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Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative disorders that share pathological features, including the aberrant accumulation of ubiquitinated protein inclusions within motor neurons. Previously, we have shown that the sequestration of ubiquitin (Ub) into inclusions disrupts Ub homeostasis in cells expressing ALS-associated variants superoxide dismutase 1 (SOD1), fused in sarcoma (FUS) and TAR DNA-binding protein 43 (TDP-43). Here, we investigated whether an ALS/FTD-linked pathogenic variant in the CCNF gene, encoding the E3 Ub ligase Cyclin F (CCNF), also perturbs Ub homeostasis. The presence of a pathogenic CCNF variant was shown to cause ubiquitin-proteasome system (UPS) dysfunction in induced pluripotent stem cell-derived motor neurons harboring the CCNF S621G mutation. The expression of the CCNFS621G variant was associated with an increased abundance of ubiquitinated proteins and significant changes in the ubiquitination of key UPS components. To further investigate the mechanisms responsible for this UPS dysfunction, we overexpressed CCNF in NSC-34 cells and found that the overexpression of both wild-type (WT) and the pathogenic variant of CCNF (CCNFS621G) altered free Ub levels. Furthermore, double mutants designed to decrease the ability of CCNF to form an active E3 Ub ligase complex significantly improved UPS function in cells expressing both CCNFWT and the CCNFS621G variant and were associated with increased levels of free monomeric Ub. Collectively, these results suggest that alterations to the ligase activity of the CCNF complex and the subsequent disruption to Ub homeostasis play an important role in the pathogenesis of CCNF-associated ALS/FTD.
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Esclerose Lateral Amiotrófica , Demência Frontotemporal , Doença de Pick , Humanos , Esclerose Lateral Amiotrófica/metabolismo , Demência Frontotemporal/genética , Demência Frontotemporal/metabolismo , Ciclinas/genética , Neurônios Motores/metabolismo , Ubiquitina/genética , Ubiquitina/metabolismo , Complexo de Endopeptidases do Proteassoma/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Doença de Pick/metabolismo , Homeostase/genética , MutaçãoRESUMO
Light-matter interaction between quantum emitters and optical cavities plays a vital role in fundamental quantum photonics and the development of optoelectronics. Resonant metasurfaces are proven to be an efficient platform for tailoring the spontaneous emission (SE) of the emitters. In this work, we study the interplay between quasi-2D perovskites and dielectric TiO2 metasurfaces. The metasurface, functioning as an open cavity, enhances electric fields near its plane, thereby influencing the emissions of the perovskite. This is verified through angle-resolved photoluminescence (PL) studies. We also conducted reflectivity measurements and numerical simulations to validate the coupling between the quasi-2D perovskites and photonic modes. Notably, our work introduces a spatial mapping approach to study Purcell enhancement. Using fluorescence lifetime imaging microscopy (FLIM), we directly link the PL and lifetimes of the quasi-2D perovskites in spatial distribution when positioned on the metasurface. This correlation provides unprecedented insights into emitter distribution and emitter-resonator interactions. The methodology opens a new (to the best of our knowledge) approach for studies in quantum optics, optoelectronics, and medical imaging by enabling spatial mapping of both PL intensity and lifetime, differentiating between uncoupled quantum emitters and those coupled with different types of resonators.
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Flavonoids and stilbenoids, crucial secondary metabolites abundant in plants and fungi, display diverse biological and pharmaceutical activities, including potent antioxidant, anti-inflammatory, and antimicrobial effects. However, conventional production methods, such as chemical synthesis and plant extraction, face challenges in sustainability and yield. Hence, there is a notable shift towards biological production using microorganisms like Escherichia coli and yeast. Yet, the drawbacks of using E. coli and yeast as hosts for these compounds persist. For instance, yeast's complex glycosylation profile can lead to intricate protein production scenarios, including hyperglycosylation issues. Consequently, Corynebacterium glutamicum emerges as a promising alternative, given its adaptability and recent advances in metabolic engineering. Although extensively used in biotechnological applications, the potential production of flavonoid and stilbenoid in engineered C. glutamicum remains largely untapped compared to E. coli. This review explores the potential of metabolic engineering in C. glutamicum for biosynthesis, highlighting its versatility as a cell factory and assessing optimization strategies for these pathways. Additionally, various metabolic engineering methods, including genomic editing and biosensors, and cofactor regeneration are evaluated, with a focus on C. glutamicum. Through comprehensive discussion, the review offers insights into future perspectives in production, aiding researchers and industry professionals in the field.
