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PURPOSE: Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best efforts of surgery, radiation, and other therapies. For better therapy, we explored the efficacy and toxicity of a novel therapy that combines apatinib and temozolomide in DMG. METHODS: A retrospective analysis of 32 patients with DMG who underwent apatinib plus temozolomide treatment was performed. Apatinib was given 500 mg in adults, 250 mg in pediatric patients once daily. Temozolomide was administered at 200 mg/m2/d according to the standard 5/28 days regimen. The main clinical data included basic information of patients, radiological and pathological characteristics of tumors, treatment, adverse reactions, prognosis. RESULTS: The objective response rate was 24.1%, and the disease control rate was 79.3%. The median PFS of all patients was 5.8 months, and median OS was 10.3 months. A total of 236 cycles of treatment were available for safety assessment and the toxicity of the combination therapy was relatively well tolerated. The most common grade 3 toxicities were myelosuppression including leukopenia (5.08%), neutropenia (4.24%), lymphopenia (2.12%), thrombocytopenia (1.69%) and anemia (1.27%). Grade 4 toxicities included neutropenia (2.12%), thrombocytopenia (2.12%) and proteinuria (1.69%). All the adverse events were relieved after symptomatic treatment or dose reduction. CONCLUSIONS: Apatinib plus temozolomide could be an effective regimen with manageable toxicities and favorable efficacy and may outperform temozolomide monotherapy, particularly in newly diagnosed adults with tumors located outside the pons. The novel therapy deserves further investigation in adult DMG patients.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas , Glioma , Piridinas , Temozolomida , Humanos , Temozolomida/administración & dosificación , Temozolomida/uso terapéutico , Temozolomida/efectos adversos , Femenino , Masculino , Adulto , Piridinas/administración & dosificación , Piridinas/efectos adversos , Piridinas/uso terapéutico , Glioma/tratamiento farmacológico , Glioma/patología , Adolescente , Estudios Retrospectivos , Niño , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Preescolar , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Hemisphere functional lateralization is a prominent feature of the human brain. However, it is not known whether hemispheric lateralization features are altered in end-stage knee osteoarthritis (esKOA). In this study, we performed resting-state functional magnetic imaging on 46 esKOA patients and 31 healthy controls (HCs) and compared with the global and inter-hemisphere network to clarify the hemispheric functional network lateralization characteristics of patients. A correlation analysis was performed to explore the relationship between the inter-hemispheric network parameters and clinical features of patients. The node attributes were analyzed to explore the factors changing in the hemisphere network function lateralization in patients. We found that patients and HCs exhibited "small-world" brain network topology. Clustering coefficient increased in patients compared with that in HCs. The hemisphere difference in inter-hemispheric parameters including assortativity, global efficiency, local efficiency, clustering coefficients, small-worldness, and shortest path length. The pain course and intensity of esKOA were positively correlated with the right hemispheric lateralization in local efficiency, clustering coefficients, and the small-worldness, respectively. The significant alterations of several nodal properties were demonstrated within group in pain-cognition, pain-emotion, and pain regulation circuits. The abnormal lateralization inter-hemisphere network may be caused by the destruction of regional network properties.
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Lateralidad Funcional , Imagen por Resonancia Magnética , Osteoartritis de la Rodilla , Humanos , Masculino , Femenino , Osteoartritis de la Rodilla/fisiopatología , Persona de Mediana Edad , Lateralidad Funcional/fisiología , Imagen por Resonancia Magnética/métodos , Anciano , Encéfalo/fisiopatología , Red Nerviosa/fisiopatología , Red Nerviosa/diagnóstico por imagen , Mapeo Encefálico/métodos , AdultoRESUMEN
In order to cope with the complexity and variability of the terrestrial environment, amphibians have developed a wide range of reproductive and parental behaviors. Nest building occurs in some anuran species as parental care. Species of the Music frog genus Nidirana are known for their unique courtship behavior and mud nesting in several congeners. However, the evolution of these frogs and their nidification behavior has yet to be studied. With phylogenomic and phylogeographic analyses based on a wide sampling of the genus, we find that Nidirana originated from central-southwestern China and the nidification behavior initially evolved at ca 19.3 Ma but subsequently lost in several descendants. Further population genomic analyses suggest that the nidification species have an older diversification and colonization history, while N. adenopleura complex congeners that do not exhibit nidification behavior have experienced a recent rapid radiation. The presence and loss of the nidification behavior in the Music frogs may be associated with paleoclimatic factors such as temperature and precipitation. This study highlights the nidification behavior as a key evolutionary innovation that has contributed to the diversification of an amphibian group under past climate changes.
