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Cancer cells frequently develop resistance to chemotherapeutic therapies and targeted drugs, which has been a significant challenge in cancer management. With the growing advances in technologies in isolation and identification of natural products, the potential of natural products in combating cancer multidrug resistance has received substantial attention. Importantly, natural products can impact multiple targets, which can be valuable in overcoming drug resistance from different perspectives. In the current review, we will describe the well-established mechanisms underlying multidrug resistance, and introduce natural products that could target these multidrug resistant mechanisms. Specifically, we will discuss natural compounds such as curcumin, resveratrol, baicalein, chrysin and more, and their potential roles in combating multidrug resistance. This review article aims to provide a systematic summary of recent advances of natural products in combating cancer drug resistance, and will provide rationales for novel drug discovery.
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Antineoplásicos , Produtos Biológicos , Neoplasias , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos AntineoplásicosRESUMO
Stroke poses a serious risk to the physical and mental health of patients. Endogenous compounds are widely used to treat ischemic stroke. Lipoic acid, a naturally occurring (R)-5-(1,2-dithiolan-3-yl)pentanoic acid, has therapeutic potential for the treatment of ischemic stroke. However, the direct application of lipoic acid is limited by its relatively low efficacy and instability. Therefore, there is a need to modify the structure of lipoic acid to improve its pharmaceutical capabilities. Currently, 37 lipoic acid derivatives have been synthesized, and compound AA-9 demonstrated optimal therapeutic potential in an in vitro model of induced oxidative damage using tert-butyl hydroperoxide (t-BHP). In addition, in vitro experiments have shown that compound AA-9 has an excellent safety profile. Subsequently, the therapeutic effect of AA-9 was significant in the rat MCAO ischemic stroke model, which may be attributed to the antioxidant and anti-inflammatory effects of compound AA-9 by activating PGC-1α and inhibiting NLRP3. Notably, compound AA-9 exhibited higher stability and better bioavailability properties than ALA in plasma stability and pharmacokinetic properties. In conclusion, AA-9 may be a promising neuroprotective agent for the treatment of ischemic stroke and warrants further investigation.
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AVC Isquêmico , Fármacos Neuroprotetores , Estresse Oxidativo , Ratos Sprague-Dawley , Ácido Tióctico , Ácido Tióctico/química , Ácido Tióctico/farmacologia , Ácido Tióctico/síntese química , Animais , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/síntese química , Estresse Oxidativo/efeitos dos fármacos , Ratos , AVC Isquêmico/tratamento farmacológico , Estrutura Molecular , Relação Estrutura-Atividade , Masculino , Descoberta de Drogas , Relação Dose-Resposta a Droga , Inflamação/tratamento farmacológico , Inflamação/metabolismo , HumanosRESUMO
Neuroprotective agents with attenuation of oxidative stress by directly scavenging ROS and indirectly through Keap1-Nrf2 signal pathway activation may be a promising cerebral ischemic stroke therapeutic strategy. In this study, a series of novel danshensu derivatives bearing pyrazolone moieties with dual antioxidant effects were synthesized for the treatment of ischemic stroke. Most compounds exhibited considerable DPPH free radical scavenging ability and neuroprotective activity against H2O2-induced oxidative injury in PC12 neuronal cells, without cytotoxicity. Among these target compounds, Del03 displayed the strongest dose-dependent neuroprotective activity in vitro, directly downregulated intracellular ROS levels, and improved the oxidative stress parameters MDA, SOD, and LDH. Del03 also promoted Nrf2 translocation to the nucleus, subsequently increasing the expression of the Nrf2 downstream target HO-1. Molecular docking analysis revealed that Del03 could anchor to the key site of Keap1. Del03 possessed the ability to penetrate blood-brain barrier and displayed good ability on pharmacokinetic properties in rats Del03 possessed good BBB penetration efficiency, suitable pharmacokinetic properties in vivo. Del03 reduced cerebral infarction volume and promoted neurological function in a middle cerebral artery occlusion (MCAO) mouse model at a dose of 20 mg/kg by intravenous injection. The characteristics of Del03 detailed in this study demonstrate its potential as a therapeutic agent in the treatment of ischemic stroke.
