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With the depletion of non-renewable fossil fuels, there has been an increasing emphasis on renewable biomass. Penicillium oxalicum is notable for its exceptional capacity to secrete a diverse array of enzymes that degrade plant polysaccharides into monosaccharides. These valuable monosaccharides can be harnessed in the production of bioethanol and other sustainable forms of energy. By enhancing the production of plant-polysaccharide-degrading enzymes (PPDEs) in P. oxalicum, we can optimize the utilization of plant biomass. This paper presents recent advances in augmenting PPDE expression in P. oxalicum through genetic engineering strategies involving protoplast preparation, transformation, and factors influencing PPDE gene expression.
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OBJECTIVES: The aim of this study was to determine the phenotypic and molecular characteristics of antibiotic-resistant Bacillus spp. isolated from probiotic preparations in China. METHODS: Bacillus strains were isolated from probiotic preparations and then identified using 16S rDNA sequencing. Drug sensitivity tests were conducted to determine their susceptibility to seven antibiotics. Whole genome sequencing was performed on the most resistant strains, followed by analysis of their molecular characteristics, resistance genes, and virulence factors. RESULTS: In total, we isolated 21 suspected Bacillus species from seven compound probiotics, which were identified by 16S rDNA as 12 Bacillus licheniformis, six Bacillus subtilis and three Bacillus cereus. The determination of antimicrobial susceptibility showed widespread resistance to chloramphenicol (95.2%), erythromycin (85.7%) and gentamicin (42.9%). Whole genome sequencing of seven resistant strains revealed that J-6-A (Bacillus subtilis) and J-7-A (Bacillus cereus) contained a plasmid. The resistance gene analysis revealed that each strain contained more than ten resistance genes, among which J-7-A was the most. The streptomycin resistance gene strA was detected in all strains. The chloramphenicol resistance genes ykkC and ykkD were found in J-1-A to J-5-A and were first reported in Bacillus subtilis. The erythrocin resistance gene ermD was detected in strains J-1-A to J-4-A. There were also more than 15 virulence factors and gene islands (GIs) involved in each strain. CONCLUSIONS: These results confirm the potential safety risks of probiotics and remind us to carefully select probiotic preparations containing strains of Bacillus species, especially Bacillus cereus, to avoid the potential spread of resistance and pathogenicity.
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Di-2-ethylhexyl phthalate (DEHP) is frequently used as a plasticizer to enhance the plasticity and durability of agricultural products, which pose adverse effects to human health and the environment. Aquaporin 1 (AQP1) is a main water transport channel protein and is involved in the maintenance of intestinal integrity. However, the impact of DEHP exposure on gut health and its potential mechanisms remain elusive. Here, we determined that DEHP exposure induced a compromised duodenum structure, which was concomitant with mitochondrial structural injury of epithelial cells. Importantly, DEHP exposure caused duodenum inflammatory epithelial cell damage and strong inflammatory response accompanied by activating the TLR4/MyD88/NF-κB signaling pathway. Mechanistically, DEHP exposure directly inhibits the expression of AQP1 and thus leads to an inflammatory response, ultimately disrupting duodenum integrity and barrier function. Collectively, our findings uncover the role of AQP1 in phthalate-induced intestinal disorders, and AQP1 could be a promising therapeutic approach for treating patients with intestinal disorders or inflammatory diseases.
