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1.
Artículo en Inglés | MEDLINE | ID: mdl-38430150

RESUMEN

Objective: Gaucher disease (GD) is a clinically rare single-gene recessive lysosomal storage disease mainly divided into three subtypes I to III. This report aims to present a case of type IIIb GD in a Chinese child with a focus on the manifestation of hearing loss and the importance of early diagnosis and monitoring. Methods: The patient underwent a routine physical examination upon admission, followed by CT scans of the chest and abdomen, MRI of the brain, and bone marrow smear examination. The patient's GBA enzyme activity, Lyso-GL-1 levels, and GBA gene expression were analyzed using tandem mass spectrometry (MS/MS) and next-generation sequencing technology. Finally, auditory brainstem response (ABR) testing was conducted. Results: This report presented a case of a Chinese boy with hematological manifestations as the first symptom, followed by hepatosplenomegaly, and the bilateral femurs showed obvious Erlenmeyer flask-like changes. Combined with GBA enzyme activity, Lyso-GL-1 and GBA genotype analysis results, the boy was initially diagnosed as type I GD. During the follow-up, the boy developed nystagmus, bilateral ABR V wave threshold increased, V/I amplitude ratio <0.5, accompanied by delayed growth and development, and finally diagnosed as type IIIb. Conclusions: This case suggests the necessity of neuropathy monitoring in patients with type I GD during the early stages of the disease. This includes EEG, neuro-ophthalmological examination, and auditory function assessment, which can help reflect the progression of neuropathy and facilitate the early diagnosis of type III GD.

2.
Sci Adv ; 9(49): eadi2465, 2023 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-38055816

RESUMEN

Adenosine 5'-triphosphate citrate lyase (ACLY) is a cytosolic enzyme that converts citrate into acetyl-coenzyme A for fatty acid and cholesterol biosynthesis. ACLY is up-regulated or activated in many cancers, and targeting ACLY by inhibitors holds promise as potential cancer therapy. However, the role of ACLY in cancer immunity regulation remains poorly understood. Here, we show that ACLY inhibition up-regulates PD-L1 immune checkpoint expression in cancer cells and induces T cell dysfunction to drive immunosuppression and compromise its antitumor effect in immunocompetent mice. Mechanistically, ACLY inhibition causes polyunsaturated fatty acid (PUFA) peroxidation and mitochondrial damage, which triggers mitochondrial DNA leakage to activate the cGAS-STING innate immune pathway. Pharmacological and genetic inhibition of ACLY overcomes cancer resistance to anti-PD-L1 therapy in a cGAS-dependent manner. Furthermore, dietary PUFA supplementation mirrors the enhanced efficacy of PD-L1 blockade by ACLY inhibition. These findings reveal an immunomodulatory role of ACLY and provide combinatorial strategies to overcome immunotherapy resistance in tumors.


Asunto(s)
Antígeno B7-H1 , Neoplasias , Ratones , Animales , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Ácidos Grasos Insaturados , Nucleotidiltransferasas , Inmunoterapia
3.
Ren Fail ; 44(1): 1409-1416, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36000910

RESUMEN

BACKGROUND: Vascular calcification (VC) and secondary hyperparathyroidism (SHPT) are important causes of the high incidence of cardiovascular events in chronic kidney disease (CKD) patients. The relationship between parathyroid hormone (PTH) and VC is very complex. The aim of this study was to determine the correlation between PTH levels and abdominal aortic calcification (AAC) in patients starting hemodialysis who had not received calcium tablets, calcium-containing phosphorus binders, calcitriol, or vitamin D analogs. METHODS: Seventy-one patients were included. Latero-lateral X-ray lumbar radiography, serum intact PTH (iPTH) levels, and predialysis biochemical parameters were obtained. The degree of AAC was evaluated according to the methods described previously by Kauppila et al. RESULTS: We found that there was a strong negative correlation between serum PTH and AAC (Spearman's rho -0.76, p < 0.001). Receiver operating characteristic (ROC) curve analysis showed that low serum PTH level could predict the presence and extent of AAC (area under the curve values were 0.9013 [p < 0.0001] and 0.780 [p = 0.0041], respectively). CONCLUSIONS: Our results indicate that serum PTH level is significantly negatively correlated with AAC within a certain concentration range in patients starting hemodialysis who had not received calcium tablets, calcium-containing phosphorus binders, calcitriol, or vitamin D analogs.


