover, gut microbiota can metabolize choline into trimethylamine-N-oxide, and be involved in the pathogenesis of various diseases such as nonalcoholic fatty liver disease (NAFLD), cancer, cardiovascular disease, etc. Since choline metabolism is implicated in the development of NAFLD and diverse cancers, including liver cancer, it may serve as a therapeutic target for these diseases in the future. Currently, there are numerous therapeutic agents targeting choline metabolism to treat NAFLD and cancers, but most of them are ineffective and some even have adverse effects that lead to a series of complications. Therefore, further research and clinical validation are required to obtain safe and efficacious drugs. This review comprehensively summarizes the choline metabolic pathway and its regulatory mechanisms, elucidates the roles and mechanisms of choline metabolism in the aforementioned diseases, and provides a discussion of the current advances and immense potential of this field.


Subject(s)
Choline , Non-alcoholic Fatty Liver Disease , Humans , Choline/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Animals , Gastrointestinal Microbiome/physiology , Neoplasms/metabolism , Liver Neoplasms/metabolism , Lipid Metabolism
5.
Acta Biomater ; 181: 117-132, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705224

ABSTRACT

Human stem cell-derived organoids enable both disease modeling and serve as a source of cells for transplantation. Human retinal organoids are particularly important as a source of human photoreceptors; however, the long differentiation period required and lack of vascularization in the organoid often results in a necrotic core and death of inner retinal cells before photoreceptors are fully mature. Manipulating the in vitro environment of differentiating retinal organoids through the incorporation of extracellular matrix components could influence retinal development. We investigated the addition of hyaluronan (HA), a component of the interphotoreceptor matrix, as an additive to promote long-term organoid survival and enhance retinal maturation. HA treatment had a significant reduction in the proportion of proliferating (Ki67+) cells and increase in the proportion of photoreceptors (CRX+), suggesting that HA accelerated photoreceptor commitment in vitro. HA significantly upregulated genes specific to photoreceptor maturation and outer segment development. Interestingly, prolonged HA-treatment significantly decreased the length of the brush border layer compared to those in control retinal organoids, where the photoreceptor outer segments reside; however, HA-treated organoids also had more mature outer segments with organized discs structures, as revealed by transmission electron microscopy. The brush border layer length was inversely proportional to the molar mass and viscosity of the hyaluronan added. This is the first study to investigate the role of exogenous HA, viscosity, and polymer molar mass on photoreceptor maturation, emphasizing the importance of material properties on organoid culture. STATEMENT OF SIGNIFICANCE: Retinal organoids are a powerful tool to study retinal development in vitro, though like many other organoid systems, can be highly variable. In this work, Shoichet and colleagues investigated the use of hyaluronan (HA), a native component of the interphotoreceptor matrix, to improve photoreceptor maturation in developing human retinal organoids. HA promoted human photoreceptor differentiation leading to mature outer segments with disc formation and more uniform and healthy retinal organoids. These findings highlight the importance of adding components native to the developing retina to generate more physiologically relevant photoreceptors for cell therapy and in vitro models to drive drug discovery and uncover novel disease mechanisms.


Subject(s)
Cell Differentiation , Hyaluronic Acid , Organoids , Retina , Hyaluronic Acid/pharmacology , Hyaluronic Acid/chemistry , Humans , Organoids/drug effects , Organoids/cytology , Organoids/metabolism , Cell Differentiation/drug effects , Retina/drug effects , Retina/cytology , Retina/growth & development , Photoreceptor Cells, Vertebrate/drug effects , Photoreceptor Cells, Vertebrate/cytology , Photoreceptor Cells, Vertebrate/metabolism
6.
Soft Matter ; 20(16): 3436-3447, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38564251

ABSTRACT

Flexible actuation materials play a crucial role in biomimetic robots. Seeking methods to enhance actuation and functionality is one of the directions in which actuators strive to meet the high-performance and diverse requirements of environmental conditions. Herein, by utilizing the method of adsorbing N-doped carbon dots (NCDs) onto SiO2 to form clusters of functional particles, a NCDs@SiO2/PDMS elastomer was prepared and its combined optical and electrical co-stimulation properties were effectively harnessed to develop a biomimetic crawling robot resembling Rhagophthalmus (firefly). The introduction of NCDs@SiO2 cluster particles not only effectively improves the mechanical and dielectric properties of the elastomer but also exhibits fluorescence response and actuation response under the co-stimulation of UV and electricity, respectively. Additionally, a hybrid dielectric elastomer actuator (DEA) with a transparent SWCNT mesh electrode exhibits two notable advancements: an 826% increase in out-of-plane displacement under low electric field stimulation compared to the pure matrix and the ability of NCDs to maintain a stable excited state within the polymer for an extended duration under UV-excitation. Simultaneously, the transparent biomimetic crawling robot can stealthily move in specific environments and fluoresce under UV light.

