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1.
Zhongguo Zhong Yao Za Zhi ; 49(4): 902-911, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38621897

RESUMEN

Alzheimer's disease(AD), vascular dementia(VD), and traumatic brain injury(TBI) are more common cognitive impairment diseases characterized by high disability and mortality rates, imposing a heavy burden on individuals and their families. Although AD, VD, and TBI have different specific mechanisms, their pathogenesis is closely related to the nucleotide-binding oligome-rization domain-like receptor protein 3(NLRP3). The NLRP3 inflammasome is involved in neuroinflammatory responses, mediating microglial polarization, regulating the reduction of amyloid ß-protein(Aß) deposition, neurofibrillary tangles(NFTs) formation, autophagy regulation, and maintaining brain homeostasis, and synaptic stability, thereby contributing to the development of AD, VD, and TBI. Previous studies have shown that traditional Chinese medicine(TCM) can alleviate neuroinflammation, promote microglial polarization towards the M2 phenotype, reduce Aß deposition and NFTs formation, regulate autophagy, and maintain brain homeostasis by intervening in NLRP3 inflammasome, hence exerting a role in preventing and treating cognitive impairment-related diseases, reducing psychological and economic pressure on patients, and improving their quality of life. Therefore, this article elucidated the role of NLRP3 inflammasome in AD, VS, and TBI, and provided a detailed summary of the latest research results on TCM intervention in NLRP3 inflammasome for the prevention and treatment of these diseases, aiming to inherit the essence of TCM and provide references and foundations for clinical prevention and treatment of cognitive impairment-related diseases with TCM. Meanwhile, this also offers insights and directions for further research in TCM for the prevention and treatment of cognitive impairment-related diseases.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Péptidos beta-Amiloides/metabolismo , Medicina Tradicional China , Calidad de Vida , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/prevención & control , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/prevención & control
2.
Fitoterapia ; 175: 105926, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38537887

RESUMEN

Hyperuricemia (HUA) is a metabolic disease characterized by the increase of serum uric acid (UA) level. Sargentodoxae Caulis (SC) is a commonly used herbal medicine for the treatment of gouty arthritis, traumatic swelling, and rheumatic arthritis in clinic. In this study, a total of fifteen compounds were identified in SC water extract using UHPLC-Q-TOF-MS/MS, including three phenolic acids, seven phenolic glycosides, four organic acids, and one lignan. Then, to study the hypouricemia effect of SC, a HUA mouse model was induced using a combination of PO, HX, and 20% yeast feed. After 14 days of treatment with the SC water extract, the levels of serum UA, creatinine (CRE), blood urea nitrogen (BUN) were reduced significantly, and the organ indexes were restored, the xanthine oxidase (XOD) activity were inhibited as well. Meanwhile, SC water extract could ameliorate the pathological status of kidneys and intestine of HUA mice. Additionally, quantitative real-time PCR (qRT-PCR) and western blotting results showed that SC water extract could increase the expression of ATP binding cassette subfamily G member 2 (ABCG2), organic cation transporter 1 (OCT1), organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3), whereas decrease the expression of glucose transporter 9 (GLUT9). This study provided a data support for the clinical application of SC in the treatment of HUA.


Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Hiperuricemia , Ácido Úrico , Xantina Oxidasa , Animales , Ratones , Hiperuricemia/tratamiento farmacológico , Masculino , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Ácido Úrico/sangre , Xantina Oxidasa/metabolismo , Modelos Animales de Enfermedad , Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Riñón/efectos de los fármacos , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Extractos Vegetales/farmacología , Extractos Vegetales/química , Transportadores de Anión Orgánico/metabolismo , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Proteína 1 de Transporte de Anión Orgánico/metabolismo , Hidroxibenzoatos/aislamiento & purificación , Hidroxibenzoatos/farmacología
3.
Chin J Nat Med ; 22(2): 161-170, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38342568

RESUMEN

Our continued works on the chemical constituents of Ginkgo biloba (G. biloba) leaves has led to the isolation of two novel phenylbutenoids (1, 2), along with five previously unidentified terpene glycosides (3-7). Among them, compounds 1 and 2 represent unique (Z)-phenylbutenoids, 3-6 are megastigmane glycosides, and 7 is identified as a rare bilobanone glycoside (Fig. 1). This study marks the first reported isolation of phenylbutenoid and bilobanone glycoside from G. biloba. The chemical structures of these compounds were elucidated through extensive spectroscopic analysis, including HR-ESI-MS and various 1D and 2D NMR experiments. Furthermore, the absolute configurations of these molecules were determined using Mosher's method, ECD experiments, and Cu-Kα X-ray crystallographic analyses.


