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Lycium barbarum polysaccharides (LBPs) are recognized as key bioactive constituents of Lycium barbarum with diverse biological activities. However, current research on LBPs is largely confined to crude extracts, offering limited insight into the structural properties underlying their biological effects. In this study, we separated crude LBP into acidic LBP (ALBP) and neutral LBP (NLBP), which exhibited distinct physicochemical properties. ALBP, consisting of 76.18â¯% galacturonic acid (GalA), demonstrated crystallinity, thermal stability and gelatinous characteristics. In contrast, NLBP, with only 3.16â¯% GalA, displayed a more porous structure and superior fluidity. Furthermore, functional analysis revealed that NLBP exhibited enhanced immunoregulatory effects by activating dendritic cells and repolarizing macrophages. In a B16F10 melanoma-bearing C57BL/6â¯J mice model, NLBP significantly inhibited tumor growth with an inhibition rate of 66.7â¯% through macrophage repolarization. The findings highlight the distinct biological effects of NLBP and ALBP, providing a theoretical foundation for the refined utilization of LBP.
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Rising glbal population and plastic consumption have caused a dramatic increase in plastic waste, leading to micro- and nanoplastic ingestion by aquatic organisms and subsequent bioaccumulation in their tissues. This transfer to higher trophic levels raises nanoplastic concentrations and bioavailability, potentially harming organisms' health and development. This poses a risk to human health via seafood. To address these issues, this study assesses the toxicological impacts of nanoplastics (NPs) on brine shrimp (Artemia franciscana) and their trophic transfer to zebrafish. The research unveiled concentration-dependent bioaccumulation of NPs in zebrafish and Artemia franciscana (A. franciscana). Polystyrene nanoplastics (PS-NPs) exhibited higher accumulation in A. franciscana whereas PP-NPs showed greater accumulation in zebrafish gut. Histopathological analysis under PS-NPs exposure revealed significant tissue alterations, indicative of inflammatory responses and impaired mucosal barrier integrity. Gene expression analyses confirmed these findings, showing activation of the P38-MAPK pathway by PS-NPs, which correlated with increased inflammatory cytokines. Additionally, PE-NPs activated the JNK-MAPK pathway, while PP-NPs exposure triggered the NOD-like receptor signaling pathway. Moreover, the composition of gut microbiota shifted to a dysbiotic state, characterized by an increase in pathogenic bacteria in the PS-NPs and PP-NPs groups, elevating the risk of developing Inflammatory Bowel Disease (IBD). PS-NPs were regarded as the most toxic due to their lower stability and higher aggregation tendencies, followed by PP-NPs and PE-NPs. Taken together, the overall study highlighted the complex interactions between NPs, gut microbiota, and host health, emphasizing the importance of thoroughly assessing the ecological and physiological impacts of nanoplastic pollution.
