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Herb compatibility is the soul of traditional Chinese Medicine prescriptions. Coptidis rhizoma (CR) (Coptis chinensis Franch., Coptis deltoidea C.Y.Cheng et Hsiao, or Coptis teeta Wall.; family Ranunculaceae), is a well-known herb. The bitter and cold nature of CR can irritate the spleen and stomach, and certain ingredients in CR may trigger allergic reactions. Herb combinations can help alleviate the side effects caused by CR. Through data analysis and literature research, there are many herbs combined with CR have a high frequency, but only a few are currently used as formulae in clinical practice. The results showed that these six herb pairs are usually widely studied or used as prescriptions in the clinic. This paper describes the six herb pairs from the key traditional uses, changes in bioactive constituents, and compatibility effects, especially with Euodiae fructus (family Rutaceae), Scutellariae radix (family Lamiaceae), Magnoliae Officinalis cortex (family Magnoliaceae), Glycyrrhizae radix et rhizoma (family Fabaceae), Ginseng radix et rhizoma (family Araliaceae), and Aucklandiae radix (family Asteraceae), and found that herbs are more effective when used in combination. Therefore, it is feasible to establish some methods to study herb pairs comprehensively from different perspectives. This paper aims to provide the latest and most comprehensive information on the six herb pairs and summarize the pattern of CR compatibility effects. It aims to attract more attention, and further experimental studies will be conducted to investigate and evaluate the effects of herb pairs containing CR. These data can also provide valuable references for researchers and also provide more possibilities for future applications in clinical practice and new drug development.
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Introduction: Differences in transmissibility of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) in different districts are hard to assess. To address this, our study focused on calculating the Real-time reproduction number (R t ) for these variants in different regions. Methods: According to the criteria defined by the World Health Organization (WHO), the global landscape was categorized into six distinct regions. In each region, the predominant SARS-CoV-2 variant was first identified based on the proportion of variant sequencing analysis results. Then, using serial interval (SI) parameters, we calculated R t for the relevant Variant of Concern (VOC) in each region. This approach enabled us to compare the R t values of the same variant across different regions and analyze the transmissibility of each region's variant in relation to the overall situation in that region. Results: The progression of VOC for SARS-CoV-2 shows regional variations. However, a common sequence of evolution is observed: Wild-type â Alpha â Beta â Delta â Omicron. Moreover, an increasing trend is discerned within diverse regions where the shift in R t of distinct VOC corresponds with the overarching R t route of SARS-CoV-2 in specific regions. Conclusion: As the COVID-19 pandemic advances, regional epidemiological trends are aligning, likely due to similar virus mutations and shared public health strategies, suggesting opportunities for standardized global responses.
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The mathematical method to which theoretical epidemiology belongs is one of the three major methodologies in epidemiology. It is of great value in diagnosing infectious disease epidemic trends and evaluating the effectiveness of prevention and control measures. This paper aims to summarize the brief history of the development of theoretical epidemiology, common types of mathematical models, and key steps to develop a mathematical model. It also provides some thoughts and perspectives on the development and application of theoretical epidemiology in China.
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The Guohe River Basin in Anhui Province was selected as the research area for this study. By collecting surface water, shallow groundwater, and middle-deep groundwater samples, various hydrochemical parameters and stable isotopes of water in different water bodies were analyzed using methods such as the Gibbs diagram, ion ratios, and MixSIAR model to reveal and quantify the transformation relationships between these water bodies. The results indicated that both surface water and groundwater in the study area were predominantly neutral to weakly alkaline. The hydrochemical types of surface water were mainly characterized by Cl·SO4·HCO3-Na and Cl·SO4-Na types, whereas the shallow groundwater exhibited HCO3-Ca·Mg and HCO3-Mg·Na types, and the middle-deep groundwater was of the Cl·HCO3-Na type. The hydrochemical characteristics of various water bodies were influenced by multiple factors such as rock weathering, evaporation concentration, and positive cation exchange. The distribution characteristics of δ18O and δ2H values in surface water and groundwater indicated that atmospheric precipitation was the main water source. The δ18O and δ2H in groundwater were significantly correlated with K+, Na+, Cl-, SO42-, and NO3-. According to the analysis using the MixSIAR model, the contribution of atmospheric precipitation to surface water was 46.5 %, whereas the contribution from shallow groundwater was 53.5 %. The sources of shallow groundwater were identified as atmospheric precipitation (57.4 %) and surface water (42.6 %), and the main source of supply for middle-deep groundwater was lateral flow from upstream groundwater.