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Corynebacterium glutamicum , Flavonoides , Engenharia Metabólica , Estilbenos , Corynebacterium glutamicum/metabolismo , Corynebacterium glutamicum/genética , Engenharia Metabólica/métodos , Flavonoides/biossíntese , Flavonoides/metabolismo , Estilbenos/metabolismoRESUMO
Extracorporeal membrane oxygenation (ECMO) has been used sporadically in adult orthotopic liver transplantation (OLT) recipients for the treatment of acute cardiopulmonary failure. This retrospective study aimed to identify OLT patients who would benefit from ECMO support. We reviewed 109 OLT patients who received ECMO support for more than 24 h from January 2007 to December 2020. Among the enrolled patients, 15 (13.8%) experienced 18 ECMO-related complications and 12 (11.0%) experienced ECMO reapplication after weaning during the same hospitalization period. The successful weaning rates were 50.98% in patients who received ECMO support during the peritransplantation period (0-30 days from transplantation) and 51.72% in patients who received ECMO support in the post-OLT period (more than 30 days after OLT); 24 (47.1%) and 23 (39.7%) patients survived until hospital discharge, respectively. The 109 enrolled OLT recipients who received ECMO support during the perioperative period had a 1-year survival rate of 42.6%. Multivariate analyses identified the following as significant and independent risk factors for in-hospital mortality: ECMO treatment prior to 2011 ( p = 0.04), septic shock as the indication for ECMO treatment ( p = 0.001), and a total bilirubin level of ≥5.0 mg/dl ( p = 0.02). The outcomes of adult OLT recipients with ECMO treatment were acceptable in terms of weaning success and survival until hospital discharge. This study confirmed that ECMO treatment for OLT recipients with septic shock and elevated bilirubin levels might be associated with a higher in-hospital mortality and demonstrated the importance of a multidisciplinary ECMO team approach.
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Oxigenação por Membrana Extracorpórea , Transplante de Fígado , Choque Séptico , Adulto , Humanos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Transplante de Fígado/efeitos adversos , Terapia de Salvação , Estudos Retrospectivos , Choque Séptico/etiologia , Bilirrubina , Resultado do TratamentoRESUMO
Technology-enabled approaches to conducting 24-h dietary recalls (24HR) may reduce dietary assessment bottlenecks in low-resource settings. However, few studies have assessed their performance relative to conventional pen-and-paper interview (PAPI) approaches and none have validated performance against a benchmark (e.g. weighed food record (WFR)) in a low- and middle-income country (LMIC). This study assessed relative accuracy and cost-effectiveness of INDDEX24, a technology-enabled approach to conducting 24HR, compared with a PAPI approach and against an observer WFR. Women aged 18-49 years from northern Viet Nam (n 234) were randomly assigned to be interviewed using INDDEX24 or PAPI 24HR following a WFR. The two one-sided t test approach assessed the equivalence of each recall modality to the benchmark. Difference-in-differences analysis compared the recall-benchmark results across modalities. Cost per percentage point of accuracy for INDDEX24 and PAPI was derived from accuracy results and the cost to conduct the 24HR. The PAPI and INDDEX24 24HR were statistically equivalent to the WFR for all nutrients except vitamin A. INDDEX24 diverged significantly less than PAPI from the WFR for Fe (0·9 v. -1·3 mg) and PAPI diverged less for protein (-3·7 v. 7·9 g). At the individual level, 26 % of PAPI and 32 % of INDDEX24 respondents had energy intakes within +/- 10 % of the WFR. INDDEX24 cost $111 004 and the PAPI cost $120 483 (USD 2019), making INDDEX24 more cost-effective across most indicators. INDDEX24 was an accurate and cost-effective method for assessing dietary intake in the study context and represents a preferred alternative to PAPI 24HR in Viet Nam and other LMIC.