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Fármacos Neuroprotetores , Acidente Vascular Cerebral , Camundongos , Ratos , Animais , Antioxidantes/uso terapêutico , Proteína 1 Associada a ECH Semelhante a Kelch , Espécies Reativas de Oxigênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Peróxido de Hidrogênio/farmacologia , Simulação de Acoplamento Molecular , Acidente Vascular Cerebral/tratamento farmacológico , Estresse Oxidativo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
True sea snakes (Hydrophiini) are among the last and most successful clades of vertebrates that show secondary marine adaptation, exhibiting diverse phenotypic traits and lethal venom systems. To better understand their evolution, we generated the first chromosome-level genomes of two representative Hydrophiini snakes, Hydrophis cyanocinctus and H. curtus. Through comparative genomics we identified a great expansion of the underwater olfaction-related V2R gene family, consisting of more than 1,000 copies in both snakes. A series of chromosome rearrangements and genomic structural variations were recognized, including large inversions longer than 30 megabase (Mb) on sex chromosomes which potentially affect key functional genes associated with differentiated phenotypes between the two species. By integrating multiomics we found a significant loss of the major weapon for elapid predation, three-finger toxin genes, which displayed a dosage effect in H. curtus. These genetic changes may imply mechanisms that drove the divergent evolution of adaptive traits including prey preferences between the two closely related snakes. Our reference-quality sea snake genomes also enrich the repositories for addressing important issues on the evolution of marine tetrapods, and provide a resource for discovering marine-derived biological products.
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Hydrophiidae , Animais , Venenos Elapídicos/genética , Evolução Molecular , Genoma , Hydrophiidae/genética , FenótipoRESUMO
A transocular infection has been proved as one of the main approaches that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades the body, and angiotensin-converting enzyme 2 (ACE2) plays a key role in this procedure. Dynamic and quantitative details on virus distribution are lacking for virus prevention and drug design. In this study, a radiotraceable pseudovirus packed with an enhanced green fluorescent protein (EGFP) gene, 125 I-CoV, was prepared and inoculated in the unilateral eye of humanized ACE2 (hACE2) mice or ACE2-knockout (ACE2-KO) mice. Single-photon emission computed tomography/computed tomography images were acquired at multiple time points to exhibit ACE2-dependent procedures from invasion to clearance. Positron emission tomography (PET) and western blot were performed to quantify ACE2 expression and verify the factors affecting transocular infection. For the transocular infection of coronavirus (CoV), the renin-angiotensin-aldosterone system (RAAS), lungs, intestines, and genital glands were the main targeted organs. Due to the specific anchor to ACE2-expressed host cells, virus concentrations in genital glands, liver, and lungs ranked the top three most and stabilized at 3.75 ± 0.55, 3.30 ± 0.25, and 2.10 ± 0.55% inoculated dose (ID)/mL at 48 h post treatment. Meanwhile, ACE2-KO mice had already completed the in vivo clearance. In consideration of organ volumes, lungs (14.50 ± 3.75%ID) and liver (10.94 ± 0.71%ID) were the main in-store reservoirs of CoV. However, the inoculated eye (5.52 ± 1.85%ID for hACE2, 5.24 ± 1.45%ID for ACE2-KO, p > 0.05) and the adjacent brain exhibited ACE2-independent virus infection at the end of 72 h observation, and absolute amount of virus played a key role in host cell infection. These observations on CoV infection were further manifested by infection-driven intracellular EGFP expression. ACE2 PET revealed an infection-related systematic upregulation of ACE2 expression in the organs involved in RAAS (e.g., brain, lung, heart, liver, and kidney) and the organ that was of own local renin-angiotensin system (e.g., eye). Transocular infection of CoV is ACE2-dependent and constitutes the cause of disturbed ACE2 expression in the host. The brain, genital glands, and intestines were of the highest unit uptake, potentially accounting for the sequelae. Lungs and liver were of the highest absolute amount, closely related to the respiratory diffusion and in vivo duplication. ACE2 expression was upregulated in the short term after infection with CoV. These visual and quantitative results are helpful to fully understanding the transocular path of SARS-CoV-2 and other CoVs.
