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1.
Eur J Neurosci ; 59(7): 1428-1440, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38151046

RESUMEN

Methamphetamine use disorder (MAUD) can substantially jeopardize public security due to its high-risk social psychology and behaviour. Given that the dopamine reward system is intimately correlated with MAUD, we investigated the association of single nucleotide polymorphisms (SNPs), as well as methylation status of dopamine receptor type 4 (DRD4), catechol-O-methyltransferase (COMT) genes, and paranoid and motor-impulsive symptoms in MAUD patients. A total of 189 MAUD patients participated in our study. Peripheral blood samples were used to detect 3 SNPs and 35 CpG units of methylation in the DRD4 gene promoter region and 5 SNPs and 39 CpG units in the COMT gene. MAUD patients with the DRD4 rs1800955 C allele have a lower percentage of paranoid symptoms than those with the rs1800955 TT allele. Individuals with paranoid symptoms exhibited a reduced methylation degree at a particular DRD4 CpG2.3 unit. The interaction of the DRD4 rs1800955 C allele and the reduced DRD4CpG2.3 methylation degree were associated with a lower occurrence of paranoid symptoms. Meanwhile, those with the COMT rs4818 CC allele had lower motor-impulsivity scores in MAUD patients but greater COMT methylation levels in the promoter region and methylation degree at the COMT CpG 51.52 unit. Therefore, based only on the COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor-impulsive scores. Our preliminary results provide a clue that the combination of SNP genotype and methylation status of the DRD4 and COMT genes serve as biological indicators for the prevalence of relatively high-risk psychotic symptoms in MAUD patients.


Asunto(s)
Metanfetamina , Polimorfismo de Nucleótido Simple , Humanos , Catecol O-Metiltransferasa/genética , Dopamina , Metanfetamina/efectos adversos , Genotipo , Metilación
2.
Pharmacol Res ; 166: 105510, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33610720

RESUMEN

Cardiovascular disease (CVD), including heart failure, myocardial fibrosis and myocardial infarction, etc, remains one of the leading causes of mortality worldwide. Evidence shows that miRNA plays an important role in the pathogenesis of CVD. miR-29 family is one of miRNA, and over the past decades, many studies have demonstrated that miR-29 is involved in maintaining the integrity of arteries and in the regulation of atherosclerosis, especially in the process of myocardial fibrosis. Besides, heart failure, myocardial fibrosis and myocardial infarction are inseparable from the regulatory role of miR-29. Here, we comprehensively review recent studies regarding miR-29 and CVD, illustrate the possibility of miR-29 as a potential marker for prevention, treatment and prognostic observation.


Asunto(s)
Enfermedades Cardiovasculares/genética , MicroARNs/genética , Animales , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/patología , Enfermedades Cardiovasculares/terapia , Fibrosis , Regulación de la Expresión Génica , Humanos , MicroARNs/análisis , Miocardio/patología , Pronóstico
3.
Pharmacol Res ; 167: 105563, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33746053

RESUMEN

Macrophages are heterogeneous cells that have different physiological functions, such as chemotaxis, phagocytosis, endocytosis, and secretion of various factors. All physiological functions of macrophages are integral to homeostasis, immune defense and tissue repair. However, in several diseases, macrophages are recruited from the blood towards inflammatory sites. This process is called macrophage migration, which promotes deleterious disease progression. Macrophage migration is a key player in many inflammatory diseases, autoimmune diseases and cancers because it contributes to the accumulation of proinflammatory factors, the destruction of tissues and the development of tumors. Therefore, macrophage migration is proposed to be a potential therapeutic target. Macrophages migrate between two-dimensional (2D) and three-dimensional (3D) environments, implying that distinct migratory features and mechanisms are involved. Compared with the 2D migration of macrophages, 3D migration involves more complex variations in cellular morphology and dynamics. The structure of the extracellular matrix, a key factor, is modified in diseases that influence macrophage 3D migration. Macrophage 3D migration relates to disease pathology. Research that focuses on macrophage 3D migration is an emerging field and was reviewed in this article to indicate the molecular and cellular mechanisms of macrophage migration in 3D environments and to provide potential targets for controlling disease progression associated with this migration.


