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Nanoceria have demonstrated a wide array of catalytic activity similar to natural enzymes, holding considerable significance in the colorimetric detection of alkaline phosphatase (ALP), which is a biomarker of various biological disorders. However, the issues of physiological stability and formation of protein corona, which are strongly related to their surface chemistry, limit their practical application. In this work, CeO2 nanoparticles characterized by enhanced dimensional uniformity and specific surface area were synthesized, followed by encapsulation with various polymers to further increase catalytic activity and physiological stability. Notably, the CeO2 nanoparticles encapsulated within each polymer exhibited improved catalytic characteristics, with PAA-capped CeO2 exhibiting the highest performance. We further demonstrated that the PAA-CeO2 obtained with enhanced catalytic activity was attributed to an increase in surface negative charge. PAA-CeO2 enabled the quantitative assessment of AA activity within a wide concentration range of 10 to 60 µM, with a detection limit of 0.111 µM. Similarly, it allowed for the evaluation of alkaline phosphatase activity throughout a broad range of 10 to 80 U/L, with a detection limit of 0.12 U/L. These detection limits provided adequate sensitivity for the practical detection of ALP in human serum.
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OBJECTIVES: Haplogroup C2a-M48 is the predominant paternal lineage of Tungusic-speaking populations, one of the largest population groups in Siberia. Up until now, the origins and dispersal of Tungusic-speaking populations have remained unclear. In this study, the demographic history of Tungusic-speaking populations was explored using the phylogenetic analysis of haplogroup C2a-M86, the major subbranch of C2a-M48. MATERIALS AND METHODS: In total, 18 newly generated Y chromosome sequences from C2a-M48 males and 20 previously available Y-chromosome sequences from this haplogroup were analyzed. A highly revised phylogenetic tree of haplogroup C2a-M86 with age estimates was reconstructed. Frequencies of this lineage in the literature were collected and a comprehensive analysis of this lineage in 13 022 individuals from 245 populations in Eurasia was performed. RESULTS: The distribution map of C2a-M48 indicated the most probable area of origin and diffusion route of this paternal lineage in North Eurasia. Most C2a-M86 samples from Tungusic-speaking populations belonged to the sublineage C2a-F5484, which emerged about 3300 years ago. We identified six unique sublineages corresponding to the Manchu, Evenks, Evens, Oroqen, and Daurpopulations; these sublineages diverged gradually over the past 1900 years. Notably, we observed a clear north-south dichotomous structure for sublineages derived from C2a-F5484, consistent with the internal north-south divergence of Tungusic languages and ethnic groups. CONCLUSIONS: We identified the important founding paternal haplogroup, C2a-F5484, for Tungusic-speaking populations as well as numerous unique subgroups of this haplogroup. We propose that the timeframe for the divergence of C2a-F5484 corresponds with the early differentiation of ancestral Tungusic-speaking populations.
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Cromossomos Humanos Y/genética , Etnicidade/genética , Migração Humana , Filogenia , Haplótipos , Humanos , Masculino , Sibéria/etnologiaRESUMO
Mitochondria, as the energy factory of most cells, are not only responsible for the generation of adenosine triphosphoric acid (ATP) but also essential targets for therapy and diagnosis of various diseases, especially cancer. The safe and potential nanoplatform which can deliver various therapeutic agents to cancer cells and mitochondrial targeted imaging is urgently required. Herein, Au nanoparticles (AuNPs), mesoporous silica nanoparticles (MSN), cationic ligand (triphenylphosphine (TPP)), doxorubicin (DOX), and carbon nanodots (CDs) were utilized to fabricate mitochondrial targeting drug delivery system (denoted as CDs(DOX)@MSN-TPP@AuNPs). Since AuNPs, as the gatekeepers, can be etched by intracellular glutathione (GSH) via ligand exchange induced etching process, DOX can be released into cells in a GSH-dependent manner which results in the superior GSH-modulated tumor inhibition activity. Moreover, after etching by GSH, the CDs(DOX)@MSN-TPP@AuNPs can serve as promising fluorescent probe (λex = 633 nm, λem = 650 nm) for targeted imaging of mitochondria in living cells with near-infrared fluorescence. The induction of apoptosis derived from the membrane depolarization of mitochondria is the primary anti-tumor route of CDs(DOX)@MSN-TPP@AuNPs. As a kind of GSH-responsive mitochondrial targeting nanoplatform, it holds great promising for effective cancer therapy and mitochondrial targeted imaging. The mitochondrial targeting drug delivery system was fabricated by AuNPs, MSN, TPP, and CDs. The nanoplatform can realize redox-responsive drug delivery and targeted imaging of mitochondria in living cells to improve the therapeutic efficiency and security.
