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OBJECTIVE: There is a significant association between cardiovascular diseases (CVD) and prostate cancer (PCa), leading to high mortality. This study evaluates the trends in mortality associated with CVDs and PCa among older (≥ 65 years) men in the United States (US). METHODS: This analysis utilized the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER). The analysis of Multiple Cause of Death Files was carried out from 1999 to 2019 to identify fatalities with CVD and PCa listed as either contributory or underlying causes of death. Crude and age-adjusted mortality rates (AAMRs) per 100,000 populations for variables such as year, race and ethnicity, and geographic regions were determined. To assess annual percent change (APC), a Joinpoint regression program was employed. RESULTS: Overall AAMR was 54.3 in 1999 and 34.6 in 2019. After a decline in AAMR from 1999 to 2015, an alarming rise in mortality was observed until 2019. Mortality rates were highest among Non-Hispanic (NH) Black and African American men (74.9). Geographically, the highest mortalities were witnessed in the West (46.4) and non-metropolitan areas (44.6). States with AAMRs ranking in the 90th percentile were Nebraska, California, North Dakota, the District of Columbia, and Mississippi. CONCLUSION: After decreasing death rates associated with CVD and PCa from 1999 to 2015, a reversal in the trend was observed from 2015 to 2019. Addressing this increase in death rates, especially among the vulnerable population, requires focused attention and targeted strategies to implement necessary safeguards in the upcoming years.
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The pharmacological activation of peroxisome proliferator-activated receptor gamma (PPARγ) is a convenient and promising strategy for promoting beige adipocyte biogenesis to combat obesity-related metabolic disorders. However, thiazolidinediones (TZDs), the full agonists of PPARγ exhibit severe side effects in animal models and in clinical settings. Therefore, the development of efficient and safe PPARγ modulators for the treatment of metabolic diseases is emerging. In this study, using comprehensive methods, we report a previously unidentified ligand-binding pocket (LBP) in PPARγ and link it to beige adipocyte differentiation. Further virtual screening of 4097 natural compounds based on this novel LBP revealed that saikosaponin A (NJT-2), a terpenoid compound, can bind to PPARγ to induce coactivator recruitment and effectively activate PPARγ-mediated transcription of the beige adipocyte program. In a mouse model, NJT-2 administration efficiently promoted beige adipocyte biogenesis and improved obesity-associated metabolic dysfunction, with significantly fewer adverse effects than those observed with TZD. Our results not only provide an advanced molecular insight into the structural ligand-binding details in PPARγ, but also develop a linked selective and safe agonist for obesity treatment.
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Kidney-associated human lysozyme amyloidosis leads to renal impairments;thus, patients are often prescribed furosemide. Based on this fact, the effect of furosemide on induced human lysozyme fibrillation, in vitro, is evaluated by spectroscopic, calorimetric, computational, and cellular-based assays/methods. Results show that furosemide increases the lag phase and decreases the apparent rate of aggregation of human lysozyme, thereby decelerating the nucleation phase and amyloid fibril formation, as confirmed by the decrease in the level of Thioflavin-T fluorescence. Fewer entities of hydrodynamic radii of â¼171 nm instead of amyloid fibrils (â¼412 nm) are detected in human lysozyme in the presence of furosemide by dynamic light scattering. Moreover, furosemide decreases the extent of conversion of the α/ß structure of human lysozyme into a predominant ß-sheet. The isothermal titration calorimetry established that furosemide forms a complex with human lysozyme, which was also confirmed through fluorescence quenching and computational studies. Also, human lysozyme lytic activity is inhibited competitively by furosemide due to the involvement of amino acid residues of the active site in catalysis, as well as complex formation. Conclusively, furosemide interacts with Gln58, Ile59, Asn60, Ala108, and Trp109 of aggregation-prone regions 2 and 4 of human lysozyme, thereby masking its sites of aggregation and generating only lower-order entities that are less toxic to red blood cells than the fibrils. Thus, furosemide slows the progression of amyloid fibrillation in human lysozyme.