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Dieta , Avaliação Nutricional , Humanos , Feminino , Análise Custo-Benefício , Vietnã , Ingestão de Energia , Registros de Dieta , Reprodutibilidade dos TestesRESUMO
Glinus oppositifolius is an endemic herbaceous plant found in tropical Asian countries and is native in Vietnam. It is used in traditional folk medicine because of its flavor and antiseptic and laxative effects. In the current research, the effects of Tox-off, Biovip, and the purified compounds isolated from G. oppositifolius in the previous study were evaluated on the activation of adenosine 5'-monophosphate-activated protein kinase (AMPK)-activated protein kinase (AMPK) and acetyl-coenzyme A carboxylase (ACC) in C2C12 myoblasts. In addition, the most potent active compounds, traphanoside-GO1 (TRA-GO1) and TRA-GO5 have validated the reduction of fatty acid synthase (FAS) and sterol regulatory element binding protein (SREBP)-1c in HepG2 cells. We found that Tox-off and Biovip significantly increased the phosphorylation of AMPK and ACC in C2C12 myoblasts. Furthermore, TRA-GO1 and TRA-GO5 significantly increased the AMPK activation and phosphorylation of its downstream substrate ACC in a concentration-dependent way compared to the dimethyl sulfoxide (DMSO) control. Besides, the protein level of FAS and SREBP-1c decreased by TRA-GO1 and TRA-GO5 in a concentration-dependent manner. Taken together, our results showed that the increased AMPK and ACC phosphorylation by active components of G. oppositifolius may activate the AMPK signaling pathways, which are useful for the anti-obesity and its related metabolic disorders.
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Proteínas Quinases Ativadas por AMP , Molluginaceae , Humanos , Células Hep G2 , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Metabolismo dos Lipídeos , Ácido Graxo Sintases/metabolismo , Acetil-CoA Carboxilase/metabolismoRESUMO
OBJECTIVES: To estimate the cost and affordability of healthy diets recommended by the 2016-2020 Vietnamese food-based dietary guidelines (FBDG). DESIGN: Cross-sectional analysis. The Cost of a Healthy Diet (CoHD) indicator was used to estimate the lowest cost of healthy diets and compare the cost differences by food group, region and seasonality. The affordability of healthy diets was measured by further comparing the CoHD to food expenditures and incomes. SETTING: Food prices of 176 food items from January 2016 to December 2020 were derived using data from monthly Consumer Price Index databases nationally and regionally. PARTICIPANTS: Food expenditures and incomes of participants from three latest Vietnam Household Living Standard Surveys were used. RESULTS: The average CoHD between 2016 and 2020 in Vietnam was 3·08 international dollars using 2017 Purchasing Power Parity (24 070 Vietnamese Dongs). The nutrient-rich food groups, including protein-rich foods, vegetables, fruits and dairy, comprised approximately 80 % of the total CoHD in all regions, with dairy accounting for the largest proportion. Between 2016 and 2020, the cheapest form of a healthy diet was affordable for all high-income and upper-middle-income households but unaffordable for approximately 70 % of low-income households, where adherence to the Vietnamese FBDG can cost up to 70 % of their income. CONCLUSIONS: Interventions in local food systems must be implemented to reduce the cost of nutrient-rich foods to support the attainment of healthier diets in the Vietnamese population, especially for low-income households.