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Anuros , Filogenia , Animales , Anuros/fisiología , Anuros/genética , China , Filogeografía , Cambio Climático , Evolución Biológica , Comportamiento de NidificaciónRESUMEN
Background: GLI3 gene mutations can result in various forms of polysyndactyly, such as Greig cephalopolysyndactyly syndrome (GCPS, MIM: #175700), Pallister-Hall syndrome (PHS, MIM: #146510), and isolated polydactyly (IPD, MIM: #174200, #174700). Reports on IPD-associated GLI3 mutations are rare. In this study, a novel GLI3 mutation was identified in a Chinese family with IPD. Results: We report a family with six members affected by IPD. The family members demonstrated several special phenotypes, including sex differences, abnormal finger joint development, and different polydactyly types. We identified a novel frameshift variant in the GLI3 gene (NM_000168.6: c.1820_1821del, NP_000159.3: p.Tyr607Cysfs*9) by whole-exome sequencing. Further analysis suggested that this mutation was the cause of polydactyly in this family. Conclusions: The discovery of this novel frameshift variant in our study further solidifies the relationship between IPD and GLI3 and expands the previously established spectrum of GLI3 mutations and associated phenotypes.
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The study investigated the effect of different sodium chloride (NaCl) concentrations (10%, 15%, and 20%) on the ripening fermentation of Pixian-Douban, a traditional fermented condiment. The results showed that NaCl affected the dynamics of physicochemical parameters, volatile components, fatty acids, amino metabolites, organic acids, and microbial composition, and their dynamic modes were different. After 253 days fermentation, the 10% NaCl Pixian-Douban had significantly (p < 0.05) higher levels of total organic acids (20,308.25 mg/kg), amino metabolites (28,144.96 mg/kg), and volatiles (3.36 mg/kg) compared to 15% and 20% NaCl Pixian-Douban. Notably, the possible health risk associated with high concentration of biogenic amines in 10% NaCl Pixian-Douban is of concern. Moreover, correlation analyses indicated that the effect of NaCl on the quality of Pixian-Douban may be mainly related to bacteria. This study deepens the knowledge about the role of NaCl in ripening fermentation of Pixian-Douban and contributes to develop low-NaCl Pixian-Douban product.
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Bacterias , Fermentación , Cloruro de Sodio , Cloruro de Sodio/metabolismo , Cloruro de Sodio/farmacología , Cloruro de Sodio/análisis , Bacterias/metabolismo , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/efectos de los fármacos , Compuestos Orgánicos Volátiles/metabolismo , Compuestos Orgánicos Volátiles/química , Alimentos Fermentados/análisis , Alimentos Fermentados/microbiología , Ácidos Grasos/metabolismo , Ácidos Grasos/química , Condimentos/análisis , Condimentos/microbiología , Aminoácidos/metabolismo , Aminoácidos/análisisRESUMEN
Based on the widespread application and under-research of mechanized preparation Cantonese soy sauce koji (MP), absolute quantitative approaches were utilized to systematically analyze the flavor formation mechanism in MP. The results indicated that the enzyme activities increased greatly during MP fermentation, and 4 organic acids, 15 amino acids, and 2 volatiles were identified as significantly different flavor actives. The flavor parameters of MP4 were basically identical to those of MP5. Furthermore, microorganisms were dominated by Staphylococcus, Weissella, and Aspergillus in MP, and their biomass demonstrated an increasing trend. A precise enumeration of microorganisms exposed the inaccuracy of relative quantitative data. Concurrently, Staphylococcus and Aspergillus were positively correlated with numerous enzymes and flavor compounds, and targeted strains for enhancing MP quality. The flavor formation network comprises pathways including carbohydrate metabolism, lipid metabolism and oxidation, and protein degradation and amino acid metabolism. In summary, the fermentation period of MP can be substantially shortened without compromising the product quality. These findings lay the groundwork for refining parameters in modern production processes.