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Enzima de Conversão de Angiotensina 2 , COVID-19 , Infecções Oculares Virais , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , COVID-19/diagnóstico por imagem , COVID-19/genética , COVID-19/metabolismo , Infecções Oculares Virais/genética , Infecções Oculares Virais/metabolismo , Infecções Oculares Virais/virologia , Camundongos , Imagem Molecular , Peptidil Dipeptidase A/genética , SARS-CoV-2RESUMO
Ischemic stroke (IS) is a severe neurological disease caused by the narrowing or occlusion of cerebral blood vessels and is known for high morbidity, disability, and mortality rates. Clinically available treatments of stroke include the surgical removal of the thrombus and thrombolysis with tissue fibrinogen activator. Pharmaceuticals targeting IS are uncommon, and the development of new therapies is hindered by the low bioavailability and stability of many drugs. Nanomedicine provides new opportunities for the development of novel neuroprotective and thrombolytic strategies for the diagnosis and treatment of IS. Numerous nanotherapeutics with different physicochemical properties are currently being developed to facilitate drug delivery by accumulation and controlled release and to improve their restorative properties. In this review, we discuss recent developments in IS therapy, including assisted drug delivery and targeting, neuroprotection through regulation of the neuron environment, and sources of endogenous biomimetic specific targeting. In addition, we discuss the role and neurotoxic effects of inorganic metal nanoparticles in IS therapy. This study provides a theoretical basis for the utilization of nano-IS therapies that may contribute to the development of new strategies for a range of embolic diseases.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Humanos , AVC Isquêmico/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Terapia Trombolítica , Ativador de Plasminogênio TecidualRESUMO
The emotion-cause pair extraction task is a fine-grained task in text sentiment analysis, which aims to extract all emotions and their underlying causes in a document. Recent studies have addressed the emotion-cause pair extraction task in a step-by-step manner, i.e., the two subtasks of emotion extraction and cause extraction are completed first, followed by the pairing task of emotion-cause pairs. However, this fail to deal well with the potential relationship between the two subtasks and the extraction task of emotion-cause pairs. At the same time, the grammatical information contained in the document itself is ignored. To address the above issues, we propose a deep neural network based on span association prediction for the task of emotion-cause pair extraction, exploiting general grammatical conventions to span-encode sentences. We use the span association pairing method to obtain candidate emotion-cause pairs, and establish a multi-dimensional information interaction mechanism to screen candidate emotion-cause pairs. Experimental results on a quasi-baseline corpus show that our model can accurately extract potential emotion-cause pairs and outperform existing baselines.
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Emoções , Redes Neurais de ComputaçãoRESUMO
In this study, we explored the role and mechanism of repulsive guidance molecule B (RGMb, also known as Dragon) in the protective effects of curcumin against renal fibrosis and verified Dragon's effect on renal tubular epithelial cell apoptosis and cell programmability. Unilateral ureteral obstruction (UUO) was surgically induced in rats to establish a model of renal interstitial fibrosis (RIF). The rats were then treated with curcumin. Curcumin prominently decreased the serum creatinine (SCr) and blood urea nitrogen (BUN) levels, and also improved the tubular injury in the UUO-induced rats. Curcumin significantly downregulated the TGF-ß1, P-Smad2/3, cleaved caspase-3, cleaved caspase-8 and Dragon levels. Dragon knockdown also markedly reduced the TGF-ß1, P-Smad2/3, Smad2/3, cleaved caspase-3, cleaved caspase-8, fibronectin, collagen I, collagen IV, vimentin, and α-SMA expression levels. Conversely, Dragon overexpression caused higher expression levels of these proteins, and curcumin reversed this effect. Furthermore, Dragon knockdown increased the E-cadherin levels, whereas Dragon overexpression decreased these levels. Overexpressing Dragon significantly decreased the cell viability, and curcumin reversed this effect. In conclusion, curcumin acted on Dragon and attenuated RIF in UUO rat models. Curcumin downregulated the TGF-ß1/Smad signaling pathway and inhibited Dragon and fibrogenic molecules in both rats and HK-2 cells.