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Dieta Saudável , Frutas , Humanos , Vietnã , Estudos Transversais , Custos e Análise de Custo , DietaRESUMO
The strong interaction between charge and lattice vibration gives rise to a polaron, which has a profound effect on optical and transport properties of matters. In magnetic materials, polarons are involved in spin dependent transport, which can be potentially tailored for spintronic and opto-spintronic device applications. Here, we identify the signature of ultrafast formation of polaronic states in CrBr3. The polaronic states are long-lived, having a lifetime on the time scale of nanoseconds to microseconds, which coincides with the emission lifetime of â¼4.3 µs. Transition of the polaronic states is strongly screened by the phonon, generating a redshift of the transition energy â¼0.2 eV. Moreover, energy-dependent localization of polaronic states is discovered followed by transport/annihilation properties. These results shed light on the nature of the polarons and their formation and transport dynamics in layered magnetic materials, which paves the way for the rational design of two-dimensional magnetic devices.
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OBJECTIVE: To understand the factors influencing the implementation of salt reduction interventions in low- and middle-income countries (LMIC). DESIGN: Retrospective policy analysis based on desk reviews of existing reports and semi-structured stakeholder interviews in four countries, using Walt and Gilson's 'Health Policy Triangle' to assess the role of context, content, process and actors on the implementation of salt policy. SETTING: Argentina, Mongolia, South Africa and Vietnam. PARTICIPANTS: Representatives from government, non-government, health, research and food industry organisations with the potential to influence salt reduction programmes. RESULTS: Global targets and regional consultations were viewed as important drivers of salt reduction interventions in Mongolia and Vietnam in contrast to local research and advocacy, and support from international experts, in Argentina and South Africa. All countries had population-level targets and written strategies with multiple interventions to reduce salt consumption. Engaging industry to reduce salt in foods was a priority in all countries: Mongolia and Vietnam were establishing voluntary programs, while Argentina and South Africa opted for legislation on salt levels in foods. Ministries of Health, the WHO and researchers were identified as critical players in all countries. Lack of funding and technical capacity/support, absence of reliable local data and changes in leadership were identified as barriers to effective implementation. No country had a comprehensive approach to surveillance or regulation for labelling, and mixed views were expressed about the potential benefits of low sodium salts. CONCLUSIONS: Effective scale-up of salt reduction programs in LMIC requires: (1) reliable local data about the main sources of salt; (2) collaborative multi-sectoral implementation; (3) stronger government leadership and regulatory processes and (4) adequate resources for implementation and monitoring.
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Países em Desenvolvimento , Formulação de Políticas , Argentina , Política de Saúde , Humanos , Mongólia , Estudos Retrospectivos , Cloreto de Sódio na Dieta , África do Sul , VietnãRESUMO
As one of the most state-of-the-art procedures for retinal and choroidal imaging, ultra-widefield optical coherence tomography (UWF-OCT) offers significant gains in terms of information pertaining to peripheral retinal lesions and their differential diagnoses. In particular, it enables the presence of minimal accumulations of subretinal fluid to be assessed in detail and then documented. It also enables choroidal expansion of choroidal lesions to be precisely measured. Similar to conventional OCT, its only limitations relate to patient compliance and opacities of the ocular media. While the pupil width is somewhat less important here, the quality of the images is nevertheless better with the patient under medication-induced mydriasis. Used in combination with UWF fundus photography, UWF-OCT is a helpful tool for assessing and monitoring peripheral retinal and choroidal lesions.
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Relevância Clínica , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Angiofluoresceinografia/métodos , Corioide/diagnóstico por imagem , TecnologiaRESUMO
Autism spectrum disorders (ASD) have heterogeneous etiologies involving dysfunction of central nervous systems, for which no effective pan-specific treatments are available. Ilex kudingcha (IK) C.J. Tseng is a nootropic botanical used in Asia for neuroprotection and improvement of cognition. This study establishes that a chemically characterized extract from IK (IKE) mitigates behavioral traits in the Drosophila melanogaster rugose mutant, whose traits resemble human ASD, and examines possible mechanisms. IKE treatment significantly ameliorated deficits in social interaction, short-term memory, and locomotor activity in Drosophila rugose, and significantly increased synaptic bouton number of size more than 2 µm2 in the neuromuscular junctions (NMJs) of Drosophila rugose. To clarify mechanism(s) of IKE action, methylphenidate (MPH), a dopamine transporter inhibitor, was included as a reference drug in the behavioral assays: MPH significantly improved social interaction and short-term memory deficit in Drosophila rugose; administration of the dopamine D1 receptor antagonist SCH23390 and dopamine D2 receptor antagonist sulpiride reversed the ameliorative effects of both MPH and IKE on the social interaction deficits of Drosophila rugose. To extend analysis of IKE treatment to the vertebrate central nervous system, ASD-associated gene expression in mouse hippocampus was studied by RNA-seq: IKE treatment altered the expression of genes coding phosphoinositide 3-kinases/protein kinase B (PI3K-Akt), proteins in glutamatergic, dopaminergic, serotonergic, and GABAergic synapses, cAMP response element-binding protein (CREB), and RNA transporter proteins. These results provide a foundation for further analysis of IKE as a candidate for treatment of some forms of ASD.
