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INTRODUCTION: To evaluate the effect of the cardiac cycle for the coronary artery opening and coronary stenosis at the plaque to determine the phase of measuring maximum diameters required for coronary artery disease (CAD). METHODS: This retrospective study assessed data for 208 consecutive patients who underwent coronary computed tomography angiography (CTA). The cross-sectional area and diameters of the opening of the left main coronary artery (LM), left anterior descending branch (LAD), left circumflex branch (LCX) and right coronary artery (RCA), the stenosis rate of involved vessels were measured in 10 cardiac cycles. And all their dynamic changes were estimated by the linear mixed model. The relationship between stenosis rate and opening orifice were analyzed by monofactorial variance. RESULTS: The opening parameters and stenosis rate of the four main coronary arteries varied within the cardiac cycle (p < .05). The maximum opening area occurred at the 45%-55% phase; The range of stenosis rate varied approximately 11%-14% and the maximum stenosis rate was at the 65% phase. The degree of vascular stenosis for LM, LAD and LCX were not associated with their corresponding opening diameters, but were positively intercorrelation with each other. CONCLUSION: For patients with CAD, the maximum coronary artery stenosis rate were at 65% phase and the maximum value of coronary artery opening were at 45%-55% phase, which were chosen for the appropriate measurement and evaluation by CTA.
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Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Angiografía por Tomografía Computarizada , Vasos Coronarios/diagnóstico por imagen , Estudios Retrospectivos , Constricción Patológica , Angiografía Coronaria/métodos , Estenosis Coronaria/diagnóstico por imagenRESUMEN
PURPOSE: To explore the characteristics of the hepatic fat content in athletes, and predict late gadolinium enhancement (LGE) based on magnetic resonance imaging-proton density fat fraction (MRI-PDFF). MATERIAL AND METHODS: From March 2020 to March 2021, 233 amateur athletes and 42 healthy sedentary controls were prospectively recruited. The liver fat content of four regions of interest (ROIs 1-4), the mean liver fat fraction (FF), cardiac function, and myocardium LGE were recorded, respectively. The values of ROIs 1-4 and FF were compared between athletes and controls. According to the liver fat content threshold for distinguishing athletes and controls, the cutoff total exercise time that induced a change in liver fat was obtained. The correlations among the liver fat content, cardiac function, and other parameters were analyzed. Moreover, the liver fat content was used to predict myocardium LGE by logistic regression. RESULTS: There were significant differences for the values of ROI 1, ROI 3, ROI 4, and FF between athletes and controls (allp< 0.05). The cutoff total exercise time for inducing a change in the liver fat content was 1680 h (area under the curve [AUC] = 0.593, specificity = 83.3,p< 0.05). Blood indexes, cardiac function, and basic clinical parameters were related to liver fat content (allp< 0.05). The prediction model for LGE had an AUC value of 0.829 for the receiver operator characteristic curve. CONCLUSION: MRI-PDFF could assess liver fat content and predict cardiac fibrosis in athletes for risk stratification and follow-up.
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Medios de Contraste , Protones , Humanos , Gadolinio , Hígado/diagnóstico por imagen , Hígado/patología , Imagen por Resonancia Magnética , Fibrosis , AtletasRESUMEN
BACKGROUND: Benign prostatic hyperplasia (BPH) is a progressive urological disease occurring in middle-aged and elderly men, which can be characterized by the non-malignant overgrowth of stromal and epithelial cells in the transition zone of the prostate. Previous studies have demonstrated that lycopene can inhibit proliferation, while curcumin can strongly inhibit inflammation. This study aims to determine the inhibitory effect of the combination of lycopene and curcumin on BPH. METHOD: To induce BPH models in vitro and in vivo, the BPH-1 cell line and Sprague Dawley (SD) rats were used, respectively. Rats were divided into six groups and treated daily with a vehicle, lycopene (12.5 mg/kg), curcumin (2.4 mg/kg), a combination of lycopene and curcumin (12.5 mg/kg + 2.4 mg/kg) or finasteride (5 mg/kg). Histologic sections were examined via hematoxylin and eosin (H&E) staining and immunohistochemistry. Hormone and inflammatory indicators were detected via ELISA. Network pharmacology analysis was used to fully predict the therapeutic mechanism of the combination of lycopene and curcumin on BPH. RESULTS: Combination treatment significantly attenuated prostate hyperplasia, alleviated BPH pathological features and decreased the expression of Ki-67 in rats. The upregulation of the expression of testosterone, dihydrotestosterone (DHT), 5α-reductase, estradiol (E2) and prostate-specific antigen (PSA) in BPH rats was significantly blocked by the combination treatment. The expression levels of inflammatory factors including interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α were strongly inhibited by the combination treatment. From the network pharmacology analysis, it was found that the main targets for inhibiting BPH are AKT1, TNF, EGFR, STAT3 and PTGS2, which are enriched in pathways in cancer. CONCLUSION: The lycopene and curcumin combination is a potential and more effective agent to prevent or treat BPH.