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Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Corantes Fluorescentes/química , Nanopartículas Metálicas/química , Mitocôndrias/metabolismo , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Carbono/química , Carbono/toxicidade , Linhagem Celular Tumoral , Doxorrubicina/química , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Corantes Fluorescentes/toxicidade , Glutationa/metabolismo , Ouro/química , Ouro/toxicidade , Humanos , Nanopartículas Metálicas/toxicidade , Camundongos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Compostos Organofosforados/química , Compostos Organofosforados/toxicidade , Pontos Quânticos/química , Pontos Quânticos/toxicidade , Dióxido de Silício/química , Dióxido de Silício/toxicidade , Prata/química , Prata/toxicidadeRESUMO
A redox-responsive chemodynamic therapy (CDT)-based theranostic system composed of hollow mesoporous MnO2 (H-MnO2), doxorubicin (DOX), and fluorescent (FL) carbon nanodots (CDs) is reported for the diagnosis and therapy of cancer. In general, since H-MnO2 can be degraded by intracellular glutathione (GSH) to form Mn2+ with excellent Fenton-like activity to generate highly reactive ·OH, the normal antioxidant defense system can be injured via consumption of GSH. This in turn can potentiate the cytotoxicity of CDT and release DOX. The cancer cells can be eliminated effectively by the nanoplatform via the synergistic effect of chemotherapy and CDT. The FL of CDs can be restored after H-MnO2 is degraded which blocked the fluorescence resonance energy transfer process between CDs as an energy donor and H-MnO2 as an FL acceptor. The GSH can be determined by recovery of the FL and limit of detection is 1.30 µM with a linear range of 0.075-0.825 mM. This feature can be utilized to efficiently distinguish cancerous cells from normal ones based on different GSH concentrations in the two types of cells. As a kind of CDT-based theranostic system responsive to GSH, simultaneously diagnostic (normal/cancer cell differentiation) and therapeutic function (chemotherapy and CDT) in a single nanoplatform can be achieved. The redox-responsive chemodynamic therapy (CDT)-based theranostic system is fabricated by H-MnO2, DOX, and fluorescent CDs. The nanoplatform can realize simultaneously diagnostic (normal/cancer cell differentiation) and therapeutic function (chemotherapy and CDT) to improve the therapeutic efficiency and security.
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Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Corantes Fluorescentes/química , Glutationa/análise , Medicina de Precisão/métodos , Pontos Quânticos/química , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Carbono/química , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Doxorrubicina/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Tratamento Farmacológico , Humanos , Limite de Detecção , Camundongos , Molibdênio/química , Neoplasias/diagnóstico , Óxidos/química , Espectrometria de FluorescênciaRESUMO
Human Y-chromosome haplogroup C2b-F1067 is one of the dominant paternal lineages of populations in Eastern Eurasia. In order to explore the origin, diversification, and expansion of this haplogroup, we generated 206 new Y-chromosome sequences from C2b-F1067 males and coanalyzed 220 Y-chromosome sequences of this haplogroup. BEAST software was used to reconstruct a revised phylogenetic tree of haplogroup C2b-F1067 with age estimates. The revised phylogeny of C2b-F1067 included 155 sublineages, 1986 non-private variants, and >6000 private variants. The age estimation suggested that the initial splitting of C2b-F1067 happened at about 32.8 thousand years ago (kya) and the major sublineages of this haplgroup experienced continuous expansion in the most recent 10,000 years. We identified numerous sublineages that were nearly specific for Korean, Mongolian, Chinese, and other ethnic minorities in China. In particular, we evaluated the candidate-specific lineage for the Dayan Khan family and the Confucius family, the descendants of the ruling family of the Chinese Shang dynasty. These findings suggest that ancient populations with varied C2b-F1067 sublineages played an important role during the formation of most modern populations in Eastern Eurasia, and thus eventually became the founding paternal lineages of these populations.
