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Objective: To explore whether resveratrol can postpone the fibrosis associated with diabetic cardiomyopathy (DCM) by modulating the mitochondrial autophagy response through the AMPK/SIRT1-mediated IRE1α/PINK signaling pathway. Methods: A DCM mouse model was established using a high-sugar high-fat diet and streptozotocin. Resveratrol was administered to a subset of the DCM mouse models for comparison. Echocardiography, Masson staining, TNUEL assay, and transmission electron microscopy were employed to evaluate the cardiac status, myocardial fibrosis, myocardial cell apoptosis, and morphological changes of myocardial cells and their internal mitochondria in each group of mice. Western blot staining was performed on myocardial tissues to assess the protein expression levels of p-AMPK, SIRT1, SIRT3, p22, GP91, p-IRE1α, XBP1s PINK, Parkin, LC3I, and Beclin. Mouse myocardial cells were cultured in vitro and intervened with a high-sugar high-fat diet, resveratrol, and GSK690693 (an AMPK inhibitor) to observe the protein expression levels of p-AMPK, p22, XBP1s, and PINK in mouse myocardial cells in each group. Results: Results from echocardiography, Masson staining, TNUEL assay, and transmission electron microscopy showed that resveratrol administration alleviated cardiac damage, myocardial fibrosis, myocardial cell apoptosis, and mitochondrial autophagy in DCM mice. Resveratrol administration promoted the expression of phosphorylated AMP-activated protein kinase (p-AMPK), sirtuin 1 (SIRT1), and sirtuin 3 (SIRT3) in the myocardial tissue of mice, while lowering the elevated protein expression levels of p22 subunit (p22), guanine nucleotide-binding protein q polypeptide 1 (GP91), phosphorylated inositol-requiring enzyme 1 alpha (p-IRE1α), X-box binding protein 1 spliced form (XBP1s), PTEN-induced putative kinase 1 (PINK), Parkin, microtubule-associated proteins light chain 3 isoform I (LC3I), and Beclin (Bcl-2 interacting protein) caused by DCM. GSK690693 (an AMPK inhibitor) suppressed the expression of p-AMPK, SIRT1, and SIRT3 and enhanced the protein expression of p22, XBP1s, and PINK. Conclusion: Resveratrol postpones dilated cardiomyopathy fibrosis by regulating the mitochondrial autophagy response through the AMP-activated protein kinase (AMPK)/silent mating type information regulation 2 homolog 1 (SIRT1)-mediated inositol-requiring enzyme 1 alpha (IRE1α)/PTEN-induced putative kinase 1 (PINK) signaling pathway.
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Although Alzheimer's disease (AD) characterized with senile plaques and neurofibrillary tangles has been found for over 100 years, its molecular mechanisms are ambiguous. More worsely, the developed medicines targeting amyloid-beta (Aß) and/or tau hyperphosphorylation did not approach the clinical expectations in patients with moderate or severe AD until now. This review unveils the role of a vicious cycle between Aß-derived formaldehyde (FA) and FA-induced Aß aggregation in the onset course of AD. Document evidence has shown that Aß can bind with alcohol dehydrogenase (ADH) to form the complex of Aß/ADH (ABAD) and result in the generation of reactive oxygen species (ROS) and aldehydes including malondialdehyde, hydroxynonenal and FA; in turn, ROS-derived H2O2 and FA promotes Aß self-aggregation; subsequently, this vicious cycle accelerates neuron death and AD occurrence. Especially, FA can directly induce neuron death by stimulating ROS generation and tau hyper hyperphosphorylation, and impair memory by inhibiting NMDA-receptor. Recently, some new therapeutical methods including inhibition of ABAD activity by small molecules/synthetic polypeptides, degradation of FA by phototherapy or FA scavengers, have been developed and achieved positive effects in AD transgenic models. Thus, breaking the vicious loop may be promising interventions for halting AD progression.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , Álcool Desidrogenase , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio , Peptídeos beta-Amiloides/metabolismo , FormaldeídoRESUMO
