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1.
BMC Pregnancy Childbirth ; 24(1): 251, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589784

RESUMO

BACKGROUND: Inflammatory Bowel Disease (IBD) affects reproductive-aged women. Active disease can lead to decreased fertility. Although the vast majority of international guidelines recommend for the continuation of anti-TNF-α during pregnancy, recent studies have raised concerns about the safety of anti-tumor necrosis factor-α (TNF-α) therapy during pregnancy, both for patients and for physicians. METHODS: Studies that evaluate the safety of anti-TNF-α therapy in pregnant women with IBD were identified using bibliographical searches. An updated meta-analysis was performed for pregnancy outcomes, such as live birth, abortion, still birth, preterm birth, low birth weight, congenital abnormalities, and neonatal infection. Odds ratio (OR) with 95% confidence interval (CI) are reported. Data on disease activity, timing of anti-TNF-α therapy were collected for further analysis. RESULTS: Overall, 11 studies were screened from on-line databases and international meeting abstracts. An increased risk of abortion (OR, 1.33; 95% CI, 1.02-1.74; P = 0.04) and preterm birth (OR, 1.16; 95% CI, 1.05-1.28; P = 0.004), and a decreased risk of live birth (OR, 0.83; 95% CI, 0.74-0.94; P = 0.002]) were found in the anti-TNF-α therapy group compared with the control group (no use of anti-TNF-α therapy). The subgroup analyses based on the disease activity showed there is no significant association between the use of anti-TNF-α therapy during pregnancy on adverse pregnancy outcomes of abortion, preterm birth, and live birth. The rates of still birth, low birth weight, and congenital abnormalities in the anti-TNF-α therapy group were not significantly different from those in the control group. CONCLUSIONS: Anti-TNF-α therapy does not increase the risks of still birth, low birth weight, and congenital abnormalities; however it may be assicated with increased risks of abortion and preterm birth, which are accompanied by a lower rate of live birth. Although these findings may be confounding by potential disease activity, they offer some opposite viewpoints with biologic agent use. Therefore, more studies are required to further confirm the safety of anti-TNF-α therapy in pregnancy with IBD.


Assuntos
Doenças Inflamatórias Intestinais , Complicações na Gravidez , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Adulto , Nascimento Prematuro/epidemiologia , Inibidores do Fator de Necrose Tumoral , Resultado da Gravidez/epidemiologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Natimorto , Necrose , Complicações na Gravidez/tratamento farmacológico
2.
Eur J Pharmacol ; 971: 176496, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38508437

RESUMO

Patients with myocardial infarction have a much worse prognosis when they have myocardial ischemia-reperfusion (I/R) injury. Further research into the molecular basis of myocardial I/R injury is therefore urgently needed, as well as the identification of novel therapeutic targets and linkages to interventions. Three cysteine residues are present in DJ-1 at amino acids 46, 53, and 106 sites, with the cysteine at position 106 being the most oxidation-prone. This study sought to understand how oxidized DJ-1(C106) contributes to myocardial I/R damage. Rats' left anterior descending branches were tied off to establish a myocardial I/R model in vivo. A myocardial I/R model in vitro was established via anoxia/reoxygenation (A/R) of H9c2 cells. The results showed that autophagy increased after I/R, accompanied by the increased expression of oxidized DJ-1 (ox-DJ-1). In contrast, after pretreatment with NAC (N-acetylcysteine, a ROS scavenger) or Comp-23 (Compound-23, a specific antioxidant binding to the C106 site of DJ-1), the levels of ox-DJ-1, autophagy and LDH release decreased, and cell survival rate increased. Furthermore, the inhibition of interaction between ox-DJ-1 and PTEN could increase PTEN phosphatase activity, inhibit the p-IKK/NF-κB/Beclin1 pathway, reduce injurious autophagy, and alleviate A/R injury. However, BA (Betulinic acid, a NF-κB agonist) was able to reverse the protective effects produced by Comp-23 pretreatment. In conclusion, ox-DJ-1 could activate detrimental autophagy through the PTEN/p-IKK/NF-κB/Beclin1 pathway and exacerbate myocardial I/R injury.


