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M-N-C-type single-atom catalysts (SACs) are highly efficient for the electrocatalytic oxygen evolution reaction (OER). And the isolated metal atoms are usually considered real active sites. However, the oxidative structural evolution of coordinated N during the OER will probably damage the structure of M-N-C, hence resulting in a completely different reaction mechanism. Here, we reveal the aggregation of M-N-C materials during the alkaline OER. Taking Ni-N-C as an example, multiple characterizations show that the coordinated N on the surface of Ni-N-C is almost completely dissolved in the form of NO3-, accompanied by the generation of abundant O functional groups on the surface of the carbon support. Accordingly, the Ni-N bonds are broken. Through a dissolution-redeposition mechanism and further oxidation, the isolated Ni atoms are finally converted to NiOOH nanoclusters supported by carbon as the real active sites for the enhanced OER. Fe-N-C and Co-N-C also have similar aggregation mechanism. Our findings provide unique insight into the structural evolution and activity origin of M-N-C-based catalysts under electrooxidative conditions.
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The mitochondrial unfolded protein response (UPRmt) is a cytoprotective response in response to cellular stress that is activated in response to mitochondrial stress to maintain intra-protein homeostasis, thereby protecting the cell from a variety of stimuli. The activation of this response has been linked to cardiovascular diseases. Here, we reviewed the current understanding of UPRmt and discussed its specific molecular mechanism, mainly in mammals, as well as addressing its protective role against cardiovascular diseases, so as to provide direction for further research on UPRmt and therapies targeting cardiovascular diseases in the future.
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Doenças Cardiovasculares , Mitocôndrias , Resposta a Proteínas não Dobradas , Resposta a Proteínas não Dobradas/fisiologia , Humanos , Animais , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/metabolismo , Mitocôndrias/metabolismo , Transdução de SinaisRESUMO
M-N-C single-atom catalysts (SACs) are promising electrode materials for many electro-reduction reactions. However, their stability is far from practical applications, and their deactivation mechanism has been rarely investigated. Herein, we demonstrate the structural degradation of M-N-C (M=Co, Ni, and Fe) at industrial-grade current density for long-term electro-reduction. Both M-N and N-C bonds are broken, resulting in the gradual hydrogenation and dissolution of N in the form of ammonia. The residual M is finally converted to M-containing core-shell nanoparticles after sequential dissolution, redeposition, and electro-reduction. The destruction of the M-N-C structure and the formation of nanoparticles greatly affect the electrocatalytic performance. Our work highlights the structural degradation and deactivation mechanism of M-N-C-type SACs under strong reductive conditions and provides useful information for inspiring researchers to develop new strategies to improve the electrocatalytic stability of similar types of materials.
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INTRODUCTION: The dysregulation of deubiquitination has been shown to affect the development of pre-eclampsia (PE). A disintegrin and metalloprotease 9 (ADAM9) plays roles in diverse physiological contexts, including PE. Here, this study aimed to investigate whether ADAM9 regulated trophoblast cell dysfunction through ubiquitin-specific protease 22 (USP22) deubiquitinase-mediated deubiquitination during PE. METHODS: Levels of genes and proteins were tested via qRT-PCR and western blotting assays. Cell proliferation, migration, and invasion were detected using cell counting kit-8, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell and wound healing assays, respectively. Epithelial-mesenchymal transition related markers were assayed using western blotting. Proteins between USP22 and ADAM9 were identified by co-immunoprecipitation assay. RESULTS: ADAM9 was highly expressed in PE patients, functionally, ADAM9 overexpression weakened the proliferation, migration, invasion, and EMT progression in trophoblast cells. Mechanistically, the deubiquitinase USP22 removed ubiquitination on ADAM9 and maintained its stability. Forced expression of USP22 also suppressed the proliferation and mobility in trophoblast cells. Moreover, the regulatory effects of USP22 on trophoblast cells were reversed by ADAM9 silencing. In addition, USP22 interacted with ADAM9 to regulate the activation of Wnt/ß-catenin pathway. DISCUSSION: ADAM9 was deubiquitinated and stabilized by USP22 and then suppressed the proliferation, migration, invasion, and EMT progression in trophoblast cells, indicating a new pathway of USP10/RUNX1 axis in PE process.