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Transtorno do Espectro Autista/tratamento farmacológico , Nootrópicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Transtorno do Espectro Autista/metabolismo , Ritmo Circadiano/efeitos dos fármacos , Drosophila melanogaster/genética , Expressão Gênica/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Ilex/química , Locomoção/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Metilfenidato/uso terapêutico , Fenótipo , Folhas de Planta/química , Terminações Pré-Sinápticas/efeitos dos fármacos , Interação Social/efeitos dos fármacos , VietnãRESUMO
Vibrio cholerae and Vibrio vulnificus are critical foodborne pathogens that need to be intensively controlled for their infection due to the intake and distribution of seafood, especially raw oysters. For this reason, various methods have already been developed for the detection and enumeration of these bacteria. The most probable number (MPN)-PCR (polymerase chain reaction) method is commonly used with the selective-differential medium for the efficiency and convenience of cell enumeration. One of the most frequently used for detecting Vibrio spp. is thiosulfate-citrate-bile salts-sucrose (TCBS) agar. But this selective-differential medium can fail to distinguish between V. cholerae, V. vulnificus, and Vibrio alginolyticus. For this reason, the conventional MPN-PCR method with TCBS medium for the detection of Vibrio spp. has a problem with processing PCR two times. This study suggests a simple and minimized detection method using one-time PCR and non-NaCl Luria-Bertani (LB-0) medium culture. This detection method is based on the difference in salt requirement between V. cholerae and V. vulnificus. Employing the developed methodology, the simultaneous cell enumeration of V. cholerae and V. vulnificus can be possible at a low cost. Furthermore, this study proposes a new specific primer to detect virulence-related genes from V. cholerae and V. vulnificus. This advanced MPN-PCR method was verified using bioaccumulated pacific oysters (Crassostrea gigas) by V. cholerae and V. vulnificus.
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Ostreidae , Vibrio cholerae , Vibrio parahaemolyticus , Vibrio vulnificus , Animais , Reação em Cadeia da Polimerase , Vibrio cholerae/genética , Vibrio parahaemolyticus/genética , Vibrio vulnificus/genéticaRESUMO
Taste sensors can identify various tastes, including saltiness, bitterness, sweetness, sourness, and umami, and have been useful in the food and beverage industry. Metal-organic frameworks (MOFs) and MXenes have recently received considerable attention for the fabrication of high-performance biosensors owing to their large surface area, high ion transfer ability, adjustable chemical structure. Notably, MOFs with large surface areas, tunable chemical structures, and high stability have been explored in various applications, whereas MXenes with good conductivity, excellent ion-transport characteristics, and ease of modification have exhibited great potential in biochemical sensing. This review first outlines the importance of taste sensors, their operation mechanism, and measuring methods in sensing utilization. Then, recent studies focusing on MOFs and MXenes for the detection of different tastes are discussed. Finally, future directions for biomimetic tongues based on MOFs and MXenes are discussed.