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Acuaporina 1 , Mucosa Intestinal , Animales , Acuaporina 1/genética , Acuaporina 1/metabolismo , Ratones , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Ratones Endogámicos C57BL , Inflamación/metabolismo , Inflamación/genética , Inflamación/inducido químicamente , Masculino , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , FN-kappa B/metabolismo , FN-kappa B/genética , Dietilhexil Ftalato/toxicidad , Ácidos Ftálicos , Transducción de Señal/efectos de los fármacosRESUMEN
Hemocyanin, an oxygen-transport protein, is widely distributed in the hemolymph of marine arthropods and mollusks, playing an important role in their physiological processes. Recently, hemocyanin has been recognized as a multifunctional glycoprotein involved in the immunological responses of aquatic invertebrates. Consequently, the link between hemocyanin functions and their potential applications has garnered increased attention. This review offers an integrated overview of hemocyanin's structure, physicochemical characteristics, and bioactivities to further promote the utilization of hemocyanin derived from marine products. Specifically, we review its implication in two aspects of food and aquaculture industries: quality and health. Hemocyanin's inducible phenoloxidase activity is thought to be an inducer of melanosis in crustaceans. New anti-melanosis agents targeted to hemocyanin need to be explored. The red-color change observed in shrimp shells is related to hemocyanin, affecting consumer preferences. Hemocyanin's adaptive modification in response to the aquatic environment is available as a biomarker. Additionally, hemocyanin is endowed with bioactivities encompassing anti-microbial, antiviral, and therapeutic activities. Hemocyanin is also a novel allergen and its allergenic features remain incompletely characterized.
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Hemocianinas , Hemocianinas/química , Animales , Industria de Alimentos , Organismos Acuáticos/química , HumanosRESUMEN
Ulcerative colitis (UC), a prevalent form of inflammatory bowel disease (IBD), may result from immune system dysfunction, leading to the sustained overproduction of reactive oxygen species (ROS) and subsequent cellular oxidative stress damage. Recent studies have identified both peroxisome proliferator-activated receptor-γ (PPARγ) and endoplasmic reticulum (ER) stress as critical targets for the treatment of IBD. Oroxyloside (C22H20O11), derived from the root of Scutellariabaicalensis Georgi, has traditionally been used in treating inflammatory diseases. In this study, we investigated the molecular mechanisms by which oroxyloside mitigates dextran sulfate sodium (DSS)-induced colitis. We examined the effects of oroxyloside on ROS-mediated ER stress in colitis, including the protein expressions of GRP78, p-PERK, p-eIF2α, ATF4, and CHOP, which are associated with ER stress. The beneficial impact of oroxyloside was reversed by the PPARγ antagonist GW9662 (1 mg·kg-1, i.v.) in vivo. Furthermore, oroxyloside decreased pro-inflammatory cytokines and ROS production in both bone marrow-derived macrophages (BMDM) and the mouse macrophage cell line RAW 264.7. However, PPARγ siRNA transfection blocked the anti-inflammatory effect of oroxyloside and even abolished ROS generation and ER stress activation inhibited by oroxyloside in vitro. In conclusion, our study demonstrates that oroxyloside ameliorates DSS-induced colitis by inhibiting ER stress via PPARγ activation, suggesting that oroxyloside might be a promising effective agent for IBD.
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Colitis , Sulfato de Dextran , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico , Ratones Endogámicos C57BL , PPAR gamma , Especies Reactivas de Oxígeno , Animales , PPAR gamma/metabolismo , PPAR gamma/genética , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ratones , Especies Reactivas de Oxígeno/metabolismo , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Masculino , Humanos , Sustancias Protectoras/farmacologíaRESUMEN
The last few decades have witnessed the increasing consumption of functional foods, leading to the expansion of the worldwide market. However, the illegal addition drugs in functional foods remains incessant despite repeated prohibition, making it a key focus of strict crackdowns by regulatory authorities. Effective analytical tools and procedures are desperately needed to rapidly screen and identify illegally added drugs in a large number of samples, given the growing amount and diversity of these substances in functional foods. The MRSIT-HRMS (Multiple Sample Rapid Introduction combined with High Resolution Mass Spectrometry) without chromatographic separation, after direct sampling, utilizes NIST software (National Institute of Standards and Technology) matching with a home-built library to target identification and non-targeted screen of illegal additives. When applied to 50 batches of suspicious samples, the targeted method detected illegal added drugs in 41 batches of samples, while the non-targeted method screened a new phosphodiesterase-5 (PDE-5) inhibitor type structural derivative. The positive results obtained by the targeted method were consistent with LC-MS/MS (QQQ). The novel MRSIT-HRMS with a limit of quantification (LOD) of 1 µg/mL achieved 100 % correct identification for all 50 batches of actual samples, demonstrating its potential as a highly promising and powerful tool for fast screening of illegally added drugs in functional food, especially when compared to traditional LC-MS/MS methods. This is essential for ensuring drug safety and public health.
