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1.
J Enzyme Inhib Med Chem ; 39(1): 2292006, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38086769

RESUMEN

In this study, seventeen isobavachalcone (IBC) derivatives (1-17) were synthesised, and evaluated for their cytotoxic activity against three human lung cancer cell lines. Among these derivatives, compound 16 displayed the most potent cytotoxic activity against H1975 and A549 cells, with IC50 values of 4.35 and 14.21 µM, respectively. Compared with IBC, compound 16 exhibited up to 4.11-fold enhancement of cytotoxic activity on human non-small cell lung cancer H1975 cells. In addition, we found that compound 16 suppressed H1975 cells via inducing apoptosis and necroptosis. The initial mechanism of compound 16 induced cell death in H1975 cells involves the increasing of Bax/Bcl-2 ratio and Cyt C protein level, down-regulating of Akt protein level, and cleaving caspase-9 and -3 induced apoptosis; the up-regulation of RIP3, p-RIP3, MLKL, and p-MLKL levels induced necroptosis. Moreover, compound 16 also caused mitochondrial dysfunction, thereby decreasing cellular ATP levels, and resulting in excessive reactive oxygen species (ROS) accumulation.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Necroptosis , Apoptosis , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo
2.
Chem Pharm Bull (Tokyo) ; 71(11): 798-803, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37914257

RESUMEN

Four new magnolol derivatives were synthesized and evaluated for their in vitro anti-cancer properties. Among these, compound 3 showed the most potent cytotoxic activity against the SMMC-7721, SUN-449, and HepG2 human hepatocellular carcinoma cell lines, with IC50 values of 3.39, 4.11, and 6.88 µM, respectively. Compound 3 also induced apoptosis of SMMC-7721 cells by down-regulating Bcl-2 and Akt protein levels, up-regulating of Bax protein level, and cleaving caspase-9 and -3. In addition, transwell assays showed that compound 3 significantly suppressed the migration and invasion of SMMC-7721 cells, which was confirmed based on the down-regulation of hypoxia inducible factor-1α (HIF-1α), matrix metalloproteinase-2 and -9 (MMP-2, and MMP-9) protein levels.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Metaloproteinasa 2 de la Matriz/metabolismo , Línea Celular Tumoral , Movimiento Celular , Invasividad Neoplásica , Apoptosis , Proliferación Celular
3.
J Asian Nat Prod Res ; 25(8): 731-740, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36448521

RESUMEN

AbstactA total of 16 fungal strains were isolated from fresh leaves and flowers of Magnolia grandiflora and the EtOAc extracts of them were assayed for antitumor activities. Among these, the fungus Dothideomycetes sp. BMC-101 with broad spectrum inhibition was selected for further study. Four alkaloids (1-4) including two new compounds (2-(hydroxyimino)-3-phenylpropanoyl)-L-phenylalanine (1) and 8-Acetyl-bisdethiobis(methylsulfanyl)apoaranotin (4)) were isolated from Dothideomycetes sp. BMC-101. The structure of 1 was characterized with an oxime moiety formed by the condensation of two phenylalanines. To our knowledge, this is the first report on a fungal phenylalanine derivative with an oxime moiety.

4.
Molecules ; 28(17)2023 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-37687063

RESUMEN

As a biodegradable and renewable material, polylactic acid is considered a major environmentally friendly alternative to petrochemical plastics. Microbial fermentation is the traditional method for lactic acid production, but it is still too expensive to compete with the petrochemical industry. Agro-industrial wastes are generated from the food and agricultural industries and agricultural practices. The utilization of agro-industrial wastes is an important way to reduce costs, save energy and achieve sustainable development. The present study aimed to develop a method for the valorization of Zizania latifolia waste and cane molasses as carbon sources for L-lactic acid fermentation using Rhizopus oryzae LA-UN-1. The results showed that xylose derived from the acid hydrolysis of Z. latifolia waste was beneficial for cell growth, while glucose from the acid hydrolysis of Z. latifolia waste and mixed sugars (glucose and fructose) from the acid hydrolysis of cane molasses were suitable for the accumulation of lactic acid. Thus, a three-stage carbon source utilization strategy was developed, which markedly improved lactic acid production and productivity, respectively reaching 129.47 g/L and 1.51 g/L·h after 86 h of fermentation. This work demonstrates that inexpensive Z. latifolia waste and cane molasses can be suitable carbon sources for lactic acid production, offering an efficient utilization strategy for agro-industrial wastes.