Asunto(s)
Hiperparatiroidismo Secundario , Calcificación Vascular , Calcitriol , Calcio , Humanos , Hiperparatiroidismo Secundario/tratamiento farmacológico , Hiperparatiroidismo Secundario/etiología , Hormona Paratiroidea , Fósforo , Diálisis Renal/efectos adversos , Comprimidos , Calcificación Vascular/complicaciones , Calcificación Vascular/etiología , Vitamina D
4.
Sci Total Environ ; 847: 157620, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-35901899

RESUMEN

Aquaculture is one of the fastest growing fields of global food production industry in recent years. To maintain the ecological health of aquaculture water body and the sustainable development of aquaculture industry, the treatment of aquaculture tail water (ATW) is becoming an indispensable task. This paper discussed the demand of environmentally friendly and cost-effective technologies for ATW treatment and the potential of algal-bacterial symbiosis system (ABSS) in ATW treatment. The characteristics of ABSS based technology for ATW treatment were analyzed, such as energy consumption, greenhouse gas emission, environmental adaptability and the possibility of removal or recovery of carbon, nitrogen and phosphorus as resource simultaneously. Based on the principle of ABSS, this paper introduced the key environmental factors that should be paid attention to in the establishment of ABSS, and then summarized the species of algae, bacteria and the proportion of algae and bacteria commonly used in the establishment of ABSS. Finally, the reactor technologies and the relevant research gaps in the establishment of ABSS were reviewed and discussed.


Asunto(s)
Gases de Efecto Invernadero , Purificación del Agua , Acuicultura , Bacterias , Carbono , Nitrógeno/análisis , Fósforo/análisis , Simbiosis , Aguas Residuales/microbiología
5.
J Ethnopharmacol ; 297: 115540, 2022 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-35870685

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Guizhi Fuling decoction (GZFL decoction) is a famous formula in the Synopsis of the Golden Chamber, which has a long history in treating endometriosis. However, its exact mechanism remains unclear. AIM OF STUDY: This study aims to explore the mechanism of GZFL decoction in treating endometriosis, especially in alleviating endometriosis-associated pain. MATERIALS AND METHODS: A combination of system pharmacology and pharmacodynamics was used to explore the specific mechanism of GZFL decoction in the treatment of endometriosis-associated pain. First, the TCMSP database was used to search the components of the GZFL decoction; the parameter index was set as oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18, while the active ingredients of the drug were screened out. The disease targets of endometriosis were obtained from the TTD, OMIM, Genecards, and DisGeNET databases; the keyword was "endometriosis pain". Network construction and analysis were performed using Cytoscape 3.7.2 software; the David database was used to enrich and analyze the pathways for alleviating endometriosis pain after GZFL decoction treatment. In addition, the network results were verified using experimental animal and cell research. RESULTS: The results showed the following targets: 76 for the effective chemical components in the prescription, 1329 for disease pain, and 278 for the intersection of drugs and endometriosis pain. The enrichment results for these targets showed that the TNF-PI3K/Akt pathway exhibited research significance. In endometriosis rat models, the GZFL decoction reduced the volume of lesions and relieved pain symptoms. It also reduced the serum levels of IL-6, IL-1ß, and TNF-α as well as their expression in the lesion tissues. The GZFL decoction also suppressed the activation of PI3K/Akt downstream signaling proteins. CONCLUSIONS: GZFL decoction could reduce the volume of lesions, suppress inflammation, and decrease the sensitivity to pain in endometriosis rat models through inhibiting PI3K/Akt pathway. This study provides a possible target for traditional Chinese medicine in treating endometriosis-associated pain.


Asunto(s)
Medicamentos Herbarios Chinos , Endometriosis , Wolfiporia , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Endometriosis/tratamiento farmacológico , Femenino , Humanos , Simulación del Acoplamiento Molecular , Dolor/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Ratas
6.
Molecules ; 27(9)2022 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-35566098

RESUMEN

Shikonin is the main component of root extracts from the Chinese herbal medicine Lithospermum erythrorhizon, which is commonly used for the treatment of various diseases including cancer. Previous research showed that shikonin suppressed pancreatic cancer growth; nevertheless, its molecular targets and mechanisms have not been elucidated. This study aimed to investigate the interaction and regulatory mechanisms of shikonin on its potential target p21-activated kinase 1 (PAK1). Through a labchip-based screening method, shikonin was identified as a potential bioactive PAK1 inhibitor. Molecular docking technology was used to detect the interaction sites of shikonin and PAK1 kinase. Western blot was performed to validate the mechanism. MTT and flow cytometry were practiced to investigate the effect of shikonin against pancreatic cancer cells. The results show that shikonin significantly inhibited the activity of PAK1 kinase with IC50 value of 7.252 ± 0.054 µM. Molecular docking studies showed that shikonin binds to the ATP-binding pocket of the PAK1 kinase domain. Moreover, shikonin inhibited PAK1 activation and its downstream signaling pathway proteins, while reducing proliferation and inducing apoptosis of pancreatic cancer cells. Further studies showed that the treatment of shikonin sensitized pancreatic cancer cells to chemotherapeutic drugs. These results suggest that shikonin, a potential natural inhibitor targeting PAK1 kinase, has promising potent applications in the treatment of pancreatic cancer and chemotherapy sensitization.