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MicroRNAs , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Pré-Eclâmpsia/metabolismo , Trofoblastos/metabolismo , Via de Sinalização Wnt , Transição Epitelial-Mesenquimal , Proliferação de Células/genética , Movimento Celular/genética , MicroRNAs/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Proteínas de Membrana/metabolismo , Proteínas ADAM/metabolismoRESUMO
BACKGROUND: The global obesity pandemic has led to an alarming rise in the prevalence of metabolic-associated fatty liver disease (MAFLD), making it a substantial clinical and economic burden on society. Early detection and effective treatment of MAFLD are imperative to mitigate its impact. METHODS: This cross-sectional study was conducted involving 4634 adults from the National Health and Nutrition Examination Surveys (NHANES) 2017-2018 cycle. Transient elastography (TE) was used to diagnose MAFLD and assess the extent of liver steatosis and fibrosis. Multivariate logistic regression models were utilized to examine the association between the triglyceride and glucose index-waist circumference (TyG-WC) and the risk of MAFLD, liver fibrosis, and steatosis. RESULTS: A positive association between TyG-WC and MAFLD persisted across all three models: model1: OR = 8.44, 95% CI: 6.85-10.38 (unadjusted), model2: OR = 8.28, 95% CI: 6.53-10.50 (partially adjusted), and model3: OR = 7.98, 95% CI: 4.11-15.46 (fully adjusted). Further investigation through interaction and stratified analysis revealed that this association was more pronounced in the non-obese and Non-Hispanic White persons groups. Moreover, a non-linear relationship analysis unveiled threshold and saturation effects between TyG-WC and MAFLD. Specifically, a TyG-WC value of approximately 600 may represent the threshold effect for MAFLD risk, while 1200 may signify the saturation effect of MAFLD risk. Finally, a robust correlation between TyG-WC and the severity of liver steatosis and fibrosis was found. CONCLUSIONS: The findings suggest that the TyG-WC index exhibits excellent predictive value for MAFLD in the general American population.
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Glicemia , Técnicas de Imagem por Elasticidade , Cirrose Hepática , Inquéritos Nutricionais , Triglicerídeos , Circunferência da Cintura , Humanos , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Triglicerídeos/sangue , Cirrose Hepática/sangue , Adulto , Estados Unidos/epidemiologia , Glicemia/metabolismo , Glicemia/análise , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Modelos Logísticos , Índice de Gravidade de Doença , Fatores de Risco , Idoso , Fígado Gorduroso/sangueRESUMO
The use of two-dimensional heterostructure composite as electrode modification material has become a new strategy to improve the electrocatalytic activity and electroactive sites of electrochemical sensor. Herein, a soluble heterostructure, namely rGO-PSS@MXene, was designed and synthesized by integrating poly (sodium p-styrenesulfonate)-functionalized reduced graphene oxide into MXene nanosheets via ultrasonic method. The interactive heterostructure can effectively alleviate the self-stacking of MXene and rGO, endowing them with superior electron transfer capacity and large specific surface area, thereby producing prominent synergistic electrocatalytic effect towards rutin. In addition, the excellent enrichment effect of rGO-PSS@MXene for rutin also plays an important role through the electrostatic and π-π stacking interactions. The electrochemical characteristics of rutin on the sensor were examined in detail and a sensitive sensing method was proposed. Under optimized conditions, the method showed satisfactory linear relationship for rutin in the concentration range of 0.005-10.0 µM, with limit of detection of 1.8 nM (S/N = 3). The quantitative validation results in herbal medicine and commercial Tartary buckwheat tea were highly consistent with the labeled quantity and the results of HPLC determination, respectively, suggesting the sensor possessed excellent selectivity and accuracy. This proposed strategy for rutin determination is expected to expand the application of MXene heterostructure in electrochemical sensors, and is envisioned as a promising candidate for quality monitoring of drugs and foods.