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Técnicas Biossensoriais , Estruturas Metalorgânicas , Biomimética , Glucose , PaladarRESUMO
A considerable number of human diseases have an inflammatory component, and a key mediator of immune activation and inflammation is inducible nitric oxide synthase (iNOS), which produces nitric oxide (NO) from l-arginine. Overexpressed or dysregulated iNOS has been implicated in numerous pathologies including sepsis, cancer, neurodegeneration, and various types of pain. Extensive knowledge has been accumulated about the roles iNOS plays in different tissues and organs. Additionally, X-ray crystal and cryogenic electron microscopy structures have shed new insights on the structure and regulation of this enzyme. Many potent iNOS inhibitors with high selectivity over related NOS isoforms, neuronal NOS, and endothelial NOS, have been discovered, and these drugs have shown promise in animal models of endotoxemia, inflammatory and neuropathic pain, arthritis, and other disorders. A major issue in iNOS inhibitor development is that promising results in animal studies have not translated to humans; there are no iNOS inhibitors approved for human use. In addition to assay limitations, both the dual modalities of iNOS and NO in disease states (ie, protective vs harmful effects) and the different roles and localizations of NOS isoforms create challenges for therapeutic intervention. This review summarizes the structure, function, and regulation of iNOS, with focus on the development of iNOS inhibitors (historical and recent). A better understanding of iNOS' complex functions is necessary before specific drug candidates can be identified for classical indications such as sepsis, heart failure, and pain; however, newer promising indications for iNOS inhibition, such as depression, neurodegenerative disorders, and epilepsy, have been discovered.
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Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/química , Animais , Doença , Inibidores Enzimáticos/farmacologia , Humanos , Modelos Biológicos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/genética , Transdução de Sinais/efeitos dos fármacosRESUMO
This study examined the postoperative pain management practices among registered nurses in an urban hospital in Vietnam. Data of 90 nurses about postoperative pain management practices and pain management at the department were collected. Results indicated that 83.3% of nurses reported that they regularly assessed the degree of pain for postoperative patients. Only 32.2% used assessment tools such as the numeric rating scale to measure pain. Experience in pain management and having guidelines in the department were associated with a higher score in pain management practice. Findings suggested that facilitating the use of pain instruments and developing pain management guidelines should be prioritized.
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Hospitais , Papel do Profissional de Enfermagem , Enfermeiras e Enfermeiros , Manejo da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/terapia , Adulto , Estudos Transversais , Análise Fatorial , Feminino , Humanos , Masculino , Manejo da Dor/métodos , Medição da Dor , Assistência ao Paciente/métodos , Assistência ao Paciente/normas , Padrões de Prática em Enfermagem , VietnãRESUMO
Alzheimer's disease (AD), Parkinson's disease (PD), and depression are growing burdens for society globally, partly due to a lack of effective treatments. Mangosteen (Garcinia mangostana L.,) pericarp (MP) and its xanthones may provide therapeutic advantages for these disorders. In this review, we discuss potential therapeutic value of MP-derived agents in AD, PD, and depression with their pharmacokinetic and safety profiles. MP-derived agents have shown multifunctional effects including neuroprotective, antioxidant, and anti-neuroinflammatory actions. In addition, they target specific disease pathologies, such as amyloid beta production and deposition as well as cholinergic dysfunction in AD; α-synuclein aggregation in PD; and modulation of monoamine disturbance in depression. Particularly, the xanthone derivatives, including α-mangostin and γ-mangostin, exhibit potent pharmacological actions. However, low oral bioavailability and poor brain penetration may limit their therapeutic applications. These challenges can be overcome in part by administering as a form of MP extract (MPE) or using specific carrier systems. MPE and α-mangostin are generally safe and well-tolerated in animals. Furthermore, mangosteen-based products are safe for humans. Therefore, MPE and its bioactive xanthones are promising candidates for the treatment of AD, PD, and depression. Further studies including clinical trials are essential to decipher their efficacy, and pharmacokinetic and safety profiles in these disorders.