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Curcumina , Hiperplasia Prostática , Propionato de Testosterona , Masculino , Humanos , Ratas , Animales , Hiperplasia Prostática/inducido químicamente , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/metabolismo , Propionato de Testosterona/efectos adversos , Ratas Sprague-Dawley , Licopeno/farmacología , Licopeno/uso terapéutico , Curcumina/farmacología , Curcumina/uso terapéutico , Propionatos/farmacología , Extractos Vegetales/farmacología , Testosterona/metabolismo , Inflamación/tratamiento farmacológico , Proliferación CelularRESUMEN
Although the loss of brain laterality is one of the most consistent modalities in schizophrenia (SCZ) and bipolar disorder (BD), its molecular basis remains elusive. Our limited previous studies indicated that epigenetic modifications are key to the asymmetric transcriptomes of brain hemispheres. We used whole-genome expression microarrays to profile postmortem brain samples from subjects with SCZ, psychotic BD [BD[+]] or non-psychotic BD [BD(-)], or matched controls (10/group) and performed whole-genome DNA methylation (DNAM) profiling of the same samples (3-4/group) to identify pathways associated with SCZ or BD[+] and genes/sites susceptible to epigenetic regulation. qRT-PCR and quantitative DNAM analysis were employed to validate findings in larger sample sets (35/group). Gene Set Enrichment Analysis (GSEA) demonstrated that BMP signaling and astrocyte and cerebral cortex development are significantly (FDR q < 0.25) coordinately upregulated in both SCZ and BD[+], and glutamate signaling and TGFß signaling are significantly coordinately upregulated in SCZ. GSEA also indicated that collagens are downregulated in right versus left brain of controls, but not in SCZ or BD[+] patients. Ingenuity Pathway Analysis predicted that TGFB2 is an upstream regulator of these genes (p = .0012). While lateralized expression of TGFB2 in controls (p = .017) is associated with a corresponding change in DNAM (p ≤ .023), lateralized expression and DNAM of TGFB2 are absent in SCZ or BD. Loss of brain laterality in SCZ and BD corresponds to aberrant epigenetic regulation of TGFB2 and changes in TGFß signaling, indicating potential avenues for disease prevention/treatment.
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Trastorno Bipolar/genética , Encéfalo/patología , Esquizofrenia/genética , Adulto , Autopsia , Metilación de ADN/genética , Epigénesis Genética/genética , Epigenoma/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas , Trastornos Psicóticos/genética , Transducción de Señal/genética , Transcriptoma/genética , Factor de Crecimiento Transformador beta/metabolismo , Secuenciación Completa del Genoma/métodosRESUMEN
Major mental diseases such as autism, bipolar disorder, schizophrenia, and major depressive disorder are debilitating illnesses with complex etiologies. Recent findings show that the onset and development of these illnesses cannot be well described by the one-gene; one-disease approach. Instead, their clinical presentation is thought to result from the regulative interplay of a large number of genes. Even though the involvement of many genes are likely, up regulating and activation or down regulation and silencing of these genes by the environmental factors play a crucial role in contributing to their pathogenesis. Much of this interplay may be moderated by epigenetic changes. Similar to genetic mutations, epigenetic modifications such as DNA methylation, histone modifications, and RNA interference can influence gene expression and therefore may cause behavioral and neuronal changes observed in mental disorders. Environmental factors such as diet, gut microbiota, and infections have significant role in these epigenetic modifications. Studies show that bioactive nutrients and gut microbiota can alter either DNA methylation and histone signatures through a variety of mechanisms. Indeed, microbes within the human gut may play a significant role in the regulation of various elements of "gut-brain axis," via their influence on inflammatory cytokines and production of antimicrobial peptides that affect the epigenome through their involvement in generating short chain fatty acids, vitamin synthesis, and nutrient absorption. In addition, they may participate in-gut production of many common neurotransmitters. In this review we will consider the potential interactions of diet, gastrointestinal microbiome, inflammation, and epigenetic alterations in psychiatric disorders.
