RESUMO

BACKGROUND: Numerous observational studies have indicated that patients with Guillain-Barré syndrome (GBS) frequently had infections with various pathogens before the onset of the disease, particularly several viral infections. Some of these infections are linked to specific clinical and immunological subgroups of GBS, suggesting a potential correlation between viral infections and the development of GBS. However, observational studies have several limitations, including the presence of confounding factors. METHOD: We explored the potential correlation between HIV, SARS-CoV-2, varicella-zoster virus, herpes simplex virus, Epstein-Barr virus, hepatitis B virus, and influenza virus with GBS using a two-sample Mendelian randomization approach. The data was derived from published summary statistics from genome-wide association studies (GWAS). After removing linkage disequilibrium, selecting strong instrumental variables and addressing confounding factors, we would conduct a two-sample Mendelian randomization analysis along with sensitivity testing and the MR-Steiger directional test. RESULT: HIV may have a causal association with GBS (IVW: p = 0.010, OR [95% CI] 1.240 [1.052-1.463]), while no such relationship exists with COVID-19 (IVW: p = 0.275, OR [95% CI] 0.831[0.596-1.159]), varicella (IVW: p = 0.543, OR [95% CI] 0.919 [0.701-1.206]), herpes zoster (IVW: p = 0.563, OR [95% CI] 0.941 [0.766-1.156]), HSV (IVW: p = 0.280, OR [95% CI] 1.244 [0.837-1.851]), EBV (IVW: p = 0.218, OR [95% CI] 0.883 [0.724-1.076]), HBV (IVW: p = 0.179, OR [95% CI] 1.072 [0.969-1.187]), or influenza virus (IVW: p = 0.917, OR [95% CI] 0.971 [0.553-1.703]). We did not find any abnormal SNPs, pleiotropy, or heterogeneity, nor is there any reverse causation. CONCLUSION: Our study results indicate a causal relationship between HIV and GBS, providing new research directions for the etiology of GBS.

Assuntos

Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Síndrome de Guillain-Barré , Análise da Randomização Mendeliana , Viroses , Humanos , Síndrome de Guillain-Barré/genética , Síndrome de Guillain-Barré/virologia , Viroses/genética , Viroses/complicações , Fatores de Risco , Polimorfismo de Nucleotídeo Único/genética , SARS-CoV-2/genética

RESUMO

The rapid advancement of cell therapies underscores the importance of understanding fundamental cellular attributes. Among these, cell fitness-how transplanted cells adapt to new microenvironments and maintain functional stability in vivo-is crucial. This study identifies a chemical compound, FPH2, that enhances the fitness of human chondrocytes and the repair of articular cartilage, which is typically nonregenerative. Through drug screening, FPH2 was shown to broadly improve cell performance, especially in maintaining chondrocyte phenotype and enhancing migration. Single-cell transcriptomics indicated that FPH2 induced a super-fit cell state. The mechanism primarily involves the inhibition of carnitine palmitoyl transferase I and the optimization of metabolic homeostasis. In animal models, FPH2-treated human chondrocytes substantially improved cartilage regeneration, demonstrating well-integrated tissue interfaces in rats. In addition, an acellular FPH2-loaded hydrogel proved effective in preventing the onset of osteoarthritis. This research provides a viable and safe method to enhance chondrocyte fitness, offering insights into the self-regulatory mechanisms of cell fitness.

Assuntos

Cartilagem Articular , Condrócitos , Regeneração , Condrócitos/metabolismo , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Animais , Humanos , Cartilagem Articular/metabolismo , Ratos , Osteoartrite/metabolismo , Osteoartrite/terapia , Hidrogéis/química , Movimento Celular/efeitos dos fármacos

