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The objective of this study was to examine the association between the serum copper concentration and the prevalence of diabetes among US adults with hypertension using the data from the National Health and Nutrition Examination Survey (NHANES). The study population was selected from adults aged over 20 years old in the three survey cycles of NHANES from 2011 to 2016. Logistic regression model analyses were applied to determine the independent risky effect of copper to the prevalence of diabetes. Also, a restricted cubic spline (RCS) model was performed to explore the potential nonlinear association between serum copper concentration and the prevalence of diabetes. A total of 1786 subjects (742 cases and 1044 controls) were included, and 924 were men (51.7%), and 742 (41.5%) were diabetic. Compared with non-diabetic individuals, the concentration of serum copper in diabetic patients with hypertension was higher. After adjusting for age, sex, race, education, marital status, body mass index (BMI), family poverty income ratio (PIR), smoking, alcohol drinking, physical activity, systolic blood pressure (SBP), diastolic blood pressure (DBP), and hyperlipidemia, the highest quartile of serum copper concentration significantly increased the risk of diabetes as compared with the lowest quartile (OR: 1.38, 95% CI: 1.01-1.92, ptrend = 0.036). The results of RCS analysis showed significant non-linear relationship between serum copper concentration and prevalence of diabetes (p-non-linear = 0.010). This study finds that serum copper concentration are significantly associated with risk of diabetes in hypertensive patients, which suggests copper as an important risk factor of diabetes development.
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Diabetes Mellitus , Hipertensão , Adulto , Masculino , Humanos , Feminino , Inquéritos Nutricionais , Cobre , Prevalência , Diabetes Mellitus/epidemiologia , Hipertensão/epidemiologiaRESUMO
The aim of the present study was to explore the molecular mechanisms by which miR-193b-3p-trans-fected bone marrow mesenchymal stem cells (BMSCs) transplantation improves neurological impairment after traumatic brain injury (TBI) through sphingosine-1-phosphate receptor 3 (S1PR3)-mediated regulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway at the cellular and animal levels. BMSCs were transfected with miR-193b-3p. A TBI cell model was established by oxygen-glucose deprivation (OGD)-induced HT22 cells, and a TBI animal model was established by controlled cortical impact (CCI). Cell apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL), and cell activity was detected by a cell counting kit 8 (CCK-8) assay. Western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of related proteins and genes. In this study, transfection of miR-193b-3p into BMSCs significantly enhanced BMSCs proliferation and differentiation. Transfection of miR-193b-3p reduced the levels of the interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-alpha (TNF-α) inflammatory factors in cells and mouse models, and it inhibited neuronal apoptosis, which alleviated OGD-induced HT22 cell damage and neural function damage in TBI mice. Downstream experiments showed that miR-193b-3p targeting negatively regulated the expression of S1PR3, promoted the activation of the PI3K/AKT/mTOR signaling pathway, and inhibited the levels of apoptosis and inflammatory factors, which subsequently improved OGD-induced neuronal cell damage and nerve function damage in TBI mice. However, S1PR3 overexpression or inhibition of the PI3K/AKT/mTOR signaling pathway using the IN-2 inhibitor weakened the protective effect of miR-193b-3p-transfected BMSCs on HT22 cells. Transplantation of miR-193b-3p-transfected BMSCs inhibits neurological injury and improves the progression of TBI in mice through S1PR3-mediated regulation of the PI3K/AKT/mTOR pathway.