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Epigenómica , Inflamación/complicaciones , Trastornos Mentales/etiología , Trastornos Mentales/patología , Microbiota , Animales , HumanosRESUMEN
The origins of Alzheimer's disease (AD) and Parkinson's disease (PD) involve genetic mutations, epigenetic changes, neurotoxin exposure and gut microbiota dysregulation. The gut microbiota's dynamic composition and its metabolites influence intestinal and blood-brain barrier integrity, contributing to AD and PD development. This review explores protein misfolding, aggregation and epigenetic links in AD and PD pathogenesis. It also highlights the role of a leaky gut and the microbiota-gut-brain axis in promoting these diseases through inflammation-induced epigenetic alterations. In addition, we investigate the potential of diet, probiotics and microbiota transplantation for preventing and treating AD and PD via epigenetic modifications, along with a discussion related to current challenges and future considerations. These approaches offer promise for translating research findings into practical clinical applications.
Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common age-related brain diseases. The incidence of AD is almost 20% in individuals over the age of 80 years, and the incidence of PD is 14% in individuals over the age of 60 years. Research scientists are studying various links among key factors involved in AD and PD pathogenesis, including diet, gut microbiota (communal bacteria living in our gut), neuroinflammation, epigenetic modifications (regulation of gene expression that is affected by environmental factors) and genetic changes to obtain greater insights into the mechanisms of disease development to design better therapeutics for these disabling diseases. The discovery of these relationships will provide opportunities to maintain favorable health via dietmicrobiotaepigenetic modifications, since diet and surrounding environments play crucial roles in gut microbial alterations. Here, we discuss the interactions between destructive protein misfolding/aggregation in AD and PD, with neuroinflammation and epigenetic alterations that all are affected by nutrition, microbiota dysbiosis (imbalance), leaky gut (gutblood barrier disruption) and internal or environmental toxins. We also present thought-provoking discussions and ideas about recent preventive/therapeutic approaches like special diets, probiotics, fecal microbiota transplantation and even specific antibiotics for preventing or improving neuropsychiatric symptoms in AD and PD.
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Enfermedad de Alzheimer , Microbioma Gastrointestinal , Enfermedad de Parkinson , Humanos , Microbioma Gastrointestinal/fisiología , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/terapia , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , EpigenomaRESUMEN
Background: Cardiac chamber dimensions and left ventricle (LV) wall thickness change with the cardiac cycle, in which researchers have set different time points for systole and diastole. OBJECTIVE: This study aimed to provide characteristics of normal heart and choose the correct cardiac cycle to measure maximum cardiac parameters for cardiovascular disease. METHODS: The parameters of left atrium (LA), LV, right atrium (RA), and right ventricle (RV), as well as the wall thickness of LV, were measured in different cardiac phases using cardiac computed tomography (CT). Then, their differences in different phases and the correlation between these parameters and traditional risk factors were analyzed. In addition, receiver operator characteristic curve (ROC) analyses was performed to estimate LA enlargement. RESULTS: The dimensions of LA and RA as well as the wall thickness of LV reached the maximum at the phase of 35% - 45%, while the dimensions of LV and RV reached the maximum at 95% - 5%. However, the changes of LA-B (antero-posterior diameter), LV-D1 (basal dimension), RA-B (minor dimension), and RV-D2 (mid cavity dimension) were relatively more stable than other diameters during the cardiac cycle. The maximum LA-B diameter, LV-D1 diameter, RA-B diameter, and RV-D2 diameter as well as the maximum interventricular septum thickness were acquired. Heart rate (HR) and smoking were potential indicators of LV-D2 (mid cavity dimension), while HR and LV myocardial mass were potential indicators of LV-D3 (apical-basal dimension). In phase 45%, the cut-off value of LA-B was 37.12 mm, with high sensitivity for predicting LA enlargement. CONCLUSION: Choosing the adaptive cardiac phase for evaluating cardiac chamber dimensions and wall thickness obtained by cardiac CT could provide a more accurate clinical measurement of the heart.
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Excessive inflammatory reactions and oxidative stress are well-recognized molecular findings in autism and these processes can affect or be affected by the epigenetic landscape. Nonetheless, adequate therapeutics are unavailable, as patient-specific brain molecular markers for individualized therapies remain challenging. METHODS: We used iPSC-derived neurons and astrocytes of patients with autism vs. controls (5/group) to examine whether they replicate the postmortem brain expression/epigenetic alterations of autism. Additionally, DNA methylation of 10 postmortem brain samples (5/group) was analyzed for genes affected in PSC-derived cells. RESULTS: We found hyperexpression of TGFB1, TGFB2, IL6 and IFI16 and decreased expression of HAP1, SIRT1, NURR1, RELN, GPX1, EN2, SLC1A2 and SLC1A3 in the astrocytes of patients with autism, along with DNA hypomethylation of TGFB2, IL6, TNFA and EN2 gene promoters and a decrease in HAP1 promoter 5-hydroxymethylation in the astrocytes of patients with autism. In neurons, HAP1 and IL6 expression trended alike. While HAP1 promoter was hypermethylated in neurons, IFI16 and SLC1A3 promoters were hypomethylated and TGFB2 exhibited increased promoter 5-hydroxymethlation. We also found a reduction in neuronal arborization, spine size, growth rate, and migration, but increased astrocyte size and a reduced growth rate in autism. In postmortem brain samples, we found DNA hypomethylation of TGFB2 and IFI16 promoter regions, but DNA hypermethylation of HAP1 and SLC1A2 promoters in autism. CONCLUSION: Autism-associated expression/epigenetic alterations in iPSC-derived cells replicated those reported in the literature, making them appropriate surrogates to study disease pathogenesis or patient-specific therapeutics.