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Alimentos Funcionales , Drogas Ilícitas , Alimentos Funcionales/análisis , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem , Inhibidores de Fosfodiesterasa 5/análisis , Inhibidores de Fosfodiesterasa 5/química , Cromatografía Líquida de Alta PresiónRESUMEN
Enterococci can act as reservoirs for antibiotic-resistant genes that are potentially at risk of being transferred to other bacteria that inhabit in the gastrointestinal tract. The aim of this study was to determine the phenotypic and molecular characteristics of antibiotic-resistant enterococci isolated from probiotic preparations. In total, we isolated 15 suspected Enterococcus species from 5 compound probiotics, which were identified by 16S rDNA as 12 Enterococcus faecium and 3 Enterococcus faecalis. Determination of antimicrobial susceptibility by the microdilution broth method showed widespread resistance to sulfamethoxazole (100%), norfloxacin (99.3%), azithromycin (99.3%), gentamicin (86.7%), and chloramphenicol (20%). Whole genome sequencing of five resistant strains revealed that all had circular DNA chromosomes and that E. faecium J-1-A to J-4-A contained a plasmid, while E. faecalis J-5-A did not. The results of the resistance gene analysis revealed that each strain contained approximately 30 resistance genes, with the antibiotic resistance genes and the multidrug resistance efflux pump genes mdtG, lmrC, and lmrD detected in all strains. The chloramphenicol resistance genes ykkC and ykkD were first identified in E. faecalis. And there were 21, 19, 21, 21, and 29 virulence factors involved in strains, respectively. Further analysis of the gene islands (GIs) revealed that each strain contained more than 10 GIs. The above results confirm the existence of hidden dangers in the safety of probiotics and remind us to carefully select probiotic preparations containing enterococcal strains to avoid the potential spread of resistance and pathogenicity.
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Enterococcus faecium , Probióticos , Enterococcus/genética , Farmacorresistencia Bacteriana/genética , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Enterococcus faecium/genética , Enterococcus faecalis/genética , Cloranfenicol , Factores de Virulencia/genéticaRESUMEN
Neurodegenerative diseases seriously affect patients' physical and mental health, reduce their quality of life, and impose a heavy burden on society. However, their treatment remains challenging. Therefore, exploring factors potentially related to the pathogenesis of neurodegenerative diseases and improving their diagnosis and treatment are urgently needed. Recent studies have shown that P2 × 7R plays a crucial role in regulating neurodegenerative diseases caused by neuroinflammation. P2 × 7R is an adenosine 5'-triphosphate ligand-gated cation channel receptor present in most tissues of the human body. An increase in P2 × 7R levels can affect the progression of neurodegenerative diseases, and the inhibition of P2 × 7R can alleviate neurodegenerative diseases. In this review, we comprehensively describe the biological characteristics (structure, distribution, and function) of this gene, focusing on its potential association with neurodegenerative diseases, and we discuss the pharmacological effects of drugs (P2 × 7R inhibitors) used to treat neurodegenerative diseases.