Both exogenous gaseous and liquid forms of formaldehyde (FA) can induce depressive-like behaviors in both animals and humans. Stress and neuronal excitation can elicit brain FA generation. However, whether endogenous FA participates in depression occurrence remains largely unknown. In this study, we report that midbrain FA derived from lipopolysaccharide (LPS) is a direct trigger of depression. Using an acute depressive model in mice, we found that one-week intraperitoneal injection (i.p.) of LPS activated semicarbazide-sensitive amine oxidase (SSAO) leading to FA production from the midbrain vascular endothelium. In both in vitro and in vivo experiments, FA stimulated the production of cytokines such as IL-1ß, IL-6, and TNF-α. Strikingly, one-week microinfusion of FA as well as LPS into the midbrain dorsal raphe nucleus (DRN, a 5-HT-nergic nucleus) induced depressive-like behaviors and concurrent neuroinflammation. Conversely, NaHSO3 (a FA scavenger), improved depressive symptoms associated with a reduction in the levels of midbrain FA and cytokines. Moreover, the chronic depressive model of mice injected with four-week i.p. LPS exhibited a marked elevation in the levels of midbrain LPS accompanied by a substantial increase in the levels of FA and cytokines. Notably, four-week i.p. injection of FA as well as LPS elicited cytokine storm in the midbrain and disrupted the blood-brain barrier (BBB) by activating microglia and reducing the expression of claudin 5 (CLDN5, a protein with tight junctions in the BBB). However, the administration of 30 nm nano-packed coenzyme-Q10 (Q10, an endogenous FA scavenger), phototherapy (PT) utilizing 630-nm red light to degrade FA, and the combination of PT and Q10, reduced FA accumulation and neuroinflammation in the midbrain. Moreover, the combined therapy exhibited superior therapeutic efficacy in attenuating depressive symptoms compared to individual treatments. Thus, LPS-derived FA directly initiates depression onset, thereby suggesting that scavenging FA represents a promising strategy for depression treatment.
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Depressão , Lipopolissacarídeos , Humanos , Camundongos , Animais , Lipopolissacarídeos/farmacologia , Depressão/tratamento farmacológico , Doenças Neuroinflamatórias , Citocinas/metabolismo , Mesencéfalo/metabolismo , FormaldeídoRESUMO
Classical trigeminal neuralgia (CTN) refers to episodic pain that is strictly confined to the trigeminal distribution area, and the thalamus is an important component of the trigeminal sensory pathway. Probabilistic tracking imaging algorithm was used to identify specific connections between the thalamus and the cortex, in order to identify structural changes in the thalamus of patients with CTN and perform thalamic segmentation. A total of 32 patients with CTN and 32 healthy controls underwent DTI-MRI scanning (3.0 T). Differences in fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) between the groups were studied. Correlation analysis was performed with clinical course and pain level. Compared to the healthy controls, patients in the CTN group had significantly reduced FA, increased AD, RD and MD in somatosensory subregion of the bilateral thalamus, increased RD in frontal subregion, increased RD and MD in motor subregion. Correlation analysis showed that patient history was positively correlated with pain grading, and that medical history was positively correlated with significantly reduced FA in somatosensory subregion, negatively correlated with increased RD and MD in motor subregion. We used DTI-based probabilistic fiber tracking to discover altered structural connectivity between the thalamus and cerebral cortex in patients with CTN and to obtain a thalamic segmentation atlas, which will help to further understand the pathophysiology of CTN and serve as a future reference for thalamic deep brain stimulation electrode implantation for the treatment of intractable pain.
