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Importance: Nutritional status of infants, measured by birth weight and length, is an essential factor in neonatal development. Malnutrition in newborns may lead to a higher risk of mortality, neurological and cognitive impairment, and poor language development. Objective: This study aims to assess the nutritional status of infants and related factors regarding maternal anthropometric characteristics and medical history. Methods: A cross-sectional study was conducted at the National Hospital of Obstetrics and Gynecology, Vietnam from May 2021 to May 2022 on 340 infants and mothers. Low birth weight was defined following the Intergrowth-21 standards. Stunting was evaluated using the Fenton growth chart when the length was below the 10% percentile line of the gestational week. Multivariate regression models were applied to identify factors associated with the nutritional status of infants. Results: We found that 12.4% and 14.1% of infants in our study fell into stunted and underweight categories, respectively. Infants of mothers over 35 years old, having a height lower than 150â¯cm or experiencing anemia during pregnancy were more likely to be stunted or have low birth weight. Serum albumin deficiency during pregnancy was strongly associated with the infant being underweight (odds ratio [OR] = 2.8, 95% confidence interval [95%CI] 1.1-7.3). Newborns were more likely to be stunted if their mothers had a history of preterm birth (OR = 3.3, 95%CI 1.1-10.2). Interpretation: Maternal nutritional status is closely related to infant malnutrition, particularly in preterm infants. Improving the understanding of mothers regarding prenatal care, reproductive healthcare, adequate nutritional diet, and multi-micronutrient supplements during pregnancy is therefore important.
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Difficulty falling asleep is one of the typical insomnia symptoms. However, intervention therapies available nowadays, ranging from pharmaceutical to hi-tech tailored solutions, remain ineffective due to their lack of precise real-time sleep tracking, in-time feedback on the therapies, and an ability to keep people asleep during the night. This paper aims to enhance the efficacy of such an intervention by proposing a novel sleep aid system that can sense multiple physiological signals continuously and simultaneously control auditory stimulation to evoke appropriate brain responses for fast sleep promotion. The system, a lightweight, comfortable, and user-friendly headband, employs a comprehensive set of algorithms and dedicated own-designed audio stimuli. Compared to the gold-standard device in 883 sleep studies on 377 subjects, the proposed system achieves (1) a strong correlation (0.89 ± 0.03) between the physiological signals acquired by ours and those from the gold-standard PSG, (2) an 87.8% agreement on automatic sleep scoring with the consensus scored by sleep technicians, and (3) a successful non-pharmacological real-time stimulation to shorten the duration of sleep falling by 24.1 min. Conclusively, our solution exceeds existing ones in promoting fast falling asleep, tracking sleep state accurately, and achieving high social acceptance through a reliable large-scale evaluation.
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Distúrbios do Início e da Manutenção do Sono , Dispositivos Eletrônicos Vestíveis , Humanos , Estimulação Acústica , Sono/fisiologia , PolissonografiaRESUMO
In rice (Oryza sativa L.), rice bran contains valuable nutritional constituents, such as high unsaturated fat content, tocotrienols, inositol, γ-oryzanol, and phytosterols, all of which are of nutritional and pharmaceuticals interest. There is now a rising market demand for rice bran oil, which makes research into their content and fatty acid profile an area of interest. As it is evident that lipid content has a substantial impact on the eating, cooking, and storage quality of rice, an understanding of the genetic mechanisms that determine oil content in rice is of great importance, equal to that of rice quality. Therefore, in this study, we performed a genome-wide association study on the composition and oil concentration of 161 Vietnamese rice varieties. Five categories of fatty acids in rice bran were discovered and the bran oil concentration profile in different rice accessions was identified. We also identified 229 important markers related to the fatty acid composition of bran oil, distributed mainly on chromosomes 1 and 7. Seven quantitative trait loci and five potential genes related to unsaturated fatty acid content were detected, including OsKASI, OsFAD, OsARF, OsGAPDH, and OsMADS29. These results provide insights into the genetic basis of rice bran oil composition, which is pivotal to the metabolic engineering of rice plants with desirable bran oil content through candidate genes selection.
