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BACKGROUND: Mushroom poisoning is a significant food safety issue in Guizhou Province, China. Studies on this topic are essential for its prevention and control. We aimed to analyze the epidemiological characteristics of mushroom poisoning and study the correlation between its cases and meteorological factors in Guizhou Province. METHODS: We collected data on mushroom poisoning and meteorological factors in Guizhou Province in 2023. A descriptive analysis was conducted on the epidemiological features of mushroom poisoning and meteorological factors. We used Spearman correlation analysis and the generalized additive model to examine the relationship between meteorological factors and the number of mushroom poisoning cases. RESULTS: In 2023, mushroom poisoning cases in Guizhou Province were concentrated among individuals aged 20-59. Clinical symptoms were primarily gastrointestinal symptoms and occurrences peaked from June to October, mainly in the northeastern region of the province. Most incidents occurred in households. In 72 mushroom poisoning incidents where species were identified, 33 poisonous mushrooms were found. The number of mushroom poisoning cases in Guizhou Province was positively correlated with each meteorological factor(P < 0.05). The generalized additive model showed a significant nonlinear relationship between DGT, PRE, RHU, SSD, and the number of mushroom poisoning cases (P < 0.05). Interaction analysis showed that the risk of mushroom poisoning in Guizhou Province increased with the rising values of any two of these four meteorological factors. CONCLUSION: Mushroom poisoning incidents in Guizhou Province are characterized by high-risk groups, seasonality, and specific high-incidence regions and places. Public awareness for high-risk groups and early warnings for high-incidence regions and places should be strengthened every summer and fall. There is a correlation between meteorological factors and the number of mushroom poisoning cases, suggesting that these factors could serve as early warning indicators for the prevention and control of mushroom poisoning.
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Intoxicación por Setas , Humanos , China/epidemiología , Intoxicación por Setas/epidemiología , Adulto , Persona de Mediana Edad , Masculino , Femenino , Adulto Joven , Adolescente , Preescolar , Conceptos Meteorológicos , Niño , Lactante , Anciano , Incidencia , Modelos EstadísticosRESUMEN
BACKGROUND: Mushroom poisoning is a major public health issue in China. The integration of medical resources from different institutes of different levels is crucial in reducing the harm of mushroom poisoning. However, few studies have provided comprehensive implementation procedures and postimplementation effectiveness evaluations. To reduce the harm caused by mushroom poisoning, a network system for the prevention and treatment of mushroom poisoning (NSPTMP) was established in Chuxiong, Yunnan Province, a high-risk area for mushroom poisoning. METHODS: The NSPTMP consists of three types of institutions, namely, centers for disease prevention, hospitals, and health administration departments, with each kind of institution comprising prefecture, county/city, town, and village levels. After three years of implementation, the network was evaluated by comparing the indices before and after network implementation using data from the "Foodborne Disease Outbreak Surveillance System" and 17 hospitals in Chuxiong. The indices included the fatalities caused by mushroom poisoning, the composition ratios of different types of mushrooms for both outpatients and inpatients and the hospitalization rates. RESULTS: Compared to the average fatality rate of mushroom poisoning from 2015 to 2017, the average fatality rate from 2018 to 2020 significantly decreased from 0.57 to 0.06% (P < 0.001). Regarding the poisonous genus containing lethal mushrooms, the outpatient and inpatient composition ratios significantly decreased for Amanita (9.36-2.91% and 57.23-17.68%, respectively) and Russula (15.27-8.41%) (P < 0.05). Regarding poisonous mushrooms that caused mild symptoms, the outpatient and inpatient composition ratios significantly increased for Scleroderma (5.13-13.90% and 2.89-18.90%, respectively) and Boletaceae (19.08-31.71%) (P < 0.05), and the hospitalization rates significantly increased for Scleroderma (6.33-18.02%) and Boletaceae (5.65-12.71%) (P < 0.05). CONCLUSIONS: These findings suggest that the NSPTMP effectively reduced the harm caused by mushroom poisoning. In addition to the integration of medical resources, the development of poisonous mushroom identification, hierarchical treatment systems in hospitals, public education, and professional training also played important roles in improving the system's effectiveness. The establishment and evaluation of the NSPTMP in Chuxiong Prefecture can provide valuable insights and serve as a model for other regions facing similar challenges in managing mushroom poisoning.