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Astrocitos , Trastorno Autístico , Encéfalo , Metilación de ADN , Epigénesis Genética , Células Madre Pluripotentes Inducidas , Neuronas , Humanos , Astrocitos/metabolismo , Astrocitos/patología , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/patología , Trastorno Autístico/genética , Trastorno Autístico/patología , Trastorno Autístico/metabolismo , Neuronas/metabolismo , Neuronas/patología , Metilación de ADN/genética , Encéfalo/patología , Encéfalo/metabolismo , Masculino , Femenino , Regiones Promotoras Genéticas/genética , Forma de la Célula , Niño , Regulación de la Expresión Génica , Proteína ReelinaRESUMEN
Lung cancer is the leading cause of cancer death in the world, and the searching for novel efficacious and safe agents for lung cancer prevention remains the top priority of lung cancer research. In the present study, we evaluated the effect of bioactive tanshinones from a Chinese herb Salvia miltiorrhiza, cryptotanshinone (CT), tanshinone I (T1) and tanshinone IIA (T2A), on the proliferation inhibition of lung cancer cell lines. Tanshinones inhibited the lung cancer cell proliferation in vitro, with T1 the most potent, via cell cycle arrest and apoptosis induction. Gene function assay showed that Aurora A knockdown by siRNA dramatically eliminated the T1 activity in vitro, suggesting that Aurora A is an important functional target for T1. We further evaluated the effectiveness of T1 on the growth of H1299 nonsmall lung cancer cell in a mouse model. Tanshinone I inhibited the growth of H1299 lung tumor in a dose-dependent manner. Tanshinone I at 200 mg/kg body weight significantly reduced final tumor weight by 34% (P < 0.05) associated with inhibiting proliferation and inducing apoptosis of lung cancer cells by 54% (P < 0.001) and 193% (P < 0.001), respectively, inhibiting lung tumor angiogenesis by 72% (P < 0.001), and reducing Aurora A expression by 67% (P < 0.001). On the other hand, T1 did not significantly alter food intake or body weight. Our results provided experimental evidence to suggest that T1 may be an efficacious and safe agent for the prevention of lung cancer progression and Aurora A may be an important molecular target for T1 action against lung cancer.
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Abietanos/uso terapéutico , Carcinoma Pulmonar de Lewis/prevención & control , Carcinoma de Pulmón de Células no Pequeñas/prevención & control , Proliferación Celular/efectos de los fármacos , Neoplasias Pulmonares/prevención & control , Neovascularización Patológica/prevención & control , Proteínas Serina-Treonina Quinasas/metabolismo , Animales , Antineoplásicos Fitogénicos/uso terapéutico , Apoptosis/efectos de los fármacos , Aurora Quinasa A , Aurora Quinasas , Western Blotting , Peso Corporal/efectos de los fármacos , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Adhesión Celular/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Femenino , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Ratones SCID , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/genética , ARN Interferente Pequeño/genética , Células Tumorales CultivadasRESUMEN
During aging, several tissues and biological systems undergo a progressive decline in function, leading to age-associated diseases such as neurodegenerative, inflammatory, metabolic, and cardiovascular diseases and cancer. In this review, we focus on the molecular underpinning of senescence and neurodegeneration related to age-associated brain diseases, in particular, Alzheimer's and Parkinson's diseases, along with introducing nutrients or phytochemicals that modulate age-associated molecular dysfunctions, potentially offering preventive or therapeutic benefits. Based on current knowledge, the dysregulation of microglia genes and neuroinflammation, telomere attrition, neuronal stem cell degradation, vascular system dysfunction, reactive oxygen species, loss of chromosome X inactivation in females, and gut microbiome dysbiosis have been seen to play pivotal roles in neurodegeneration in an interactive manner. There are several phytochemicals (e.g., curcumin, EGCG, fucoidan, galangin, astin C, apigenin, resveratrol, phytic acid, acacetin, daucosterol, silibinin, sulforaphane, withaferin A, and betulinic acid) that modulate the dysfunction of one or several key genes (e.g., TREM2, C3, C3aR1, TNFA, NF-kb, TGFB1&2, SIRT1&6, HMGB1, and STING) affected in the aged brain. Although phytochemicals have shown promise in slowing down the progression of age-related brain diseases, more studies to identify their efficacy, alone or in combinations, in preclinical systems can help to design novel nutritional strategies for the management of neurodegenerative diseases in humans.