7.
Behav Sci (Basel) ; 14(3)2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38540505

ABSTRACT

The objective of this study was to examine the intervention effect of group sensory integration training on social responsiveness, and the latency and amplitude of N170 event-related potential of children with autism. The social responsiveness scale was employed to assess alterations in the social response of individuals with ASD before and after training, while event-related potentials were utilized to measure changes in N170 latency and amplitude. This study revealed that group sensory integration training can significantly enhance social responsiveness in children diagnosed with ASD. Children with ASD exhibit atypical N170 responses to faces in the right parietal region. The latency of N170 changes may serve as a valuable indicator for assessing the effectiveness of an intervention or diagnosing ASD.

8.
Mol Nutr Food Res ; 68(6): e2300443, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38456781

ABSTRACT

SCOPE: Gut microbiota can convert a variety of alkaloids and TMAO into TMA, which is then transported by the blood to the liver, and converted into TMAO. In recent years, TMAO has attracted wide attention as a metabolic risk factor in cardiovascular disease, diabetes, and other diseases. However, it is still unclear about the role of gut microbial metabolite TMA in the adverse health impacts of TMAO. METHODS AND RESULTS: Male C57BL/6J is treated with intraperitoneal (i.p.) or oral TMAO for 8 weeks, the area under the OGTT curve of oral group is significantly increased by about 15% compared to the control and injection groups. Serum triglyceride levels in the oral group are significantly higher by 28.2% and 24.6% than those in the control and injection groups, respectively. Meanwhile, cholesterol content in serum is significantly elevated by 27.6% and 30.7%. Similarly, proinflammatory factors gene expressions are significantly increased with oral but not i.p. TMAO intervention. Furthermore, transformation in HepG2 cells shows that TMAO could not be converted into TMA by hepatocytes. CONCLUSION: The adverse effects of TMAO on glucose and lipid metabolism in C57BL/6J mice may act through gut microbiota metabolite TMA.


Subject(s)
Gastrointestinal Microbiome , Mice , Animals , Male , Mice, Inbred C57BL , Lipid Metabolism , Glucose/pharmacology , Methylamines , Choline/pharmacology
9.
Stem Cell Res Ther ; 15(1): 79, 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38486269

ABSTRACT

BACKGROUND: The discovery of material transfer between transplanted and host mouse photoreceptors has expanded the possibilities for utilizing transplanted photoreceptors as potential vehicles for delivering therapeutic cargo. However, previous research has not directly explored the capacity for human photoreceptors to engage in material transfer, as human photoreceptor transplantation has primarily been investigated in rodent models of late-stage retinal disease, which lack host photoreceptors. METHODS: In this study, we transplanted human stem-cell derived photoreceptors purified from human retinal organoids at different ontological ages (weeks 10, 14, or 20) into mouse models with intact photoreceptors and assessed transfer of human proteins and organelles to mouse photoreceptors. RESULTS: Unexpectedly, regardless of donor age or mouse recipient background, human photoreceptors did not transfer material in the mouse retina, though a rare subset of donor cells (< 5%) integrated into the mouse photoreceptor cell layer. To investigate the possibility that a species barrier impeded transfer, we used a flow cytometric assay to examine material transfer in vitro. Interestingly, dissociated human photoreceptors transferred fluorescent protein with each other in vitro, yet no transfer was detected in co-cultures of human and mouse photoreceptors, suggesting that material transfer is species specific. CONCLUSIONS: While xenograft models are not a tractable system to study material transfer of human photoreceptors, these findings demonstrate that human retinal organoid-derived photoreceptors are competent donors for material transfer and thus may be useful to treat retinal degenerative disease.