Asunto(s)
Movimiento Celular , Inflamación/patología , Macrófagos/patología , Animales , Antiinflamatorios/farmacología , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Movimiento Celular/efectos de los fármacos , Progresión de la Enfermedad , Descubrimiento de Drogas , Humanos , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Activación de Macrófagos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Terapia Molecular Dirigida , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/patología
4.
Int J Legal Med ; 135(3): 783-785, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33141282

RESUMEN

Y-chromosome haplotypes of 527 non-related males (176 Han, 186 Tibetan, and 165 Yi) in the Tibetan-Yi corridor were analyzed using SureID® PathFinder Plus. In the populations of Han, Tibetans, and Yi, the haplotype diversity was 0.9989, 0.9981, and 0.9993, respectively, and the discrimination capacity was 0.9148, 0.8925, and 0.9576, respectively. Phylogenetic relationships among 12 studied ethnic groups and 7 other ethnic groups in the Tibetan-Yi corridor were investigated. Both multi-dimensional scaling analysis and phylogenetic reconstructions indicated that Tibetans appeared separated from the Han and Yi ethnic groups in the Tibetan-Yi corridor. Their genetic homogeneity or heterogeneity has not entirely been affected by their geographical distance and linguistic origin.


Asunto(s)
Pueblo Asiatico/etnología , Pueblo Asiatico/genética , Cromosomas Humanos Y , Etnicidad/genética , Haplotipos , Repeticiones de Microsatélite , Alelos , Variación Genética , Genética de Población , Humanos , Masculino , Filogenia , Tibet/etnología
5.
Zhongguo Zhong Yao Za Zhi ; 45(10): 2425-2430, 2020 May.
Artículo en Zh | MEDLINE | ID: mdl-32495602

RESUMEN

Thin layer chromatography, high performance liquid chromatography and multivariate statistical analysis were integrated in current study to provide a basis for the quality evaluation and the standard improvement of Paridis Rhizoma(Chinese name: Chong-lou). The results demonstrated that the primary saponins in the two authorized sources of Paridis Rhizoma were polyphyllinsⅠ, Ⅱ and Ⅶ, while the rhizome of Trillium tschonoskii an adulterant of Paridis Rhizoma was rich of polyphyllin Ⅵ. Therefore, the apparent content of polyphyllin Ⅵ plays a determinant role towards the source authentication of raw materials and decoction slices of Paridis Rhizoma, whose adulterants frequently occur in the market. Moreover, the contents of polyphyllin Ⅵ in the two authorized sources could meet the requirements of Chinese Pharmacopoeia. Therefore, we suggested that polyphyllin Ⅵ should not be omitted from the quality standard of Paridis Rhizoma in the Chinese Pharmacopoeia, and on the other side, polyphyllinsⅠ, Ⅱ and Ⅶ should be the eligible quality indicators. The study aims to sound information and evidences for the quality evaluation of Paridis Rhizoma, and also to provide a theoretical basis for the standard revision of Paridis Rhizoma in the future Chinese Pharmacopoeia.


Asunto(s)
Medicamentos Herbarios Chinos , Saponinas , Trillium , Cromatografía Líquida de Alta Presión , Rizoma
6.
Zhongguo Zhong Yao Za Zhi ; 44(1): 68-76, 2019 Jan.
Artículo en Zh | MEDLINE | ID: mdl-30868814