RESUMO

Inflammation is an essential driver of colorectal cancer (CRC). Identifying phenotypes and targets associated with inflammation and cancer may be an effective way to treat CRC. R was used to analyze interleukin 6 cytokine family signal transducer (IL6ST) expression in The Cancer Genome Atlas Colon Adenocarcinoma database. Immunohistochemistry, western blotting, and quantitative PCR were used to detect IL6ST and ferroptosis-related genes expression in our cohort. Receiver operating characteristic curves evaluated the specificity and sensitivity of IL6ST to predict CRC. Cell counting kit-8 investigated cell viability. Mitochondrial morphology, total iron, and reactive oxygen species (ROS) levels were evaluated to assess cell ferroptosis. The correlation of IL6ST and immune cells filtration were also analyzed based on R. IL6ST was significantly upregulated in CRC tissues (P < .05). The specificity and sensitivity of IL6ST for predicting CRC were high (area under the curve (AUC): 0.919, CI: 0.896-0.942). IL6ST was significantly associated with ferroptosis-related genes. IL6ST knockdown decreased SW480 cells viability (knockdown vs. vector, P = .004), promoted the ferroptosis phenotype, and increased iron accumulation (knockdown vs. vector P = .014) and ROS production (knockdown vs. vector P = .005). IL6ST upregulation increased SW620 cells viability (overexpression vs. blank, P = .001), inhibited the ferroptosis phenotype, and decreased iron accumulation (overexpression vs. vector P = 0.006) and ROS production (overexpression vs. vector P = .05). IL6ST increased FTH1 and GPX4 expression and reduced PTGS2, NOX1, and ACSL4 expression (P < .01). Additionally, IL6ST level is linked to immune cell infiltration. A higher enrichment score of T cells was observed in IL6ST up-regulated group. IL6ST inhibits ferroptosis and may be a potential novel therapeutic target in CRC via the modulation of ferroptosis.

Assuntos

Neoplasias Colorretais , Ferroptose , Regulação para Cima , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Regulação Neoplásica da Expressão Gênica , Sobrevivência Celular , Ferro/metabolismo , Interleucina-6/metabolismo , Sensibilidade e Especificidade , Feminino , Masculino

RESUMO

The original version of this article (Zhao et al., 2021) unfortunately contained two mistakes.

Assuntos

Restrição Calórica , Diabetes Mellitus Tipo 2 , Peptídeos Semelhantes ao Glucagon , Hipoglicemiantes , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/dietoterapia , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Restrição Calórica/métodos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade

RESUMO

OBJECTIVE: The Generic Version of China Health Related Outcomes Measures (CHROME-G) was a new preference-based health-related quality of life (HRQoL) instrument designed specifically for the Chinese population. This study aimed to validate and compare measurement properties of CHROME-G with EuroQol-5 Dimensions-5 Levels (EQ-5D-5L), Short Form-6 Dimensions version 2 (SF-6Dv2), and Diabetes-Specific Quality of Life (DSQL) scales among the elderly Chinese population with type 2 diabetes. METHODS: A representative sample population was recruited across the country. Internal consistency was assessed using Cronbach's alpha. Hypotheses testing including convergent validity and known-groups validity were evaluated using Spearman's rank correlation and effect sizes, respectively. Sensitivity was examined using relative efficiency and receiver operating characteristic curve. RESULTS: A total of 131 individuals with type 2 diabetes (54.20% male; mean age 69.03 years) were enrolled. Cronbach's alpha was 0.94 for DSQL, 0.93 for CHROME-G, 0.87 for EQ-5D-5L, and 0.88 for SF-6Dv2. For the convergent validity of CHROME-G, 24/29 (82.76%) correlations met the predefined hypotheses, with Spearman's rank correlation coefficients ranging from 0.51 to 0.96. Among the different health subgroups, the effect sizes for CHROME-G, DSQL, EQ-5D-5L, and SF-6Dv2 were 0.19-1.26, 0.36-1.62, 0.22-1.06, and 0.49-0.87, respectively. CHROME-G, DSQL, and SF-6Dv2 had higher efficiency compared with EQ-5D-5L in detecting differences in self-reported health status, with relative efficiency of 3.18 and 1.76, 4.38 and 6.52, and 1.56 and 2.09, respectively. CONCLUSIONS: CHROME-G demonstrates relatively good measurement properties compared with EQ-5D-5L and SF-6Dv2 for measuring the HRQoL among the elderly Chinese population with type 2 diabetes. The sensitivity of DSQL appears to be better than that of the three generic instruments.

