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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-ß outside neurons and Tau protein inside neurons. Various pathological mechanisms are implicated in AD, including brain insulin resistance, neuroinflammation, and endocrinal dysregulation of adrenal corticosteroids. These factors collectively contribute to neuronal damage and destruction. Recently, bile acids (BAs), which are metabolites of cholesterol, have shown neuroprotective potential against AD by targeting the above pathological changes. BAs can enter the systematic circulation and cross the blood-brain barrier, subsequently exerting neuroprotective effects by targeting several endogenous receptors. Additionally, BAs interact with the microbiota-gut-brain (MGB) axis to improve immune and neuroendocrine function during AD episodes. Gut microbes impact BA signaling in the brain through their involvement in BA biotransformation. In this review, we summarize the role and molecular mechanisms of BAs in AD while considering the MGB axis and propose novel strategies for preventing the onset and progression of AD.
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Doença de Alzheimer , Ácidos e Sais Biliares , Eixo Encéfalo-Intestino , Microbioma Gastrointestinal , Humanos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/microbiologia , Microbioma Gastrointestinal/fisiologia , Ácidos e Sais Biliares/metabolismo , Eixo Encéfalo-Intestino/fisiologia , Animais , Encéfalo/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologiaRESUMO
Background: In-stent restenosis (ISR) has become a significant obstacle to interventional therapy for atherosclerotic cardiovascular disease. The optimal percutaneous coronary intervention (PCI) strategy for patients with coronary ISR remains controversial. This network meta-analysis (NMA) was aimed to compare and estimate the effectiveness of different PCI strategies and commercial devices for the treatment of patients with coronary ISR. Methods: In present study, we systematically searched PubMed, Embase, Web of Science, and Cochrane Library from database inception to October 20, 2022, to identify randomized controlled trials. We included studies comparing various PCI strategies for the treatment of any type of coronary ISR. The study was registered with PROSPERO, CRD 42022364308. Results: We included 44 eligible trials including 8479 patients, 39 trials comparing the treatment effects of 10 PCIs, and 5 trials comparing the efficacy between different types of drug-eluting stent (DES) or drug-coated balloon (DCB) devices. Among the PCIs, everolimus-eluting stent was the optimal strategy considering target lesion revascularization (TLR), percent diameter stenosis (%DS), and binary restenosis (BR), and sirolimus-coated balloon was the optimal strategy considering late lumen loss (LLL). In the comparison of commercial devices, the combination strategy excimer laser coronary angioplasty plus SeQuent Please paclitaxel-coated balloon showed promising therapeutic prospects. Conclusions: DCB and DES remain the preferred treatment strategies for coronary ISR, considering both the primary clinical outcome (TLR) and the angiographic outcomes (LLL, BR, %DS). Personalized combination interventions including DCB or DES hold promise as a novel potential treatment pattern for coronary ISR.
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Alcohol-related liver disease (ALD) is chronic liver damage caused by long-term heavy drinking with, extremely complicated pathogenesis. The current studies speculated that excessive alcohol and its metabolites are the major causes of liver cell toxicity. Autophagy is evolutionarily conserved in eukaryotes and aggravates alcoholic liver damage, through various mechanisms, such as cellular oxidative stress, inflammation, mitochondrial damage and lipid metabolism disorders. Therefore, autophagy plays an critical role in the occurrence and development of ALD. Some studies have shown that traditional Chinese medicine extracts improve the histological characteristics of ALD, as reflected in the improvement of oxidative stress and lipid droplet clearance, which might be achieved by inducing autophagy. This article reviews the mechanisms of quercetin, baicalin, glycycoumarin, salvianolic acid A, resveratrol, ginsenoside rg1, and dihydromyricetin inducing autophagy and their participation in the inhibition of ALD. The regulation of autophagy in ALD by these traditional Chinese medicine extracts provides novel ideas for the treatment of the disease; however, its molecular mechanism needs to be elucidated further.
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Hepatopatias Alcoólicas , Medicina Tradicional Chinesa , Humanos , Autofagia , Hepatopatias Alcoólicas/tratamento farmacológico , Etanol , EucariotosRESUMO
Patients after liver transplantation are often impacted by mental and even neuropsychiatric disorders, including depression, sleep disorders, anxiety, and post-traumatic stress disorder. Neuropsychiatric sequelae have an adverse impact on rehabilitation and can even incapacitate people, reducing their quality of life. Despite screening tools and effective treatments, neuropsychiatric sequelae after liver transplantation (NSALT) have not been fully diagnosed and treated. Current research suggests that NSALT may be partly related to intestinal microbial variation, but the detailed mechanism remains unclear. In this review, we describe the clinical and diagnostic features, prevalence, prediction, clinical course and outcome, management, and treatment of NSALT; we also summarize their mechanisms through the microbiota-gut-liver-brain axis. Finally, we propose to improve NSALT on the basis of adjusting the gastrointestinal flora, immune inflammation or vagus nerve (VN), providing a novel strategy for clinical prevention and treatment.