Assuntos
Traumatismo por Reperfusão Miocárdica , NF-kappa B , Animais , Humanos , Ratos , Autofagia , Proteína Beclina-1 , Cisteína/farmacologia , Traumatismo por Reperfusão Miocárdica/metabolismo , NF-kappa B/metabolismo , PTEN Fosfo-Hidrolase , Ratos Sprague-Dawley
3.
World J Gastroenterol ; 30(3): 252-267, 2024 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-38314135

RESUMO

BACKGROUND: Ulcerative colitis (UC) is an inflammatory condition with frequent relapse and recurrence. Evidence suggests the involvement of SLC6A14 in UC pathogenesis, but the central regulator remains unknown. AIM: To explore the role of SLC6A14 in UC-associated pyroptosis. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR), immunoblotting, and immunohistochemical were used to assess SLC6A14 in human UC tissues. Lipopolysaccharide (LPS) was used to induce inflammation in FHC and NCM460 cells and model enteritis, and SLC6A14 levels were assessed. Pyroptosis markers were quantified using enzyme-linked immunosorbent assay, Western blotting, and qRT-PCR, and EdU incubation, CCK-8 assays and flow cytometry were used to examine proliferation and apoptosis. Mouse models of UC were used for verification. RESULTS: SLC6A14 was increased and correlated with NLRP3 in UC tissues. LPS-induced FHC and NCM460 cells showed increased SLC6A14 levels. Reducing SLC6A14 increased cell proliferation and suppressed apoptosis. Reducing SLC6A14 decreased pyroptosis-associated proteins (ASC, IL-1ß, IL-18, NLRP3). NLRP3 overexpression counteracted the effects of sh-SLC6A14 on LPS-induced FHC and NCM460 cell pyroptosis. SLC6A14 improved the mucosa in mice with dextran sulfate sodium-induced colitis. CONCLUSION: SLC6A14 promotes UC pyroptosis by regulating NLRP3, suggesting the therapeutic potential of modulating the SLC6A14/NLRP3 axis.


Assuntos
Sistemas de Transporte de Aminoácidos , Colite Ulcerativa , Colite , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Humanos , Camundongos , Sistemas de Transporte de Aminoácidos/genética , Sistemas de Transporte de Aminoácidos/metabolismo , Colite Ulcerativa/induzido quimicamente , Inflamassomos/metabolismo , Lipopolissacarídeos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose
4.
Molecules ; 29(3)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38338359

RESUMO

In this study, two previously undescribed nitrogen-containing compounds, penisimplicins A (1) and B (2), were isolated from Penicillium simplicissimum JXCC5. The structures of 1 and 2 were elucidated on the basis of comprehensive spectroscopic data analysis, including 1D and 2D NMR and HRESIMS data. The absolute configuration of 2 was determined by Marfey's method, ECD calculation, and DP4+ analysis. Both structures of 1 and 2 feature an unprecedented manner of amino acid-derivatives attaching to a polyketide moiety by C-C bond. The postulated biosynthetic pathways for 1 and 2 were discussed. Additionally, compound 1 exhibited significant acetylcholinesterase inhibitory activity, with IC50 values of 6.35 µM.


Assuntos
Alcaloides , Penicillium , Policetídeos , Estrutura Molecular , Policetídeos/química , Acetilcolinesterase/metabolismo , Penicillium/química , Peptídeos/metabolismo , Alcaloides/química
5.
Eur J Clin Pharmacol ; 80(3): 383-393, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38151504