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Hepatocellular carcinoma (HCC), one of the leading causes of cancerrelated mortality worldwide, is challenging to identify in its early stages and prone to metastasis, and the prognosis of patients with this disease is poor. Treatment options for HCC are limited, with even radical treatments being associated with a risk of recurrence or transformation in the short term. Furthermore, the multityrosine kinase inhibitors approved for firstline therapy have marked drawbacks, including drug resistance and side effects. The rise and breakthrough of immune checkpoint inhibitors (ICIs) have provided a novel direction for HCC immunotherapy but these have the drawback of low response rates. Since avoiding apoptosis is a universal feature of cancer, the induction of nonapoptotic regulatory cell death (NARCD) is a novel strategy for HCC immunotherapy. At present, NARCD pathways, including ferroptosis, pyroptosis and necroptosis, are novel potential forms of immunogenic cell death, which have synergistic effects with antitumor immunity, transforming immune 'cold' tumors into immune 'hot' tumors and exerting antitumor effects. Therefore, these pathways may be targeted as a novel treatment strategy for HCC. In the present review, the roles of ferroptosis, pyroptosis and necroptosis in antitumor immunity in HCC are discussed, and the relevant targets and signaling pathways, and the current status of combined therapy with ICIs are summarized. The prospects of targeting ferroptosis, pyroptosis and necroptosis in HCC immunotherapy are also considered.
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Carcinoma Hepatocelular , Ferroptosis , Inmunoterapia , Neoplasias Hepáticas , Necroptosis , Piroptosis , Humanos , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Piroptosis/efectos de los fármacos , Piroptosis/inmunología , Ferroptosis/efectos de los fármacos , Necroptosis/inmunología , Necroptosis/efectos de los fármacos , Inmunoterapia/métodos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Transducción de Señal/efectos de los fármacos , AnimalesRESUMEN
The coronavirus disease 2019 (COVID-19) pandemic, along with the implementation of public health and social measures (PHSMs), have markedly reshaped infectious disease transmission dynamics. We analysed the impact of PHSMs on 24 notifiable infectious diseases (NIDs) in the Chinese mainland, using time series models to forecast transmission trends without PHSMs or pandemic. Our findings revealed distinct seasonal patterns in NID incidence, with respiratory diseases showing the greatest response to PHSMs, while bloodborne and sexually transmitted diseases responded more moderately. 8 NIDs were identified as susceptible to PHSMs, including hand, foot, and mouth disease, dengue fever, rubella, scarlet fever, pertussis, mumps, malaria, and Japanese encephalitis. The termination of PHSMs did not cause NIDs resurgence immediately, except for pertussis, which experienced its highest peak in December 2023 since January 2008. Our findings highlight the varied impact of PHSMs on different NIDs and the importance of sustainable, long-term strategies, like vaccine development.