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Microbioma Gastrointestinal , Transplante de Fígado , Humanos , Microbioma Gastrointestinal/fisiologia , Encéfalo , Transplante de Fígado/efeitos adversos , Qualidade de Vida , FígadoRESUMO
Garcinia mangostana L. (Mangosteen), a functional food, belongs to the Garcinaceae family and has various pharmacological effects, including anti-oxidative, anti-inflammatory, anticancer, antidiabetic, and neuroprotective effects. Mangosteen has abundant chemical constituents with powerful pharmacological effects. After searching scientific literature databases, including PubMed, Science Direct, Research Gate, Web of Science, VIP, Wanfang, and CNKI, we summarized the traditional applications, botanical features, chemical composition, and pharmacological effects of mangosteen. Further, we revealed the mechanism by which it improves health and treats disease. These findings provide a theoretical basis for mangosteen's future clinical use and will aid doctors and researchers who investigate the biological activity and functions of food.
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Garcinia mangostana , Extratos Vegetais , Extratos Vegetais/farmacologia , Garcinia mangostana/química , Frutas/química , Alimento Funcional , Anti-Inflamatórios/farmacologiaRESUMO
Background: Liver diseases are a spectrum of diseases that include hepatic steatosis, nonalcoholic fatty liver disease, hepatitis, liver fibrosis, cirrhosis, and hepatic cancer. These diseases not only severely decrease the quality of life for patients, but also cause financial burden. Although apigenin (APG) has recently become the primary treatment for liver injuries and diseases (LIADs), there has been no systematic review of its use. Purpose: To review the existing literature and put forward novel strategies for future APG research on LIADs. Methods: A search was conducted in PubMed, Science Direct, Research Gate, Web of Science, VIP, Wanfang, and CNKI, and 809 articles were obtained. After applying inclusion and exclusion criteria, 135 articles were included. Results: APG is promising in treating LIADs via various mechanisms arising from its anti-inflammation, anti-proliferation, anti-infection, anti-oxidation, and anti-cancer properties. Conclusion: This review summarizes the evidence supporting the use of APG as a treatment for LIADs and provides an insight into the intestinal microbiota, which may have important implications in its future clinical use.
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Depression is a common and severe mental disease that places a heavy burden on human society, which can lead to decreased cognitive function, energy loss, insomnia, and even suicide. Although medication plays an important role in improving the symptoms of depression, approximately one third of people with depression do not significantly benefit from medication and experience various adverse reactions. Recently, increasing evidence has shown that gut microbes play an important role in the occurrence and development of depression. There have been illuminating studies previously conducted on the relationship between antidepressant chemicals, traditional Chinese medicine, and the microbiota-gut-brain axis (MGBA). Therefore, in this review, we summarize the role of the MGBA in the occurrence and development of depression, especially the important role of the MGBA in the mechanism of action of antidepressants. Modulation of the MGBA is proposed to enhance the efficacy of antidepressant drugs and reduce their side effects and disease recurrence, so as to provide a new method for the treatment of depression.
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Microbioma Gastrointestinal , Medicina Tradicional Chinesa , Antidepressivos/efeitos adversos , Eixo Encéfalo-Intestino , Depressão/tratamento farmacológico , HumanosRESUMO
Objectives: We conducted a meta-analysis to quantitatively evaluate the effect of melatonin therapy on patients with myocardial ischemia-reperfusion injury (MIRI) and explore the influencing factors. Background: Although preclinical studies have shown that melatonin can alleviate MIRI, its protective effect on MIRI in patients remains controversial. Methods: We searched PubMed, the Cochrane Library, and Embase. The primary outcome was cardiac function (left ventricular ejection fraction [LVEF], left ventricular end-diastolic volume [LVEDV], and left ventricular end-systolic volume [LVESV]) and myocardial infarct parameters (total left ventricular mass and infarct size). Results: We included nine randomized controlled clinical trials with 631 subjects. Our results showed that melatonin had no significant effects on the primary outcome, but subgroup analyses indicated that when melatonin was administered by intravenous and intracoronary injection at the early stage of myocardial ischemia, LVEF was improved (<3.5 h; standardized mean difference [SMD]:0.50; 95% CI: 0.06 to 0.94; P = 0.03) and the infarct size was reduced (<2.5 h, SMD: -0.86; 95% CI: -1.51 to -0.22; P = 0.01), whereas when melatonin was injected at the late stage of myocardial ischemia (≥3.5 h or 2.5 h), the results were the opposite. Furthermore, melatonin intervention reduced the level of cardiac injury markers, inflammatory cytokines, oxidation factors, and increased the level of antioxidant factors (P < 0.001). Conclusions: The results indicated that the cardioprotective function of melatonin for MIRI was influenced by the route and timing regimen of melatonin administration; the mechanism of which may be associated with the production of inflammatory cytokines, the balance of oxidation, and antioxidant factors.