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Intoxicación por Setas , Humanos , Intoxicación por Setas/epidemiología , Intoxicación por Setas/prevención & control , China/epidemiología , Amanita , Brotes de Enfermedades , Instituciones de SaludRESUMEN
Approximately 70-90% of mushroom poisoning deaths are caused by α-amanitin-induced liver injury resulting from RNA polymerase II (RNAP II) inhibition. Liver regeneration ability may contribute greatly to individual survival after α-amanitin poisoning. However, it is unclear what cellular pathways are activated to stimulate regeneration. We conducted dose-effect and time-effect studies in mice that were intraperitoneally injected with 0.33-0.66 mg/kg α-amanitin to establish a poisoning model. The liver/body weight ratio, serological indices, and pathology were evaluated to characterize the liver injury. In the time-effect study, the liver transcriptome was analyzed to explore the mRNA changes resulting from RNAP II inhibition and the underlying pathways associated with recovery. Based on the two animal studies, we established a poisoning model with three sequential liver states: early injury, regulation, and recovery. The mRNA changes reflected by the differentially expressed genes (DEGs) in the transcriptome could be used to illustrate the inhibition of RNAP II by α-amanitin. DEGs at four key time points were well matched with the three liver states, including 8-h downregulated genes in the early injury state, 16-h and 72-h upregulated genes in the regulation state, and 96-h upregulated/downregulated genes in the recovery state. By clustering analysis, the mTOR signaling pathway was screened out as the most promising potential pathway promoting recovery. The results of our investigations of the pathways and events downstream of the mTOR pathway indicated that the activation of mTOR probably contributes crucially to liver regeneration, which could be a promising basis for drug development.
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Agaricales , Alfa-Amanitina , Hígado , Intoxicación por Setas , Transcriptoma , Alfa-Amanitina/envenenamiento , Animales , Perfilación de la Expresión Génica , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Intoxicación por Setas/metabolismo , ARN Polimerasa II/genética , ARN Polimerasa II/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND: Botulinum toxin-A (BTX-A) injection of regional platysma has been utilized in the lower-part elevation and mandibular contour sculpture. However, the relative research, especially in quantitative assessment appears very spare. Our aim is to investigate the efficacy of three-dimensional (3D) technology as a method for regional platysma injection with BTX-A. MATERIALS AND METHODS: From October 2019 to September 2020, patients with mild or moderate degrees of facial sagging on the lower face were recruited to regional platysma BTX-A injection, and 3D scanning and measurement technology was used to evaluate the difference of curved distances and angels. Patients' improvement was assessed by the global aesthetic improvement scale (GAIS). RESULTS: A total of 57 patients underwent regional platysma BTX-A injection and 32 patients were followed up successfully. Compared with Pre-operative, postoperative facial reference curves distance and cervico-mental angles had statistical differences (p < 0.05). GAIS suggested that the 3D imaging measurement technology could improve satisfaction. CONCLUSION: 3D technology can evaluate the improvement of the lower face with BTX-A. It provides effective measurement methods and raises satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Toxinas Botulínicas Tipo A , Sistema Músculo-Aponeurótico Superficial , Humanos , Estudios de Seguimiento , Resultado del Tratamiento , TecnologíaRESUMEN
OBJECTIVE: Computer-aided diagnosis using deep learning algorithms has been initially applied in the field of mammography, but there is no large-scale clinical application. METHODS: This study proposed to develop and verify an artificial intelligence model based on mammography. Firstly, mammograms retrospectively collected from six centers were randomized to a training dataset and a validation dataset for establishing the model. Secondly, the model was tested by comparing 12 radiologists' performance with and without it. Finally, prospectively enrolled women with mammograms from six centers were diagnosed by radiologists with the model. The detection and diagnostic capabilities were evaluated using the free-response receiver operating characteristic (FROC) curve and ROC curve. RESULTS: The sensitivity of model for detecting lesions after matching was 0.908 for false positive rate of 0.25 in unilateral images. The area under ROC curve (AUC) to distinguish the benign lesions from malignant lesions was 0.855 [95% confidence interval (95% CI): 0.830, 0.880]. The performance of 12 radiologists with the model was higher than that of radiologists alone (AUC: 0.852 vs. 0.805, P=0.005). The mean reading time of with the model was shorter than that of reading alone (80.18 s vs. 62.28 s, P=0.032). In prospective application, the sensitivity of detection reached 0.887 at false positive rate of 0.25; the AUC of radiologists with the model was 0.983 (95% CI: 0.978, 0.988), with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 94.36%, 98.07%, 87.76%, and 99.09%, respectively. CONCLUSIONS: The artificial intelligence model exhibits high accuracy for detecting and diagnosing breast lesions, improves diagnostic accuracy and saves time.