Asunto(s)
Melaza , Rhizopus oryzae , Bastones , Residuos Industriales , Ácido Láctico , Carbono , Glucosa
5.
Opt Lett ; 47(4): 917-920, 2022 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-35167558

RESUMEN

The angle-sensitive photonic bandgap (PBG) is one of the typical features of one-dimensional photonic crystals. Based on the phase-variation compensation effect between the dielectric and hyperbolic metamaterials (HMMs), angle-insensitive PBGs can be realized in photonic hypercrystals. However, since hypercrystals are usually constructed using metal components, these angle-insensitive PBGs are mostly limited to narrow bandwidths in visible range. Here, we replace metal with indium tin oxide (ITO) to construct HMMs in the near-infrared range. In these ITO-based HMMs, we experimentally demonstrate the negative refraction of light in transverse magnetic polarization. With this HMM component, we realize a photonic hypercrystal with an angle-insensitive PBG in the wavelength range of 1.15-2.02 µm. These ITO-based hypercrystals with large angle-insensitive PBGs can find applications in near-infrared reflectors or filters.

6.
Molecules ; 27(20)2022 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-36296386

RESUMEN

Standardized treatment guidelines and effective drugs are not available for human triple-negative breast cancer (TNBC). Many efforts have recently been exerted to investigate the efficacy of natural compounds as anticancer agents owing to their low toxicity. However, no study has examined the effects of isobavachalcone (IBC) on the programmed cell death (PCD) of human triple-negative breast MDA-MB-231 cancer cells. In this study, IBC substantially inhibited the proliferation of MDA-MB-231 cells in concentration- and time-dependent manners. In addition, we found that IBC induced multiple cell death processes, such as apoptosis, necroptosis, and autophagy in MDA-MB-231 cells. The initial mechanism of IBC-mediated cell death in MDA-MB-231 cells involves the downregulation of Akt and p-Akt-473, an increase in the Bax/Bcl-2 ratio, and cleaved caspases-3 induced apoptosis; the upregulation of RIP3, p-RIP3 and MLKL induced necroptosis; as well as a simultaneous increase in LC3-II/I ratio induced autophagy. In addition, we observed that IBC induced mitochondrial dysfunction, thereby decreasing cellular ATP levels and increasing reactive oxygen species accumulation to induce PCD. These results suggest that IBC is a promising lead compound with anti-TNBC activity.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular Tumoral , Proteína X Asociada a bcl-2 , Apoptosis , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Adenosina Trifosfato/farmacología , Proliferación Celular
7.
Opt Express ; 29(12): 17736-17745, 2021 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-34154050

RESUMEN

Contrary to conventional Tamm plasmon (TP) absorbers of which narrow absorptance peaks will shift toward short wavelengths (blueshift) as the incident angle increases for both transverse magnetic (TM) and transverse electric (TE) polarizations, here we theoretically and experimentally achieve nonreciprocal absorption in a planar photonic heterostructure composed of an isotropic epsilon-near-zero (ENZ) slab and a truncated photonic crystal for TM polarization. This exotic phenomenon results from the interplay between ENZ and material loss. And the boundary condition across the ENZ interface and the confinement effect provided by the TP can enhance the absorption in the ENZ slab greatly. As a result, a strong and nonreciprocal absorptance peak is observed experimentally with a maximum absorptance value of 93% in an angle range of 60∼70°. Moreover, this TP absorber shows strong angle-independence and polarization-dependence. As the characteristics above are not at a cost of extra nanopatterning, this structure is promising to offer a practical design in narrowband thermal emitter, highly sensitive biosensing, and nonreciprocal nonlinear optical devices.

8.
Inorg Chem ; 60(15): 11081-11089, 2021 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-34242020

RESUMEN

A CuI-TbIII heterometallic MOF, namely 1·DMF, was obtained via a coordination assembly process of isonicotinic acid with CuI and TbIII. 1·DMF can be switched to 1·MeOH in methanol with a luminescent emission response. Meanwhile, 1·MeOH exhibits a reversible single-crystal transformation to 1·DMF after immersion in DMF. Both MOFs have superior physicochemical stability. The 1·DMF-based biosensor has a remarkable sensing performance toward penicillin.


