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Ochratoxin A (OTA) is a common fungal toxin frequently detected in food and human plasma samples. Currently, the physiologically based toxicokinetic (PBTK) model plays an active role in dose translation and can improve and enhance the risk assessment of toxins. In this study, the PBTK model of OTA in rats and humans was established based on knowledge of OTA-specific absorption, distribution, metabolism, and excretion (ADME) in order to better explain the disposition of OTA in humans and the discrepancies with other species. The models were calibrated and optimized using the available kinetic and toxicokinetic (TK) data, and independent test datasets were used for model evaluation. Subsequently, sensitivity analyses and population simulations were performed to characterize the extent to which variations in physiological and specific chemical parameters affected the model output. Finally, the constructed models were used for dose extrapolation of OTA, including the rat-to-human dose adjustment factor (DAF) and the human exposure conversion factor (ECF). The results showed that the unbound fraction (Fup) of OTA in plasma of rat and human was 0.02-0.04% and 0.13-4.21%, respectively. In vitro experiments, the maximum enzyme velocity (Vmax) and Michaelis-Menten constant (Km) of OTA in rat and human liver microsomes were 3.86 and 78.17⯵g/g min-1, 0.46 and 4.108⯵g/mL, respectively. The predicted results of the model were in good agreement with the observed data, and the models in rats and humans were verified. The PBTK model derived a DAF of 0.1081 between rats and humans, whereas the ECF was 2.03. The established PBTK model can be used to estimate short- or long-term OTA exposure levels in rats and humans, with the capacity for dose translation of OTA to provide the underlying data for risk assessment of OTA.
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Modelos Biológicos , Ocratoxinas , Toxicocinética , Ocratoxinas/toxicidad , Ocratoxinas/farmacocinética , Animales , Ratas , Humanos , Medición de Riesgo , MasculinoRESUMEN
Parkinson's disease is a health-threatening neurodegenerative disease of the elderly with clinical manifestations of motor and non-motor deficits such as tremor palsy and loss of smell. Alpha-synuclein (α-Syn) is the pathological basis of PD, it can abnormally aggregate into insoluble forms such as oligomers, fibrils, and plaques, causing degeneration of nigrostriatal dopaminergic neurons in the substantia nigra in the patient's brain and the formation of Lewy bodies (LBs) and Lewy neuritis (LN) inclusions. As a result, achieving α-Syn aggregate detection in the early stages of PD can effectively stop or delay the progression of the disease. In this paper, we provide a brief overview and analysis of the molecular structures and α-Syn in vivo and in vitro detection methods, such as mass spectrometry, antigen-antibody recognition, electrochemical sensors, and imaging techniques, intending to provide more technological support for detecting α-Syn early in the disease and intervening in the progression of Parkinson's disease.
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Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Anciano , Humanos , Enfermedad de Parkinson/diagnóstico , alfa-Sinucleína , Biomarcadores , TemblorRESUMEN
BACKGROUND: Vacuum sealing drainage (VSD) is widely applied in complex wound repair. We aimed to compare traditional debridement and drainage and VSD in treating Fournier's gangrene (FG). METHODS: Data of patients surgically treated for FG were retrospectively analyzed. RESULTS: Of the 36 patients (men: 31, women: 5; mean age: 53.5 ± 11.3 [range: 28-74] years) included in the study, no patients died. Between-group differences regarding sex, age, BMI, time from first debridement to wound healing, number of debridements, FGSI, and shock were not statistically significant (P > 0.05). However, lesion diameter, colostomy, VAS score, dressing changes, analgesic use, length of hospital stay, and wound reconstruction method (χ2 = 5.43, P = 0.04) exhibited statistically significant differences. Tension-relieving sutures (6 vs. 21) and flap transfer (4 vs. 2) were applied in Groups I and II, respectively. CONCLUSION: VSD can reduce postoperative dressing changes and analgesic use, and shrunk the wound area, thereby reducing flap transfer in wound reconstruction.