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Furosemida , Muramidasa , Muramidasa/química , Muramidasa/metabolismo , Humanos , Furosemida/química , Furosemida/farmacología , Agregado de Proteínas/efectos de los fármacos , Amiloide/metabolismo , Amiloide/química , Simulación de Dinámica MolecularRESUMEN
Aortic dissection (AD) is a potentially fatal cardiovascular issue that needs to be diagnosed and treated very away. While early detection is essential for bettering patient outcomes, there are substantial obstacles with the diagnostic techniques used today. Promising pathways for improving AD prognosis evaluation and early detection are presented by recent developments in serum biomarkers. The most recent research on serum biomarkers for AD is reviewed here, with an emphasis on the prognostic and diagnostic utility of these indicators. A number of biomarkers, including as matrix metalloproteinases, soluble elastin fragments, smooth muscle myosin heavy chain, and D-dimer, have been identified as putative markers of AD. These indicators are indicative of multiple pathophysiological mechanisms associated with AD, including inflammation, extracellular matrix remodeling, and vascular damage. Research has indicated that they are useful in differentiating AD from other acute cardiovascular diseases, facilitating prompt diagnosis and risk assessment.
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Human islet amyloid polypeptide (amylin or hIAPP) is a 37 residue hormone co-secreted with insulin from ß cells of the pancreas. In patients suffering from type-2 diabetes, amylin self-assembles into amyloid fibrils, ultimately leading to the death of the pancreatic cells. However, a research gap exists in preventing and treating such amyloidosis. Plumbagin, a natural compound, has previously been demonstrated to have inhibitory potential against insulin amyloidosis. Our investigation unveils collapsible regions within hIAPP that, upon collapse, facilitates hydrophobic and pi-pi interactions, ultimately leading to aggregation. Intriguingly plumbagin exhibits the ability to bind these specific collapsible regions, thereby impeding the aforementioned interactions that would otherwise drive hIAPP aggregation. We have used atomistic molecular dynamics approach to determine secondary structural changes. MSM shows metastable states forming native like hIAPP structure in presence of PGN. Our in silico results concur with in vitro results. The ThT assay revealed a striking 50% decrease in fluorescence intensity at a 1:1 ratio of hIAPP to Plumbagin. This finding suggests a significant inhibition of amyloid fibril formation by plumbagin, as ThT fluorescence directly correlates with the presence of these fibrils. Further TEM images revealed disappearance of hIAPP fibrils in plumbagin pre-treated hIAPP samples. Also, we have shown that plumbagin disrupts the intermolecular hydrogen bonding in hIAPP fibrils leading to an increase in the average beta strand spacing, thereby causing disaggregation of pre-formed fibrils demonstrating overall disruption of the aggregation machinery of hIAPP. Our work is the first to report a detailed atomistic simulation of 22 µs for hIAPP. Overall, our studies put plumbagin as a potential candidate for both preventive and therapeutic candidate for hIAPP amyloidosis.
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Polipéptido Amiloide de los Islotes Pancreáticos , Simulación de Dinámica Molecular , Naftoquinonas , Naftoquinonas/química , Naftoquinonas/farmacología , Polipéptido Amiloide de los Islotes Pancreáticos/química , Polipéptido Amiloide de los Islotes Pancreáticos/metabolismo , Polipéptido Amiloide de los Islotes Pancreáticos/antagonistas & inhibidores , Humanos , Cadenas de Markov , Unión Proteica , Interacciones Hidrofóbicas e Hidrofílicas , Agregado de Proteínas/efectos de los fármacos , Enlace de HidrógenoRESUMEN
PURPOSE: To investigate and to raise awareness about the influence of AI-powered software on the cognitive development of medical students, as well as the possible long-term ramifications. METHOD: This study combed through the literature on the use of AI in clinical settings and medical education, including chatbots powered by AI such as Chatgpt and Dale. The potential advantages and disadvantages of employing AI software for learning and complementing medical education, as well as its influence on critical thinking and problem-solving abilities, were assessed. RESULTS: no data analysis was performed. CONCLUSIONS: AI-powered software in medical education has potential benefits and drawbacks. While it can improve medical diagnosis and treatment and provide access to learning resources, the misuse of AI as a shortcut may hinder cognitive development and have long-term implications.