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Ba-Wei-Long-Zuan granule (BWLZ) is a traditional herbal preparation. It has been widely used for the treatment of rheumatoid arthritis (RA). However, its active ingredients and mechanisms of action are still unclear. The present study aims to reveal the active compounds and anti-arthritic mechanisms of BWLZ against collagen-induced arthritis (CIA) by using 1 H-NMR-based metabolomics, molecular docking and network pharmacology methods. After 30â days of administration, BWLZ could effectively improve the metabolic disorders in CIA rats. The anti-arthritic effect of BWLZ was related to its restoration of 16 disturbed serum metabolites. Molecular docking and network analysis showed that 20 compounds present in BWLZ could act on multiple targets. Among them, coclaurine and hesperidin showed the highest hit rates for target proteins related to both metabolic regulation and RA, indicating that these two compounds might be potential active ingredients of BWLZ. Moreover, pathway enrichment analysis suggested that the anti-arthritic mechanisms of BWLZ might be attributed to its network regulation of several biological processes, such as steroid hormone biosynthesis, mTOR signaling pathway, alanine, aspartate and glutamate metabolism, and synthesis and degradation of ketone bodies. These results provide further evidence for the anti-arthritic properties of BWLZ and are beneficial for its quality control and clinical application. The potential targets and biological processes found in this study may provide valuable information for further studying the molecular mechanisms of BWLZ against RA. In addition, our work provides new insights for revealing the active ingredients and regulatory mechanisms of complex herbal preparations.
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Antirreumáticos/química , Medicamentos Herbarios Chinos/química , Metabolómica , Animales , Antirreumáticos/metabolismo , Antirreumáticos/farmacología , Artritis Experimental/inducido químicamente , Artritis Experimental/tratamiento farmacológico , Sitios de Unión , Biomarcadores/sangre , Biomarcadores/metabolismo , Citocromo P-450 CYP1A2/química , Citocromo P-450 CYP1A2/metabolismo , Análisis Discriminante , Medicamentos Herbarios Chinos/metabolismo , Medicamentos Herbarios Chinos/uso terapéutico , Hesperidina/química , Hesperidina/metabolismo , Hesperidina/uso terapéutico , Isoquinolinas/química , Isoquinolinas/metabolismo , Isoquinolinas/uso terapéutico , Espectroscopía de Resonancia Magnética , Masculino , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Análisis de Componente Principal , Estructura Terciaria de Proteína , Ratas , Ratas WistarRESUMEN
Bawei Longzuan granule (BLG) is a representative Zhuang medicine preparation. The present work aims to characterize the chemical constituents of BLG and evaluate its anti-arthritic activity. The major chemical constituents of BLG were tentatively identified by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), which revealed the presence of some alkaloids (e. g., magnoflorine, sinomenine and nitidine) and flavonoids (e. g., hesperidin, diosmin and sinensetin) that may be partly responsible for the anti-arthritic effect of BLG. In addition, the collagen-induced arthritis (CIA) model in rats was induced by intradermal injection of bovine collagen-II in complete Freund's adjuvant at the base of tail. The CIA rats received oral administration of BLG (1.25, 2.5 and 5â g/kg) for 30â days. Then, various indicators were determined to evaluate its anti-arthritic activity, including paw swelling, arthritic score, body weight, knee joint pathology, thymus index and spleen index. Additionally, the serum levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1ß, IL-6, IL-4 and IL-10 were measured to determine the underlying mechanisms. The results showed that BLG efficiently ameliorated the severity of arthritis in CIA rats by decreasing paw swelling and arthritis score and improving the histological lesions of knee joint. Moreover, the serum levels of several pro-inflammatory cytokines (i. e., IL-1ß, TNF-α, IL-6 and IFN-γ) were downregulated, whereas two anti-inflammatory factors (i. e., IL-4 and IL-10) were upregulated after BLG administration. These results indicated that BLG possessed promising therapeutic effect on collagen-induced arthritis by inhibiting inflammatory responses. BLG can be used as a complementary or alternative traditional medicine to treat rheumatoid arthritis.