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In this study, the effects of different enzymes (lysozyme, α-amylase and neutral protease) on sludge hydrolysis efficiency and microbial community in sequencing batch reactor (SBR) were introduced. The results showed that the hydrolysis efficiencies of the three enzymes were 48.5, 22.5 and 31%, respectively, compared with the accumulated sludge discharge of the blank control group. However, it has varying degrees of impact on the effluent quality, and the denitrification and phosphorus removal effect of the system deteriorates. The lysozyme that achieves the optimal sludge hydrolysis effect of 48.5% has the greatest impact on the chemical oxygen demand (COD), total nitrogen (TN), and nitrate nitrogen (NO3--N) of the effluent. The sludge samples of the control group and the groups supplemented with different enzyme preparations were subjected to high-throughput sequencing. It was found that the number of OTUs (Operational Taxonomic Units) of the samples was lysozyme > α-amylase > blank control > neutral protease. Moreover, the abundance grade curve of the sludge samples supplemented with lysozyme and α-amylase was smoother, and the community richness and diversity were improved by lysozyme and α-amylase. The species diversity of the sludge supplemented with lysozyme and neutral protease was great, and the community succession was obvious. The introduction of enzymes did not change the main microbial communities of the sludge, which were mainly Proteobacteria, Actinobacteria and Bacteroidetes. The effects of three enzyme preparations on sludge reduction and microbial diversity during pilot operation were analyzed, the gap in microbial research was filled, which provided theoretical value for the practical operation of enzymatic sludge reduction.
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Diabetic peripheral neuropathy (DPN) refers to the development of peripheral nerve dysfunction in patients with diabetes when other causes are excluded. Diabetic distal symmetric polyneuropathy (DSPN) is the most representative form of DPN. As one of the most common complications of diabetes, its prevalence increases with the duration of diabetes. 10-15% of newly diagnosed T2DM patients have DSPN, and the prevalence can exceed 50% in patients with diabetes for more than 10 years. Bilateral limb pain, numbness, and paresthesia are the most common clinical manifestations in patients with DPN, and in severe cases, foot ulcers can occur, even leading to amputation. The etiology and pathogenesis of diabetic neuropathy are not yet completely clarified, but hyperglycemia, disorders of lipid metabolism, and abnormalities in insulin signaling pathways are currently considered to be the initiating factors for a range of pathophysiological changes in DPN. In the presence of abnormal metabolic factors, the normal structure and function of the entire peripheral nervous system are disrupted, including myelinated and unmyelinated nerve axons, perikaryon, neurovascular, and glial cells. In addition, abnormalities in the insulin signaling pathway will inhibit neural axon repair and promote apoptosis of damaged cells. Here, we will discuss recent advances in the study of DPN mechanisms, including oxidative stress pathways, mechanisms of microvascular damage, mechanisms of damage to insulin receptor signaling pathways, and other potential mechanisms associated with neuroinflammation, mitochondrial dysfunction, and cellular oxidative damage. Identifying the contributions from each pathway to neuropathy and the associations between them may help us to further explore more targeted screening and treatment interventions.
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Diabetes Mellitus , Neuropatías Diabéticas , Hiperglucemia , Insulinas , Humanos , Neuroglía , Amputación QuirúrgicaRESUMEN
Background: As a chronic disease that affects the whole world, there is no definite treatment for knee osteoarthritis (KOA). Wu Qin Xi (WQX) is still in preliminary exploration as a traditional Chinese exercise in the treatment of osteoarthritis of the knee. The purpose of this study was to conduct a meta-analysis of previous studies and to investigate the efficacy of the WQX exercises on pain and function in patients with KOA. Methods: We searched six databases (Pubmed, Embase, Cochrane Library, Wanfang, CQVIP, and CNKI) for articles on WQX for KOA up to May 10, 2022. Literature search, study selection, data extraction, and quality evaluation were performed by two independent authors. In terms of statistical results, we presented mean differences (MD), 95% CI, and I 2 to show heterogeneity, and, based on that, we chose either a random effects model or a fixed effects model. Results: Seven studies were selected for inclusion in this meta-analysis. The WQX intervention group showed statistical differences for both the total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and its various bylaws, the Visual Analogue Score (VAS), and the presence of general functional exercise in the control group. We also demonstrated the clinically meaningful efficacy of WQX treatment by calculating minimum clinical importance difference (MCID) values that met the MCID values on the WOMAC score. A sensitivity analysis was also performed in this study by subgroup analysis for greater heterogeneity, and it was inferred that the difference in follow-up time was a likely source of heterogeneity. Conclusion: Despite some limitations, the current study showed a definite effect of WQX in improving pain symptoms and joint function in patients with KOA. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022332209.