Asunto(s)
Cobre/química , Luminiscencia , Compuestos Organometálicos/química , Penicilinas/análisis , Terbio/química , Teoría Funcional de la Densidad , Modelos Moleculares , Conformación Molecular , Penicilinas/química
9.
Molecules ; 26(14)2021 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-34299577

RESUMEN

Magnolol (MAG), a biphenolic neolignan, has various biological activities including antitumor effects. In this study, 15 MAG derivatives were semi-synthesized and evaluated for their in vitro anticancer activities. From these derivatives, compound 6a exhibited the best cytotoxic activity against four human cancer cell lines, with IC50 values ranging from 20.43 to 28.27 µM. Wound-healing and transwell assays showed that compound 6a significantly inhibited the migration and invasion of MDA-MB-231 cells. In addition, Western blotting experiments, performed using various concentrations of 6a, demonstrated that it downregulates the expression of HIF-1α, MMP-2, and MMP-9 in a concentration-dependent manner. Overall, these results suggest that substituting a benzyl group having F atoms substituted at the C2 position on MAG is a viable strategy for the structural optimization of MAG derivatives as anticancer agents.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Compuestos de Bifenilo/química , Compuestos de Bifenilo/farmacología , Lignanos/química , Lignanos/farmacología , Antineoplásicos/síntesis química , Compuestos de Bifenilo/síntesis química , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Lignanos/síntesis química , Invasividad Neoplásica/prevención & control , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico
10.
Pain Med ; 21(6): 1216-1223, 2020 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-31722404

RESUMEN

OBJECTIVES: Central neuropathic pain (CNP) often appears following spinal cord injury (SCI), but current treatments are not always successful. In this study, we evaluated the analgesic effects of repetitive transcranial magnetic stimulation (rTMS) applied over the hand area of the motor cortex in patients with acute CNP after SCI. METHODS: A total of 48 patients with complete or incomplete SCI and acute CNP participated in this study and were randomized to receive either rTMS (10 Hz, 1,500 stimuli; N = 24) or a sham intervention (N = 24) for three weeks. The numeric rating scale (NRS) and Short-Form McGill Pain Questionnaire-2 (Chinese Edition; SF-MPQ-2-CN) were analyzed to assess the degree of pain. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were collected to explore expression influenced by rTMS. Motor-evoked potential (MEP) latency and maximal amplitude were measured to determine neurophysiological changes. The assessments were carried out at baseline (T0), three days (T1), one week (T2), two weeks (T3), and three weeks (T4) after onset of treatment. RESULTS: The analysis showed significant treatment-time interactions for the quality and intensity of pain, as measured by NRS (P < 0.001, η2 = 0.441) and SF-MPQ-2 (P < 0.001, η2 = 0.590). Compared with the sham group, the NRS and SF-MPQ2-CN scores were significantly lower on the third day (P < 0.001, Cohen's d = 1.135; P = 0.006, Cohen's d = 0.616) and after one week (P < 0.001, Cohen's d = 0.846; P = 0.012, Cohen's d = 0.557) of treatment. In addition, the serum levels of BDNF and NGF were significantly higher in the treated group after three weeks (P = 0.015, Cohen's d = 0.539; P = 0.009, Cohen's d = 0.580), and the MEP amplitude increased by 109.59% (P = 0.033, Cohen's d = 0.464). CONCLUSIONS: These findings indicate that 10 Hz rTMS over the hand area of the motor cortex could alleviate acute CNP in the early phase of SCI and could enhance MEP parameters and modulate BDNF and NGF secretion.


Asunto(s)
Neuralgia , Traumatismos de la Médula Espinal , Analgésicos , Humanos , Neuralgia/etiología , Neuralgia/terapia , Dimensión del Dolor , Traumatismos de la Médula Espinal/complicaciones , Estimulación Magnética Transcraneal
11.
J Stroke Cerebrovasc Dis ; 26(1): 125-131, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27645612