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Antioxidantes/uso terapêutico , Melatonina/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Antioxidantes/farmacologia , Feminino , Humanos , Masculino , Melatonina/farmacologia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: T long-term effects of cognitive therapy and behavior therapy (CTBT) for menopausal symptoms are unknown, and whether the effects are different between natural menopause and treatment-induced menopause are currently unclear. Therefore, we sought to conduct an accurate estimate of the efficacy of CTBT for menopausal symptoms. METHODS: We conducted searches of Cochrane Library, EMBASE, PsycINFO, PubMed, and Web of Science databases for studies from 1 January 1977 to 1 November 2021. Randomized controlled trials (RCTs) comparing intervention groups to control groups for menopausal symptoms were included. Hedge's g was used as the standardized between-group effect size with a random-effects model. RESULTS: We included 14 RCTs comprising 1618 patients with a mean sample size of 116. CTBT significantly outperformed control groups in terms of reducing hot flushes [g = 0.39, 95% confidence interval (CI) 0.23-0.55, I2 = 45], night sweats, depression (g = 0.50, 95% CI 0.34-0.66, I2 = 51), anxiety (g = 0.38, 95% CI 0.23-0.54, I2 = 49), fatigue, and quality of life. Egger's test indicated no publication bias. CONCLUSIONS: CTBT is an effective psychological treatment for menopausal symptoms, with predominantly small to moderate effects. The efficacy is sustained long-term, although it declines somewhat over time. The efficacy was stronger for natural menopause symptoms, such as vasomotor symptoms, than for treatment-induced menopause symptoms. These findings provide support for treatment guidelines recommending CTBT as a treatment option for menopausal symptoms.
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Terapia Cognitivo-Comportamental , Fogachos , Feminino , Fogachos/terapia , Humanos , Menopausa , Qualidade de VidaRESUMO
Intestinal microorganisms are closely associated with immunity, metabolism, and inflammation, and play an important role in health and diseases such as inflammatory bowel disease, diabetes, cardiovascular disease, Parkinson's disease, and cancer. Liver cancer is one of the most fatal cancers in humans. Most of liver cancers are slowly transformed from viral hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease. However, the relationship between intestinal microbiota and their metabolites, including short-chain fatty acids, bile acids, indoles, and ethanol, and liver cancer remains unclear. Here, we summarize the molecular immune mechanism of intestinal microbiota and their metabolites in the occurrence and development of liver cancer and reveal the important role of the microbiota-gut-liver axis in liver cancer. In addition, we describe how the intestinal flora can be balanced by antibiotics, probiotics, postbiotics, and fecal bacteria transplantation to improve the treatment of liver cancer. This review describes the immunomolecular mechanism of intestinal microbiota and their metabolites in the occurrence and development of hepatic cancer and provides theoretical evidence support for future clinical practice.
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INTRODUCTION: Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson's disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD. MATERIALS AND METHODS: The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs. RESULTS: Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum) than R-NPs. The pharmacodynamic study revealed a significant difference (P<0.05) in contralateral rotations between rats treated with Lf-R-NPs and those treated with R-NPs. Furthermore, Lf-R-NPs significantly alleviated nigrostriatal dopaminergic neurodegeneration in the rat model of 6-hydroxydopamine-induced PD. CONCLUSION: Our findings show that Lf-R-NPs deliver rotigotine more efficiently to the brain, thereby enhancing efficacy. Therefore, Lf-R-NPs might have therapeutic potential for the treatment of PD.
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Encéfalo/efeitos dos fármacos , Nanopartículas/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Tetra-Hidronaftalenos/administração & dosagem , Tiofenos/administração & dosagem , Administração Intranasal , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/farmacocinética , Agonistas de Dopamina/farmacologia , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Lactoferrina/química , Masculino , Nanopartículas/química , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacocinética , Nariz/efeitos dos fármacos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Tetra-Hidronaftalenos/farmacocinética , Tiofenos/farmacocinética , Distribuição TecidualRESUMO
Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson's disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box-Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD.
