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1.
J Environ Manage ; 356: 120719, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38520863

RESUMO

Nitrate pollution in surface water and ground water has drawn wide attention, which has brought challenges to human health and natural ecology. Electroreduction of nitrate to NH3 in waste water was a way to turn waste into wealth, which has attracted interest of many researchers. Using Nickel foam as substrate, we prepared Pd/In bimetallic electrode (NF-Pd/In) according to a two-step electrodeposition method. There are many irregularly shaped particles in the size range of 10 nm-100 nm accumulated on the surface of prepared NF-Pd/In electrode, which could supply high specific area and more active sites for nitrate electroreduction. FESEM-EDS, XRD and XPS analysis confirmed the uniform distribution of Pd and In on the surface of prepared NF-Pd/In electrode, with a mass ratio of 4.5/1. Above 96% of 100 mg/L NO3--N was removed and 95% of NH3 selectivity was reached after 5 h of reaction under -1.6 V vs. Ag/AgCl sat. KCl when using 0.05 mol/L of Na2SO4 as electrolyte. High concentration of NaCl (0.05 mol/L) in the test solution dramatically decreased the NH3 selectivity because the produced NH3 could be further oxidized to N2 by the formed HClO from Cl-. EIS tests indicated that the prepared NF-Pd/In electrode showed much lower electrode resistance than NF due to the adsorptive property and electrocatalytic ability for nitrate removal. Density functional theory (DFT) calculations indicated that the presence of In could promote the conversion of NO3- to *NO3 during the process of nitrate electroreduction to NH3. Circulating tests demonstrated the stability of prepared NF-Pd/In electrode.


Assuntos
Níquel , Nitratos , Humanos , Nitratos/química , Níquel/química , Amônia , Paládio/química , Eletrodos
2.
J Med Virol ; 96(2): e29472, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38373201

RESUMO

Interferons (IFNs) are critical for immune defense against pathogens. While type-I and -III IFNs have been reported to inhibit SARS-CoV-2 replication, the antiviral effect and mechanism of type-II IFN against SARS-CoV-2 remain largely unknown. Here, we evaluate the antiviral activity of type-II IFN (IFNγ) using human lung epithelial cells (Calu3) and ex vivo human lung tissues. In this study, we found that IFNγ suppresses SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Moreover, IFNγ treatment does not significantly modulate the expression of SARS-CoV-2 entry-related factors and induces a similar level of pro-inflammatory response in human lung tissues when compared with IFNß treatment. Mechanistically, we show that overexpression of indoleamine 2,3-dioxygenase 1 (IDO1), which is most profoundly induced by IFNγ, substantially restricts the replication of ancestral SARS-CoV-2 and the Alpha and Delta variants. Meanwhile, loss-of-function study reveals that IDO1 knockdown restores SARS-CoV-2 replication restricted by IFNγ in Calu3 cells. We further found that the treatment of l-tryptophan, a substrate of IDO1, partially rescues the IFNγ-mediated inhibitory effect on SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Collectively, these results suggest that type-II IFN potently inhibits SARS-CoV-2 replication through IDO1-mediated antiviral response.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Replicação Viral , Pulmão , Interferons , Células Epiteliais , Antivirais/farmacologia
3.
Environ Res ; 241: 117616, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37956750

RESUMO

High nitrate concentration in water can lead to eutrophication and the disruption of healthy aquatic ecosystems. Additionally, in the human digestive system, it has the potential to be reduced to nitrite, which can be damaging to people's physical health. Catalytic hydrogenation of nitrate is one of the strategies for removing nitrate from water. Using A520E resin as support, we prepared Pd/Cu nano-catalyst (Pd/Cu@A520E) according to a liquid phase reduction method. A520E could improve the transfer process of nitrate in the solution to the activity sites of Pd/Cu nanoparticles, thus increase the reaction rate of nitrate reduction. Pd/Cu bimetallic nano-particles were evenly distributed on/in the resin with a size range from 2 nm to 10 nm. The External Circulating System equipped with Venturi tube (ECSV) was designed to improve the utilization efficiency of H2 in both batch tests and long-term continuous-flow tests. Nearly 100% of nitrate removal efficiency and above 90% of N2 selectivity were achieved in both batch tests and continuous-flow tests. Coexisting Cl- and SO42- at 300 mg/L showed little impact on the property of Pd/Cu@A520E. Pd/Cu@A520E also showed high nitrate removal property and stability in continuous-flow tests of more than 800 h. NO3- was adsorbed onto the active sites (functional groups and Pd/Cu particle sites), meanwhile H2 was adsorbed onto the active sites of Pd/Cu@A520E to form Pd [H]. Then the adsorbed NO3- was reduced into N2 (main product) or NH4+ by Pd [H]. In addition, Pd/Cu@A520E showed high nitrate removal property from municipal waste water.