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Background: Proximal humeral fractures are the third most common fracture in the body, and their incidence is rising year by year as the population ages. However, the treatment of the proximal humerus in parts 3 and 4 is still debatable, necessitating a network meta-analysis to determine the best treatment for each treatment modality. Methods: We searched PubMed, Embase, Cochrane Library for randomized controlled trials on proximal humeral fractures up to June 21, 2022. We performed data extraction and literature quality assessment by two independent authors and extracted constant score and reoperation rate as indicators for evaluation. Stata software, Revman software, JAGS software and the R-based BlandAltmanLeh package, gemtc package and riags package were used to perform this Bayesian network meta-analysis. Results: Following screening, 11 papers with a total of 648 participants were included in the analysis. The SUCRA values for the constant score were in the following order: RSA, IMN, Conservative, HA, and LP, and the SUCRA values for the reoperation rate were LP, HA, IMN, Conservative, and RSA. Conclusion: The elderly with 3- or 4-part proximal humeral fractures should consider RSA because it received the best evaluation ranking in terms of constant score and reoperation rate. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022341209, identifier: CRD42022341209.
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A Gram-stain-negative, motile, non-spore-forming, strictly aerobic and rod-shaped bacterial strain, Adcm-6AT, was isolated from a seawater sample collected from the deep chlorophyll maximum layer in the West Pacific Ocean. Strain Adcm-6AT grew at 20-37 °C (optimum, 28-32 °C), at pH 6-11 (pH 7) and in the presence of 0-6â% (1-2â%) NaCl (w/v). Phylogenetic analysis based on 16S rRNA gene sequences indicated that it belonged to the genus Zavarzinia and had 97.7 and 96.9â% sequence similarity to Zavarzinia compransoris DSM 1231T and Zavarzinia aquatilis JCM 32263T, respectively. Digital DNA-DNA hybridization and average nucleotide identity values between strain Adcm-6AT and the two type strains were 22.2-22.9â% and 79.7-80.4â%, respectively. The principal fatty acids were C19:0 cyclo ω8c, summed feature 8 (C18:1 ω6c and/or C18:1 ω7c) and C16:0. The predominant respiratory quinone was Q-10. The polar lipids were diphosphatidylglycerol, two phosphatidylethanolamines, two phosphatidyglycerols and an unidentified lipid. The genomic DNA G+C content of strain Adcm-6AT was 67.7 %. Based on phylogenetic analysis and genomic-based relatedness indices, as well as phenotypic and genotypic characteristics, strain Adcm-6AT represents a novel species within the genus Zavarzinia, for which the name Zavarzinia marina sp. nov. is proposed. The type strain is Adcm-6AT (=MCCC M24951T=KCTC 82849T).
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Cardiolipinas , Clorofila , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Hidrocarburos , Nucleótidos , Océano Pacífico , Fosfatidiletanolaminas , Fosfolípidos/química , Filogenia , Quinonas , ARN Ribosómico 16S/genética , Agua de Mar/microbiología , Análisis de Secuencia de ADN , Cloruro de SodioRESUMEN
Diabetes mellitus and its complications are major health concerns worldwide that should be routinely monitored for evaluating disease progression. And there is currently much evidence to suggest a critical role for mitochondria in the common pathogenesis of diabetes and its complications. Mitochondrial dynamics are involved in the development of diabetes through mediating insulin signaling and insulin resistance, and in the development of diabetes and its complications through mediating endothelial impairment and other closely related pathophysiological mechanisms of diabetic cardiomyopathy (DCM). noncoding RNAs (ncRNAs) are closely linked to mitochondrial dynamics by regulating the expression of mitochondrial dynamic-associated proteins, or by regulating key proteins in related signaling pathways. Therefore, this review summarizes the research progress on the regulation of Mitochondrial Dynamics by ncRNAs in diabetes and its complications, which is a promising area for future antibodies or targeted drug development.