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Povo Asiático/genética , Cromossomos Humanos Y/genética , Etnicidade/genética , Haplótipos/genética , Migração Humana , Filogenia , Povo Asiático/classificação , Povo Asiático/história , Etnicidade/história , Ásia Oriental , História Antiga , Humanos , Masculino , Paternidade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Oxygen-containing heterocycles are widely encountered in natural products that display diverse pharmacological properties and have potential benefits to human health. The formation of O-heterocycles catalyzed by different types of enzymes in the biosynthesis of natural products not only contributes to the structural diversity of these compounds, but also enriches our understanding of nature's ability to construct complex molecules. This minireview focuses on the various modes of enzymatic O-heterocyclization identified in natural product biosynthesis and summarizes the possible mechanisms involved in ring closure.
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Produtos Biológicos/metabolismo , Enzimas , Compostos Heterocíclicos/metabolismo , Oxigênio/metabolismo , Catálise , Ciclização , Enzimas/química , Enzimas/metabolismoRESUMO
Patients with type 2 diabetes mellitus (T2DM) are usually with poor immunity and easier to suffer from cancer and microbial infections. Herein, we report an efficient anti-diabetic medicinal mushroom, Coriolus versicolor (CV). This study aimed to investigate the anti-diabetic and anti-insulin-resistance effects of CV aqueous extract in myoblasts (L6 cells) and skeletal muscle of T2DM rat. Our results showed that CV extract treatment significantly reduced blood glucose levels of T2DM rats, whereas CV extract increased glucose consumption in insulin resistant L6 cells. Besides, the translocation and expression of glucose transporter 4 were enhanced by CV extract, which indicated that CV extract was effective in diabetic skeletal muscle. Moreover, CV extract treatments resulted in remarkable anti-insulin-resistance effects, which was reflected by the change of gene and protein expression levels in PI3K/Akt and p38 MAPK pathways. PI3K inhibitor, LY29004, and p38 MAPK inhibitor, SB203580 confirmed it further. In conclusion, our results demonstrated that the CV extract exhibited anti-diabetic and anti-insulin-resistance effects in diabetic skeletal muscle, and the effects were mediated by PI3K/Akt and p38 MAPK pathways. These findings are remarkable when considering the use of commercially available CV by diabetic patients who also suffer from cancer or microbial infections.
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Agaricales/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Resistência à Insulina/fisiologia , Músculo Esquelético/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Masculino , Ratos , Ratos Wistar , Transdução de SinaisRESUMO
As a commercial antibiotic, bicyclomycin (BCM) is currently the only known natural product targeting the transcription termination factor rho. It belongs to a family of highly functionalized diketopiperazine (DKP) alkaloids and bears a unique O-bridged bicyclo[4.2.2]piperazinedione ring system, a C1 triol, and terminal exo-methylene groups. We have identified and characterized the BCM biosynthetic pathway by heterologous biotransformations, inâ vitro biochemical assays, and one-pot enzymatic synthesis. A tRNA-dependent cyclodipeptide synthase guides the heterodimerization of leucine and isoleucine to afford the DKP precursor; subsequently, six redox enzymes, including five α-ketoglutarate/Fe2+ -dependent dioxygenases and one cytochrome P450 monooxygenase, regio- and stereoselectively install four hydroxy groups (primary, secondary, and two tertiary), an exo-methylene moiety, and a medium-sized bridged ring through the functionalization of eight unactivated C-H bonds.