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ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygii wilfordii Radix, (TW) as a toxic herbal medicine, is the root of Tripterygium wilfordii Hook. F. , which commonly used in China for the treatment of rheumatoid arthritis and autoimmune diseases, but its severe toxicity, particularly hepatotoxicity, significantly impacts its clinical application. AIM OF THE STUDY: The hepatotoxicity and its molecular mechanism of 70% TW ethanol extract (TWE) on male mice were demonstrated based on metabolomics, network pharmacological analysis and experimental validation. MATERIALS AND METHODS: The toxic and bioactive ingredients in TWE were quantitative analyzed by Triple quadrupole (TQ) mass spectrometry method. The liver organ index, as well as the liver function indexes AST and ALT were evaluated after administering different doses of TWE for 24 h, and a pathological change was analyzed in liver tissue. Non-targeted metabolomics using UPLC-QTOF/MS was performed on both the plasma and liver tissue samples in combination with network toxicology to screen for key targets related to TWE toxicity in the liver. These key targets including caspase 3, NF-κB, TLR4, TNF-α, NQO1, and Bcl2 were subsequently verified through Western blotting experiments. RESULTS: The six toxic and active ingredients of raphenolactone, ranolactone, triptolide tripterine, wilforlide A, demethylzeylasterain in TWE for the contents of 0.709, 1.408, 0.353, 0.354, 0.882, 0.227 mg g-1, respectively. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels increased and liver index decreased after administration of TWE for 24 h. Pathological analysis showed that TWE could produce toxicity to mouse liver, and its toxicity was dose-dependent. In the high-dose group, TW-D (11.23 g/kg) and TW-E (22.46 g/kg) caused a large amount of rupture in mouse liver nucleus and a large amount of inflammatory infiltration at the same time. Furthermore, 64 metabolites in plasma and 59 metabolites in the liver tissue were identified. The main metabolic pathways involved glycerol phospholipid metabolism, glycosylphosphatidylinositol-ether lipid metabolism, fatty acid metabolism, sphingomyelin metabolism, and ether lipid metabolism in plasma and liver tissue. Through analysis of the top 10 correlated targets, 6 out of the top 10 selected target proteins exhibited consistent expression patterns with liver injury. The levels of Bcl2 and NQO1 decreased with increasing exposure dose. The expression of Caspase 3, NF-κB, TLR4, and TNF-α increased with increasing dose. These findings suggest that protein expression has a regulatory effect at different doses groups compared to the control group.These findings suggest a regulatory effect of protein expression in different dose groups compared to the control group. CONCLUSION: The hepatotoxic effects of TWE can increase ALT and AST levels in plasma, leading to hepatic oxidative damage and inflammatory response. The toxic mechanisms that produce are closely related to the regulating of the abnormal metabolites in plasma and liver tissue. Furthermore, the regulating the expression levels of targeted proteins of TNF-α, NF-κB, Caspase 3, NQO1, and Bcl2 were confirmed by examining the liver tissue. These data clearly elucidate the toxicity mechanism of TW, laying the foundation for ensuring the quality and safety of drugs.
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The antibody response to vaccination and infection is a key component of the immune response to pathogens. Sequencing of peripheral B cells may not represent the complete B cell receptor repertoire. Here we present a method for sequencing human plasma-derived polyclonal IgG using a combination of mass spectrometry and B-cell sequencing. We investigate the IgG response to the Moderna Spikevax COVID-19 vaccine. From the sequencing data of the natural polyclonal response to vaccination, we generate 12 recombinant antibodies. Six derived recombinant antibodies, including four generated with de novo protein sequencing, exhibit similar or higher binding affinities than the original natural polyclonal antibody. Neutralization tests reveal that the six antibodies possess neutralizing capabilities against the target antigen. This research provides insights into sequencing polyclonal IgG antibodies and the potential of our approach in generating recombinant antibodies with robust binding affinity and neutralization capabilities. Directly examining the circulating IgG pool is crucial due to potential misrepresentations by B-cell analysis alone.
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Anticorpos Neutralizantes , Análise de Sequência de Proteína , Humanos , Feminino , Pessoa de Meia-Idade , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/imunologia , Linfócitos B/imunologia , Afinidade de Anticorpos , Espectrometria de Massas , Anticorpos Antivirais/sangue , Anticorpos Antivirais/química , Anticorpos Antivirais/imunologiaRESUMO
Oxidative stress is a crucial concept in redox biology, and significant progress has been made in recent years. Excessive levels of reactive oxygen species (ROS) can lead to oxidative damage, heightening vulnerability to various diseases. By contrast, ROS maintained within a moderate range plays a role in regulating normal physiological metabolism. Choosing suitable animal models in a complex research context is critical for enhancing research efficacy. While rodents are frequently utilized in medical experiments, they pose challenges such as high costs and ethical considerations. Alternatively, non-rodent model organisms like zebrafish, Drosophila, and C. elegans offer promising avenues into oxidative stress research. These organisms boast advantages such as their small size, high reproduction rate, availability for live imaging, and ease of gene manipulation. This review highlights advancements in the detection of oxidative stress using non-rodent models. The oxidative homeostasis regulatory pathway, Kelch-like ECH-associated protein 1-Nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2), is systematically reviewed alongside multiple regulation of Nrf2-centered pathways in different organisms. Ultimately, this review conducts a comprehensive comparative analysis of different model organisms and further explores the combination of novel techniques with non-rodents. This review aims to summarize state-of-the-art findings in oxidative stress research using non-rodents and to delineate future directions.