RESUMEN

BACKGROUND: Anticoagulation therapy has been recommended by major guidelines to reduce the risk of recurrent stroke in patients with atrial fibrillation-associated ischemic stroke (AFAIS). However, in real-world clinical practice, oral anticoagulants with either vitamin K antagonists or nonvitamin K antagonists are often underused for these patients. Here, we sought to investigate the current status of oral anticoagulant use in patients with AFAIS in northwestern China. METHODS: We reviewed medical records of consecutive patients with AFAIS discharged from 14 hospitals in northwestern China between January 2012 and May 2015. RESULTS: A total of 1014 cases were included in this study. The mean age of the patients was 70.3 ± 10.8 years. Fifty-four percent were female. Among all participants, only 20.0% received anticoagulants (19.4% warfarin and .6% nonvitamin K antagonist oral anticoagulants), whereas 57.5% took antiplatelet drugs and 22.5% received neither anticoagulant nor antiplatelet treatment. Anticoagulant use decreased with increasing age and CHA2DS2-VASc scores. The proportions of anticoagulant use at discharge in patients younger than 65 years, 65-74 years, and 75 years or older were 28.5%, 20.7%, and 13.9%, respectively. Nonvalvular atrial fibrillation patients with CHA2DS2-VASc scores of 2, 3, 4, 5, 6, and 7 had anticoagulant use rates at discharge of 19.2%, 24.8%, 20.3%, 13.7%, 8.1%, and 8.0%, respectively. CONCLUSIONS: In northwestern China, oral anticoagulants are substantially underutilized in patients with AFAIS, especially in patients at higher risk of stroke, suggesting a large treatment gap in the secondary prevention management in patients with AFAIS.


Asunto(s)
Anticoagulantes/administración & dosificación , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/prevención & control , Administración Oral , Factores de Edad , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/complicaciones , China/epidemiología , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Prevención Secundaria , Estadísticas no Paramétricas , Accidente Cerebrovascular/etiología
12.
J Neuroinflammation ; 13(1): 180, 2016 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-27391369

RESUMEN

BACKGROUND: Reactive astrogliosis is a remarkable pathogenetic hallmark of the brains of Parkinson's disease (PD) patients, but its progressive fate and regulation mechanisms are poorly understood. In this study, growth arrest specific 1 (Gas1), a tumor growth suppressor oncogene, was identified as a novel modulator of the cell apoptosis of reactive astrocytes in primary culture and the injured substantia nigra. METHODS: Animal models and cell cultures were utilized in the present study. Lipopolysaccharide (LPS)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated animal models were used to detect Gas1 expression in the brain via immunohistochemistry and western blot. Cell cultures were performed to analyze Gas1 functions in the viability and apoptosis of reactive astrocytes and SH-SY5Y cells by double labeling, CCK-8, LDH, TUNEL, flow cytometry, and siRNA knockdown methods. RESULTS: Gas1 expressions were significantly elevated in the majority of the reactive astrocytes of the brains with LPS or MPTP insults. In the injured substantia nigras, GFAP-positive astrocytes exhibited higher levels of cleaved caspase-3. In cell culture, the up-regulated Gas1 expression induced apoptosis of reactive astrocytes that were insulted by LPS in combination with interferon-γ and tumor necrosis factor-a. This effect was confirmed through siRNA knockdown of Gas1 gene expression. Finally and interestingly, the potential underlying signaling pathways were evidently related to an increase in the Bax/Bcl-2 ratio, the abundant generation of reactive oxygen species and the activation of cleaved caspase-3. CONCLUSIONS: This study demonstrated that the up-regulation of inducible Gas1 contributed to the apoptosis of reactive astrocytes in the injured nigra. Gas1 signaling may function as a novel regulator of astrogliosis and is thus a potential intervention target for inflammatory events in PD conditions.


Asunto(s)
Apoptosis/fisiología , Astrocitos/metabolismo , Proteínas de Ciclo Celular/biosíntesis , Intoxicación por MPTP/metabolismo , Sustancia Negra/metabolismo , Regulación hacia Arriba/fisiología , Animales , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Astrocitos/efectos de los fármacos , Astrocitos/patología , Línea Celular Tumoral , Células Cultivadas , Proteínas Ligadas a GPI/biosíntesis , Humanos , Lipopolisacáridos/toxicidad , Intoxicación por MPTP/patología , Ratones , Ratones Endogámicos C57BL , Ratas , Ratas Sprague-Dawley , Sustancia Negra/efectos de los fármacos , Sustancia Negra/patología , Regulación hacia Arriba/efectos de los fármacos
13.
Neurochem Res ; 41(4): 933-42, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26700432