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COVID-19 , Enfermedades Transmisibles , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/transmisión , COVID-19/prevención & control , China/epidemiología , Enfermedades Transmisibles/epidemiología , Pandemias/prevención & control , Incidencia , Estaciones del Año , Salud Pública , Control de Enfermedades Transmisibles/métodosRESUMEN
Tripterygium glycosides (TG) is extracted from the roots of Chinese herbal medicine named Tripterygium wilfordii Hook F (TwHF). TG tablets are the representative TwHF-based agents with anti-inflammatory and immunomodulatory activities for treating rheumatoid arthritis. Although the curative effect of TG is remarkable, the clinical application is limited by a variety of organ toxicity. One of the most serious side-effects induced by TG is damage of the male reproductive system and the toxic mechanism is still not fully elucidated. TG-induced testicular injury was observed in male mice by treated with different concentrations of TG. The results showed that TG induced a significant decrease in testicular index. Pathological observation showed that spermatogenic cells were obviously shed, arranged loosely, and the spermatogenic epithelium was thin compared with control mice. In addition, the toxic effect of TG on mouse spermatogonia GC-1 cells was investigated. The results displayed that TG induced significant cytotoxicity in mouse GC-1 cells. To explore the potential toxic components that triggered testicular injury, the effects of 8 main components of TG on the viability of GC-1 cells were detected. The results showed that celastrol was the most toxic component of TG to GC-1 cells. Western blot analysis showed that LC3-II and the ratio of LC3-II/LC3-I were significantly increased and the expression level of p62 were decreased in both TG and celastrol treated cells, which indicated the significant activation of autophagy in spermatogonia cells. Therefore, autophagy plays an important role in the testicular injury induced by TG, and inhibition of autophagy is expected to reduce the testicular toxicity of TG.
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Autofagia , Glicósidos , Triterpenos Pentacíclicos , Espermatogonias , Testículo , Tripterygium , Triterpenos , Animales , Masculino , Tripterygium/química , Tripterygium/toxicidad , Autofagia/efectos de los fármacos , Testículo/efectos de los fármacos , Testículo/patología , Glicósidos/toxicidad , Glicósidos/farmacología , Espermatogonias/efectos de los fármacos , Ratones , Triterpenos/farmacología , Triterpenos/toxicidad , Línea Celular , Supervivencia Celular/efectos de los fármacosRESUMEN
Kuiper's statistic is a good measure for the difference of ideal distribution and empirical distribution in the goodness-of-fit test. However, it is a challenging problem to solve the critical value and upper tail quantile, or simply Kuiper pair, of Kuiper's statistics due to the difficulties of solving the nonlinear equation and reasonable approximation of infinite series. In this work, the contributions lie in three perspectives: firstly, the second order approximation for the infinite series of the cumulative distribution of the critical value is used to achieve higher precision; secondly, the principles and fixed-point algorithms for solving the Kuiper pair are presented with details; finally, finally, a mistake about the critical value cnα for (α,n)=(0.01,30) in Kuiper's distribution table has been labeled and corrected where n is the sample capacity and α is the upper tail quantile. The algorithms are verified and validated by comparing with the table provided by Kuiper. The methods and algorithms proposed are enlightening and worth of introducing to the college students, computer programmers, engineers, experimental psychologists and so on.
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Since the COVID-19 pandemic began, a plethora of modeling studies related to COVID-19 have been released. While some models stand out due to their innovative approaches, others are flawed in their methodology. To assist novices, frontline healthcare workers, and public health policymakers in navigating the complex landscape of these models, we introduced a structured framework named MODELS. This framework is designed to detail the essential steps and considerations for creating a dependable epidemic model, offering direction to researchers engaged in epidemic modeling endeavors.
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COVID-19 , Enfermedades Transmisibles , Humanos , Pandemias , COVID-19/epidemiología , Enfermedades Transmisibles/epidemiología , Personal de Salud , Salud PúblicaRESUMEN
CONTEXT: Congenital hypothyroidism (CH) is the most common endocrine disorder in neonates, but its etiology is still poorly understood. OBJECTIVE: We performed whole exome sequencing to identify novel causative gene for CH and functional studies to validate its role in the occurrence of CH. METHODS: Whole exome sequencing in 98 CH patients not harboring known CH candidate genes and bioinformatic analysis were performed. Functional analysis was performed using morpholino, a synthetic short antisense oligonucleotide that contains 25 DNA bases on a methylene morpholine backbone, in zebrafish and CRISPRâCas9-mediated gene knockout in mice. RESULTS: Eukaryotic translation initiation factor 4B (EIF4B) was identified as the most promising candidate gene. The EIF4B gene was inherited in an autosomal recessive model, and one patient with thyroid dysgenesis carried EIF4B biallelic variants (p.S430F/p.P328L). In zebrafish, the knockdown of eif4ba/b expression caused thyroid dysgenesis and growth retardation. Thyroid hormone levels were significantly decreased in morphants compared with controls. Thyroxine treatment in morphants partially rescued growth retardation. In mice, the homozygous conceptuses of Eif4b+/- parents did not survive. Eif4b knockout embryos showed severe growth retardation, including thyroid dysgenesis and embryonic lethality before E18.5. CONCLUSION: These experimental data supported a role for EIF4B function in the pathogenesis of the hypothyroid phenotype seen in CH patients. Our work indicated that EIF4B was identified as a novel candidate gene in CH. EIF4B is essential for animal survival, but further studies are needed to validate its role in the pathogenesis of CH.