Asunto(s)
Glicósidos Cardíacos , Glicósidos , Glicósidos/química , Ginkgo biloba/química , Terpenos/química , Hojas de la Planta/química , Extractos Vegetales/química
4.
Fitoterapia ; 173: 105827, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38266661

RESUMEN

Aspercitrininone A (1), a novel polyketide featuring an unprecedented tetracyclic 6/6/6/5 spiral skeleton, was obtained from the rice fermentation cultures of the fungus Aspergillus cristatus together with five known compounds (2-6). Their structures were determined by HRESIMS data, 1D and 2D NMR spectroscopic analysis, and electronic circular dichroism (ECD) calculations. Aspercitrininone A was revealed as a new type of C/D cycle spiral structure and an unusual addition product of o-quinoid form citrinin with 2-methylterrefuranone. Compounds 1, 4, and 5 exhibited potent antibacterial activities with minimal inhibitory concentration (MIC) values from 13.2 to 67.3 µg/mL against four strains of human pathogenic bacteria in vitro.


Asunto(s)
Aspergillus , Policétidos , Humanos , Policétidos/farmacología , Policétidos/química , Estructura Molecular , Antibacterianos/farmacología , Antibacterianos/química , Esqueleto
5.
Vet Comp Oncol ; 22(1): 57-69, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38081660

RESUMEN

Mammary tumour is the most common type of tumour in dogs, especially in unneutered female dogs. Homoharringtonine (HHT) is a natural alkaloid that can be used to treat various types of human tumour. However, the inhibitory effect and mechanism of HHT on canine mammary carcinomas (CMC) remain unclear. This study aimed to evaluate the inhibitory effect of HHT on CMC in vitro and determine its underlying molecular mechanism. The effects of HHT on the cytotoxicity of CMC U27 cells were evaluated by the cell counting kit-8, wound healing, and Transwell assays. HHT-induced apoptosis of U27 cells was detected by JC-1 and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. Moreover, the gene expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) were analysed using quantitative reverse transcription-polymerase chain reaction (RT-qPCR), and the protein expression of protein kinase B/mammalian target of rapamycin (AKT/mTOR) and mitochondrial apoptosis proteins were determined by western blotting. Furthermore, mammary tumour-bearing mouse models were established using 4T1 cells to evaluate the therapeutic effect of HHT. It was found that HHT could significantly down-regulated the protein expression of p-AKT, p-mTOR, and Bcl-2, and up-regulated the protein expression of P53, Bax, cleaved caspase-3, and cleaved caspase-9. In addition, HHT significantly suppressed both tumour volume and mass in mammary tumour mice. In conclusion, HHT damages CMC cells by inhibiting the AKT/mTOR signalling pathway and inducing mitochondrial apoptosis. Such findings lay a theoretical foundation for the clinical treatment of CMC and provide more options for clinical medication.


Asunto(s)
Carcinoma , Enfermedades de los Perros , Enfermedades de los Roedores , Animales , Femenino , Perros , Humanos , Ratones , Homoharringtonina/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/farmacología , Proteína X Asociada a bcl-2 , Enfermedades de los Perros/tratamiento farmacológico , Transducción de Señal , Apoptosis , Serina-Treonina Quinasas TOR/metabolismo , Carcinoma/veterinaria , Proliferación Celular , Mamíferos/metabolismo
6.
Res Sq ; 2023 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-37502961

RESUMEN

The uptake of Ca2+ into and extrusion of calcium from the mitochondrial matrix, regulated by the mitochondrial Ca2+ uniporter (MCU), is a fundamental biological process that has crucial impacts on cellular metabolism, signaling, growth and survival. Herein, we report that the embryonic lethality of Mcu-deficient mice is fully rescued by orally supplementing ferroptosis inhibitor lipophilic antioxidant vitamin E and ubiquinol. Mechanistically, we found MCU promotes acetyl-CoA-mediated GPX4 acetylation at K90 residue, and K90R mutation impaired the GPX4 enzymatic activity, a step that is crucial for ferroptosis. Structural analysis supports the possibility that GPX4 K90R mutation alters the conformational state of the molecule, resulting in disruption of a salt bridge formation with D23, which was confirmed by mutagenesis studies. Finally, we report that deletion of MCU in cancer cells caused a marked reduction in tumor growth in multiple cancer models. In summary, our study provides a first direct link between mitochondrial calcium level and sustained GPX4 enzymatic activity to regulate ferroptosis, which consequently protects cancer cells from ferroptosis.