Assuntos

Diabetes Mellitus Tipo 2 , Qualidade de Vida , Diabetes Mellitus Tipo 2/psicologia , Humanos , Masculino , Feminino , Idoso , China , Pessoa de Meia-Idade , Inquéritos e Questionários , Reprodutibilidade dos Testes , Avaliação de Resultados em Cuidados de Saúde/métodos , Psicometria/métodos

RESUMO

RATIONALE: Anaphylactic shock, a severe and rapid systemic allergic reaction, poses significant treatment challenges. Epinephrine, the first-line treatment, effectively reverses symptoms but can complicate the clinical picture by elevating lactate levels, blurring the distinction between shock-induced hypoperfusion and drug-induced metabolic effects. PATIENT CONCERNS: A 26-year-old female presented with anaphylactic shock following an antibiotic infusion, experiencing chest tightness, hypotension, and pulmonary edema, without significant past medical history apart from a noted allergy to fish and shrimp. DIAGNOSES: Anaphylaxis was diagnosed based on clinical presentation and supported by imaging that revealed pulmonary edema, despite normal troponin levels and electrocardiogram. INTERVENTIONS: Treatment included 0.5 mg of intramuscular epinephrine and 5 mg of intravenous dexamethasone, with subsequent intubation and mechanical ventilation in the intensive care unit. An intravenous epinephrine infusion was also administered for hemodynamic support. OUTCOMES: While epinephrine resolved the pulmonary edema and stabilized circulation, it led to a significant, albeit transient, increase in lactate levels, which normalized following discontinuation of epinephrine, indicating the metabolic effect of the drug rather than ongoing tissue hypoperfusion. LESSONS: This case illustrates the importance of recognizing epinephrine-induced lactate elevation in anaphylactic shock, necessitating a nuanced interpretation of lactate dynamics. Clinicians must differentiate between lactate elevations due to tissue hypoperfusion and those arising from epinephrine's pharmacologic effects to optimize patient care.

Assuntos

Anafilaxia , Epinefrina , Ácido Láctico , Humanos , Anafilaxia/tratamento farmacológico , Anafilaxia/sangue , Feminino , Adulto , Epinefrina/administração & dosagem , Ácido Láctico/sangue , Dexametasona/uso terapêutico , Dexametasona/administração & dosagem , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/tratamento farmacológico , Antibacterianos/efeitos adversos , Antibacterianos/administração & dosagem

RESUMO

The escalating prevalence of obesity presents a formidable global health challenge, underscoring the imperative for efficacious pharmacotherapeutic interventions. However, current anti-obesity medications often exhibit limited efficacy and adverse effects, necessitating the exploration of alternative therapeutic approaches. Growth differentiation factor 15 (GDF15) has emerged as a promising target for obesity management, given its crucial role in appetite control and metabolic regulation. In this study, we aimed to investigate the efficacy of curcumol, a sesquiterpene compound derived from plants of the Zingiberaceae family, in obesity treatment. Our findings demonstrate that curcumol effectively induces the expression of GDF15 through the activation of the endoplasmic reticulum stress pathway. To confirm the role of GDF15 as a critical target for curcumol's function, we compared the effects of curcumol in wild-type mice and Gdf15-knockout mice. Using a high-fat diet-induced obese murine model, we observed that curcumol led to reduced appetite and altered dietary preferences mediated by GDF15. Furthermore, chronic curcumol intervention resulted in promising anti-obesity effects. Additionally, curcumol administration improved glucose tolerance and lipid metabolism in the obese mice. These findings highlight the potential of curcumol as a GDF15 inducer and suggest innovative strategies for managing obesity and its associated metabolic disorders. In conclusion, our study provides evidence for the efficacy of curcumol in obesity treatment by inducing GDF15 expression. The identified effects of curcumol on appetite regulation, dietary preferences, glucose tolerance, and lipid metabolism emphasize its potential as a therapeutic agent for combating obesity and related metabolic disorders.