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Ácidos Graxos , Oryza , Óleo de Farelo de Arroz , Ácidos Graxos/química , Estudo de Associação Genômica Ampla , Oryza/genética , Locos de Características Quantitativas , Óleo de Farelo de Arroz/químicaRESUMO
To leverage complementary mechanisms for cancer cell removal, we developed a novel cell engineering and therapeutic strategy co-opting phagocytic clearance and antigen presentation activity into T cells. We engineered a chimeric engulfment receptor (CER)-1236, which combines the extracellular domain of TIM-4, a phagocytic receptor recognizing the "eat me" signal phosphatidylserine, with intracellular signaling domains (TLR2/TIR, CD28, and CD3ζ) to enhance both TIM-4-mediated phagocytosis and T cell cytotoxic function. CER-1236 T cells demonstrate target-dependent phagocytic function and induce transcriptional signatures of key regulators responsible for phagocytic recognition and uptake, along with cytotoxic mediators. Pre-clinical models of mantle cell lymphoma (MCL) and EGFR mutation-positive non-small cell lung cancer (NSCLC) demonstrate collaborative innate-adaptive anti-tumor immune responses both in vitro and in vivo. Treatment with BTK (MCL) and EGFR (NSCLC) inhibitors increased target ligand, conditionally driving CER-1236 function to augment anti-tumor responses. We also show that activated CER-1236 T cells exhibit superior cross-presentation ability compared with conventional T cells, triggering E7-specific TCR T responses in an HLA class I- and TLR-2-dependent manner, thereby overcoming the limited antigen presentation capacity of conventional T cells. Therefore, CER-1236 T cells have the potential to achieve tumor control by eliciting both direct cytotoxic effects and indirect-mediated cross-priming.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Adulto , Linfócitos T , Apresentação Cruzada , Fosfatidilserinas , Antígenos de Neoplasias , Receptores ErbB , Imunoterapia Adotiva , Receptores de Antígenos de Linfócitos T/genéticaRESUMO
BACKGROUND: The current state of practices in health care remediation is not well known. The purpose of this review is to characterize, assess, and present synthesized results of current student and professional remediation practices described in the literature. METHODS: This study used an integrative review process including article extraction and review, descriptive characterization and statistics, classification of levels of evidence, assessment of risk of bias, and examination of relationships between factors and types of remediation. Articles were located in a search of PubMed (MEDLINE) and EBSCO (CINAHL Complete) last accessed in May 2022. INCLUSION CRITERIA: Full text journal articles and Briefs published between January 2001 and May 2022, English language, focus on remediation in health science education programs and professionals, identified key words in title, abstract, or article. EXCLUSION CRITERIA: Published outside the date range; focus of study or article outside health sciences; main focus not on remediation process or program (defined above), books, presentations and abstracts. RESULTS: 97 articles were included. Design rigor clustered around Level 6 (case-controlled studies, case series, case reports). All programs and activities were reported as successful. There was a statistically significant relationship (p < 0.01) between healthcare discipline and type of remediation. CONCLUSIONS: A variety of remediation methods for health care students and professionals are reported to be successful. Higher level studies are needed to help define best practices for remediation activities in health care professional knowledge and skill.
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Atenção à Saúde , Estudantes de Ciências da Saúde , Humanos , Estudos de Casos e Controles , Aprendizagem , Ocupações em SaúdeRESUMO
Beneficial natural products utilized in cosmetics formulation and pharmaceutical applications are of enormous interest. Lily (Lilium) serves as an essential edible and medicinal plant species with wide classification. Here, we have performed the screening of various extracts that were prepared from flower petals grown from the bulbs of eight Lilium varieties, with a viewpoint to their applicability as a viable source of natural anti-inflammatory and antioxidants agent. Interestingly, our findings indicated that all ethanol and water extracts exhibited a substantially differential spectrum of antioxidant as well as anti-inflammatory properties. Specifically, Serrano showed a close similarity among ethanol and water extracts among all tested lily petal extracts. Therefore, to obtain a detailed analysis of chemical compounds, liquid chromatography-mass spectroscopy was performed in ethanolic and water extracts of Serrano petals. Together, our preliminary results indicated that lily petals extracts used in this study could serve as a basis to develop a potential new whitening agent with powerful antioxidant and anti-inflammatory properties for medicinal, functional food, and cosmetic applications.