RESUMO

BACKGROUND: Spontaneous reporting of adverse drug reactions (ADRs) is essential for the post-marketing safety evaluation of drugs. Therefore, good monitoring of ADRs is vital for strengthening drug supervision, management, and guiding rational drug use. Chinese medical institutions are the primary source of ADR case reports, but the proportion of the reports in grade IIIA hospitals is still low due to serious under-reporting. The 3rd Affiliated Hospital of Chengdu Medical College, Chengdu Pidu District People's Hospital, also has such a problem. OBJECTIVE: To improve the quantity and quality of ADR reports and enhance the level of pharmacovigilance in hospitals, the Third Affiliated Hospital of Chengdu Medical College, People's Hospital of Chengdu Pidu District experienced 10 years to gradually establish a management model to improve the medical staff's reporting rate of spontaneous reporting of ADRs. The management model is led by clinical pharmacists and combines the PDCA with Teach-back methods. The purpose of this paper is to introduce the management model and discuss its advantages and shortcomings of this model. METHODS: This study was conducted at the Third Affiliated Hospital of Chengdu Medical College-Chengdu Pidu District People's Hospital. From 2016, the daily management of reporting, auditing, and data improvement of adverse drug reactions in the hospital was carried out by clinical pharmacists, who used the PDCA method combined with the Teach-back method to continuously improve the reporting program of ADRs in the hospital during 2016-2021. Then, the proportion of spontaneous reports of total, new, and serious ADRs was compared before and after the intervention. Also, we performed a time series analysis using an autoregressive moving average model to assess changes in the total number of spontaneous ADR reports before the intervention (2013-2015), the first intervention (2016-2018), and the second intervention (2019-2021). RESULTS: After the combined PDCA and Teach-back method intervention, the median number of reported ADRs per year increased from 50 (range 37-55) in the pre-intervention period to 88 (range 83-162) in the first intervention period and to 374 in the second (range 312-566). Breakpoint regression analysis of the spontaneous reporting rate of ADRs showed that the instantaneous increase after the first intervention was not statistically significant (P = 0.526). However, the reporting rate of ADRs increased at a month-by-month growth rate during the second intervention compared to the first intervention. Its spontaneous reporting rate improved 1.034 times (P = 0.002). After the second intervention, the spontaneous reporting rate of ADRs transiently increased 6.111-fold (P < 0.001), and the month-to-month growth rate increased 1.024-fold (P < 0.001) again. CONCLUSION: The management model that combines the PDCA and the Teach-back method significantly improves the reporting rate of adverse drug reactions.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Fatores de Tempo , Hospitais , Farmacovigilância , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , China
6.
Nat Prod Bioprospect ; 13(1): 46, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37919477

RESUMO

Three previously undescribed compounds, cordycicadione (1), cordycicadin F (2), and 7-hydroxybassiatin (3), were isolated from the cultures of Cordyceps cicadae JXCH1, an entomopathogenic fungus. Their structures and relative configurations were elucidated primarily by NMR spectroscopic analysis. The absolute configurations of 1 and 2 were determined by ECD calculations. Single-crystal X-ray diffraction method was adopted to determine the absolute configuration of 3. Compound 2 is a polycyclic polyketide with an unusual enol ether moiety and a spiro ring. The compounds obtained in this study were subjected to screening their inhibition against the proliferation of the human lung cancer cell line A549 and the production of nitric oxide in murine macrophages RAW264.7.

7.
Sensors (Basel) ; 23(20)2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37896709

RESUMO

Timely and accurate flame detection is a very important and practical technology for preventing the occurrence of fire accidents effectively. However, the current methods of flame detection are still faced with many challenges in video surveillance scenarios due to issues such as varying flame shapes, imbalanced samples, and interference from flame-like objects. In this work, a real-time flame detection method based on deformable object detection and time sequence analysis is proposed to address these issues. Firstly, based on the existing single-stage object detection network YOLOv5s, the network structure is improved by introducing deformable convolution to enhance the feature extraction ability for irregularly shaped flames. Secondly, the loss function is improved by using Focal Loss as the classification loss function to solve the problems of the imbalance of positive (flames) and negative (background) samples, as well as the imbalance of easy and hard samples, and by using EIOU Loss as the regression loss function to solve the problems of a slow convergence speed and inaccurate regression position in network training. Finally, a time sequence analysis strategy is adopted to comprehensively analyze the flame detection results of the current frame and historical frames in the surveillance video, alleviating false alarms caused by flame shape changes, flame occlusion, and flame-like interference. The experimental results indicate that the average precision (AP) and the F-Measure index of flame detection using the proposed method reach 93.0% and 89.6%, respectively, both of which are superior to the compared methods, and the detection speed is 24-26 FPS, meeting the real-time requirements of video flame detection.

