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1.
Mar Drugs ; 22(6)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38921568

RESUMO

The formation of phytoene by condensing two geranylgeranyl diphosphate molecules catalyzed by phytoene synthase (PSY) is the first committed and rate-limiting step in carotenoid biosynthesis, which has been extensively investigated in bacteria, land plants and microalgae. However, this step in macroalgae remains unknown. In the present study, a gene encoding putative phytoene synthase was cloned from the economic red alga Pyropia yezoensis-a species that has long been used in food and pharmaceuticals. The conservative motifs/domains and the tertiary structure predicted using bioinformatic tools suggested that the cloned PyPSY should encode a phytoene synthase; this was empirically confirmed by pigment complementation in E. coli. This phytoene synthase was encoded by a single copy gene, whose expression was presumably regulated by many factors. The phylogenetic relationship of PSYs from different organisms suggested that red algae are probably the progeny of primary endosymbiosis and plastid donors of secondary endosymbiosis.


Assuntos
Geranil-Geranildifosfato Geranil-Geraniltransferase , Filogenia , Rodófitas , Rodófitas/genética , Rodófitas/enzimologia , Geranil-Geranildifosfato Geranil-Geraniltransferase/genética , Geranil-Geranildifosfato Geranil-Geraniltransferase/metabolismo , Carotenoides/metabolismo , Escherichia coli/genética , Clonagem Molecular , Algas Comestíveis , Porphyra
2.
Org Lett ; 26(24): 5092-5097, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38848493

RESUMO

New carbonyl sulfoxonium ylide glyco-reagents have been developed, enabling the synthesis of versatile heteroarene C-glycosides through a Ru-catalyzed C-H activation/annulation strategy. These reactions tolerate various saccharide donors and represent a significant advance in the stereoselective synthesis of heterocyclic C-glycosides. Furthermore, the strategy and methods could be applied to large-scale reactions and late-stage modifications of some structurally complex natural products or drugs.

3.
Heliyon ; 10(10): e31307, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38803884

RESUMO

Objectives: N7-methylguanosine (m7G) plays a crucial role in mRNA metabolism and other biological processes. However, its regulators' function in Primary Sjögren's Syndrome (PSS) remains enigmatic. Methods: We screened five key m7G-related genes across multiple datasets, leveraging statistical and machine learning computations. Based on these genes, we developed a prediction model employing the extreme gradient boosting decision tree (XGBoost) method to assess PSS risk. Immune infiltration in PSS samples was analyzed using the ssGSEA method, revealing the immune landscape of PSS patients. Results: The XGBoost model exhibited high accuracy, AUC, sensitivity, and specificity in both training, test sets and extra-test set. The decision curve confirmed its clinical utility. Our findings suggest that m7G methylation might contribute to PSS pathogenesis through immune modulation. Conclusions: m7G regulators play an important role in the development of PSS. Our study of m7G-realted genes may inform future immunotherapy strategies for PSS.

4.
J Cell Mol Med ; 28(7): e18174, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38494839

RESUMO

This study investigates genetic mutations and immune cell dynamics in stomach adenocarcinoma (STAD), focusing on identifying prognostic markers and therapeutic targets. Analysis of TCGA-STAD samples revealed C > A as the most common single nucleotide variant (SNV) in both high and low-risk groups. Key mutated driver genes included TTN, TP53 and MUC16, with frame-shift mutations more prevalent in the low-risk group and missense mutations in the high-risk group. Interaction analysis of hub genes such as C1QA and CD68 showed significant correlations, impacting immune cell infiltration patterns. Using ssGSEA, we found higher immune cell infiltration (B cells, CD4+ T cells, CD8+ T cells, DC cells, NK cells) in the high-risk group, correlated with increased risk scores. xCell algorithm results indicated distinct immune infiltration levels between the groups. The study's risk scoring model proved effective in prognosis prediction and immunotherapy efficacy assessment. Key molecules like CD28, CD27 and SLAMF7 correlated significantly with risk scores, suggesting potential targets for high-risk STAD patients. Drug sensitivity analysis showed a negative correlation between risk scores and sensitivity to certain treatments, indicating potential therapeutic options for high-risk STAD patients. We also validated the carcinogenic role of RPL14 in gastric cancer through phenotypic experiments, demonstrating its influence on cancer cell proliferation, invasion and migration. Overall, this research provides crucial insights into the genetic and immune aspects of STAD, highlighting the importance of a risk scoring model for personalized treatment strategies and clinical decision-making in gastric cancer management.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Linfócitos T CD8-Positivos , Imunoterapia , Mutação/genética
5.
Fitoterapia ; 173: 105827, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38266661