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Gangrena de Fournier , Terapia de Presión Negativa para Heridas , Masculino , Humanos , Femenino , Adulto , Persona de Mediana Edad , Gangrena de Fournier/cirugía , Estudios Retrospectivos , Desbridamiento/métodos , DrenajeRESUMEN
As an emerging sequencing technology, single-cell RNA sequencing (scRNA-Seq) has become a powerful tool for describing cell subpopulation classification and cell heterogeneity by achieving high-throughput and multidimensional analysis of individual cells and circumventing the shortcomings of traditional sequencing for detecting the average transcript level of cell populations. It has been applied to life science and medicine research fields such as tracking dynamic cell differentiation, revealing sensitive effector cells, and key molecular events of diseases. This review focuses on the recent technological innovations in scRNA-Seq, highlighting the latest research results with scRNA-Seq as the core technology in frontier research areas such as embryology, histology, oncology, and immunology. In addition, this review outlines the prospects for its innovative application in traditional Chinese medicine (TCM) research and discusses the key issues currently being addressed by scRNA-Seq and its great potential for exploring disease diagnostic targets and uncovering drug therapeutic targets in combination with multiomics technologies.
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Secuenciación de Nucleótidos de Alto Rendimiento , Análisis de la Célula Individual , Análisis de la Célula Individual/métodos , Análisis de Secuencia de ARN/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Multiómica , Tecnología , Perfilación de la Expresión Génica/métodosRESUMEN
ABC efflux proteins are a kind of transporters mediating diversified endogenous and exogenous efflux protein substrates across the plasma membrane by depending on the chemical energy released by ATP hydrolysis. As a vitally important functional membrane, it is widely found in various tissues and organs. The drug changes the expressions and/or functions of the transport proteins, which will affect the disposal process of substrate drugs corresponding to transporters in vivo, and finally lead to the pharmacokinetic interactions. The efflux proteins take part in the absorption, distribution, metabolism and excretion of drugs, and mainly consist of P-glycoprotein(P-gp), multidrug resistance associated protein(MRP) and breast cancer resistance protein(BCRP). The induction effect or inhibition effect of drugs on efflux protein plays a greatly significant role in the drug interaction produced by the compatibility of traditional Chinese medicine, which may be one of the important mechanisms of the theory of seven features of compatibility. In this article, the effects of seven features of compatibility on the ABC efflux transporters were reviewed, in order to reveal the roles of efflux protein in the herb-pairs compatibility, and provide new ideas for the mechanism and rationality of herb compatibility.
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Transportadoras de Casetes de Unión a ATP/metabolismo , Medicina Tradicional China , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Preparaciones de Plantas/farmacología , Interacciones Farmacológicas , HumanosRESUMEN
More and more studies demonstrated that ß2 adrenergic receptor (ß2-AR) plays a crucial role for the treatment of heart failure. Chuanwu and Fuzi have been used over thousands of years in China for the treatment of heart failure. Considering the effects of these herbs are very similar to ß2-AR agonists, we presume whether ß2-AR agonists can be found from Fuzi and Chuanwu. Fuzi and Chuanwu decoction were used to receive the luciferase reporter activity assay to verify the hypothesis, and the result is positive and encouraging. For it is very difficult to get all of the monomer compounds of Fuzi and Chuanwu, virtual screening was used to find potential ß2-AR agonists and a cell-based ß2-AR agonist functional evaluation model, combined with a luciferase reporter assay system, was used to confirm the final result. In this research, 45 compounds were identified as ß2-AR agonists, and four compounds were verified and the rest need further experiment.
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Agonistas de Receptores Adrenérgicos beta 2/farmacología , Luciferasas/metabolismo , Extractos Vegetales/química , China , Diterpenos , Medicamentos Herbarios Chinos , Humanos , Estructura Molecular , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: Resveratrol, a phytoalexin, is reported to activate AMP-activated protein kinase (AMPK) in vascular cells. Activation of AMPK induces vasorelaxation to lower blood pressure (BP). Whether resveratrol via activation of AMPK decreases, BP remains unknown. METHODS: Male wild-type (WT) mice and mice deficient in AMPKα2 (AMPKα2(-/-)) were fed with resveratrol (400 mg/kg). After 7 d, mice were implanted with deoxycorticosterone acetate (DOCA)-salt (150 mg/kg) for 35 d. BP was detected by the radiotelemetry method. Vessel contraction was determined by organ chamber. Active RhoA, Rho-associated kinase (ROCK) activity, phosphorylations of myosin light chain (MLC), and myosin phosphatase targeting subunit 1 (MYPT1) were assayed by western blot. RESULTS: Implantation of DOCA-salt dramatically increased systemic BPs (systolic BP and diastolic BP) in WT and AMPKα2(-/-) mice. However, treatment of resveratrol significantly decreased systemic BP in WT mice but not in AMPKα2(-/-) mice. In the organ chamber study, resveratrol inhibited agonist-induced vessel relaxation in WT mice aortas. Loss of AMPKα2 or AMPK inhibition by compound C reversed resveratrol-suppressed vasoconstriction in isolated mice aortas. In cultured vascular smooth muscle cells (VSMCs), activation of AMPK by resveratrol inhibited phenylephrine-enhanced MLC phosphorylation in a dose-dependent manner. CONCLUSIONS: Resveratrol via activation of AMPK lowers BP in DOCA-hypertensive mice through an AMPK/RhoA/ROCK2/MLCMLC pathway.