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Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Espécies Reativas de Oxigênio , Animais , Espécies Reativas de Oxigênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Transdução de Sinais , Oxirredução , Drosophila/metabolismo , Modelos Animais , Peixe-Zebra/metabolismoRESUMO
Traditional food testing methods, primarily confined to laboratory settings, are increasingly inadequate to detect covert food adulteration techniques. Hence, a crucial review of recent technological strides to combat food fraud is essential. This comprehensive analysis explores state-of-the-art technologies in food analysis, accentuating the pivotal role of sophisticated data processing methods and the amalgamation of diverse technologies in enhancing food authenticity testing. The paper assesses the merits and drawbacks of distinct data processing techniques and explores their potential synergies. The future of food authentication hinges on the integration of portable smart detection devices with mobile applications for real-time food analysis, including miniaturized spectrometers and portable sensors. This integration, coupled with advanced machine learning and deep learning for robust model construction, promises to achieve real-time, on-site food detection. Moreover, effective data processing, encompassing preprocessing, chemometrics, and regression analysis, remains indispensable for precise food authentication.
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The multivariate statistical analysis was performed to compare the therapeutic effects of Lycii Fructus from different origins on the retinal degenerative diseases(RDD) in mice. The mouse model of RDD was established by intraperitoneal injection of NaIO_3, and the visual function and retinal apoptosis were assessed by dark-light transition and TUNEL assay. Retinal thickness was measured by fundus optical coherence tomography(OCT), and the levels of antioxidant, inflammatory, and angiogenic markers in the serum and eyeball were determined. The therapeutic effects were compared by hierarchical cluster analysis, principal component analysis, and partial least squares-discriminant analysis. The results showed that the extracts of Lycii Fructus from different origins reversed NaIO_3-induced visual damage and retinal apoptosis, reduced oxidative stress, and restored the expression of inflammatory mediators and angiogenic markers in mice. The multivariate statistical analysis based on 17 pharmacodynamic indices suggested that the extract of Lycii Fructus from Ningxia demonstrated better therapeutic effects on RDD than the samples from the other four origins. The results of this study provide a scientific basis for the selection of the advantageous production region of Lycii Fructus for the prevention and treatment of RDD.
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Medicamentos de Ervas Chinesas , Lycium , Animais , Camundongos , Lycium/química , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Análise Multivariada , Masculino , Degeneração Retiniana/tratamento farmacológico , Frutas/química , Retina/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Humanos , Modelos Animais de Doenças , Apoptose/efeitos dos fármacosRESUMO
Glycopeptides of traditional Chinese medicine(GTCM), as a type of natural products with important biological activities, have received increasing attention in recent years. These substances have a variety of pharmacological effects, including anti-tumor, immunomodulatory, neuroprotective, and anti-inflammatory effects. The extraction and separation processes directly affect the yield and purity of GTCM, and structural characterization is essential for probing into the properties and pharmacological mechanisms of glycopeptides. This article reviews the research progress and prospects the research directions in the extraction, separation, structural identification, and pharmacological effects of GTCM. Despite the progress in the research on GTCM, challenges such as low extraction efficiency, long separation cycles, difficult structural characterization, and complex mechanisms still exist. To address these issues, efforts should be made to optimize the extraction methods, explore new separation technologies, and develop efficient structural characte-rization methods. Additionally, the future work should decipher the pharmacological mechanisms of GTCM, which will provide a scientific basis for the drug development and clinical applications of GTCM.