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Antiinflamatorios/farmacología , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Citocinas/antagonistas & inhibidores , Medicamentos Herbarios Chinos/farmacología , Inflamación/tratamiento farmacológico , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Artritis Experimental/inducido químicamente , Artritis Experimental/metabolismo , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/metabolismo , Colágeno , Citocinas/metabolismo , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Inflamación/metabolismo , Masculino , Medicina Tradicional China , Ratas , Ratas WistarRESUMEN
Fecal Tibetan medicines have a long history of application in China, with a good clinical efficacy. In order to promote the development and modernization of these medicines, we consulted ancient and modern Tibetan medicine literatures to collect and summarize the names, original species, natures, flavor, functions and processing methods of fecal Tibetan medicines. A total of 35 fecal Tibetan medicines were collected, such as Jiufen, Heibingpian, Langfen, Mafen, Goufen, Gezifen. The most commonly used medicines were Jiufen and Heibingpian. Both were mainly used for the treatment of indigestion, food abdominal distension, gastric ulcer, and other gastrointestinal diseases. At present, there are only a few studies on the active ingredients, pharmacodynamics and mechanism of action of these medicines. Therefore, further study shall be conducted. The regulation of gut microbiota may be a new way to evaluate the effectiveness of fecal Tibetan medicines and their mechanism of action.
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Heces , Microbioma Gastrointestinal , Medicina Tradicional Tibetana , ChinaRESUMEN
Lepiota brunneoincarnata is a highly toxic mushroom species known to cause acute liver failure. However, there are limited reports investigating L. brunneoincarnata causing acute hepatic and renal damage. The present article reports 2 cases of L. brunneoincarnata poisoning in a mother and son from Chuxiong City, Yunnan Province, China. Both patients presented with gastrointestinal symptoms approximately 8-9 h after ingesting the suspect mushrooms and sought medical attention 27-28 h post-ingestion, both exhibiting acute hepatic and kidney injuries. Morphological and molecular biology studies confirmed the species of the mushrooms as L. brunneoincarnata. Liquid chromatography-tandem mass spectrometry analysis revealed mean fresh-weight concentrations of 123.5 µg/g α-amanitin and 45.7 µg/g ß-amanitin in the mushrooms. The patients underwent standard treatments, including multiple-dose activated charcoal, oral silibinin capsules, N-acetylcysteine, penicillin G, hemoperfusion, and plasma exchange. One patient recovered completely and was discharged after 16 days of hospitalization. The other patient exhibited gradual improvement in liver and renal function; however, renal function deteriorated 9 days after ingestion, and the patient declined renal replacement therapy and returned home 14 days post-ingestion. The patient was then re-hospitalized due to oliguria and edema in both lower extremities. Renal biopsy revealed acute tubular necrosis, inflammatory cell infiltration, minor glomerular capsular fibrosis, loss of microvilli in the renal tubular epithelial cells, and interstitial edema. The patient underwent 2 rounds of continuous renal replacement therapy, which eventually resulted in improvement, and was discharged 31 days after mushroom consumption. It is noteworthy that this patient had already progressed to chronic kidney insufficiency 11 months after intoxication.