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Proteínas Quinasas Activadas por AMP/metabolismo , Presión Sanguínea/fisiología , Hipertensión/tratamiento farmacológico , Músculo Liso Vascular/efectos de los fármacos , Estilbenos/farmacología , Proteínas Quinasas Activadas por AMP/efectos de los fármacos , Animales , Anticarcinógenos/farmacología , Presión Sanguínea/efectos de los fármacos , Acetato de Desoxicorticosterona/toxicidad , Modelos Animales de Enfermedad , Activación Enzimática , Hipertensión/metabolismo , Hipertensión/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiopatología , Resveratrol , Vasoconstricción/efectos de los fármacos , Vasoconstricción/fisiología , VasodilatadoresRESUMEN
The Chinese herb Qianghuo is an antiphlogistic herb with many effects and complex components. In this study, the chemical composition of Qianghuo and its components in rat plasma after oral administration were investigated using ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). The extracts, blank plasma, and plasma containing the drug were analyzed by mass spectrometry, and data collected in both positive and negative ion modes were analyzed using Masslynx software, and the structures were confirmed by combining the compound fragment ions and mass spectrometry cleavage pathways. A total of 62 in vitro chemical components were identified, including 27 coumarins, 18 organic acids, 5 amino acids, 5 glycosides, 2 flavonoids, 4 nucleotides, and 1 ester, which were summarized from the obtained compounds in terms of their possible cleavage patterns. Among the identified 31 compounds in rat plasma, 21 were prototypes, mostly coumarins, organic acids, and flavonoids, and 10 were metabolites, which were mainly generated via hydroxylation and methylation pathways. Based on these, this study provides a theoretical foundation for quality control and basic research on Qianghuo medicinal substances.
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Medicamentos Herbarios Chinos , Espectrometría de Masas en Tándem , Ratas , Animales , Espectrometría de Masas en Tándem/métodos , Medicamentos Herbarios Chinos/química , Cromatografía Líquida de Alta Presión/métodos , Estructura Molecular , Flavonoides/análisis , Ácidos , Cumarinas/análisisRESUMEN
BACKGROUND: Gastrointestinal stromal tumors (GISTs) are typical gastrointestinal tract neoplasms. Imatinib is the first-line therapy for GIST patients. Drug resistance limits the long-term effectiveness of imatinib. The regulatory effect of insulin-like growth factor 2 (IGF2) has been confirmed in various cancers and is related to resistance to chemotherapy and a worse prognosis. AIM: To further investigate the mechanism of IGF2 specific to GISTs. METHODS: IGF2 was screened and analyzed using Gene Expression Omnibus (GEO: GSE225819) data. After IGF2 knockdown or overexpression by transfection, the phenotypes (proliferation, migration, invasion, apoptosis) of GIST cells were characterized by cell counting kit 8, Transwell, and flow cytometry assays. We used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition (EMT)-associated proteins. We injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of GIST. RESULTS: Data from the GEO indicated that IGF2 expression is high in GISTs, associated with liver metastasis, and closely related to drug resistance. GIST cells with high expression of IGF2 had increased proliferation and migration, invasiveness and EMT. Knockdown of IGF2 significantly inhibited those activities. In addition, OE-IGF2 promoted GIST metastasis in vivo in nude mice. IGF2 activated IGF1R signaling in GIST cells, and IGF2/IGF1R-mediated glycolysis was required for GIST with liver metastasis. GIST cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib resistance. Moreover, 2-deoxy-D-glucose (a glycolysis inhibitor) treatment reversed IGF2 overexpression-mediated imatinib resistance in GISTs. CONCLUSION: IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.