RESUMO

Aspercitrininone A (1), a novel polyketide featuring an unprecedented tetracyclic 6/6/6/5 spiral skeleton, was obtained from the rice fermentation cultures of the fungus Aspergillus cristatus together with five known compounds (2-6). Their structures were determined by HRESIMS data, 1D and 2D NMR spectroscopic analysis, and electronic circular dichroism (ECD) calculations. Aspercitrininone A was revealed as a new type of C/D cycle spiral structure and an unusual addition product of o-quinoid form citrinin with 2-methylterrefuranone. Compounds 1, 4, and 5 exhibited potent antibacterial activities with minimal inhibitory concentration (MIC) values from 13.2 to 67.3 µg/mL against four strains of human pathogenic bacteria in vitro.


Assuntos
Aspergillus , Policetídeos , Humanos , Policetídeos/farmacologia , Policetídeos/química , Estrutura Molecular , Antibacterianos/farmacologia , Antibacterianos/química , Esqueleto
6.
Chem Commun (Camb) ; 60(5): 598-601, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38099839

RESUMO

A new Cp*Rh(III)-catalyzed regioselective cyclization reaction of aromatic amides with allenes is reported. The use of allenyl derivatives bearing a directing-group assistant as a reaction promoter was the key to the success of this protocol. In this catalytic system, N-(pivaloyloxy)benzamide substrates react with allenes via Rh-σ-alkenyl intermediates, while N-(pivaloyloxy) indol substrates react via Rh-π-allyl intermediates. These reactions were characterized by mild reaction conditions, a broad substrate scope, and high functional-group compatibility to yield several high-value isoquinolinone and pyrimido[1,6-a]indol-1(2H)-one skeleton-containing compounds. The synthetic applications and primary mechanisms were also investigated.

7.
Int Wound J ; 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872696

RESUMO

A meta-analysis was performed to compare the effects of laparoscopic splenectomy (LS) and open splenectomy (OS) for splenic rupture on postoperative surgical site wound infections and postoperative complications. A comprehensive computerised search was conducted for studies comparing LS with OS for the treatment of splenic rupture in the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang databases, with the search including studies published in any language between the creation of the databases and August 2023. Two researchers independently screened the literature and extracted the data. Literature quality was assessed using the Newcastle-Ottawa Scale, and the included data were collated and analysed using Stata 17.0 software for meta-analysis. Twenty-two studies involving 1545 patients were included. LS was superior to OS in the following aspects: reduced risk of postoperative surgical site wound infection (OR = 0.19, 95% CI: 0.11-0.34, p = 0.000), shortened hospital stay (standardised mean difference = -1.73, 95% CI: -2.05 to -1.40, p = 0.000), and reduced postoperative complication rate (OR = 0.22, 95% CI: 0.16-0.31, p = 0.000). Compared with OS, LS has a lower rate of postoperative wound infection, shorter hospital stay, and reduced rate of postoperative complications. LS is safe and effective for the treatment of splenic rupture and can be promoted clinically.

8.
Org Lett ; 25(27): 5022-5026, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37395740

RESUMO

This study describes the nickel-catalyzed reductive decarboxylative/deaminative glycosylation of activated aliphatic acids/amines. Various alkyl C-glycosides were efficiently constructed under simple and mild reaction conditions. The reactions were high-yielding and exhibited a broad substrate scope, thereby enabling the transformation of some structurally complex natural products and late-stage modifications of drugs.