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Medicamentos de Ervas Chinesas , Glicopeptídeos , Medicina Tradicional Chinesa , Humanos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Glicopeptídeos/química , Glicopeptídeos/farmacologia , Glicopeptídeos/isolamento & purificação , AnimaisRESUMO
Medical device research and development are characterized by high costs, extended timelines, inherent risks, and the necessity for interdisciplinary knowledge and skills. It is significantly influenced by policies, making the understanding of medical device innovation both important and challenging. This paper takes a dual approach to analyze medical device innovation. We reviewed representative clinical product of bougie and stylet and summarized the common characteristics and trend of these product. Innovations in these products often involve adding depth markings, replacing material and design structure, enhancing visualization, deciding between reusable or disposable designs, and integrating multi-functional features. This underscores the delicate balance between technological advancements and medical costs for widespread clinical applicability. We explored the guiding role of policy in medical device innovation, emphasizing its impact through an analysis of medical device regulations and policies in China. By offering insights from the perspectives of medical device companies and regulators, this paper aims to elucidate the critical aspects of medical device innovation, assisting researchers in mitigating risks during product development.
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BACKGROUND: Totally robotic distal gastrectomy (TRDG) is being used more and more in gastric cancer (GC) patients. The study aims to evaluate the short-term efficacy of TRDG and robotic-assisted distal gastrectomy (RADG) in the treatment of GC. METHODS: We retrospectively collected the clinical data of patients who underwent TRDG or RADG, of which 60 patients were included in the study: 30 cases of totally robotic and 30 cases of robotic-assisted. The short-term efficacy of the two groups was compared. RESULTS: There was no significant difference in the clinicopathological data between the two groups. Compared to RADG, TRDG had less intraoperative blood loss(P = 0.019), less postoperative abdominal drainage(P = 0.031), shorter time of exhaust( P = 0.001) and liquid diet(P = 0.001), shorter length of incision(P<0.01), shorter postoperative hospital stays(P = 0.033), lower postoperative C-reactive protein(CRP)(P = 0.024) and lower postoperative Visual Analogue Scale(VAS) scores(P = 0.048). However, no significant statistical differences were found in terms of total operation time(P = 0.108), number of lymph nodes retrieved(P = 0.307), time for anastomosis(P = 0.450), proximal resection margin(P = 0.210), distal resection margin(P = 0.202), postoperative complication(P = 0.506), total hospital cost(P = 0.286) and postoperative white blood cell(WBC)(P = 0.113). CONCLUSIONS: In terms of security and technology, TRDG could serve as a better treatment method for GC.
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Gastrectomia , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Gastrectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/economia , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Seguimentos , Prognóstico , Idoso , Tempo de Internação/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Duração da Cirurgia , Resultado do Tratamento , AdultoRESUMO
As a continuation of our efforts to develop new agrochemicals with typical architecture and efficient bioactivity from plant natural products, natural neolignan honokiol was used as a lead compound to prepare novel analogs bearing the core 2-aminobenzoxazole scaffold. Their insecticidal potency against two representative agricultural pests, Plutella xylostella Linnaeus and Mythimna separata (Walker), were evaluated in vivo. The pesticide bioassay results revealed that compounds 7â³a, 9, 10d, and 10j exhibited prominent larvicidal activity against the larvae of P. xylostella (LC50 = 7.95, 11.85, 15.51, and 12.06 µg/mL, respectively), superior to the precursor honokiol (LC50 = 43.35 µg/mL) and two botanical insecticides, toosendanin (LC50 = 26.20 µg/mL) and rotenone (LC50 = 23.65 µg/mL). Compounds 7d, 10d, and 10j displayed a more pronounced nonchoice antifeedant effect (AFC50 = 9.48, 9.14, and 12.41 µg/mL, respectively) than honokiol (AFC50 = 54.81 µg/mL) on P. xylostella. Moreover, compounds 7b, 7â³a, 9, 10d, 10f, and 10j showed better growth inhibitory activity against M. separata (LC50 = 0.36, 0.34, 0.28, 0.16, 0.26, and 0.11 mg/mL, respectively) than honokiol, toosendanin, and rotenone (LC50 = 1.48, 0.53, and 0.46 mg/mL, respectively). A potted plant assay under greenhouse conditions illustrated that compounds 10d and 10j continued to provide good control efficacy against P. xylostella and an apparent protective effect on plants. Further cytotoxicity assay revealed that the aforementioned potent compounds showed relatively moderate toxicity and a good safety profile for non-target mammalian cells. Overall, the current work provides valuable insight into the agrochemical innovation of honokiol-derived analogs for use as natural-inspired pesticides in agricultural pest management.