Assuntos
Resinas de Troca Aniônica , Nitratos , Humanos , Nitratos/química , Ecossistema , Compostos Orgânicos , Nitritos , Catálise
4.
EBioMedicine ; 99: 104916, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38101297

RESUMO

BACKGROUND: Earlier Omicron subvariants including BA.1, BA.2, and BA.5 emerged in waves, with a subvariant replacing the previous one every few months. More recently, the post-BA.2/5 subvariants have acquired convergent substitutions in spike that facilitated their escape from humoral immunity and gained ACE2 binding capacity. However, the intrinsic pathogenicity and replication fitness of the evaluated post-BA.2/5 subvariants are not fully understood. METHODS: We systemically investigated the replication fitness and intrinsic pathogenicity of representative post-BA.2/5 subvariants (BL.1, BQ.1, BQ.1.1, XBB.1, CH.1.1, and XBB.1.5) in weanling (3-4 weeks), adult (8-10 weeks), and aged (10-12 months) mice. In addition, to better model Omicron replication in the human nasal epithelium, we further investigated the replication capacity of the post-BA.2/5 subvariants in human primary nasal epithelial cells. FINDINGS: We found that the evaluated post-BA.2/5 subvariants are consistently attenuated in mouse lungs but not in nasal turbinates when compared with their ancestral subvariants BA.2/5. Further investigations in primary human nasal epithelial cells revealed a gained replication fitness of XBB.1 and XBB.1.5 when compared to BA.2 and BA.5.2. INTERPRETATION: Our study revealed that the post-BA.2/5 subvariants are attenuated in lungs while increased in replication fitness in the nasal epithelium, indicating rapid adaptation of the circulating Omicron subvariants in the human populations. FUNDING: The full list of funding can be found at the Acknowledgements section.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Humanos , Animais , Camundongos , Virulência , Células Epiteliais , Mucosa Nasal
5.
Food Funct ; 14(24): 10784-10795, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37982421

RESUMO

Over the past few decades, food allergy has continued to rise, significantly affecting our health, economy, and quality of life. However, current therapeutic strategies have limited efficacy and need to be improved. One alternative to prevent or reduce allergies is to modulate immunity and microbiota. Human milk (HM) could be considered a protective factor against food allergy, but how probiotics in human milk impact the susceptibility to food allergy remains unknown. Therefore, we studied the preventive impact of human milk Lactobacillus rhamnosus Probio-M9 on food allergy in ovalbumin (OVA)-sensitized mice. We studied the effects of oral administration of Probio-M9 on allergic signatures, immune response, gut microbiota, and metabolism. Oral therapeutic administration of live Probio-M9, but not heat-killed Probio-M9, significantly reduces OVA-specific IgE (OVA-sIgE), histamine, and mMCP-1 (mouse mast cell protease-1) levels in OVA-sensitized mice. Moreover, Probio-M9 supplementation reduced allergic inflammation and changes in the Th2/Th1 balance toward a dampened Th2 response. 16S rDNA sequencing analysis revealed an increased ratio of Firmicutes/Bacteroidota (F/B) and the relative abundance of short-chain fatty acid (SCFA)-producing Clostridia in the feces after Probio-M9 intake. Simultaneously, Probio-M9 significantly increased the levels of SCFAs and promoted the phosphorylation of signal transducer and activator of transcription 3 (STAT3), thereby inducing the expression of the antimicrobial peptides (AMPs) Reg3b and Reg3g. Our findings suggest that the use of Probio-M9 can be a potent strategy in food allergy prevention.