RESUMEN

The content of tyrosol,salidroside,echinacoside,rutin,acteoside,ligustroflavone,specnuezhenide,and quercetin were determined by HPLC,and the color of Ligustri Lucidi Fructus was determined by comparison with color card.Hundred-seed weight was analyzed by using gravimetric method.The correlation analysis and One-way ANOVA were used to analyze the relationship between the characters,the chemical composition,the harvest time and the geographical location of Ligustri Lucidi Fructus,for giving a comprehensive evaluation of the quality of Ligustri Lucidi Fructus The results showed that 92% of Ligustri Lucidi Fructus were all up to quality standard of Chinese Pharmacopoeia,and the contents of 7 components in Ligustri Lucidi Fructus(except quercetin) were higher than those in samples with black colors.The content of salidroside in Ligustri Lucidi Fructus harvested in June was the highest and the other7 components of Ligustri Lucidi Fructus were relatively high in 8-10 months.According to the quality parameters of Ligustri Lucidi Fructus,the Ligustri Lucidi Fructus from six habitats can not be distinguished effectively.The results showed that there was a certain relationship between the color,harvest season and component content of Ligustri Lucidi Fructus,and the habitats were not related to the quality parameters of Ligustri Lucidi Fructus.The study aimsat providing data support for the resource status of native Ligustri Lucidi Fructus,and a theoretical basis for the revision of standards of Ligustri Lucidi Fructusin the future.


Asunto(s)
Medicamentos Herbarios Chinos/normas , Frutas/química , Ligustrum/química
7.
Zhongguo Zhong Yao Za Zhi ; 44(18): 4034-4042, 2019 Sep.
Artículo en Zh | MEDLINE | ID: mdl-31872742

RESUMEN

This study aims to compare the internal chemical composition and appearance indifferent growth patterns and years of Saposhnikovia divaricata decoction pieces,which was applied to explore the effect of growth patterns and years on its quality. The appearance characteristic data of 55 batches of different growth patterns and years of S. divaricata were collected using PANTONE color card.High performance liquid chromatography( HPLC) was used to determine the contents of prim-O-glucosyl-cinmifugin,cimifugin,4-O-ß-D-glucosyl-5-O-methylvisamminol and sec-O-glucosylhamaudol. The content of alcohol soluble extract and water-soluble extract were determined by hot-dip method. The content of volatile oil was determined by steam distillation. The correlation between growth patterns and years and the contents of 4 chromones,extracts and volatile oil were analyzed by modern statistical methods. Also,the method of comprehensively evaluating the quality of Chinese herbal pieces was developed by combining the growth patterns and years,appearance and chemical indexes. MTT assay was used to evaluate the effects on the survival rate of RAW264. 7 cells at four different concentrations of chromones and LPS was used to stimulate well-growing RAW264. 7 cells to establish an inflammatory model. The contents of NO and TNF-α in cell supernatant were detected by NO test kit and ELISA method. The contents of alcohol soluble extracts and water-soluble extracts in different growth patterns and years are: wild productsperennial cultivation>annual cultivation; the contents of four chromones are: wild products>perennial cultivation and annual cultivation. There was no significant difference between the sum of the two indexes in the Pharmacopoeia of perennial cultivation and wild products. 4 chromones showed no toxicity to RAW264. 7 cells at 5 mg·L-1. The release of NO and TNF-α was inhibited by 4 chromones and the anti-inflammatory effect of cimifugin was the best. In summary,there are obvious differences in appearance characteristics,internal quality and effects between different growth patterns and years. It showed that the wild products were superior to the perennial cultivation and the perennial cultivation was superior to the annual cultivation. In order to alleviate the shortage of wild S. divaricata resources,it is suggested that the Chinese Pharmacopoeia standard should increase the character of decoction pieces of perennial cultivation,and properly raise the limit requirement of the sum of the two indexes in the Chinese Pharmacopoeia to ensure the clinical demands and effect.