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Lesões Encefálicas Traumáticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , MicroRNAs , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Receptores de Esfingosina-1-Fosfato , Serina-Treonina Quinases TOR , Animais , Humanos , Masculino , Camundongos , Apoptose , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/genética , Lesões Encefálicas Traumáticas/terapia , Modelos Animais de Doenças , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Receptores de Esfingosina-1-Fosfato/metabolismo , Receptores de Esfingosina-1-Fosfato/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: Alzheimer's disease (AD) is the most common neurogenerative disorder without effective treatments. Defects in mitochondrial complex I are thought to contribute to AD pathogenesis. The aim of this study is to explore whether a novel gene therapy transducing yeast complex I gene NDI1 can be used to treat AD with severely reduced complex I function in cell and animal models. METHODS: The differentiated human neural cells were induced by Aß1-42 to establish the AD cell model, and adeno-associated virus serotype 9 (AAV9) was used to transduce yeast NDI1 into the cell model. Aß1-42 was injected into the hippocampus area of the brain to establish the AD mouse model. AAV9-NDI1 was injected stereotaxically into the hippocampus area to test the therapeutic effect. RESULTS: The expressed yeast complex I had an ameliorating effect on the defective function of human complex I and cellular pathological characteristics in the AD cell model. Furthermore, AAV9-NDI1 gene therapy in the hippocampus had a therapeutic effect on various aspects of mitochondrial function, histopathological characteristics and neurological defects in the AD mouse model. In addition, AAV9-NDI1 injection into the hippocampus of normal mice did not cause any adverse effect. CONCLUSIONS: Compensating mitochondrial complex I function with yeast NDI1 is effective for gene therapy in Aß-induced AD cell and mouse models. The results of this study offer a novel strategy and approach for treating AD types characterized by complex I abnormalities.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Modelos Animais de Doenças , Complexo I de Transporte de Elétrons , Terapia Genética , Mitocôndrias , Animais , Doença de Alzheimer/terapia , Doença de Alzheimer/patologia , Doença de Alzheimer/genética , Complexo I de Transporte de Elétrons/metabolismo , Complexo I de Transporte de Elétrons/genética , Humanos , Peptídeos beta-Amiloides/metabolismo , Mitocôndrias/metabolismo , Dependovirus/genética , Hipocampo/patologia , Hipocampo/metabolismo , Camundongos , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Fragmentos de Peptídeos , MasculinoRESUMO
Ginsenosides, the primary pharmacologically active constituents of the Panax genus, have demonstrated a variety of medicinal properties, including anticardiovascular disease, cytotoxic, antiaging, and antidiabetes effects. However, the low concentration of ginsenosides in plants and the challenges associated with their extraction impede the advancement and application of ginsenosides. Heterologous biosynthesis represents a promising strategy for the targeted production of these natural active compounds. As representative triterpenoids, the biosynthetic pathway of the aglycone skeletons of ginsenosides has been successfully decoded. While the sugar moiety is vital for the structural diversity and pharmacological activity of ginsenosides, the mining of uridine diphosphate-dependent glycosyltransferases (UGTs) involved in ginsenoside biosynthesis has attracted a lot of attention and made great progress in recent years. In this paper, we summarize the identification and functional study of UGTs responsible for ginsenoside synthesis in both plants, such as Panax ginseng and Gynostemma pentaphyllum, and microorganisms including Bacillus subtilis and Saccharomyces cerevisiae. The UGT-related microbial cell factories for large-scale ginsenoside production are also mentioned. Additionally, we delve into strategies for UGT mining, particularly potential rapid screening or identification methods, providing insights and prospects. This review provides insights into the study of other unknown glycosyltransferases as candidate genetic elements for the heterologous biosynthesis of rare ginsenosides.
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Ginsenosídeos , Glicosiltransferases , Ginsenosídeos/biossíntese , Ginsenosídeos/química , Ginsenosídeos/metabolismo , Glicosiltransferases/metabolismo , Saccharomyces cerevisiae , Estrutura Molecular , Panax/química , Difosfato de Uridina/metabolismo , Bacillus subtilis/enzimologia , Vias BiossintéticasRESUMO
The fruits of Amomum villosum are often considered a medicinal and food homologous material and have been found to have therapeutic effects in chronic enteritis, gastroenteritis, and duodenal ulcer. The aim of this study is to discover the anti-inflammatory active ingredients from dried ripe fruits of A. villosum and to elucidate the molecular mechanisms. We verified that the inhibitory activity of the ethyl acetate extract was superior to Dexamethasone (Dex), so we ultimately chose to study the ethyl acetate extract from the fruits of A. villosum. A total of 33 compounds were isolated from its ethyl acetate extract, including nine known diterpenoids (compounds 1-9), twelve known sesquiterpenoids (compounds 10-21), ten known phenolics (compounds 22, 23, 25-29, 31-33) and two new phenolics (24 and 30). On the basis of chemical evidences and spectral data analysis (UV, ECD, Optical rotation data, 1D and 2D-NMR, HR-ESI-MS, NMR chemical shift calculations), the structures of new compounds were elucidated. Among these compounds, isocoronarin D (5) was found to have good anti-inflammatory activity. Further research has found that isocoronarin D can down-regulate the protein levels of COX2 and NOS2, activate Nrf2/Keap1 and suppress NF-κB signaling pathway in LPS-induced RAW264.7 cells. In addition, isocoronarin D inhibited inflammasome assembly during inflammasome activation by hampering the binding of NLRP3 and ASC. Further evidence revealed that isocoronarin D suppressed the assembly of the NLRP3 inflammasome via blocking the formation of ASC specks. From these results, isocoronarin D may be the important bioactive compound of A. villosum and exhibits anti-inflammatory effects by regulating the NF-κB/Nrf2/NLRP3 axis in macrophages.