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Antibacterianos/metabolismo , Oxirredutases/química , Antibacterianos/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Carbono/química , Cromatografia Líquida , Dimerização , Genes Bacterianos , Hidrogênio/química , Espectrometria de Massas , Família Multigênica , Peptídeo Sintases/metabolismo , RNA de Transferência/química , Streptomyces/genéticaRESUMO
Aromatic-fused γ-pyrones are structural features of many bioactive natural products and valid scaffolds for medicinal chemistry. However, the enzymology of their formation has not been completely established. Now it is demonstrated that TxnO9, a CalC-like protein belonging to a START family, functions as an unexpected anthraquinone-γ-pyrone synthase involved in the biosynthesis of antitumor antibiotic trioxacarcinâ A (TXN-A). Structural analysis by NMR identified a likely substrate/product-binding mode and putative key active sites of TxnO9, which allowed an enzymatic mechanism to be proposed. Moreover, a subset of uncharacterized homologous proteins bearing an unexamined Lys-Thr dyad exhibit the same function. Therefore, the functional assignment and mechanistic investigation of this γ-pyrone synthase elucidated an undescribed step in TXN-A biosynthesis, and the discovery of this new branch of polyketide heterocyclases expands the functions of the START superfamily.
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Aminoglicosídeos/biossíntese , Antraquinonas/química , Antibióticos Antineoplásicos/biossíntese , Ligases/metabolismo , Policetídeos/metabolismo , Pironas/química , Aminoglicosídeos/química , Antibióticos Antineoplásicos/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura MolecularRESUMO
Apart from its vital role as the terminal electron acceptor in oxidative phosphorylation in nature, dioxygen also serves as a universal agent which diversifies natural products by oxidative transformations. Ferrous iron and α-ketoglutarate (αKG)-dependent dioxygenases (αKGDs) are versatile enzymes that use dioxygen as an oxidant to catalyse various reactions via CH bond activation, including hydroxylation, dealkylation, desaturation, epoxidation, epimerisation, halogenation, cyclisation, peroxide formation, and ring expansion/contraction reactions. This review updates the reported αKGDs that catalyse reactions related to microbial natural product biosynthesis in the past 10 years. We hope that the versatility of αKGDs shown here can serve as an inspiration for future engineering and catalyst design, which could provide alternative methods to meet the on-going demand for fine chemicals and pharmaceutics.
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Bactérias/enzimologia , Produtos Biológicos/metabolismo , Complexo Cetoglutarato Desidrogenase/metabolismo , Oxirredução , Produtos Biológicos/química , Catálise , Cristalografia por Raios X , Compostos Ferrosos/metabolismo , Hidroxilação , Ferro/metabolismo , Complexo Cetoglutarato Desidrogenase/química , Complexo Cetoglutarato Desidrogenase/genética , Oxigênio/metabolismoRESUMO
BACKGROUND This study aimed to establish an easy, safe, and cost-saving intestinal anastomotic method. MATERIAL AND METHODS Between January 2014 and February 2016, a total of 150 patients with gastric cancer who underwent surgery in the Department of General Surgery of Xuzhou Medical University Affiliated Hospital were divided into 2 groups: the treatment group (80) using new hand-sewn anastomoses, and the control group (70) using stapled anastomoses. Briefly, a new hand-sewn anastomosis of continuous suture without inversion was performed, with the first layer encompassing the entire layer of the intestinal wall. The edge was about 5 mm, and the stitch spacing was about 6 mm. Continuous suturing was performed only in the seromuscular layer of intestinal wall for the second layer, with the same edge and stitch spacing as the first layer. All 70 patients in the control group underwent intestinal stapled anastomoses. Surgical anastomotic time and cost, postoperative anastomotic bleeding, leakage, and stricture were recorded and analyzed. RESULTS The surgical anastomotic time using the new method was relatively short compared with the control group (8±1.6 min vs. 9±2.8 min), and the cost of anastomosis using the new method was significantly lower compared to the control group ($30±6.8 vs. $1000±106.2). The new method exhibited lower anastomotic bleeding (0/80 vs. 2/70) and anastomotic leakage (0/80 vs. 1/70), but similar anastomotic stricture (0/80 vs. 0/70). CONCLUSIONS Our results suggest the new hand-sewn intestinal anastomosis is a safe, easy-to-learn, cost-saving, and time-saving method that also avoids some of the drawbacks of the stapled anastomoses.