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Depressão/metabolismo , Garcinia mangostana/química , Doenças Neurodegenerativas/metabolismo , Xantonas/farmacocinética , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Aminas/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Depressão/tratamento farmacológico , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Extratos Vegetais/química , Xantonas/química , Xantonas/uso terapêutico , alfa-Sinucleína/metabolismoRESUMO
Chemokine-receptor interactions play multiple roles in cancer progression. It was reported that the overexpression of X-C motif chemokine receptor 1 (XCR1), a specific receptor for chemokine X-C motif chemokine ligand 1 (XCL1), stimulates the migration of MDA-MB-231 triple-negative breast cancer cells. However, the exact mechanisms of this process remain to be elucidated. Our study found that XCL1 treatment markedly enhanced MDA-MB-231 cell migration. Additionally, XCL1 treatment enhanced epithelial-mesenchymal transition (EMT) of MDA-MB-231 cells via E-cadherin downregulation and upregulation of N-cadherin and vimentin as well as increases in ß-catenin nucleus translocation. Furthermore, XCL1 enhanced the expression of hypoxia-inducible factor-1α (HIF-1α) and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Notably, the effects of XCL1 on cell migration and intracellular signaling were negated by knockdown of XCR1 using siRNA, confirming XCR1-mediated actions. Treating MDA-MB-231 cells with U0126, a specific mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, blocked XCL1-induced HIF-1α accumulation and cell migration. The effect of XCL1 on cell migration was also evaluated in ER-/HER2+ SK-BR-3 cells. XCL1 also promoted cell migration, EMT induction, HIF-1α accumulation, and ERK phosphorylation in SK-BR-3 cells. While XCL1 did not exhibit any significant impact on the matrix metalloproteinase (MMP)-2 and -9 expressions in MDA-MB-231 cells, it increased the expression of these enzymes in SK-BR-3 cells. Collectively, our results demonstrate that activation of the ERK/HIF-1α/EMT pathway is involved in the XCL1-induced migration of both MDA-MB-231 and SK-BR-3 breast cancer cells. Based on our findings, the XCL1-XCR1 interaction and its associated signaling molecules may serve as specific targets for the prevention of breast cancer cell migration and metastasis.
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Neoplasias da Mama/metabolismo , Movimento Celular , Quimiocinas C/metabolismo , Transdução de Sinais , Células A549 , Transição Epitelial-Mesenquimal , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Receptores Acoplados a Proteínas G/metabolismoRESUMO
Eleven novel isoquinoline-1-carboxamides (HSR1101~1111) were synthesized and evaluated for their effects on lipopolysaccharide (LPS)-induced production of pro-inflammatory mediators and cell migration in BV2 microglial cells. Three compounds (HSR1101~1103) exhibited the most potent suppression of LPS-induced pro-inflammatory mediators, including interleukin (IL)-6, tumor necrosis factor-alpha, and nitric oxide (NO), without significant cytotoxicity. Among them, only N-(2-hydroxyphenyl) isoquinoline-1-carboxamide (HSR1101) was found to reverse LPS-suppressed anti-inflammatory cytokine IL-10, so it was selected for further characterization. HSR1101 attenuated LPS-induced expression of inducible NO synthase and cyclooxygenase-2. Particularly, HSR1101 abated LPS-induced nuclear translocation of NF-κB through inhibition of IκB phosphorylation. Furthermore, HSR1101 inhibited LPS-induced cell migration and phosphorylation of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase, and p38 MAPK. The specific MAPK inhibitors, U0126, SP600125, and SB203580, suppressed LPS-stimulated pro-inflammatory mediators, cell migration, and NF-κB nuclear translocation, indicating that MAPKs may be the upstream kinase of NF-κB signaling. Collectively, these results demonstrate that HSR1101 is a potent and promising compound suppressing LPS-induced inflammation and cell migration in BV2 microglial cells, and that inhibition of the MAPKs/NF-κB pathway mediates its anti-inflammatory and anti-migratory effects. Based on our findings, HSR1101 may have beneficial impacts on various neurodegenerative disorders associated with neuroinflammation and microglial activation.