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Curcumina/farmacologia , Fibrose/tratamento farmacológico , Proteínas Ligadas por GPI/biossíntese , Rim/efeitos dos fármacos , Proteínas do Tecido Nervoso/biossíntese , Receptores de Superfície Celular/biossíntese , Obstrução Ureteral/tratamento farmacológico , Animais , Nitrogênio da Ureia Sanguínea , Caspase 3/metabolismo , Creatinina/metabolismo , Fibrose/metabolismo , Fibrose/patologia , Proteínas Ligadas por GPI/efeitos dos fármacos , Humanos , Rim/metabolismo , Rim/patologia , Masculino , Proteínas do Tecido Nervoso/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores de Superfície Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo , Obstrução Ureteral/metabolismoRESUMO
Although within-cluster information is commonly used in most clustering approaches, other important information such as between-cluster information is rarely considered in some cases. Hence, in this study, we propose a new novel measure of between-cluster distance in subspace, which is to maximize the distance between the center of a cluster and the points that do not belong to this cluster. Based on this idea, we firstly design an optimization objective function integrating the between-cluster distance and entropy regularization in this paper. Then, updating rules are given by theoretical analysis. In the following, the properties of our proposed algorithm are investigated, and the performance is evaluated experimentally using two synthetic and seven real-life datasets. Finally, the experimental studies demonstrate that the results of the proposed algorithm (ERKM) outperform most existing state-of-the-art k-means-type clustering algorithms in most cases.
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BACKGROUND: Jellyfish respond quickly to external stress that stimulates mucus secretion as a defense. Neither the composition of secreted mucus nor the process of secretion are well understood. METHODS: Aurelia coerulea jellyfish were stimulated by removing them from environmental seawater. Secreted mucus and tissue samples were then collected within 60 min, and analyzed by a combination of proteomics and metabolomics using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), respectively. RESULTS: Two phases of sample collection displayed a quick decrease in volume, followed by a gradual increase. A total of 2421 and 1208 proteins were identified in tissue homogenate and secreted mucus, respectively. Gene Ontology (GO) analysis showed that the mucus-enriched proteins are mainly located in extracellular or membrane-associated regions, while the tissue-enriched proteins are distributed throughout intracellular compartments. Tryptamine, among 16 different metabolites, increased with the largest-fold change value of 7.8 in mucus, which is consistent with its involvement in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway 'tryptophan metabolism'. We identified 11 metalloproteinases, four serpins, three superoxide dismutases and three complements, and their presence was speculated to be related to self-protective defense. CONCLUSIONS: Our results provide a composition profile of proteins and metabolites in stress-induced mucus and tissue homogenate of A. coerulea. This provides insight for the ongoing endeavors to discover novel bioactive compounds. The large increase of tryptamine in mucus may indicate a strong stress response when jellyfish were taken out of seawater and the active self-protective components such as enzymes, serpins and complements potentially play a key role in innate immunity of jellyfish.