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Lesión Renal Aguda , Agaricales , Intoxicación por Setas , Humanos , Intoxicación por Setas/diagnóstico , China , Agaricales/química , Hígado/patología , Amanitinas/análisis , Riñón/patología , Edema , Ingestión de Alimentos , Lesión Renal Aguda/inducido químicamenteRESUMEN
Amatoxins are responsible for most fatal mushroom poisoning cases, as it causes both hepatotoxicity and nephrotoxicity. However, studies on amatoxin nephrotoxicity are limited. Here, we investigated nephrotoxicity over 4 days and nephrotoxicity/hepatotoxicity over 14 days in mice. The organ weight ratio, serological indices, and tissue histology results indicated that a nephrotoxicity mouse model was established with two stages: (1) no apparent effects within 24 h; and (2) the appearance of adverse effects, with gradual worsening within 2-14 days. For each stage, the kidney transcriptome revealed patterns of differential mRNA expression and significant pathway changes, and Western blot analysis verified the expression of key proteins. Amanitin-induced nephrotoxicity was directly related to RNA polymerase II because mRNA levels decreased, RNA polymerase II-related pathways were significantly enriched at the transcription level, and RNA polymerase II protein was degraded in the early poisoning stage. In the late stage, nephrotoxicity was more severe than hepatotoxicity. This is likely associated with inflammation because inflammation-related pathways were significantly enriched and NF-κB activation was increased in the kidney.
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Agaricales , Enfermedad Hepática Inducida por Sustancias y Drogas , Intoxicación por Setas , Masculino , Ratones , Animales , Alfa-Amanitina/toxicidad , Ratones Endogámicos ICR , ARN Polimerasa II/genética , Riñón , Inflamación , Perfilación de la Expresión Génica , ARN MensajeroRESUMEN
PURPOSE: The purpose of the current investigation is to compare the efficacy of different diffusion models and diffusion kurtosis imaging (DKI) in differentiating stage IA endometrial carcinoma (IAEC) from benign endometrial lesions (BELs). METHODS: Patients with IAEC, endometrial hyperplasia (EH), or a thickened endometrium confirmed between May 2016 and August 2022 were retrospectively enrolled. All of the patients underwent a preoperative pelvic magnetic resonance imaging (MRI) examination. The apparent diffusion coefficient (ADC) from the mono-exponential model, pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) from the bi-exponential model, distributed diffusion coefficient (DDC), water molecular diffusion heterogeneity index from the stretched-exponential model, diffusion coefficient (Dk) and diffusion kurtosis (K) from the DKI model were calculated. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficiency. RESULTS: A total of 90 patients with IAEC and 91 patients with BELs were enrolled. The values of ADC, D, DDC and Dk were significantly lower and D* and K were significantly higher in cases of IAEC (p < 0.05). Multivariate analysis showed that K was the only predictor. The area under the ROC curve of K was 0.864, significantly higher compared with the ADC (0.601), D (0.811), D* (0.638), DDC (0.743) and Dk (0.675). The sensitivity, specificity and accuracy of K were 78.89%, 85.71% and 80.66%, respectively. CONCLUSION: Advanced diffusion-weighted imaging models have good performance for differentiating IAEC from EH and endometrial thickening. Among all of the diffusion parameters, K showed the best performance and was the only independent predictor. Diffusion kurtosis imaging was defined as the most valuable model in the current context.