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Alimentos de Soja , Fermentación , Metabolómica , Aminoácidos , ÁcidosRESUMEN
To investigate the mechanism of flavor formation during the traditional preparation Cantonese soy sauce koji (TP), the changes of microorganisms, physicochemical properties, and flavor compounds in TP were comprehensively and dynamically monitored by absolute quantitative methods. Results demonstrated that inoculating Aspergillus oryzae 3.042 in TP was crucial role in enhancing enzyme activity properties. Absolute quantification of flavor combined with multivariate statistical analysis yielded 5 organic acids, 15 amino acids, and 2 volatiles as significantly different flavors of TP. Amplicon sequencing and RT-qPCR revealed that the dominant genera were Staphylococcus, Weissella, Enterobacter, Lactic streptococci, Lactobacillus, and Aspergillus, which exhibited a increasing trend in TP. Correlation analysis exhibited that Staphylococcus and Aspergillus were the pivotal genera contributing to the enzyme activities and flavor of TP. The flavor formation network involved lipid and protein degradation, carbohydrate metabolism and other pathways. Simultaneously, TP can appropriately increase the fermentation time to improve product quality.
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Aspergillus oryzae , Alimentos de Soja , Alimentos de Soja/análisis , Fermentación , Aminoácidos/metabolismo , Ácidos/metabolismoRESUMEN
The olfactory bulbectomy (OBX) animal model of depression reproduces the behavioral and neurochemical changes observed in depressed patients. We assessed the therapeutic effects of the Jieyu Chufan (JYCF) capsule on OBX rats. JYCF ameliorated the hedonic and anxiety-like behavior of OBX rats and attenuated the cortical and hippocampal damage. JYCF enhanced the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2), and adiponectin (ADPN) in the cortex and hippocampus of OBX rats. JYCF also reduced cortisol levels and restored the levels of excitatory neurotransmitters, such as 5-hydroxytryptamine (5-HT), acetylcholine (ACH), and glutamic acid (Glu), in the brain tissue of OBX rats. Our results suggest that JYCF preserves the synaptic structure by increasing the levels of synaptophysin (SYN) and postsynaptic density protein 95 (PSD95) and alleviates the histological alterations of brain tissue by activating AKT/PKA-CREB-BDNF pathways, and by upregulating ADPN and FGF2 expression in OBX rats. JYCF exerts multiple therapeutic effects on depression, including modulating neurotransmitters, repairing neuronal damage, and maintaining synaptic integrity. These findings support the potential of JYCF as a novel antidepressant agent with therapeutic effects on depression and related neurological disorders.
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Factor Neurotrófico Derivado del Encéfalo , Depresión , Humanos , Ratas , Animales , Depresión/tratamiento farmacológico , Depresión/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Neurotransmisores/metabolismo , Bulbo Olfatorio/metabolismo , Modelos Animales de EnfermedadRESUMEN
Phenyllactic acid (PLA), a promising food preservative, is safe and effective against a broad spectrum of food-borne pathogens. However, its mechanisms against toxigenic fungi are still poorly understood. In this study, we applied physicochemical, morphological, metabolomics, and transcriptomics analyses to investigate the activity and mechanism of PLA inhibition of a typical food-contaminating mold, Aspergillus flavus. The results showed that PLA effectively inhibited the growth of A. flavus spores and reduced aflatoxin B1 (AFB1) production by downregulating key genes associated with AFB1 biosynthesis. Propidium iodide staining and transmission electron microscopy analysis demonstrated a dose-dependent disruption of the integrity and morphology of the A. flavus spore cell membrane by PLA. Multi-omics analyses showed that subinhibitory concentrations of PLA induced significant changes in A. flavus spores at the transcriptional and metabolic levels, as 980 genes and 30 metabolites were differentially expressed. Moreover, KEGG pathway enrichment analysis indicated PLA-induced cell membrane damage, energy-metabolism disruption, and central-dogma abnormality in A. flavus spores. The results provided new insights into the anti-A. flavus and -AFB1 mechanisms of PLA.