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BACKGROUND: Patients with obesity are more sensitive to pain and more likely to have acute postoperative pain (APP). Studies have shown that the depth of anesthesia may affect the incidence of APP. The purpose of the study was to look into the connection between APP and depth of anesthesia in patients with obesity undergoing laparoscopic sleeve gastrectomy. METHODS: This is a prospective, double-blinded randomized clinical trial, 90 patients undergoing laparoscopic sleeve gastrectomy were randomly divided into two groups: the light anesthesia group (Bispectral Index of 50, BIS 50) and the deep anesthesia group (BIS 35). The degree of pain was evaluated by the visual analogue scale (VAS) at 0, 12, 24, 48, and 72 h after surgery. The use of analgesics, grade of postoperative nausea and vomiting (PONV), and the Quality of Recovery-15 (QoR-15) score were recorded. RESULTS: The VAS scores at rest or coughing at 0, 12, and 24 h after surgery in the BIS 35 group were lower than those in the BIS 50 group (P < 0.05). Fewer patients in the deep anesthesia group needed analgesia during the recovery period, and patient satisfaction was higher on the 3rd day after surgery (P < 0.015, P < 0.032, respectively). CONCLUSIONS: For patients with obesity, maintaining a deeper depth of anesthesia during surgery is beneficial to reduce APP causes less need for additional analgesic drugs, and improves patient satisfaction.
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Anestesia , Laparoscopía , Obesidad Mórbida , Humanos , Laparoscopía/efectos adversos , Estudios Prospectivos , Obesidad Mórbida/cirugía , Anestesia/efectos adversos , Analgésicos/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/epidemiología , Obesidad/cirugía , Gastrectomía/efectos adversosRESUMEN
The NLRP3 inflammasome has been recognized as a promising therapeutic target in drug discovery for inflammatory diseases. Our initial research identified a natural sesquiterpene isoalantolactone (IAL) as the active scaffold targeting NLRP3 inflammasome. To improve its activity and metabolic stability, a total of 64 IAL derivatives were designed and synthesized. Among them, compound 49 emerged as the optimal lead, displaying the most potent inhibitory efficacy on nigericin-induced IL-1ß release in THP-1 cells, with an IC50 value of 0.29 µM, approximately 27-fold more potent than that of IAL (IC50: 7.86 µM), and exhibiting higher metabolic stability. Importantly, 49 remarkably improved DSS-induced ulcerative colitis in vivo. Mechanistically, we demonstrated that 49 covalently bound to cysteine 279 in the NACHT domain of NLRP3, thereby inhibiting the assembly and activation of NLRP3 inflammasome. These results provided compelling evidence to further advance the development of more potent NLRP3 inhibitors based on this scaffold.