Asunto(s)
Naftoquinonas , Neoplasias Pancreáticas , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Humanos , Simulación del Acoplamiento Molecular , Naftoquinonas/farmacología , Neoplasias Pancreáticas/tratamiento farmacológico , Quinasas p21 Activadas , Neoplasias Pancreáticas
7.
J Sci Food Agric ; 102(14): 6432-6442, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35567370

RESUMEN

BACKGROUND: Aging causes decreased antioxidant capacity and chronic inflammation and may even elevate cancer risks. Previous studies reported that flaxseed oil (FO) can alleviate age-related diseases, including improving alcoholic liver disease, atherosclerosis and diabetes. However, whether the intestinal microbiota accountable for this alleviation is still unknown. This study aims to study the antioxidant effects of FO in an aging rat model and the underlying mechanism between the intestinal microbiota and aging. RESULTS: Our results presented that serum and liver antioxidant capacities in FO group were up-regulated, and liver inflammation in FO group was reduced. The 16S rDNA sequencing showed that FO regulated the microbial community, including up-regulation of four families of Lactobacillus and six families of Clostridium. In addition, FO had also adjusted the relative abundance of several genera such as Ruminococcaceae_UCG-005 and Prevotella_9, which may be the key bacteria associated with the aging process. Colonic transcriptome analysis showed that there were 1679 differentially expressed genes (DEGs) in the Model group and the FO group (134 up-regulated and 1545 down-regulated). Gene set enrichment analysis (GSEA) revealed FO down-regulates the expression of the upstream genes Ptprc, Lck, Zap70, Lat and Lcp2 in the T cell receptor signaling pathway. CONCLUSION: In conclusion, FO improved antioxidant capacity and reduced intestinal microbial disturbances caused by aging damage, indicating that dietary FO has the potential to fight aging damage. This study provides a more comprehensive view of dietary intervention to improve aging. © 2022 Society of Chemical Industry.


Asunto(s)
Microbioma Gastrointestinal , Aceite de Linaza , Envejecimiento , Animales , Antioxidantes/farmacología , ADN Ribosómico/farmacología , Galactosa/efectos adversos , Inflamación , Estrés Oxidativo , Ratas , Receptores de Antígenos de Linfocitos T
8.
ACS Appl Mater Interfaces ; 14(18): 20762-20777, 2022 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-35476413

RESUMEN

The tumor immunosuppressive microenvironment (TIM) greatly hindered the efficacy of cancer immunotherapy. Overexpressed indoleamine 2,3-dioxygenase-1 (IDO1) in tumor tissues plays a vital role in TIM generation, and downregulation of IDO1 expression may reverse TIM. Inspired by the Watson-Crick base-pairing rule, a versatile noncationic miRNA vector (miDAC@PDA) is developed for cancer immunotherapy. Doxorubicin (DOX), adenosine triphosphate (ATP), and copper ions (Cu2+) are coassembled into coordination polymer nanoparticles (DAC) and bind miRNA via the hydrogen bond interaction (miDAC) between adenine residues (ATP) and uracil residues (miRNA). Polydopamine (PDA) is deposited onto the surface of miDAC for photothermal therapy. miDAC@PDA can efficiently accumulate into tumor tissues for cellular uptake. Under laser irradiation and high intracellular GSH levels, the PDA shell of miDAC@PDA can dissociate from miDAC for miRNA release due to local hyperthermia. Cu2+-mediated GSH consumption and intracellular ATP release can amplify the DOX-based immunogenic cell death (ICD) cascade, together with miR-448-mediated IDO1 inhibition, and these versatile nanoplexes will not only restrain primary tumor growth but also display a remarkable abscopal effect on distant tumors. Collectively, our study provides a unique strategy for intracellular gene delivery and an inspirational approach for multimechanism cancer management.