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Imagem de Tensor de Difusão , Neuralgia do Trigêmeo , Humanos , Imagem de Tensor de Difusão/métodos , Neuralgia do Trigêmeo/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Dor , Tálamo/diagnóstico por imagem , AnisotropiaRESUMO
Accumulating evidence has highlighted a strong association between gut microbiota and the occurrence, development, prevention, and treatment of atopic dermatitis (AD). The regulation of gut microbial dysbiosis by oral traditional Chinese medicine (TCM) has garnered significant attention. In the treatment of AD, the TCM formula Qingre-Qushi Recipe (QRQS) has demonstrated clinical efficacy. However, both the therapeutic mechanisms of QRQS and its impact on gut microbiota remain unclear. Thus, our study aimed to assess the efficacy of QRQS and evaluate its influence on the composition and diversity of gut microbiota in AD animal models. First, we investigated the therapeutic effect of QRQS on AD using two animal models: filaggrin-deficient mice (Flaky tail, ft/ft) and MC903-induced AD-like mice. Subsequently, we explored its influence on the composition and diversity of gut microbiota. Our results demonstrated that QRQS treatment ameliorated the symptoms in both ft/ft mice and MC903-induced AD-like mice. It also reduced the levels of serum IgE and pro-inflammatory cytokines, including IL-1ß, IL-4, IL-5, IL-9, IL-13, IL-17A, and TNF-α. Furthermore, QRQS remarkably regulated gut microbiota diversity by increasing Lactobacillaceae and decreasing Bacteroidales. The inflammatory factors in peripheral serum of ft/ft mice showed a close correlation with gut microbiota, as determined using the Spearman correlation coefficient. Additionally, PICRUSt analysis revealed an enrichment in ascorbate and aldarate metabolism, fatty acid metabolism and biosynthesis, and propanoate metabolism in the QRQS group compared to the ft/ft group. Finally, we identified liquiritin as the primary active ingredient of QRQS using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). Our findings revealed that QRQS improved AD-like symptoms and alleviated skin inflammation in ft/ft and MC903-induced mice. This suggests that modulating the gut microbiota may help elucidate its anti-inflammation activation mechanism, highlighting a new therapeutic strategy that targets the intestinal flora to prevent and treat AD.
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ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder that poses a significant global health challenge. There is a lack of safe and effective medications to treat AD. Astragalus membranaceous is a traditional Chinese medicine widely used in clinical treatment of skin diseases. Calycosin (CA), derived from the root of Astragalus membranaceous, exhibits dual attributes of anti-inflammatory and antioxidant properties, suggesting its promise for addressing cutaneous inflammation. Nonetheless, the precise mechanisms underlying CA's therapeutic actions in AD remain elusive. AIM OF THE STUDY: This study aimed to evaluate the efficacy and safety of CA in treating AD while also delving into the mechanistic underpinnings of CA's action in AD. MATERIALS AND METHODS: The cell viability and anti-inflammatory impacts of CA in vitro were first gauged using CCK-8 and RT-qPCR. The potential mechanisms of CA were then probed using modular pharmacology. Flow cytometry was employed to ascertain the differentiation of Treg and Th17 cells derived from naïve T cells, as well as the proportions and mean fluorescence intensity (MFI) of human iTreg cells. The expressions of IL-10 and TGF-ß1 were measured and Treg suppression assay was performed. The in vivo therapeutic efficacy of topical CA application was assessed using a calcipotriol (MC903)-induced AD mouse model. The expression metrics of inflammatory cytokines, IL-17A, FOXP3, and RORγt were authenticated via immunohistochemistry, RT-qPCR, Western blot, and ELISA. RESULTS: CA exhibited a favorable safety profile and reduced the mRNA expressions of Th2 inflammatory cytokines in HaCaT cells. Modular pharmacology analysis pinpointed Th17 differentiation as the pivotal mechanism behind CA's therapeutic effect on AD. In vitro, CA fostered the differentiation of naïve T cells into Tregs while inhibiting their differentiation into Th17 cells. Furthermore, CA augmented the proliferation of human iTregs. In vivo, CA alleviated skin manifestations and decreased the levels of inflammatory mediators (IL-4, IL-5, IL-13, TSLP, and NF-κB related cytokines) in AD-like mouse models. Simultaneously, it regulated Treg/Th17 balance through suppressing IL-17A and RORγt expressions and bolstering FOXP3 expression. CONCLUSIONS: The study provides insights into the mechanistic pathways through which CA exerts its anti-inflammatory effects, particularly through promoting Treg cell differentiation and inhibiting Th17 cell differentiation. Furthermore, CA emerges as an alternative or adjunctive treatment strategy for managing AD.