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Encefalopatías , Enfermedades Neurodegenerativas , Humanos , Anciano , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/prevención & control , Enfermedades Neurodegenerativas/metabolismo , Encéfalo/metabolismo , Envejecimiento , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Fitoquímicos/metabolismoRESUMEN
Introduction: Cognition decline is associated with aging and certain diseases, such as neurodegenerative or neuropsychiatric disorders, diabetes and chronic kidney disease. Inflammation/neuroinflammation is considered an important causal factor, and experimental evidence suggests that anti-inflammatory natural compounds may effectively prevent cognitive decline. The goal of this study was to evaluate the effects of two natural bioactive agents, oligo-lactic acid (LAP) and fermented soy extract (ImmunBalance, IMB), on cognition in an adenine-induced cognitive impairment mouse model and to investigate the modulation of related biomarkers. Methods: Male C57 black mice were randomly assigned into the following experimental groups and received the corresponding treatments for 2 weeks before the use of adenine for model development: (1) negative control; (2) model control: injection of adenine at 50 mg/kg daily for 4 weeks; (3, 4) IMB groups: adenine injection and IMB oral gavage at 250 and 1,000 mg/kg BW, respectively; and (5) LAP group: adenine injection and LAP oral gavage at 1,000 mg/kg BW. One week after the model was developed, mice were evaluated for cognitive performances by using Y maze test, novel object recognition test, open field test, and Barnes maze tests. At the end of the experiment, brain tissues and cecum fecal samples were collected for analysis of gene expression and gut microbiota. Results: Mice treated with LAP or IMB had significantly improved spatial working memory, spatial recognition memory (LAP only), novel object recognition, and spatial learning and memory, compared with those in the model group. Gene expression analysis showed that, among a panel of cognition related genes, six of them (ELOVL2, GLUT4, Nestein, SNCA, TGFB1, and TGFB2) were significantly altered in the model group. LAP treatment significantly reversed expression levels of inflammatory/neuroinflammatory genes (SNCA, TGFB1), and IMB significantly reversed expression levels of genes related to inflammation/neuroinflammation, neurogenesis, and energy metabolism (ELOVL2, GLUT4, Nestin, TGFB1, and TGFB2). The altered microbiome was attenuated only by IMB. Discussion: In conclusion, our data showed that LAP improved cognition associated with regulating biomarkers related to neuroinflammation and energy metabolism, whereas IMB improved cognition associated with regulating biomarkers related to neuroinflammation, energy metabolism, and neurogenesis, and modulating gut microbiota. Our results suggest that LAP and IMB may improve cognitive performance in mice via distinct mechanisms of action.
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The tissue-specific expression and epigenetic dysregulation of many genes in cells derived from the postmortem brains of patients have been reported to provide a fundamental biological framework for major mental diseases such as autism, schizophrenia, bipolar disorder, and major depression. However, until recently, the impact of non-neuronal brain cells, which arises due to cell-type-specific alterations, has not been adequately scrutinized; this is because of the absence of techniques that directly evaluate their functionality. With the emergence of single-cell technologies, such as RNA sequencing (RNA-seq) and other novel techniques, various studies have now started to uncover the cell-type-specific expression and DNA methylation regulation of many genes (e.g., TREM2, MECP2, SLC1A2, TGFB2, NTRK2, S100B, KCNJ10, and HMGB1, and several complement genes such as C1q, C3, C3R, and C4) in the non-neuronal brain cells involved in the pathogenesis of mental diseases. Additionally, several lines of experimental evidence indicate that inflammation and inflammation-induced oxidative stress, as well as many insidious/latent infectious elements including the gut microbiome, alter the expression status and the epigenetic landscapes of brain non-neuronal cells. Here, we present supporting evidence highlighting the importance of the contribution of the brain's non-neuronal cells (in particular, microglia and different types of astrocytes) in the pathogenesis of mental diseases. Furthermore, we also address the potential impacts of the gut microbiome in the dysfunction of enteric and brain glia, as well as astrocytes, which, in turn, may affect neuronal functions in mental disorders. Finally, we present evidence that supports that microbiota transplantations from the affected individuals or mice provoke the corresponding disease-like behavior in the recipient mice, while specific bacterial species may have beneficial effects.