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Acetatos , Amomum , Diterpenos , Imidazóis , Sulfonamidas , Tiofenos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Amomum/química , Terpenos , NF-kappa B/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch , Frutas/química , Fator 2 Relacionado a NF-E2/metabolismo , Anti-Inflamatórios/farmacologia , Lipopolissacarídeos/farmacologiaRESUMO
The dried fruit of Amomum villosum is an important spice and medicinal plant that has received great attention in recent years due to its high content of bioactive components and its potential for food additives and drug development. However, the stems and leaves of A. villosum are usually disposed of as waste. Based on the study of the fruits of A. villosum, we also systematically studied its stems and leaves. Fourteen aromatic compounds (1-14) were isolated and identified from A. villosum, including five new compounds (1-5) and nine known compounds (6-14). Among them, compounds 2-5, 8-10, 12-13 were obtained from the fruits of A. villosum, and compounds 1, 6-7,11, 14 were isolated from the stems and leaves of A. villosum. Based on chemical evidence and spectral data analysis (UV, ECD, Optical rotation data, 1D and 2D-NMR, and HR-ESI-MS), the structures of new compounds were elucidated. Furthermore, all compounds were tested for their effects on the survival rate of BV-2 cells in the presence of hydrogen peroxide. Among them, compound 5 showed antioxidant effects. Through network pharmacology screening and the cell thermal shift assay (CETSA), the Phosphoglycerate Mutase 5 (PGAM5) protein was identified as the antioxidant target of compound 5. Molecular docking results showed that compound 5 maintains binding to PGAM5 by forming hydrogen bond interactions with Lys93 and Agr214. In summary, A. villosum had potential medicinal and food values due to the diverse bioactive components.
Assuntos
Amomum , Antioxidantes , Simulação de Acoplamento Molecular , Amomum/química , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Estrutura Molecular , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Sobrevivência Celular/efeitos dos fármacos , Humanos , Animais , Folhas de Planta/químicaRESUMO
Given the markedly different pharmacological activities between enantiomeric isomers, it is crucial to encourage the stereoselective determination of chiral drugs in the biological and pharmaceutical fields, and the combination of drugs makes this analysis more complicated and challenging. Herein, a capillary electrophoresis (CE) method for the enantioseparation of ofloxacin and duloxetine was established, enabling the simultaneous identification of four isomers in nonracemic mixtures with enantiomeric excess (ee%) values exceeding 5%. This was achieved through the integration of theoretical simulation and electron circular dichroism (ECD), all without reliance on individual standards. Molecular modeling explained and verified the migration time differences of these isomers in electrophoretic separation. Moreover, the correlation coefficients (R2 ) between the enantiomeric peak area differentials and ee% were both above 0.99. Recovery rates were quantified using bovine serum as the matrix, with results ranging from 93.32% to 101.03% (RSD = 0.030) and 92.69% to 100.52% (RSD = 0.028) for these two chiral drugs at an ee value of 23.1%, respectively.