Assuntos
Hipersensibilidade Alimentar , Microbioma Gastrointestinal , Lacticaseibacillus rhamnosus , Probióticos , Camundongos , Humanos , Animais , Ovalbumina , Qualidade de Vida , Camundongos Endogâmicos BALB C
6.
Food Res Int ; 173(Pt 2): 113398, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37803736

RESUMO

In recent years, with the increasing health needs of people, plant-based meat products have gradually entered the public's vision. However, many plant-based meats on the market today are so heavily processed and use so many additives that they can be classified as ultra-processed foods (UPFs). Very limited studies report whether the benefits of these plant-based meats are discounted when lots of additives were added. In this experiment, mice were fed with processed plant-based meat, ultra-processed plant-based meat, low-processed red meat, ultra-processed red meat to compare the health effects. In this experiment, some serum biochemical indexes, hematoxylin-eosin (HE) staining of liver and intestine, 16s rDNA and short-chain fatty acids of mouse feces were detected. Compared with the negative control group, it was found that mice in the ultra-processed plant-based meat group, ultra-processed red meat group, and low-processed red meat group gained significant weight, and there exist intestinal inflammation and liver inflammation. In terms of gut microbiota, the diversity and structure of gut microbiota in both two plant-meat group was better than that in both two red-meat group. It can be concluded that plant-based meat and red meat cause different gut microbiota outcomes, which in turn affect body weight and the occurrence of liver and intestinal inflammation. What's more, plant-based meat is healthier than red meat, but overprocessing reduces the benefits of plant-based meat. There is a need to improve the way plant-based meat is processed and reduce the amount of additives used.


Assuntos
Produtos da Carne , Carne Vermelha , Humanos , Camundongos , Animais , Carne , Inflamação , Intestinos
7.
Reproduction ; 166(5): 357-368, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37699083

RESUMO

In brief: Autophagy is important for trophoblast cells at the maternal-fetal interface during early pregnancy. This study suggests that trophoblast cells can promote the autophagy under a regulation of the LPA/LPAR 1-NHE1 axis. Abstract: The autophagy of trophoblasts is necessary for developing and maintaining a healthy pregnancy. Autophagy dysfunction in trophoblast cells is linked to recurrent spontaneous abortion (RSA). However, the mechanism underlying trophoblast autophagy is unknown. In this study, we investigated the expression of autophagy-related genes in both normal and RSA villi. We also examined the production of LPA and LPAR1 in trophoblast cells during early pregnancy. We found that the activation of the LPA-LPAR1 axis triggered the autophagy of trophoblast cells and increased the expression of NHE1. Inhibition of NHE1 suppressed the autophagy in trophoblast cells and we confirmed that NHE1 regulates LPA production in trophoblast cells. Additionally, we found decreased expression of autophagy-related genes and LPAR1 in villi from RSA patients. These observations indicate that the LPA/LPAR1-NHE1 axis regulates the autophagy of trophoblast cells during pregnancy. Insufficient autophagy and poor expression of LPAR1 in trophoblast cells may result in the dysfunction of the trophoblasts and an increased risk of spontaneous abortion. Overall, our research elucidated that a positive LPA/LPAR1-NHE1 axis can promote the autophagy of trophoblast cells and the abnormal axis leads to the autophagy deficiency of trophoblast cells in recurrent spontaneous abortion.

8.
Foods ; 12(17)2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37685223

RESUMO

Changes in behavior, lifestyle, and nutritional patterns have influenced many potential risk variables globally. In recent decades, food allergies (FAs) have been elevated to a severe public health issue both in developed countries and developing countries (third-world countries). This study aims to evaluate the effects caused by certain factors such as lifestyle and dietary habits on food allergies, review the association of lifestyle and dietary habit status with FAs, and outline why more people are allergic to food sources as a result of lifestyle changes and dietary habits. We searched electronic international databases including Scopus, PubMed, Google Scholar, and Web of Science using combinations of keywords. Utilizing Excel, the relevant studies were included and the irrelevant studies were excluded, and Mendeley was used for referencing and also to remove duplicates. The framework proposed by Arksey and O'Malley was used for this scoping review. The papers published in the databases from 2016 to 2020 were extracted. A total of eight studies were extracted, and this scoping review was carried out according to the risk factors. In our review, we found that some lifestyle choices (Caesarean section and antibiotics) and dietary habits (n-3 PUFA, fast food, duration of dietary intervention, and vitamin D), were important contributing factors for FA.