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Fagopyrum , Grafite , Nitritos , Elementos de Transição , Rutina/análise , Grafite/química , Fagopyrum/química , Chá , Técnicas Eletroquímicas/métodosRESUMO
The difference between solution pH and local pH near an electrode surface greatly determines the electrocatalytic performance. However, there is still a lack of a facile and universal method for the local pH detection of various electrode reactions, leaving the origin of local pH changes unclear. Herein, by using phosphate species in phosphate buffer solution (PBS) as the pH probe, we demonstrate a universal local pH detection strategy through in situ Raman spectroscopy for various electrode reactions. Oxygen evolution is chosen as the example to detect the potential-dependent local pH change. Then the strategy extends to nitrate reduction, nitrobenzene reduction, and benzylamine oxidation. By comparing the local pH changes in different reactions, we reveal that the local pH change is strongly dependent on the reaction current, the ability of the system to replenish the local H+/OH-, and the number of H+/OH- per electron transfer of the electrode reaction.
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Active sites identification in metal-free carbon materials is crucial for developing practical electrocatalysts, but resolving precise configuration of active site remains a challenge because of the elusive dynamic structural evolution process during reactions. Here, we reveal the dynamic active site identification process of oxygen modified defective graphene. First, the defect density and types of oxygen groups were precisely manipulated on graphene, combined with electrocatalytic performance evaluation, revealing a previously overlooked positive correlation relationship between the defect density and the 2 e- oxygen reduction performance. An electrocatalytic-driven oxygen groups redistribution phenomenon was observed, which narrows the scope of potential configurations of the active site. The dynamic evolution processes are monitored via multiple in-situ technologies and theoretical spectra simulations, resolving the configuration of major active sites (carbonyl on pentagon defect) and key intermediates (*OOH), in-depth understanding the catalytic mechanism and providing a research paradigm for metal-free carbon materials.
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Neurotransmitters (NTs) are essential for intercellular communication and primarily include monoamine, amino acid, and cholinergic NTs. These molecules play important roles in the body's stress response, motor coordination, neuronal communication, and homeostatic functions. Previous studies have shown that abnormal changes in NT levels are associated with various neurological disorders. Therefore, the development of accurate analytical methods for NT detection will enhance the current understanding on complex neuropathophysiology by providing functional knowledge and techniques for early diagnosis, thereby facilitating the development of new therapeutic options for the related diseases. The solid phase microextraction (SPME) technique combines sample preparation, separation, and enrichment in a single step and is minimally invasive, low cost, solvent free, and high throughput. SPME has been successfully applied to the in vivo analysis of target analytes in animal, human, and plant tissues. The coating material plays a significant role in the development of in vivo SPME methods and must meet various analytical requirements, including a suitable geometry for the SPME device, high extraction capacity, excellent selectivity, and wide extraction coverage for the target analytes. Covalent organic frameworks (COFs) are porous crystalline polymers constructed from organic framework units through strong covalent bonds; these materials are characterized with a low density, large specific surface area, permanent porosity, excellent chemical/thermal stability, and easy functionalization.In this study, a sulfonic acid-functionalized COF material (COF-SO3H) with good crystallinity, excellent chemical/thermal stability, strong hydrophobicity, a uniform mesoporous structure, and narrow pore size distribution was prepared using 