7.
Chin J Integr Med ; 29(3): 213-223, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36044114

RESUMEN

OBJECTIVE: To evaluate the apoptosis and cycle arrest effects of Oldenlandia diffusa flavonoids on human gastric cancer cells, determine the action mechanisms in association with the mitochondrial dependent signal transduction pathway that controls production of reactive oxygen species (ROS), and evaluate the pharmacodynamics of a mouse xenotransplantation model to provide a reference for the use of flavonoids in prevention and treatment of gastric cancer. METHODS: Flavonoids were extracted by an enzymatic-ultrasonic assisted method and purified with D-101 resin. Bioactive components were characterized by high-performance liquid chromatography. Cell lines MKN-45, AGS, and GES-1 were treated with different concentrations of flavonoids (64, 96, 128, 160 µg/mL). The effect of flavonoids on cell viability was evaluated by MTT method, and cell nuclear morphology was observed by Hoechst staining. The apoptosis rate and cell cycle phases were measured by flow cytometry, the production of ROS was detected by laser confocal microscope, the mitochondrial membrane potential (MMP) were observed by fluorescence microscope, and the expression of apoptotic proteins related to activation of mitochondrial pathway were measured by immunoblotting. MKN-45 cells were transplanted into BALB/c nude mice to establish a xenograft tumor model. Hematoxylin and eosin staining was used to reveal the subcutaneous tumor tissue. The tumor volume and tumor weight were measured, the expression levels of proliferation markers proliferating cell nuclear antigen (PCNA) and Ki-67 were detected by immunohistochemistry, and the expression levels of CA72-4 were measured by enzyme linked immunosorbent assay. RESULTS: Oldenlandia diffusa flavonoids inhibited proliferation of MKN-45 and AGS human gastric cancer cells, arrested the cell cycle in G1/S phase, induced accumulation of ROS in the process of apoptosis, and altered MMP. In addition, flavonoids increased Apaf-1, Cleaved-Caspase-3, and Bax, and decreased Cyclin A, Cdk2, Bcl-2, Pro-Caspase-9, and Mitochondrial Cytochrome C (P<0.05). The MKN-45 cell mouse xenotransplantation model further clarified the growth inhibitory effect of flavonoids towards tumors. The expression levels of PCNA and Ki-67 decreased in each flavonoid dose group, the expression level of CA72-4 decreased (P<0.05). CONCLUSION: Flavonoids derived from Oldenlandia diffusa can inhibit proliferation and induce apoptosis of human gastric cancer cells by activating the mitochondrial controlled signal transduction pathway.


Asunto(s)
Oldenlandia , Neoplasias Gástricas , Humanos , Animales , Ratones , Oldenlandia/metabolismo , Antígeno Nuclear de Célula en Proliferación , Flavonoides/farmacología , Especies Reactivas de Oxígeno/metabolismo , Ratones Desnudos , Antígeno Ki-67 , Línea Celular Tumoral , Apoptosis , Extractos Vegetales/farmacología , Caspasas , Proliferación Celular
8.
Artículo en Inglés | WPRIM | ID: wpr-971328

RESUMEN

OBJECTIVE@#To evaluate the apoptosis and cycle arrest effects of Oldenlandia diffusa flavonoids on human gastric cancer cells, determine the action mechanisms in association with the mitochondrial dependent signal transduction pathway that controls production of reactive oxygen species (ROS), and evaluate the pharmacodynamics of a mouse xenotransplantation model to provide a reference for the use of flavonoids in prevention and treatment of gastric cancer.@*METHODS@#Flavonoids were extracted by an enzymatic-ultrasonic assisted method and purified with D-101 resin. Bioactive components were characterized by high-performance liquid chromatography. Cell lines MKN-45, AGS, and GES-1 were treated with different concentrations of flavonoids (64, 96, 128, 160 µg/mL). The effect of flavonoids on cell viability was evaluated by MTT method, and cell nuclear morphology was observed by Hoechst staining. The apoptosis rate and cell cycle phases were measured by flow cytometry, the production of ROS was detected by laser confocal microscope, the mitochondrial membrane potential (MMP) were observed by fluorescence microscope, and the expression of apoptotic proteins related to activation of mitochondrial pathway were measured by immunoblotting. MKN-45 cells were transplanted into BALB/c nude mice to establish a xenograft tumor model. Hematoxylin and eosin staining was used to reveal the subcutaneous tumor tissue. The tumor volume and tumor weight were measured, the expression levels of proliferation markers proliferating cell nuclear antigen (PCNA) and Ki-67 were detected by immunohistochemistry, and the expression levels of CA72-4 were measured by enzyme linked immunosorbent assay.@*RESULTS@#Oldenlandia diffusa flavonoids inhibited proliferation of MKN-45 and AGS human gastric cancer cells, arrested the cell cycle in G1/S phase, induced accumulation of ROS in the process of apoptosis, and altered MMP. In addition, flavonoids increased Apaf-1, Cleaved-Caspase-3, and Bax, and decreased Cyclin A, Cdk2, Bcl-2, Pro-Caspase-9, and Mitochondrial Cytochrome C (P<0.05). The MKN-45 cell mouse xenotransplantation model further clarified the growth inhibitory effect of flavonoids towards tumors. The expression levels of PCNA and Ki-67 decreased in each flavonoid dose group, the expression level of CA72-4 decreased (P<0.05).@*CONCLUSION@#Flavonoids derived from Oldenlandia diffusa can inhibit proliferation and induce apoptosis of human gastric cancer cells by activating the mitochondrial controlled signal transduction pathway.