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Disfunción Cognitiva , Estudiantes de Medicina , Humanos , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Cognición , Aprendizaje , Síndrome , Inteligencia ArtificialRESUMEN
Solar energy has emerged as a viable and competitive renewable resource due to its abundance and cost-effectiveness. To meet the global energy demands, there is a growing need for efficient devices with unique compositions. In this study, we designed and analyzed a perovskite solar cell (PSC) incorporating methylammonium tin iodide (CH3NH3SnI3) as the active optical absorber material, tin iodide (SnO2) as the electron transport layer (ETL), and copper thiocyanate (CuSCN) as the hole transport layer (HTL) using SCAPS-1D software for numerical investigations. Subsequently, the optimized outcomes were implemented in the PVSyst software package to derive the characteristics of a solar module based on the proposed novel solar cell composition. The objective of our research was to enhance the stability of solar cell for use in solar module. This was achieved by optimizing the thicknesses of the compositional layers which resulted in the enhancement of excess electron and hole mobilities and a reduction in defect densities, thereby leading to an improvement in the device performance. The optimization of excess electron and hole mobilities, as well as defect densities, was conducted to improve the device performance. SCAPS calculations indicated that the perovskite absorber layer (CH3NH3SnI3) may achieve the best possible performance with a maximum optimized thickness of 3.2 µm. The optimized thickness value for CuSCN-HTL and SnO2-ETL were found to be 0.07 µm and 0.05 µm respectively resulting in a maximum power conversion efficiency (PCE) of 23.57%. Variations in open circuit voltage (Voc), short circuit current (Jsc), fill factor (FF %), and quantum efficiency (QE) associated with the optimized thickness values of all layers in the ITO/SnO2/CH3NH3SnI3/CuSCN/Mo composition were critically analyzed. The use of these input parameters resulted in power creation of 557.4 W for a module consisting of 72 cells with an annual performance ratio of 80.3%. These recent investigations are expected to be effective in the design and fabrication of eco-friendly and high-performance solar cells in terms of efficiency.
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PURPOSE: To describe the clinical features, imaging characteristics, and genetic test results associated with a novel compound heterozygous mutation of the BEST1 gene in two siblings with autosomal recessive bestrophinopathy. METHODS: Two siblings underwent a complete ophthalmic examination, including dilated fundus examination, fundus photography, fundus autofluorescence imaging, spectral-domain optical coherence tomography, fluorescein angiography, electroretinography, and electrooculography. A clinical diagnosis of autosomal recessive bestrophinopathy was established based on ocular examination and multimodal retinal imaging. Subsequently, clinical exome sequencing consisting of a panel of 6670 genes was carried out to confirm the diagnosis and assess genetic alterations in the protein-coding region of the genome of the patients. The identified mutations were tested in the two affected siblings and one of their parents. RESULTS: Two siblings (a 17-year-old female and a 15-year-old male) presented with reduced visual acuity and bilaterally symmetrical subretinal deposits of hyperautofluorescent materials in the posterior pole, which showed staining in the late phase of fluorescein angiogram. Spectral-domain optical coherence tomography demonstrated hyperreflective subretinal deposits and subretinal fluid accumulation. Both patients shared two mutations in the protein-coding region of the BEST1 gene, c.103G > A, p.(Glu35Lys) and c.313C > A, p.(Arg105Ser) (a novel disease-causing mutation). Sanger sequencing confirmed that the unaffected mother of the proband was carrying p.(Glu35Lys) variant in a heterozygous state. CONCLUSIONS: We have identified and described the phenotype of a novel disease-causing mutation NM_004183.4:c.313C > A, p.(Arg105Ser) in a heterozygous state along with a previously reported mutation NM_004183.4:c.103G > A, p.(Glu35Lys) of the BEST1 gene in two related patients with autosomal recessive bestrophinopathy.