Asunto(s)
Hipertermia Inducida , MicroARNs , Nanopartículas , Neoplasias , Adenosina Trifosfato , Animales , Línea Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacología , Rayos Láser , Ratones , Nanopartículas/química , Neoplasias/terapia , Fototerapia , Polímeros/química , Microambiente Tumoral
9.
J Ethnopharmacol ; 290: 115121, 2022 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-35182668

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: In the practice of traditional Chinese medicine, endometriosis is believed to be caused by blood stasis and is characterised by dysmenorrhea, which is difficult to control. Shixiao San (SXS) has a long history of use in the treatment of gynaecological diseases. The prescriptions composed of SXS include Typhae Pollen and Faeces Trogopterori, both of which have anti-inflammatory activity. In addition, Typhae Pollen can be used to treat many kinds of blood stasis diseases. AIM OF THE STUDY: The purpose of the present study was to investigate the effect of SXS on pain relief in rats with endometriosis and to preliminarily explore its mechanism of action in alleviating pain. MATERIAL AND METHODS: Ten rats received sham operation as the Sham group, and 30 endometriosis model rats were randomly divided into three groups: the Model, Shixiao San-Low (SXS-L), and Shixiao San-High (SXS-H) groups. The rats were administered the appropriate treatment via intragastric gavage for 4 weeks. The thermal radiation pain and mechanical pain thresholds of the rats were measured every 7 days after treatment. Finally, the distribution density of nerve fibres in endometrial tissue, the inflammatory infiltration of the dorsal root ganglion (DRG), the expression of TRPV1 in the DRG, and the expression of IL-1ß, TNF-α, and IL-6 in ectopic tissue were measured. RESULTS: After SXS treatment, the growth of ectopic tissue in rats with endometriosis was significantly suppressed, their thermal radiation pain and mechanical pain thresholds increased, the density of nerve fibres and the expression of inflammatory factors in ectopic tissues reduced, and inflammatory cells infiltration in the DRG of the animals alleviated. Meanwhile, the expression of TRPV1 in the DRG was downregulated in rats with endometriosis. CONCLUSIONS: SXS could possibly inhibit the development of endometriosis and relieve pain in patients with endometriosis by reducing inflammatory responses in ectopic tissue and the DRG.


Asunto(s)
Endometriosis , Ganglios Espinales , Medicina Tradicional China , Animales , Femenino , Ratas , Endometriosis/patología , Endometrio/efectos de los fármacos , Ganglios Espinales/efectos de los fármacos , Interleucina-1beta/efectos de los fármacos , Interleucina-6/metabolismo , Medicina Tradicional China/métodos , Dolor/patología , Distribución Aleatoria , Ratas Sprague-Dawley , Canales Catiónicos TRPV/efectos de los fármacos , Factor de Necrosis Tumoral alfa/efectos de los fármacos
10.
Front Pharmacol ; 12: 728937, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34630106

RESUMEN

An optimized support vector machine model was used to construct a lung cancer diagnosis model based on serological indicators, and a molecular regulation model of Wogonin, a component of Scutellaria baicalensis, was established. Serological indexes of patients were collected, the grid search method was used to identify the optimal penalty coefficient C and parameter g of the support vector machine model, and the benign and malignant auxiliary diagnosis model of isolated pulmonary nodules based on serological indicators was established. The regulatory network and key targets of Wogonin in lung cancer were analyzed by network pharmacology, and key targets were detected by western blot. The relationship between serological susceptibility genes and key targets of Wogonin was established, and the signaling pathway of Wogonin regulating lung cancer was constructed. After support vector machine parameter optimization (C = 90.597, g = 32), the accuracy of the model was 90.8333%, with nine false positives and two false negative cases. Ontology functional analysis of 67 common genes between Wogonin targets and lung cancer-related genes showed that the targets were associated with biological processes involved in peptidye-serine modification and regulation of protein kinase B signaling; cell components in the membrane raft and chromosomal region; and molecular function in protein serine/threonine kinase activity and heme binding. Kyoto Encyclopedia of Genes and Genomes analysis showed that the regulation pathways involved the PI3K-Akt signaling pathway, ERBB signaling pathway, and EGFR tyrosine kinase inhibitor resistance. In vitro analyses using lung cancer cells showed that Wogonin led to significantly increased levels of cleaved caspase-3 and Bad and significantly decreased Bcl-2 expression in a concentration-dependent manner. ErbB4 expression also significantly decreased in lung cancer cells after treatment with Wogonin. A regulatory network of Wogonin regulating lung cancer cell apoptosis was constructed, including the participation of serological susceptibility genes. There is a certain regulatory effect between the serological indexes that can be used in the diagnosis of lung cancer and the key targets of Chinese herbal medicine treatment of lung cancer, which provides a new idea for the diagnosis, treatment and prognosis of clinical lung cancer.