Subject(s)
Retina , Retinal Degeneration , Humans , Animals , Mice , Tissue Donors , Photoreceptor Cells, Vertebrate , Retinal Degeneration/therapy , Biological Assay , Disease Models, Animal
10.
Anal Chem ; 96(10): 4205-4212, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38433457

ABSTRACT

Accurate identification of single-nucleotide mutations in circulating tumor DNA (ctDNA) is critical for cancer surveillance and cell biology research. However, achieving precise and sensitive detection of ctDNAs in complex physiological environments remains challenging due to their low expression and interference from numerous homologous species. This study introduces single-nucleotide-specific lipidic nanoflares designed for the precise and visible detection of ctDNA via toehold-initiated self-priming DNA polymerization (TPP). This system can be assembled from only a single cholesterol-conjugated multifunctional molecular beacon (MMB) via hydrophobicity-mediated aggregation. This results in a compact, high-density, and nick-hidden arrangement of MMBs on the surface of lipidic micelles, thereby enhancing their biostability and localized concentrations. The assay commences with the binding of frequently mutated regions of ctDNA to the MMB toehold domain. This domain is the proximal holding point for initiating the TPP-based strand-displacement reaction, which is the key step in enabling the discrimination of single-base mutations. We successfully detected a single-base mutation in ctDNA (KRAS G12D) in its wild-type gene (KRAS WT), which is one of the most frequently mutated ctDNAs. Notably, coexisting homologous species did not interfere with signal transduction, and small differences in these variations can be visualized by fluorescence imaging. The limit of detection was as low as 10 amol, with the system functioning well in physiological media. In particular, this system allowed us to resolve genetic mutations in the KRAS gene in colorectal cancer, suggesting its high potential in clinical diagnosis and personalized medicine.


Subject(s)
Circulating Tumor DNA , Proto-Oncogene Proteins p21(ras) , Proto-Oncogene Proteins p21(ras)/genetics , Nucleotides , Polymerization , Mutation , Circulating Tumor DNA/genetics
11.
Mar Drugs ; 22(2)2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38393047

ABSTRACT

Patients with ulcerative colitis (UC) have higher rates of depression. However, the mechanism of depression development remains unclear. The improvements of EPA and DHA on dextran sulfate sodium (DSS)-induced UC have been verified. Therefore, the present study mainly focused on the effects of EPA and DHA on UC-induced depression in C57BL/6 mice and the possible mechanisms involved. A forced swimming test and tail suspension experiment showed that EPA and DHA significantly improved DSS-induced depressive-like behavior. Further analysis demonstrated that EPA and DHA could significantly suppress the inflammation response of the gut and brain by regulating the NLRP3/ASC signal pathway. Moreover, intestine and brain barriers were maintained by enhancing ZO-1 and occludin expression. In addition, EPA and DHA also increased the serotonin (5-HT) concentration and synaptic proteins. Interestingly, EPA and DHA treatments increased the proportion of dominant bacteria, alpha diversity, and beta diversity. In conclusion, oral administration of EPA and DHA alleviated UC-induced depressive-like behavior in mice by modulating the inflammation, maintaining the mucosal and brain barriers, suppressing neuronal damage and reverting microbiota changes.


Subject(s)
Colitis, Ulcerative , Humans , Mice , Animals , Dextran Sulfate/toxicity , Mice, Inbred C57BL , Colitis, Ulcerative/metabolism , Signal Transduction , Inflammation/metabolism , Disease Models, Animal , Colon/metabolism
12.
Adv Mater ; 36(19): e2310637, 2024 May.
Article in English | MEDLINE | ID: mdl-38349174

ABSTRACT

Engineered biomaterial scaffolds are becoming more prominent in research laboratories to study drug efficacy for oncological applications in vitro, but do they have a place in pharmaceutical drug screening pipelines? The low efficacy of cancer drugs in phase II/III clinical trials suggests that there are critical mechanisms not properly accounted for in the pre-clinical evaluation of drug candidates. Immune cells associated with the tumor may account for some of these failures given recent successes with cancer immunotherapies; however, there are few representative platforms to study immune cells in the context of cancer as traditional 2D culture is typically monocultures and humanized animal models have a weakened immune composition. Biomaterials that replicate tumor microenvironmental cues may provide a more relevant model with greater in vitro complexity. In this review, the authors explore the pertinent microenvironmental cues that drive tumor progression in the context of the immune system, discuss how these cues can be incorporated into hydrogel design to culture immune cells, and describe progress toward precision oncological drug screening with engineered tissues.