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Dermatite Atópica , Isoflavonas , Animais , Camundongos , Humanos , Dermatite Atópica/induzido quimicamente , Interleucina-17 , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Linfócitos T Reguladores , Citocinas/metabolismo , Anti-Inflamatórios/efeitos adversos , Diferenciação Celular , Inflamação/tratamento farmacológico , Fatores de Transcrição Forkhead/metabolismo , Células Th17RESUMO
Neurological disorders with various etiologies impacting the nervous system are prevalent in clinical practice. Long non-coding RNA (lncRNA) molecules are functional RNA molecules exceeding 200 nucleotides in length that do not encode proteins, but participate in essential activities. Research indicates that lncRNAs may contribute to the pathogenesis of neurological disorders, and may be potential targets for their treatment. Phytochemicals in traditional Chinese herbal medicine (CHM) have been found to exert neuroprotective effects by targeting lncRNAs and regulating gene expression and various signaling pathways. We aim to establish the development status and neuroprotective mechanism of phytochemicals that target lncRNAs through a thorough literature review. A total of 369 articles were retrieved through manual and electronic searches of PubMed, Web of Science, Scopus and CNKI databases from inception to September 2022. The search utilized combinations of natural products, lncRNAs, neurological disorders, and neuroprotective effects as keywords. The included studies, a total of 31 preclinical trials, were critically reviewed to present the current situation and the progress in phytochemical-targeted lncRNAs in neuroprotection. Phytochemicals have demonstrated neuroprotective effects in preclinical studies of various neurological disorders by regulating lncRNAs. These disorders include arteriosclerotic ischemia-reperfusion injury, ischemic/hemorrhagic stroke, Alzheimer's disease, Parkinson's disease, glioma, peripheral nerve injury, post-stroke depression, and depression. Several phytochemicals exert neuroprotective roles through mechanisms such as anti-inflammatory, antioxidant, anti-apoptosis, autophagy regulation, and antagonism of Aß-induced neurotoxicity. Some phytochemicals targeted lncRNAs and served a neuroprotective role by regulating microRNA and mRNA expression. The emergence of lncRNAs as pathological regulators provides a novel direction for the study of phytochemicals in CHM. Elucidating the mechanism of phytochemicals regulating lncRNAs will help to identify new therapeutic targets and promote their application in precision medicine.
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Doenças do Sistema Nervoso , Fármacos Neuroprotetores , RNA Longo não Codificante , Humanos , Neuroproteção , RNA Longo não Codificante/genética , Fármacos Neuroprotetores/farmacologia , Doenças do Sistema Nervoso/tratamento farmacológico , Compostos Fitoquímicos/farmacologiaRESUMO
Background: The recurrence of colorectal adenomas (CRAs) after endoscopy predisposes patients to a risk of colorectal cancer. Guided by the traditional Chinese medicine (TCM), patients with colorectal diseases usually manifest with spleen deficiency syndrome (SDS) and are treated with Sijunzi decoction (SJZD). Therefore, this trial aims to explore the efficacy and safety of SJZD in the prevention and treatment of CRAs recurrence. Methods: SJZD on prevention and treatment of CRAs recurrence after resection: a multicenter, randomized, double-blind, placebo-controlled trial was designed. Patients who undergo polypectomy of CRAs will be recruited and randomized into a SJZD group and a placebo group in a 1:1 ratio. The intervention phase will be 12 months. The follow-up period will last 24 months. The primary outcome is the CRA recurrence rate after intervention. The secondary outcomes include the CRA recurrence rate at the second year post-polypectomy, the pathological type of adenoma and the alterations in SDS scores after intervention. Discussion: Previous clinical practice has observed the sound effect of SJZD in the context of gastrointestinal diseases. A number of experiments have also validated the active components in SJZD. This trial aims to provide tangible evidence for the usage of SJZD, hoping to reduce the recurrence of CRAs.