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Art therapy has been widely offered to reduce symptoms of psychological disturbance. Pooled evidence about its effectiveness in epidemic contexts, particularly during the COVID-19 pandemic, has not been yet established. This study reviewed the effectiveness, feasibility, and acceptability of art therapy on children and adolescents during the COVID-19 pandemic and past epidemics. We searched PubMed/Medline, PsycINFO, CENTRAL (Cochrane Library), and CINAHL for articles on art therapy during COVID-19. Included studies reported improvements in measures of mental health, sleep quality, and psychological well-being in children with or without disabilities in the epidemic context. Results also showed that art therapy was highly feasible and accepted by children and adolescents as well as their families during epidemics in reviewed studies. Art therapy can be effective at improving various aspects of mental health, sleep quality, and psychological well-being. More empirical evidence is needed with larger sample sizes and longer duration of interventions.
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Arteterapia , COVID-19 , Adolescente , Criança , Estudos de Viabilidade , Humanos , Saúde Mental , PandemiasRESUMO
The global market of the medicinal plant ginseng is worth billions of dollars. Many ginseng species are threatened in the wild and effective sustainable development initiatives are necessary to preserve biodiversity at species and genetic level whilst meeting the demand for medicinal produce. This is also the case of Panax vietnamensis Ha & Grushv., an endemic and threatened ginseng species in Vietnam that is locally cultivated at different scales and has been the object of national breeding programs. To investigate the genetic diversity within cultivated and wild populations of P. vietnamensis we captured 353 nuclear markers using the Angiosperm-353 probe set. Genetic diversity and population structure were evaluated for 319 individuals of Vietnamese ginseng across its area of distribution and from wild and a varying range of cultivated areas. In total, 319 individuals were sampled. After filtering, 1,181 SNPs were recovered. From the population statistics, we observe high genetic diversity and high genetic flow between populations. This is also supported by the STRUCTURE analysis. The intense gene flow between populations and very low genetic differentiation is observed regardless of the populations' wild or cultivated status. High levels of admixture from two ancestral populations exist in both wild and cultivated samples. The high gene flow between populations can be attributed to ancient and on-going practices of cultivation, which exist in a continuum from understorey, untended breeding to irrigated farm cultivation and to trade and exchange activities. These results highlight the importance of partnering with indigenous peoples and local communities and taking their knowledge into account for biodiversity conservation and sustainable development of plants of high cultural value.
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This is a comprehensive review of the literature focusing on the use of prolotherapy in the treatment of osteoarthritis of the knee. It covers the background, efficacy, and advantages of prolotherapy in the management of osteoarthritis symptoms and then covers the existing evidence of the use of prolotherapy for this purpose. Current treatments for osteoarthritis of the knee are numerous, yet patients continue to endorse chronic pain and poor quality of life. Prolotherapy is a treatment that has been inadequately studied with poor sample sizes and lack of standardization between trials. However, in recent years the literature on prolotherapy in the treatment of knee osteoarthritis has grown. Although there is still a lack of homogeneity, trials have shown that dextrose prolotherapy, autologous conditioned serum, hyaluronic injections, and normal saline administered either intra- or peri-articularly are comparable in reducing pain scores to other primary treatment options. The mechanism of action for prolotherapy is still unclear, but researchers have found that prolotherapy plays some role in cartilage growth or chondrogenesis and has been shown to have improved radiographic outcomes. Prolotherapy appears to be a safe treatment alternative that has been shown to improve stiffness, pain, function, and quality of life in osteoarthritis of the knee. Knee osteoarthritis is remarkably prevalent in the United States and is one of the most common causes of disability in the elderly population. Although there are many treatment options, patients continue to live with chronic pain which can incur high costs for patients. A safe, long-term, and effective solution has not yet been identified. Prolotherapy has been shown to be a safe option for improving pain, function, and quality of life as effectively as other treatment options.
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Potato is one of the most important food crops worldwide in terms of human consumption. However, potato farmers employ a variety of pesticides to protect crops from harmful insects and illnesses, and difenoconazole is a commonly used one that has severe effects on human health and the environment. Therefore, detecting difenoconazole quickly and correctly is critical. In this work, we fabricated AgNPs/cicada wing substrates using natural cicada segments, decorated with silver nanoparticles for surface-enhanced Raman scattering (SERS) measurements to detect trace amounts of difenoconazole in potatoes. Results indicated that a linear relationship with the coefficient of detection (R2) of 0.987 and the detection limit (LOD) of 0.016 ppm was observed by targeting a distinctive peak at 808 cm-1 and logarithmic difenoconazole concentrations of 0.1 to 100 ppm. In addition, difenoconazole LODs in potatoes were 63 µg/kg, lower than those specified by the EU (0.1 mg/kg) and Vietnam (4 mg/kg) utilizing this new technique. Therefore, this proposed SERS method could be used to detect difenoconazole in potatoes at trace levels.