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Eletroforese Capilar , Ofloxacino , Cloridrato de Duloxetina , Ofloxacino/análise , Estereoisomerismo , Eletroforese Capilar/métodosRESUMO
BACKGROUND Cryopreservation preserves male fertility, crucial in oncology, advanced age, and infertility. However, it damages sperm motility, membrane, and DNA. Zinc (Zn), an antioxidant, shows promise in improving sperm quality after thawing, highlighting its potential as a cryoprotectant in reproductive medicine. MATERIAL AND METHODS Gradient concentration of ZnSO4 (0, 12.5, 25, 50, and 100 µM) was added in the Glycerol-egg yolk-citrate (GEYC) cryopreservative medium as an extender. Alterations in sperm viability and motility parameters after cryopreservation were detected in each group. Sperm plasma membrane integrity (PMI), acrosome integrity (ACR), DNA fragment index (DFI), and changes in sperm mitochondrial function were examined, including: mitochondrial potential (MMP), sperm reactive oxygen species (ROS), and sperm ATP. RESULTS We found that 50 µM ZnSO4 was the most effective for the curvilinear velocity (VCL) and the average path velocity (VAP) of sperm after cryo-resuscitation. Compared to the Zn-free group, sperm plasma membrane integrity (PMI) was increased, DNA fragmentation index (DFI) was decreased, reactive oxygen species (ROS) was reduced, and mitochondrial membrane potential (MMP) was increased after cryorevival in the presence of 50 µM ZnSO4. CONCLUSIONS Zn ion is one of the antioxidants in the cell. The results of our current clinical study are sufficient to demonstrate that Zn can improve preserves sperm quality during cryopreservation when added to GEYC. The addition of 50 µM ZnSO4 increased curve velocity, mean path velocity, sperm survival (or plasma membrane integrity), and mitochondrial membrane potential while reducing ROS production and DNA breaks compared to GEYC thawed without ZnSO4.
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Criopreservação , Crioprotetores , Fragmentação do DNA , Potencial da Membrana Mitocondrial , Espécies Reativas de Oxigênio , Preservação do Sêmen , Motilidade dos Espermatozoides , Espermatozoides , Zinco , Masculino , Criopreservação/métodos , Humanos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Crioprotetores/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Motilidade dos Espermatozoides/efeitos dos fármacos , Preservação do Sêmen/métodos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Zinco/farmacologia , Zinco/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Análise do Sêmen , Sobrevivência Celular/efeitos dos fármacos , Adulto , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Acrossomo/efeitos dos fármacos , Acrossomo/metabolismo , CongelamentoRESUMO
Macrophytes are crucial in maintaining the equilibrium of aquatic ecosystems. However, the pattern of macrophyte-derived caffeic acid (CA) release under heavy metal stress is yet to be fully understood. More importantly, due to its functional groups, CA may be a precursor to the formation of disinfection by-products, posing threats to water ecology and even safety of human drinking water. This study analyzed the responses of CA released by Vallisneria natans (V. natans) and Pistia stratiotes (P. Stratiotes) when exposed to Cu2+ and Mn2+ stress. Additionally, the CA levels in two constructed wetland ponds were detected and the degradation kinetics of CA during chlorination were investigated. Results indicated that CA occurred in two constructed wetland ponds with the concentrations of 44.727⯵g/L (planted with V. natans) and 61.607⯵g/L (planted with P. Stratiotes). Notably, heavy metal stress could significantly affect CA release from V. natans and P. Stratiotes. In general, under Cu2+ stress, V. natans secreted far more CA than under Mn2+ stress, the level could reach up to 435.303⯵g/L. However, compared to V. natans, P. Stratiotes was less affected by Cu2+ and Mn2+ stress, releasing a maximum CA content of 55.582⯵g/L under 5â¯mg/L Mn2+ stress. Aquatic macrophytes secreted more CA in response to heavy metal stresses and protected macrophytes from harmful heavy metals. CA degradation followed the pseudo first-order kinetics model, and the chlorination of CA conformed to a second-order reaction. The reaction rate significantly accelerated as NaClO, pH, temperature and Br- concentration increased. A new pathway for CA degradation and a new DBP 2, 2, 3, 3-tetrachloropropanal were observed. These findings pointed at a new direction into the adverse effect of CA, potentially paving the way for new strategies to solve drinking water safety problems.
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Araceae , Ácidos Cafeicos , Água Potável , Metais Pesados , Poluentes Químicos da Água , Humanos , Ecossistema , Poluentes Químicos da Água/análise , Halogenação , Araceae/metabolismo , Metais Pesados/análiseRESUMO
In this study, two new (1, 13) and fourteen known (2-12, 14-16) compounds were isolated from the branches and leaves of Daphne retusa. On the basis of chemical evidence and spectral data analysis (UV, ECD NMR, and HR-ESI-MS), the structures of new compounds were elucidated. Furthermore, all compounds have been tested for their inhibitory effects on NO production in LPS-induced RAW 264.7 cells, and compound 3 showed obvious inhibitory effect. Through target screening and molecular docking technology, potential binding targets for compound 3 to exert anti-inflammatory effects have been predicted.