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Compostos de Bifenilo , Inseticidas , Larva , Lignanas , Mariposas , Animais , Lignanas/farmacologia , Lignanas/química , Inseticidas/química , Inseticidas/farmacologia , Mariposas/efeitos dos fármacos , Mariposas/crescimento & desenvolvimento , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Compostos de Bifenilo/química , Relação Estrutura-Atividade , Benzoxazóis/química , Benzoxazóis/farmacologia , Estrutura Molecular , Compostos Alílicos , Aminas , Oxazóis , FenóisRESUMO
The high polysaccharide content of Lycii fructus agri-food waste should be reclaimed for value liberation from both environmental and economic perspectives. In this study, waste from L. fructus pigment products was valorized on a bench scale by upcycling into active polysaccharide-rich extracts. The methodological feasibility of polysaccharide recovery from L. fructus waste was evaluated using sequential extraction techniques. Three fractions LFP-30, LFP-100, and LFP-121, were obtained under stepwise increases in temperature and pressure. Highly heterogeneous xyloglucan (XG)-pectin macromolecules composed of linear homogalacturonan (HG) and alternating intra-RG-I-linkers, with topological neutral branches and XG participation, were predominant among the L. fructus polysaccharides (LFPs). Antioxidant activities in LFPs were unaffected by waste resources and severe extraction methodology conditions. Additionally, the direct investment potential of polysaccharide recovery was evaluated for full-scale implementation. This study demonstrated the necessity and feasibility of extracting bioactive polysaccharides with potential applications from L. fructus waste, and provided a sustainable strategy for transforming L. fructus waste disposal problems into value-added products using cost-effective methodologies.
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Antioxidantes , Lycium , Extratos Vegetais , Polissacarídeos , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Lycium/química , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Resíduos/análise , Fracionamento Químico/métodos , Xilanos/química , Xilanos/isolamento & purificação , Glucanos/química , Glucanos/isolamento & purificação , Glucanos/farmacologia , Frutas/química , Estudos de Viabilidade , Pectinas/química , Pectinas/isolamento & purificação , Fenômenos QuímicosRESUMO
This paper introduces a novel digital triangular-trapezoidal double-channel shaping algorithm to enhance the counting rate of resistive anode detectors. The algorithm is based on the trapezoidal shaping algorithm and improves it. At the extreme counting rate, the trapezoidal shaping algorithm cannot alleviate the pulse pileup, so the counting rate cannot meet the requirements of a high performance detector. The triangular-trapezoidal double-channel shaping algorithm is introduced in the resistance anode detector, which can replace the trapezoidal shaping filtering algorithm to process the output signal of the resistance anode detector and obtain the single photon position information. This improvement improves the counting rate of the resistor anode detector and reduces the resolution degradation caused by pulse pileup. The algorithm is simulated by System Generator software and implemented on FPGA (field programmable gate array). The triangular-trapezoidal double-channel shaping algorithm presented in this paper plays an important role in reducing electronic noise and pulse pileup. The algorithm is subjected to simulation testing, and it can recognize signals with a minimum pulse interval of 1 µs and counting rate up to 1000 kcps.