Asunto(s)
Apiaceae/química , Medicamentos Herbarios Chinos/normas , Aceites Volátiles/análisis , Animales , Apiaceae/crecimiento & desarrollo , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/análisis , Ratones , Óxido Nítrico/metabolismo , Células RAW 264.7 , Factor de Necrosis Tumoral alfa/metabolismo
8.
BMC Urol ; 17(1): 38, 2017 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-28558682

RESUMEN

BACKGROUND: Renal cell carcinoma (RCC) is one of the most common types of cancer in urological system worldwide. Recently, the anticancer role of Glucosamine has been studied in many types of cancer. The aim of this study was to investigate the effects of Glucosamine on RCC. METHODS: The effects of Glucosamine on RCC cell proliferation and apoptosis were investigated by MTT assay and Annexin V-FITC Apoptosis assay, respectively in vitro. Cell cycle was detected by flow cytometry after treatment with Glucosamine. Protein levels of several cell cycle associated markers were examined by Western Blot. RESULTS: Our data showed that Glucosamine significantly inhibited the proliferation of renal cancer 786-O and Caki-1 cells in a dose-dependent manner. Besides, Glucosamine treatment resulted in cell cycle arrest at G0/G1 phase in both cell lines. Meanwhile, the expression of several regulators that contribute to G1/S phased transition, such as Cyclin D1, CDK4 and CDK6, were significantly down-regulated with the up-regulation of cell cycle inhibitors, p21 and p53, after treatment with glucosamine. However, the apoptosis rate of RCC cells was down-regulated when treatment with Glucosamine at 1 mM and 5 mM, while up-regulated at 10 mM. CONCLUSIONS: Our findings indicated that Glucosamine inhibited the proliferation of RCC cells by promoting cell cycle arrest at G0/G1 phase, but not promoting apoptosis. The present results suggested that Glucosamine might be a potential therapeutic agent in RCC treatment in the future.


Asunto(s)
Carcinoma de Células Renales/patología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Glucosamina/farmacología , Neoplasias Renales/patología , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Fase G1/efectos de los fármacos , Humanos , Células Tumorales Cultivadas
9.
Molecules ; 22(5)2017 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-28468295

RESUMEN

In traditional Chinese medicine practice, drying method is an essential factor to influence the components of Chinese medicinal herbs. In this study, an ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS)-based approach was used to compare the content of chemical compounds of mountain cultivated ginseng that had been natural air dried (LX-P) and vacuum freeze-dried (LX-L). Multivariate statistical analysis such as principal component analysis (PCA) and supervised orthogonal partial least squared discrimination analysis (OPLS-DA) were used to select the influential components of different samples. There were 41 ginsenosides unambiguously identified and tentatively assigned in both LX-L and LX-P. The results showed that the characteristic components in LX-P were ginsenoside Rb1, ginsenoside Rc, ginsenoside Rg6, dendrolasin, and ginsenoside Rb2. The characteristic components in LX-L were malonyl-ginsenoside Re, malonyl-ginsenoside Rb1, malonyl-ginsenoside Rc, malonyl-ginsenoside Rb1 isomer, malonyl-ginsenoside Rb2, malonyl-ginsenoside Rb3, malonyl-ginsenoside Rd isomer, gypenoside XVII, and notoginsenoside Fe. This is the first time that the differences between LX-L and LX-P have been observed systematically at the chemistry level. It was indicated that vacuum freeze-drying method can improve the content of malonyl-ginsensides in mountain cultivated ginseng.


Asunto(s)
Medicamentos Herbarios Chinos/química , Ginsenósidos/análisis , Panax/química , Cromatografía Líquida de Alta Presión , Desecación , Composición de Medicamentos/métodos , Ginsenósidos/química , Peso Molecular , Análisis Multivariante , Análisis de Componente Principal , Espectrometría de Masas en Tándem
10.
Yao Xue Xue Bao ; 51(4): 552-7, 2016 04.
Artículo en Zh | MEDLINE | ID: mdl-29859523

RESUMEN

This study was designed to investigate the inhibitory effect of supernatant from co-culture of human embryonic stem cells and tumor MDA-MB-231 cells on the breast cancer. The direct co-culture system of human embryonic stem cells H9 and breast cancer MDA-MB-231 cells was established, and the supernatant was tested in the inhibition of MDA-MB-231 cells. The inhibitory effects were examined in tumor cell morphology using microscope, cell proliferation with MTT assay, and cell apoptosis using the Hoechst staining and flow cytometry. Transwell assay was used to detect the migration and invasion of tumor cells. The results suggest that the supernatant significantly inhibited the proliferation, invasion and migration, and promoted cell apoptosis of MDA-MB-231 cells. However, the supernatant of H9 cells alone had little effect on MDA-MB-231 cells. Therefore, we conclude that the supernatant of co-culture cells had an inhibitory effect on tumor cells in vitro.