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Epigénesis Genética , Trastornos Mentales , Animales , Ratones , Epigénesis Genética/genética , Trastornos Mentales/genética , Trastornos Mentales/metabolismo , Encéfalo/metabolismo , Microglía/metabolismo , Inflamación/genética , Inflamación/metabolismo , Glicoproteínas de Membrana/genética , Receptores Inmunológicos/genéticaRESUMEN
Major depressive disorder (MDD) is a complex disorder and a leading cause of disability in 280 million people worldwide. Many environmental factors, such as microbes, drugs, and diet, are involved in the pathogenesis of depressive disorders. However, the underlying mechanisms of depression are complex and include the interaction of genetics with epigenetics and the host immune system. Modifications of the gut microbiome and its metabolites influence stress-related responses and social behavior in patients with depressive disorders by modulating the maturation of immune cells and neurogenesis in the brain mediated by epigenetic modifications. Here, we discuss the potential roles of a leaky gut in the development of depressive disorders via changes in gut microbiota-derived metabolites with epigenetic effects. Next, we will deliberate how altering the gut microbiome composition contributes to the development of depressive disorders via epigenetic alterations. In particular, we focus on how microbiota-derived metabolites such as butyrate as an epigenetic modifier, probiotics, maternal diet, polyphenols, drugs (e.g., antipsychotics, antidepressants, and antibiotics), and fecal microbiota transplantation could positively alleviate depressive-like behaviors by modulating the epigenetic landscape. Finally, we will discuss challenges associated with recent therapeutic approaches for depressive disorders via microbiome-related epigenetic shifts, as well as opportunities to tackle such problems.
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Trastorno Depresivo Mayor , Microbioma Gastrointestinal , Microbiota , Probióticos , Humanos , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/genética , Probióticos/uso terapéutico , Probióticos/farmacología , Epigénesis GenéticaRESUMEN
BACKGROUND: Osteoporosis is a major health problem in postmenopausal women, and characterized by deteriorated bone mass and micro-architecture. There have been some clinical trials demonstrating the beneficial effects of vitamin-D and some trace elements on calcium absorption and attenuation of osteoporosis development. However, effects of the combination of vitamin-D and zinc on calcium absorption and osteoporosis have not been adequately investigated. METHODS: Network pharmacology was first performed to explore possible correlations between calcium/vitamin D/zinc and osteoporosis. Forty-nine female Sprague-Dawley rats (6 months old, 250 ± 20 g) were randomized into 7 experimental groups with 7 animals per group for the in vivo study, including one sham surgery control group, one ovariectomizing (OVX) group, and 5 OVX plus treatment groups. At the end of animal experiment, animal tibia and femur leg bones and blood were collected for H&E staining, bone microstructure analysis by a micro-CT, measurement of bone and serum Ca, P and Zn concentrations, and immunohistochemical detection of macrophage-colony stimulating factor receptor (M-CSFR) and receptor activator of nuclear factor-kappa B ligand (RANKL). RESULTS: The network pharmacology analysis identified 57 candidate targets that were related to the osteoporosis-Ca/VitD/Zn interconnections. Further pathway analysis suggested that the combined treatment of Ca, VitD and Zn attenuated osteoporosis via modulation of metabolic pathways. We found that a therapy with Ca/VitD-M/Zn-M (73 mg/kg/day Ca, 0.6 g/kg/day VitD3 and 0.6 mg/kg/day zinc citrate) could significantly suppress the progression of osteoporosis in rats. After the Ca/VitD-M/Zn-M treatment, the ratio of bone volume/tissue volume, trabecular number and the trabecular thickness were all significantly elevated while the extent of trabecular separation was significantly reduced. Additionally, both serum calcium and bone calcium levels were significantly upregulated by the Ca/VitD/Zn treatment in a dose-dependent manner. The combination of Ca/VitD-M/Zn-M was superiou to either Ca/VitD-L/Zn-L or Ca/VitD-H/Zn-H treatment for such an effect. Moreover, the osteoporosis-associated M-CSFR and RANKL factors were both significantly downregulated by the Ca/VitD-M/Zn-M treatment in bone tissues of OVX rats. CONCLUSIONS: The combined supplement of VitD and Zn facilitates the Ca(2 +) absorption and attenuates the development of osteoporosis via down-regulation of osteoporosis-associated factors M-CSFR and RANKL, thus potentially constitutes an alternative therapy for the postmenopausal osteoporosis.