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Human telomerase reverse transcriptase (hTERT) may have noncanonical functions in transcriptional regulation and metabolic reprogramming in cancer cells, but it is a challenging target. We thus developed small-molecule ligands targeting hTERT promoter G-quadruplex DNA structures (hTERT G4) to downregulate hTERT expression. Ligand 5 showed high affinity toward hTERT G4 (Kd = 1.1 µM) and potent activity against triple-negative breast cancer cells (MDA-MB-231, IC50 = 1 µM). In cell-based assays, 5 not only exerts markedly inhibitory activity on classical telomere functions including decreased telomerase activity, shortened telomere length, and cellular senescence but also induces DNA damage, acute cellular senescence, and apoptosis. This study reveals that hTERT G4-targeting ligand may cause mitochondrial dysfunction, disrupt iron metabolism and activate ferroptosis in cancer cells. The in vivo antitumor efficacy of 5 was also evaluated in an MDA-MB-231 xenograft mouse model and approximately 78.7% tumor weight reduction was achieved. No observable toxicity against the major organs was observed.
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Antineoplásicos , Regulación hacia Abajo , G-Cuádruplex , Regiones Promotoras Genéticas , Telomerasa , Neoplasias de la Mama Triple Negativas , Telomerasa/antagonistas & inhibidores , Telomerasa/metabolismo , Humanos , G-Cuádruplex/efectos de los fármacos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Animales , Ligandos , Femenino , Regulación hacia Abajo/efectos de los fármacos , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Apoptosis/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Desnudos , Senescencia Celular/efectos de los fármacos , Ratones Endogámicos BALB CRESUMEN
OBJECTIVE: To investigate the status of household disaster preparedness in 4 counties of Shaanxi province and explore the affecting factors. METHODS: During the period from September to October in 2008, multi-stage sampling was used to select subjects from urban and rural residents in Xincheng district, Hantai district, Fuping county and Xunyang county of Shaanxi province. Questionnaire survey was conducted among 1945 subjects aged 18-88 years to investigate their experience and expectation of disaster events, preparedness knowledge, activities and emergency supplies. Logistic regression was used to analyze the factors influencing household disaster preparedness. RESULTS: The average age of the 1945 subjects was (43.55 ± 12.76) years old. A total of 7.12% (138/1939) of respondents never experienced disaster. Earthquake and fire (57.35% (1175/2049), 19.81% (406/2049), respectively) were rated as the two disasters most likely to occur. The awareness rate of knowledge about household disaster preparedness was 51.43% (989/1923), and 23.41% (454/1939) discussed how to prepare for disaster with their family, only 9.27% (179/1932) attended evacuation drill. The rates of preparing household emergency supplies were 23.64% (230/973), 30.56% (55/180), 31.19% (141/452) and 54.49% (97/178) for urban residents, subjects with junior college or above education, subjects having frequent family discussions of disaster preparedness and subjects participating in emergency rescue drills, respectively. For subjects with junior high school, senior high school and junior college or higher education, the likelihood of preparing household emergency supplies was 5.02 (95%CI: 1.12 - 22.42), 5.74 (95%CI: 1.27 - 26.04) and 6.84 (95%CI: 1.44 - 32.39) times as that of illiterate, respectively. Urban residents, subjects who often discussed disaster preparedness with their family, and who participated in emergency rescue drills were more likely to prepare emergency supplies than rural residents (OR = 4.38, 95%CI: 2.74 - 7.00), those who never discussed (OR = 4.99, 95%CI: 2.52 - 9.91), and who didn't participate (OR = 5.72, 95%CI: 3.84 - 8.51). CONCLUSION: The residents in 4 counties of Shaanxi lack comprehensive knowledge and appropriate activities of disaster preparedness, the rate of preparing household emergency supplies is low. Higher education, living in urban area, frequent family discussions of disaster preparedness and participating in emergency rescue drills are facilitating factors of preparing household emergency supplies.