Asunto(s)
Humanos , Animales , Ratones , Oldenlandia/metabolismo , Antígeno Nuclear de Célula en Proliferación , Neoplasias Gástricas , Flavonoides/farmacología , Especies Reactivas de Oxígeno/metabolismo , Ratones Desnudos , Antígeno Ki-67 , Línea Celular Tumoral , Apoptosis , Extractos Vegetales/farmacología , Caspasas , Proliferación Celular
9.
Front Pediatr ; 10: 707136, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35529335

RESUMEN

Background: Preclinical and clinical evidence suggests that hyperbaric oxygen therapy (HBOT) may benefit newborns. The effectiveness of HBOT for neonatal hypoxic-ischemic encephalopathy (HIE) remains controversial. We conducted a meta-analysis to evaluate the efficacy and prognosis of HBOT in neonates with HIE. Methods: A systematic search of eight databases was performed for available articles published between January 1, 2015, and September 30, 2020, to identify randomized controlled clinical trials (RCTs) on HBOT for neonatal HIE. Methodological quality assessment was performed by applying the simple procedure detailed by the Cochrane collaboration. Afterward, quality assessment and data analysis were performed using Revman 5.3 software. STATA 15 software was used to detect publication bias as well as for sensitivity analysis. Results: A total of 46 clinical RCTs were selected for the study and included 4,199 patients with neonatal HIE. The results indicated that HBOT significantly improved the total efficiency (TEF) of treatment for neonatal HIE patients [odds ratio (OR) = 4.61, 95% confidence interval (CI) (3.70, 5.75), P < 0.00001] and reduced the risk of sequelae (OR = 0.23, 95% CI (0.16, 0.33), P < 0.00001) and the neonatal behavioral neurological assessment (NBNA) scores [mean difference (MD) = 4.51, 95%CI (3.83,5.19, P < 0.00001)]. Conclusion: In light of the effectiveness of HBOT neonatal HIE, this meta-analysis suggested that HBOT can be a potential therapy for the treatment of neonatal HIE. Due to the heterogeneity of studies protocol and patient selection being only from China, more research is needed before this therapy can be widely implemented in the clinic. Protocol Registration: PROSPERO (ID: CRD42020210639). Available online at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020210639.

10.
J Comp Neurol ; 530(13): 2254-2285, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35579973

RESUMEN

The macroscale neuronal connections of the lateral preoptic area (LPO) and the caudally adjacent lateral hypothalamic area anterior region (LHAa) were investigated in mice by anterograde and retrograde axonal tracing. Both hypothalamic regions are highly and diversely connected, with connections to >200 gray matter regions spanning the forebrain, midbrain, and rhombicbrain. Intrahypothalamic connections predominate, followed by connections with the cerebral cortex and cerebral nuclei. A similar overall pattern of LPO and LHAa connections contrasts with substantial differences between their input and output connections. Strongest connections include outputs to the lateral habenula, medial septal and diagonal band nuclei, and inputs from rostral and caudal lateral septal nuclei; however, numerous additional robust connections were also observed. The results are discussed in relation to a current model for the mammalian forebrain network that associates LPO and LHAa with a range of functional roles, including reward prediction, innate survival behaviors (including integrated somatomotor and physiological control), and affect. The present data suggest a broad and intricate role for LPO and LHAa in behavioral control, similar in that regard to previously investigated LHA regions, contributing to the finely tuned sensory-motor integration that is necessary for behavioral guidance supporting survival and reproduction.


Asunto(s)
Área Preóptica , Núcleos Septales , Animales , Corteza Cerebral , Área Hipotalámica Lateral , Hipotálamo , Mamíferos , Ratones
11.
Comput Math Methods Med ; 2022: 3921021, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35586674