Asunto(s)
Neoplasias de la Mama , Técnicas de Cocultivo , Medios de Cultivo Condicionados/farmacología , Células Madre Embrionarias Humanas , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Humanos
11.
Heliyon ; 10(12): e32652, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38994040

RESUMEN

Aging causes degenerative changes in organs, leading to a decline in physical function. Over the past two decades, researchers have made significant progress in understanding the rejuvenating effects of young blood on aging organs, benefiting from heterochronic parabiosis models that connect the blood circulation of aged and young rodents. It has been discovered that young blood can partially rejuvenate organs in old animals by regulating important aging-related signaling pathways. Clinical trials have also shown the effectiveness of young blood in treating aging-related diseases. However, the limited availability of young blood poses a challenge to implementing anti-aging therapies on a large scale for older individuals. As a promising alternative, scientists have identified some specific anti-aging circulating factors in young blood that have been shown to promote organ regeneration, reduce inflammation, and alleviate fibrosis associated with aging in animal experiments. While previous reviews have focused primarily on the effects and mechanisms of circulating factors on aging, it is important to acknowledge that studying the rejuvenating effects and mechanisms of young blood has been a significant source of inspiration in this field, and it will continue to be in the future. In recent years, new findings have emerged, further expanding our knowledge in this area. This review aims to summarize the rejuvenating effects and mechanisms of young blood and circulating factors, discussing their similarities and connections, addressing discrepancies in previous studies, outlining future research directions, and highlighting the potential for clinical translation in anti-aging interventions.

12.
Cardiovasc Toxicol ; 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39365552

RESUMEN

The Hippo-yes-associated protein (YAP) signaling pathway plays a crucial role in cell proliferation, differentiation, and death. It is known to have impact on the progression and development of cardiovascular diseases (CVDs) as well as in the regeneration of cardiomyocytes (CMs). However, further research is needed to understand the molecular mechanisms by which the Hippo-YAP pathway affects the pathological processes of CVDs in order to evaluate its potential clinical applications. In this review, we have summarized the recent findings on the role of the Hippo-YAP pathway in CVDs such as myocardial infarction, heart failure, and cardiomyopathy, as well as its in CM development. This review calls attention to the potential roles of the Hippo-YAP pathway as a relevant target for the future treatment of CVDs.

13.
ACS Appl Mater Interfaces ; 16(30): 39079-39089, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39021338

RESUMEN

For chronic wounds, frequent replacement of bandages not only increases the likelihood of secondary damage and the risk of cross infection but also wastes medication. Therefore, in situ real-time monitoring of the concentrations of residual drugs in bandages is crucial. Here, we propose a novel strategy that combines a triboelectric nanogenerator (TENG) with medical bandages to develop a smart bandage based on zeolite imidazolate framework TENG. During the process of wound healing, the electrical output of TENG changes with the continuous release of drugs. Based on the correlation between the electrical signal of TENG and drug concentration, the concentration of residual drugs in the bandage can be monitored in real-time in situ, guiding medical staff to replace the bandage at the most appropriate time. The smart bandage based on TENG provides a new strategy for in situ real-time monitoring of drug concentration and also provides an ideal and feasible solution for the field of biomedical drug sensing.


