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1.
Curr Res Food Sci ; 8: 100772, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38840807

RESUMO

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.

2.
Anal Bioanal Chem ; 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704473

RESUMO

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.

3.
bioRxiv ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38168313

RESUMO

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.

4.
Front Genet ; 14: 1243730, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37554407

RESUMO

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.

5.
J Ethnopharmacol ; 315: 116653, 2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37236383

RESUMO

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.


Assuntos
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/farmacologia
6.
Food Chem ; 423: 136299, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37178602

RESUMO

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.


Assuntos
Lipólise , Compostos Orgânicos Voláteis , Cetonas , Alimentos , Fermentação
7.
Org Lett ; 25(6): 961-965, 2023 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-36735280

RESUMO

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.


Assuntos
Streptomyces griseus , Streptomyces , Streptomyces/genética , Família Multigênica , Espectroscopia de Ressonância Magnética
8.
Artigo em Inglês | MEDLINE | ID: mdl-35591750

RESUMO

In September 2021, a household cluster of three typhoid cases was investigated by Queensland public health authorities. Through case interviews and molecular typing, the investigation revealed chronic carriage of Salmonella Typhi persisting at least 12 years in the index case. This case report summarises the investigation and highlights the complexity of chronic pathogen carriage in the control and management of typhoid disease. Our findings raise considerations for prevention and treatment guidelines in Australia and demonstrate the beneficial role of molecular typing for complex case investigations.


Assuntos
Salmonella typhi , Febre Tifoide , Austrália/epidemiologia , Humanos , Queensland/epidemiologia , Salmonella , Febre Tifoide/epidemiologia
9.
J Hazard Mater ; 435: 128976, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35472541

RESUMO

Since the excess exposure to F- may induce serious issues to human health, the effective adsorption and sensitive detection of F- is essential. Therefore, carbon dots (CDs) capped CeO2 (CeO2@CDs) was synthesized via hydrothermal treatment of tannic acid and CeCl3. Due to abundant phenolic hydroxyl are reserved and excellent hydrophilicity, CeO2@CDs possess high F- adsorption capacity. The partition coefficient parameters (PC) are determined to be 2.65 L/g, which is comparable with previous work. The kinetics results and adsorption isotherm are consistent with pseudo-second-order model and Freundlich model, respectively, indicating the chemisorption dominate the adsorption, mainly via the ion exchange between hydroxyl and F-. Since phenolic hydroxyl existed on the CeO2@CDs, synergetic effect of CDs and CeO2 contribute to superior ROS eliminating capacity, even at acidic conditions. Moreover, due to the ROS scavenging of CeO2 @CDs abilities can be potentiated by F-, colorimetric detection of F- can be realized via horseradish peroxidase as an indicator. The linear range is 0.3-2.1 mM with limit of detection is 0.13 mg/L. The current results imply that CeO2@CDs possess potential in both efficient removal and sensitive detection of F- related contamination issues and elucidation of development to address other anions related issues.


Assuntos
Cério , Nanopartículas , Carbono , Fluoretos , Humanos , Espécies Reativas de Oxigênio
10.
Oncol Lett ; 23(2): 48, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34992681

RESUMO

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.

11.
Asian J Surg ; 45(6): 1231-1236, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34507839

RESUMO

OBJECTIVE: To investigate the expression of long non-coding RNA LINC01279 in gastric cancer and its relationship with the clinicopathological features and prognosis of gastric cancer patients. METHODS: Serum, gastric cancer and adjacent tissue samples from 90-patients with gastric-cancer treated by surgery and serum samples from 90-healthy adults were collected. The expression level of LINC01279 was analyzed by RT-PCR. The clinical baseline data of gastric cancer patients were obtained. Correlation between the expression level of LINC01279 and the clinicopathological characteristics of gastric cancer patients was assessed. RESULTS: LINC01279 was highly expressed in gastric cancer tissues and serum of gastric cancer patients (P < 0.05). The expression level of lncRNA 01279 was closely related to vascular invasion, nerve invasion, T-stage, lymph node metastasis, and advanced clinical-stage of gastric cancer (P < 0.05). The expression level was not correlated with gender, age, tumor size, location, and differentiation. There was a significant negative correlation between the expression of LINC01279 and the overall survival of gastric-cancer patients (P < 0.05). CONCLUSION: LINC01279 is highly expressed in gastric-cancer tissues and serum, which is closely related to tumor-invasion. Serum LINC01279 is a better prognostic indicator of invasive cancer than current tumor markers.