8.
J Nat Prod ; 86(7): 1736-1745, 2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37436927

RESUMO

In our ongoing study of fungal bioactive natural products, 12 previously undescribed triquinane sesquiterpene glycosides, namely, antrodizonatins A-L (1-12), and four known compounds (13-16) have been obtained from the fermentation of the basidiomycete Antrodiella zonata. The structures were established unambiguously via extensive spectroscopic analysis and theoretical calculations of electronic circular dichroism spectra. This is the first report of triquinane sesquiterpene glycosides. Compounds 1, 5, and 12 displayed antibacterial activity against Staphylococcus aureus with MIC50 values of 35, 34, and 69 µM, respectively.


Assuntos
Basidiomycota , Polyporales , Sesquiterpenos , Glicosídeos/farmacologia , Glicosídeos/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Basidiomycota/química , Estrutura Molecular
9.
Arch Biochem Biophys ; 743: 109672, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37336341

RESUMO

Autophagy is a highly conserved biological process that has evolved across evolution. It can be activated by various external stimuli including oxidative stress, amino acid starvation, infection, and hypoxia. Autophagy is the primary mechanism for preserving cellular homeostasis and is implicated in the regulation of metabolism, cell differentiation, tolerance to starvation conditions, and resistance to aging. As a multifunctional protein, DJ-1 is commonly expressed in vivo and is associated with a variety of biological processes. Its most widely studied role is its function as an oxidative stress sensor that inhibits the production of excessive reactive oxygen species (ROS) in the mitochondria and subsequently the cellular damage caused by oxidative stress. In recent years, many studies have identified DJ-1 as another important factor regulating autophagy; it regulates autophagy in various ways, most commonly by regulating the oxidative stress response. In particular, DJ-1-regulated autophagy is involved in cancer progression and plays a key role in alleviating neurodegenerative diseases(NDS) and defective reperfusion diseases. It could serve as a potential target for the regulation of autophagy and participate in disease treatment as a meaningful modality. Therefore, exploring DJ-1-regulated autophagy could provide new avenues for future disease treatment.


Assuntos
Neoplasias , Estresse Oxidativo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/fisiologia , Hipóxia/metabolismo , Autofagia/fisiologia , Proteína Desglicase DJ-1/metabolismo
10.
Eur J Pharmacol ; 951: 175748, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37149277

RESUMO

Resveratrol (RES), a natural polyphenolic compound found in red wine and grape skins, has attracted significant attention due to its cardioprotective properties. DJ-1, a multifunctional protein that participated in transcription regulation and antioxidant defense, was shown to provide a significant protective impact in cardiac cells treated with ischemia-reperfusion. We created a myocardial ischemia-reperfusion (I/R) model in vivo and in vitro by ligating the left anterior descending branch of rats and subjecting H9c2 cells to anoxia/reoxygenation (A/R) to investigate whether RES reduces myocardial ischemia-reperfusion injury by upregulating DJ-1. We discovered that RES dramatically enhanced cardiac function in rats with I/R. Subsequently, we found that RES prevented the rise in autophagy (P62 degradation and LC3-II/LC3-I increase) induced by cardiac ischemia-reperfusion in vitro and in vivo. Notably, the autophagic agonist rapamycin (RAPA) eliminated RES-induced cardioprotective effects. In addition, Further data showed that RES significantly increased the expression of DJ-1 in the myocardium with the treatment of I/R. At the same time, pretreatment with RES reduced phosphorylation of MAPK/ERK kinase kinase 1 (MEKK1) and Jun N-terminal Kinase (JNK) stimulated by cardiac ischemia-reperfusion, and Beclin-1 mRNA and protein levels while decreasing lactate dehydrogenase (LDH) and improving cell viability. However, the lentiviral shDJ-1 and JNK agonist anisomycin disrupted the effects of RES. In summary, RES could inhibit autophagy against myocardial ischemia-reperfusion injury through DJ-1 modulation of the MEKK1/JNK pathway, providing a novel therapeutic strategy for cardiac homeostasis.