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Hemípteros , Nanopartículas Metálicas , Solanum tuberosum , Animais , Dioxolanos , Humanos , Prata , Análise Espectral Raman/métodos , TriazóisRESUMO
Carcinogenesis is a major concern that severely affects the human population. Owing to persistent demand for novel therapies to treat and prohibit this lethal disease, research interest among scientists is drawing its huge focus toward natural products, as they have minimum toxicity comparable with existing treatment methods. The plants produce secondary metabolites, which are known to have the anticancer potential for clinical drug development. Furthermore, the use of nanocarriers could boost the solubility and stability of phytocompounds to obtain site-targeting delivery. The identification of potential phytochemicals in natural compounds would be beneficial for the synthesis of biocompatible nanoemulsions. The present study aimed to investigate the potential cytotoxicity of ethanol extracts of Hibiscus syriacus and Cinnamomum loureirii Nees plant parts on human skin melanoma (G361) and lung adenocarcinoma (A549) cells. Importantly, biochemical analysis results showed the presence of high phenol (50-55 µgGAE/mg) and flavonoids [42-45 µg quercetin equivalents (QE)/mg] contents with good antioxidant activity (40-58%) in C. loureirii Nees plants extracts. This plant possesses potent antiproliferative activity (60-90%) on the malignant G361 and A549 and cell lines correlated with the production of nitric oxide. Especially, C. loureirii plant extracts have major metabolites that exhibit cancer cell death associated with cell cycle arrest. These findings support the potential application of Cinnamomum for the development of therapeutic nanoemulsion in future cancer therapy.
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The parasitic gastrointestinal nematode Haemonchus contortus causes serious economic losses to agriculture due to infection and disease in small ruminant livestock. The development of new therapies requires appropriate viability testing, with methods nowadays relying on larval motility or development using procedures that involve microscopy. None of the existing biochemical methods, however, are performed in adults, the target stage of the anthelmintic compounds. Here we present a new test for the viability of H. contortus adults and exsheathed third-stage larvae which is based on a bioluminescent assay of ATP content normalized to total protein concentration measured using bicinchoninic acid. All the procedure steps were optimized to achieve maximal sensitivity and robustness. This novel method can be used as a complementary assay for the phenotypic screening of new compounds with potential antinematode activity in exsheathed third-stage larvae and in adult males. Additionally, it might be used for the detection of drug-resistant isolates.
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Trifosfato de Adenosina/uso terapêutico , Hemoncose/veterinária , Haemonchus/isolamento & purificação , Medições Luminescentes/veterinária , Técnicas de Diagnóstico Molecular/veterinária , Doenças dos Ovinos/diagnóstico , Animais , Feminino , Hemoncose/diagnóstico , Hemoncose/parasitologia , Haemonchus/crescimento & desenvolvimento , Larva/crescimento & desenvolvimento , Medições Luminescentes/instrumentação , Masculino , Técnicas de Diagnóstico Molecular/instrumentação , Ovinos , Doenças dos Ovinos/parasitologia , Carneiro DomésticoRESUMO
This study was performed to analyze the accuracy of health-related information on Twitter during the coronavirus disease 2019 (COVID-19) pandemic. Authors queried Twitter on three dates for information regarding COVID-19 and five terms (cure, emergency or emergency room, prevent or prevention, treat or treatments, vitamins or supplements) assessing the first 25 results with health-related information. Tweets were authoritative if written by governments, hospitals, or physicians. Two physicians assessed each tweet for accuracy. Metrics were compared between accurate and inaccurate tweets using χ 2 analysis and Mann-Whitney U. A total of 25.4% of tweets were inaccurate. Accurate tweets were more likely written by Twitter authenticated authors (49.8% vs. 20.9%, 28.9% difference, 95% confidence interval [CI]: 17.7-38.2) with accurate tweet authors having more followers (19,491 vs. 7346; 3446 difference, 95% CI: 234-14,054) versus inaccurate tweet authors. Likes, retweets, tweet length, botometer scores, writing grade level, and rank order did not differ between accurate and inaccurate tweets. We found 1/4 of health-related COVID-19 tweets inaccurate indicating that the public should not rely on COVID-19 health information written on Twitter. Ideally, improved government regulatory authority, public/private industry oversight, independent fact-checking, and artificial intelligence algorithms are needed to ensure inaccurate information on Twitter is removed.