Assuntos
Aminas , Ácidos Graxos , Níquel , Glicosilação , Catálise
9.
BMJ Open ; 13(2): e067475, 2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-36797020

RESUMO

OBJECTIVE: Diabetes affects 1 in 10 adults in China. Diabetic retinopathy (DR) is a diabetes-related complication that, if untreated, impairs vision and causes blindness. Evidence on DR diagnosis and risk factors is limited. This study aimed to add evidence from socioeconomic factors. DESIGN: A cross-sectional survey of people with diabetes conducted in 2019 was analysed by using logistic regression to evaluate the association of socioeconomic factors with the glycated haemoglobin (HbA1c) level and DR. SETTING: Five counties/districts of western China (Sichuan) were included. PARTICIPANTS: Registered participants with diabetes aged from 18 to 75 years were selected, and at last 2179 participants were included in the analysis. RESULTS: In this cohort, 37.13% (adjusted value 36.52%), 19.78% (adjusted value 19.59%) and 17.37% of participants had HbA1c<7.0%, DR (24.96% of those in the high-HbA1c group) and non-proliferative DR, respectively. Participants with higher social health insurance coverage (urban employee insurance (UEI)), higher income and urban residents tended to have glycaemic control (HbA1c) compared with their counterparts (OR: 1.48, 1.08 and 1.39, respectively). Participants with UEI or higher income had a lower risk of DR (OR: 0.71 and 0.88, respectively); higher education was associated with a 53%-69% decreased risk of DR. CONCLUSION: This study shows disparities in the effect of socioeconomic factors on glycaemic (HbA1c) management and DR diagnosis among people with diabetes in Sichuan. Lower socioeconomic (especially non-UEI) status conferred a higher risk of high HbA1c and DR. The insights from this study indicate the need for national programmes to implement community-level measures to facilitate access to better HbA1c management and early detection of DR in patients with lower socioeconomic status and diabetes. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR1800014432).


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Adolescente , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adulto Jovem , China/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/diagnóstico , Hemoglobinas Glicadas , Prevalência , Fatores de Risco , Classe Social
10.
Food Chem ; 405(Pt A): 134817, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36370577

RESUMO

In order to extract sulforaphane (SFN) from broccoli via green and efficient ways, a novel method based on salting-out assisted deep eutectic solvent (DES) has been developed. Compared to known organic solvent- (such as dichloromethane, ethyl acetate, n-hexane, etc.) based liquid-liquid extraction, this new N8881Cl-based DES method exhibited excellent extraction efficiency for SFN, including a significant improvement due to the salting-out effect of KH2PO4. Under optimal conditions, 97.77 % of SFN was extracted by N8881Cl-EG DES and more than 82.5 % of SFN was recovered by activated carbon from DES. In addition, further studies with Kamlet-Taft parameters and density functional theory showed that the H-bond accepting capacity of hydrophobic DES, the existing vdW interaction, and the electrostatic interaction between N8881Cl-EG DES all contributed to efficient extraction of SFN. This is the first time that the underlying mechanism for SFN extraction by DES was revealed.


Assuntos
Brassica , Brassica/química , Solventes Eutéticos Profundos , Sulfóxidos , Isotiocianatos , Solventes/química , Cloreto de Sódio
11.
ACS Omega ; 7(41): 36904, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36278109

RESUMO

[This corrects the article DOI: 10.1021/acsomega.2c04064.].

12.
ACS Omega ; 7(38): 34420-34427, 2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36188322

RESUMO

Through thermodynamic calculation and high-temperature simulation experiments, the coupling behavior between gasification of high- and low-reactivity cokes and reduction of sintering ore in CO-N2-H2 mixed gas with 25% H2 volume fraction was studied, and the evolution of the coke carbon structure and the pore structure was analyzed. The results show that the reaction rate of the two cokes increases with the increase in temperature after the coupling reaction, and the strength after drumming decreases with the increase in temperature. The strength of low-reactivity coke after the reaction is higher than that of high-reactivity coke, and the reduction degree of sintering ore after the coupling reaction with low-reactivity coke is higher than that with high-reactivity coke. At high temperatures and high hydrogen-rich atmospheres with φ(H2) of 25%, the strength of high-reactivity coke after drum rotation is greater than 60.4%. The graphitization degree and carbon structure order of low-reactivity coke are higher than those of high-reactivity coke.