12.
Medicine (Baltimore) ; 99(41): e21913, 2020 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-33031257

RESUMEN

INTRODUCTION: The incidence of psoriasis vulgaris is increasing worldwide. Chronic recurrence of the disease, as well as accompanying cardiovascular disease, metabolic syndrome, and depression has affected the physical and mental health of these patients. Psoriasis vulgaris is a difficult and major disease in the dermatology field. Short-term curative effects using conventional therapy for psoriasis vulgaris has made major strides. However, traditional Chinese medicine (TCM) treatment has long-term curative advantages for psoriasis vulgaris but lacks the scientific and clinical evidence for its use. This study intends to demonstrate and provide scientific and clinical evidence for the use of TCM to delay the recurrence of psoriasis vulgaris. METHODS AND ANALYSIS: This will be a prospective, multicenter cohort study. We intend to recruit 1521 psoriasis vulgaris patients from 14 hospitals in Beijing, Tianjin, and Hebei. Treatment will be based on the diagnosis specifications and clinical practice guidelines of TCM and conventional therapy. During inclusion and the subsequent follow-up period, doctors through electronic case reports will collect different therapeutic TCM regimens and conventional therapy that were administered. Information on life condition, skin lesions at each visit, World Health Organization Quality of Life Instruments, Zung Self-rating Anxiety Scale, Zung Self-assessment of Depression, laboratory examinations, incidence of new rash and recurrence during the remission and recurrence stages will be recorded. ETHICS AND DISSEMINATION: The clinical trial protocol for this study was approved by the ethics committee of the Beijing hospital of TCM affiliated to capital medical university (Ethics number: 2019BL02-010-02). We will publish and present our results at national and international conferences and in peer-reviewed journals specialized in dermatology. TRIAL REGISTRATION: This protocol has been registered in clinicaltrials. gov (ChiCTR1900021629).


Asunto(s)
Medicina Tradicional China , Psoriasis/terapia , Humanos , Estudios Multicéntricos como Asunto , Estudios Prospectivos
13.
J Tradit Chin Med ; 40(2): 340-342, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32242401

RESUMEN

The management of dilated cardiomyopathy (DCM) is well established. However, a subset of patients does not have recovery from or have recurrences of left ventricular (LV) dysfunction despite receiving optimal medical therapy. Coronary microvascular dysfunction (CMD) can result from structural and functional abnormalities at the intramural and small coronary vessel level affecting coronary blood flow autoregulation and consequently leading to impaired coronary flow reserve. Dilated myocardial phenotype may be responsible for CMD in DCM. Anisodamine can exert a significant effect on relieving microvascular spasm, and improving and dredging the coronary microcirculation. However, whether CMD can be potentially improved with anisodamine to make DCM better remains incompletely understood.


Asunto(s)
Cardiomiopatía Dilatada/tratamiento farmacológico , Enfermedad Coronaria/complicaciones , Medicamentos Herbarios Chinos/administración & dosificación , Alcaloides Solanáceos/administración & dosificación , Adulto , Anciano , Cardiomiopatía Dilatada/etiología , Cardiomiopatía Dilatada/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Microcirculación/efectos de los fármacos , Persona de Mediana Edad , Scopolia/química , Función Ventricular Izquierda/efectos de los fármacos
14.
Environ Sci Process Impacts ; 22(2): 340-349, 2020 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-31934690

RESUMEN

Diffusive gradients in thin films (DGT) have gained wide attention for in situ measurement of reactive phosphorus species (PO4) in natural water, sediments and potentially soils. In this study, a novel Mg(OH)2 binding gel was formed using magnesium hydroxide obtained by in situ hydration of calcined magnesium oxide. Laboratory scale experiments showed that the novel Mg(OH)2 gel had a homogeneous dispersion of fine particles of Mg(OH)2 with a particle size of 2-5 µm. With 10 mL of 2.0 mol L-1 NaOH as the eluting agent, the optimal elution efficiency of PO4 on the Mg(OH)2 gel was 72 ± 5%. There were linear relationships between the accumulated PO4 mass and the applied PO4 concentration (0.1 to 20 mg P per L), time (0 to 24 h) and temperature (22 to 40 °C). The capacity of the Mg(OH)2 binding layer was determined to be 99.5 µg P per disc. Tests in synthetic seawater, Chaohu Lake and Yihai Pond confirmed that Mg(OH)2-DGT was able to accurately measure phosphorus up to 10 days. This was indicated by the good agreements between the concentrations measured by DGT (CDGT) technology and by an ex situ chemical method in solution (Csoln), with a CDGT/Csoln ratio between 0.91 and 1.09.