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Imagen de Difusión por Resonancia Magnética , Neoplasias Endometriales , Femenino , Humanos , Sensibilidad y Especificidad , Estudios Retrospectivos , Curva ROC , Imagen de Difusión por Resonancia Magnética/métodos , Neoplasias Endometriales/diagnóstico por imagenRESUMEN
Mushroom poisoning is a significant contributor to foodborne disease outbreaks in China. This study focuses on two Panaeolus subbalteatus poisoning incidents accompanied by epidemiological investigations, species identification, and toxin detection in Ningxia, northwest China. In these two poisoning incidents, some patients exhibited gastrointestinal or neurological symptoms approximately 0.5 h after ingestion of a large amount of wild mushroom. Specifically, in Case 1, one of the three patients experienced nausea, vomiting, and numbness in the throat and limbs; in Case 2, one patient reported dizziness and an abnormal sense of direction. Through morphological and phylogenetic analyses, mushroom specimens were identified as P. subbalteatus. Psilocybin and psilocin were detected in mushroom samples, and only psilocin was detected in biological samples by liquid chromatography-triple quadrupole-linear ion trap mass spectrometry screening. The average psilocybin and psilocin contents in mushroom samples were 1532.2-1760.7 and 114.5-136.0 mg/kg (n = 3), respectively. Moreover, only psilocin was detected in blood and urine samples, with average concentrations 0.5-1.2 ng/mL (n = 3) and 2.5-3.1 ng/mL (n = 3), respectively. These findings provide technical support for managing similar incidents in the future.
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Intoxicación por Setas , Psilocibina , Intoxicación por Setas/diagnóstico , China , Psilocibina/análogos & derivados , Humanos , Triptaminas/análisis , Masculino , Adulto , Femenino , Filogenia , Persona de Mediana EdadRESUMEN
What is already known about this topic?: Mushroom poisoning poses a significant food safety concern in China, with a total of 196 species identified in poisoning incidents by the end of 2022. What is added by this report?: In 2023, the China CDC conducted an investigation into 505 cases of mushroom poisoning spanning 24 provincial-level administrative divisions. This investigation resulted in 1,303 patients and 16 deaths, yielding a case fatality rate of 1.23%. A total of 97 mushrooms were identified as the cause of 6 distinct clinical disease types, with 12 species newly documented as poisonous mushrooms in China. What are the implications for public health practice?: Close collaboration among CDC staff, physicians, and mycologists remains crucial for the control and prevention of mushroom poisoning in the future.
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Taxonomic and phylogenetic studies on Megasporoporia s.l. were carried out. Phylogenetic analysis based on ITS and nLSU sequences showed that Megasporoporia s.l. belonging to the core polyporoid clade, however, it is not monophyletic, and four clades were recognized. The Megasporoporia s.s. clade includes M. setulosa and two new species, M. bannaensis and M. minor spp. nov. Two monophyletic clades were segregated from Megasporoporia s.l., and two new genera were established. Megasporia gen. nov. is composed of M. cystidiolophora, M. ellipsoidea, M. hexagonoides, M. major, M. violacea, and two new species, M. guangdongensis and M. hengduanensis spp. nov. Megasporoporiella gen. nov. including M. cavernulosa, M. rhododendri, M. subcavernulosa, and two new species, M. lacerata and M. pseudocavernulosa spp. nov. Megasporoporia quercina grouped with Grammothele fuligo in the Grammothele clade, so it is transferred to Grammothele and a new combination, G. quercina, is proposed. The main morphological characters of Megasporoporia and the two new genera are discussed, and identification keys to the three genera are provided.
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Coriolaceae/clasificación , Secuencia de Bases , China , Coriolaceae/citología , Coriolaceae/genética , Coriolaceae/aislamiento & purificación , ADN de Hongos/química , ADN de Hongos/genética , ADN Ribosómico/química , ADN Ribosómico/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Cuerpos Fructíferos de los Hongos/citología , Hifa , Datos de Secuencia Molecular , Filogenia , Análisis de Secuencia de ADN , Esporas Fúngicas/citologíaRESUMEN
In this study, Podoscypha was taxonomically and phylogenetically evaluated. In total, five specimens collected from the tropical areas of Yunnan Province in Southwest China were studied. In combination with morphological observations and phylogenetic analyses based on ITS and LSU loci, two new species and one new subspecies, Podoscypha subinvoluta, P. tropica, and P. petalodes subsp. cystidiata, respectively, were discovered. The illustrated descriptions of the new species and subspecies are provided. Moreover, the main morphological differences between related species are discussed.