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Calcio , Osteoporosis , Humanos , Ratas , Femenino , Animales , Ratas Sprague-Dawley , Zinc/farmacología , Zinc/uso terapéutico , Osteoporosis/tratamiento farmacológico , Osteoporosis/metabolismo , Vitamina D/farmacología , Vitamina D/uso terapéutico , Densidad Ósea , Vitaminas/farmacología , OvariectomíaRESUMEN
BACKGROUND: Struma ovarii is a rare specific ovarian tumor. It is a highly differentiated monodermal teratoma with a malignant transformation rate as low as 5%. Thus, malignant transformation and metastasis are extremely rare. The clinical manifestations of this disease are not typical and are easily misdiagnosed. CASE SUMMARY: A 55-year-old female patient had a history of pain in the right hepatic region for approximately 1 year. Computed tomography and magnetic resonance imaging showed a solid cystic mass in the right adnexal region and a solid mass in the right retroperitoneum. The patient underwent surgical resection, and the combined morphological and immunohistochemical results led to the final diagnosis of right struma ovarii with papillary carcinoma and right retroperitoneal lymph node metastasis. CONCLUSION: Malignant struma ovarii with distant metastasis is extremely rare, and the clinical manifestations of this disease are nonspecific. Accurate preoperative diagnoses are difficult to obtain, and pathological examination is the gold standard for diagnosing this disease.
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Searching for efficacious and safe agents for the chemoprevention and therapy of prostate cancer has become the top priority of research. The objective of this study was to determine the effects of a group of tanshinones from a Chinese herb Salvia Miltiorrhiza, cryptotanshinone (CT), tanshinone IIA (T2A) and tanshinone I (T1) on prostate cancer. The in vitro studies showed that these tanshinones inhibited the growth of human prostate cancer cell lines in a dose-dependent manner via cell cycle arrest and apoptosis induction. Among three compounds, T1 had the most potent activity with IC(50) s around 3-6 µM. On the other hand, tanshinones had much less adverse effects on the growth of normal prostate epithelial cells. The epigenetic pathway focused array assay identified Aurora A kinase as a possible target of tanshinone actions. The expression of Aurora A was overexpressed in prostate cancer cell lines. Moreover, knockdown of Aurora A in prostate cancer cells significantly decreased cell growth. Tanshinones significantly downregulated the Aurora A expression, suggesting Aurora A may be a functional target of tanshinones. Tanshinones, especially T1, also showed potent anti-angiogenesis activity in vitro and in vivo. Furthermore, T1 inhibited the growth of DU145 prostate tumor in mice associated with induction of apoptosis, decrease of proliferation, inhibition of angiogenesis and downregulation of Aurora A, whereas it did not alter food intake or body weight. Our results support that T1 may be an efficacious and safe chemopreventive or therapeutic agent against prostate cancer progression.
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Abietanos/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias de la Próstata/tratamiento farmacológico , Salvia miltiorrhiza/química , Animales , Aurora Quinasa A , Aurora Quinasas , Western Blotting , Adhesión Celular/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Humanos , Técnicas para Inmunoenzimas , Técnicas In Vitro , Masculino , Ratones , Ratones SCID , Fenantrenos/uso terapéutico , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/genética , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales CultivadasRESUMEN
During the last two decades, diverse epigenetic modifications including DNA methylation, histone modifications, RNA editing and miRNA dysregulation have been associated with psychiatric disorders. A few years ago, in a review we outlined the most common epigenetic alterations in major psychiatric disorders (e.g., aberrant DNA methylation of DTNBP1, HTR2A, RELN, MB-COMT and PPP3CC, and increased expression of miR-34a and miR-181b). Recent follow-up studies have uncovered other DNA methylation aberrations affecting several genes in mental disorders, in addition to dysregulation of many miRNAs. Here, we provide an update on new epigenetic findings and highlight potential origin of the diversity and inconsistencies, focusing on drug effects, tissue/cell specificity of epigenetic landscape and discuss shortcomings of the current diagnostic criteria in mental disorders.
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Trastorno Autístico/etiología , Susceptibilidad a Enfermedades , Epigénesis Genética , Variación Genética , Trastornos Mentales/etiología , Trastorno Autístico/diagnóstico , Trastorno Autístico/tratamiento farmacológico , Biomarcadores , Metilación de ADN , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Predisposición Genética a la Enfermedad , Humanos , Trastornos Mentales/diagnóstico , Trastornos Mentales/tratamiento farmacológico , MicroARNs/genética , Fenotipo , Factores de RiesgoRESUMEN
WangShiBoChiWan (WSBCW) is a commonly used Chinese herbal medicine for the treatment of functional gastrointestinal disorders. However, its preclinical efficacy and the mechanisms of action have not been adequately studied. The goals of this study were to evaluate the effects of WSBCW on gastrointestinal health and modulation of related biomarkers. Female C57BL mice were randomly assigned into one of the experimental groups consisting of the control, drug controls, and WSBCW at 40, 120, and 360 mg/kg BW. Whole gut transit, small intestinal motility, and intestinal barrier permeability were determined. The castor oil-induced diarrhea mouse model was used to determine the effect of WSBCW on the diarrhea type of irritable bowel syndrome (IBS-D). WSBCW increased whole gut transit and intestinal motility, improved intestinal permeability in healthy animals and alleviated diarrhea symptoms in IBS-D mice. WSBCW upregulated intestinal junction proteins, increased the abundance of Bifidobacterium genus, Desulfovibrio genus and inhibited Bacteroides fragillis group in the gut microbiota, increased intestinal villi lengths, and decreased blood levels of inflammatory cytokines. Our study provided preclinical evidence to verify the effectiveness of WSBCW in gastrointestinal health and elucidate mechanistic insights. The results warrant further investigations to evaluate the therapeutic efficacy of WSBCW on gastrointestinal disorders, such as IBS and IBD.