RESUMEN

Objective: To explore the effect of moxibustion instrument combined with ultrashort wave on pain and oxidative stress in elderly patients with knee osteoarthritis (KOA). Method: 84 elderly patients with knee osteoarthritis treated in our hospital from May 2020 to June 2021 were randomly divided into observation group (n = 42) and control group (n = 42). The observation group was treated with moxibustion instrument combined with ultrashort wave, while the control group was treated with moxibustion instrument. The clinical efficacy of the two groups was compared, and the pain of the two groups was evaluated by visual analogue scale (VAS). Lysholm knee joint score scale and osteoarthritis index (WOMAC) scale of Western Ontario and McMaster University were used to evaluate the knee joint function of the two groups, and the levels of interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α), serum superoxide dismutase (SOD), serum malondialdehyde (MDA), serum miR-155, and NLRP3 were detected in the two groups, and the comprehensive quality of life assessment questionnaire-74 was used, and the adverse reactions were compared between the two groups. Results: The total effective rate of observation group (90.48%) was higher than that of control group (69.05%) (P < 0.05). After treatment, VAS, Lysholm knee joint, WOMAC, quality of life scores, IL-1ß, TNF-α, SOD, MDA, miR-155, and NLRP3 in the observation group were better than those in the control group, and the differences were statistically significant (P < 0.05). There were no obvious adverse reactions in both groups. Conclusion. Moxibustion instrument combined with ultrashort wave can effectively improve knee joint pain, knee joint function, inflammatory reaction, oxidative stress reaction, and quality of life in elderly KOA patients, and the therapeutic effect is good.


Asunto(s)
Moxibustión , Osteoartritis de la Rodilla , Terapia por Ultrasonido , Factores de Edad , Anciano , Humanos , Articulación de la Rodilla , MicroARNs , Proteína con Dominio Pirina 3 de la Familia NLR , Osteoartritis de la Rodilla/metabolismo , Osteoartritis de la Rodilla/terapia , Estrés Oxidativo , Dolor/etiología , Manejo del Dolor , Calidad de Vida , Superóxido Dismutasa/metabolismo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/metabolismo
12.
Zhongguo Zhong Yao Za Zhi ; 47(23): 6264-6270, 2022 Dec.
Artículo en Chino | MEDLINE | ID: mdl-36604870

RESUMEN

The quality of Chinese medicine is the foundation of the clinical effects and industrial development. Component analysis ensures the consistency and stability of medicinals, but fails to evaluate the clinical efficacy. Bioassay is an analytical method to evaluate the effect of a substance on living organisms, tissues, or cells, which is an optimal option for assessing the quality of Chinese medicine. Bioassay of Chinese medicine starts early but progresses slowly. At the moment, it has attracted the interest of scholars. However, no systematic research is available. This study aims to summarize the research on the application of bioassay in quality evaluation of Chinese medicine, focusing on the application of key techniques and experimental systems in bioassay in heat-clearing and blood-activating and stasis-eliminating Chinese medicine and the common problems. Meanwhile, suggestions were proposed in terms of the association with clinical efficacy and chemical analysis and the status quo of biological assay. This study is expected to promote the study and application of bioassay.


Asunto(s)
Medicamentos Herbarios Chinos , Medicina Tradicional China , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Control de Calidad , Bioensayo , Calor
13.
Molecules ; 26(24)2021 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-34946657

RESUMEN

The rapid emergence of bacterial coinfection caused by cytosolic bacteria has become a huge threat to public health worldwide. Past efforts have been devoted to discover the broad-spectrum antibiotics, while the emergence of antibiotic resistance encourages the development of antibacterial agents. In essence, bacterial virulence is a factor in antibiotic tolerance. However, the discovery and development of new antibacterial drugs and special antitoxin drugs is much more difficult in the antibiotic resistance era. Herein, we hypothesize that antitoxin hemolytic activity can serve as a screening principle to select antibacterial drugs to combat coinfection from natural products. Being the most abundant natural drug of plant origins, flavonoids were selected to assess the ability of antibacterial coinfections in this paper. Firstly, we note that four flavonoids, namely, baicalin, catechin, kaempferol, and quercetin, have previously exhibited antibacterial abilities. Then, we found that baicalin, kaempferol, and quercetin have better inhibitions of hemolytic activity of Hla than catechin. In addition, kaempferol and quercetin, have therapeutic effectivity for the coinfections of Staphylococcus aureus and Pseudomonas aeruginosa in vitro and in vivo. Finally, our results indicated that kaempferol and quercetin therapied the bacterial coinfection by inhibiting S. aureus α-hemolysin (Hla) and reduced the host inflammatory response. These results suggest that antitoxins may play a promising role as a potential target for screening flavonoids to combat bacterial coinfection.