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Diseño de Fármacos , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Sesquiterpenos , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Humanos , Inflamasomas/metabolismo , Inflamasomas/antagonistas & inhibidores , Animales , Sesquiterpenos/farmacología , Sesquiterpenos/síntesis química , Sesquiterpenos/química , Ratones , Relación Estructura-Actividad , Interleucina-1beta/metabolismo , Células THP-1 , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Ratones Endogámicos C57BLRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Xinyang tablet (XYT) has been used for heart failure (HF) for over twenty years in clinical practice, but the underlying molecular mechanism remains poorly understood. AIMS OF THE STUDY: In the present study, we aimed to explore the protective effects of XYT in HF in vivo and in vitro. MATERIALS AND METHODS: Transverse aortic constriction was performed in vivo to establish a mouse model of cardiac pressure overload. Echocardiography, tissue staining, and real-time quantitative PCR (qPCR) were examined to evaluate the protective effects of XYT on cardiac function and structure. Adenosine 5'-triphosphate production, reactive oxygen species staining, and measurement of malondialdehyde and superoxide dismutase was used to detect mitochondrial damage. Mitochondrial ultrastructure was observed by transmission electron microscope. Immunofluorescence staining, qPCR, and Western blotting were performed to evaluate the effect of XYT on the mitochondrial unfolded protein response and mitophagy, and to identify its potential pharmacological mechanism. In vitro, HL-1 cells and neonatal mouse cardiomyocytes were stimulated with Angiotensin II to establish the cell model. Western blotting, qPCR, immunofluorescence staining, and flow cytometry were utilized to determine the effects of XYT on cardiomyocytes. HL-1 cells overexpressing receptor-interacting serum/three-protein kinase 3 (RIPK3) were generated by transfection of RIPK3-overexpressing lentiviral vectors. Cells were then co-treated with XYT to determine the molecular mechanisms. RESULTS: In the present study, XYT was found to exerta protective effect on cardiac function and structure in the pressure overload mice. And it was also found XYT reduced mitochondrial damage by enhancing mitochondrial unfolded protein response and restoring mitophagy. Further studies showed that XYT achieved its cardioprotective role through regulating the RIPK3/FUN14 domain containing 1 (FUNDC1) signaling. Moreover, the overexpression of RIPK3 successfully reversed the XYT-induced protective effects and significantly attenuated the positive effects on the mitochondrial unfolded protein response and mitophagy. CONCLUSIONS: Our findings indicated that XYT prevented pressure overload-induced HF through regulating the RIPK3/FUNDC1-mediated mitochondrial unfolded protein response and mitophagy. The information gained from this study provides a potential strategy for attenuating mitochondrial damage in the context of pressure overload-induced heart failure using XYT.
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Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Ratones Endogámicos C57BL , Mitofagia , Miocitos Cardíacos , Respuesta de Proteína Desplegada , Animales , Mitofagia/efectos de los fármacos , Respuesta de Proteína Desplegada/efectos de los fármacos , Ratones , Masculino , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/ultraestructura , Comprimidos , Línea Celular , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismoRESUMEN
Background Detection of extranodal extension (ENE) at pathology is a poor prognostic indicator for rectal cancer, but whether ENE can be identified at pretreatment MRI is, to the knowledge of the authors, unknown. Purpose To evaluate the performance of pretreatment MRI in detecting ENE using a matched pathologic reference standard and to assess its prognostic value in patients with rectal cancer. Materials and Methods This single-center study included a prospective development data set consisting of participants with rectal adenocarcinoma who underwent pretreatment MRI and radical surgery (December 2021 to January 2023). MRI characteristics were identified by their association with ENE-positive nodes (χ2 test and multivariable logistic regression) and the performance of these MRI features was assessed (area under the receiver operating characteristic curve [AUC]). Interobserver agreement was assessed by Cohen κ coefficient. The prognostic value of ENE detected with MRI for predicting 3-year disease-free survival was assessed by Cox regression analysis in a retrospective independent validation cohort of patients with locally advanced rectal cancer (December 2019 to July 2020). Results The development data set included 147 participants (mean age, 62 years ± 11 [SD]; 87 male participants). The retrospective cohort included 110 patients (mean age, 60 years ± 9; 79 male participants). Presence of vessel interruption and fusion (both P < .001), heterogeneous internal structure, and the broken-ring and tail signs (odds ratio range, 4.10-23.20; P value range, <.001 to .002) were predictors of ENE at MRI, and together achieved an AUC of 0.91 (95% CI: 0.88, 0.93) in detecting ENE. Interobserver agreement was moderate for the presence of vessel interruption and fusion (κ = 0.46 for both) and substantial for others (κ = 0.61-0.67). The presence of ENE at pretreatment MRI was independently associated with worse 3-year disease-free survival (hazard ratio, 3.00; P = .02). Conclusion ENE can be detected at pretreatment MRI, and its presence was associated with worse prognosis for patients with rectal cancer. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Eberhardt in this issue.