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Anastomose Cirúrgica/métodos , Intestinos/cirurgia , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/economia , Estudos de Casos e Controles , Demografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Complicações Pós-Operatórias/etiologia , Fatores de TempoRESUMO
AIM: This study sought to explore the exact mechanism of Matrine inhibited migration and invasion of human pancreatic cancer cells. METHODS: HPAC or Capan-1 cells were cultured in completed RPMI-1640 medium, contained with 50 µg/ml Matrine or 0.05 µg/ml docetaxel, respectively. Cell viability was evaluated by spectrophotometric analysis using MTT assay. Wound healing assay and transwell approach were used to detect the effects of Matrine on HPAC cell migration and invasion. Western Blot and RT-PCR were performed to detect the expressions of MT1-MMP, Wnt and ß-Catenin. CHIP assay was used to detect whether the MT1-MMP transcription activity correlated with Wnt signaling pathway. RESULTS: MTT results indicated that cell proliferration was inhibited by Matrine at a range of concentrations, especially at high dose. We further found that Matrine treatment significantly induced cell migration and invasion decreased. Interestingly, the expression of MT1-MMP decreased evidently upon Matrine treatment, paralleled with the expressions of Wnt and ß-Catenin detected by Western Blot and RT-PCR assay. Further analysis of MT1-MMP transcription activity revealed that Matrine reduced the expression of MT1-MMP mediated by Wnt signaling pathway. CONCLUSION: Matrine play a vital role in inhibiting HPAC cellular migration and invasion through down-regulating the expression of MT1-MMP via Wnt signaling pathway.
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The aroma types of cream cheese affect its commercial value and consumer acceptability. However, the types of volatile substances and sensory characteristics of cream cheese at different fermentation stages are still unclear. Therefore, in this study, headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) and headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) were used to analyze the volatile substances in cream cheese fermentation. Orthogonal partial least squares discriminant analysis (OPLS-DA), odor activity value (OAV), relative odor activity value (ROAV) and variable projection importance (VIP) were used to identify the characteristic flavor substances in cream cheese fermentation. Finally, the relationship between key flavor substances and sensory characteristics was determined by partial least squares (PLS) analysis. A total of 34 and 36 volatile organic compounds were identified by HS-SPME-GC-MS and HS-GC-MS, respectively, and 14 characteristic flavor substances were found, based on VIP, ROAV and OAV models. Combined with sensory analysis and flavor substance changes, it was found that the cream cheese fermented for 15 d had the best flavor and taste. This study reveals the characteristics and contribution of volatile substances in cream cheese at different fermentation stages, which provides new insights into improving flavor and quality control.
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Actinobacteria, the bacterial phylum most renowned for natural product discovery, has been established as a valuable source for drug discovery and biotechnology but is underrepresented within accessible genome and strain collections. Herein, we introduce the Natural Products Discovery Center (NPDC), featuring 122,449 strains assembled over eight decades, the genomes of the first 8490 NPDC strains (7142 Actinobacteria), and the online NPDC Portal making both strains and genomes publicly available. A comparative survey of RefSeq and NPDC Actinobacteria highlights the taxonomic and biosynthetic diversity within the NPDC collection, including three new genera, hundreds of new species, and ~7000 new gene cluster families. Selected examples demonstrate how the NPDC Portal's strain metadata, genomes, and biosynthetic gene clusters can be leveraged using genome mining approaches. Our findings underscore the ongoing significance of Actinobacteria in natural product discovery, and the NPDC serves as an unparalleled resource for both Actinobacteria strains and genomes.
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Neogrisemycin (1) was isolated from recombinant Streptomyces albus J1074 strain SB4061 expressing an engineered thioangucycline (TAC) biosynthetic gene cluster (BGC). The structure and absolute configuration of 1 were established by a combination of mass spectrometry, nuclear magnetic resonance, and single-crystal X-ray diffraction analyses. Like the TACs, 1 was also proposed to derive non-enzymatically from the common epoxide (8), the nascent product encoded by the tac BGC, mediated by endogenous hydrogen trisulfide.