Subject(s)
Biocompatible Materials , Neoplasms , Tissue Engineering , Tumor Microenvironment , Humans , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Animals , Neoplasms/immunology , Neoplasms/drug therapy , Neoplasms/therapy , Tumor Microenvironment/drug effects , Tissue Engineering/methods , Hydrogels/chemistry , Tissue Scaffolds/chemistry
13.
ACS Appl Mater Interfaces ; 16(1): 281-291, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38156775

ABSTRACT

Intelligent DNA nanomachines are powerful and versatile molecular tools for bioimaging and biodiagnostic applications; however, they are generally constrained by complicated synthetic processes and poor reaction efficiencies. In this study, we developed a simple and efficient molecular machine by coupling a self-powered rolling motor with a lipidic nanoflare (termed RMNF), enabling high-contrast, robust, and rapid probing of cancer-associated microRNA (miRNA) in serum and living cells. The lipidic nanoflare is a cholesterol-based lipidic micelle decorated with hairpin-shaped tracks that can be facilely synthesized by stirring in buffered solution, whereas the 3D rolling motor (3D RM) is a rigidified tetrahedral DNA scaffold equipped with four single-stranded "legs" each silenced by a locking strand. Once exposed to the target miRNA, the 3D RM can be activated, followed by self-powered precession based on catalyzed hairpin assembly (CHA) and lighting up of the lipidic nanoflare. Notably, the multivalent 3D RM that moves using four DNA legs, which allows the motor to continuously and acceleratedly interreact with DNA tracks rather than dissociate from the surface of the nanoflare, yielded a limit of detection (LOD) of 500 fM at 37 °C within 1.5 h. Through the nick-hidden and rigidified structure design, RMNF exhibits high biostability and a low false-positive signal under complex physiological settings. The final application of RMNF for miRNA detection in clinical samples and living cells demonstrates its considerable potential for biomedical imaging and clinical diagnosis.


Subject(s)
Biosensing Techniques , MicroRNAs , Humans , MicroRNAs/genetics , DNA/chemistry , MCF-7 Cells , Limit of Detection , Biosensing Techniques/methods
14.
Food Chem ; 433: 137200, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37678117

ABSTRACT

In this study, we develop a competitive ratiometric fluorescent lateral flow immunoassay (CRF-LFIA) based on dual emission fluorescence signal, which has great advantage in visual and quantitative detection of Chlorothalonil (CTN). Red-emitted fluorescent magnetic nanobeads (FMNBs) and green-emitted aggregation-induced emission fluorescent microsphere (AIEFM) are synthesized and conjugated to antibodies and antigens respectively, resulting in competitive binding with the analyte. The ratiometric fluorescence signal which comes from the overlap of these two fluorescence emissions. FMNBs probes also provide immunomagnetic separation (IMS) to enrich the analysts and resist complex matrix effects. This strip generates a visually discernible yellow-to-green fluorescence color change in the presence of CTN (2 ng/mL), which could be incisively observed by naked eye. Moreover, the limit of detection (LOD) reached 0.152 ng/mL by measurement of color (Red-Green-Blue, RGB) signals. Method validation shows a good correlation between CRF-LFIA and LC-MS/MS.


Subject(s)
Fluorescent Dyes , Nitriles , Tandem Mass Spectrometry , Chromatography, Liquid , Immunoassay/methods , Limit of Detection
15.
Nanoscale ; 15(47): 19292-19303, 2023 Dec 07.
Article in English | MEDLINE | ID: mdl-37997180