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Encéfalo/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Lactoferrina/administração & dosagem , Nanopartículas/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Poliésteres/química , Polietilenoglicóis/química , Tetra-Hidronaftalenos/administração & dosagem , Tiofenos/administração & dosagem , Administração Intranasal , Animais , Barreira Hematoencefálica , Brônquios/citologia , Brônquios/efeitos dos fármacos , Células Cultivadas , Portadores de Fármacos/química , Humanos , Lactoferrina/química , Masculino , Camundongos , Nanopartículas/química , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia , Tamanho da Partícula , Distribuição TecidualRESUMO
Picrasma quassioides (P. quassioides) has been widely used as a traditional Chinese medicine for clearing fever and detoxification. Previous phytochemical studies have identified a novel dihydrobenzofuran-type neolignan, picrasmalignan A, isolated from the stems of P. quassioides. In the present study, the in vitro anti-inflammatory effects and molecular mechanisms of picrasmalignan A have been investigated in cultured RAW 264.7 cells, a mouse macrophagelike cell line. A Griess assay was used to demonstrate the inhibitory effect of picrasmalignan A on the overproduction of nitric oxide (NO). An enzyme-linked immunosorbent assay was used to determine the levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The inhibitory effect on the enzymatic activity of cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) was observed by colorimetric and fluorimetric assays, respectively. Western blotting was conducted to detect the expression of iNOS and COX-2. Results showed that picrasmalignan A suppressed lipopolysaccharide-stimulated NO production and pro-inflammatory cytokine secretion, including TNF-α and IL-6, in a dose-dependent manner. It also significantly inhibited the expression and enzymatic activity of iNOS and COX-2. These results may demonstrate the anti-inflammatory mechanism of picrasmalignan A.
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Anti-Inflamatórios/farmacologia , Benzofuranos/farmacologia , Ciclo-Oxigenase 2/química , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Animais , Western Blotting , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Ensaio de Imunoadsorção Enzimática , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Interleucina-6/antagonistas & inibidores , Interleucina-6/metabolismo , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismoRESUMO
3-(Hydroxymethyl)-6,7-dihydroindolo[2,3-a]quinolizin-(12H)-one is a bioactive indole alkaloid isolated from Nauclea officinalis, a plant species which is used as a traditional Chinese medicine. We investigated the anti-inflammatory properties of 3-(hydroxymethyl)-6,7-dihydroindolo[2,3-a]quinolizin-(12H)-one in RAW 264.7 murine macrophages. The results indicated that it inhibited the overproduction of NO and the release of TNF-α. Furthermore, this compound inhibited the expression of iNOS and COX-2 proteins, the enzymatic activity of iNOS, and the translocation of NF-κB to the nucleus induced by LPS. Therefore, we suggested that the effect of 3-(hydroxymethyl)-6,7-dihydroindolo[2,3-a]quinolizin-(12H)-one-mediated inhibition of the expression of LPS-induced iNOS and COX-2 genes is due to the suppression of NF-κB activation in the transcriptional level.
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Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Alcaloides Indólicos/química , Indóis/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Quinolizinas/farmacologia , Animais , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Alcaloides Indólicos/farmacologia , Indóis/química , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Transporte Proteico/efeitos dos fármacos , Quinolizinas/química , Rubiaceae/química , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Surface soil samples around Guanting Reservoir ranging from 2-10 km were measured for pesticide residues (HCHs and DDTs) concentrations in 2009. Occurrences and related environmental risk were analyzed; furthermore, GIS and geostatistical techniques were applied to analyze the spatial variation of organochlorine pesticides. The results show that concentrations of HCHs in soils range from n.d. to 14.97 ng x g(-1) with a mean value of 0.73 ng x g(-1), and DDTs range from n.d. to 64.91 ng x g(-1) with a mean value of 6.46 ng x g(-1). According to the isomers of HCHs and metabolites of DDTs, HCHs and DDTs residues in soils were primarily from historical use. The land use showed great effect on the degradation of HCHs and DDTs, with the residual level sequence of orchard >> crop land > barren land. Based on kriging interpolation, the spatial distribution of HCHs and DDTs around Guanting Reservoir was observed. Spatial variability indicated how HCHs and DDTs had been applied and distributed in the past. Compared with those in other national or international regions, the concentrations of HCHs and DDTs in soils around Guanting Reservoir were very low.