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Stimuli-responsive cross-linked micelles (SCMs) are ideal nanocarriers for anti-cancer drugs. Compared with non-cross-linked micelles, SCMs exhibit superior structural stability. At the same time, the introduction of an environmentally sensitive crosslinker into a drug delivery system allows SCMs to respond to single or multiple stimuli in the tumor microenvironment, which can minimize drug leakage during the blood circulation process. In this study, curcumin (CUR) was modified as the hydrophobic core crosslinker by utilizing the bisphenol structure, and redox sensitive disulfide bonds were introduced to prepare the glutathione (GSH) stimulated responsive core crosslinker (abbreviated as N3-ss-CUR-ss-N3). In addition, amphiphilic polymer APEG-b-PBYP was prepared through the ring opening reaction, and reacted with the crosslinker through the "click" reaction. After being dispersed in the aqueous phase, core cross-linked nanoparticles (CCL NPs) were obtained. Finally, monoclonal antibody CD326 (mAb-CD326) was reduced and coupled to the hydrophilic chain ends to obtain the nanoparticles with surface modified antibodies (R-mAb-CD326@CCL NPs) for further enhancing targeted drug delivery. The structures of the polymer and crosslinker were characterized by 1H NMR, UV-Vis, FT-IR, and GPC. The morphology, size and stability of CCL NPs and R-mAb-CD326@CCL NPs were investigated by DLS and TEM. The in vitro drug release behavior of CCL NPs was also studied. The results showed that the CCL NPs exhibited reduction-responsiveness and were able to release the original drug CUR under 10 mM GSH conditions. Additionally, the CCL NPs exhibited excellent stability in both the simulated body fluid environment and organic solvents. Especially, R-mAb-CD326@CCL NPs can actively target tumor cells and showed better therapeutic efficacy in in vivo experiments with a tumor suppression rate of 78.7%. This work provides a new idea for the design of nano-drugs targeting breast cancer.
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Curcumina , Neoplasias , Profármacos , Profármacos/química , Curcumina/química , Micelas , Anticuerpos Monoclonales/uso terapéutico , Espectroscopía Infrarroja por Transformada de Fourier , Polímeros/química , Neoplasias/tratamiento farmacológicoRESUMEN
The Auriculariaceae accounts for most of the species in the Auriculariales, and all species in the family are wood-decaying fungi with gelatinous, crustaceous, or woody basidiomes. Many new taxa were published recently, but the taxonomy and phylogeny of the corticioid species in the Auriculariaceae are far from resolved. We undertook a comprehensive taxonomic and phylogenetic study of the family with emphasis on corticioid specimens collected from East and Southeast Asia. Phylogenetic analyses on concatenated ITS and 28S rDNA sequences of representative taxa of the Auriculariaceae and the genera Eichleriella and Heteroradulum were carried out that resolved five new lineages. Heterocorticium gen. nov. is established for two species with resupinate coriaceous basidiomes with smooth, pigmented hymenophores. Five new species, H. bambusicola (generic type), H. latisporum, Eichleriella alpina, E. bambusicola, and Heteroradulum maolanense, are described and illustrated. In addition, Heterochaete delicata, H. discolor, and H. sinensis are transferred to Eichleriella, whereas H. roseola is regarded as a synonym of Kneiffia discolor (= H. discolor). Eichleriella aculeobasidiata is treated as a synonym of Heterochaete sinensis (= E. sinensis). Heterochaete mussooriensis is transferred to Heteroradulum with Heteroradulum semis as a heterotypic synonym. The present study contributes to the understanding of species diversity, taxonomy, and phylogeny of corticioid fungi in Asia.