RESUMO

This study aimed to explore the isomer-specific, sex-specific, and joint associations of PFAS and red blood cell indices. We used data of 1,238 adults from the Isomers of C8 Health Project in China. Associations of PFAS isomers and red blood cell indices were explored using multiple linear regression models, Bayesian Kernel Machine Regression models and subgroup analysis across sex. We found that serum concentration of linear (n-) and branched (Br-) isomers of perfluorooctane sulfonate (PFOS) and perfluorohexanesulfonic acid (PFHxS) were significantly associated with red blood cell indices in single-pollutant models, with stronger associations observed for n-PFHxS than Br-PFHxS, in women than in men. For instance, the estimated percentage change in hemoglobin concentration for n-PFHxS (3.65%; 95% CI: 2.95%, 4.34%) was larger than that for Br-PFHxS (0.96%; 95% CI: 0.52%, 1.40%). The estimated percentage change in red blood cell count for n-PFHxS in women (2.55%; 95% CI: 1.81%, 3.28%) was significantly higher than that in men (0.12%; 95% CI: -1.04%, 1.29%) (Pinter < 0.001). Similarly, sex-specific positive association of PFAS mixture and outcomes was observed. Therefore, the structure, susceptive population, and joint effect of PFAS isomers should be taken into consideration when evaluating the health risk of chemicals.

Assuntos

Ácidos Alcanossulfônicos , Poluentes Ambientais , Índices de Eritrócitos , Fluorocarbonos , Humanos , Feminino , Masculino , China , Fluorocarbonos/sangue , Ácidos Alcanossulfônicos/sangue , Adulto , Pessoa de Meia-Idade , Poluentes Ambientais/sangue , Isomerismo , Ácidos Sulfônicos/sangue , Exposição Ambiental/análise , Fatores Sexuais

RESUMO

The nonradical oxidation pathway for pollutant degradation in Fenton-like catalysis is favorable for water treatment due to the high reaction rate and superior environmental robustness. However, precise regulation of such reactions is still restricted by our poor knowledge of underlying mechanisms, especially the correlation between metal site conformation of metal atom clusters and pollutant degradation behaviors. Herein, we investigated the electron transfer and pollutant oxidation mechanisms of atomic-level exposed Ag atom clusters (AgAC) loaded on specifically crafted nitrogen-doped porous carbon (NPC). The AgAC triggered a direct electron transfer (DET) between the terminal oxygen (Oα) of surface-activated peroxodisulfate and the electron-donating substituents-containing contaminants (EDTO-DET), rendering it 11-38 times higher degradation rate than the reported carbon-supported metal catalysts system with various single-atom active centers. Heterocyclic substituents and electron-donating groups were more conducive to degradation via the EDTO-DET system, while contaminants with high electron-absorbing capacity preferred the radical pathway. Notably, the system achieved 79.5% chemical oxygen demand (COD) removal for the treatment of actual pharmaceutical wastewater containing 1053 mg/L COD within 30 min. Our study provides valuable new insights into the Fenton-like reactions of metal atom cluster catalysts and lays an important basis for revolutionizing advanced oxidation water purification technologies.

RESUMO

BACKGROUND: Previous research has highlighted correlations between blood cell counts and chronic liver disease. Nonetheless, the causal relationships remain unknown. AIM: To evaluate the causal effect of blood cell traits on liver enzymes and nonalcoholic fatty liver disease (NAFLD) risk. METHODS: Independent genetic variants strongly associated with blood cell traits were extracted from a genome-wide association study (GWAS) conducted by the Blood Cell Consortium. Summary-level data for liver enzymes were obtained from the United Kingdom Biobank. NAFLD data were obtained from a GWAS meta-analysis (8434 cases and 770180 controls, discovery dataset) and the Fingen GWAS (2275 cases and 372727 controls, replication dataset). This analysis was conducted using the inverse-variance weighted method, followed by various sensitivity analyses. RESULTS: One SD increase in the genetically predicted haemoglobin concentration (HGB) was associated with a ß of 0.0078 (95%CI: 0.0059-0.0096), 0.0108 (95%CI: 0.0080-0.0136), 0.0361 (95%CI: 0.0156-0.0567), and 0.0083 (95%CI: 00046-0.0121) for alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase, and gamma-glutamyl transferase, respectively. Genetically predicted haematocrit was associated with ALP (ß = 0.0078, 95%CI: 0.0052-0.0104) and ALT (ß = 0.0057, 95%CI: 0.0039-0.0075). Genetically determined HGB and the reticulocyte fraction of red blood cells increased the risk of NAFLD [odds ratio (OR) = 1.199, 95%CI: 1.087-1.322] and (OR = 1.157, 95%CI: 1.071-1.250). The results of the sensitivity analyses remained significant. CONCLUSION: Novel causal blood cell traits related to liver enzymes and NAFLD development were revealed through Mendelian randomization analysis, which may facilitate the diagnosis and prevention of NAFLD.