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AMP-activated protein kinase (AMPK) plays a crucial role in the regulation of energy homeostasis in both peripheral metabolic organs and the central nervous system. Recent studies indicated that p-Coumaric acid (CA), a hydroxycinnamic phenolic acid, potentially activated the peripheral AMPK pathway to exert beneficial effects on glucose metabolism in vitro. However, CA's actions on central AMPK activity and whole-body glucose homeostasis have not yet been investigated. Here, we reported that CA exhibited different effects on peripheral and central AMPK activation both in vitro and in vivo. Specifically, while CA treatment promoted hepatic AMPK activation, it showed an inhibitory effect on hypothalamic AMPK activity possibly by activating the S6 kinase. Furthermore, CA treatment enhanced hypothalamic leptin sensitivity, resulting in increased proopiomelanocortin (POMC) expression, decreased agouti-related peptide (AgRP) expression, and reduced daily food intake. Overall, CA treatment improved blood glucose control, glucose tolerance, and insulin sensitivity. Together, these results suggested that CA treatment enhanced hypothalamic leptin signaling and whole-body glucose homeostasis, possibly via its differential effects on AMPK activation.
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Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Glucose/metabolismo , Leptina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Homeostase/efeitos dos fármacos , Hipotálamo/metabolismo , Resistência à Insulina , Camundongos , Pró-Opiomelanocortina/metabolismoRESUMO
Oral administration of sucralose has been reported to stimulate food intake through inducing hypothalamic neuropeptide Y (NPY) in mice and fruit flies. However, the underlying mechanisms of action of sucralose in hypothermia and NPY and monoamine regulation remain unknown. The aim of the present study was to investigate central effects of sucralose on body temperature, NPY, and monoamine regulation, as well as its peripheral effects, in chicks. In Experiment 1, 5-day-old chicks were centrally injected with 1 µmol of sucralose, other sweeteners (erythritol and glucose), or saline. In Experiment 2, chicks were centrally injected with 0.2, 0.4, and 1.6 µmol of sucralose or saline. In Experiment 3, chicks were centrally injected with 0.8 µmol of sucralose or saline, with a co-injection of 100 µg fusaric acid (FA), an inhibitor of dopamine-ß-hydroxylase, to examine the role dopamine in sucralose induced hypothermia. In Experiment 4, 7-16-day-old chicks were orally administered with 75, 150, and 300 mg/2 ml distilled water or sucralose, daily. We observed that the central injection of sucralose, but not other sweeteners, decreased body temperature (P < .05) in chicks; however, the oral injection did not influence body temperature, food intake, and body weight gain. Central sucralose administration decreased dopamine and serotonin and stimulated dopamine turnover rate in the hypothalamus significantly (P < .05). Notably, sucralose co-injection with FA impeded sucralose-induced hypothermia. Sucralose decreases body temperature potentially via central monoaminergic pathways in the hypothalamus.
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Dopamina/análise , Hipotálamo/metabolismo , Hipotermia/metabolismo , Serotonina/análise , Sacarose/análogos & derivados , Administração Oral , Animais , Temperatura Corporal , Encéfalo/metabolismo , Galinhas , Eritritol/análise , Ácido Fusárico/química , Glucose/análise , Infusões Intraventriculares , Masculino , Neuropeptídeo Y/metabolismo , Sacarose/químicaRESUMO
Viola is the largest genus in the Violaceae plant family and is known for its ubiquitous natural production of cyclotides. Many Viola species are used as medicinal herbs across Asia and are often consumed by humans in teas for the treatment of diseases, including ulcers and asthma. Previous studies reported the isolation of cyclotides from Viola species in many countries in the hope of discovering novel compounds with anti-cancer activities; however, Viola species from Vietnam have not been investigated to date. Here, the discovery of cyclotides from three Viola species (V. arcuata, V. tonkinensis, and V. austrosinensis) collected in the northern mountainous region of Vietnam is reported. Ten cyclotides were isolated from these three Viola species: four are novel and six were previously reported to be expressed in other plants. The structures of three of the new bracelet cyclotides are similar to that of cycloviolacin O2. Because cycloviolacin O2 has previously been shown to have potent activity against a wide range of cancer cell lines including HeLa (human cervical cancer cells) and PC-3 (human prostate cancer cells), the cancer cytotoxicity of the cyclotides isolated from V. arcuata was assessed. All tested cyclotides were cytotoxic against cancer cells, albeit to varying degrees. The sequences discovered in this study significantly expand the understanding of cyclotide diversity, especially in comparison with other cyclotides found in plants from the Asian region.