Asunto(s)
Antibacterianos , Proteínas Bacterianas , Flavonoides , Proteínas Hemolisinas , Pseudomonas aeruginosa/metabolismo , Staphylococcus aureus/metabolismo , Antibacterianos/química , Antibacterianos/farmacología , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/metabolismo , Evaluación Preclínica de Medicamentos , Flavonoides/química , Flavonoides/farmacología , Proteínas Hemolisinas/antagonistas & inhibidores , Proteínas Hemolisinas/metabolismo
14.
Nature ; 598(7879): 188-194, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34616074

RESUMEN

The cortico-basal ganglia-thalamo-cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative1-4. Yet this three-channel view cannot explain the myriad functions of the basal ganglia. We previously subdivided the dorsal striatum into 29 functional domains on the basis of the topography of inputs from the entire cortex5. Here we map the multi-synaptic output pathways of these striatal domains through the globus pallidus external part (GPe), substantia nigra reticular part (SNr), thalamic nuclei and cortex. Accordingly, we identify 14 SNr and 36 GPe domains and a direct cortico-SNr projection. The striatonigral direct pathway displays a greater convergence of striatal inputs than the more parallel striatopallidal indirect pathway, although direct and indirect pathways originating from the same striatal domain ultimately converge onto the same postsynaptic SNr neurons. Following the SNr outputs, we delineate six domains in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify six parallel cortico-basal ganglia-thalamic subnetworks that sequentially transduce specific subsets of cortical information through every elemental node of the cortico-basal ganglia-thalamic loop. Thalamic domains relay this output back to the originating corticostriatal neurons of each subnetwork in a bona fide closed loop.


Asunto(s)
Ganglios Basales/citología , Corteza Cerebral/citología , Vías Nerviosas , Neuronas/citología , Tálamo/citología , Animales , Ganglios Basales/anatomía & histología , Corteza Cerebral/anatomía & histología , Masculino , Ratones , Ratones Endogámicos C57BL , Tálamo/anatomía & histología
15.
Parasit Vectors ; 14(1): 309, 2021 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-34099029

RESUMEN

BACKGROUND: Haemaphysalis longicornis is an obligate hematophagous ectoparasite that transmits a variety of pathogens causing life-threatening diseases in humans and animals. Paramyosin (Pmy) is not only an invertebrate-specific myofibrillar protein but also an important immunomodulatory protein. Therefore, it is one of the ideal candidate antigens for vaccines. METHODS: We conducted two vaccine trials to evaluate the protective efficacy of Pmy recombinant protein (rPmy) and peptide vaccine (KLH-LEE). Each rabbit was immunized with three doses of rPmy or KLH-LEE adjuvanted with Freund's complete/incomplete at 500 µg/dose at 2-week intervals before challenge with 40 female H. longicornis/rabbit. PBS plus adjuvant, Trx or KLH was used as control group. The antibodies of rabbits were detected by ELISA. Then, female ticks were fed on the rabbits until detachment. RESULTS: ELISA results showed that both vaccines induced rabbits to produce antibodies. Compared with the Trx group, the engorgement weight, oviposition and hatchability of the rPmy group decreased by 8.87%, 26.83% and 38.86%, respectively. On the other hand, engorgement weight, oviposition and hatchability of female ticks in the KLH-LEE group correspondingly resulted in 27.03%, 53.15% and 38.40% reduction compared with that of the KLH group. Considering the cumulative effect of vaccination on the evaluated parameters, results showed 60.37% efficacy of the rPmy vaccine formulation and 70.86% efficacy in the KLH-LEE group. CONCLUSIONS: Pmy and particularly epitope LEE have potential for further development of an effective candidate vaccine to protect the host against tick infection. GRAPHIC ABSTARCT.


Asunto(s)
Proteínas de Artrópodos/administración & dosificación , Ixodidae/inmunología , Conejos/inmunología , Infestaciones por Garrapatas/veterinaria , Tropomiosina/administración & dosificación , Vacunas/administración & dosificación , Animales , Anticuerpos/sangre , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/inmunología , Evaluación Preclínica de Medicamentos , Femenino , Inmunización , Ixodidae/genética , Conejos/sangre , Conejos/parasitología , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Infestaciones por Garrapatas/sangre , Infestaciones por Garrapatas/parasitología , Infestaciones por Garrapatas/prevención & control , Tropomiosina/genética , Tropomiosina/inmunología , Vacunas/genética , Vacunas/inmunología , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/genética , Vacunas de Subunidad/inmunología
16.
Zhongguo Zhong Yao Za Zhi ; 46(5): 1079-1083, 2021 Mar.
Artículo en Chino | MEDLINE | ID: mdl-33787100