9.
EBioMedicine ; 95: 104753, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37579626

RESUMO

BACKGROUND: Among the Omicron sublineages that have emerged, BA.1, BA.2, BA.5, and their related sublineages have resulted in the largest number of infections. While recent studies demonstrated that all Omicron sublineages robustly escape neutralizing antibody response, it remains unclear on whether these Omicron sublineages share any pattern of evolutionary trajectory on their replication efficiency and intrinsic pathogenicity along the respiratory tract. METHODS: We compared the virological features, replication capacity of dominant Omicron sublineages BA.1, BA.2 and BA.5 in the human nasal epithelium, and characterized their pathogenicity in K18-hACE2, A129, young C57BL/6, and aged C57BL/6 mice. FINDINGS: We found that BA.5 replicated most robustly, followed by BA.2 and BA.1, in the differentiated human nasal epithelium. Consistently, BA.5 infection resulted in higher viral gene copies, infectious viral titres and more abundant viral antigen expression in the nasal turbinates of the infected K18-hACE2 transgenic mice. In contrast, the Omicron sublineages are continuously attenuated in lungs of infected K18-hACE2 and C57BL/6 mice, leading to decreased pathogenicity. Nevertheless, lung manifestations remain severe in Omicron sublineages-infected A129 and aged C57BL/6 mice. INTERPRETATION: Our results suggested that the Omicron sublineages might be gaining intrinsic replication fitness in the upper respiratory tract, therefore highlighting the importance of global surveillance of the emergence of hyper-transmissive Omicron sublineages. On the contrary, replication and intrinsic pathogenicity of Omicron is suggested to be further attenuated in the lower respiratory tract. Effective vaccination and other precautions should be in place to prevent severe infections in the immunocompromised populations at risk. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.


Assuntos
COVID-19 , Camundongos , Animais , Humanos , Idoso , Camundongos Endogâmicos C57BL , SARS-CoV-2 , Virulência , Anticorpos Neutralizantes , Camundongos Transgênicos , Anticorpos Antivirais
10.
Nanotechnology ; 34(39)2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37356427

RESUMO

An innovative Pd-Me (Pd-Cu, Pd-In and Pd-Sn) bimetallic catalyst supported on porous chelating DOWEX M4195 resin (D) was established to reduce the nitrate almost entirely and achieved high selectivity to the expected harmless form of nitrogen. In this study, sodium borohydride (NaBH4) was applied in preparing bimetallic catalysts by liquid-phase reduction as the prestoring reductant. Pd-In/D and Pd-Sn/D groups performed well in N2selectivity (all above 97%). In addition, Pd-In and Pd-Sn bimetallic catalysis yields higher selectivity towards N2than the Pd-Cu pair in the presence of HCO3-, Cl-, SO42-and humic acid. Likewise, in terms of N2selectivity, Pd-In/D and Pd-Sn/D bimetallic catalysts were superior to that of Pd-Cu/D (72.16%) in the municipal wastewater treatment plant sewage. The current results provide insight into the superb reactivity, excellent stability, and most important-extremely high harmless N2selectivity of Pd-In and Pd-Sn-based bimetallic catalysts in practical application and provide new ideas for enhancing the feasibility of the catalytic reduction of nitrate by minimizing environmentally harmful by-products.


Assuntos
Nitratos , Purificação da Água , Água , Cobre , Purificação da Água/métodos , Catálise
11.
Int Heart J ; 64(3): 462-469, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37258122

RESUMO

The research aimed to study the mechanism of how trimethylamine N-oxide (TMAO) regulates autophagy to promote atherosclerosis (AS). The AS in vitro model was constructed with vascular smooth muscle cells (VSMCs) treated with ox-LDL. The Cell Counting Kit-8 (CCK-8) trial was chosen to examine VSMCs' absorbance (OD) value. A transmission electron microscope (TEM) was selected for monitoring autophagosomes. Western blotting (WB) was adopted for examining the expression of Beclin-1, p62, LC3, α-SMA, SM22-α, OPN, PI3K, AKT, mTOR, p-PI3K, p-AKT, and p-mTOR proteins. Real-time fluorescent quantitative PCR (RT-qPCR) was accepted for testing the expression of α-SMA, SM22-α, OPN, PI3K, AKT, mTOR, Beclin-1, p62, and LC3 genes. The transwell assay was employed to examine the ability of migration in VSMCs. Oil red O staining assay was accepted to stain lipid droplets in VSMCs. TMAO noticeably promoted autophagy inhibition and the phenotypic transformation of AS. Protein expressions of p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR, and p62 of the TMAO+ox-LDL group were higher than the ox-LDL group, while Beclin-1 and LC3 were lower than the ox-LDL group. Gene expressions of PI3K, AKT, mTOR, and p62 of the TMAO+ox-LDL group were higher than the ox-LDL group, while Beclin-1 and LC3 were lower than the ox-LDL group. The intervention of LY294002 reversed the regulation of the corresponding proteins and genes. The study proved that TMAO could promote autophagy inhibition of AS via activating the PI3K/AKT/mTOR pathway. It supplied a reliable basis for improving clinical diagnostic methods and developing targeted AS drugs.