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To comprehensively reveal and utilize the plant resources of Lycium in China, this study determined and compared the content of monosaccharides, polysaccharides, proteins, carotenoids, organic acids, and phenols in the dried fruits of 8 different Lycium species. Furthermore, the traits including the hundred-fruit weight, shape index, and the ratio of seed to fruit were measured, and the correlations between the content of chemical compounds and fruit traits were assessed. The results showed that L. truncatum, L. barbarum var. auranticarpum, and L. dasystemum var. rubricaulium were the species with high content of monosaccharides. L. barbarum and L. barbarum var. auranticarpum were the species with high content of total polysaccharides, and L. barbarum was the species with high content of carotenoids. L. yunnanense and L. chinense var. potaninii had high content of soluble proteins. L. truncatum, L. dasystemum, and L. barbarum showed high content of organic acids and phenols. L. barbarum and L. barbarum var. auranticarpum demonstrated high fruit weight, while L. yunnanense and L. chinense had high ratios of seed to fruit. The multivariate statistical analysis indicated that polysaccharides, carotenoids, hundred-fruit weight, ratio of seed to fruit, scopolamine, fructose, 5-O-feruloylquinic acid, kaempferol-3-O-rutinoside, scopoletin, cryptochlorogenic acid, and caffeic acid were the main differential compounds in the fruits among different species of Lycium. Moreover, the results of correlation ananysis showed strong correlations between fruit traits and compound content. Specifically, the hundred-fruit weight had positive correlations with the content of total polysaccharides and scopola-mine. The ratio of seed to fruit was negatively correlated with the content of rutin, kaempferol-3-O-rutinoside, fructose, and glucose and positively correlated with the content of succinic acid, soluble proteins, and zeaxanthin. The results implied that chemical compounds presented different distribution patterns in the fruits of 8 Lycium species. This study provides a basis for the comprehensive development and utilization, targeted breeding, and value-added application of Lycium plants.
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Carotenoides , Frutas , Lycium , Lycium/química , Lycium/crescimento & desenvolvimento , Frutas/química , Frutas/crescimento & desenvolvimento , Carotenoides/análise , Fenóis/análise , Polissacarídeos/análise , Polissacarídeos/química , Monossacarídeos/análise , China , Proteínas de Plantas/análiseRESUMO
China cultivates characteristic resource plant Zingiber officinale for both medicine and food use, with a long history of cultivation, production, and application. With the continuous excavation of the health and skin care values of ginger products due to scientific and technological progress, the scale expansion and quality improvement of the ginger industry have been effectively promoted, forming an industrial cluster with rich germplasm resources and diverse product categories represented by the north and south regions of China, and China has been developed as the biggest producer and exporter of raw materials and processed products of ginger.The present situation of ginger germplasm resources, ginger production, market price, and quality control of ginger products was reviewed in this paper. According to data from the Food and Agriculture Organization of the United Nations(FAO), United Nations International Trade Database, Chinese Network for Ginger Trade, and China Industry Information Network, the market fluctuation and trend of ginger products in China and abroad were discussed, and the current development and utilization of Chinese and international ginger industries were analyzed. In addition, through the research group's field investigation of the main producing area of ginger in China, analysis and prediction were made, and measures to improve the quality and efficiency of ginger industry use were put forward,so as to offer experience for relevant departments to study and formulate the development plan and production layout of ginger industry,help practitioners in ginger industry to cope with challenges, and provide a reference for promoting the quality and efficiency of ginger industry and high-quality development.
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Zingiber officinale , Zingiber officinale/química , Zingiber officinale/crescimento & desenvolvimento , China , Controle de Qualidade , Medicamentos de Ervas Chinesas/normas , HumanosRESUMO
BACKGROUND: Primary malignant melanoma of the cervix (PMMC) is an extremely rare disease that originates from primary cervical malignant melanoma and frequently represents a challenge in disease diagnosis due to unclarified clinical and histological presentations, particularly those without melanin. CASE SUMMARY: Here, we report a case of amelanotic PMMC, with a history of breast cancer and thyroid carcinoma. The patient was finally diagnosed by immunohistochemical staining and staged as IB2 based on the International Federation of Gynecology and Obstetrics with reference to National Comprehensive Cancer Network guidelines and was treated with radical hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy. She then received combination therapy consisting of immunotherapy with tislelizumab and radiofrequency hyperthermia. She has remained free of disease for more than 1 year. CONCLUSION: The differential diagnosis process reenforced the notion that immunohistochemical staining is the most reliable approach for amelanotic PMMC diagnosis. Due to the lack of established therapeutic guidelines, empirical information from limited available studies does not provide the rationale for treatment-decision making. By integrating 'omics' technologies and patient-derived xenografts or mini-patient-derived xenograft models this will help to identify selective therapeutic window(s) and screen the appropriate therapeutics for targeted therapies, immune checkpoint blockade or combination therapy strategies effectively and precisely that will ultimately improve patient survival.