2,4,6-triformylphloroglucinol and 1,4-diamino-2-nitrobenzene as monomers. Then, the COF-SO3H was coated onto the surface of stainless-steel fibers and used for in vivo enrichment of NTs. The structural properties of COF-SO3H were characterized using various techniques, such as scanning electron microscopy (SEM), Fourier transform-infrared spectroscopy (FT-IR), and X-ray diffraction (XRD), all of which showed that COF-SO3H had a good crystalline structure and uniform mesopore distribution with a specific surface area of 46.17 m2/g. Compared with the SPME fibers of HLB, C18, MCX, amino, and PXC columns, the prepared COF-SO3H fibers showed better extraction efficiency for the target NTs. Next, the factors affecting SPME efficiency were optimized. The optimal desorption solvent was formic acid-methanol-water (0.5â¶49.5â¶50, v/v/v), and the optimal extraction and desorption times were 15 min. A method for the in vivo analysis of NTs in the brains of mice was established by combining the COF-SO3H fibers with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) under optimal conditions. The NTs were separated on an Acquity UPLC BEH-C18 analytical column (100 mm×2.1 mm, 1.7 µm) with 0.1% formic acid aqueous solution (A) and acetonitrile (B) as the mobile phases. The flow rate was set to 0.2 mL/min, and the gradient elution procedure was as follows: 0-4 min, 5%B-6%B; 4-7 min, 6%B-5%B; 7-11 min, 5%B. Under optimal conditions, the method showed good linearity (r2>0.99). The limits of quantification (S/N≥5) were in the range of 0.003-0.005 µg/mL and 3-5 µg/mL for monoamine and amino acid NTs, respectively, with RSDs of less than 20%. The method showed good precision (0.80%-9.70%) and accuracy (2.08%-17.72%), with absolute matrix effects in the range of 82.22%-117.92%. These values reflect the good purification and enrichment abilities of the proposed fibers for the target analytes. Finally, the established SPME method was combined with UPLC-MS/MS and successfully applied to quantify target NTs in the brains of mice. The proposed strategy provides a practical method for the in vivo detection and quantitative analysis of NTs and expands the applications of functionalized COF materials for the analysis of various targets.
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Estruturas Metalorgânicas , Humanos , Animais , Camundongos , Cromatografia Líquida , Microextração em Fase Sólida , Espectroscopia de Infravermelho com Transformada de Fourier , Espectrometria de Massas em Tandem , Aminas , Aminoácidos , Encéfalo , Neurotransmissores , Extração em Fase Sólida , Cromatografia Líquida de Alta PressãoRESUMO
The aim of this study was to investigate the role of ubiquitin-specific peptidase 8 (USP8) in human trophoblast cells and its molecular mechanism. Based on the GSE30186 dataset, USP8 was identified as a downregulated gene in pre-eclampsia (PE). Analysis of clinical samples also revealed that USP8 expression at both the mRNA and protein levels in placental tissue from patients with PE was significantly lower than that from healthy pregnant women. Plate clone formation, scratch-wound healing, Transwell, tubule formation, and western blot assays collectively revealed that USP8 overexpression promoted the proliferation, migration, invasion, and pro-angiogenesis function of trophoblast cells, while USP8 knockdown induced the opposite effects. Bioinformatics analysis and luciferase reporter assay results indicated that the 3' untranslated region of USP8 was targeted by miR-874-3p. USP8 expression in the placental tissue of patients with PE was significantly lower than that of healthy pregnant women. USP8 actively regulated the growth and invasion of human trophoblast cells and stabilized the epithelial sodium channel (ENaC) on the cell membrane. MiR-874 targeted USP8 in the trophoblast cells and upregulation of miR-874-3p resulted in a decrease in the proliferation, migration, invasion, and pro-angiogenesis ability of trophoblast cells. These results indicate that USP8 can reverse the above mentioned negative effects of miR-874-3p on trophoblast cells. USP8 targeted by miR-874-3p facilitates the invasion of trophoblastic cells by stabilizing the expression of the ENaC, which may be a possible therapeutic target for PE.