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Desastres , Urgencias Médicas , Conocimientos, Actitudes y Práctica en Salud , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Composición Familiar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The aim was to develop a high performance liquid chromatography method for simultaneous determination of five organic acids in Kudiezi injection. The Diamonsil C18 column (4.6 mm x 200 mm, 5 microm) was adopted with acetonitrile and water as the mobile phase at a gradient mode program. The flow rate was 1.0 mL min-1 , detection wavelength was 325 nm, and column temperature was 35 degree C. The linear range of monocaffeyltartaric acid, chlorogenic acid, caffeic acid, ferulic acid, and chicoric acid were 0. 64-81.60 (r =0. 999 9),0.09-11. 10 (r =0.999 8) ,0.09-11.30 (r =0. 999 8),0.10-12.80 (r =0.999 9),0.43-55. 50 mg L-1 (r = 0.999 8) , respectively. The average recoveries were 101.8% ,100. 9% ,99. 24% ,99. 83% ,101.9%, respectively, with RSD of less than 2.0%. The developed HPLC method was simple, sensitive and accurate with good repeatability. This work provided helpful information for comprehensive quality control of Kudiezi injection. [Key words] Kudiezi injection; organic acids; content determination; HPLC
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Ácidos Cafeicos/análisis , Ácido Clorogénico/análisis , Cromatografía Líquida de Alta Presión/métodos , Ácidos Cumáricos/análisis , Medicamentos Herbarios Chinos/química , Ácido Quínico/análogos & derivados , Succinatos/análisis , Ácido Quínico/análisisRESUMEN
OBJECTIVE: To study the constituents of essential oil from Shunaoxin dropping pills by GC-MS. METHODS: The essential oil from Shunaoxin dropping pills were extracted by absolute alcohol and analyzed by GC-MS. RESULTS: 15 components from the essential oil of Shunaoxin dropping pills were identified. CONCLUSION: The main components in the essential oil of Shunaoxin dropping pills are lactones such as Z-ligustilide, senkyunolide A,3-butylphthalide and 3-butylidenephthalide, other components are organic acids such as ethyl linoleate, 9,12-octadecadienoic acid and ethyl palmitate.
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Angelica/química , Apiaceae/química , Medicamentos Herbarios Chinos/química , Lactonas/análisis , Aceites Volátiles/análisis , 4-Butirolactona/análogos & derivados , 4-Butirolactona/análisis , Benzofuranos/análisis , Medicamentos Herbarios Chinos/aislamiento & purificación , Cromatografía de Gases y Espectrometría de Masas , Aceites Volátiles/aislamiento & purificación , Anhídridos Ftálicos/análisisRESUMEN
Fructus Psoraleae (FP), one of the important traditional Chinese medicines, is widely used in clinic and has been reported to be hepatotoxic. However, there is no report on the mechanism of FP-induced hepatotoxicity based on the theory of You Gu Wu Yun. In this study, plasma samples of rats with different kidney deficiency syndromes were investigated using a lipidomics approach based on UPLC/Q-TOF-MS technique. Firstly, multivariate statistical analysis, VIP value test, statistical test and other methods were used to find the lipid metabolites in the two syndrome model groups that were different from the normal group. The screening of differential lipid metabolites revealed that there were 12 biomarkers between the blank group and the kidney-yang deficiency model group as well as 16 differential metabolites between the kidney-yin deficiency model group, and finally a total of 17 relevant endogenous metabolites were identified, which could be used as differential lipid metabolites to distinguish between kidney-yin deficiency and kidney-yang deficiency evidence. Secondly, the relative content changes of metabolites in rats after administration of FP decoction were further compared to find the substances associated with toxicity after administration, and the diagnostic ability of the