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Diabetes Mellitus , Cardiomiopatías Diabéticas , Humanos , Dinámicas Mitocondriales/genética , Cardiomiopatías Diabéticas/metabolismo , ARN no Traducido/genética , ARN no Traducido/metabolismo , Insulina/metabolismo , Mitocondrias/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismoRESUMEN
Inflammatory bowel disease (IBD) is a complex, chronic intestinal inflammatory disorder that primarily includes Crohn's disease (CD) and ulcerative colitis (UC). Although traditional antibiotics and immunosuppressants are known as the most effective and commonly used treatments, some limitations may be expected, such as limited efficacy in a small number of patients and gut flora disruption. A great many research studies have been done with respect to the etiology of IBD, while the composition of the gut microbiota is suggested as one of the most influential factors. Along with the development of synthetic biology and the continuing clarification of IBD etiology, broader prospects for novel approaches to IBD therapy could be obtained. This study presents an overview of the currently existing treatment options and possible therapeutic targets at the preclinical stage with respect to microbial synthesis technology in biological therapy. This study is highly correlated to the following topics: microbiota-derived metabolites, microRNAs, cell therapy, calreticulin, live biotherapeutic products (LBP), fecal microbiota transplantation (FMT), bacteriophages, engineered bacteria, and their functional secreted synthetic products for IBD medical implementation. Considering microorganisms as the main therapeutic component, as a result, the related clinical trial stability, effectiveness, and safety analysis may be the major challenges for upcoming research. This article strives to provide pharmaceutical researchers and developers with the most up-to-date information for adjuvant medicinal therapies based on synthetic biology.
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A Gram-stain-positive, aerobic bacterium, designated GW1C4-4T, was isolated from the seawater sample from the tidal zone of Guanyinshan Coast, Xiamen, Fujian Province, PR China. The strain was reddish-orange, rod-shaped and non-motile. Cells of strain GW1C4-4T were oxidase-negative and catalase-positive. The strain could grow at 10-42 °C (optimum, 32-35 °C), pH 5-9 (optimum, pH 6) and with 0-10â% NaCl (w/v; optimum, 1â%). Phylogenetic analysis based on the 16S rRNA sequences indicated that strain GW1C4-4T belonged to the genus Gordonia, having the highest similarity to Gordonia mangrovi HNM0687T (98.5â%), followed by Gordonia bronchialis DSM 43247T (98.4â%). The G+C DNA content was 66.5âmolâ%. Average nucleotide identity and digital DNA-DNA hybridization values between strain GW1C4-4T and G. mangrovi HNM0687T were 85.8 and 30.0â%, respectively. The principal fatty acids of strain GW1C4-4T were C16â:â0, C18â:â0 10-methyl (TBSA) and summed feature 3 (C16â:â1 ω7c/C16â:â1 ω6c). MK-9 (H2) was the sole respiratory quinone. The polar lipids included diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and an unidentified lipid. Based on its phylogenetic, phenotypic, chemotaxonomic and genomic characteristics, it is proposed that strain GW1C4-4T represents a novel species within the genus Gordonia, for which the name Gordonia tangerina sp. nov. is proposed. The type strain is GW1C4-4T (=MCCC 1A18727T=KCTC 49729T).