Assuntos
Adenocarcinoma , RNA Longo não Codificante , Neoplasias Gástricas , Adenocarcinoma/genética , Adulto , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Humanos , Metástase Linfática , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
12.
Nat Commun ; 12(1): 5672, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34584078

RESUMO

Nature forms S-S bonds by oxidizing two sulfhydryl groups, and no enzyme installing an intact hydropersulfide (-SSH) group into a natural product has been identified to date. The leinamycin (LNM) family of natural products features intact S-S bonds, and previously we reported an SH domain (LnmJ-SH) within the LNM hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly line as a cysteine lyase that plays a role in sulfur incorporation. Here we report the characterization of an S-adenosyl methionine (SAM)-dependent hydropersulfide methyltransferase (GnmP) for guangnanmycin (GNM) biosynthesis, discovery of hydropersulfides as the nascent products of the GNM and LNM hybrid NRPS-PKS assembly lines, and revelation of three SH domains (GnmT-SH, LnmJ-SH, and WsmR-SH) within the GNM, LNM, and weishanmycin (WSM) hybrid NRPS-PKS assembly lines as thiocysteine lyases. Based on these findings, we propose a biosynthetic model for the LNM family of natural products, featuring thiocysteine lyases as PKS domains that directly install a -SSH group into the GNM, LNM, or WSM polyketide scaffold. Genome mining reveals that SH domains are widespread in Nature, extending beyond the LNM family of natural products. The SH domains could also be leveraged as biocatalysts to install an -SSH group into other biologically relevant scaffolds.


Assuntos
Produtos Biológicos/metabolismo , Liases de Carbono-Enxofre/metabolismo , Cisteína/análogos & derivados , Metiltransferases/metabolismo , Policetídeo Sintases/metabolismo , Sulfetos/metabolismo , Animais , Produtos Biológicos/química , Cisteína/metabolismo , Cistina/química , Cistina/metabolismo , Humanos , Lactamas/síntese química , Lactamas/química , Lactamas/metabolismo , Macrolídeos/síntese química , Macrolídeos/química , Macrolídeos/metabolismo , Modelos Químicos , Estrutura Molecular , Peptídeo Sintases/metabolismo , Streptomyces/genética , Streptomyces/metabolismo , Especificidade por Substrato , Sulfetos/química , Tiazóis/síntese química , Tiazóis/química , Tiazóis/metabolismo , Tionas/síntese química , Tionas/química , Tionas/metabolismo , Domínios de Homologia de src
13.
Mikrochim Acta ; 188(5): 154, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33821295

RESUMO

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.


Assuntos
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/toxicidade
14.
Mikrochim Acta ; 188(4): 141, 2021 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-33774694

RESUMO

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.


Assuntos
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 Fluorescência
15.
Am J Hum Biol ; 33(2): e23462, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32657006

RESUMO

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.


Assuntos
Cromossomos Humanos Y/genética , Etnicidade/genética , Migração Humana , Filogenia , Haplótipos , Humanos , Masculino , Sibéria/etnologia
16.
Biomed Pharmacother ; 128: 110258, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32516749

RESUMO

Endothelial dysfunction (ED) and hyperpermeability are considered as the initiating steps in early atherosclerosis. Phosphorylation of myosin light chain (MLC) is key to cause vascular hyperpermeability via endothelial cell contraction. However, it is unclear whether MLC phosphorylation can also regulate the balance between contraction and relaxation of endothelial cells, thereby affecting endothelium-dependent diastolic function and leading to ED. The present study investigated relationships between ED and MLC phosphorylation and underlying mechanisms. Twenty-four male New Zealand white rabbits were randomly divided into three groups: control, AS, and ML7 (MLCK inhibitor) groups, and fed with normal diet, high-fat diet (HFD), and HFD plus oral ML7 (1 mg/kg daily) respectively. HFD-fed rabbits showed typical atheromatous lesions and endothelial hyperpermeability, and these lesions could be partly reversed following ML7 therapy. Western blotting revealed significant increased expression of myosin light chain kinase (MLCK) and phosphorylation of MLC, JNK, and ERK in the arterial wall of rabbits in the AS group compared with those of the control group (p < 0.05), whereas the ML7 group showed markedly decreased levels of these proteins compared with the AS group (p < 0.05). The endothelium-dependent relaxation rate was significantly reduced both in vitro and in vivo in AS group, and was improved using ML7 therapy. Taken together, these results indicate that MLCK expression and subsequent MLC phosphorylation increase vascular endothelial permeability and endothelium-dependent diastolic dysfunction by promoting endothelial cell contraction, which may be initiated by the activation of the MAP/ERK (MEK) and MAP/JNK (MEK) pathways.


Assuntos
Aorta Torácica/efeitos dos fármacos , Aterosclerose/tratamento farmacológico , Azepinas/farmacologia , Endotélio Vascular/efeitos dos fármacos , Artéria Ilíaca/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Quinase de Cadeia Leve de Miosina/antagonistas & inibidores , Naftalenos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Aorta Torácica/enzimologia , Aorta Torácica/patologia , Aorta Torácica/fisiopatologia , Aterosclerose/enzimologia , Aterosclerose/patologia , Aterosclerose/fisiopatologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Endotélio Vascular/enzimologia , Endotélio Vascular/fisiopatologia , Ativação Enzimática , Artéria Ilíaca/enzimologia , Artéria Ilíaca/fisiopatologia , Masculino , Quinase de Cadeia Leve de Miosina/metabolismo , Permeabilidade , Fosforilação , Placa Aterosclerótica , Coelhos , Transdução de Sinais
17.
J Hum Genet ; 65(10): 823-829, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32427951

RESUMO

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.