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Streptomyces griseus , Streptomyces , Streptomyces/genética , Família Multigênica , Espectroscopia de Ressonância MagnéticaRESUMO
Previous studies demonstrated Y chromosome haplogroup C2a-M48-SK1061 is the only founding paternal lineage of all Tungusic-speaking populations. To infer the differentiation history of these populations, we studied more sequences and constructed downstream structure of haplogroup C2a-M48-SK1061 with better resolution. In this study, we generated 100 new sequences and co-analyzed 140 sequences of C2a-M48-SK1061 to reconstruct a highly revised phylogenetic tree with age estimates. We also performed the analysis of the geographical distribution and spatial autocorrelation of sub-branches. Dozens of new sub-branches were discovered, many sub-branches were nearly unique for Ewenki, Evens, Oroqen, Xibe, Manchu, Daur, and Mongolian. The topology of these unique sub-branches is the key evidence for understanding the complex evolutionary relationship between different Tungusic-speaking populations. The revised phylogeny provided a clear pattern for the differentiation history of haplogroup C2a-M48-SK1061 in the past 2,000 years. This study showed that the divergence pattern of founder lineage is essential to understanding the differentiation history of populations.
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Lipolysis and flavor development during fermentation of sour cream were studied by evaluating the physicochemical changes, sensory differences and volatile components. The fermentation caused significant changes in pH, viable count and sensory evaluation. The peroxide value (POV) decreased after reaching the maximum value of 1.07 meq/kg at 15 h, while thiobarbituric acid reactive substances (TBARS) increased continuously with the accumulation of secondary oxidation products. The Free fatty acids (FFAs) in sour cream were mainly myristic, palmitic and stearic. GC-IMS was used to identify the flavor properties. A total of 31 volatile compounds were identified, among which the contents of characteristic aromatic substances such as ethyl acetate, 1-octen-3-one and hexanoic acid were increased. The results suggest that lipid changes and flavor formation in sour cream are influenced by fermentation time. Furthermore, flavor compounds may be related to lipolysis such as 1-octen-3-one and 2- heptanol were also observed.
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Lipólise , Compostos Orgânicos Voláteis , Cetonas , Alimentos , FermentaçãoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia minax Hance, whose seeds are known as "Ku-shi-lian" in China, have been used in Chinese folk medicine for treatment of rheumatism, dysentery, and skin itching. However, the anti-neuroinflammatory constituents of its leaves and their mechanism are rarely reported. AIM OF THE STUDY: To search for new anti-neuro-inflammatory compounds from the leaves of C. minax and elucidate their mechanism on anti-neuroinflammatory effect. MATERIALS AND METHODS: The main metabolites of the ethyl acetate fraction from C. minax were analyzed and purified via HPLC and various column chromatography techniques. Their structures were elucidated on the basis of 1D and 2D NMR, HR-ESI-MS, and single crystal X-ray diffraction analysis. Anti-neuroinflammatory activity was evaluated in BV-2 microglia cells induced by LPS. The expression levels of molecules in NF-κB and MAPK signaling pathways were analyzed through western blotting. Meanwhile, the time- and dose-dependent expression of associated proteins such as iNOS and COX-2 were detected by western blotting. Furthermore, Compounds 1 and 3 were performed on the NF-κB p65 active site using molecular docking simulation to elucidate the molecular level inhibition mechanism. RESULTS: 20 cassane diterpenoids, including two novel ones (caeminaxins A and B) were isolated from the leaves of C. minax Hance. Caeminaxins A and B possessed a rare unsaturated carbonyl moiety in their structures. Most of the metabolites exhibited potent inhibition effects with IC50 values ranging from 10.86 ± 0.82 to 32.55 ± 0.47 µM. Among them, caeminaxin A inhibited seriously the expression of iNOS and COX-2 proteins and restrained the phosphorylation of MAPK and the activation of NF-κB signaling pathways in BV-2 cells. The anti-neuro-inflammatory mechanism of caeminaxin A has been studied systematically for the first time. Furthermore, biosynthesis pathways for compounds 1-20 were discussed. CONCLUSIONS: The new cassane diterpenoid, caeminaxin A, alleviated the expression of iNOS and COX-2 protein and down-regulated of intracellular MAPK and NF-κB signaling pathways. The results implied that cassane diterpenoids had potential to be developed into therapeutic agents for neurodegenerative disorders such as Alzheimer's disease.