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Bacteria Gordonia , Filogenia , Agua de Mar , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Bacteria Gordonia/clasificación , Bacteria Gordonia/aislamiento & purificación , Fosfolípidos/química , ARN Ribosómico 16S/genética , Agua de Mar/microbiología , Análisis de Secuencia de ADN , ChinaRESUMEN
This study evaluates the effectiveness of traditional Chinese opera on older adults with dementia; those who met the inclusion criteria were categorized into intervention (nâ¯=â¯21) and control (nâ¯=â¯22) groups. Traditional Chinese opera was organized for the intervention group for 12 weeks. The Mini-Mental State Examination (MMSE), the Chinese version of the neuropsychiatric inventory (CNPI), and Quality of Life in Alzheimer's disease (QOL-AD) assessed the effectiveness at the pre-test stage and after 6 and 12 weeks of the intervention, and generalized estimated equation was used for statistical analysis. Statistically significant (P < 0.05) differences were observed between the intervention and control groups in terms of MMSE, CNPI, and QOL-AD. Traditional Chinese opera can potentially be an effective therapy for improving the cognitive function of older adults with dementia, reducing their behavioral and psychiatric symptoms and enhancing their quality of life.
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Demencia/terapia , Musicoterapia , Anciano , Anciano de 80 o más Años , China , Cognición , Estudios Controlados Antes y Después , Demencia/psicología , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Calidad de Vida , Conducta SocialRESUMEN
OBJECTIVE: To investigate the role of PPARα in oxidative damage of BRL-3A cells induced by perfluorooctanoic acid( PFOA) by inhibiting and activating gene expression. METHODS: In vitro culture of rat liver BRL-3A cells were divided into blank control group, PFOA experimental control group, PPARα inhibition group( GW6471), PPARα agonist group( WY14643), PPARα inhibitor pretreatment PFOA group( GW6471 + PFOA), PPARα agonist pretreatment PFOA group( WY14643 + PFOA). Fluorescence immunocytochemistry was used to detect the expression of PPARα. The expression of PPARα and its downstream target gene was detected by q PCR. The expression of related protein was detected by Western blot. RESULTS: The expression of PPARα in rat liver BRL-3A cells was successfully inhibited and stimulated by inhibitors and agonists( P < 0. 05). Compared with the blank control group and the PFOA experimental control group, there was a significant decrease in the content of ROS in the WY14643 + PFOA group compared with the blank control group and the PFOA experimental control group( P < 0. 05). The expression of PPARα and its downstream gene Cyp4a1 in GW6471 + PFOA group was higher than that in PPARα inhibitor group( P < 0. 05), but it was significantly lower than that in PFOA experimental control group( P < 0. 05). The expression of related genes in WY14643 + PFOA group was significantly lower than that in PPARα agonist group( P < 0. 05). The protein expression of PPARα in GW6471 + PFOA group was up-regulated compared with the inhibitor group, there was no difference compared with the blank control group. The protein expression of PPARα in WY14643 + PFOA group was not significantly different from that in agonist group, but it was significantly higher than that in PFOA experimental control group( P < 0. 05). CONCLUSION: PFOA exposure can activate the expression of PPARα, remove ROS, PPARα played a protective role in PFOA-induced rat liver cell oxidative damage.
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Caprilatos/farmacología , Fluorocarburos/toxicidad , Hígado/efectos de los fármacos , Hígado/lesiones , Estrés Oxidativo/efectos de los fármacos , PPAR alfa/efectos de los fármacos , Animales , Caprilatos/toxicidad , Estrés Oxidativo/fisiología , RatasRESUMEN
A rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of codeine, ephedrine, guaiphenesin and chlorpheniramine in beagle dog plasma has been developed and validated. Following liquid-liquid extraction, the analytes were separated on a reversed-phase C(18) column (150 mm × 2.0 mm, 3 µm) using formic acid:10 mM ammonium acetate:methanol (0.2:62:38, v/v/v) as mobile phase at a flow rate of 0.2 mL/min and analyzed by a triple-quadrupole mass spectrometer in the selected reaction monitoring (SRM) mode. The method was linear for all analytes over the following concentration (ng/mL) ranges: codeine 0.08-16; ephedrine 0.8-160; guaiphenesin 80-16,000; chlorpheniramine 0.2-40. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. It is the first time that the validated HPLC-MS/MS method was successfully applied to a bioequivalence study in 6 healthy beagle dogs.