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Tumor-associated macrophages (TAMs)-based immunotherapy is a promising strategy. Since TAMs are mainly composed of M2-type macrophages, they have a promoting effect on tumor growth, invasion, and metastasis. M2-type macrophages contain a specific receptor CD163 on their surface, providing a prerequisite for active targeting to TAMs. In this study, we prepared CD163 monoclonal antibody modified doxorubicin-polymer prodrug nanoparticles (abbreviated as mAb-CD163-PDNPs) with pH responsiveness and targeted delivery. First, DOX was bonded with the aldehyde group of a copolymer by Schiff base reaction to form an amphiphilic polymer prodrug, which could self-assemble into nanoparticles in the aqueous solution. Then, mAb-CD163-PDNPs were generated through a "Click" reaction between the azide group on the surface of the prodrug nanoparticles and dibenzocyclocytyl-coupled CD163 monoclonal antibody (mAb-CD163-DBCO). The structure and assembly morphology of the prodrug and nanoparticles were characterized by 1H NMR, MALDI-TOF MS, FT-IR UV-vis spectroscopy, and dynamic light scattering (DLS). In vitro drug release behavior, cytotoxicity, and cell uptake were also investigated. The results show that the prodrug nanoparticles have regular morphology and stable structure, especially mAb-CD163-PDNPs, which can actively target TAMs at tumor sites, respond to the acidic environment in tumor cells, and release drugs. While depleting TAMs, mAb-CD163-PDNPs can actively enrich drugs at the tumor site and have a strong inhibitory effect on TAMs and tumor cells. The result of the in vivo test also shows a good therapeutic effect, with a tumor inhibition rate of 81%. This strategy of delivering anticancer drugs in TAMs provides a new way to develop targeted drugs for immunotherapy of malignant tumors.
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Approximately 70%â¼90% of mushroom poisoning deaths are caused by the class of mushroom toxins known as amatoxins. However, the rapid elimination of amatoxins from plasma within 48 h after mushroom ingestion limits the practical value of plasma amatoxin analysis as a diagnostic indicator of Amanita mushroom poisoning. To increase the positive detection rate and extend the detection window of amatoxin poisoning, we developed a new method to detect protein-bound α-amanitin based on the hypothesis that RNAP II-bound α-amanitin released from the tissue into the plasma could be degraded by trypsin hydrolysis and then detected by conventional liquid chromatography-mass spectrometry (LCâMS). Toxicokinetic studies on mice intraperitoneally injected with 0.33 mg/kg α-amanitin were conducted to obtain and compare the concentration trends, detection rates, and detection windows of both free α-amanitin and protein-bound α-amanitin. By comparing detection results with and without trypsin hydrolysis in the liver and plasma of α-amanitin-poisoned mice, we verified the credibility of this method and the existence of protein-bound α-amanitin in plasma. Under the optimized trypsin hydrolysis conditions, we obtained a time-dependent trend of protein-bound α-amanitin in mouse plasma at 1-12 days postexposure. In contrast to the short detection window (0-4 h) of free α-amanitin in mouse plasma, the detection window of protein-bound α-amanitin was extended to 10 days postexposure, with a total detection rate of 53.33%, ranging from the limit of detection to 23.94 µg/L. In conclusion, protein-bound α-amanitin had a higher positive detection rate and a longer detection window than free α-amanitin in mice.
Asunto(s)
Alfa-Amanitina , Intoxicación por Setas , Animales , Ratones , Intoxicación por Setas/diagnóstico , Tripsina/metabolismo , Amanitinas/química , Cromatografía Liquida , Amanita/químicaRESUMEN
In southwestern China, wild boletes are generally considered as safe and tasty edible mushrooms. However, in fact, significant adverse effects after ingestion of boletes is commonly reported in this region. In June 2022, four cases occurred in central and southwestern of China. In these case series, five adults and one child ingested wild boletoi mushrooms known locally as "Yanyoujun" (). This study carried out a detailed epidemiological investigation and mushroom identification. Based on morphological and phylogenetic analysis, the suspected mushrooms were identified as Anthracoporus nigropurpureus (Boletaceae). All five adult victims reported dizziness and blurred vision. Some of them also reported different symptoms, such as muscle weakness, red eyes, headache, muscle cramps, even tremors in the extremities. Reportedly, the symptoms began to subside about 4 to 8 h after ingestion. Among six victims, the child was asymptomatic possibly because a small amount of mushroom was ingested. This possible poisoning appears to be a self-limited illness with a short latency and a relatively short duration. Unfortunately, laboratory investigations of the victims were not performed. Further observations and formal medical examination of victims are required in the future. It is the first detailed report of possible poisoning the genus Anthracoporus.