Assuntos
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 Único
18.
Am J Surg ; 220(3): 725-730, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32014297

RESUMO

BACKGROUND: Sleeve gastrostomy (SG) induces significant weight loss primarily as a result of increased satiety and reduced food intake. Growth differentiation factor-15 (GDF15) is a satiety hormone which induces a dramatic reduction of food intake and body weight. OBJECTIVE: To assess the effect of sleeve gastrectomy on plasma GDF 15 level and the association with the weight loss and diabetes control after SG. METHOD: We assessed plasma GDF15 level in 21 patients (15 with obesity and 6 with obesity and diabetes) before and then at 1, 3 and 12 months after SG. RESULTS: GDF15 was significantly increased at 1 month after SG compared to before surgery level (301.9 ± 135.2 pg/ml vs 215.1 ± 119.9 pg/ml, respectively p<0.05) and increased even further at 3 months (338.86 ± 131.14 pg/ml, p<0.01) and remain elevated at 12 months (329.39 ± 152.1 pg/ml p<0.05) after SG. At 3 months after surgery, the increased GDF15 level was correlated with the magnitude of BMI loss (r2 = 0.204, p<0.05). CONCLUSION: SG induces a significant increase in GDF15 level which is correlated with the magnitude of BMI loss.


Assuntos
Gastrectomia/métodos , Fator 15 de Diferenciação de Crescimento/sangue , Redução de Peso , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem
19.
Sci Rep ; 9(1): 9981, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31292518

RESUMO

Recent studies suggest the possibility of the stomach playing a role in diabetes remission after bariatric surgery. In this study, we investigated whether bypassing the stomach alleviates diabetes in diabetic rodent model. Eighteen moderately obese and diabetic Sprague-Dawley rats were randomly assigned to Esophagoduodenostomy with or without gastric preservation (EDG and EDNG/total gastrectomy, respectively), and SHAM groups. Bodyweight, food intake, fasting glucose level, oral glucose tolerance test result (OGTT), and hormone levels (insulin, glucagon-like peptide-1, ghrelin, gastrin and glucagon) were measured preoperative and postoperatively. Postoperatively, bodyweight and food intake did not differ significantly between the EDG and EDNG groups. Postoperative fasting blood glucose and OGTT results declined significantly in the EDG and EDNG group when compared with the respective preoperative levels. Postoperative glucose control improvements in EDNG group was significantly inferior when compared to EDG. Compared preoperatively, postoperative plasma ghrelin and gastrin levels declined significantly in EDNG group. Preoperative and postoperative plasma GLP-1 level did not differ significantly among all the groups. Postoperatively, EDG group had significantly higher insulin and lower glucagon levels when compared with SHAM. In conclusion, bypassing and preserving the stomach resulted in superior glucose control improvements than total gastrectomy.


Assuntos
Diabetes Mellitus Experimental/cirurgia , Diabetes Mellitus Tipo 2/cirurgia , Derivação Gástrica/métodos , Gastrinas/sangue , Grelina/sangue , Glucose/análise , Animais , Cirurgia Bariátrica , Peso Corporal , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Duodenostomia , Ingestão de Alimentos , Esofagostomia , Teste de Tolerância a Glucose , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Estreptozocina , Resultado do Tratamento
20.
Int J Clin Exp Pathol ; 12(8): 2959-2966, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31934132

RESUMO

The purpose of this article is to study whether the overexpression of urokinase-type plasminogen activator (uPA) can promote the proliferation and fibrinolytic activity of human umbilical vein endothelial cells (HUVECs). The recombinant adenovirus vectors containing the human uPA gene were constructed and transfected into HUVECs. In this study, the mRNA of uPA was detected by qPCR, and the uPA protein was measured by Western blot. The cell proliferation was measured using MTT. The fibrinolytic activity of uPA was quantified using a colorimetric assay. We also measured MMP2 (metalloproteinase-2), MMP9 (metalloproteinase-9), and VEGF (vascular endothelial growth factor) proteins using ELISA. The results showed that the levels of the uPA mRNA and the protein in the overexpression group were significantly higher compared to the other groups, (P < 0.05). The cell proliferation and uPA activity were increased significantly in the overexpression group, compared to the other groups, (P < 0.05). The secretions of MMP2, MMP9, and VEGF in the overexpression group were significantly higher than they were in the other two groups (P < 0.05). In conclusion, we successfully transfected a recombined adenovirus vector carrying uPA into a HUVEC. The exogenous uPA gene could transcribe and secrete the uPA protein in the HUVECs. The overexpression of uPA can increase cell proliferation and uPA activity. It can improve the invasion and angiogenesis ability in HUVECs by promoting their secretions of MMP2, MMP9, and VEGF.

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