RESUMEN

Accumulating data suggest that sodium-hydrogen exchangers (NHEs) play a key role in modulating seizure activity by regulating neuronal pH in the brain. Amiloride, an inhibitor of NHEs, has been demonstrated to be effective in many seizure models, although its efficacy for prolonged febrile seizures (FS) remains unclear. In this study, we investigated whether amiloride could produce neuroprotective effects in a prolonged FS model in which FS were induced in rat pups at postnatal day 10 using a heated air approach. Amiloride was administered by intraperitoneal injection at three different doses (0.65, 1.3 and 2.6 mg/kg). Pretreatment with amiloride significantly delayed the onset of the first episode of limbic seizures, whereas posttreatment with amiloride decreased escape latency in the Morris water maze test compared to post-FS treatment with saline. Amiloride also inhibited seizure-induced aberrant neurogenesis. In conclusion, this study demonstrated the antiseizure activity of amiloride. In particular, posttreatment with amiloride resulted in cognitive improvement; this finding provides crucial evidence of the neuroprotective function of amiloride and of the therapeutic potential of amiloride in FS.


Asunto(s)
Amilorida/uso terapéutico , Proteínas de Transporte de Catión/antagonistas & inhibidores , Trastornos del Conocimiento/tratamiento farmacológico , Convulsiones Febriles/tratamiento farmacológico , Intercambiadores de Sodio-Hidrógeno/antagonistas & inhibidores , Animales , Presión Sanguínea/efectos de los fármacos , Proteínas de Transporte de Catión/metabolismo , Trastornos del Conocimiento/psicología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Aprendizaje por Laberinto/efectos de los fármacos , Neurogénesis , Neuronas/patología , Ratas Sprague-Dawley , Convulsiones Febriles/patología , Convulsiones Febriles/fisiopatología , Convulsiones Febriles/psicología , Intercambiador 1 de Sodio-Hidrógeno , Intercambiadores de Sodio-Hidrógeno/metabolismo , Factores de Tiempo
14.
Crit Care ; 20: 46, 2016 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-26916702

RESUMEN

BACKGROUND: Prediction of the functional outcome for patients with convulsive status epilepticus (CSE) has been a challenge. The aim of this study was to characterize the prognostic factors and functional outcomes of patients after CSE in order to develop a practicable scoring system for outcome prediction. METHODS: We performed a retrospective explorative analysis on consecutive patients diagnosed with CSE between March, 2008 and November, 2014 in a tertiary academic medical center in northwest China. The modified Rankin Scale (mRS) was used to measure the functional outcome at three months post discharge. RESULTS: A total of 132 CSE patients was included, with a median age of 25.5 years and 60.6% were male. Three months post discharge, an unfavorable outcome with mRS of 3-6 was seen in 62 (47.0%) patients, 25 (18.9%) of whom died. Logistic regression analysis revealed that encephalitis (p = 0.029), nonconvulsive SE (p = 0.018), diazepam resistance (p = 0.005), image abnormalities (unilateral lesions, p = 0.027; bilateral lesions or diffuse cerebral edema, p < 0.001) and tracheal intubation (p = 0.032) were significant independent predictors for unfavorable outcomes. Based on the coefficients in the model, these predictors were assigned a value of 1 point each, with the exception of the image, creating a 6-point scoring system, which we refer to as END-IT, for the outcome prediction of CSE. The area under the receiver operating characteristic curve for the END-IT score was 0.833 and using a cut-off point of 3 produced the highest sum sensitivity (83.9%) and specificity (68.6%). Compared with status epilepticus severity score (STESS) and Epidemiology-based Mortality score in SE (EMSE), END-IT score showed better discriminative power and predictive accuracy for the outcome prediction. CONCLUSIONS: We developed an END-IT score with a strong discriminative power for predicting the functional outcome of CSE patients. External prospective validation in different cohorts is needed for END-IT score.


Asunto(s)
Evaluación del Resultado de la Atención al Paciente , Estado Epiléptico/mortalidad , Adolescente , Adulto , China , Femenino , Predicción/métodos , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Resultado del Tratamiento
15.
Sheng Li Ke Xue Jin Zhan ; 46(3): 170-4, 2015 Jun.
Artículo en Zh | MEDLINE | ID: mdl-26521480

RESUMEN

Neurotrophic factor is a kind of protein family that plays an important role in the nutrition, support and differentiation to central neurons as well as synaptic plasticity. Growing evidences have revealed that pro-forms of various neurotrophic factors, which are generated in process of protein synthesis and might exert opposite roles involving in inducement of neuronal apoptosis and implication in pathogenesis of neurodegenerative diseases. This paper reviews "Yin/Yang" features of neurotrophic factors in the anabolism, receptor regulation, functional aspects, and their related role in pathogenesis of neurodegenerative diseases. It is hopefully to provide new idea on understanding and investigation of the neurotrophic factors regarding on their functional, pathological and potential therapeutic significance.