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MicroRNAs , Pré-Eclâmpsia , Humanos , Feminino , Gravidez , Trofoblastos , Placenta , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células/genética , Movimento Celular/genética , Pré-Eclâmpsia/genética , Regiões 3' não Traduzidas/genética , Endopeptidases/genética , Endopeptidases/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismoRESUMO
We propose and experimentally demonstrate a tunable and switchable multi-wavelength erbium-doped fiber ring pulsed laser based on a nonlinear optical loop mirror (NOLM) and an improved Sagnac filter. To achieve multi-wavelength pulsed laser output, we adopt a NOLM as a quasi-saturable absorber and an improved Sagnac loop as a wavelength selected filter. The constructed laser has a maximum output wavelength number of five with a pulse repetition frequency of 40.45 kHz and pulse duration of 108 ns. The laser can output single-wavelength and dual-wavelength pulsed lasers within a certain wavelength tuning range and a five-wavelength pulsed laser with a constant wavelength interval of 3 nm by adjusting the polarization controller. Dual-wavelength, three-wavelength, and four-wavelength pulsed lasers with various wavelength intervals are also obtained. The output performance of the constructed laser is tested with a maximum average output power of 127.45 µW and minimum pulse duration of 52 ns, and the stability of the laser output is also tested with a maximum power fluctuation of 0.62 dB and minimum wavelength drift of 0.51 nm with pump power of 350 mW.
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Background: Gut microbiota influence food allergy. We showed that the natural compound berberine reduces IgE and others reported that BBR alters gut microbiota implying a potential role for microbiota changes in BBR function. Objective: We sought to evaluate an oral Berberine-containing natural medicine with a boiled peanut oral immunotherapy (BNP) regimen as a treatment for food allergy using a murine model and to explore the correlation of treatment-induced changes in gut microbiota with therapeutic outcomes. Methods: Peanut-allergic (PA) mice, orally sensitized with roasted peanut and cholera toxin, received oral BNP or control treatments. PA mice received periodic post-therapy roasted peanut exposures. Anaphylaxis was assessed by visualization of symptoms and measurement of body temperature. Histamine and serum peanut-specific IgE levels were measured by ELISA. Splenic IgE+B cells were assessed by flow cytometry. Fecal pellets were used for sequencing of bacterial 16S rDNA by Illumina MiSeq. Sequencing data were analyzed using built-in analysis platforms. Results: BNP treatment regimen induced long-term tolerance to peanut accompanied by profound and sustained reduction of IgE, symptom scores, plasma histamine, body temperature, and number of IgE+ B cells (p <0.001 vs Sham for all). Significant differences were observed for Firmicutes/Bacteroidetes ratio across treatment groups. Bacterial genera positively correlated with post-challenge histamine and PN-IgE included Lachnospiraceae, Ruminococcaceae, and Hydrogenanaerobacterium (all Firmicutes) while Verrucromicrobiacea. Caproiciproducens, Enterobacteriaceae, and Bacteroidales were negatively correlated. Conclusions: BNP is a promising regimen for food allergy treatment and its benefits in a murine model are associated with a distinct microbiota signature.
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Berberina , Hipersensibilidade Alimentar , Microbiota , Hipersensibilidade a Amendoim , Camundongos , Animais , Arachis , Hipersensibilidade a Amendoim/diagnóstico , Berberina/farmacologia , Berberina/uso terapêutico , Histamina , Modelos Animais de Doenças , Dessensibilização Imunológica , Imunoglobulina ERESUMO
As alcohol consumption increases, alcoholic liver disease (ALD) has become more popular and is threating our human life. In this study, we found mulberry fruit extract (MFE) repaired alcohol-caused liver diseases by regulating hepatic lipid biosynthesis pathway and oxidative singling in alcoholically liver injured (ALI) rats. MFE administration inhibited hepatic lipid accumulation and improved liver steatosis in ALI rats. MFE also enhanced the antioxidant capacity and alleviated the inflammatory response by increasing the activities of antioxidant enzymes and decreasing the contents of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α. Additionally, MFE regulated the expression of miRNA-155 and lipid metabolism-related PPARα protein in rats. Both miR-155 and PPARα play important roles in liver function. The results indicate that MFE has hepatoprotective effects against ALI in rats.