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Enfermedades de la Retina , Distrofias Retinianas , Masculino , Femenino , Humanos , Bestrofinas/genética , Hermanos , Proteínas del Ojo/genética , Canales de Cloruro/genética , Análisis Mutacional de ADN , Linaje , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/genética , Electrorretinografía , Angiografía con Fluoresceína , Tomografía de Coherencia Óptica , MutaciónRESUMEN
Stem cell homeostasis by the WUSCHEL-CLAVATA (WUS-CLV) feedback loop is generally conserved across species; however, its links with other meristem regulators can be species-specific, rice being an example. We characterized the role of rice OsbZIP47 in vegetative and reproductive development. The knockdown (KD) transgenics showed meristem size abnormality and defects in developmental progression. The size of the shoot apical meristem (SAM) in 25-day OsbZIP47KD plants was increased as compared to the wild-type (WT). Inflorescence of KD plants showed reduced rachis length, number of primary branches, and spikelets. Florets had defects in the second and third whorl organs and increased organ number. OsbZIP47KD SAM and panicles had abnormal expression for CLAVATA peptide-like signaling genes, such as FON2-LIKE CLE PROTEIN1 (FCP1), FLORAL ORGAN NUMBER 2 (FON2), and hormone pathway genes, such as cytokinin (CK) ISOPENTEYLTRANSFERASE1 (OsIPT1), ISOPENTEYLTRANSFERASE 8 (OsIPT8), auxin biosynthesis OsYUCCA6, OsYUCCA7 and gibberellic acid (GA) biosynthesis genes, such as GRAIN NUMBER PER PANICLE1 (GNP1/OsGA20OX1) and SHORTENED BASAL INTERNODE (SBI/OsGA2ox4). The effects on ABBERANT PANICLE ORGANIZATION1 (APO1), OsMADS16, and DROOPING LEAF (DL) relate to the second and third whorl floret phenotypes in OsbZIP47KD. Protein interaction assays showed OsbZIP47 partnerships with RICE HOMEOBOX1 (OSH1), RICE FLORICULA/LEAFY (RFL), and OsMADS1 transcription factors. The meta-analysis of KD panicle transcriptomes in OsbZIP47KD, OsMADS1KD, and RFLKD transgenics, combined with global OSH1 binding sites divulge potential targets coregulated by OsbZIP47, OsMADS1, OSH1, and RFL. Further, we demonstrate that OsbZIP47 redox status affects its DNA binding affinity to a cis element in FCP1, a target locus. Taken together, we provide insights on OsbZIP47 roles in SAM development, inflorescence branching, and floret development.
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Since the first appearance of a novel coronavirus pneumonia (NCP) caused by a novel human coronavirus, and especially after the infection started its rapid spread over the world causing the COVID-19 (coronavirus disease 2019) pandemics, a very substantial part of the scientific community is engaged in the intensive research dedicated to finding of the potential therapeutics to cure this disease. As repurposing of existing drugs represents the only instant solution for those infected with the virus, we have been working on utilization of the structure-based virtual screening method to find some potential medications. In this study, we screened a library of 646 FDA approved drugs against the receptor-binding domain of the SARS-CoV-2 spike (S) protein and the main protease of this virus. Scoring functions revealed that some of the anticancer drugs (such as Pazopanib, Irinotecan, and Imatinib), antipsychotic drug (Risperidone), and antiviral drug (Raltegravir) have a potential to interact with both targets with high efficiency. Further we performed molecular dynamics simulations to understand the evolution in protein upon interaction with drug. Also, we have performed a phylogenetic analysis of 43 different coronavirus strains infecting 12 different mammalian species.Communicated by Ramaswamy H. Sarma.
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COVID-19 , Animales , Humanos , SARS-CoV-2 , Filogenia , Reposicionamiento de Medicamentos/métodos , Simulación del Acoplamiento Molecular , Antivirales/farmacología , Antivirales/química , Simulación de Dinámica Molecular , Inhibidores de Proteasas/química , MamíferosRESUMEN
Tumor-associated macrophages (TAMs) are the most widely infiltrating immune cells in the tumor microenvironment (TME). Clinically, the number of TAMs is closely correlated with poor outcomes in multiple cancers. The biological actions of TAMs are complex and diverse, including mediating angiogenesis, promoting tumor invasion and metastasis, and building an immunosuppressive microenvironment. Given these pivotal roles of TAMs in tumor development, TAM-based strategies are attractive and used in certain tumor therapies, including inhibition of angiogenic signalling, blockade of the immune checkpoint, and macrophage enhancement phagocytosis. Several attempts to develop TAM-targeted agents have been made to deplete TAMs or reprogram the behaviour of TAMs. Some have shown a favourable curative effect in monotherapy, combination with chemotherapy or immunotherapy in clinical trials. Additionally, a new macrophage-based cell therapeutic technology was recently developed by equipping macrophages with CAR molecules. It is expected to break through barriers to solid tumor treatment. Although TAM-related studies have yielded positive antitumor outcomes, further investigations are needed to better characterize TAMs, which will benefit further establishment of novel strategies for tumor therapy. Here, we concisely summarize the functions of TAMs in the TME and comprehensively introduce the latest TAM-based regimens in cancer treatment.