ABSTRACT

Potassium ion batteries (PIBs) have attracted great research interest in new-generation large-scale energy storage considering their abundant source, low cost, and suitable working potential. Herein, a hierarchical TiO2/Ti3C2 hybrid is developed via a green, facile water steam etching method for realizing an efficient and durable anode material for PIBs. In this hierarchical assembly, the TiO2 nanoparticles anchored on the Ti3C2 surface contribute a high pseudocapacitance while mitigating the restacking of the Ti3C2 MXene skeleton, which ensures mechanical robustness to accommodate large K+ ions. Benefiting from the amalgamation of structural properties and the synergistic effects stemming from the individual constituents, the optimized TiO2/Ti3C2 anode harvests remarkable performance in the potassium ion storage, including a high reversible capacity of ∼255 mA h g-1 at 0.2 A g-1 after 1300 cycles as well as an outstanding long-term cycling performance and rate capability (a high capacity of ∼230 mA h g-1 even after intensive 10 000 cycles at 2 A g-1). The excellent TiO2/Ti3C2 anode enables the assembled pouch-cell coupling PTCDA cathode to deliver a capacity of ∼173 mA h g-1 at 0.05 A g-1 and retain 120 mA h g-1 after 30 cycles. The employment of the pouch-cell in successfully powering the LED module showcases its application prospect for advanced PIBs.

16.
Mitochondrial DNA B Resour ; 8(9): 981-984, 2023.
Article in English | MEDLINE | ID: mdl-37727834

ABSTRACT

Adonis pseudoamurensis W.T. Wang 1980 is an important traditional medicinal plant used for the treatment of cardiac diseases. The complete chloroplast (cp) genome of Adonis pseudoamurensis is reported for the first time in this study. The circular cp genome is 156,917 bp in length, consisting of a large single-copy region (86,262 bp), a small single-copy region (18,067 bp), and two inverted repeat regions (26,294 bp). The genome encodes 129 genes, comprising 84 protein-coding genes, 37 transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. Phylogenetic analysis showed that A. pseudoamurensis is closely related to A. amurensis.

17.
J Reprod Immunol ; 160: 104154, 2023 12.
Article in English | MEDLINE | ID: mdl-37774536

ABSTRACT

Pelvic inflammatory disease (PID) is commonly encountered in gynecological practice. Kangfuxiaomi suppository, made from the compound extract of Periplaneta Americana, is a Traditional Chinese Medicine remedy widely used for the treatment of gynecological disorders. This study aimed to preliminarily explore the therapeutic effect of Kangfuxiaomi suppository in a rat model of PID established by chemical injury and pathogen infection. The key parameters assessed were vulvar inflammation score, vaginal + uterine organ index, and serum levels of interleukin (IL)- 8; tumor necrosis factor (TNF)-α; C-reactive protein (CRP); superoxide dismutase (SOD); and malondialdehyde (MDA). In addition, levels of IL-6, cyclooxygenase (COX)- 2, and IL-2 in cervical tissues as well as that of IL-1ß and prostaglandin E-2 (PGE2) in uterine tissues were measured. The expression levels of nuclear factor-kappa B (NF-κB) p65 and Toll-like receptor 4 (TLR4) in uterine tissues were detected by immunohistochemical method. After Kangfuxiaomi suppository treatment, the vulva inflammation score and histopathological score of PID rats showed a tendency to decrease. Serum IL-8, TNF-α, CRP, and MDA levels were reduced, while SOD levels were significantly increased. Levels of IL-6, IL-2, and COX-2 in cervical tissues were somewhat decreased, and PGE2 and IL-1ß levels in uterine tissue were significantly decreased. Moreover, the levels of NF-κB p65 and TLR4 protein expression were also decreased. These findings demonstrated the therapeutic effect of Kangfuxiaomi suppository in PID rats. The underlying mechanism may involve enhanced antioxidant capacity and decreased secretion of proinflammatory factors via the NF-κB/TLR4 signaling pathway.


Subject(s)
NF-kappa B , Pelvic Inflammatory Disease , Humans , Female , Rats , Animals , NF-kappa B/metabolism , Toll-Like Receptor 4/metabolism , Pelvic Inflammatory Disease/drug therapy , Interleukin-6 , Dinoprostone , Interleukin-2 , Tumor Necrosis Factor-alpha/metabolism , Inflammation/drug therapy , Inflammation/metabolism , Superoxide Dismutase/therapeutic use
18.
Cancer Cell ; 41(9): 1662-1679.e7, 2023 09 11.
Article in English | MEDLINE | ID: mdl-37625402