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Neoplasias Primarias Secundarias , Neoplasias del Recto , Humanos , Masculino , Persona de Mediana Edad , Extensión Extranodal , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Neoplasias del Recto/diagnóstico por imagen , Imagen por Resonancia MagnéticaRESUMEN
Men are inevitably plagued by prostate disease throughout their lives. However, the understanding of the pathogenesis of prostate diseases is still limited. In the 1960s, McNeal proposed the theory of prostate zones: the prostate was divided into three main zones: transition zone, central zone, and peripheral zone. Over the past 50 years, significant differences between different prostate zones have been gradually revealed. We summarized the most significant differences in different zones of the prostate. For the first time, we proposed the "apparent difference in prostate zones" concept. This new concept has been proposed to understand the different zones of the prostate better. It also provided new ideas for exploring the susceptibility of lesions in different prostate zones. Despite the reported differences between zones, the treatment of prostate-related diseases remains partition agnostic. Therefore, we also discussed the clinical significance of the "apparent difference in the prostate zone" and emphasized the necessity of prostate zones.
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Próstata , Hiperplasia Prostática , Neoplasias de la Próstata , Prostatitis , Humanos , Masculino , Neoplasias de la Próstata/patología , Próstata/patología , Susceptibilidad a EnfermedadesRESUMEN
5F-MDMB-PICA, an indole-type synthetic cannabinoid (SC), was classified illicit globally in 2020. Although the extensive metabolism of 5F-MDMB-PICA in the human body warrants the development of robust analytical methods for metabolite detection and quantification, a current lack of reference standards for characteristic metabolites hinders such method creation. This work described the synthesis of 18 reference standards for 5F-MDMB-PICA and its possible Phase I metabolites, including three hydroxylated positional isomers R14 to R16. All the compounds were systematic characterized via nuclear magnetic resonance, Fourier transform infrared spectroscopy, and high-resolution mass spectrometry. Furthermore, two methods were developed for the simultaneous detection of all standards using liquid chromatography-tandem mass spectrometry and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. By comparison with authentic samples, R17 was identified as a suitable urine biomarker for 5F-MDMB-PICA uptake.
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ETHNOPHARMACOLOGICAL RELEVANCE: Shicao is the aerial part of Achillea alpina L., a common herb found mainly in Europe, Asia, and North America. Traditional Chinese medicine has a history of thousands of years and is widely used to treat various diseases. AIM OF STUDY: To explore the hepatoprotective effects of Shicao on CCl4-induced acute liver injury. METHODS: A rat model of acute liver injury was established and liver function indices were assessed to evaluate the protective effect of Shicao on the liver. Untargeted metabolomics of the serum and liver tissues was conducted using UPLC-Q-TOF/MS to identify differential metabolites related to acute liver injury. A network of metabolite-reaction-enzyme-gene constituents was constructed using network pharmacology. Hub targets and key components of the effect of Shicao on acute liver injury were screened from the network. RESULTS: Compared to the model group, Shicao improved the degree of liver damage through the assessment of the liver index, ALT and AST levels, and hepatic pathology slices, demonstrating its hepatoprotective effect against acute liver injury in rats. 10 and 38 differential metabolites involved in acute liver injury were identified in serum and liver tissues, respectively. Most of these were regulated or restored following treatment with Shicao, which mainly consisted of bile acids, lipids, and nucleotides such as taurocholic acid, LysoPC (17:0), and adenosine diphosphate ribose. Through the network of metabolite-reaction-enzyme-gene-constituents, 10 key components and 5 hub genes, along with 7 crucial differential metabolites, were mainly involved in glycerophospholipid metabolism, purine metabolism, biosynthesis of unsaturated fatty acids, and primary bile acid biosynthesis, which may play important roles in the prevention of acute liver injury by Shicao. CONCLUSION: This study revealed that Shicao had protective effects against CCl4-induced liver injury in rats. It was speculated that the ingredients of Shicao might be closely related to the hub targets, thereby regulating the levels of key metabolites, affecting inflammatory response and oxidative stress and attenuate the liver injury consequently. This study provides a basis for further investigation of its therapeutic potential and the mechanism of action.