Asunto(s)
Vendajes , Zeolitas/química , Animales , Cicatrización de Heridas/efectos de los fármacos , Humanos , Nanotecnología/instrumentación , Monitoreo de Drogas/instrumentación , Monitoreo de Drogas/métodos , Estructuras Metalorgánicas/química
14.
Front Pharmacol ; 15: 1337633, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38650630

RESUMEN

Globally, alcohol-associated liver disease (ALD) has become an increased burden for society. Disulfirams, Benzodiazepines (BZDs), and corticosteroids are commonly used to treat ALD. However, the occurrence of side effects such as hepatotoxicity and dependence, impedes the achievement of desirable and optimal therapeutic efficacy. Therefore, there is an urgent need for more effective and safer treatments. Hovenia dulcis is an herbal medicine promoting alcohol removal clearance, lipid-lowering, anti-inflammatory, and hepatoprotective properties. Hovenia dulcis has a variety of chemical components such as dihydromyricetin, quercetin and beta-sitosterol, which can affect ALD through multiple pathways, including ethanol metabolism, immune response, hepatic fibrosis, oxidative stress, autophagy, lipid metabolism, and intestinal barrier, suggesting its promising role in the treatment of ALD. Thus, this work aims to comprehensively review the chemical composition of Hovenia dulcis and the molecular mechanisms involved in the process of ALD treatment.

15.
Life Sci ; 355: 122998, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39173998

RESUMEN

Myocardial ischemia-reperfusion injury (MIRI) is an injury to cardiomyocytes due to restoration of blood flow after myocardial infarction (MI). It has recently gained much attention in clinical research with special emphasis on the roles of mitochondrial autophagy and inflammation. A mild inflammatory response promotes recovery of post-ischemic cardiomyocyte function and vascular regeneration, but a severe inflammatory response can cause irreversible and substantial cellular damage. Similarly, moderate mitochondrial autophagy can help inhibit excessive inflammation and protect cardiomyocytes. However, MIRI is aggravated when mitochondrial function is disrupted, such as inadequate clearance of damaged mitochondria or excessive activation of mitophagy. How to moderately control mitochondrial autophagy while promoting its balance with nucleotide-binding oligomerization structural domain receptor protein 3 (NLRP3) inflammasome activation is critical. In this paper, we reviewed the molecular mechanisms of mitochondrial autophagy and NLRP3 inflammasome, described the interaction between NLRP3 inflammasome and mitochondrial autophagy, and the effects of different signaling pathways and molecular proteins on MIRI, to provide a reference for future research.


Asunto(s)
Inflamasomas , Mitofagia , Daño por Reperfusión Miocárdica , Proteína con Dominio Pirina 3 de la Familia NLR , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Humanos , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Inflamasomas/metabolismo , Animales , Transducción de Señal , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Mitocondrias/metabolismo , Mitocondrias/patología
16.
Mol Neurobiol ; 60(7): 3708-3723, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36933147

RESUMEN

Posttraumatic stress disorder (PTSD) is a neuropsychiatric disease closely related to life-threatening events and psychological stress. Re-experiencing, hyperarousal, avoidance, and numbness are the hallmark symptoms of PTSD, but their underlying neurological processes have not been clearly elucidated. Therefore, the identification and development of drugs for PTSD that targets brain neuronal activities have stalled. Considering that the persistent fear memory induced by traumatic stimulation causes high alertness, high arousal, and cognitive impairment of PTSD symptoms. While the midbrain dopamine system can affect physiological processes such as aversive fear memory learning, consolidation, persistence, and extinction, by altering the functions of the dopaminergic neurons, our viewpoint is that the dopamine system plays a considerable role in the PTSD occurrence and acts as a potential therapeutic target of the disorder. This paper reviews recent findings on the structural and functional connections between ventral tegmental area neurons and the core synaptic circuits involved in PTSD, gene polymorphisms related to the dopamine system that confer susceptibility to clinical PTSD. Moreover, the progress of research on medications that target the dopamine system as PTSD therapies is also discussed. Our goal is to offer some hints for early detection and assist in identifying novel, efficient approaches for treating PTSD.