13.
Planta ; 255(6): 122, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35554686

RESUMO

MAIN CONCLUSION: AaZFP1, a C2H2-type transcription factor, was found to bind the AGT-N1-10-AGT box of AaIPPI1pro and activate the expression of AaIPPI1 involved in artemisinin biosynthesis. Artemisinin, an endoperoxide sesquiterpene lactone, is a widely used antimalarial drug isolated from Artemisia annua L. Isopentenyl pyrophosphate isomerase (AaIPPI1) catalyzes the interconversion of isopentenyl diphosphate and dimethylallyl diphosphate and is the key gene involved in the biosynthesis of artemisinin. However, the AaIPPI1 gene regulation network remains largely unknown. Here, we isolated the AaIPPI1 promoter (AaIPPI1pro) and predicted that it contains cis-elements involved in stress responses, including the TGACG motif (a methyl jasmonate-responsive element), GARE motif (a gibberellin-responsive element), ABRE (an abscisic acid-responsive element), TC-rich repeats (a stress-responsive element), and the AGT-N1-10-AGT box, which is the binding site of Cys/His2 zinc finger protein (C2H2 ZFP). The C2H2 ZFP gene AaZFP1 was discovered by screening a cDNA library using AaIPPI1pro as bait in yeast. AaZFP1 contains two conserved C2H2 regions, a nuclear localization domain (B box), a Leu-rich domain (L box), and a conserved DLN sequence (DLN box) close to its C terminus. A subcellular localization assay indicated that AaZFP1 protein is localized in the nucleus and cytoplasm. An electrophoretic mobility shift assay demonstrated that AaZFP1 binds to the AGT-N1-10-AGT box of AaIPPI1pro. A dual-luciferase assay indicated that AaZFP1 enhanced the promoter activity of AaIPPI1 in vivo. Transient overexpression of AaZFP1 in A. annua increased the expression of AaIPPI1 and the content of artemisinin. Our data demonstrated that AaZFP1 functions as a transcriptional activator that regulates the expression of AaIPPI1 by directly binding to its promoter. The present study provides insights into the transcriptional regulation of genes involved in artemisinin biosynthesis in A. annua.


Assuntos
Artemisia annua , Artemisininas , Dedos de Zinco CYS2-HIS2 , Ácido Abscísico/metabolismo , Artemisia annua/genética , Artemisia annua/metabolismo , Artemisininas/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
14.
BMJ Open ; 12(4): e052457, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35365515

RESUMO

OBJECTIVES: This study explored the prevalence of and individual influencing factors for metabolic syndrome (MS) as well as associated socioeconomic factors and regional aggregation. DESIGN: Four cross-sectional surveys were analysed for trends in MS and associations with socioeconomic and individual factors through multilevel logistic regression analyses. The risk associated with nutrient intake was also assessed through a dietary survey in 2015. SETTING: From 2010 to 2018, 8-15 counties/districts of West China were included. PARTICIPANTS: A total of 28 274 adults were included in the prevalence analysis. A total of 23 708 adults were used to analyse the related factors. RESULTS: The overall prevalence of MS ranged from 21.4% to 27.8% over the 8 years, remaining basically stable within the 95% CI. Our study found that the urbanisation rate and hospital beds per 1000 people were positively associated with MS, and the number of doctors in healthcare institutions per 1000 persons was negatively associated with MS. The ORs for females, people with college education and higher and unmarried or single people were 1.49, 0.67 and 0.51, respectively (p<0.05). The ORs of people who smoked at least 20 cigarettes/day, ate more than 100 g of red meat/day, consumed fruit or vegetable juice and drank carbonated soft drinks less than weekly were 1.10, 1.16, 1.19-1.27 and 0.81-0.84, respectively. The ORs rose with increasing sedentary time and decreased with higher physical activity. CONCLUSION: The high burden of MS, unreasonable proportions of energy and micronutrient intake and low percentage of high levels of physical activity were the major challenges to public health in western China. Improving the human resources component of medical services, such as the number of doctors, increasing the availability of public sports facilities and E-health tools and improving individual dietary quality and education might help prevent MS.