Assuntos
Isquemia Miocárdica , Traumatismo por Reperfusão Miocárdica , Ratos , Animais , Traumatismo por Reperfusão Miocárdica/metabolismo , Resveratrol/uso terapêutico , Sistema de Sinalização das MAP Quinases , MAP Quinase Quinase Quinases/metabolismo , Autofagia , Miócitos Cardíacos , Apoptose
11.
Risk Manag Healthc Policy ; 16: 563-571, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37035270

RESUMO

Background: In 2021, National Health Commission of the People's Republic of Chinese issued a document that no longer recommended the routine skin test for cephalosporin (RSTC). However, there is still resistance to the cancellation of RSTC in a primary hospital. The study aimed to explore the potential factors for hindering the abolition of the RSTC in a county-level hospital based on the PRECEDE model. Methods: The cross-sectional study was conducted on healthcare workers in the Pidu District People's Hospital, Chengdu, by online questionnaire from September 10 to September 25 in the 2021.The PRECEDE model was used to divide the potential factors of healthcare professionals in hindering the abolition of the RSTC into predisposing factors, enabling factors and reinforcing factors. Data were analyzed by ANOVA, Chi-square test, multiple linear and multiple logistic regression analysis. Results: We collected 605 respondents' valid questionnaires. 254 healthcare professionals were against cancellation of the RSTC, accounting for 41.98%. Multiple linear regression analysis showed that working for 6~10 years (ß = 1.953, P = 0.024), medium (ß = 1.995, P = 0.030) or senior (ß = 4.003, P = 0.007) professional qualification, pharmacists (ß = 3.830, P = 0.013) and working in surgical department (ß= 4.462, P < 0.001) were significantly associated with higher score of predisposing factors, enabling factors, and reinforcing factors on abolition of RSTC. Furthermore, multiple logistic regression analysis showed that pharmacists (OR=3.113, 95% CI: 1.341-7.223, P=0.030), medium professional qualification (OR=1.272, 95% CI: 0.702-2.302, P=0.008), scores of predisposing factors (OR=1.335, 95% CI: 1.033-1.726, P=0.009), and scores of enabling factors (OR=1.208, 95% CI: 1.109-1.315, P<0.001) were independently associated with the positive anticipated behavior on the abolition of RSTC. While nurses (OR=0.516, 95% CI: 0.284-0.938, P<0.001) were independently associated with anticipated negative behavior. Conclusion: Pharmacists, medium professional qualification, and healthcare professionals with higher scores of predisposing and enabling factors were more likely to have a positive anticipated behavior on the abolition of RSTC, while nurses did not.

12.
Bioresour Technol ; 377: 128915, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36934907

RESUMO

Candida Tropicalis was used to improve the dewaterability of activated sludge (AS) and reduce its biomass by degrading EPS in AS. The protein, polysaccharide, and hydrophilic amino acids in EPS decreased by 54.50, 29.20, and 61.01%, respectively. Meanwhile, molecular weight distribution indicated that yeast degraded macromolecular organics into small molecular ones. The direct addition of yeast to AS was more conducive to EPS degradation. With the addition of 0.75 g/L of wet yeast cells and 24 h of aeration enhanced the dewaterability of AS. The CST and MLSS decreased by 24.44 and 10.51%, respectively. After 30 days of operation of lab-scale continuous SBRs, the CST and MLSS of AS were reduced by 6.37 ± 2.01 and 3.57 ± 0.52%, respectively. FTIR spectroscopy results showed that some hydrophilic functional groups were reduced. This study provides a new approach for the in-situ reduction of AS in wastewater treatment plant.