Assuntos
Aterosclerose , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fosfatidilinositol 3-Quinases/metabolismo , Músculo Liso Vascular/metabolismo , Proteína Beclina-1/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Lipoproteínas LDL/farmacologia , Autofagia , Aterosclerose/metabolismo
12.
Sci Adv ; 9(3): eadd3867, 2023 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-36662861

RESUMO

Successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires proteolytic cleavage of the viral spike protein. While the role of the host transmembrane protease serine 2 in SARS-CoV-2 infection is widely recognized, the involvement of other proteases capable of facilitating SARS-CoV-2 entry remains incompletely explored. Here, we show that multiple members from the membrane-type matrix metalloproteinase (MT-MMP) and a disintegrin and metalloproteinase families can mediate SARS-CoV-2 entry. Inhibition of MT-MMPs significantly reduces SARS-CoV-2 replication in vitro and in vivo. Mechanistically, we show that MT-MMPs can cleave SARS-CoV-2 spike and angiotensin-converting enzyme 2 and facilitate spike-mediated fusion. We further demonstrate that Omicron BA.1 has an increased efficiency on MT-MMP usage, while an altered efficiency on transmembrane serine protease usage for virus entry compared with that of ancestral SARS-CoV-2. These results reveal additional protease determinants for SARS-CoV-2 infection and enhance our understanding on the biology of coronavirus entry.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/metabolismo , Peptídeo Hidrolases/metabolismo , Proteólise , Metaloproteases/metabolismo , Internalização do Vírus
13.
Food Chem ; 401: 134189, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36113213

RESUMO

Kiwifruit is an excellent source and has highly drawn attention due to its essential nutrients and health benefits. However, kiwifruit can trigger allergenic symptoms and cause health problems worldwide. This study aimed to evaluate the impact of microwave processing on the nutritional properties and allergenicity of kiwifruit. Samples were treated with microwave at 75 â„ƒ for 0-5 min. The microstructure, color attributes, allergen (Act d 2) content, in vitro digestibility, and secondary structure of kiwifruit protein were determined. The results found that microwave processing significantly increased the total antioxidant activity by disrupting the microstructure of kiwifruit tissues. The digestibility and peptide content of kiwifruit protein was improved. Whereas a negative effect on the color attributes and sugar content was observed. An 80 % reduction in Act d 2 content was observed after a 5-min microwave treatment. Therefore, microwave processing showed a potential application in reducing kiwifruit allergenicity.


Assuntos
Actinidia , Hipersensibilidade Alimentar , Alérgenos/química , Hipersensibilidade Alimentar/prevenção & controle , Micro-Ondas , Antioxidantes/metabolismo , Actinidia/química , Açúcares/metabolismo
14.
Crit Rev Food Sci Nutr ; : 1-17, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36576159

RESUMO

Food allergy has caused lots of global public health issues, particularly in developed countries. Presently, gut microbiota has been widely studied on allergy, while the role of dysbiosis in food allergy remains unknown. Scientists found that changes in gut microbial compositions and functions are strongly associated with a dramatic increase in the prevalence of food allergy. Altering microbial composition is crucial in modulating food antigens' immunogenicity. Thus, the potential roles of probiotics, prebiotics, synbiotics, and postbiotics in affecting gut bacteria communities and the immune system, as innovative strategies against food allergy, begins to attract high attention of scientists. This review briefly summarized the mechanisms of food allergy and discussed the role of the gut microbiota and the use of probiotics, prebiotics, synbiotics, and postbiotics as novel therapies for the prevention and treatment of food allergy. The perspective studies on the development of novel immunotherapy in food allergy were also described. A better understanding of these mechanisms will facilitate the development of preventive and therapeutic strategies for food allergy.