Assuntos
Síndrome Metabólica , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Síndrome Metabólica/epidemiologia , Prevalência , Fatores Socioeconômicos
15.
Neuroscience ; 479: 22-34, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34687796

RESUMO

Transcription factors bind specific sequences upstream of the 5' end of their target genes to ensure proper spatiotemporal expression of the target gene. This study aims to demonstrate that the transcription factor SP2 regulates expression of the Ski gene, which has specific binding sites for SP2, and thus enables Ski to regulate astrocyte proliferation. The upstream regulation mechanism of astrocyte proliferation was explored to further regulate the formation of glial scar in specific time and space after spinal cord injury. JASPAR and UCSC databases were used to predict transcription factor binding and the threshold was gradually reduced to screen transcription factors upstream of Ski, leading to the identification of SP2. Next, we analyzed the correlation between the expression of SP2 and Ski in normal astrocytes and reactive astrocytes, as well as the changes in astrocyte proliferation. To confirm that SP2 regulates Ski during astrocyte proliferation, astrocytes were transfected siRNA targeting SP2 and then astrocyte proliferation were analyzed. Finally, a dual luciferase reporter assay and Chromatin immunoprecipitation (ChIP) assay confirmed that the promoter region of Ski contained a specific SP2 binding site. This is the first that SP2 has been identified and confirmed to play an important role in astrocyte proliferation by regulating Ski expression. These results may help identify novel targets for the treatment of spinal cord injury.


Assuntos
Astrócitos , Traumatismos da Medula Espinal , Proliferação de Células , Células Cultivadas , Gliose , Humanos , Fator de Transcrição Sp2
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(2): 117-122, 2021 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-33565061

RESUMO

OBJECTIVE: To compare the mRNA level of cell proliferation-related genes Twist1, SIRT1, FGF2 and TGF-ß3 in placenta mesenchymal stem cells (PA-MSCs), umbilical cord mensenchymals (UC-MSCs) and dental pulp mesenchymal stem cells (DP-MSCs). METHODS: The morphology of various passages of PA-MSCs, UC-MSCs and DP-MSCs were observed by microscopy. Proliferation and promoting ability of the three cell lines were detected with the MTT method. Real-time PCR (RT-PCR) was used to determine the mRNA levels of Twist1, SIRT1, FGF2, TGF-ß3. RESULTS: The morphology of UC-MSCs and DP-MSCs was different from that of PA-MSCs. Proliferation ability and promoting ability of the PA-MSCs was superior to that of UC-MSCs and DP-MSCs. In PA-MSCs, expression level of Twist1 and TGF-ß3 was the highest and FGF2 was the lowest. SIRT1 was highly expressed in UC-MSCs. With the cell subcultured, different expression levels of Twist1, SIRT1, FGF2, TGF-ß3 was observed in PA-MSCs, UC-MSCs and DP-MSCs. CONCLUSION: Up-regulated expression of the Twist1, SIRT1 and TGF-ß3 genes can promote proliferation of PA-MSCs, UC-MSCs and DP-MSCs, whilst TGF-ß3 may inhibit these. The regulatory effect of Twist1, SIRT1, FGF2 and TGF-ß3 genes on PA-MSCs, UC-MSCs and DP-MSCs are different.


Assuntos
Proliferação de Células/genética , Fator 2 de Crescimento de Fibroblastos/genética , Células-Tronco Mesenquimais/citologia , Proteínas Nucleares/genética , Sirtuína 1/genética , Fator de Crescimento Transformador beta3/genética , Proteína 1 Relacionada a Twist/genética , Diferenciação Celular , Células Cultivadas , Polpa Dentária/citologia , Feminino , Humanos , Placenta/citologia , Gravidez , Cordão Umbilical/citologia
17.
Eur J Hosp Pharm ; 28(Suppl 2): e51-e55, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-32522809