Asunto(s)
Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/tratamiento farmacológico , Trastornos por Estrés Postraumático/psicología , Dopamina , Extinción Psicológica , Miedo/fisiología , Neuronas Dopaminérgicas
17.
Front Psychiatry ; 14: 1147060, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37051166

RESUMEN

Background: Co-occurring depressive disorder (DD) in patients of methamphetamine use disorder (MAUD) impacts the diagnosis, treatment, and prognosis of the disease. Although FKBP5 has been associated with a variety of psychiatric disorders, whether FKBP5 influences depression susceptibility in MAUD is unknown so far. Methods: Here, we sequenced six FKBP5 single-nucleotide polymorphism (SNP) sites (rs4713916, rs6926133, rs9470080, rs737054, rs4713902, and rs9470079) in 282 methamphetamine users. MAUD and DD were evaluated by clinical questionnaires. SPSS was used to analyze the relationship between FKBP5 SNPs and DD in individuals with MAUD. Results: Of the 282 methamphetamine users, 161 individuals met the MAUD criteria, and among them, 50 patients (31.1%) had DD co-occurring. Importantly, the incidence of DD in individuals with MAUD was 3.314 times greater than that of the methamphetamine users who did not meet the MAUD criteria (p < 0.001). Although none of the six SNPs of FKBP5 were correlated with the co-occurrence of DD in the population with MAUD, two FKBP5 alleles (rs4713916A and rs6926133A) were substantially associated with the higher DD scores in patients with MAUD (p < 0.05). Moreover, those with the two risk alleles do not have much higher scores than those with a single risk allele, and the strong linkage disequilibrium of the two SNPs may be the underlying cause of this result. Despite having weak linkage disequilibrium with either rs4713916 or rs6926133, FKBP5 rs9470079 became risky when paired with either. Conclusion: The results of this study revealed that the FKBP5 risk alleles (rs4713916A and rs6926133A) were associated with a greater probability of severe DD in patients with MAUD. These findings here would help with the development of biological early warning markers and the creation of personalized treatment strategies for MAUD.

18.
Front Aging Neurosci ; 15: 1071391, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36923118

RESUMEN

Background: Alzheimer's Disease (AD) and Type 2 Diabetes Mellitus (DM) have an increased incidence in modern society. Although more and more evidence has supported that DM is prone to AD, the interrelational mechanisms remain fully elucidated. Purpose: The primary purpose of this study is to explore the shared pathophysiological mechanisms of AD and DM. Methods: Download the expression matrix of AD and DM from the Gene Expression Omnibus (GEO) database with sequence numbers GSE97760 and GSE95849, respectively. The common differentially expressed genes (DEGs) were identified by limma package analysis. Then we analyzed the six kinds of module analysis: gene functional annotation, protein-protein interaction (PPI) network, potential drug screening, immune cell infiltration, hub genes identification and validation, and prediction of transcription factors (TFs). Results: The subsequent analyses included 339 common DEGs, and the importance of immunity, hormone, cytokines, neurotransmitters, and insulin in these diseases was underscored by functional analysis. In addition, serotonergic synapse, ovarian steroidogenesis, estrogen signaling pathway, and regulation of lipolysis are closely related to both. DEGs were input into the CMap database to screen small molecule compounds with the potential to reverse AD and DM pathological functions. L-690488, exemestane, and BMS-345541 ranked top three among the screened small molecule compounds. Finally, 10 essential hub genes were identified using cytoHubba, including PTGS2, RAB10, LRRK2, SOS1, EEA1, NF1, RAB14, ADCY5, RAPGEF3, and PRKACG. For the characteristic Aß and Tau pathology of AD, RAPGEF3 was associated significantly positively with AD and NF1 significantly negatively with AD. In addition, we also found ADCY5 and NF1 significant correlations with DM phenotypes. Other datasets verified that NF1, RAB14, ADCY5, and RAPGEF3 could be used as key markers of DM complicated with AD. Meanwhile, the immune cell infiltration score reflects the different cellular immune microenvironments of the two diseases. Conclusion: The common pathogenesis of AD and DM was revealed in our research. These common pathways and hub genes directions for further exploration of the pathogenesis or treatment of these two diseases.