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Imunidade Inata , Muco/metabolismo , Cifozoários/fisiologia , Estresse Fisiológico/imunologia , Animais , Cromatografia Líquida de Alta Pressão/métodos , Proteínas do Sistema Complemento/imunologia , Proteínas do Sistema Complemento/metabolismo , Enzimas/imunologia , Enzimas/metabolismo , Metabolômica , Muco/química , Muco/imunologia , Proteômica , Serpinas/imunologia , Serpinas/metabolismo , Espectrometria de Massas em Tandem/métodosRESUMO
The NLR pyrin domain containing 3 (NLRP3) inflammasome plays a crucial role in lung disease and may have a similar role in upper respiratory tract inflammation. We therefore constructed a C57BL/6 mouse model of acute rhinosinusitis induced by Staphylococcus aureus and investigated the role of the NLRP3 inflammasome in this model. Mice were classified as non-inoculated group (group A) and inoculated groups (groups B, C, D and E, sacrificed 1, 3, 7 and 14 days after inoculation, respectively). Hematoxylin-eosin staining showed that each group had inflammatory cell infiltration, except group A. The damage of the nasal mucosa was aggravated gradually over time. Western blot and immunofluorescence showed that the structural proteins of the NLRP3 inflammasome (NLRP3, ASC (apoptosis-associated speck-like protein containing CARD), procaspase-1) in groups B, C, D and E were increased gradually. But they were reduced in group B compared with group A, except for NLRP3. Western blot showed that the cleavage fragment of procaspase-1, p20 in groups B, C, D and E was increased gradually. Real-time PCR showed that the corresponding mRNAs of the structural proteins were changed the same as their proteins. IL-1ß mRNA and mature IL-1ß protein were increased gradually in groups A, B, C, D and E. These results indicate that NLRP3 inflammasome activation was associated with the acute rhinosinusitis, and that there was a positive correlation between the expression level of the NLRP3 inflammasome and the severity of acute rhinosinusitis.
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Proteínas de Transporte/metabolismo , Inflamassomos/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Adaptadoras de Sinalização CARD , Proteínas de Transporte/genética , Caspase 1/genética , Caspase 1/metabolismo , Modelos Animais de Doenças , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Rinite/microbiologia , Rinite/patologia , Sinusite/microbiologia , Sinusite/patologia , Staphylococcus aureus/patogenicidadeRESUMO
SCOPE: Nonalcoholic steatohepatitis (NASH) is an increasingly common chronic liver disease in which hepatic fibrosis is the major pathological change. The transforming growth factor ß (TGF-ß)/mall mothers against decapentaplegic (Smad) signaling is the main effector of fibrosis. Although the antifibrotic effect of echinacoside (Ech) on the liver has been indicated previously, the cellular and molecular mechanisms remain unclear. This study aims to investigate both in vivo and in vitro antifibrotic properties of Ech. METHODS AND RESULTS: Cell viability and scratch/wound assays show that Ech significantly inhibits the proliferation, migration, and activation of human hepatic stellate LX-2 cells. In mice with high-fat diet-induced hepatic fibrosis, Ech treatment attenuates the progression of liver injury, inflammation, and fibrosis. Furthermore, transcriptome analysis and subsequent functional validation demonstrate that Ech achieves antifibrotic effects by the activin receptor type-2A (ACVR2A)-mediated TGF-ß1/Smad signaling pathway; ultimately, ACVR2A is demonstrated to be an important target for hepatic fibrosis by inhibiting and inducing the expression of ACVR2A in LX-2 cells. CONCLUSION: Ech exerts potent antifibrotic effects by inhibiting the ACVR2A-mediated TGF-ß1/Smad signaling axis and may serve as an alternative treatment for hepatic fibrosis.
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Glicosídeos , Proteínas Smad , Fator de Crescimento Transformador beta1 , Camundongos , Humanos , Animais , Proteínas Smad/metabolismo , Fibrose , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Modelos Animais de Doenças , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologiaRESUMO
Overproduction of reactive oxygen species by damaged mitochondria after ischemia is a key factor in the subsequent cascade of damage. Delivery of therapeutic agents to the mitochondria of damaged neurons in the brain is a potentially promising targeted therapeutic strategy for the treatment of ischemic stroke. In this study, we developed a ceria nanoenzymes synergistic drug-carrying nanosystem targeting mitochondria to address multiple factors of ischemic stroke. Each component of this nanosystem works individually as well as synergistically, resulting in a comprehensive therapy. Alleviation of oxidative stress and modulation of the mitochondrial microenvironment into a favorable state for ischemic tolerance are combined to restore the ischemic microenvironment by bridging mitochondrial and multiple injuries. This work also revealed the detailed mechanisms by which the proposed nanodelivery system protects the brain, which represents a paradigm shift in ischemic stroke treatment.