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Aflatoxina B1 , Aspergillus flavus , Aspergillus flavus/metabolismo , Aflatoxina B1/metabolismo , Lactatos/metabolismo , Poliésteres/metabolismo , Poliésteres/farmacologíaRESUMEN
The objective of this research is to explore the potential of financial inclusion and low-carbon architectural design strategies as solutions to improve the thermal comfort and energy efficiency of new buildings in different architectural climate conditions. The manufacture sector, which accounts for about 40% of all yearly greenhouse gas releases, has been stimulating with trying to reduce the amount of energy it consumes and the detrimental effects it has on the climate, in accordance with the standards outlined in the 2016 Paris Agreement. In this study, panel data analysis is used to examine the connection between green property financing and carbon dioxide emissions from the building sector in one hundred and five developed and developing countries. Although this analysis finds a negative correlation among the development of environmentally friendly real estate financing and firms' worldwide carbon dioxide emissions, it finds that this correlation is most robust in developing nations. A number of these countries are experiencing an unregulated and rapid population explosion, which has boosted their demand for oil, making this discovery essential for them. The difficulty in securing green funding during this crisis is slowing and even reversing gains made in past years, making it all the more important to keep this momentum going during the COVID-19 outbreak. It's critical to keep the momentum going by doing something.
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COVID-19 , Gases de Efecto Invernadero , Humanos , Temperatura , Dióxido de Carbono/análisis , Clima , Desarrollo EconómicoRESUMEN
Catalase (CAT) is an important antioxidant enzyme that breaks down H2O2 into water and oxygen. Inhibitor-modulating CAT activity in cancer cells is emerging as a potential anticancer strategy. However, the discovery of CAT inhibitors towards the heme active center located at the bottom of long and narrow channel has made little progress. Therefore, targeting new binding site is of great importance for the development of efficient CAT inhibitors. Here, the first NADPH-binding site inhibitor of CAT, BT-Br, was designed and synthesized successfully. The cocrystal structure of BT-Br-bound CAT complex was determined with a resolution of 2.2 Å (PDB ID:8HID), which showed clearly that BT-Br bound at the NADPH-binding site. Furthermore, BT-Br was demonstrated to induce ferroptosis in castration-resistant prostate cancer (CRPC) DU145 cells and eventually reduce CRPC tumors in vivo effectively. The work indicates that CAT has potential as a novel target for CRPC therapy based on ferroptosis inducing.
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Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Catalasa/genética , Catalasa/metabolismo , NADP/metabolismo , Peróxido de Hidrógeno , Antioxidantes , Sitios de Unión , Línea Celular TumoralRESUMEN
Introduction: Osteoarthritis is a chronic, ongoing disease that affects patients, and pain is considered a key factor affecting patients, but the brain changes during the development of osteoarthritis pain are currently unclear. In this study, we used electroacupuncture (EA) to intervene the rat model of knee osteoarthritis and analyzed the changes in topological properties of brain networks using graph theory. Methods: Sixteen SD rat models of right-knee osteoarthritis with anterior cruciate ligament transection (ACLT) were randomly divided into electroacupuncture intervention group and control group. The electroacupuncture group was intervened on Zusanli (ST36) and Futu (ST32) for 20 min each time, five times a week for 3 weeks, while the control group was applied sham stimulation. Both groups were measured for pain threshold. The small-world properties and node properties of the brain network between the two groups after the intervention were statistically analyzed by graph theory methods. Results: The differences are mainly in the changes in node attributes between the two groups, such as degree centrality, betweenness centrality, and so on in different brain regions (P<0.05). Both groups showed no small-world characteristics in the brain networks of the two groups. The mechanical thresholds and thermal pain thresholds were significantly higher in the EA group than in the control group (P<0.05). Conclusion: The study demonstrated that electroacupuncture intervention enhanced the activity of nodes related to pain circuit and relieved pain in osteoarthritis, which provides a complementary basis for explaining the effect of electroacupuncture intervention on pain through graphical analysis of changes in brain network topological properties and helps to develop an imaging model for pain affected by electroacupuncture.
