RESUMEN
BACKGROUND: Innate immune memory of macrophages is closely linked to histone modifications. While various studies have demonstrated that the polysaccharide of Asparagus cochinchinensis (Lour.) Merr (ACMP), extracted through alcohol-alkali extraction, enhances macrophages' non-specific immune function; no literature currently addresses whether ACMP's regulatory effect is related to innate immune memory and histone modification. PURPOSE: This study aims to investigate if ACMP induces innate immune memory emergence in macrophages via pattern recognition receptor (PRR). STUDY DESIGN: After co-incubating different doses of ACMP with RAW264.7 cells and BMDM cells, we observed changes in signaling pathways related to PRR and assessed the presence of innate immune memory phenomenon in the cells. METHODS: We observed the morphological characteristics of the ACMP using a scanning electron microscope, infrared spectrum, and HPLC pre-column derivatization method. We used q-PCR, Western blot, RNA-seq, and CUT&Tag-seq methods to examine ACMP's regulation of macrophage immune response and innate immune memory and explored its specific mechanism. RESULTS: ACMP, primarily composed of Man, GlcN, Rha, Fuc, GalA, Xyl, Glc, Gal, Ara, and, exhibited a molar ratio of each monosaccharide (1.41: 0.35: 0.49: 0.18: 1.00: 97.12: 0.36: 3.58: 1.14). ACMP regulated immunological function in macrophages through the TLR4-MAPK-JNK/p38/ERK pathway. ACMP induced elevated levels of chromosomal H3K4me1, enhancing TNF-α, IL-1ß, and other genes' responsiveness, allowing macrophages to develop innate immune memory to ACMP stimulation. CONCLUSION: This study first time demonstrates that ACMP regulates immunological function through the TLR4-MAPK-JNK/ERK/p38 signaling pathway, distinct from prior reports. ACMP induces innate immune memory in macrophages in response to its immune stimulation by promoting increased H3K4me1 on chromosomes. This mechanism may be crucial in how plant polysaccharides regulate macrophages and the body's immune function.
Asunto(s)
Aminopiridinas , Memoria Epigenética , Receptor Toll-Like 4 , Humanos , Masculino , Receptor Toll-Like 4/metabolismo , Código de Histonas , Transducción de Señal , Macrófagos , Polisacáridos/farmacología , InmunidadRESUMEN
Small-molecule compounds with rich sources have diverse structures and activities. The active ingredients in traditional Chinese medicine(TCM) provide new sources for the discovery of new antitumor drugs. Aconitum plants as Chinese medicinal plants have the effects of dispelling wind, removing dampness, warming meridian, and relieving pain. They are mainly used to treat inflammation, pain, rheumatism, and tumors, improve heart function, and dilate blood vessels in clinical practice. Diterpenoid alkaloids are the main active components of Aconitum plants, including C20-, C19-, C18-diterpenoid alkaloids and bis-diterpenoid alkaloids. Stu-dies have demonstrated that diterpenoid alkaloids can effectively treat lung cancer, liver cancer, breast cancer, colon cancer and other cancers. Diterpenoid alkaloids are considered as the most promising natural compounds against cancers. In this review, we summarized the chemical structures and antitumor activities of C20-, C19-, C18-diterpenoid alkaloids and bis-diterpenoid alkaloids extracted from plants of Aconitum, aiming to provide reference for further development of diterpenoid alkaloids from Aconitum as antitumor drugs.
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Aconitum , Alcaloides , Antineoplásicos , Diterpenos , Humanos , Aconitum/química , Estructura Molecular , Alcaloides/análisis , Diterpenos/química , Antineoplásicos/farmacología , Antineoplásicos/química , Raíces de Plantas/químicaRESUMEN
Two new phenolic compounds 4-(4'-hydroxybenzyl) phenyl glucoside (gastrodin B, 1) and 1'-hydroxymethyl-phenyl 4-hydroxy-3-(4â³-hydroxybenzyl) benzyl ether (gastrol B, 2) were isolated from the rhizomes of Gastrodia elata. Their structures were elucidated on the basis of spectroscopic data and chemical reaction. All compounds exhibited potent neuroprotective activity against H2O2-induced PC12 cell damage.