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Public health studies indicate that artificial light is a high-risk factor for metabolic disorders. However, the neural mechanism underlying metabolic modulation by light remains elusive. Here, we found that light can acutely decrease glucose tolerance (GT) in mice by activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) innervating the hypothalamic supraoptic nucleus (SON). Vasopressin neurons in the SON project to the paraventricular nucleus, then to the GABAergic neurons in the solitary tract nucleus, and eventually to brown adipose tissue (BAT). Light activation of this neural circuit directly blocks adaptive thermogenesis in BAT, thereby decreasing GT. In humans, light also modulates GT at the temperature where BAT is active. Thus, our work unveils a retina-SON-BAT axis that mediates the effect of light on glucose metabolism, which may explain the connection between artificial light and metabolic dysregulation, suggesting a potential prevention and treatment strategy for managing glucose metabolic disorders.
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Tecido Adiposo Marrom , Hipotálamo , Camundongos , Animais , Humanos , Tecido Adiposo Marrom/metabolismo , Hipotálamo/metabolismo , Termogênese/fisiologia , Retina , Células Ganglionares da Retina , Glucose/metabolismoRESUMO
The association between micronutrient intake and the risk of periodontitis has received much attention in recent years. However, most studies focused on the linear relationship between them. This study aimed to explore the dose-response association between micronutrient intake and periodontitis. A total of 8959 participants who underwent a periodontal examination, and reported their micronutrient intake levels were derived from the US National Health and Nutrition Examination Survey (NHANES, 2009-2014) database. Logistic regression was performed to evaluate associations between micronutrient intake and periodontitis after propensity score matching (PSM), and restricted cubic splines (RCS) analysis was conducted to explore the dose-response associations. Following PSM, 5530 participants were included in the RCS analysis. The risk of periodontitis was reduced with sufficient intake of the following micronutrients: vitamin A, vitamin B1, vitamin B2, and vitamin E. In addition, the risk of periodontitis was increased with excessive intake of the following micronutrients: vitamin B1 (1.8 mg/day, males; 1.3 mg/day, females), vitamin C (90 mg/day, males), and copper (1.1 mg/day, combined). In conclusion, a linear association was found between vitamin A, vitamin B2, vitamin C, and copper and periodontitis-namely, a sufficient intake of vitamin A and vitamin B2 might help reduce the prevalence of periodontitis; by contrast, a high intake of vitamin C and copper increased the risk. In addition, a nonlinear dose-response association was found for the incidence of periodontitis with vitamin B1 and vitamin E. When within reasonable limits, supplemental intake helped reduce the prevalence of periodontitis, while excessive intake did not help significantly and might even increase the risk. However, confounding factors, such as health awareness, should still be considered.
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Periodontite , Vitamina A , Ácido Ascórbico , Cobre , Ingestão de Alimentos , Feminino , Humanos , Masculino , Micronutrientes , Inquéritos Nutricionais , Periodontite/epidemiologia , Riboflavina , Tiamina , Vitamina E , VitaminasRESUMO
Photothermal therapy (PTT) has drawn extensive attention owing to its noninvasive and great tissue penetration depth. However, the physical encapsulation of photothermal agents may lead to their rapid release. Dual-functional hydrogel systems that integrate functions and carriers can potentially solve this problem. In this work, we successfully developed a dual-functional guanosine(G)-based hydrogel integrating the photothermal effect and localized delivery by introducing dynamic borate ester utilizing the photothermal property of PDA-AuNPs and the self-assembly ability of G. Both inâ vitro and inâ vivo results confirmed that the GBPA hydrogel not only exhibited excellent photothermal toxicity, stability, injectability, and biocompatibility, but also possessed high photothermal antitumor activity. These results suggested that the GBPA hydrogel could be used as a dual-functional hydrogel integrating photothermal effect and localized delivery in one system, which would possibly provide a new opportunity for the design of new dual-functional hydrogels for highly efficient cancer therapy.