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The subfamily Megophryinae, as a representative batrachian group of the Oriental Realm and one of the most diverse groups of amphibians, has attracted considerable attention due to continued conjecture regarding its generic classification and failure to reach a satisfactory consensus. China boasts the richest diversity of Asian horned toads, containing some two thirds of the total species cataloged. However, most species have a complicated taxonomic history, resulting in multiple misidentifications. As such, an overall clarification of historical records and regional checklists is required. In the current investigation, we established the phylogeny of the Asian horned toads and performed detailed examinations with redefinitions of several important morphological traits. Based on the phylogenetic relationships and morphological differences, we propose a new ten-genus classification for the Asian horned toad subfamily Megophryinae: i.e., Brachytarsophrys, Atympanophrys, Grillitschia, Sarawakiphrys gen. nov., Jingophrys gen. nov., Xenophrys, Megophrys, Pelobatrachus, Ophryophryne, and Boulenophrys. Revisions on the diagnosability, distribution, and content of each genus are provided. Furthermore, we present a careful review of the taxonomic history of Asian horned toad species from China and provide a monograph of congeners, including six species of Brachytarsophrys, four species of Atympanophrys, five species of Jingophrys gen. nov., 10 species of Xenophrys, two species of Ophryophryne, and 60 species of Boulenophrys. Finally, we discuss the importance of traditional morphological traits based on multiple populations in taxonomic work as well as taxonomic inflation caused by the genetic species delimitation.
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Anuros , Bufonidae , Animales , Filogenia , Bufonidae/genética , ChinaRESUMEN
Cardiac glycosides (CGs) are candidate anticancer agents that function by increasing [Ca2+]i to induce apoptotic cell death in several types of cancer cells. However, new findings have shown that the anticancer effects of CGs involve complex cellsignal transduction mechanisms. Hence, exploring the potential mechanisms of action of CGs may provide insight into their anticancer effects and thus aid in the selection of the appropriate CG. Periplocymarin (PPM), which is a cardiac glycoside, is an active ingredient extracted from Cortex periplocae. The role of PPM was evaluated in HepG2 cells and xenografted nude mice. Cell proliferation, realtime ATP rate assays, western blotting, cell apoptosis assays, short interfering RNA transfection, the patch clamp technique, electron microscopy, JC1 staining, immunofluorescence staining and autophagic flux assays were performed to evaluate the function and regulatory mechanisms of PPM in vitro. The in vivo activity of the PPM was assessed using a mouse xenograft model. The present study demonstrated that PPM synchronously activated lethal apoptosis and protective autophagy in liver cancer, and the initiation of autophagy counteracted the inherent proapoptotic capacity and impaired the anticancer effects. Specifically, PPM exerted a pro-apoptotic effect in HepG2 cells and activated macroautophagy by initiation of the AMPK/ULK1 and mTOR signaling pathways. Activation of macroautophagy counteracted the proapoptotic effects of PPM, but when it was combined with an autophagy inhibitor, the anticancer effects of PPM in mice bearing HepG2 xenografts were observed. Collectively, these results indicated that a selflimiting effect impaired the proapoptotic effects of PPM in liver cancer, but when combined with an autophagy inhibitor, it may serve as a novel therapeutic option for the management of liver cancer.