identified biomarkers was evaluated using a receiver operating characteristic curve (ROC). Results a total of 14 potential differential lipid metabolites, including LysoPC(20:0/0:0) and LysoPC(16:0/0:0), which may be related to hepatotoxicity in rats with kidney-yin deficiency syndrome were further screened, namely, the potential active lipid metabolites related to hepatotoxicity in rats induced by FP. Finally, cluster analysis, MetPA analysis and KEGG database were used to analyze metabolic pathways. It was discovered that the metabolism of glycerophospholipid and sphingolipid may be strongly related to the mechanism of hepatotoxicity brought on by FP. Overall, we described the lipidomics changes in rats treated with FP decoction and screened out 14 lipid metabolites related to hepatotoxicity in rats with kidney-yin deficiency, which served as a foundation for the theory of "syndrome differentiation and treatment" in traditional Chinese medicine and a guide for further investigation into the subsequent mechanism.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Medicamentos Herbarios Chinos , Trastornos del Metabolismo de los Lípidos , Ratas , Animales , Ratas Sprague-Dawley , Deficiencia Yin/metabolismo , Medicamentos Herbarios Chinos/farmacología , Deficiencia Yang , Lipidómica , Metabolismo de los Lípidos , Riñón/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Trastornos del Metabolismo de los Lípidos/metabolismo , Biomarcadores/metabolismo , LípidosRESUMEN
BACKGROUND: Patients with diabetes mellitus are at higher risk of myocardial ischemia/ reperfusion injury (MI/RI). Shuxin decoction (SXT) is a proven recipe modi-fication from the classic herbal formula "Wu-tou-chi-shi-zhi-wan" according to the traditional Chinese medicine theory. It has been successfully used to alleviate secondary MI/RI in patients with diabetes mellitus in the clinical setting. However, the underlying mechanism is still unclear. AIM: To further determine the mechanism of SXT in attenuating MI/RI associated with diabetes. METHODS: This paper presents an ensemble model combining network pharmacology and biology. The Traditional Chinese Medicine System Pharmacology Database was accessed to select key components and potential targets of the SXT. In parallel, therapeutic targets associated with MI/RI in patients with diabetes were screened from various databases including Gene Expression Omnibus, DisGeNet, Genecards, Drugbank, OMIM, and PharmGKB. The potential targets of SXT and the therapeutic targets related to MI/RI in patients with diabetes were intersected and subjected to bioinformatics analysis using the Database for Annotation, Visualization and Integrated Discovery. The major results of bioinformatics analysis were subsequently validated by animal experiments. RESULTS: According to the hypothesis derived from bioinformatics analysis, SXT could possibly ameliorate lipid metabolism disorders and exert anti-apoptotic effects in MI/RI associated with diabetes by reducing oxidized low density lipoprotein (LDL) and inhibiting the advanced glycation end products (AGE)-receptor for AGE (RAGE) signaling pathway. Subsequent animal experiments confirmed the hypothesis. The treatment with a dose of SXT (2.8 g/kg/d) resulted in a reduction in oxidized LDL, AGEs, and RAGE, and regulated the level of blood lipids. Besides, the expression of apoptosis-related proteins such as Bax and cleaved caspase 3 was down-regulated, whereas Bcl-2 expression was up-regulated. The findings indicated that SXT could inhibit myocardial apoptosis and improve cardiac function in MI/RI in diabetic rats. CONCLUSION: This study indicated the active components and underlying molecular therapeutic mechanisms of SXT in MI/RI with diabetes. Moreover, animal experiments verified that SXT could regulate the level of blood lipids, alleviate cardiomyocyte apoptosis, and improve cardiac function through the AGE-RAGE signaling pathway.