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Hepatopatias Alcoólicas , MicroRNAs , Morus , Humanos , Ratos , Animais , PPAR alfa/genética , PPAR alfa/metabolismo , PPAR alfa/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Morus/metabolismo , Metabolismo dos Lipídeos , Frutas/metabolismo , Fígado/metabolismo , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Lipídeos , Estresse OxidativoRESUMO
Purpose: This meta-analysis compared the long-term (12 months or 24 months) efficacy and safety of intravitreal aflibercept injection (IAI) for diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). Methods: We selected 16 randomized controlled trials (RCTs) performed after 2015 that had a minimum of 12 months and up to 24 months of treatment and conducted a meta-analysis with Review Manager version 5.3. Visual acuity (VA), central subfield thickness (CST) and adverse events were the outcomes selected for evaluation from the eligible studies. Results: Based on 16 RCTs, we evaluated a total of 7125 patients. For PDR and severe DME with poor baseline vision, after a minimum of 12 months and up to 24 months of treatment, the aflibercept treatment group obtained better VA improvement than the focal/grid laser photocoagulation treatment group (MD=13.30; 95%CI: 13.01~13.58; P<0.001) or other treatments (ranibizumab, focal/grid laser photocoagulation, PRP, et al.) group (MD=1.10; 95%CI: 1.05~1.16; P<0.001). In addition, the aflibercept treatment group got higher CST reduction than the focal/grid laser photocoagulation treatment (MD=-33.76; 95%CI: -45.53 ~ -21.99; P<0.001) or other treatments (ranibizumab, focal/grid laser photocoagulation, et al.) group (MD=-33.76; 95%CI: -45.53 ~ -21.99; P<0.001). There was no significant difference in the overall incidence of ocular and non-ocular adverse events in each treatment group. Conclusions: This meta-analysis showed that the advantages of IAI are obvious in the management of DME and PDR with poor baseline vision for long-term observation (a minimum of 12 months and up to 24 months) with both VA improvement and CST reduction. Applied IAI separately trended to be more effective than panretinal photocoagulation separately in VA improvement for PDR. More parameters should be required to assess functional and anatomic outcomes.
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Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Ranibizumab/efeitos adversos , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Retinopatia Diabética/complicações , Retinopatia Diabética/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Diabetes Mellitus/induzido quimicamenteRESUMO
Heteroatom-doped carbon materials have been widely used in many electrocatalytic reduction reactions. Their structure-activity relationships are mainly explored based on the assumption that the doped carbon materials remain stable during electrocatalysis. However, the structural evolution of heteroatom-doped carbon materials is often ignored, and their active origins are still unclear. Herein, taking N-doped graphite flake (N-GP) as the research model, we present the hydrogenation of both N and C atoms and the consequent reconstruction of the carbon skeleton during the hydrogen evolution reaction (HER), accompanied by a remarkable promotion of the HER activity. The N dopants are gradually hydrogenated and almost completely dissolved in the form of ammonia. Theoretical simulations demonstrate that the hydrogenation of the N species leads to the reconstruction of the carbon skeleton from hexagonal to 5,7-topological rings (G5-7) with thermoneutral hydrogen adsorption and easy water dissociation. P-, S-, and Se-doped graphites also show similar removal of doped heteroatoms and the formation of G5-7 rings. Our work unveils the activity origin of heteroatom-doped carbon toward the HER and opens a door to rethinking the structure-performance relationships of carbon-based materials for other electrocatalytic reduction reactions.