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Nanopartículas Metálicas , Neoplasias , Boratos , Ouro/farmacologia , Guanosina/farmacologia , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fototerapia , Terapia FototérmicaRESUMO
Biochar is a promising novel material for mitigating phosphorus (P) loss and enhancing P retention in chemical-amended agricultural soils. However, the optimal application rate for aforesaid effectiveness and potential drivers of the process are not well understood. Herein, a column-based pot experiment was carried out to investigate how and to what extent reed-biochar is effective in positively triggering P loss and availability in paddy soils treated by chemical fertilizer. Compared with chemical-only treatment, the accumulated leakage of total P, dissoluble P, and particulate P in chemical fertilizer coupled with 1-4% reed-biochar treatment decreased by 5.3-13.3%, 8.3-10.4%, and 3.0-15.4%, respectively. The accumulated leakage of total P and dissoluble P in 6-8% rate treatments was increased by 5.6-7.5% and 18.3-32.9%, respectively. Increasing reed-biochar rate from 1% to 8% caused an enhancement in soil total P and available P content and P activation coefficient, and the 4% rate achieved a similar effectiveness to the higher rate. Reed-biochar application increased the abundance and diversty of soil phoD-harboring microbes (P < 0.05), while the increment had little to do with the application rate. Soil phoD-harboring community composition and total C content were the main predictors of the P leaching losses, and meanwhile, the total C content was the dominated predictor of soil P retention and availability. These results suggest that adding 1-4% reed-biochar was more beneficial to mitigate paddy P loss and to enhance soil P availability. This study highlights the importance of understanding how microbial populations mediate P transformation to decipher the biochar-driven improvement of soil P utilization.
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Oryza , Solo , Carvão Vegetal , Fertilizantes/análise , FósforoRESUMO
The primordial small gaseous molecules, such as: NO, CO, H2S and formaldehyde (FA) are present in the brains. Whether FA as well as the other molecules participates in brain functions is unclear. Recently, its pathophysiological functions have been investigated. Notably, under physiological conditions, learning activity induces a transient generation of hippocampal FA, which promotes memory formation by enhancing N-methyl-D-aspartate (NMDA)-currents. However, ageing leads to FA accumulation in brain for the dysregulation of FA metabolism; and excessive FA directly impairs memory by inhibiting NMDA-receptor. Especially, in Alzheimer's disease (AD), amyloid-beta (Aß) accelerates FA accumulation by inactivating alcohol dehydrogenase-5; in turn, FA promotes Aß oligomerization, fibrillation and tau hyperphosphorylation. Hence, there is a vicious circle encompassing Aß assembly and FA generation. Even worse, FA induces Aß deposition in the extracellular space (ECS), which blocks the medicines (dissolved in the interstitial fluid) flowing into the damaged neurons in the deep cortex. However, phototherapy destroys Aß deposits in the ECS and restores ISF flow. Coenzyme Q10, which scavenges FA, was shown to ameliorate Aß-induced AD pathological phenotypes, thus suggesting a causative relation between FA toxicity and AD. These findings suggest that the combination of these two methods is a promising strategy for treating AD.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Formaldeído/efeitos adversos , Formaldeído/toxicidade , Humanos , Hipersensibilidade RespiratóriaRESUMO
@#Oral mucosal disease is a general term for a type of disease that mainly affects the oral mucosa and surrounding soft tissues. In the treatment of oral mucosal diseases, due to the particularity of the anatomical location, the use of topical administration is relatively simple and convenient; drugs can easily accumulate in the lesions, and at the same time, they can also avoid adverse reactions caused by systemic drug delivery. Topical administration has become an important and even preferred option for the treatment of oral mucosal diseases. There are various types of topically used drugs for oral mucosal diseases, such as glucocorticoids (triamcinolone acetonide), immunomodulatory drugs (tacrolimus), antiseptic drugs (chlorhexidine), pain relievers (lidocaine) and proprietary Chinese medicines (aloe vera gel). Among these drugs, although the most widely used liquid formulations such as gargles and sprays are easy to use, they are not conducive to local retention of drugs due to the particularity of the oral environment and function. Based on this, researchers have continuously improved the dosage form of the drug, and developed a series of semi-solid pharmaceutical preparations such as gels and ointments, some of which have exerted good curative effects in clinical work. In addition, although films, patches and other solid oral mucosal topical pharmaceutical preparations have few clinical applications, they have also been widely researched and described and are expected to become the mainstream dosage form in the future. In general, with the improvement of dosage forms, topical administration is playing an increasingly important role in the treatment of oral mucosal diseases. Therefore, combined with basic research and clinical reports, this article reviews the application of topical drug delivery in the treatment of oral mucosal diseases
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To determine the effect of smoking on circulating vitamin D in adults, we performed a meta-analysis. Literature before 9 May 2021 was retrieved from electronic literature databases such as EMBASE, PubMed, and Cochrane. The quality of the included studies was assessed by two researchers against the Newcastle-Ottawa scale and JBI Evidence-based Health Care Centre criteria. All eligible studies and statistical analyses were performed using STATA 14. Twenty-four studies with 11,340 participants meeting the criteria were included in the meta-analysis. The results of meta-analysis showed that the level of circulating 25(OH)D in smokers was lower than that in nonsmokers. A subgroup analysis based on vitamin D supplement use showed that both smokers who used vitamin D supplements and smokers who did not use vitamin D supplements had lower blood 25(OH)D levels compared with the control group. In addition, subjects were divided into different subgroups according to age for meta-analysis, and the results showed that the serum 25(OH)D level in each subgroup of smokers was lower than that in the control group. This meta-analysis revealed differences in circulating vitamin D levels between smokers and nonsmokers, with smokers likely to have lower circulating vitamin D levels.