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Caesalpinia , Diterpenos , NF-kappa B/metabolismo , Caesalpinia/química , Microglia/metabolismo , Ciclo-Oxigenase 2 , Simulação de Acoplamento Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Folhas de Planta/metabolismo , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Diterpenos/química , Lipopolissacarídeos/farmacologiaRESUMO
Osteoporosis (OP) has been associated with cardiovascular disease. More specifically, osteoporosis was found to be an independent predictor of cardiovascular mortality. Recent studies revealed that platelets play a critical role in bone remodeling. Mean platelet volume (MPV) is an early marker of platelet activation, which is involved in the pathophysiology of coronary heart disease. However, little research has been conducted to investigate the relationship between MPV and OP. In this cross-sectional study, we investigated the relationship between platelet count, MPV, and bone mineral density (BMD) in 410 subjects in the geriatric department of the Second Affiliated Hospital, Harbin, China. Different biochemical parameters, platelet count, and MPV were determined, and bone mineral density (BMD) (g/cm(2)) was measured in the osteoporosis, osteopenia, and normal BMD groups. Mean age, systolic blood pressure (SBP), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), and MPV increased gradually, and body mass index (BMI), decreased as BMD decreased. A negative correlation was present between MPV and the lumbar spine (L2-L4) and femoral neck BMD after adjusting other risk factors. Univariate analysis and multivariate analysis showed that MPV was significantly associated with lumbar spine L2-L4 BMD and femoral neck BMD (ß = -0.285, P < 0.001 for lumbar spine L2-L4 BMD; ß = -0.207, P < 0.001 for femoral neck BMD in multivariate model). The findings show that MPV is negatively correlated with BMD. Further studies on the involvement of MPV in osteoporosis may contribute to the evaluation of thrombotic risk in elderly patients with osteoporosis.
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Plaquetas/citologia , Densidade Óssea/fisiologia , Tamanho Celular , Osteoporose Pós-Menopausa/sangue , Pós-Menopausa/fisiologia , Idoso , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/diagnóstico por imagem , Estudos Transversais , Feminino , Colo do Fêmur/fisiopatologia , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/fisiopatologia , Ativação Plaquetária , Radiografia , Trombose/etiologiaRESUMO
Long non-coding (lnc)RNAs have been recognized as important regulators in gastric cancer. lncRNA GAS8-AS1 is considered a tumor suppressor in multiple types of cancer, such as papillary thyroid carcinoma, ovarian cancer and colorectal cancer. However, the specific role of GAS8-AS1 in gastric cancer remains to be fully elucidated. The aim of the present study was to investigate the role of GAS8-AS1 in gastric cancer and its potential underlying mechanisms of action. The expression levels of GAS8-AS1, microRNA (miR)-21-3p, PTEN and pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) in gastric cancer and non-cancerous tissues, as well as in gastric cancer cell lines, were detected using reverse transcription-quantitative PCR. Cell proliferation was detected by using a Cell Counting Kit-8 assay. Cell migration and invasion were detected using a Transwell assay. Results of the present study demonstrated that the expression levels of GAS8-AS1 in gastric cancer tissues were significantly decreased, whereas its expression did not differ among cancer tissues at different clinical stages. Low expression levels of GAS8-AS1 predicted poor 5-year survival rates for 70 patients with gastric adenocarcinoma from the Affiliated Hospital of Xuzhou Medical University (Xuzhou, China) during patient follow-up. In addition, the expression levels of miR-21-3p were markedly increased in cancer tissues, and miR-21-3p expression was negatively associated with the expression of GAS8-AS1. The direct interaction between GAS8-AS1 and miR-21-3p was predicted using the starBase database and was confirmed by using an RNA pull-down assay. In gastric cell lines, the overexpression of GAS8-AS1 reduced the expression levels of mature miR-21-3p but did not affect the expression of miR-21-3p precursor, while the overexpression of miR-21-3p did not, in turn, affect the expression of GAS8-AS1. In addition, the overexpression of GAS8-AS1 inhibited cancer cell proliferation, while the overexpression of miR-21-3p promoted cancer cell proliferation and attenuated the effects of GAS8-AS1. Overexpression of miR-21-3p promoted cancer cell migration and invasion, whereas overexpression of GAS8-AS1 did not affect cell migration or invasion. In summary, results of the present study have demonstrated that GAS8-AS1 acts as a tumor suppressor in gastric cancer, and it may inhibit cancer cell proliferation by downregulating miR-21-3p.