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Antineoplásicos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Inmunoterapia/métodos , Neoplasias/inmunología , Microambiente Tumoral/inmunología , Macrófagos Asociados a Tumores/inmunología , Animales , Sistemas de Liberación de Medicamentos/tendencias , Humanos , Inmunosupresores/administración & dosificación , Inmunoterapia/tendencias , Neoplasias/tratamiento farmacológico , Receptores Quiméricos de Antígenos/antagonistas & inhibidores , Receptores Quiméricos de Antígenos/inmunología , Microambiente Tumoral/efectos de los fármacos , Macrófagos Asociados a Tumores/efectos de los fármacosRESUMEN
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease around the world. However, there is still no drug for NAFLD in the market, the study of potential therapeutic drugs on NAFLD is extraordinarily pressing and urgent. The rodent models for NAFLD drugs' study are always with a long time cost. Therefore, we aim to establish a short-time NAFLD drug screening model. A laboratory-made high cholesterol diet was used on larval zebrafish for 3 weeks to establish the NAFLD screen model. Lipid metabolism, oxidant stress, and pathology were studied to comprehensively demonstrate the whole spectrum of NAFLD on this model. Bezafibrate and pioglitazone were used to evaluate the model. Moreover, mechanism research was performed on this model.The NAFLD larval zebrafish model was established with the comprehensive process of NAFLD. Moreover, multiple index on lipid metabolism, oxidant stress, hepatic steatosis, and hepatic inflammation can be easily tested for drug screening. Furthermore, this model can be used to perform the mechanism research by testing mRNA expression. The NAFLD larval zebrafish model is a comprehensive short-time screening method for NAFLD drugs.
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Enfermedad del Hígado Graso no Alcohólico/metabolismo , Animales , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Larva , Metabolismo de los Lípidos/genética , Metabolismo de los Lípidos/fisiología , Enfermedad del Hígado Graso no Alcohólico/genética , Pez CebraRESUMEN
A bioactive component, 2',3,4,4'-tetrahydrochalcone (RY3-a) was first isolated from Vernohia anthelmintica (L.) willd seeds, and a set of its analogs, RY3-a-1-RY3-a-15 and RY3-c were designed and synthesized. Biological activity assays showed that RY3-c exhibited better melanogenesis and antioxidant activity and lower toxicity in comparison with RY3-a and butin. Further study tests showed that RY3-c exhibited better melanogenesis activity compared with the positive control 8-methoxypsoralan (8-MOP) in a vitiligo mouse model, suggesting that RY3-c is a good candidate antivitiligo agent. Mechanistic studies showed that RY3-c could repair cell damage induced by excessive oxidative stress and may exert melanin synthesis activity in the mouse melanoma B16F10 cell line by activating the mitogen-activated protein kinase (MAPK) pathway and the upregulation of c-kit.
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Productos Biológicos/farmacología , Chalcona/farmacología , Diseño de Fármacos , Vernonia/química , Vitíligo/tratamiento farmacológico , Animales , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Chalcona/análogos & derivados , Chalcona/química , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Estructura Molecular , Estrés Oxidativo/efectos de los fármacos , Relación Estructura-Actividad , Vitíligo/metabolismo , Vitíligo/patología , Pez CebraRESUMEN
Non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is the most common chronic liver disease in the world. However, there are still no drugs for NAFLD/NASH in the market. Gastrodin (GAS) is a bioactive compound that is extracted from Gastrodia elata, which is used as an active compound on nervous system diseases. Recent reports showed that GAS and Gastrodia elata possess anti-oxidant activity and lipid regulating effects, which makes us curious to reveal the anti-NAFLD effect of GAS. A high cholesterol diet (HCD) was used to induce a NAFLD larval zebrafish model, and the lipid regulation and anti-oxidant effects were tested on the model. Furthermore, qRT-PCR studied the underlying mechanism of GAS. To conclude, this study revealed a lipid regulation and anti-oxidant insights of GAS on NAFLD larval zebrafish model and provided a potential therapeutic compound for NAFLD treatment.