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Water buffalo horn (WBH), a traditional Chinese medicine, is known for its antipyretic, anti-inflammatory and antioxidant properties. This study aims to investigate the therapeutic potential of WBH keratin (WBHK) and its derived thiol-rich peptide fractions (SHPF) for oxidative stress and inflammation. WBHK and SHPF were prepared and tested using various models including LPS-induced fever in rabbits, H2O2-induced oxidative damage in bEnd.3 cells, TNF-α-induced inflammation in bEnd.3 cells and LPS-induced inflammation in RAW 264.7 cells. Expression of key markers, such as Nrf2, Hmox-1 and NF-κB, were analyzed using qRT-PCR, ELISA and Western blotting. Label-free quantitative proteomic analysis was used to identify key differential proteins associated with the efficacy of SHPF. Our results demonstrated that treatment with WBHK significantly reduced body temperature after 0.5 h of administration in the fever rabbit model. SHPF could alleviate cellular inflammatory injury and oxidative damage by activating the key transcription factor Nrf2 and increasing the expression level of Hmox-1. SHPF could inhibit the NF-κB pathway by reducing IκB phosphorylation. It was also found that SHPF could reduce pro-inflammatory cytokine (IL-6, COX-2 and PGE2) and inhibit the expression of VCAM-1, ICAM-1, IL-6 and MCP-1. Proteomics analysis showed that SHPF could inhibit HMGB1 expression and release. The results indicated that SHPF could significantly reduce inflammation and oxidative stress by regulating the Nrf2/Hmox-1 and NF-κB pathways. These findings suggest the potential therapeutic applications of WBH components in the treatment of oxidative stress and inflammation-related diseases.
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Heme Oxigenase-1 , Inflamação , Queratinas , Fator 2 Relacionado a NF-E2 , NF-kappa B , Estresse Oxidativo , Peptídeos , Transdução de Sinais , Animais , Estresse Oxidativo/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Coelhos , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Camundongos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Inflamação/induzido quimicamente , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/genética , Queratinas/metabolismo , Peptídeos/farmacologia , Búfalos , Células RAW 264.7 , Compostos de Sulfidrila/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Antioxidantes/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Cornos/química , Lipopolissacarídeos , Febre/tratamento farmacológico , Febre/induzido quimicamente , Febre/metabolismo , Peróxido de Hidrogênio/metabolismo , Masculino , Medicina Tradicional ChinesaRESUMO
BACKGROUND: Saiga antelope horn (SAH) is a traditional Chinese medicine for treating febrile seizure (FS) with precise efficacy, but its mechanism of action and functional substances are still unclear. Given the need for further research on SAH, our group conducted studies to elucidate its mechanisms and active substances. METHODS: An FS rat pup model was constructed through intraperitoneal injection of LPS and hyperthermia induction. Behavioural indicators of seizures, hippocampal histopathological alterations, serum levels of inflammatory cytokines and hippocampal levels of neurotransmitters were observed and measured to investigate the effects of SAH on FS model rats. Hippocampal metabolomics and network pharmacology analyses were conducted to reveal the differential metabolites, key peptides and pathways involved in the suppression of FS by SAH. RESULTS: SAH suppressed FS, decreased the inflammatory response and regulated the Glu-GABA balance. Metabolomic analysis revealed 13 biomarkers of FS, of which SAH improved the levels of 8 differential metabolites. Combined with network pharmacology, a "biomarker-core target-key peptide" network was constructed. The peptides of SAH, such as YGQL and LTGGF, could exert therapeutic effects via the arachidonic acid pathway. Molecular docking and ELISA results indicated that functional peptides of SAH could bind to PTGS2 target, inhibiting the generation of AA and its metabolites in hippocampal samples. CONCLUSION: In summary, the functional peptides contained in SAH are the main material basis for the treatment of FS, potentially acting through neurotransmitter regulation and the arachidonic acid pathway.