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Sepsis refers to the dysregulated host response to infection; its incidence and mortality rates are high. It is a worldwide medical problem but there is no specific drug for it. In recent years, clinical and experimental studies have found that many monomer components of traditional Chinese medicine have certain effects on the treatment of sepsis. This paper reviews the advances in research on the active ingredients of traditional Chinese medicine involved in the treatment of sepsis in recent years according to their chemical structure; it could provide ideas and references for further research and development in Chinese materia medica for the treatment of sepsis.
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Goals: To assess the efficacy and safety of Chinese Medicine Prescription "W-LHIT" in subjects with simple obesity, and to explore its potential mechanism of action. Methods: Thirty-seven patients aged 18 to 60 from Wei-En hospital (Weifang City, Shandong, China), participated in a double blinded, placebo-controlled study. Subjects were randomly divided into 2 groups, 18 in treatment and 19 in placebo group. The treatment group took the "W-LHIT" capsules for two months, while the control group received placebo capsules. Both groups accepted healthy lifestyle education materials. After a 2-month treatment, the placebo group transferred to open-label treatment after unblinding. Results: 72.22% participants in the treatment group lost more than 5% of their body weight, compared with 36.84% in the placebo group (p < 0.001). Body weight loss and body mass index reduction of the treatment group were also significantly higher than those of the placebo group (p < 0.05). These changes were accompanied by increased abundance of Akkermansia muciniphila and Enterococcus faecium, and decreased abundance of Proteobacteria in gut microbiota. Furthermore, the treatment group also showed improvement in obesity-related comorbidities such as hypertension and elevation of liver enzymes. No serious adverse reactions were found during the study period. Weight did not rebound at a follow-up visit 2 months after treatment. Conclusion: W-LHIT significantly improved body weight and comorbid conditions without obvious adverse reaction or rebound weight gain. These effects were associated with increased abundance of probiotics in gut microbiota. W-LHIT may have a potential for treating obesity in conjunction with healthy lifestyle modifications.
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Microbioma Gastrointestinal , Humanos , Obesidade/complicações , Obesidade/tratamento farmacológico , Redução de Peso , Resultado do Tratamento , Estilo de VidaRESUMO
BACKGROUND: Despite G-protein-coupled receptor kinase-interacting protein-1 (GIT1) being recognized as a new promoter gene in some types of cancer, its effect on human pan-cancers and liver hepatocellular carcinoma (LIHC) remains unclear. OBJECTIVES: To elucidate the molecular mechanisms of GIT1 in pan-cancer and LIHC. MATERIAL AND METHODS: Various bioinformatics approaches were utilized to elucidate the oncogenic effects of GIT1 on human pan-cancers. RESULTS: The GIT1 was aberrantly expressed in pan-cancers and associated with the clinical stage. Moreover, the upregulation of GIT1 expression was indicative of poor overall survival (OS) in patients with LIHC, skin cutaneous melanoma (SKCM) and uterine corpus endometrial carcinoma (UCEC), as well as of poor disease-free survival (DFS) in patients with LIHC and UCEC. Furthermore, GIT1 levels were correlated with cancer-associated fibroblasts (CAFs) in adrenocortical carcinoma (ACC), cervical squamous cell carcinoma (CESC) and LIHC. The analysis of single-cell sequencing data revealed an association of GIT1 levels with apoptosis, cell cycle and DNA damage. In addition, multivariate Cox analysis indicated that high GIT1 levels were an independent risk factor for shorter OS in patients with LIHC. Finally, the gene set enrichment analysis revealed INFLAMMATORY_RESPONSE pathway and IL2_STAT5_SIGNALING to be the most enriched in LIHC. CONCLUSIONS: Our data demonstrate the oncogenic effects of GIT1 on various cancers. We believe that GIT1 can serve as a biomarker for LIHC.