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Medicamentos Herbarios Chinos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/efectos de los fármacos , Medicina de Hierbas/métodos , Mediadores de Inflamación/antagonistas & inhibidores , Uniones Estrechas/efectos de los fármacos , Animales , Diarrea/tratamiento farmacológico , Diarrea/fisiopatología , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Microbioma Gastrointestinal/fisiología , Motilidad Gastrointestinal/efectos de los fármacos , Motilidad Gastrointestinal/fisiología , Tracto Gastrointestinal/fisiología , Mediadores de Inflamación/fisiología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/fisiología , Síndrome del Colon Irritable/tratamiento farmacológico , Síndrome del Colon Irritable/fisiopatología , Ratones , Ratones Endogámicos C57BL , Uniones Estrechas/fisiologíaRESUMEN
Peptide drugs, especially food-derived peptides, have a variety of functional activities including antiviral and may also have a therapeutic effect on COVID-19. In this study, comparing with the reported drugs, 79 peptides were found to bind to the key targets of COVID-19 virus with higher non-covalent interaction, while among them, six peptides showed high non-covalent interactions with the three targets, which may inhibit the COVID-19 virus. In the simulation, peptides of nine to 10 amino acids with a hydrophilic amino acid and acidic amino acid in the middle and aromatic amino acids on the side showed higher binding to angiotensin-converting enzyme 2 (ACE2). Peptides of five to six amino acids with a basic amnio acid in the head, acidic amnio acid in the neck, hydrophobicity group in the middle, and basic amino acids in the tail showed higher binding to COVID-19 virus main protease (Mpro), while those with basic amino acids and acidic amino acids in the two sides and aromatic amino acids in the middle might have stronger interaction with COVID-19 virus RNA-dependent RNA polymerase (RdRp).
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Tratamiento Farmacológico de COVID-19 , Descubrimiento de Drogas , Péptidos/química , Péptidos/farmacología , SARS-CoV-2/efectos de los fármacos , Enzima Convertidora de Angiotensina 2/química , Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/metabolismo , Diseño de Fármacos , Alimentos Funcionales , Humanos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Terapia Molecular Dirigida , SARS-CoV-2/química , SARS-CoV-2/metabolismo , Proteínas de la Matriz Viral/química , Proteínas de la Matriz Viral/metabolismoRESUMEN
The aim was to evaluate the thoracic aorta in different cardiac phases to obtain the correct cardiac phase for measuring the maximum diameter required to predict aortic disease. Cardiac CT was performed on 97 patients for suspected coronary artery disease. The average diameter of ascending (AAD) and descending aorta (DAD) in the plane of pulmonary bifurcation, in the plane of the sinus junction (AAD [STJ] and DAD [STJ]), descending aorta in the plane of the diaphragm (DAD [Dia]), the diameter of the main pulmonary artery (MPAD), distance from the sternum to the spine (S-SD), and distance from the sternum to the ascending aorta (S-AAD) were assessed at 20 different time points in the cardiac cycle. Differences in aortic diameter in different cardiac phases and the correlation between aortic diameter and traditional risk factors were analyzed by the general linear mixed model. The diameter of the thoracic aorta reached the minimum at the phase of 95-0%, and reached the maximum at 30-35%. The maximum values of AAD, AAD (STJ), DAD, DAD (STJ), and DAD (Dia) were 32.51 ± 3.35 mm, 28.86 ± 3.01 mm, 23.46 ± 2.88 mm, 21.85 ± 2.58 mm, and 21.09 ± 2.66 mm, respectively. The maximum values of MPAD/AAD and DAD/AAD (STJ) were 0.8140 ± 0.1029, 0.7623 ± 0.0799, respectively. The diameter of the thoracic aorta varies with the cardiac phase. Analyzing the changes in aortic diameter, which can be done using cardiac CT, could provide a more accurate clinical measurement for predicting aortic disease.