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Ischemia-reperfusion injury is caused by excessive production of reactive oxygen species (ROS) and inflammation accompanied by ischemic injury symptoms and blood-brain barrier (BBB) dysfunction. This causes neuronal damage, for which no effective treatments or drugs exist. Herein, we provided a stepwise targeted drug delivery strategy and successfully prepared multifunctional ORD@SHp@ANG nanoparticles (NPs) that consist of a stroke homing peptide (DSPE-PEG2000-SHp), BBB-targeting peptide (DSPE-PEG2000-ANG), and ROS-responsive Danshensu (salvianic acid A) chain self-assembly. ORD@SHp@ANG NPs effectively crossed the BBB by ANG peptide and selectively targeted the ischemic brain sites using stroke-homing peptide. The results showed that ORD@SHp@ANG NPs can effective at scavenging ROS, and protect SH-SY5Y cells from oxidative damage in vitro. Furthermore, ORD@SHp@ANG NPs showed excellent biocompatibility. These NPs recognized brain endothelial cells and crossed the BBB, regulated the transformation of microglia into the anti-inflammatory phenotype, and inhibited the production of inflammatory factors in a rat ischemia-reperfusion model, thereby reducing cerebral infarction, neuronal apoptosis and preserving BBB integrity. Sequencing revealed that ORD@SHp@ANG NPs promote cell proliferation, activate immune responses, suppress inflammatory responses, and ameliorate ischemic stroke. In conclusion, this study reports a simple and promising drug delivery strategy for managing ischemic stroke.
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Isquemia Encefálica , AVC Isquêmico , Neuroblastoma , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Ratos , Humanos , Animais , Isquemia Encefálica/tratamento farmacológico , Espécies Reativas de Oxigênio , Células Endoteliais , Acidente Vascular Cerebral/tratamento farmacológico , Barreira Hematoencefálica , Estresse Oxidativo , Peptídeos/farmacologia , Inflamação/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Infarto da Artéria Cerebral Média/tratamento farmacológicoRESUMO
The nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway is an effective mechanism involved in the treatment of hypertension. In our search for potential antihypertensive agents, a series of novel NO-donor derivatives of the 4-chromanone skeleton were designed and synthesized by coupling furoxans or nitrooxy NO-donor moieties. All derivatives showed enhanced nitric oxide releasing capacity and vasodilator activity with EC50 values ranging from 0.0215 µM to 1.46 µM, obviously superior to those of precursor 3. These biological evaluations indicated that all compounds displayed an important vasorelaxant effect, and several compounds (9c, 14b, 14c, 14d) presented good vasodilator activity, with 14c being the best. Furthermore, molecular modeling studies revealed that compound 14c occupied the pocket well with the phosphodiesterase 5 domain in a favorable conformation. In conclusion, we observed that these novel compounds can act as structural templates for the design and subsequent development of new vasodilators and antihypertensive drugs.
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Óxido Nítrico , Vasodilatadores , Vasodilatadores/farmacologia , Vasodilatadores/química , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/química , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/químicaRESUMO
A chicken farmer with cirrhosis and renal failure presented with an unusual case of catheter-related bacteremia. Testing with the VITEK® 2 Compact system, MALDI-TOF mass spectrometry, and 16S rDNA sequencing identified the pathogen as E. gallinarum. This case demonstrates the importance of maintaining a high level of contextual awareness in patients exposed to avian species to make an informed diagnosis and provide prompt treatment.