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Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ciclotídeos/química , Ciclotídeos/farmacologia , Viola/química , Sequência de Aminoácidos , Biodiversidade , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células HeLa , Hemólise/efeitos dos fármacos , Humanos , Masculino , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , VietnãRESUMO
Reducing carbohydrates digestion by having a low glycaemic index (GI) foods has been linked to weight loss. Inhibiting related enzymes is an alternative way to decrease carbohydrate digestion. RCM-107 (Slimming Plus), an eight-herb formula that is modified from RCM-104, indicated significant weight-loss action in clinical trials. However, no published research has studied its mechanism of action on reducing carbohydrate absorption via suppressing the activities of porcine pancreatic alpha-amylase (PPA). In this paper, we used fluorescence PPA inhibition assay to investigate the inhibitory effects of RCM-107 and the individual herbs present in this herbal mixture on amylase activity. Subsequently, molecular docking predicted the key active compounds that may be responsible for the enzyme inhibition. According to our results, both the RCM-107 formula and several individual herbs displayed α-amylase inhibitory effects. Also, marginal synergistic effects of RCM-107 were detected. In addition, alisol B, (-)-epigallocatechin-3-gallate (EGCG) and plantagoside have been predicted as the key active compounds that may be responsible for the α-amylase inhibition effect of RCM-107 according to inter-residue contact analysis. Finally, Glu233, Gln63, His305, Asp300 and Tyr151 are predicted to be markers of important areas with which potential amylase inhibitors would interact. Therefore, our data has provided new knowledge on the mechanisms of action of the RCM-107 formula and its individual herbal ingredients for weight loss, in terms of decreasing carbohydrate digestion via the inhibition of pancreatic alpha-amylase.
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Fármacos Antiobesidade/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Obesidade/tratamento farmacológico , alfa-Amilases Pancreáticas/antagonistas & inibidores , Redução de Peso/efeitos dos fármacos , Animais , Fármacos Antiobesidade/química , Metabolismo dos Carboidratos/efeitos dos fármacos , Catequina/análogos & derivados , Catequina/química , Catequina/farmacologia , Colestenonas/química , Colestenonas/farmacologia , Medicamentos de Ervas Chinesas/química , Ensaios Enzimáticos , Flavanonas/química , Flavanonas/farmacologia , Glucosídeos/química , Glucosídeos/farmacologia , Humanos , Simulação de Acoplamento Molecular , Obesidade/metabolismo , alfa-Amilases Pancreáticas/química , alfa-Amilases Pancreáticas/metabolismo , SuínosRESUMO
Obesity is a multifactorial disease that can lead to other health issues. Glucagon-like peptide-1(GLP-1), as one of the satiety signal, has been linked with appetite suppression and weight loss. Due to the limitations of GLP-1 and its analogues, alternative treatments such as herbal therapies have become popular. The herbal formula RCM-107 has demonstrated its inhibitory effects on lipid and carbohydrate absorption in our previous work. However, no published data described its effects on GLP-1 secretion. Therefore, this study aimed to determine the effects of RCM-107 and its individual ingredients on GLP-1 secretion via enzyme-linked immunosorbent assay (ELISA). Furthermore, molecular docking was performed to predict the key chemical compounds that are likely to be GLP-1 receptor agonists. Gardeniae fructus, one of the ingredients in RCM-107, demonstrated significantly greater effects on inducing GLP-1 secretion than the positive control epigallocatechin gallate (EGCG). Two Gardeniae fructus ligands, 3-epioleanolic acid and crocin were predicted to bind to the active form of GLP-1 receptor at the binding pocket with residues known for the receptor activation, suggesting that they could potentially serve as receptor agonists. Overall, this study reported the effects of researched herbs on GLP-1 secretion and proposed two compounds that may be responsible for antiobesity via GLP-1 receptor activation.