19.
J Ethnopharmacol ; 317: 116706, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37301305

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used clinically to treat inflammatory diseases clinically. However, the adverse effects of NSAIDs cannot be ignored. Therefore, it is critical for us to find alternative anti-inflammatory drugs that can reduce adverse reactions to herbal medicine, such as Iris tectorum Maxim., which has therapeutic effects and can treat inflammatory diseases and liver-related diseases. AIM OF THE STUDY: This study aimed to isolate active compounds from I. tectorum and investigate their anti-inflammatory effects and action mechanisms. MATERIALS AND METHODS: Fourteen compounds were isolated from I. tectorum using silica gel column chromatography, Sephadex LH-20, ODS and high performance liquid chromatography, and their structures were identified by examining physicochemical properties, ultraviolet spectroscopy, infrared spectroscopy, mass spectrometry, and nuclear magnetic resonance spectroscopy. Classical inflammatory cell models were established using lipopolysaccharide (LPS)-stimulated RAW264.7 cells and rat primary peritoneal macrophages to examine the effect of these compounds. To examine the action mechanisms, the nitric oxide (NO) levels were measured by Griess reagent and the levels of inflammatory cytokines in the supernatant were measured by ELISA; The expressions of major proteins in prostaglandin E2 (PGE2) synthesis and the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were examined by Western blotting, and the mRNA expression levels were measured by quantitative real-time polymerase chain reaction; and the nuclear translocation of p65 was examined by high content imaging. Molecular docking was used to predict the binding of active compound to target protein. RESULTS: Our findings revealed that Iristectorigenin C (IT24) significantly inhibited the levels of NO and PGE2 without affecting cyclooxygenase (COX)-1/COX-2 expression in LPS-induced RAW264.7 cells and rat peritoneal macrophages. Furthermore, IT24 was shown to decrease the expression of microsomal prostaglandin synthetase-1 (mPGES-1) in LPS-induced rat peritoneal macrophages. IT24 did not suppress the phosphorylation and nuclear translocation of proteins in the NF-κB pathway, but it inhibited the phosphorylation of p38/JNK in LPS-stimulated RAW264.7 cells. Additionally, molecular docking analysis indicated that IT24 may directly bind to the mPGES-1 protein. CONCLUSION: IT24 might inhibit mPGES-1 and the p38/JNK pathway to exert its anti-inflammatory effects and could be also developed as an inhibitor of mPGES-1 to prevent and treat mPGES-1-related diseases, such as inflammatory diseases, and holds promise for further research and drug development.


Asunto(s)
Lipopolisacáridos , Sistema de Señalización de MAP Quinasas , Ratas , Animales , Lipopolisacáridos/farmacología , FN-kappa B/metabolismo , Simulación del Acoplamiento Molecular , Antiinflamatorios/farmacología , Antiinflamatorios no Esteroideos/farmacología , Macrófagos Peritoneales , Ciclooxigenasa 2/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo
20.
RSC Adv ; 12(8): 4865-4873, 2022 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-35425505

RESUMEN

To develop an efficient solid acid catalysts for the Friedel-Crafts alkylation reaction, especially for involving bulky molecules, the direct synthesis of hierarchical nanocrystalline ß zeolites were achieved by using amphiphilic organosilane ([(CH3O)3SiC3H6N(CH3)2C18H37]Cl, TPOAC) as collaborative structure-directing agent (SDA). The growth evolution of ß crystals and the influence of TPOAC/SiO2 molar ratio on the mesoporous structure, crystal size, and acidic properties of ß zeolites were investigated and discussed in detail. The characterization results reveal that intracrystalline mesopores and intercrystalline mesopores/macropores via the stacking of ß nanocrystals were generated over the hierarchical ß zeolites. Moreover, most of the strong acid sites were well remained compared with the conventional microporous ß zeolite. Consequently, the hierarchical nanocrystalline ß zeolite synthesized under the optimized synthesis conditions shows improved specific catalytic activity of acid sites (turnover number, TON) in alkylation of benzene with benzyl alcohol, which can be attributed to the integrated balance of considerable mesoporosity, accessibility of the acid sites, and well-remained strong acid sites in the hierarchical ß zeolite.

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