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This study analyzes panel data of Chinese cities from 2003 to 2018 as a sample in the context of the dual circulation strategy in China to ascertain the impact of urban healthcare development on medical collaborative innovation efficiency by using the GS2SLS method. Furthermore, it empirically examines the influence mechanism of regional healthcare development on medical collaborative innovation efficiency by using a threshold regression model. Additionally, we identified the heterogeneity of this impact in different cities. The results show the following: (1) There is a significant positive spatial correlation between regional healthcare development and medical collaborative innovation efficiency; (2) Under the dual circulation strategy, the regional investment level in international circulation has the most significant role in the overall strategy, and domestic circulation has been significantly improved after the launch of the innovation-driven strategy; (3) The results of the threshold test show that while domestic and international circulation promote the efficiency of collaborative innovation by 0.83, the promotion effect is more obvious under a higher regional healthcare development level. The research in this paper can provide specific guidance for the development of China's healthcare industry under the background of dual-cycle strategy, and can also provide valuable reference for developing countries in the world.
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Cidades , China , Humanos , Comportamento Cooperativo , Atenção à Saúde/organização & administração , Eficiência OrganizacionalRESUMO
Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated neuropathy. While CIDP typically affects the peripheral nerves in the limbs, involvement of cranial nerves is atypical, and cases of muscle atrophy secondary to cranial nerve involvement are exceptionally rare. A 30-year-old female patient, who complained of numbness and weakness in her limbs, was diagnosed with CIDP after experiencing atrophy of the tongue and sternocleidomastoid muscles, along with tongue muscle fibrillation during a neurological examination. Additionally, the patient had hypothyroidism caused by Hashimoto's thyroiditis. Cerebrospinal fluid tests indicated albumincytological dissociation. Electrophysiological examination results confirmed the diagnosis of typical CIDP. Glucocorticoid treatment, a standard therapy for CIDP, led to a significant improvement in the patient's symptoms, including the regeneration of her tongue muscles. A literature review revealed only eight cases of CIDP with hypoglossal nerve involvement, and this case represents the first documentation of concurrent sternocleidomastoid muscle atrophy. Although muscle atrophy from cranial nerve involvement is infrequent in CIDP, the positive response to treatment is encouraging.
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Background: Reduced work readiness is associated with elevated turnover rates, necessitating efforts to enhance the positive work readiness of newly graduated nurses to alleviate the shortage in the nursing workforce. Research into the work readiness of recent nursing graduates in China is still in its infancy. Most studies employ quantitative research methods, and further exploration of the self-perception of work readiness among new nurses in China is required. Objectives: This study aimed to investigate genuine experiences and self-perceptions of work readiness among new graduate nurses. Design: A qualitative descriptive study. Methods: Sixteen new nurses from a provincial tertiary hospital in China were included in this study, which adhered to the consolidated criteria for reporting qualitative research (COREQ) checklist for reporting. The data collection process involved conducting semi-structured interviews from September to October 2021. Inductive content analysis was employed to analyze the interview data. Results: The study identified four themes encompassing new nurses' real-life experiences and self-perceptions of work readiness: psychological stress, emotional conflict, empathy fatigue, and ethical dilemmas. Psychological stress comprised three subthemes: knowledge and skill deficits, communication barriers, and fear. Empathy fatigue was primarily characterized by psychological and physical symptoms. Ethical dilemmas involved conflicts over differences in values and between clinical reality and standardized nursing practice. Conclusion: Drawing from the self-perceptions of work readiness among new nurses found in this study, nursing administrators and educators must enhance the existing transition support program for new nurses. Additionally, the establishment of individualized training programs is recommended to further improve the work readiness of new nurses.
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Autophagy is a process of self-renewal in cells, which not only provides the necessary nutrients for cells, but also clears necrotic organelles. Autophagy disorders are closely related to diseases such as cancer. UNC-51-like kinase 1 (ULK1) is a serine/threonine protein kinase that plays a crucial role in receiving input from energy and nutrient sensors, activating autophagy to maintain cellular homeostasis under stressful conditions. In recent years, targeting ULK1 has become a highly promising strategy for cancer treatment. This review introduces the regulatory mechanism of ULK1 in autophagy through the AMPK/mTOR/ULK1 pathway and reviews the research progress of ULK1 activators and inhibitors and their applications in cancer treatment. In addition, we analyze the binding modes between ULK1 and modulators through virtual molecular docking, which will provide a reliable basis and theoretical guidance for the design and development of new therapeutic drugs targeting ULK1.