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Glicósidos Cardíacos , Neoplasias Hepáticas , Animales , Ratones , Humanos , Ratones Desnudos , Proteínas Quinasas Activadas por AMP/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Glicósidos Cardíacos/farmacología , Autofagia , Apoptosis , Línea Celular Tumoral , Proliferación CelularRESUMEN
INTRODUCTION: We aimed to evaluate the efficacy of electroacupuncture in relieving acute pain after total knee arthroplasty (TKA) and related mechanism. METHODS: In this randomized, single-blind, and sham-acupuncture controlled study. Forty patients with postoperative acute pain were recruited and randomly divided electroacupuncture group (n = 20) and sham-acupuncture group (n = 20) from November 2020 to October 2021. All patients received electroacupuncture or sham-acupuncture for 5 days after TKA. Their brain regions were scanned with resting-state functional magnetic resonance imaging before and after intervention. Pain was scaled. Another 40 matched healthy controls underwent scanning once. The amplitude of low-frequency fluctuation (ALFF) values was compared. Pearson's correlation analysis was utilized to explore the correlation of ALFF with clinical variables in patients after intervention. RESULTS: Compared with the HCs, patients with acute pain following TKA had significantly decreased ALFF value in right middle frontal gyrus, right supplementary motor area, bilateral precuneus, right calcarine fissure and surrounding cortex, and left triangular part of inferior frontal gyrus (false discovery rate corrected p < .05). Patients had higher ALFF value in bilateral precuneus, right cuneus, right angular gyrus, bilateral middle occipital gyrus, and left middle temporal gyrus after electroacupuncture (AlphaSim corrected p < .01). Correlation analysis revealed that the change (postoperative day 7 to postoperative day 3) of ALFF in bilateral precuneus were negatively correlated with the change of NRS scores (r = -0.706; p = .002; 95% CI = -0.890 to -0.323) in EA group. CONCLUSIONS: The functional activities of related brain regions decreased in patients with acute pain after TKA. The enhancement of the functional activity of precuneus may be the neurobiological mechanism of electroacupuncture in treating pain following TKA.
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Dolor Agudo , Artroplastia de Reemplazo de Rodilla , Electroacupuntura , Corteza Motora , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Imagen por Resonancia Magnética/métodos , Método Simple Ciego , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Mapeo Encefálico , Plasticidad Neuronal , Dolor Postoperatorio/terapiaRESUMEN
BACKGROUND: Sophoridine (SR) has shown the potential to be an antiarrhythmic agent. However, SR's electrophysiological properties and druggability research are relatively inadequate, which limits the development of SR as an antiarrhythmic candidate. PURPOSE: To facilitate the development process of SR as an antiarrhythmic candidate, we performed integrated studies on the electrophysiological properties of SR in vitro and ex vivo to gain more comprehensive insights into the multi-ion channel blocking effects of SR, which provided the foundation for the further drugability studies in antiarrhythmic and safety studies. Firstly, SR's electrophysiological properties and antiarrhythmic potentials were recorded and assessed at the cell and tissue levels by comprehensively integrating the patch clamp with the Electrical and Optical Mapping systems. Subsequently, the antiarrhythmic effects of SR were validated by aconitine and ouabain-induced arrhythmia in vivo. Finally, the safety of SR as an antiarrhythmic candidate compound was evaluated based on the guidelines of the Comprehensive in Vitro Proarrhythmia Assay (CiPA). STUDY DESIGN: The antiarrhythmic effect of SR was evaluated at the in vitro, ex vivo, and in vivo levels. METHODS: Isolated primary cardiomyocytes and stable cell lines were prepared to explore the electrophysiologic properties of being a multiple ion-channel blocker in vitro by whole-cell patch clamp. Using electrical and optical mapping, the negative chronotropic effect of SR was determined in langendorff-perfused rat or guinea-pig hearts.The antiarrhythmic activity of SR was assessed by the ex vivo tachyarrhythmia models induced by left coronary artery ligation (LCAL) and isoproterenol (ISO). Canonical models of aconitine and ouabain-induced arrhythmia were used to verify the antiarrhythmic effects in vivo. Finally, the pro-arrhythmic risk of SR was detected in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hSCCMs) using a Microelectrode array (MEA). RESULTS: Single-cell patch assay validated the multiple ion-channel blockers of SR in transient outward current potassium currents (Ito), l-type calcium currents (ICa-l), and rapid activation delayed rectifier potassium currents (IKr). SR ex vivo depressed heart rates (HR) and ventricular conduction velocity (CV) and prolonged Q-T intervals in a concentration-dependent manner. Consistent with the changes in HRs, SR extended the active time of hearts and increased the action potential duration measured at 90% repolarization (APD90). SR could also significantly lengthen the onset time and curtail the duration of spontaneous ventricular tachycardia (VT) in the ex vivo arrhythmic model induced by LCAL. Meanwhile, SR could also significantly upregulate the programmed electrical stimulation (PES) frequency after the ISO challenge in forming electrical alternans and re-entrant excitation. Furthermore, SR exerted antiarrhythmic effects in the tachyarrhythmia models induced by aconitine and ouabain in vivo. Notably, the pro-arrhythmic risk of SR was shallow for a moderate inhibition of the human ether-à-go-go-related gene (hERG) channel. Moreover, SR prolonged field potential duration (FPDc) of hSCCMs in a concentration-dependent manner without early after depolarization (EAD) and arrhythmia occurrence. CONCLUSION: Our results indicated that SR manifested as a multiple ion-channel blocker in the electrophysiological properties and exerts antiarrhythmic effects ex vivo and in vivo. Meanwhile, due to the low pro-arrhythmic risk in the hERG inhibition assay and the induction of EAD, SR has great potential as a leading candidate in the treatment of ventricular tachyarrhythmia.
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Antiarrítmicos , Matrinas , Ratas , Humanos , Animales , Cobayas , Antiarrítmicos/efectos adversos , Ouabaína/metabolismo , Ouabaína/farmacología , Ouabaína/uso terapéutico , Aconitina/farmacología , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/tratamiento farmacológico , Canales Iónicos/metabolismo , Canales Iónicos/farmacología , Miocitos Cardíacos , Isoproterenol , Potasio/metabolismo , Potasio/farmacología , Potasio/uso terapéutico , Potenciales de Acción/fisiologíaRESUMEN
In this study, the physicochemical properties, metabolites, sensory characteristics, and microbiota of black glutinous rice wine (BGRW) during traditional fermentation (TF) and inoculated fermentation (IF) were investigated, and their correlation relationships were revealed. Results indicated that IF promoted total sugar utilization and ethanol and esters synthesis in BGRW. Altogether 67 reliable metabolites were identified, 36 of which were labeled components, primarily esters (OAV > 1). Meanwhile, the concentrations of ethanol, esters, and total flavor on the 11th day of IF were close to those on the 22nd day of TF. Combined with the sensory description indicated that the IF could improve the quality of BGRW. Besides, TF contains vast unfavorable microorganisms, such as Chaetomium, Penicillium, Stachybotrys, and Trichocladium. Therefore, IF can accelerate the fermentation and enhance the flavor of BGRW, and inhibit the growth of pathogenic and spoilage organisms. Finally, Pearson's correlation analysis demonstrated that Saccharomyces, Rhizopus, Lactobacillus, Aspergillus, and Bacillus were the pivotal functional microorganisms in BGRW. The study provided scientific and effective basis for improving the quality, shortening the fermentation cycle, and controlling pathogenic and spoilage organisms of BGRW.
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Microbiota , Vino , Fermentación , Rhizopus oryzae , Saccharomyces cerevisiae , Etanol , ÉsteresRESUMEN
Traditional fermentation of dry mutton sausages (DMSs) commonly causes some quality problems. In this study, high-throughput sequencing (HTS) and metabolomics were used to study the microorganisms and metabolites of DMSs produced by mixed strains of Pediococcus acidilactici and Rhizopus Oryzae, to discover the effect of inoculated fermentation (IF) on the metabolites of DMSs. A total of 92 volatile metabolites and 58 non-volatile significantly different metabolites were identified in DMSs. After inoculated fermentation, the volatile types increased, and the total contents of aldehydes and esters were enhanced at the end of fermentation. In addition, the levels of amino acids, fatty acids, palmitoyl carnitine, acetyl-l-carnitine, and betaine were also improved. The correlation analysis showed that the P. acidilactici and R. Oryzae were highly correlated with a variety of metabolites. Together, these findings provide excellent strain resources for improving the quality of mutton sausages.