RESUMO

OBJECTIVE: To evaluate potential risk factors that may make patients susceptible to nephrotoxicity in those concomitantly receiving vancomycin in the hospital. METHODS: This was a single-centre retrospective analysis of patients treated with vancomycin for gram-positive or mixed infections in the Renmin Hospital of Wuhan University from January 2017 to May 2018. All of them were treated for ≥48 hours and had no kidney disease. Nephrotoxicity refers to acute kidney diseases and disorders after the use of vancomycin, and includes acute kidney injury. Univariate analysis and binary logistic regression analysis with the forward stepwise method were used to assess the risk factors associated with nephrotoxicity. RESULTS: Of the 790 patients treated with vancomycin, only 257 patients met the inclusion criteria, and 40 (15.6%) subjects developed nephrotoxicity. Significant differences (p<0.05) were seen in the number of combined antimicrobials (p=0.012), dose adjustment (p<0.001), more than three antimicrobials (p=0.015), monitoring trough concentrations (p=0.001), furosemide (p<0.001), torasemide (p<0.001), cefoperazone sodium tazobactam sodium (p=0.039), voriconazole (p=0.012) and ganciclovir (p=0.008). Regression analysis further indicated that furosemide (OR 7.983, p<0.001) and torasemide (OR 3.496, p<0.001) were risk factors for vancomycin nephrotoxicity. Diabetes mellitus (OR 3.062, p=0.035), voriconazole (OR 3.515, p=0.020) and fluconazole (OR 3.326, p=0.018) might be also risk factors. CONCLUSION: Fluconazole and voriconazole might be potential risk factors for vancomycin nephrotoxicity, besides furosemide and torasemide. It is not recommended to use imipenem cilastatin sodium and vancomycin at the same time. If necessary, meropenem may be safer. Appropriate combination drugs, cautious initial dose or timely dose adjustment might reduce the occurrence of nephrotoxicity when using vancomycin.


Assuntos
Injúria Renal Aguda , Vancomicina , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Adulto , Antibacterianos/efeitos adversos , China/epidemiologia , Humanos , Estudos Retrospectivos , Fatores de Risco , Vancomicina/efeitos adversos
18.
J Asian Nat Prod Res ; 23(8): 796-802, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32608251

RESUMO

One new pentacyclic triterpenoid, urs-12,16-dien-3-one (1), together with twelve known pentacyclic triterpenoids (2‒13), were isolated from the twigs and leaves of Melaleuca linariifolia. Their structures were characterized by their 1D- and 2 D-NMR spectra analysis and mass spectra studies. Furthermore, all isolated compounds were tested the inhibitory effect on proliferation of six human cancer cell lines in vitro, including NCI-H441, NCI-H460, A549, SKOV3, hela, and caki-1 cells. Among them, compounds 3, 5, 7, 9, 12, and 13 exhibited moderate antiproliferative activities with IC50 values ranging from 3.85 to 33.31 µM.


Assuntos
Melaleuca , Triterpenos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Folhas de Planta , Triterpenos/farmacologia
19.
Oxid Med Cell Longev ; 2020: 6123459, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774680