15.
Cell Rep Med ; 3(9): 100743, 2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-36084644

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 was a dominant circulating SARS-CoV-2 variant worldwide. Recent reports hint that BA.2 is similarly potent regarding antibody evasion but may be more transmissible than BA.1. The pathogenicity of BA.2 remains unclear and is of critical public health significance. Here we investigated the virological features and pathogenicity of BA.2 with in vitro and in vivo models. We show that BA.2 is less dependent on transmembrane protease serine 2 (TMPRSS2) for virus entry in comparison with BA.1 in vitro. In K18-hACE2 mice, BA.2 replicates more efficiently than BA.1 in the nasal turbinates and replicates marginally less efficiently in the lungs, leading to decreased body weight loss and improved survival. Our study indicates that BA.2 is similarly attenuated in lungs compared with BA.1 but is potentially more transmissible because of its better replication at the nasal turbinates.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Humanos , Camundongos , SARS-CoV-2/genética , Serina , Virulência
16.
Int J Mol Sci ; 23(17)2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36077501

RESUMO

The endocrine-related cancers and hormones are undoubtedly highly interconnected. How hormones support or repress tumor induction and progression has been extensively profiled. Furthermore, advances in understanding the role of glutamine metabolism in mediating tumorigenesis and development, coupled with these in-depth studies on hormone (e.g., estrogen, progesterone, androgen, prostaglandin, thyroid hormone, and insulin) regulation of glutamine metabolism, have led us to think about the relationship between these three factors, which remains to be elucidated. Accordingly, in this review, we present an updated overview of glutamine metabolism traits and its influence on endocrine oncology, as well as its upstream hormonal regulation. More importantly, this hormone/glutamine metabolism axis may help in the discovery of novel therapeutic strategies for endocrine-related cancer.


Assuntos
Neoplasias das Glândulas Endócrinas , Neoplasias , Sistema Endócrino/metabolismo , Glutamina/metabolismo , Humanos , Insulina , Hormônios Tireóideos
17.
Int J Mol Sci ; 23(17)2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36077508

RESUMO

Galectins (Gal) are characterized by their affinity for galactoside structures on glycoconjugates. This relationship is mediated by carbohydrate recognition domains, which are multifunctional regulators of basic cellular biological processes with high structural similarity among family members. They participate in both innate and adaptive immune responses, as well as in reproductive immunology. Recently, the discovery that galectins are highly expressed at the maternal-fetal interface has garnerd the interest of experts in human reproduction. Galectins are involved in a variety of functions such as maternal-fetal immune tolerance, angiogenesis, trophoblast invasion and placental development and are considered to be important mediators of successful embryo implantation and during pregnancy. Dysregulation of these galectins is associated with abnormal and pathological pregnancies (e.g., preeclampsia, gestational diabetes mellitus, fetal growth restriction, preterm birth). Our work reviews the regulatory mechanisms of galectins in normal and pathological pregnancies and has implications for clinicians in the prevention, diagnosis and treatment of pregnancy-related diseases.


Assuntos
Galectinas , Nascimento Prematuro , Feminino , Galectinas/química , Humanos , Recém-Nascido , Placenta/patologia , Placentação , Gravidez , Nascimento Prematuro/patologia , Trofoblastos
18.
Emerg Microbes Infect ; 11(1): 2275-2287, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36039901