Asunto(s)
Neuronas , Apoptosis , Humanos , Factores de Crecimiento Nervioso , Enfermedades Neurodegenerativas , Plasticidad Neuronal
16.
Front Plant Sci ; 15: 1425759, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39119497

RESUMEN

Introduction: Currently, the development of new antiviral drugs against COVID-19 remains of significant importance. In traditional Chinese medicine, the herb Euphorbia fischeriana Steud is often used for antiviral treatment, yet its therapeutic effect against the COVID-19 has been scarcely studied. Therefore, this study focuses on the roots of E. fischeriana Steud, exploring its chemical composition, antiviral activity against COVID-19, and the underlying basis of its antiviral activity. Methods: Isolation and purification of phytochemicals from E. fischeriana Steud. The elucidation of their configurations was achieved through a comprehensive suite of 1D and 2D NMR spectroscopic analyses as well as X-ray diffraction. Performed cytopathic effect assays of SARS-CoV-2 using Vero E6 cells. Used molecular docking to screen for small molecule ligands with binding to SARS-CoV-2 RdRp. Microscale thermophoresis (MST) was used to determine the dissociation constant Kd. Results: Ultimately, nine new ent-atisane-type diterpenoid compounds were isolated from E. fischeriana Steud, named Eupfisenoids A-I (compounds 1-9). The compound of 1 was established as a C-19-degraded ent-atisane-type diterpenoid. During the evaluation of these compounds for their antiviral activity against COVID-19, compound 1 exhibited significant antiviral activity. Furthermore, with the aid of computer virtual screening and microscale thermophoresis (MST) technology, it was found that this compound could directly bind to the RNA-dependent RNA polymerase (RdRp, NSP12) of the COVID-19, a key enzyme in virus replication. This suggests that the compound inhibits virus replication by targeting RdRp. Discussion: Through this research, not only has our understanding of the antiviral components and material basis of E. fischeriana Steud been enriched, but also the potential of atisane-type diterpenoid compounds as antiviral agents against COVID-19 has been discovered. The findings mentioned above will provide valuable insights for the development of drugs against COVID-19.

17.
Int J Mol Sci ; 14(7): 14085-104, 2013 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-23880857

RESUMEN

Growing evidence has shown that proNGF-p75NTR-sortilin signaling might be a crucial factor in neurodegeneration, but it remains unclear if it may function in nigral neurons under aging and disease. The purpose of this study is to examine and quantify proNGF and sortilin expression in the substantia nigra and dynamic changes of aging in lactacystin and 6-hydroxydopamine (6-OHDA) rat models of Parkinson's disease using immunofluorescence, electronic microscopy, western blot and FLIVO staining methods. The expression of proNGF and sortilin was abundantly and selectively identified in tyrosine hydroxylase (TH)-containing dopamine neurons in the substantia nigra. These proNGF/TH, sortilin/TH-positive neurons were densely distributed in the ventral tier, while they were less distributed in the dorsal tier, where calbindin-D28K-containing neurons were numerously located. A correlated decrease of proNGF, sortilin and TH was also detected during animal aging process. While increase of proNGF, sortilin and cleaved (active) caspase-3 expression was found in the lactacystin model, dynamic proNGF and sortilin changes along with dopamine neuronal loss were demonstrated in the substantia nigra of both the lactacystin and 6-OHDA models. This study has thus revealed the presence of the proNGF-sortilin signaling complex in nigral dopamine neurons and its response to aging, lactacystin and 6-OHDA insults, suggesting that it might contribute to neuronal apoptosis or neurodegeneration during pathogenesis and disease progression of Parkinson's disease; the underlying mechanism and key signaling pathways involved warrant further investigation.