RESUMO

BACKGROUND: Acute kidney injury (AKI) is one of the common complications of sepsis. Heretofore, there is no effective treatment for septic AKI. Recent studies have revealed that besides treating hematological malignancies, human umbilical cord blood mononuclear cells (hUCBMNCs) show good therapeutic effects on other diseases. But whether hUCBMNCs can protect against septic AKI and its underlying mechanism are unknown. METHODS: The rat model of lipopolysaccharide- (LPS-) induced AKI was developed, and the injection of hUCBMNCs was executed to prevent and treat AKI. ML385, a specific nuclear factor E2-related factor 2 (Nrf2) inhibitor, was used to silence Nrf2. The cell experiments were conducted to elaborate the protective mechanism of Nrf2 pathway. RESULTS: An effective model of LPS-induced AKI was established. Compared to the rats only with LPS injection, the levels of inflammation, reactive oxygen species (ROS), and apoptosis in renal tissues after hUCBMNC injection were markedly attenuated. Pathological examination also indicated significant remission of renal tissue injury in the LPS+MNCs group, compared to rats in the LPS group. Transmission electron microscopy (TEM) showed that the damage of the mitochondria in the LPS+MNCs group was lighter than that in the LPS group. Noteworthily, the renal Nrf2/HO-1 pathway was activated and autophagy was enhanced after hUCBMNC injection. ML385 could partly reverse the renoprotective effect of hUCBMNCs, which could demonstrate that Nrf2 participated in the protection of hUCBMNCs. Cell experiments showed that increasing the expression level of Nrf2 could alleviate LPS-induced cell injury by increasing the autophagy level and decreasing the injury of the mitochondria in HK-2 cells. CONCLUSION: All results suggest that hUCBMNCs can protect against LPS-induced AKI via the Nrf2 pathway. Activating Nrf2 can upregulate autophagy to protect LPS-induced cell injury.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Sangue Fetal/metabolismo , Lipopolissacarídeos/efeitos adversos , Fator 2 Relacionado a NF-E2/uso terapêutico , Animais , Humanos , Leucócitos Mononucleares , Masculino , Ratos , Ratos Sprague-Dawley
20.
Zhongguo Zhong Yao Za Zhi ; 45(11): 2658-2667, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32627501

RESUMO

To systematically evaluate the clinical efficacy and safety of modified Qingjin Huatan Decoction in the treatment of community-acquired pneumonia in the elderly, and provide evidence-based reference for the clinical application of this prescription. Randomized controlled trials of Qingjin Huatan Decoction in the treatment of community-acquired pneumonia in the elderly were collected by searching PubMed, EMbase, Cochrane Library, CNKI, China Biomedical Literature database, VIP database and WanFang database. Outcome indicators included clinical effective rate, inflammation index, symptom improvement time, chest radiograph improvement time, hospitalization time and adverse reactions. RevMan 5.3 and Stata/IC 15.1 software were used for Meta-analysis; TSA 0.9.5.10 Beta software was used for trial sequential analysis, and GRADE profiler 3.6 was used for grade evidence quality evaluation. Thirteen studies were included finally, including 1 058 patients, 536 patients in the experimental group and 522 patients in the control group.Meta-analysis showed that, the clinical effective rate of the experimental group was significantly higher than that of the control group(RR=1.16, 95%CI[1.10, 1.21], P<0.000 01); fever time(MD=-1.32, 95%CI[-1.93,-0.71], P<0.000 1), cough time(MD=-1.95, 95%CI[-2.69,-1.21), P<0.000 01), time to rale disappearance(MD=-1.55, 95%CI[-2.37,-0.73], P=0.000 2), time to chest radiograph improvement(MD=-1.72, 95%CI[-2.98,-0.46], P=0.007), and hospitalization time(MD=-3.16, 95%CI[-4.58,-1.74], P<0.000 01) in the experimental group were significantly shorter than those in the control group. The improvement in CRP(WMD=-3.44,95%CI[-4.50,-2.38],P<0.001), WBC(WMD=-2.04,95%CI[-3.31,-0.78],P<0.01), IL-6(WMD=-4.27,95%CI[-4.62,-3.92],P<0.001), and TNF-α(WMD=-0.47,95%CI[-0.55,-0.39], P<0.001) of the experimental group was significantly better than that of the control group. There was no significant difference in PCT improvement between the two groups(WMD=-0.63, 95%CI[-1.65, 0.40], P=0.23). No serious adverse reactions occurred in both groups. Sequential analysis of the trial showed that in the studies with cumulative inclusion of clinical effective rate, the data passed the traditional threshold and TSA threshold, further confirming its clinical efficacy. GRADE evaluation showed that the evidence level was low to extremely low. Western medicine treatment combined with Qingjin Huatan Decoction may improve clinical efficiency in the treatment of community-acquired pneumonia in the elderly, improve clinical symptoms faster, reduce CRP, WBC and other inflammatory indicators, and shorten hospital stay. The level of evidence obtained in this study is low, which needs to be further verified by high-quality multi-center, randomized controlled trials.


Assuntos
Infecções Comunitárias Adquiridas , Medicamentos de Ervas Chinesas , Pneumonia , Idoso , China , Tosse , Humanos
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