RESUMEN

The study is aimed to investigate the reproductive biology characteristics of Polygonatum cyrtonema, especially including phenology, flower bud differentiation, flowering timing, floral traits, pollen vigor and stigma receptivity. The results showed that P. cyrtonema forms inflorescence before the leaves spread. In the wild, P. cyrtonema is mainly pollinated by insects such as bumblebees, with a seed setting rate of 65.12%. The seed setting rate of indoor single plant isolation or self-pollination enclosed by parchment paper bag is 0, indicating that it is self-incompatible. In Lin'an city, seedlings begin to emerge from mid-March to early April(the temperature is higher than 7.5 ℃), buds begin to emerge from the end of March to mid-April, and then undergo the full bloom stage from mid-to-late April, and the final flowering stage from the end of April to mid-May. The whole flowering period lasts 36 to 45 days. There are obvious differences in the phenology of different provenances. The flowers come into bloom from the base to the top along the aboveground main axis, which usually contain 4-22 inflorescences with(2-) 4-10(-21) flowers per inflorescence. The flowering pe-riod for a single plant is 26-38 days. The single flower lasts about 20-25 days from budding to opening and withers 2 days after pollination, and then the ovary will gradually expand. If unpollinated, it will continue to bloom for 3-5 days and then wither. Flower development period is significantly related to pollen vigor and stigma remittance. The pollen viability is the highest when the flower is fully opened with anthers gathering on the stigma, and the receptivity is the strongest when the stigma protrudes out of the perianth and secretes mucus. The fruits and seeds ripen in October, and proper shading can ensure the smooth development and maturity of the seeds. This study provides a basis for the hybrid breeding and seed production of P. cyrtonema.


Asunto(s)
Polygonatum , Flores , Fitomejoramiento , Polinización , Reproducción
17.
Artículo en Chino | WPRIM | ID: wpr-906209

RESUMEN

Objective:To observe the clinical efficacy of Sheti Zhiqiu decoction combined with intradermal needling in treatment of allergic rhinitis (AR) of deficient cold of lung Qi syndrome and its effect on cytokines of helper T cell 17 (Th17) and regulatory T cells (Treg). Method:A total of 105 patients with AR of deficient cold of lung Qi syndrome were randomly divided into traditional Chinese medicine (TCM) group, combination group and western medicine group, with 35 cases in each group. The TCM group was treated with Sheti Zhiqiu decoction, 1 dose a day. The combination group was treated with intradermal needling in addition to the therapy of the TCM group. The selected acupoints were Yintang, bilateral Yingxiang, Fengchi, Feishu and Zusanli. The needles were retained for 3 days before being replaced. The western medicine group was treated with mometasone furoate nasal spray, 100 μg/time at each side of the nasal cavity, <italic>qd</italic>, and desloratadine citrate tablet, 8.8 mg/time, <italic>qd</italic>. Three groups were treated for 4 weeks and followed up for 3 months. Nasal and ocular symptom scores and rhinoconjunctivitis quality of life questionnaire (RQLQ) scores of patients in three groups were observed before and after treatment. Levels of serum interleukin-17 (IL-17), interleukin-10 (IL-10) and transforming growth factor-<italic>β</italic><sub>1</sub> (TGF-<italic>β</italic><sub>1</sub>) were measured before and after treatment. The clinical efficacy and safety were evaluated, and the disease recurrence rate was observed during the follow-up period. Result:Compared with before treatment, nasal and ocular symptom scores and total score, and RQLQ scores and total score of patients in three groups were significantly decreased after treatment (<italic>P</italic><0.01). Compared with the TCM group and the western medicine group after treatment, except for eyes itching/foreign body sensation/red eyes score, nasal and ocular symptom scores and total score, and RQLQ scores and total score of the combination group were lower(<italic>P</italic><0.05,<italic>P</italic><0.01). Compared with before treatment, level of serum IL-17 of patients in three groups was significantly decreased (<italic>P</italic><0.01), while levels of IL-10 and TGF-<italic>β</italic><sub>1</sub> were significantly increased after treatment (<italic>P</italic><0.01). Compared with the TCM group and the western medicine group after treatment, level of serum IL-17 was lower, whereas levels of IL-10 and TGF-<italic>β</italic><sub>1</sub> were higher in the combination group (<italic>P</italic><0.05,<italic>P</italic><0.01). The clinical efficacy of the combination group was better than that of the TCM medicine group and the western medicine group (Z=-2.207,Z=-2.185,<italic>P</italic><0.05). There was no significant difference in recurrence rate between combination group and the TCM group, and the recurrence rate of both groups was lower than that of the western medicine group(<italic>χ</italic><sup>2</sup>=5.020,<italic>χ</italic><sup>2</sup>=4.835,<italic>P</italic><0.05). There was no significant adverse reaction during the treatment period in three groups. Conclusion:Sheti Zhiqiu decoction combined with intradermal needling is effective in treatment of patients with AR of deficient cold of lung Qi syndrome. It can significantly relieve patients' symptoms, improve patients' quality of life and reduce disease recurrence. It may play a role by regulating immune balance of Th17/Treg of patients and improving their immune function.