Asunto(s)
Acetilcisteína/análogos & derivados , Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Envejecimiento , Antibacterianos/toxicidad , Factor de Crecimiento Nervioso/metabolismo , Oxidopamina/toxicidad , Sustancia Negra/efectos de los fármacos , Acetilcisteína/toxicidad , Animales , Apoptosis/efectos de los fármacos , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/enzimología , Neuronas Dopaminérgicas/metabolismo , Proteínas del Tejido Nervioso , Precursores de Proteínas/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de Factores de Crecimiento , Receptores de Factor de Crecimiento Nervioso/metabolismo , Transducción de Señal/efectos de los fármacos , Sustancia Negra/metabolismo , Sustancia Negra/patología , Tirosina 3-Monooxigenasa/metabolismo
18.
Sci Total Environ ; 863: 160953, 2023 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-36543072

RESUMEN

Microplastics, defined as particles <5 mm in diameter, are emerging environmental pollutants that pose a threat to ecosystems and human health. Biofilm degradation of microplastics may be an ecologically friendly approach. This review systematically summarises the factors affecting biofilm degradation of microplastics and proposes feasible methods to improve the efficiency of microplastic biofilm degradation. Environmentally insensitive microorganisms were screened, optimized, and commercially cultured to facilitate the practical application of this technology. For strain screening, technology should focus on microorganisms/strains that can modify the hydrophobicity of microplastics, degrade the crystalline zone of microplastics, and metabolise additives in microplastics. The biodegradation mechanism is also described; microorganisms secreting extracellular oxidases and hydrolases are key factors for degradation. Measuring the changes in molecular weight distribution (MWD) enables better analysis of the biodegradation behaviour of microplastics. Biofilm degradation of microplastics has relatively few applications because of its low efficiency; however, enrichment of microplastics in freshwater environments and wastewater treatment plant tailwater is currently the most effective method for treating microplastics with biofilms.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Humanos , Plásticos/análisis , Ecosistema , Biodegradación Ambiental , Contaminantes Químicos del Agua/análisis , Biopelículas , Agua Dulce , Monitoreo del Ambiente/métodos
19.
Appl Biochem Biotechnol ; 195(1): 623-638, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36114924

RESUMEN

Aurantiochytrium is a promising source of docosahexaenoic acid (DHA) and carotenoids, but their synthesis is influenced by environmental stress factors. In this study, the effect of different light intensities on the fermentation of DHA oil and carotenoids using Aurantiochytrium sp. TZ209 was investigated. The results showed that dark culture and low light intensity conditions did not affect the normal growth of cells, but were not conducive to the accumulation of carotenoids. High light intensity promoted the synthesis of DHA and carotenoids, but caused cell damage, resulting in a decrease of oil yield. To solve this issue, a light intensity gradient strategy was developed, which markedly improved the DHA and carotenoid content without reducing the oil yield. This strategy produced 30.16 g/L of microalgal oil with 15.11 g/L DHA, 221 µg/g astaxanthin, and 386 µg/g ß-carotene. This work demonstrates that strain TZ209 is a promising DHA producer and provides an efficient strategy for the co-production of DHA oil together with carotenoids.


Asunto(s)
Carotenoides , Estramenopilos , Ácidos Docosahexaenoicos , Fermentación , beta Caroteno
20.
Front Neurol ; 14: 1175078, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37333013

RESUMEN

Background: After spinal cord injury (SCI), the excitability of the primary motor cortex (M1) lower extremity area decreases or disappears. A recent study reported that the M1 hand area of the SCI patient encodes the activity information of both the upper and lower extremities. However, the characteristics of the M1 hand area corticospinal excitability (CSE) changes after SCI and its correlation with extremities motor function are still unknown. Methods: A retrospective study was conducted on the data of 347 SCI patients and 80 healthy controls on motor evoked potentials (MEP, reflection of CSE), extremity motor function, and activities of daily living (ADL) ability. Correlation analysis and multiple linear regression analysis were conducted to analyze the relationship between the degree of MEP hemispheric conversion and extremity motor function/ADL ability. Results: The CSE of the dominant hemisphere M1 hand area decreased in SCI patients. In 0-6 m, AIS A grade, or non-cervical injury SCI patients, the degree of M1 hand area MEP hemispheric conversion was positively correlated with total motor score, lower extremity motor score (LEMS), and ADL ability. Multiple linear regression analysis further confirmed the contribution of MEP hemispheric conversion degree in ADL changes as an independent factor. Conclusion: The closer the degree of M1 hand area MEP hemispheric conversion is to that of healthy controls, the better the extremity motor function/ADL ability patients achieve. Based on the law of this phenomenon, targeted intervention to regulate the excitability of bilateral M1 hand areas might be a novel strategy for SCI overall functional recovery.

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