ABSTRACT

Stem-like CD8+ T cells are regulated by T cell factor 1 (TCF1) and are considered requisite for immune checkpoint blockade (ICB) response. However, recent findings indicate that reliance on TCF1+CD8+ T cells for ICB efficacy may differ across tumor contexts. We find that TCF1 is essential for optimal priming of tumor antigen-specific CD8+ T cells and ICB response in poorly immunogenic tumors that accumulate TOX+ dysfunctional T cells, but is dispensable for T cell priming and therapy response in highly immunogenic tumors that efficiently expand transitory effectors. Importantly, improving T cell priming by vaccination or by enhancing antigen presentation on tumors rescues the defective responses of TCF1-deficient CD8+ T cells upon ICB in poorly immunogenic tumors. Our study highlights TCF1's role during the early stages of anti-tumor CD8+ T cell responses with important implications for guiding optimal therapeutic interventions in cancers with low TCF1+CD8+ T cells and low-neo-antigen expression.


Subject(s)
CD8-Positive T-Lymphocytes , Neoplasms , T Cell Transcription Factor 1 , Humans , Antibodies , Antigens, Neoplasm , Immunotherapy , T Cell Transcription Factor 1/genetics , Neoplasms/immunology , Neoplasms/therapy
19.
Anal Chem ; 95(35): 13140-13148, 2023 09 05.
Article in English | MEDLINE | ID: mdl-37602702

ABSTRACT

DNA nanotechnology has shown great promise for biosensing and molecular recognition. However, the practical application of conventional DNA biosensors is constrained by inadequate target stimuli, intricate design schemes, multicomponent systems, and susceptibility to nuclease degradation. To overcome these limitations, we present a class of starlike branched and multiplex embedded system (SBES) with an integrated functional design and cascade exponential amplification for serum microRNA (miRNA) detection. The DNA arms can be integrated into an all-in-one system by surrounding a branch point, with each arm endowed with specific functionalities by embedding different DNA fragments. These fragments include a segment complementary to the target miRNA for the recognition element, palindromic tails for self-primed polymerization, and a region with the same sequences as the target serving as the target analogue. Upon exposure to a target miRNA, the DNA arms unwind in a stepwise manner through palindrome-mediated dimerization and polymerization. This enables target recycling for subsequent reactions while releasing the target analogue to generate a secondary response in a feedback manner. A comparative analysis illustrates that the signal-to-noise ratio (SNR) of a full SBES with a feedback strategy is approximately 250% higher than the system without a feedback design. We demonstrate that the four-arm 4pSBES has the benefits of multifunctional integration, enhanced sensitivity, and low false-positive signals, which makes this approach ideally suited for clinical diagnosis. Moreover, an upgraded SBES with additional DNA arms (e.g., 6pSBES) can be constructed to allow multifunctional extension, offering unprecedented opportunities to build versatile DNA nanostructures for biosensing.


Subject(s)
MicroRNAs , Nanostructures , Dimerization , Endonucleases , Nanotechnology
20.
J Agric Food Chem ; 71(29): 11252-11262, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37392452

ABSTRACT

Quantification of neomycin residues in food samples demands an efficient purification platform. Herein, hierarchical macroporous agarose monoliths with multiple boronate affinity sites were established for selective separation of neomycin. The silica core was synthesized by "one-step" Stöber procedures followed by modification with amino group and incorporation of polyethyleneimine. A versatile macroporous agarose monolith was prepared by emulsification strategies and functionalized with epoxy groups. After introducing polyethyleneimine-integrated silica nanoparticles onto the agarose monolith, fluorophenylboronic acids were immobilized. The physical and chemical characteristics of the composite monolith were analyzed systematically. After optimization, neomycin showed high binding ability of 23.69 mg/g, and the binding capacity can be manipulated by changing the pH and adding monosaccharides. The composite monolith was subsequently utilized to purify neomycin from the spiked model aquatic products followed by high-performance liquid chromatography analysis, which revealed a remarkable neomycin purification effect, indicating the great potential in the separation of neomycin from complicated aquatic products.


Subject(s)
Boronic Acids , Polyethyleneimine , Polyethyleneimine/chemistry , Sepharose , Boronic Acids/chemistry , Silicon Dioxide/chemistry , Binding Sites , Chromatography, Affinity/methods
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