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Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Gastrodia/química , Glucósidos/aislamiento & purificación , Glucósidos/farmacología , Fármacos Neuroprotectores/aislamiento & purificación , Fármacos Neuroprotectores/farmacología , Fenoles/aislamiento & purificación , Fenoles/farmacología , Éteres Fenílicos/aislamiento & purificación , Éteres Fenílicos/farmacología , Animales , Medicamentos Herbarios Chinos/química , Glucósidos/química , Peróxido de Hidrógeno/farmacología , Fármacos Neuroprotectores/química , Resonancia Magnética Nuclear Biomolecular , Células PC12 , Fenoles/química , Éteres Fenílicos/química , Ratas , Rizoma/químicaRESUMEN
OBJECTIVE: To investigate the effect of low-dose carvedilol combined with candesartan in the prevention of acute and chronic cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer. METHODS: Forty patients were randomly divided into two groups: the experimental group with chemotherapy plus low-dose carvedilol combined with candesartan (20 cases) and control group with chemotherapy alone (20 cases). The same chemotherapy was given to the two groups. All the 40 patients had no contraindication for carvedilol and candesartan. Patients of the experimental group received low-dose carvedilol from 2.5 mg orally twice a day at first cycle to 5 mg twice a day gradually if no side reactions, and candesartan 2.5 mg orally once a day. Electrocardiogram, ultrasonic cardiogram, arrhythmia, troponin and non-hematologic toxicity were recorded and compared after the second, forth and sixth cycle of chemotherapy. Each cycle included 21 days. RESULTS: LVEF was decreased along with the prolongation of chemotherapy in the experimental group and control group. LVEDD and LVESD showed no significant changes in the experimental group, but gradually increased in the control group. After four and six cycles of chemotherapy, LVEF were (57.00 ± 5.13)% and (45.95 ± 3.68)%, respectively, in the control group, significantly lower than that of (67.00 ± 5.13)% and (57.50 ± 2.57)%, respectively, in the experimental group (P < 0.05). After six cycles of chemotherapy, LVEDD and LVESD were (50.00 ± 10.48) mm and (35.01 ± 2.99) mm, respectively, in the control group, significantly higher than those before chemotherapy (P < 0.05) and experimental group (P < 0.001). The rate of ST segment and T wave abnormalities was 80.0% in the control group after six cycles of chemotherapy, significantly higher than that of 25.0% after four cycles of chemotherapy (P = 0.001) and 10.0% after two cycles of chemotherapy (P < 0.001). The reduction of QRS voltage, arrhythmia and abnormal troponin were 55.0%, 45.0% and 45.0%, respectively, in the control group, significantly higher than those in the experimental group (20.0%, P < 0.05), (10.0%, P = 0.010) and (10.0%, P < 0.05), respectively. The rate of abnormal expression of troponin was 45.0% in the control group, significantly higher than the 10.0% in the experimental group (P < 0.05). CONCLUSIONS: The use of low-dose carvedilol combined with candesartan can reduce the acute and chronic cardiotoxicity of anthracycline drugs, and with tolerable toxicities. This may provide a new approach to prevent cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Arritmias Cardíacas/inducido químicamente , Bencimidazoles/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Carbazoles/farmacología , Propanolaminas/farmacología , Tetrazoles/farmacología , Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas Adrenérgicos beta/farmacología , Adulto , Anciano , Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bencimidazoles/administración & dosificación , Compuestos de Bifenilo , Neoplasias de la Mama/cirugía , Carbazoles/administración & dosificación , Carvedilol , Quimioterapia Adyuvante , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Electrocardiografía/efectos de los fármacos , Epirrubicina/efectos adversos , Epirrubicina/uso terapéutico , Femenino , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Humanos , Mastectomía Radical , Persona de Mediana Edad , Propanolaminas/administración & dosificación , Volumen Sistólico/efectos de los fármacos , Tetrazoles/administración & dosificación , Troponina/metabolismoRESUMEN
Due to its numerous environmental extremes, the Tibetan Plateau--the world's highest plateau--is one of the most challenging areas of modern human settlement. Archaeological evidence dates the earliest settlement on the plateau to the Late Paleolithic, while previous genetic studies have traced the colonization event(s) to no earlier than the Neolithic. To explore whether the genetic continuity on the plateau has an exclusively Neolithic time depth, we studied mitochondrial DNA (mtDNA) genome variation within 6 regional Tibetan populations sampled from Tibet and neighboring areas. Our results confirm that the vast majority of Tibetan matrilineal components can trace their ancestry to Epipaleolithic and Neolithic immigrants from northern China during the mid-Holocene. Significantly, we also identified an infrequent novel haplogroup, M16, that branched off directly from the Eurasian M founder type. Its nearly exclusive distribution in Tibetan populations and ancient age (>21 kya) suggest that M16 may represent the genetic relics of the Late Paleolithic inhabitants on the plateau. This partial genetic continuity between the Paleolithic inhabitants and the contemporary Tibetan populations bridges the results and inferences from archaeology, history, and genetics.