Asunto(s)
Fósforo , Contaminantes Químicos del Agua , Difusión , Monitoreo del Ambiente , Lagos , Fósforo/análisis , Agua , Contaminantes Químicos del Agua/análisis
15.
J Immunother Cancer ; 7(1): 326, 2019 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-31775862

RESUMEN

BACKGROUND: It is unclear whether plant-derived extracellular vesicles (EVs) can mediate interspecies communication with mammalian cells. Tumor-associated macrophages (TAMs) display a continuum of different polarization states between tumoricidal M1 phenotype and tumor-supportive M2 phenotypes, with a lower M1/M2 ratio correlating with tumor growth, angiogenesis and invasion. We investigated whether EVs from ginseng can alter M2-like polarization both in vitro and in vivo to promote cancer immunotherapy. METHODS: A novel EVs-liked ginseng-derived nanoparticles (GDNPs) were isolated and characterized from Panax ginseng C. A. Mey. Using GDNPs as an immunopotentiator for altering M2 polarized macrophages, we analyzed associated surface markers, genes and cytokines of macrophages treated with GDNPs. Mice bearing B16F10 melanoma were treated with GDNPs therapy. Tumor growth were assessed, and TAM populations were evaluated by FACS and IF. RESULTS: GDNPs significantly promoted the polarization of M2 to M1 phenotype and produce total reactive oxygen species, resulting in increasing apoptosis of mouse melanoma cells. GDNP-induced M1 polarization was found to depend upon Toll-like receptor (TLR)-4 and myeloid differentiation antigen 88 (MyD88)-mediated signaling. Moreover, ceramide lipids and proteins of GDNPs may play an important role in macrophage polarization via TLR4 activation. We found that GDNPs treatment significantly suppressed melanoma growth in tumor-bearing mice with increased presence of M1 macrophages detected in the tumor tissue. CONCLUSIONS: GDNPs can alter M2 polarization both in vitro and in vivo, which contributes to an antitumor response. The polarization of macrophages induced by GDNPs is largely dependent on TLR4 and MyD88 signalling. GDNPs as an immunomodulator participate in mammalian immune response and may represent a new class of nano-drugs in cancer immunotherapy.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Activación de Macrófagos/efectos de los fármacos , Activación de Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Nanopartículas , Panax/química , Extractos Vegetales/farmacología , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Centrifugación por Gradiente de Densidad , Modelos Animales de Enfermedad , Estabilidad de Medicamentos , Humanos , Lípidos/química , Macrófagos/metabolismo , Masculino , Melanoma/tratamiento farmacológico , Melanoma/inmunología , Melanoma/metabolismo , Melanoma/patología , Melanoma Experimental , Ratones , Factor 88 de Diferenciación Mieloide/metabolismo , Nanopartículas/química , Fagocitosis , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Distribución Tisular , Receptor Toll-Like 4/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Nat Commun ; 10(1): 1371, 2019 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-30914652

RESUMEN

Mitochondrial fragmentation and bioenergetic failure manifest in Huntington's disease (HD), a fatal neurodegenerative disease. The factors that couple mitochondrial fusion/fission with bioenergetics and their impacts on neurodegeneration however remain poorly understood. Our proteomic analysis identifies mitochondrial protein ATAD3A as an interactor of mitochondrial fission GTPase, Drp1, in HD. Here we show that, in HD, ATAD3A dimerization due to deacetylation at K135 residue is required for Drp1-mediated mitochondrial fragmentation. Disturbance of ATAD3A steady state impairs mtDNA maintenance by disrupting TFAM/mtDNA binding. Blocking Drp1/ATAD3A interaction with a peptide, DA1, abolishes ATAD3A oligomerization, suppresses mitochondrial fragmentation and mtDNA lesion, and reduces bioenergetic deficits and cell death in HD mouse- and patient-derived cells. DA1 treatment reduces behavioral and neuropathological phenotypes in HD transgenic mice. Our findings demonstrate that ATAD3A plays a key role in neurodegeneration by linking Drp1-induced mitochondrial fragmentation to defective mtDNA maintenance, suggesting that DA1 might be useful for developing HD therapeutics.


Asunto(s)
ATPasas Asociadas con Actividades Celulares Diversas/genética , Metabolismo Energético/genética , Enfermedad de Huntington/genética , Proteínas de la Membrana/genética , Dinámicas Mitocondriales/genética , Proteínas Mitocondriales/genética , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Animales , Muerte Celular , Línea Celular , ADN Mitocondrial/metabolismo , Proteínas de Unión al ADN/metabolismo , Dinaminas/metabolismo , GTP Fosfohidrolasas/metabolismo , Técnicas de Silenciamiento del Gen , Células HEK293 , Proteínas del Grupo de Alta Movilidad/metabolismo , Humanos , Enfermedad de Huntington/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Ratones Transgénicos , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Mitocondriales/metabolismo , Mutación , Neuronas/metabolismo , Proteómica , Factores de Transcripción/metabolismo
17.
Biomaterials ; 197: 380-392, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30703743