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Antioxidantes/uso terapéutico , Alcoholes Bencílicos/uso terapéutico , Gastrodia/química , Glucósidos/uso terapéutico , Metabolismo de los Lípidos/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Animales , Antioxidantes/aislamiento & purificación , Alcoholes Bencílicos/aislamiento & purificación , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Glucósidos/aislamiento & purificación , Larva/efectos de los fármacos , Larva/genética , Larva/metabolismo , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Pez Cebra/genética , Pez Cebra/metabolismoRESUMEN
This study aims to reveal the potential relationship between 5-HT and oxidative stress in the organism. Our in vitro experiments in RIN-14B cells showed that anoxia leads the cells to the state of oxidative stress. Administration of exogenous 5-HT exacerbated this effect, whereas the inhibition of Tph1, LP533401 alleviated the oxidative stress. Several research articles reported that Cinnabar (consists of more than 96% mercury sulfide, HgS), which is widely used in both Chinese and Indian traditional medicine prescriptions, has been involved in the regulation of 5-HT. The present research revealed that HgS relieved the level of oxidative stress of RIN-14B cells. This pharmacological activity was also observed in the prescription drug Zuotai, in which HgS accounts for 54.5%, and these effects were found to be similar to LP533401, an experimental drug to treat pulmonary hypertension. Further, our in vivo experiments revealed that the administration of cinnabar or prescription drug Zuotai in zebrafish reduced the reactive oxygen species (ROS) induced by hypoxia and cured behavioral abnormalities. Taken together, in organisms with hypoxia induced oxidative stress 5-HT levels were found to be abnormally elevated, indicating that 5-HT could regulate oxidative stress, and the decrease in the 5-HT levels, behavioral abnormalities after treatment with cinnabar and Zuotai, we may conclude that the therapeutic and pharmacologic effect of cinnabar and Zuotai may be based on the regulation of 5-HT metabolism and relief of oxidative stress. Even though they aren't toxic at the present dosage in both cell lines and zebrafish, their dose dependent toxicities are yet to be evaluated.
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Compuestos de Mercurio/toxicidad , Estrés Oxidativo/efectos de los fármacos , Serotonina/metabolismo , Animales , Conducta Animal/efectos de los fármacos , Hipoxia de la Célula/efectos de los fármacos , Línea Celular , Larva/efectos de los fármacos , Larva/metabolismo , Compuestos de Mercurio/farmacología , Redes y Vías Metabólicas/efectos de los fármacos , Modelos Biológicos , Oxidación-Reducción/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Pez CebraRESUMEN
FosB, a Mg2+ dependent thioltransferase, confers antibiotic resistance to fosfomycin through enzymatic drug inactivation. Among all antibiotic resistant proteins in the Antibiotic Resistance Genes Database and the Comprehensive Antibiotic Resistance Database, FosB is within 5% of the most number of ARPs identified in Human Microbiome Project reference database but mainly distributed in limited genera, i.e., 122 of total 133 FosB homologues are found from Bacillus and Staphylococcus. Furthermore, these FosB sequences could be divided into three clusters based on their phylogenetic relationship, i.e., two groups of FosB were mainly from Bacillus, and another was mainly from Staphylococcus. Finally, we confirmed that FosB from the group of Staphylococcus presented the highest resistance ability to fosfomycin by in silico and in vitro comparisons. In summary, this study elaborates the specific taxonomic characteristics and resistant abilities of FosB in human microbiota, which might help in developing more promising fosfomycin-like antibiotics.