18.
Zhongguo Zhong Yao Za Zhi ; 45(13): 3120-3127, 2020 Jul.
Artículo en Chino | MEDLINE | ID: mdl-32726020

RESUMEN

Glucomannan is the key active ingredient of Dendrobium catenatum, and CSLA family is responsible for glucomannan biosynthesis. In order to systematically evaluate the CSLA family members of D. catenatum, the bioinformatics methods were performed for genome-wide identification of DcCSLA gene family members through the genomic data of D. catenatum downloaded from the NCBI database, and further analyses of their phylogenetic relationship, gene structure, protein conserved domains and motifs, promoter cis-elements and gene expression profiles in response to stresses. The results showed that D. catenatum contains 13 CSLA members, all of which contain 9-10 exons. In the evolutionary relationship, CSLA genes were clustered into 5 groups, DcCSLA genes were distributed in all branches. Among which the ancestral genes of groupI existed before the monocot-dicot divergence, and groupⅡ-Ⅴ only existed in the monocot plants, indicating that group Ⅰ represents the earliest origin group. CSLA proteins are characteristic of the signature CESA_CaSu_A2 domain. Their promoter regions contain cis elements related to stresses and hormones. Under different stress treatments, low temperature induces the expression of DcCSLA5 and inhibits the expression of DcCSLA3. Infection of Sclerotium delphinii inhibits DcCSLA3/4/6/8/9/10 expression. Under the treatment of jasmonic acid, DcCSLA11 expression was significantly up-regulated, and DcCSLA2/5/7/12/13 were significantly down-regulated. These results laid a foundation for further study on the function of DcCSLA genes in glucomannan biosynthesis and accumulation.


Asunto(s)
Basidiomycota , Dendrobium/genética , Frío , Regulación de la Expresión Génica de las Plantas , Genoma de Planta , Familia de Multigenes , Filogenia , Proteínas de Plantas/genética , Estrés Fisiológico , Transcriptoma
19.
Artículo en Inglés | MEDLINE | ID: mdl-32714880

RESUMEN

Gut microbiota serves as a critical indicator for gut health during treatment of pathogenic bacterial infection. Both Pulsatilla Decoction (abbreviated to PD, a traditional Chinese medicine compound) and Levofloxacin Hydrochloride (LVX) were known to have therapeutic effects to intestinal infectious disease. However, the changes of gut microbiota after PD or LVX treatment remain unclear. Herein, this work aimed to investigate the changes of intestinal flora after PD or LVX therapy of Escherichia coli infection in rats. Results revealed that PD exhibited a valid therapeutic approach for E. coli infection via the intestinal protection, as well as the inhibited release of IL-8 and ICAM-1. Besides, PD was beneficial to rebuild the gut microbiota via restoring Bacteroidetes spp in the composition of the gut microbiota. Comparatively, LVX treatment promoted the infection and ravaged gut microbiota by significantly decreasing Bacteroidetes and increasing Firmicutes. These findings not only highlight the mechanism of Chinese herbal formula, but extend the application of PD as veterinary medicine, feed additive and pre-mixing agent for improving the production of animal derived foods.


Asunto(s)
Medicamentos Herbarios Chinos , Infecciones por Escherichia coli , Microbioma Gastrointestinal , Pulsatilla , Animales , Medicamentos Herbarios Chinos/farmacología , Escherichia coli , Infecciones por Escherichia coli/tratamiento farmacológico , Levofloxacino , Ratas
20.
Skin Res Technol ; 26(6): 851-858, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32557943

RESUMEN

BACKGROUND/PURPOSE: Synchronous microvascular vasomotion was detected at acupoints in our previous human study. This present study aimed to characterize the skin microvascular vasomotion at acupoints on the twelve meridians of beagle dogs. MATERIALS AND METHODS: Two acupoints were selected on each meridian and exactly located at the rosy red spots by an electrochemical color-appearing method, where the electrical resistance was measured. The skin blood flow at acupoints was recorded by laser Doppler flowmetry (LDF), and microvascular vasomotion was analyzed according to LDF waveforms. RESULTS: The skin electrical resistance at acupoints was significantly lower than that at control non-acupoints. The LDF waveforms at acupoints were sinusoidal, which showed the synchronization of the microvascular vasomotion. The spectral analysis revealed that the vasomotion frequencies at acupoints on the same meridian were identical but not among different meridians, and the frequencies on the twelve main meridians displayed a constant order. CONCLUSION: The skin microvascular vasomotion is synchronous at acupoints of beagle dogs and has a specific frequency along the meridian, and the electrochemical color-appearing method is a feasible strategy for the precise and visual location of acupoints. The study provides evidence for the universality of synchronous vasomotion of skin microvessels at acupoints.


Asunto(s)
Puntos de Acupuntura , Meridianos , Microvasos , Flujo Sanguíneo Regional , Piel/irrigación sanguínea , Animales , Perros , Flujometría por Láser-Doppler , Microcirculación
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