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Anti-Inflamatórios/farmacologia , Microglia/efeitos dos fármacos , Microglia/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Animais , Anti-Inflamatórios/química , Movimento Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Concentração Inibidora 50 , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Isoquinolinas/química , Isoquinolinas/farmacologia , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Doenças Neurodegenerativas/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Cicatrização/efeitos dos fármacosRESUMO
BACKGROUND: Residents in border areas are vulnerable to HIV/AIDS due to high rates of risk behaviors such as unprotected sexual practices or illicit drug use. Improving knowledge and attitude toward HIV/AIDS prevention and treatment are vital to diminish the burden of the HIV epidemic in this setting. However, evidence about this issue in Vietnam has been limited. This study aims to explore the knowledge and attitude toward HIV/AIDS among people in Vietnam border zones. METHODS: We conducted a cross-sectional study in three border communes in Thanh Hoa province with 600 HIV(-) residents. Data about socio-demographic characteristics, general HIV knowledge, knowledge about prevention of mother-to-child transmission, treatment and care, HIV testing services, and attitude toward HIV/AIDS were collected. Multivariate Tobit regression was used to determine related factors with the knowledge and attitude. RESULTS: The highest percentage of people having correct statements was for "HIV could be transmitted from mother to child" (98.2%), while the lowest percentage was for item "Know health facilities where HIV-positive people could register for care and check-up" (28.2%). People had the highest score in "Knowledge about HIV transmission routes" and the lowest score in "Knowledge about HIV/AIDS prevention measures". Most of the people were not afraid of being exposed to HIV-positive individuals (66.0%), willing to buy goods from HIV-positive sellers (78.9%), and willing to take care of people living with HIV in their family (90.1%). Education, ethnic, marital status, occupations, and HIV/AIDS information sources were found to be associated with knowledge and attitude toward HIV/AIDS. CONCLUSIONS: The general knowledge and attitude on HIV/AIDS of residents were relatively good. Educational campaigns to improve knowledge and attitude toward PLWH, involving peer educators and local associations, are potential strategies for sustaining HIV intervention in this remote setting.
Assuntos
Síndrome da Imunodeficiência Adquirida/psicologia , Infecções por HIV/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Transmissão Vertical de Doenças Infecciosas , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Síndrome da Imunodeficiência Adquirida/transmissão , Adulto , Estudos Transversais , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Educação em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Assunção de Riscos , Fatores Socioeconômicos , Inquéritos e Questionários , Vietnã , Adulto JovemRESUMO
There is mounting concern about how to support decision-makers in driving sustainable water resources management; science needs to support the decision-making process to promote evidence-based decisions. To this end, sustainability assessment is considered a useful technique, which provides enough information to assist management. This study proposed a groundwater sustainability assessment framework, which is developed from a regular sustainability assessment approach and analytical hierarchy process (AHP). In the proposed framework, the three main pillars (environmental, social, and economic) of the concept of sustainability were considered the three important sustainability criteria. Hence, we demonstrated the proposed framework for a Hanoi case study with focus on the environmental sustainability criterion. The concept of AHP was used to create the main sustainability components (the three criteria, associated with their aspects and indicators) of a hierarchy, which appropriately cover environmental sustainability issues of groundwater resources in the target area. Based on the available reliable data of the current problems in Hanoi, we proposed three main sustainability aspects (quantity, quality, and management) and, accordingly, selected their twelve environmental sustainability indicators. To determine a reasonable sustainability assessment, we considered a conventional linear and non-linear relationship between the indicators and the corresponding sustainability indices. As for the results from the Hanoi case study, the environmental sustainability indices obtained from using a combined linear and non-linear relationship case appropriately reflect the current situation, that is, the environmental sustainability assessment is close to reality. The sustainability indices of the quantity, quality, and management aspects of groundwater were appropriately assessed at acceptable levels, resulting in Hanoi being rated at the acceptable level in the final environmental sustainability index. The variability of the environmental sustainability indices indicated that the current groundwater abstraction networks are heavily concentrated in a few specific areas in Hanoi, which is not optimal for utilizing the rich natural recharge resources of the area. Improvement of the current poor groundwater quality and strict enforcement of environmental regulations are essential to enhancing the environmental sustainability and, more importantly, to drive Hanoi towards sustainable groundwater resources.