RESUMO

SARS-CoV-2 B.1.1.529.1 (Omicron BA.1) emerged in November 2021 and quickly became the predominant circulating SARS-CoV-2 variant globally. Omicron BA.1 contains more than 30 mutations in the spike protein, which contribute to its altered virological features when compared to the ancestral SARS-CoV-2 or previous SARS-CoV-2 variants. Recent studies by us and others demonstrated that Omicron BA.1 is less dependent on transmembrane serine protease 2 (TMPRSS2), less efficient in spike cleavage, less fusogenic, and adopts an altered propensity to utilize the plasma membrane and endosomal pathways for virus entry. Ongoing studies suggest that these virological features of Omicron BA.1 are in part retained by the subsequent Omicron sublineages. However, the exact spike determinants that contribute to these altered features of Omicron remain incompletely understood. In this study, we investigated the spike determinants for the observed virological characteristics of Omicron. By screening for the individual changes on Omicron BA.1 and BA.2 spike, we identify that 69-70 deletion, E484A, and H655Y contribute to the reduced TMPRSS2 usage while 25-27 deletion, S375F, and T376A result in less efficient spike cleavage. Among the shared spike mutations of BA.1 and BA.2, S375F and H655Y reduce spike-mediated fusogenicity. Interestingly, the H655Y change consistently reduces serine protease usage while increases the use of endosomal proteases. In keeping with these findings, the H655Y substitution alone reduces plasma membrane entry and facilitates endosomal entry when compared to SARS-CoV-2 WT. Overall, our study identifies key changes in Omicron spike that contributes to our understanding on the virological determinant and pathogenicity of Omicron.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Mutação , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo
19.
Nature ; 609(7928): 785-792, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35922005

RESUMO

Highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus 2 (refs. 1,2) (SARS-CoV-2), Middle East respiratory syndrome coronavirus3 (MERS-CoV) and SARS-CoV-1 (ref. 4), vary in their transmissibility and pathogenicity. However, infection by all three viruses results in substantial apoptosis in cell culture5-7 and in patient tissues8-10, suggesting a potential link between apoptosis and pathogenesis of coronaviruses. Here we show that caspase-6, a cysteine-aspartic protease of the apoptosis cascade, serves as an important host factor for efficient coronavirus replication. We demonstrate that caspase-6 cleaves coronavirus nucleocapsid proteins, generating fragments that serve as interferon antagonists, thus facilitating virus replication. Inhibition of caspase-6 substantially attenuates lung pathology and body weight loss in golden Syrian hamsters infected with SARS-CoV-2 and improves the survival of mice expressing human DPP4 that are infected with mouse-adapted MERS-CoV. Our study reveals how coronaviruses exploit a component of the host apoptosis cascade to facilitate virus replication.


Assuntos
Ácido Aspártico , Caspase 6 , Infecções por Coronavirus , Coronavirus , Cisteína , Interações Hospedeiro-Patógeno , Replicação Viral , Animais , Apoptose , Ácido Aspártico/metabolismo , Caspase 6/metabolismo , Coronavirus/crescimento & desenvolvimento , Coronavirus/patogenicidade , Infecções por Coronavirus/enzimologia , Infecções por Coronavirus/virologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/metabolismo , Cricetinae , Cisteína/metabolismo , Dipeptidil Peptidase 4/genética , Dipeptidil Peptidase 4/metabolismo , Humanos , Interferons/antagonistas & inibidores , Interferons/imunologia , Pulmão/patologia , Mesocricetus , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , SARS-CoV-2 , Taxa de Sobrevida , Redução de Peso
20.
Environ Res ; 214(Pt 4): 114141, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35995216

RESUMO

Nitrate pollution in ground water and surface water has been becoming a worldwide problem that poses a great challenge to steady water ecosystem and human health. Electrochemical reduction is a promising way to remove nitrate from water because of advantages. We prepared Pd/Sn modified nickel foam (NF) electrode according to a two-step electrodeposition method. The prepared NF-Pd/Sn electrode showed a micromorphology like "Karst Fengcong" with peaks, saddles and nadirs intertwined with each other. Pd0 and Sn0 were detected on the NF-Pd/Sn electrode and the mass ratio of Pd/Sn was 4.3/1. The NF-Pd/Sn electrode showed the highest reaction rate (kobs: 0.543 h-1) and removal efficiency (94%) under the condition of 100 mg N/L, 0.05 mol/L Na2SO4 and -1.6 V vs. Ag/AgCl sat. KCl. The highest N2-selectivity (100%) was reached under the condition of 100 mg N/L, 0.05 mol/L NaCl and -1.6 V vs. Ag/AgCl sat. KCl. The microstructure of NF-Pd/Sn electrode like "Karst Fengcong" could provide large specific surface area and more active sites for nitrate adsorption and electrocatalytic reduction in aqueous solution. The adsorption and the reduction reaction of nitrate on the surface of NF-Pd/Sn could increase the electric current response in the test system.


Assuntos
Níquel , Nitratos , Ecossistema , Eletrodos , Humanos , Nitratos/química , Óxidos de Nitrogênio , Paládio/química , Água
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