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Medicamentos Herbarios Chinos , Ratas , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/metabolismo , Ratas Sprague-Dawley , Farmacología en Red , Hígado , MetabolómicaRESUMEN
Colorectal cancer is the third most common type of cancer worldwide and has become one of the major human disease burdens. In clinical practice, the treatment of colorectal cancer has been closely related to the use of irinotecan. Irinotecan combines with many other anticancer drugs and has a broader range of drug combinations. Combination therapy is one of the most important means of improving anti-tumor efficacy and overcoming drug resistance. Reasonable combination therapy can lead to better patient treatment options, and inappropriate combination therapy will increase patient risk. For the colorectal therapeutic field, the significance of combination therapy is to improve the efficacy, reduce the adverse effects, and improve the ease of treatment. Therefore, we explored the clinical advantages of its combination therapy based on mechanism or metabolism and reviewed the rationale basis and its limitations in conducting exploratory clinical trials on irinotecan combination therapy, including the results of clinical trials on the combination potentiation of cytotoxic drugs, targeted agents, and herbal medicine. We hope that these can evoke more efforts to conduct irinotecan in the laboratory for further studies and evaluations, as well as the possibility of more in-depth development in future clinical trials.
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Chinese medicine cinobufacini is an extract from the dried skin of Bufo bufo gargarizans Cantor, with active ingredients of bufadienolides and indole alkaloids. With further research and clinical applications, it is found that cinobufacini alone or in combination with other therapeutic methods can play an anti-tumor role by controlling proliferation of tumor cells, promoting apoptosis, inhibiting formation of tumor neovascularization, reversing multidrug resistance, and regulating immune response; it also has the functions of relieving cancer pain and regulating immune function. In this paper, the chemical composition, pharmacological effects, clinical applications, and adverse reactions of cinobufacini are summarized. However, the extraction of monomer components of cinobufacini, the relationship between different mechanisms, and the causes of adverse reactions need to be further studied. Also, high-quality clinical studies should be conducted.
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Venenos de Anfibios , Bufanólidos , Neoplasias , Animales , Humanos , Neoplasias/tratamiento farmacológico , Bufonidae , Venenos de Anfibios/farmacología , Venenos de Anfibios/uso terapéutico , Venenos de Anfibios/química , Bufanólidos/farmacología , Bufanólidos/uso terapéuticoRESUMEN
Acanthocephalans of the order Polymorphida mainly parasitic in birds and mammals, are of veterinary, medical and economic importance. However, the evolutionary relationships of its 3 families (Centrorhynchidae, Polymorphidae and Plagiorhynchidae) remain under debate. Additionally, some species of Polymorphida (i.e. Bolbosoma spp. and Corynosoma spp.) are recognized as zoonotic parasites, associated with human acanthocephaliasis, but the mitochondrial genomes for representatives of Bolbosoma and Corynosoma have not been reported so far. In the present study, the complete mitochondrial genomes B. nipponicum and C. villosum (Acanthocephala: Polymorphidae) are reported for the first time, which are 14 296 and 14 241 bp in length, respectively, and both contain 36 genes [including 12 PCGs, 22 tRNA genes and 2 rRNA genes] and 2 non-coding regions (NCR1 and NCR2). The gene arrangement of some tRNAs in the mitogenomes of B. nipponicum and C. villosum differs from that found in all other acanthocephalans, except Polymorphus minutus. Phylogenetic results based on concatenated amino acid (AA) sequences of the 12 protein-coding genes (PCGs) strongly supported that the family Polymorphidae is a sister to the Centrorhynchidae rather than the Plagiorhynchidae, and also confirmed the sister relationship of the genera Bolbosoma and Corynosoma in the Polymorphidae based on the mitogenomic data for the first time. Our present findings further clarified the phylogenetic relationships of the 3 families Plagiorhynchidae, Centrorhynchidae and Polymorphidae, enriched the mitogenome data of the phylum Acanthocephala (especially the order Polymorphida), and provided the resource of genetic data for diagnosing these 2 pathogenic parasites of human acanthocephaliasis.