Assuntos
Matriz Extracelular de Substâncias Poliméricas , Esgotos , Esgotos/química , Água/química , Polissacarídeos/química , Proteínas , Eliminação de Resíduos Líquidos
13.
Molecules ; 28(6)2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36985677

RESUMO

The ethnobotanical plant Marsdenia tenacissima has been used for hundreds of years for Dai people in Yunnan Province, China. Previously, chemical investigations on this plant have revealed that pregnane glycosides were the main biological constituents. Nine new pregnane glycosides, marsdeosides A-I (1-9), were isolated from cultivated dried stems of the medicinal plant Marsdenia tenacissima in this study. The structures were analyzed by extensive spectroscopic analysis, including 1D, 2D NMR, HRESIMS, and IR spectroscopic analysis. The absolute configurations of the sugar moieties were identified by comparing the Rf values and specific optical rotations with those of the commercially available standard samples and the data reported in the literature. Marsdeosides A (1) featured an unusual 8,14-seco-pregnane skeleton. Compounds 1, 8, and 9 showed activity against nitric oxide production in lipopolysaccharide-activated macrophage RAW264.7, with IC50 values of 37.5, 38.8, and 42.8 µM (L-NMMA was used as a positive control, IC50 39.3 µM), respectively. This study puts the knowledge of the chemical profile of the botanical plant M. tenacissima one step forward and, thereby, promotes the sustainable utilization of the resources of traditional folk medicinal plants.


Assuntos
Marsdenia , Plantas Medicinais , Humanos , Plantas Medicinais/química , Marsdenia/química , China , Pregnanos/química , Glicosídeos/química
14.
Polymers (Basel) ; 15(4)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36850158

RESUMO

As a result of their rapid development, polymer composites are seeing wider use in transportation infrastructure in China and worldwide [...].

15.
Pharmaceuticals (Basel) ; 15(12)2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36558971

RESUMO

Two triterpenes, ganoaustralins A (1) and B (2), featuring unprecedented 6/6/6/5/6 scaffolds were isolated from the fruiting bodies of the mushroom Ganoderma australe. The structures were determined by extensive NMR and HRESIMS spectroscopic analysis. The absolute configuration of the C-25 in ganoaustralin A was assigned by the phenylglycine methyl ester (PGME) method. The relative and absolute configurations of the polycyclic backbones were determined by NMR and ECD calculations, respectively. The plausible biosynthetic pathways of ganoaustralins A and B were proposed. Ganoaustralin B showed weak inhibition against ß-secretase 1.

16.
Front Microbiol ; 13: 1051281, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36483193

RESUMO

One new prenylated benzenoid, (±)-chevalieric acid (1), and four new anthraquinone derivatives, (10S,12S)-, (10S,12R)-, (10R,12S)-, and (10R,12R)-chevalierone (2-5), together with ten previously described compounds (6-15), were isolated from the fungus Aspergillus chevalieri (L. Mangin) Thom and Church. The structures of new compounds were elucidated by extensive 1D and 2D nuclear magnetic resonance (NMR), and HRESIMS spectroscopic analysis. The absolute configurations of 2-5 were determined by experimental and calculated electronic circular dichroism (ECD) and DP4+ analysis. Compound 10 showed weak cytotoxicity against human lung cancer cell line A549 with IC50 39.68 µM. Compounds 2-5 exhibited antibacterial activities against the methicillin-resistant Staphylococcus aureus (MRSA) and opportunistic pathogenic bacterium Pseudomonas aeruginosa. The MIC value for compound 6 against MRSA is 44.02 µM. Additionally, Compounds 8, 10, 11 showed weak to moderate inhibitory activities against the ß-secretase (BACE1), with IC50 values of 36.1, 40.9, 34.9 µM, respectively.

17.
Biochem Biophys Res Commun ; 637: 276-285, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-36410277

RESUMO

Myocardial Ischemic Injury is a serious threat to human health, and DJ-1 is involved in cardioprotection. The research intended to explore the effects and mechanism of DJ-1 to protect myocardium against ischemia injury. DJ-1 overexpression lentivirus vectors were transduced into the myocardium of SD rats and H9c2 cells, and an AMI model in vivo and a hypoxia model in vitro were established, respectively. Results showed that DJ-1 overexpression alleviated myocardial ischemia injury, as demonstrated by reduced the extent of myocardial infarction, improved cell survival, decreased LDH activity and CK-MB release. Furthermore, DJ-1 interacted with RACK1, activated AMPK/mTOR pathway, induced adaptive autophagy and protected the myocardium. However, RACK1 siRNA or compound C (an AMPK inhibitor) could weaken the above effect of DJ-1 on myocardium. In conclusion, DJ-1 could activate adaptive autophagy by the RACK1/AMPK/mTOR pathway and protect the myocardium against ischemia injury.