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Growing concerns exist regarding human ingestion of contaminated seafood that contains Vibrio biofilms on microplastics (MPs). One of the mechanisms enhancing biofilm related infections in humans is due to biofilm dispersion, a process that triggers release of bacteria from biofilms into the surrounding environment, such as the gastrointestinal tract of human hosts. Dispersal of cells from biofilms can occur in response to environmental conditions such as sudden changes in temperature, pH and nutrient conditions, as the bacteria leave the biofilm to find a more stable environment to colonize. This study evaluated how brief exposures to nutrient starvation, elevated temperature, different pH levels and simulated human media affect Vibrio parahaemolyticus and Vibrio vulnificus biofilm dispersal and processes on and from low-density polyethylene (LDPE), polypropylene (PP), and polystyrene (PS) MPs. Both species were able to adequately disperse from all types of plastics under most exposure conditions. V. parahaemolyticus was able to tolerate and survive the low pH that resembles the gastric environment compared to V. vulnificus. pH had a significantly (p ≤ 0.05) positive effect on overall V. parahaemolyticus biofilm biomass in microplates and cell colonization from PP and PS. pH also had a positive effect on V. vulnificus cell colonization from LDPE and PP. However, most biofilm biomass, biofilm cell and dispersal cell densities of both species greatly varied after exposure to elevated temperature, pH, and nutrient starvation. It was also found that certain exposures to simulated human media affected both V. parahaemolyticus and V. vulnificus biofilm biomass and biofilm cell densities on LDPE, PP and PS compared to exposure to traditional media of similar pH. Cyclic-di-GMP was higher in biofilm cells compared to dispersal cells, but exposure to more stressful conditions significantly increased signal concentrations in both biofilm and dispersal states. Taken together, this study suggests that human pathogenic strains of V. parahaemolyticus and V. vulnificus can rapidly disperse with high cell densities from different plastic types in vitro. However, the biofilm dispersal process is highly variable, species specific and dependent on plastic type, especially under different human body related environmental exposures.
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Ischemia-reperfusion (I/R) injury refers to a new injury caused by reperfusion after the restoration of ischemic tissue or organ blood supply. Salvianic acid A (danshensu) is a primary active ingredient extracted from Salvia miltiorrhiza. It has a protective function against I/R injury in the cardiovascular system, brain, liver, kidney, gastrointestinal tract, and other organs. This article reviews evidence of the protective effects of Salvianic acid A and its potential mechanisms of action in organ I/R injury protection. The aim of this review is to investigate the role of Salvianic acid A in the treatment of I/R injury, providing a reference resource that could facilitate subsequent studies.
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In recent years, brain diseases have seriously threatened human health due to their high morbidity and mortality. Achieving efficient drug delivery to provide satisfactory therapeutic outcomes is currently the greatest challenge in treating brain diseases. The main challenges are the structural peculiarities of the brain and the inability to transport drugs across the blood-brain barrier. Biomimetic nanodelivery systems (BNDSs) applied to the brain have been extensively developed in the preclinical phase to surmount these challenges. Considering the inherent properties of BNDSs, the substantially enhanced ability of BNDS to carry therapeutic agents and their higher selectivity toward lesions offer new opportunities for developing safe and effective therapies. This review summarizes brain-targeting nanotherapies, particularly advanced therapies with biomimetic nano-assistance. Prospects for developing BNDSs and the challenges of their clinical translation are discussed. Understanding and implementing biomimetic nanotherapies may facilitate the development of new targeted strategies for brain disorders.
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Encefalopatias , Nanopartículas , Humanos , Sistemas de Liberação de Fármacos por Nanopartículas , Nanomedicina , Biomimética , Encéfalo , Sistemas de Liberação de Medicamentos , Barreira HematoencefálicaRESUMO
Atherosclerosis, the leading cause of death worldwide, is responsible for ≈17.6 million deaths globally each year. Most therapeutic drugs for atherosclerosis have low delivery efficiencies and significant side effects, and this has hampered the development of effective treatment strategies. Diversified nanomaterials can improve drug properties and are considered to be key for the development of improved treatment strategies for atherosclerosis. The pathological mechanisms underlying atherosclerosis is summarized, rationally designed nanoparticle-mediated therapeutic strategies, and potential future therapeutic targets for nanodelivery. The content of this study reveals the potential and challenges of nanoparticle use for the treatment of atherosclerosis and highlights new effective design ideas.