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OBJECTIVE: To investigate the effects of herbs capable of activating blood circulation or inducing diuresis on the expressions of tumor necrosis factor-alpha (TNF-alpha), nuclear factor-kappaB (NF-kappaB), and aquaporin-4 (AQP-4) in rats with intracerebral hemorrhage (ICH), and to study their possible mechanisms. METHODS: The ICH rat model was established by injecting autologous arterial blood into the right caudate nucleus. The 168 male rats were randomly divided into four groups, the sham-operative group, the model group, the blood activating group, and the diuresis inducing group, 42 in each group. Chinese compound decoction (consisting of 0.2 g rhubarb, 0.02 g leech, and 0.3 g notoginseng in each milliliter decoction) was given to rats in the blood activating group by gastrogavage at the dose of 10 mL/kg, once daily. Chinese compound decoction (consisting of 0.2 g poria, 0.2 g water plantain tuber, and 0.2 g acori graninei in each milliliter decoction) was given to rats in the diuresis inducing group by gastrogavage at the dose of 10 mL/kg, once daily. 4.0 mL/kg normal saline was given to rats in the model group and the sham-operative group by gastrogavage, once daily. A series of brain samples were obtained on the 1st, 3rd, and 5th day, respectively. The mRNA and protein expressions of TNFalpha, NF-kappaB p65, and AQP-4 were determined by immunohistochemical staining and Real-time fluorescent quantitative PCR respectively. RESULTS: After ICH, TNF-alpha, NF-KB, and AQP-4 protein positive cells in the brain tissue and their protein and mRNA expressions significantly increased in rats of the model group at each time point when compared with the sham-operative group (P < 0.01, P < 0.05). The gene and protein expressions of TNF-alpha and AQP-4 significantly decreased in the blood activating group and the diuresis inducing group at each time point when compared with the model group (PP < 0.05). The expression of NF-kappaB p65 in the blood activating group obviously decreased when compared with the model group (P < 0.05), but there was no statistical difference in the NF-KB expression when compared with the diuresis inducing group (P > 0.05). Compared with the model group, the water content of the brain tissue decreased to some degree in the blood activating group and the diuresis inducing group at each time point. There was statistical difference between the blood activating group and the diuresis inducing group (P < 0.05). CONCLUSIONS: Chinese herbs capable of activating blood circulation or inducing diuresis could inhibit the release of TNF-alpha, down-regulate the expression of AQP-4, and alleviate the brain edema around hematoma. But the action strength and the effect links were different.
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Acuaporina 4/metabolismo , Encéfalo/metabolismo , Hemorragia Cerebral/metabolismo , Medicamentos Herbarios Chinos/farmacología , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Hemorragia Cerebral/tratamiento farmacológico , Diuresis , Medicamentos Herbarios Chinos/uso terapéutico , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: The role of the intersphincteric space in the pathogenesis of fistula-in-ano is being increasingly recognized. Submucosal and intersphincteric rectal abscesses have been surgically managed by laying open and draining the intersphincteric space as well as by the modified ligation of intersphincteric fistula tract (LIFT) procedure. In 2017, the transanal opening of intersphincteric space (TROPIS) technique was reported for the treatment of high, complex anal fistulae. AIM: We aim to investigate the advantages of performing the TROPIS procedure in patients with fistula-in-ano. METHODS: This was a prospective cohort study investigating the outcomes in patients who had undergone a procedure using the TROPIS technique for the treatment of fistula-in-ano. Preoperative magnetic resonance imaging scans and electronic colonoscopies were performed on all patients. A clinical database evaluating the following variables was constructed: age, gender, body mass index (BMI), previous fistula surgery, type of fistula, postoperative complications, duration of follow-up, success rate, and incontinence scores pre- and postoperatively. RESULTS: The TROPIS procedure was performed on 41 patients with fistula-in-ano with a follow-up time of 6-23 months. The characteristics of the patients were as follows: 36 males, 6 females, mean age 38.6±13.2 years, and mean BMI 23.5±3.9 kg·m-2. All patients (41) had transsphincteric fistulae, and 90.2% (37) had high fistula. Of the 41 patients, 22% (9) had recurrent fistulae, 29.27% (12) had horseshoe fistulae, 7.3% (3) had supralevator fistulae, and 14.6% (6) had an associated abscess. The fistula healed completely in 85.3% (35) of patients and failed to heal in 14.7% (6) of patients, and the healing of high fistula was 86.5% (32). Of those patients who had not healed completely, 2 were found to have contracted iatrogenic infections due to foreign residues and underwent surgery with the passing of a loose seton. The additional 4 patients who had not healed underwent a fistulotomy and healed completely thereafter. There were no significant changes in incontinence scores. The incontinence scores were .15 ± .36 preoperatively and .22 ± .47 3 months postoperatively (t = -1.438, P = .16). CONCLUSIONS: The TROPIS technique is a novel sphincter-preserving procedure, which can be effectively used in treating fistula-in-ano.