Assuntos
Proteínas Quinases Ativadas por AMP , Neoplasias , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Simulação de Acoplamento Molecular , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Autofagia , Neoplasias/tratamento farmacológicoRESUMO
Six undescribed alkaloids, neotuberostemonol C (1), dehydrostenines C-D (2-3), tuberostemonines Q-R (10-11), and (6R,8R,8aR)-8-hydroxy-6-methyl-hexahydroindolizin-5-one (32), along with twenty-six known analogues were isolated from the dried roots of Stemona tuberosa Lour. The structures and absolute stereochemistry of these compounds were delineated by extensive spectroscopy (1D NMR, 2D NMR, HRESIMS), quantum chemical calculations of the electronic circular dichroism spectra, and pyridine-induced solvent shifts. Tuberostemonines Q-R (10-11) represent tuberostemonine skeleton alkaloids possessing an α-methyl-γ-butyrolactone moiety attached to C-3. In addition, all these isolated compounds were assayed for their inhibitory activity against LPS-induced NO production in RAW264.7 cells using Griess assay.
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Alcaloides , Stemonaceae , Stemonaceae/química , Estrutura Molecular , Alcaloides/química , Raízes de Plantas/química , Anti-Inflamatórios/farmacologiaRESUMO
Synthetic preservatives are widely used in the food industry to control spoilage and growth of pathogenic microorganisms, inhibit lipid oxidation processes and extend the shelf life of food. However, synthetic preservatives have some side effects that can lead to poisoning, cancer and other degenerative diseases. With the improvement of living standards, people are developing safer natural preservatives to replace synthetic preservatives, including plant derived preservatives (polyphenols, essential oils, flavonoids), animal derived preservatives (lysozyme, antimicrobial peptide, chitosan) and microorganism derived preservatives (nisin, natamycin, ε-polylysine, phage). These natural preservatives exert antibacterial effects by disrupting microbial cell wall/membrane structures, interfering with DNA/RNA replication and transcription, and affecting protein synthesis and metabolism. This review summarizes the natural bioactive compounds (polyphenols, flavonoids and terpenoids, etc.) in these preservatives, their antioxidant and antibacterial activities, and safety evaluation in various products.
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Antioxidantes , Conservantes de Alimentos , Conservantes de Alimentos/farmacologia , Antioxidantes/farmacologia , Antibacterianos/farmacologia , Conservação de Alimentos/métodos , Animais , Inocuidade dos Alimentos , Humanos , Flavonoides/farmacologia , Polifenóis/farmacologia , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Terpenos/farmacologiaRESUMO
Rhododendron dauricum L. is a perennial herb belonging to the genus Rhododendron, commonly utilized in formulations for treating coughs and bronchitis, as well as in herbal teas for enhancing immunity and preventing tracheitis. In this study, fifteen previously undescribed chromene meroterpenoids (1a/1b-4a/4b, 5-8, 9b, 10a, 11b), along with twenty-one known compounds were isolated from the dried twigs and leaves of Rhododendron dauricum L. Of these, (-)-rhodonoid E (9b), (+)-confluentin (10a), and (-)-rubiginosin D (11b) were separated for the first time by chiral HPLC separation. The elucidation of their structures, including absolute configurations, was achieved through a combination of techniques such as NMR, HRESIMS, modified Mosher's method and quantum-chemical calculation of electronic circular dichroism (ECD) spectra. Seven pairs of enantiomers, compounds 1a/1b-4a/4b and 9a/9b-11a/11b, were initially obtained in a racemic manner and were further separated by chiral HPLC preparation. The biological assessment of these compounds against NO production was conducted in the LPS-induced RAW264.7 macrophage cells model. Compounds 9a, 9b, and 11a displayed inhibitory rates exceeding 80%, with IC50 values ranging from 8.69 ± 0.94 to 13.01 ± 1.11 µM. A preliminary examination of the structure-activity relationship (SAR) for these isolates indicated that chromene meroterpenoids with α, ß-unsaturated ketone carbonyl and Δ12(13) double bond functionalities exhibited enhanced anti-inflammatory properties.