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Vitiligo is an intriguing depigmentation disorder that affects about 0.5-2% of the world population. In the past decade, first-line treatments of vitiligo have involved the use of calcineurin inhibitors and corticosteroids. Sodium tanshinone IIA sulfonate (STS) has been widely applied in the treatment of cardiovascular and cerebrovascular diseases in China. In the present study, the effect of STS on melanogenesis was confirmed in the B16F10 cells and zebrafish by direct observation. The prevention of hydrogen peroxide (H2O2)-induced oxidative stress has been proven to be beneficial to vitiligo patients, and STS that can protect the B16F10 cells against oxidative stress has been investigated in the present reversed study. Moreover, we found that pre-treatment with STS led to a concentration-dependent mitochondrial impairment and decreased cell apoptosis of the B16F10 cells in response to H2O2. In addition, we demonstrated that STS increased melanin synthesis in the B16F10 cells by activating the mitogen-activated protein kinase (MAPK) and protein kinase A (PKA) pathways. STS also increased the Cdc42 and KIF5b expression to stimulate the translocation of melanin. These results suggest that STS protects the B16F10 cells against H2O2-induced oxidative stress and exerts melanin synthesis activity in the B16F10 cells by activating the MAPK and PKA pathways; thus, it shows therapeutic potential for vitiligo.
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Nonalcoholic fatty liver disease (NAFLD)1 is the most common chronic liver disease worldwide. Cichorium glandulosum Boiss. et Huet (CG) is a common traditional Uighur medicine, and it has been widely used as active therapy on various hepatic diseases. Recently, lipid-lowering effect has been revealed on CG. Polysaccharides are principal component of CG which could be the possible lipid-lowering compound in CG. In this study, extraction and purification of CG polysaccharides (CGP) was performed, and the lipid regulation effect of CGP was investigated on NAFLD zebrafish model. The results showed that CGP significantly decreased the levels of TC, TG, and decreased the mRNA expression of srebf-1, and fas, increased the expression of pparab. The findings suggest that the lipid-lowering effects of CGP mainly depend on facilitation of lipolysis (mainly beta-oxidation) or inhibition of lipogenesis. Furthermore, CGP could prevent and causes the regression of steatosis in NAFLD via its lipid metabolism regulation effect.
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Asteraceae , Hipolipemiantes/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Polisacáridos/uso terapéutico , Animales , Modelos Animales de Enfermedad , Hipolipemiantes/farmacología , Larva , Metabolismo de los Lípidos/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Fitoterapia , Polisacáridos/farmacología , Transcriptoma/efectos de los fármacos , Pez CebraRESUMEN
Cerebral infections have been reported after endovascular interventions such as embolization and coiling. Such complications are extremely rare and only one other case has been reported in a patient who underwent an endovascular therapy for ischemic stroke. We report a 32-year-old woman, who presented to our hospital with headaches lasting four weeks after an endovascular intervention for ischemic stroke via mechanical thrombectomy. Further investigations revealed a cerebral abscess in the area of the infarct. She was effectively treated with antibiotics in combination with stereotactic drainage and was discharged after she made a good recovery. A review of literature on cerebral abscesses after minimally invasive procedures such as endovascular intervention was also done and is being presented in this paper. A cerebral abscess can occur rarely after endovascular interventions. A high degree of suspicion is important in identifying patients with an abscess and appropriate treatment can prevent significant morbidity or even death.
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Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with a broad spectrum of liver injury. Oxidant stress is believed to be the pathogenesis of NAFLD as the "second hit". Hydrogen peroxide is widely used as an oxidant reagent to induce the oxidant injury of cells and larval zebrafish. Recently, cichoric acid is being studied extensively for its obesity attenuating, hepatic steatosis reduction and anti-oxidant effects. In this study, to identify whether CRA could protect the H2O2 induced oxidant injury via anti-oxidant impact by using L02 and HepG2 hepatocytes as in vitro and larval zebrafish as in vivo injury models, and evaluated the protective and anti-oxidant effects of CRA by pretreated it on both in vitro and in vivo models. CRA was found to reduce the production of ROS and MDA, activate the anti-oxidant enzymes SOD and GSH-px, and pathways Keap1-Nrf2 and HO-1. These results demonstrated that CRA might protect the liver injury by its anti-oxidant effect, which could be a potential therapeutic agent of NAFLD.