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Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Peptídeo 1 Semelhante ao Glucagon/biossíntese , Peptídeo 1 Semelhante ao Glucagon/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Redução de Peso/efeitos dos fármacos , Sítios de Ligação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Conformação Molecular , Ligação Proteica , Relação Estrutura-AtividadeRESUMO
INTRODUCTION: The aim of this study is to identify the profiles of young people who use drugs (YPUD) and their exposure to HIV risks in the 3 main cities of Vietnam, Haiphong, Hanoi, and Ho Chi Minh City (HCMC), in order to design a community-based intervention to prevent HIV. METHODS: A survey using respondent-driven sampling (RDS) was conducted among YPUD aged 16-24. Participants were eligible if they reported drug use, confirmed by a urine test. After obtaining informed consent, they were screened for HIV/HCV and assessed using face-to-face questionnaires and self-report. A cluster analysis was conducted, taking into account risk behaviors and confirmed HIV-positive status. RESULTS: Seven hundred and three YPUD aged 16-24 were recruited between October 2016 and February 2017, 584 of whom were included in the final analysis. Median age was 21 (17.7, 23.0); 79% were male, 18% female, and 2% transgender. Methamphetamines use was reported by 77%, followed by cannabis (51%) and heroin (17%); polydrug use was common; 15% had "ever" injected drugs. HIV prevalence was 7%. Among all participants, 48% reported non-consistent condom use and 1% reported needle/syringe sharing during the previous month. Four distinct profiles of HIV risk behaviors were identified: The high multiple-risk group mixed unsafe drug use with unsafe sexual practices and had higher prevalence of HIV; the second group practiced high-risk sex with non-consistent condom combined with methamphetamine use; the third group was a moderate-risk group with limited unsafe sexual practices; and the fourth was considered at "low-risk" as reportedly, most never had sex and never injected. The highest risk group included more female YPUD, living in HCMC, who used heroin and had unsafe sex with their regular partners. The second high-risk group included most of the MSM and all transgender people and frequently reported mental health disorders. CONCLUSIONS: The profiles of YPUD who are at risk of HIV vary according to age, location, and population group. Injecting YPUD are the most exposed to risk and need immediate attention. Sexual exposure to HIV is very common. Mental health is a major concern. Interventions need to be integrated in a differentiated but holistic approach.
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Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Uso Comum de Agulhas e Seringas/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Sexo sem Proteção/estatística & dados numéricos , Adolescente , Adulto , Análise por Conglomerados , Comorbidade , Feminino , Humanos , Masculino , Assunção de Riscos , População Urbana/estatística & dados numéricos , Vietnã/epidemiologia , Adulto JovemRESUMO
Cabozantinib, a multi-kinase inhibitor, is approved in the United States and European Union for treatment of patients with hepatocellular carcinoma following prior sorafenib treatment. In the Phase III CELESTIAL trial, hepatocellular carcinoma patients receiving cabozantinib showed longer overall survival (OS) and progression-free survival (PFS) than those receiving placebo. The approved cabozantinib (Cabometyx®) dose is 60 mg once daily with allowable dose modifications to manage adverse events (AE). Time-to-event Cox proportional hazard exposure-response (ER) models were developed to characterize the relationship between predicted cabozantinib exposure and the likelihood of various efficacy and safety endpoints. The ER models were used to predict hazard ratios (HR) for efficacy and safety endpoints for starting doses of 60, 40, or 20 mg daily. Statistically significant relationships between cabozantinib exposure and efficacy and safety endpoints were observed. For efficacy endpoints, predicted HR were lower for OS and PFS at 40 and 60 mg relative to the 20 mg dose: HR for death (OS) are 0.84 (40 mg) and 0.70 (60 mg); HR for disease progression/death (PFS) are 0.73 (40 mg) and 0.62 (60 mg). For safety endpoints, predicted HR were lower for palmar-plantar erythrodysaesthesia (PPE), diarrhea, and hypertension at 20 or 40 mg relative to the 60 mg dose: HR for PPE are 0.31 (20 mg) and 0.66 (40 mg); HR for diarrhea are 0.61 (20 mg) and 0.86 (40 mg); HR for hypertension are 0.46 (20 mg) and 0.76 (40 mg). The rate of dose modifications was predicted to increase in patients with lower cabozantinib apparent clearance. OS and PFS showed the greatest benefit at the 60 mg dose. However, higher cabozantinib exposure was predicted to increase the likelihood of AE and subsequent dose reductions appeared to decrease these risks.