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Cancer is a leading cause of death worldwide and seriously threatens the health of humans. The current clinical treatments for cancer are not efficient and always lead to significant side effects. Herein, a biocompatible and powerful theranostic agent (Bi@mSiO2@MnO2/DOX) is fabricated using a facile stepwise reaction method. The Bi nanoparticles (NPs) are coated by mesoporous silica to protect the Bi NPs from oxidation, which guarantees the stable photothermal effect of the Bi NPs. When the Bi@mSiO2@MnO2/DOX nanocomposites (NCs) accumulate in the tumour site, hyperthermia is generated by Bi NPs under near-infrared (NIR) light irradiation for photothermal therapy (PTT), and the generated heat triggers the release of DOX for chemotherapy in the tumour. In addition, the MnO2 of the NCs responsively catalyses endogenous H2O2 to generate O2, raising the oxygen level to enhance the effect of chemotherapy in the tumour microenvironment (TME), and consumes glutathione (GSH) to produce Mn2+ for magnetic resonance (MR) imaging. Under acidic TME conditions, H2O2 and Mn2+ also produce toxic hydroxyl radical (·OH) for chemodynamic therapy (CDT). Furthermore, the Bi NPs can also be used as excellent contrast agents for X-ray computed tomography (CT) imaging of tumours with a high CT value (6.865 HU mM-1). The Bi@mSiO2@MnO2/DOX NCs exhibit a powerful theranostic performance for CT/MR imaging-guided enhanced PTT/CDT/chemotherapy, which opens a new prospect to rationally design theranostic agents for tumour imaging.
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Nanopartículas , Neoplasias , Bismuto , Humanos , Peróxido de Hidrogênio , Imageamento por Ressonância Magnética , Compostos de Manganês , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Óxidos , Fototerapia , Medicina de Precisão , Nanomedicina Teranóstica , Tomografia Computadorizada por Raios X , Microambiente TumoralRESUMO
The worldwide emergence and spread of antimicrobial resistance is accelerated by irrational administration and use of empiric antibiotics. A key point to the crisis is a lack of rapid diagnostic protocols for antimicrobial susceptibility testing (AST), which is crucial for a timely and rational antibiotic prescription. Here, a recombinant bacteriophage tail fiber protein (TFP) was functionalized on magnetic particles to specifically capture Pseudomonas aeruginosa, while fluorescein isothiocyanate-labeled-magainin II was utilized as the indicator. For solving the magnetic particles' blocking effects, a reverse assaying protocol based on TFP recognition was developed to investigate the feasibility of detection and AST of P. aeruginosa. P. aeruginosa can be rapidly, sensitively and specifically detected within 1.5 h with a linear range of 1.0 × 102 to 1.0 × 106 colony forming units (CFU)â mL-1 and a detection limit of 3.3 × 10 CFUâ mL-1. Subsequently, AST results, which were consistent with broth dilution results, can be obtained within 3.5 h. Due to the high specificity of the TFP, AST can actually be conducted without the need for bacterial isolation and identification. Based on the proof-of-principle work, the detection and AST of other pathogens can be extended by expressing the TFPs of their bacteriophages.