Assuntos
Proteínas Quinases Ativadas por AMP , Traumatismos Cardíacos , Proteína Desglicase DJ-1 , Animais , Humanos , Ratos , Autofagia , Hipóxia , Isquemia , Miocárdio , Proteínas de Neoplasias , Ratos Sprague-Dawley , Receptores de Quinase C Ativada , Serina-Treonina Quinases TOR , Proteína Desglicase DJ-1/metabolismo
18.
Org Lett ; 24(47): 8627-8632, 2022 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-36394522

RESUMO

Cordycicadins A-D (1-4) are four novel polyketides that were isolated from the liquid fermentation of the insect-pathogenic fungus Cordyceps cicadae JXCH1. The structures were determined by a combination of spectroscopic analysis, single-crystal X-ray diffraction, and computational methods. Compounds 1, 3, and 4 harbor an unusual exocyclic enol ether bridge that connects the separated ring systems. Hypothetical biosynthetic pathways for 1-4 were proposed. Cordycicadins A (1) and B (2) showed antifeedant activity against silkworm larvae (Bombyx mori) with EC50 values of 65.4 and 57.0 µg/cm2, respectively.


Assuntos
Bombyx , Cordyceps , Policetídeos , Animais , Policetídeos/farmacologia , Cristalografia por Raios X
19.
Sci Transl Med ; 14(674): eabm9151, 2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-36137009

RESUMO

Obesity, characterized by chronic low-grade inflammation of the adipose tissue, is associated with adverse coronavirus disease 2019 (COVID-19) outcomes, yet the underlying mechanism is unknown. To explore whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of adipose tissue contributes to pathogenesis, we evaluated COVID-19 autopsy cases and deeply profiled the response of adipose tissue to SARS-CoV-2 infection in vitro. In COVID-19 autopsy cases, we identified SARS-CoV-2 RNA in adipocytes with an associated inflammatory infiltrate. We identified two distinct cellular targets of infection: adipocytes and a subset of inflammatory adipose tissue-resident macrophages. Mature adipocytes were permissive to SARS-CoV-2 infection; although macrophages were abortively infected, SARS-CoV-2 initiated inflammatory responses within both the infected macrophages and bystander preadipocytes. These data suggest that SARS-CoV-2 infection of adipose tissue could contribute to COVID-19 severity through replication of virus within adipocytes and through induction of local and systemic inflammation driven by infection of adipose tissue-resident macrophages.


Assuntos
COVID-19 , RNA Viral , Humanos , SARS-CoV-2 , Autopsia , Tecido Adiposo
20.
Phytochemistry ; 204: 113421, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36055425

RESUMO

Eight undescribed phenylpropanoid-dihydrochalcone hybrids, namely (+)- and (-)-malahupin A, (+)- and (-)-malahupin B, (±)-malahupin C, malahupinosides A and B, 7‴-epi-malahupinoside B, together with two known compounds, phloretin and phlorizin, were isolated from the leaves of the folk medicinal plant Malus hupehensis. Their structures were elucidated by extensive NMR and MS spectroscopic methods, chiral-phase analysis, and ECD calculations. Compounds (+)-malahupin B and malahupinoside B showed weak inhibition activities against the nitric oxide production in liposaccharide-induced murine RAW264.7 macrophages with IC50 values of 36.7 and 27.0 µM, respectively. Compounds (+)- and (-)-malahupin A, (+)- and (-)-malahupin B exhibited significant α-glucosidase inhibitory activity, with IC50 values of 22.5, 19.1, 19.2, and 17.4 µM, respectively. The postulated biosynthetic pathways to these hybrid compounds were proposed. This work represents the first report of the natural phenylpropanoid-dihydrochalcone hybrid compound, and lays foundation for the study on the bioactive principles of the ethnic hypoglycemic medicinal plant.

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