RESUMEN

Systemic lupus erythematosus (SLE) constitutes an autoimmune disease characterized by the breakdown of tolerance to self-antigens, sustained production of pathogenic autoantibodies, and damage to multiple organs and tissues. Nanoparticle (NP)-based therapeutics have demonstrated efficacy in attenuating the progression of SLE. However, investigations of nano-drugs that address the crucial initiating factor in the pathogenesis of SLE; e.g., inefficient clearance of apoptotic cells by phagocytes and consequent accumulation of self-antigens, have seldom been reported. Here, an apoptotic cell-mimicking gold nanocage (AuNC)-based nano drug carrier capable of correcting the impaired clearance of apoptotic cells in SLE was rationally designed and generated by conjugating phosphatidylserine (PS) on the surface of liposome-coated AuNCs for liver X receptor (LXR) agonist T0901317 delivery. Notably, PS-lipos-AuNC@T0901317 could efficiently enhance apoptotic cell clearance by elevating the expression of Mer, one of the pivotal phagocytosis-associated receptors on macrophages, resulting in decreased production of anti-dsDNA autoantibodies, reduced inflammatory response, and alleviation of kidney damage in lupus model mice. Additionally, PS-lipos-AuNC could be tracked by photoacoustic imaging for nano drug carrier biodistribution. By addressing the crucial pathogenic factor of SLE, the NP-based delivery system in this study is envisioned to provide a promising strategy to treat this complex and challenging disease.


Asunto(s)
Apoptosis , Sistemas de Liberación de Medicamentos , Oro/administración & dosificación , Hidrocarburos Fluorados/administración & dosificación , Receptores X del Hígado/agonistas , Lupus Eritematoso Sistémico/tratamiento farmacológico , Nanocápsulas/administración & dosificación , Sulfonamidas/administración & dosificación , Animales , Autoanticuerpos/análisis , Citocinas/metabolismo , Progresión de la Enfermedad , Evaluación Preclínica de Medicamentos , Femenino , Oro/farmacocinética , Hidrocarburos Fluorados/uso terapéutico , Hidrocarburos Fluorados/toxicidad , Liposomas/administración & dosificación , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos MRL lpr , Fosfatidilserinas , Sulfonamidas/uso terapéutico , Sulfonamidas/toxicidad , Distribución Tisular , Tirosina Quinasa c-Mer/biosíntesis , Tirosina Quinasa c-Mer/genética
18.
BMC Complement Altern Med ; 19(1): 46, 2019 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-30755185

RESUMEN

BACKGROUND: Quinoa is a food crop native to the Andes. The process of dehulling quinoa can produce approximately 8-12% husk, which is often discarded because it contains bitter saponin. Saponin derived from quinoa has been reported to exhibit anti-inflammatory and antifungal activity. However, the antibacterial effects of quinoa saponin against halitosis-related bacteria are still unclear. METHODS: In this study, quinoa saponin (QS) and alkali-transformed saponin (ATS) were separated by AB-2 resin to obtain QS-30, QS-80, ATS-30 and ATS-80. Halitosis-related bacteria included Porphyromonas gingivalis (P. gingivalis), Clostridium perfringens (C. perfringens) and Fusobacterium nucleatum (F. nucleatum). The MIC and MBC were determined using gradient dilutions in 96-well plates, and the saponins were identified by HPLC and mass spectrometry. The changes in membrane integrity were tested using a microplate reader, the membrane potential was tested by spectrofluorometry, and the morphological characteristics were examined using a transmission electron microscope to explore the antibacterial mechanisms. RESULTS: Antibacterial assays indicated that QS-80 and ATS-80 showed inhibitory activity. In addition, ATS-80 exerted a stronger inhibitory effect than QS-80, especially against Fusobacterium nucleatum, with a lower minimum inhibitory concentration (31.3 µg/mL) and a lower minimum bactericidal concentration (125 µg/mL). ATS-80 destroyed the bacterial membrane structure, leading to bacterial death. CONCLUSIONS: Based on the excellent antibacterial activity and economic prospects of quinoa husk, ATS-80 could be used as an antibacterial agent to treat halitosis.


Asunto(s)
Antibacterianos/farmacología , Chenopodium quinoa/química , Halitosis/microbiología , Saponinas/farmacología , Álcalis , Antibacterianos/química , Fusobacterium nucleatum/efectos de los fármacos , Humanos , Potenciales de la Membrana/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/química , Porphyromonas gingivalis/efectos de los fármacos , Saponinas/química
19.
BMC Complement Altern Med ; 18(1): 307, 2018 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-30458808