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Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa , HumanosRESUMO
Biochar has been widely applied for the remediation of petroleum-contaminated soil. However, the effect of biochar on the transport of petroleum degradation bacteria has not been studied. A typical Gram-positive petroleum degradation bacteria-Corynebacterium variabile HRJ4 was used to study the effect of different biochars on bacterial transport and retention. Results indicated that the addition of biochar in sand was effective for reducing the transport of bacteria and poplar sawdust biochar (PSBC) had a stronger hinder effect than corn straw biochar (CSBC). The hindrance was more evident with pyrolysis temperature of biochar raised from 300°C to 600°C, which was attributed to the increase of specific surface area (309 times). The hindrance effect also enhanced with higher application rate of biochar. Furthermore, the reduction of HRJ4 transport was more obvious in higher (25 mmol/L) concentration of NaCl solution owing to electrostatic attraction enhancement. The adsorption of biochar to HRJ4 was defined to contribute to the hindrance of HRJ4 transport mainly. Combining the influence of feedstocks and pyrolysis temperature on HRJ4 transport, it suggested that specific surface area had the greatest effect on HRJ4 transport, and pore-filling, electrostatic force also contributed to HRJ4 retained in quartz sand column. At last, phenol transportation experiment indicated that the restriction of biochar on HRJ4 enhanced the phenol removal rate in the column. This study provides a theoretical basis for the interaction of biochar and bacteria, which is vital for the remediation of oil-contaminated soil and groundwater in the field.
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Petróleo , Pirólise , Bactérias , Carvão Vegetal , Corynebacterium , Porosidade , Solo , TemperaturaRESUMO
Photothermal therapy (PTT) is a promising treatment for tumors due to its efficiency and non-invasiveness. However, during the PTT treatment, reactive oxygen species (ROS) are produced in response to hyperthermia and thus harm the neighboring normal cells. In this work, a multifunctional theranostic agent (Se@SiO2@Au-PEG/DOX NCs) was exploited to solve this problem by introducing selenium, which can efficiently prevent normal cells from oxidative damage by scavenging reactive oxygen species during photothermal therapy. In addition, the Se@SiO2@Au-PEG/DOX nanocomposites (NCs) not only exhibited excellent properties of combined chemo-thermal synergistic therapy, but also showed no appreciable toxicity towards normal tissues due to the protective effect for continuous release of selenium. Thus, the fabricated Se@SiO2@Au-PEG/DOX NCs provide an integrated solution to overcome the limitations of selenium and PTT, and demonstrate great prospects as a safe and highly reliable theranostic agent.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Fotoquimioterapia , Nanomedicina Teranóstica , Células A549 , Animais , Antibióticos Antineoplásicos/síntese química , Antibióticos Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Doxorrubicina/síntese química , Doxorrubicina/química , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Ouro/química , Ouro/farmacologia , Humanos , Camundongos , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Selênio/química , Selênio/farmacologia , Dióxido de Silício/química , Dióxido de Silício/farmacologiaRESUMO
Erythrina corallodendron L., a kind of landscape tree, has long been used as a traditional medicine. In this study, the composition of essential oil extracted from the leaves was analysed by GC-MS (gas chromatograph-mass spectrometer), with linalool identified as the main compound. Its cytotoxicity against MDA-MB-231, MCF-7 and HMLE cells was examined by MTT and cloning assays. Transwell and wound-healing assays were used to examine the inhibition of migration and invasion. Western blot, qRT-PCR and immunofluorescence staining were used to measure the mRNA and protein expression of factors related to EMT (snail, slug, E-cadherin, N-cadherin and vimentin). The essential oil of Erythrina corallodendron leaves was found to inhibit the proliferation, migration and invasion of breast cancer cells in a dose-dependent manner. The findings of this study suggest that the essential oil of E. corallodendron leaves may merit further investigation as a potential clinical or adjuvant drug for treating breast cancer migration and invasion.