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Myocardial ischemia (MI) is a significant contributor to ischemic heart diseases like angina pectoris and myocardial infarction. Reactive oxygen species produced during MI can trigger lipid peroxidation, damaging cell structure and function. Salvia miltiorrhiza (SM) has been widely used clinically in the treatment of cardiovascular diseases. However, in the process of rooting, the aboveground parts of this plant are usually discarded by tons. To make better use of these plant resources, the phenolic acids extracted and purified from the aerial part of SM were studied and chemically transformed, and the potential protective effect and possible mechanism of salvianolic acids containing a higher content of salvianolic acid A on MI were obtained. The transformed products of SM stem-leaves total phenolic acids with 8.16â¯% salvianolic acid A showed a better protective effect on the isoproterenol (ISO)-induced acute MI injury rat model. It can improve ST segment changes and has good antioxidant, anti-inflammatory and anticoagulant effects. In addition, the dysbiosis of gut microbiota and the related metabolic levels of short chain fatty acids (SCFAs), phenylalanine and glycerophospholipids were improved. This was achieved by reducing the abundance of Bacteroides, Faecalibaculum, and L-phenylalanine levels. In addition, the abundance of probiotics in Butyricoccus, Roseburia, and norank_f_Eubacterium_coprostanoligenes_group, as well as the contents of propionic acid and isobutyric acid, LPCs and PCs were increased. In conclusion, total phenolic acids of SM stem-leaves showed protective effects against ISO-induced rats, especially the strongest effect after conversion, which is a new option for the prevention and treatment of MI.
Assuntos
Microbioma Gastrointestinal , Hidroxibenzoatos , Isquemia Miocárdica , Caules de Planta , Ratos Sprague-Dawley , Salvia miltiorrhiza , Salvia miltiorrhiza/química , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Hidroxibenzoatos/isolamento & purificação , Masculino , Caules de Planta/química , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/tratamento farmacológico , Ratos , Folhas de Planta , Metaboloma/efeitos dos fármacos , Antioxidantes/farmacologia , DisbioseRESUMO
Polarization imaging has achieved a wide range of applications in military and civilian fields such as camouflage detection and autonomous driving. However, when the imaging environment involves a low-light condition, the number of photons is low and the photon transmittance of the conventional Division-of-Focal-Plane (DoFP) structure is small. Therefore, the traditional demosaicing methods are often used to deal with the serious noise and distortion generated by polarization demosaicing in low-light environment. Based on the aforementioned issues, this paper proposes a model called Low-Light Sparse Polarization Demosaicing Network (LLSPD-Net) for simulating a sparse polarization sensor acquisition of polarization images in low-light environments. The model consists of two parts: an intensity image enhancement network and a Stokes vector complementation network. In this work, the intensity image enhancement network is used to enhance low-light images and obtain high-quality RGB images, while the Stokes vector is used to complement the network. We discard the traditional idea of polarization intensity image interpolation and instead design a polarization demosaicing method with Stokes vector complementation. By using the enhanced intensity image as a guide, the completion of the Stokes vector is achieved. In addition, to train our network, we collected a dataset of paired color polarization images that includes both low-light and regular-light conditions. A comparison with state-of-the-art methods on both self-constructed and publicly available datasets reveals that our model outperforms traditional low-light image enhancement demosaicing methods in both qualitative and quantitative experiments.