RESUMEN

BACKGROUND: The phytochemical constituents and biological activities of Rosa rugosa Thunb. var. plena Regal flower cell sap (RFCS) were investigated. METHODS: Volatile constituent, such as linalool, phenylethyl alcohol, citronellol, α-bisabolol, were identified by GC-MS. The contents of hyperoside, kaempferol-3-O-rutinosid, rutin, and luteolin as well as the total flavonoid content in RFCS were determined by HPLC and HPLC-MS. The total polyphenol content was evaluated by the Folin-Ciocalteu colorimetric method. The antioxidant activities of RFCS and the standards were evaluated by DPPH and ABTS radical scavenging assays. The tyrosinase inhibitory activities of the rose samples and standard substance were determined by a spectrophotometric method. The antimicrobial effects of RFCS were evaluated in terms of minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) or minimum Fungicidal concentrations (MFCs). RESULTS: The rose fraction exhibited a high content of biologically active ingredients. The total content of volatile compounds in RFCS was approximately 48.21 ± 2.76 ng/mL. The total phenolic acid content and total flavonoid content were 0.31 ± 0.01 mg/mL and 0.43 ± 0.01 mg/mL, respectively. Its IC50 value in the DPPH assay was 1120 ± 42 µg/mL, and its IC50 value for ABTS radical scavenging activity was 1430 ± 42 µg/mL.RFCS strongly inhibited L-tyrosine oxidation with an IC50 value of 570 ± 21 µg/mL. Every compound identified in RFCS exhibited broad-spectrum antimicrobial activity. F. nucleatum was most susceptible to RFCS with an MIC of 64 µg/mL and MBC of 250 µg/mL. CONCLUSIONS: Due to its rose-like aroma, phenylethyl alcohol may be combined with linalool for use as a natural skin-whitening agent and skin care additive in the and pharmaceutical industries.


Asunto(s)
Antiinfecciosos/química , Antioxidantes/química , Inhibidores Enzimáticos/química , Monofenol Monooxigenasa/antagonistas & inhibidores , Extractos Vegetales/química , Polifenoles/química , Rosa/química , Compuestos Orgánicos Volátiles/química , Antiinfecciosos/farmacología , Antioxidantes/farmacología , Bacterias/efectos de los fármacos , Bacterias/crecimiento & desarrollo , Cromatografía Líquida de Alta Presión , Inhibidores Enzimáticos/farmacología , Flores/química , Hongos/efectos de los fármacos , Hongos/crecimiento & desarrollo , Cromatografía de Gases y Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Monofenol Monooxigenasa/química , Extractos Vegetales/farmacología , Polifenoles/farmacología , Compuestos Orgánicos Volátiles/farmacología , Residuos/análisis
20.
Environ Sci Pollut Res Int ; 25(22): 22106-22119, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29802615

RESUMEN

To unravel the ecological function played by pioneer plants in the practical restoration of mine tailings, it is vital to explore changes of soil characteristics and microbial communities in rhizosphere and bulk soil following the adaptation and survival of plants. In the present study, the diversity and structure of rhizospheric bacterial communities of three pioneer plants in copper mine tailings were investigated by Illumina MiSeq sequencing, and the effects of pioneer plants on soil properties were also evaluated. Significant soil improvement was detected in rhizospheric samples, and Alnus cremastogyne showed higher total organic matter, total nitrogen, and available phosphorus than two other herbaceous plants. Microbial diversity indices in rhizosphere and bulk soil of reclaimed tailings were significantly higher than bare tailings, even the soil properties of bulk soil in reclaimed tailings were not significantly different from those of bare tailings. A detailed taxonomic composition analysis demonstrated that Alphaproteobacteria and Deltaproteobacteria, Chloroflexi, Acidobacteria, and Gemmatimonadetes showed significantly higher relative abundance in rhizosphere and bulk soil. In contrast, Gammaproteobacteria and Firmicutes were abundant in bare tailings, in which Bacillus, Pseudomonas, and Lactococcus made up the majority of the bacterial community (63.04%). Many species within known heavy metal resistance and nutrient regulatory microorganism were identified in reclaimed tailings, and were more abundant among rhizospheric microbes. Hierarchical clustering and principal coordinate analysis (PCoA) analysis demonstrated that the bacterial profiles in the rhizosphere clustered strictly together according to plant types, and were distinguishable from bulk soil. However, we also identified a large shared OTUs that occurred repeatedly and was unaffected by highly diverse soil properties in rhizosphere and bulk samples. Redundancy analysis indicated that water content and Cu and As concentrations were the main environmental regulators of microbial composition. These results suggest that the interactive effect of pioneer plants and harsh soil environmental conditions remodel the specific bacterial communities in rhizosphere and bulk soil in mine tailings. And A. cremastogyne might be approximate candidate for phytoremediation of mine tailings for better soil amelioration effect and relative higher diversity of bacterial community in rhizosphere.


Asunto(s)
Biodegradación Ambiental , Plantas , Rizosfera , Microbiología del Suelo , Bacterias/genética , China , Cobre , Contaminación Ambiental , Metales Pesados/análisis , Microbiota , Minería , Nitrógeno/análisis , Nitrógeno/metabolismo , Fósforo/análisis , Fósforo/metabolismo , Suelo/química
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