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Carcinoma Hepatocelular , Carcinoma de Células Escamosas , Neoplasias Hepáticas , Melanoma , Neoplasias Cutâneas , Neoplasias do Colo do Útero , Feminino , Humanos , Carcinoma Hepatocelular/genética , Quinases de Receptores Acoplados a Proteína G , Neoplasias Hepáticas/genética , Melanoma Maligno CutâneoRESUMO
Introduction: Food allergy is a significant public health problem with limited treatment options. As Food Allergy Herbal Formula 2 (FAHF-2) showed potential as a food allergy treatment, we further developed a purified version named EBF-2 and identified active compounds. We investigated the mechanisms of EBF-2 on IgE-mediated peanut (PN) allergy and its active compound, berberine, on IgE production. Methods: IgE plasma cell line U266 cells were cultured with EBF-2 and FAHF-2, and their effects on IgE production were compared. EBF-2 was evaluated in a murine PN allergy model for its effect on PN-specific IgE production, number of IgE+ plasma cells, and PN anaphylaxis. Effects of berberine on IgE production, the expression of transcription factors, and mitochondrial glucose metabolism in U266 cells were evaluated. Results: EBF-2 dose-dependently suppressed IgE production and was over 16 times more potent than FAHF-2 in IgE suppression in U266 cells. EBF-2 significantly suppressed PN-specific IgE production (70%, p<0.001) and the number of IgE-producing plasma cells in PN allergic mice, accompanied by 100% inhibition of PN-induced anaphylaxis and plasma histamine release (p<0.001) without affecting IgG1 or IgG2a production. Berberine markedly suppressed IgE production, which was associated with suppression of XBP1, BLIMP1, and STAT6 transcription factors and a reduced rate of mitochondrial oxidation in an IgE-producing plasma cell line. Conclusions: EBF-2 and its active compound berberine are potent IgE suppressors, associated with cellular regulation of immunometabolism on IgE plasma cells, and may be a potential therapy for IgE-mediated food allergy and other allergic disorders.
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Anafilaxia , Berberina , Hipersensibilidade Alimentar , Hipersensibilidade a Amendoim , Camundongos , Animais , Imunoglobulina E , Anafilaxia/prevenção & controle , Berberina/farmacologia , Berberina/uso terapêutico , Interferon gama/metabolismo , Hipersensibilidade Alimentar/tratamento farmacológico , Imunoglobulina G , Fatores de TranscriçãoRESUMO
BACKGROUND: To systematically evaluate the quality of the guidelines for the diagnosis and treatment of Helicobacter pylori infection and to analyze the differences and reasons for the key recommendations in the guidelines. METHODS: Databases and websites were systematically searched to obtain guidelines for the diagnosis and treatment of Helicobacter pylori infection. Four independent reviewers used the Guideline Evaluation Tool (AGREE II) to evaluate the included guidelines. The intraclass correlation coefficient (ICC) and Fleiss' kappa coefficient were used to measure the consistency of evaluation guidelines between guide reviewers. Differences between guidelines and the reasons for the differences were analyzed by comparing the recommendations of different guidelines and the evidence supporting the recommendations. RESULTS: A total of 17 guidelines for Helicobacter pylori infection were included in this study. The AGREE II scores of these guidelines were low overall, with 4 of them had a score of over 60%, which indicates that the guidelines are recommended, and 13 of them having a score ranging from 30 to 60%, which indicates that the guidelines are recommended but need to be revised, while no guideline had a score of 30% or less, which indicates that they were not recommended. The analysis of these guidelines found that there were some differences in the main recommendations. Not all guidelines recommend sequential therapy as the recommended therapy. Whether bismuth quadruple therapy should be used as the recommended first-line therapy is unclear. The antibiotic resistance rate is different in different regions. Combined with the local antibiotic sensitivity test, the eradication rate of Helicobacter pylori can be improved. CONCLUSION: There are significant differences in the quality of Helicobacter pylori infection guidelines and the key recommendations. Improving the deficiencies of existing guidelines is an effective way to develop high-quality guidelines and make reasonable recommendations for the treatment of Helicobacter pylori infection in the future.