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Anti-Inflamatórios , Benzopiranos , Rhododendron , Terpenos , Rhododendron/química , Terpenos/química , Terpenos/farmacologia , Terpenos/isolamento & purificação , Camundongos , Células RAW 264.7 , Animais , Benzopiranos/farmacologia , Benzopiranos/química , Benzopiranos/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Estrutura Molecular , Relação Estrutura-Atividade , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico/antagonistas & inibidores , Relação Dose-Resposta a DrogaRESUMO
Purpose: The objective of this study was to investigate latent classes of oral health and the factors associated with them in acutely admitted elderly inpatients. Patients and Methods: A cross-sectional study was conducted using purposive sampling to survey Chinese older-adult acutely inpatients. Data was collected utilizing several instruments, including a general information questionnaire, Brief Oral Health Status Examination (BOHSE), Oral Frailty Index-8 (OFI-8), Mini-Nutritional Assessment Short Form (MNA-SF), and Frailty Screening Questionnaire (FSQ). Latent class analysis was applied to identify distinct categories of oral health among elderly inpatients, and multinomial logistic regression was employed to analyze the factors associated with different oral health categories. Results: In this study, a total of 504 elderly patients were ultimately included, leading to the identification of three latent classes of oral health: "oral health-low level group (41.27%)", "oral health-moderate level group (25.4%)", and "oral health-high level group (33.33%)". The findings revealed that patients with advanced age, elevated neutrophil percentage, and higher C-reactive protein (CRP) values were more likely to be classified in the low oral health group. Additionally, individuals experiencing malnutrition and frailty had a higher risk of falling into the low oral health category. Those with comorbidities and oral frailty were more prevalent in the moderate oral health group. At the same time, elderly patients with higher BMI (22.95±3.043) ratios were more likely to be categorized in the high oral health group. Conclusion: This study sheds light on three distinct latent classes of oral health among acutely admitted elderly inpatients. These findings underscore the importance of healthcare professionals focusing on the assessment and health education of elderly patients' oral health. Furthermore, personalized interventions should be developed to promote healthy aging, with particularly attention to enhancing oral health outcomes in this population.
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As currently the most common metabolic disease, type 2 diabetes mellitus (T2DM) has shown a continuous increase in the number of patients in recent decades. Most anti-T2DM drugs tend to cause some side effects. Given the pathogenesis of T2DM, natural products have emerged as an important source of anti-T2DM drugs. This article reviews natural products with potential hypoglycemic activity from 2019 to 2023. A total of 200 previously natural products were discovered on SciFinder, PubMed and Web of Science. These products were categorized based on their structural frameworks and their biological activities were summarized. Although the mechanisms of action of most compounds are unclear, these compounds could still serve as candidates for the development of lead compounds. Therefore, further structure and activity research of natural products will significantly contribute to the development of potential anti-T2DM drugs.
Assuntos
Produtos Biológicos , Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Humanos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Objective: Previous studies have confirmed a positive correlation between the Triglyceride-Glucose (TyG) index and future risk of diabetes. However, evidence of this association in non-obese young populations remains limited. This study aims to investigate the relationship between the TyG index and the future risk of diabetes among non-obese young adults. Methods: This retrospective cohort study included 113,509 non-obese young adults from China and 9,549 from Japan. The mean age was 35.73 ± 6.38 years, and 56,469 participants (45.89%) were male. The median follow-up duration was 3.38 years. The association between baseline TyG index and risk of diabetes was examined using Cox proportional hazards regression models. Non-linear relationships between the TyG index and risk of diabetes were identified using cubic splines and smoothed curve fitting in the Cox models. Sensitivity and subgroup analyses were also conducted. Results: After adjusting for covariates, the results indicated a positive correlation between the TyG index and risk of diabetes in non-obese young adults (HR=3.57, 95% CI: 2.92-4.36, P<0.0001). A non-linear relationship was observed with an inflection point at 7.3. The HR to the right of this inflection point was 3.70 (95% CI: 3.02-4.52, P<0.0001), while to the left, it was 0.34 (95% CI: 0.06-1.88, P=0.2161). The robustness of our findings was confirmed through a series of sensitivity analyses and subgroup analyses. Conclusion: This study reveals a positive and non-linear association between the TyG index and risk of diabetes among non-obese young adults. Interventions aimed at reducing the TyG index by lowering triglycerides or fasting glucose levels could substantially decrease the future likelihood of developing diabetes in this population.