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Enfermedades del Ano , Fístula Rectal , Absceso/etiología , Canal Anal/cirugía , Enfermedades del Ano/etiología , Femenino , Humanos , Ligadura/métodos , Masculino , Estudios Prospectivos , Fístula Rectal/etiología , Fístula Rectal/cirugía , Recurrencia , Resultado del TratamientoRESUMEN
Introduction: Ginkgo biloba L. leaf extract (GBLE) has been reported to be effective for alleviating cognitive and memory impairment in Alzheimer's disease (AD). Nevertheless, the potential mechanism remains unclear. Herein, this study aimed to explore the neuroprotective effects of GBLE on AD and elaborate the underlying therapeutic mechanism. Methods: Donepezil, the most widely prescribed drug for AD, was used as a positive control. An integrated metabolomics and lipidomics approach was adopted to characterize plasma metabolic phenotype of APP/PS1 double transgenic mice and describe the metabolomic and lipidomic fingerprint changes after GBLE intervention. The Morris water maze test and immunohistochemistry were applied to evaluate the efficacy of GBLE. Results: As a result, administration of GBLE significantly improved the cognitive function and alleviated amyloid beta (Aß) deposition in APP/PS1 mice, showing similar effects to donepezil. Significant alterations were observed in metabolic signatures of APP/PS1 mice compared with wild type (WT) mice by metabolomic analysis. A total of 60 markedly altered differential metabolites were identified, including 28 lipid and lipid-like molecules, 13 organic acids and derivatives, 11 organic nitrogen compounds, and 8 other compounds, indicative of significant changes in lipid metabolism of AD. Further lipidomic profiling showed that the differential expressed lipid metabolites between APP/PS1 and WT mice mainly consisted of phosphatidylcholines, lysophosphatidylcholines, triglycerides, and ceramides. Taking together all the data, the plasma metabolic signature of APP/PS1 mice was primarily characterized by disrupted sphingolipid metabolism, glycerophospholipid metabolism, glycerolipid metabolism, and amino acid metabolism. Most of the disordered metabolites were ameliorated after GBLE treatment, 19 metabolites and 24 lipids of which were significantly reversely regulated (adjusted-p<0.05), which were considered as potential therapeutic targets of GBLE on AD. The response of APP/PS1 mice to GBLE was similar to that of donepezil, which significantly reversed the levels of 23 disturbed metabolites and 30 lipids. Discussion: Our data suggested that lipid metabolism was dramatically perturbed in the plasma of APP/PS1 mice, and GBLE might exert its neuroprotective effects by restoring lipid metabolic balance. This work provided a basis for better understanding the potential pathogenesis of AD and shed new light on the therapeutic mechanism of GBLE in the treatment of AD.
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Red yeast rice is a traditional Chinese medicine and food that has been purported to color food, ferment, and lower cholesterol. In order to study the antioxidative capacity of red yeast rice and the effects on electrical potential difference (EPD) of 12 acupuncture meridians, the pH value, oxidation reduction potential (ORP), ABTS, FRAP, T-SOD, and particle size distribution of red yeast rice were analyzed. 20 volunteers were recruited and randomly divided into two groups, the red yeast rice group (10 g red yeast rice and 40 g water) and control CK group (50 g water). The left 12 acupuncture meridians' EPD was real-time monitored. Samples were taken at the 10th minutes. The whole procedure continued for 70 minutes. It is shown that the pH value of the red yeast rice was 4.22, the ORP was 359.63 mV, the ABTS was 0.48 mmol Trolox, the FRAP was 0.08 mmol FeSO4, the T-SOD was 4.71 U, and the average particle size was 108 nm (7.1%) and 398.1 nm (92.9%). The results of 12 acupuncture meridians' EPD showed that the red yeast rice can significantly affect the EPD of stomach, heart, small intestine, and liver meridians.
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Bile acids has gradually become a new focus in various diseases, and ASBT as a transporter responsible for the reabsorption of ileal bile acids, is a key hinge associated to the bile acids-cholesterol balance and bile acids of enterohepatic circulation. The cumulative studies have also shown that ASBT is a promising target for treatment of liver, gallbladder, intestinal and metabolic diseases. This article briefly reviewed the process of bile acids enterohepatic circulation, as well as the regulations of ASBT expression, covering transcription factors, nuclear receptors and gut microbiota. In addition, the relationship between ASBT and various diseases were discussed in this paper. According to the structural classification of ASBT inhibitors, the research status of ASBT inhibitors and potential ASBT inhibitors of traditional Chinese medicine (such resveratrol, jatrorrhizine in Coptis chinensis) were summarized. This review provides a basis for the development of ASBT inhibitors and the treatment strategy of related diseases.