RESUMO

The detection of ethanol-water solution concentration plays an important role in industries, medical care, food and other aspects, which has attracted much attention. In this paper, a 632.8 nm laser combined with the oblique-incidence reflectivity difference (OIRD) method was used to obtain a signal linearly related to the solution concentration and containing the information of the dielectric constant of the solution. Combined with a variety of deep learning algorithms, ethanol-water solutions with a volume concentration of 0-95 % are detected. Among them, the prediction accuracy of the MLP, CNN, LSTM, CNN + BiLSTM + Attention models were 93.65 %, 96.54 %, 97.12 %, 99.23 %, respectively. The experimental results indicate that the OIRD method can achieve rapid, non-destructive, accurate and reliable detection of ethanol-water solutions.

RESUMO

As an important CXC chemokine, CXCL8 plays pleiotropic roles in immunological response. In teleost, CXCL8 is involved in cell migration and bacterial invasion. However, the immune antibacterial function of CXCL8 in Japanese flounder (Paralichthys olivaceus) (PoCXCL8) is largely scarce. In this research, we investigated the antibacterial property and leukocyte activation of PoCXCL8. PoCXCL8 consists of 100 amino acid residues, with a conserved chemokine CXC domain. PoCXCL8 was expressed in various tissues, with the highest level in liver and the lowest level in muscle, and sharply induced by V. harveyi or E. tarda in liver, spleen, and head kidney. In vitro, the recombinant PoCXCL8 (rPoCXCL8) could bind to Bacillus subtilis, Edwardsiella tarda, Escherichia coli, Pseudomonas fluorescens, Vibrio anguillarum, Vibrio harveyi, Staphylococcus aureus, and Micrococcus luteus, affect the growth of E. coli, E. tarda, M. luteus, and P. fluorescens, and have a direct bactericidal effect on E. coli and E. tarda. Moreover, rPoCXCL8 was able to bind the outer membranal protein rPilA of E. tarda. In addition, rPoCXCL8 could bind to PBLs, activating the PBLs activity including chemotaxis, proliferation, phagocytosis, reactive oxygen species, acid phosphatase activity. At same time, rPoCXCL8 could induce neutrophil to generate neutrophil extracellular traps (NETs) and promote the expression of inflammatory genes including IL-1ß, IL6, MMP13, TNF-α, and NF-κB. In flounder, the presence of rPoCXCL8 could enhance the in vivo resistance to E. tarda in liver, spleen, and head kidney. Moreover, the PoCXCL8-deficient could attenuate the fish defense against E. tarda infection in in spleen and head kidney. In conclusion, these results provided new insights into the antibacterial properties of CXCL8 in P. olivaceus.

RESUMO

Interleukin-8 (IL-8), a CXC chemokine, exerts pivotal effect on cell migration, inflammatory response, and immune regulation. In this study, we examined the immunological characteristics of an IL-8 like homologue (PoIL8-L) in Japanese flounder (Paralichthys olivaceus). PoIL8-L contains a conserved chemokine CXC domain and 105 amino acid residues. PoIL8-L expression in tissues was constitutive, and significantly regulated by V. havieri or E. tarda infection. In vitro, rPoIL8-L could bind to eight tested bacteria, exhibited bacteriostatic and bactericidal effects against certain bacteria, and could bind to the targeted bacterial Ⅳ pilin protein rPilA of E. tarda. Furthermore, rPoIL8-L could attach to peripheral blood leukocytes, and enhance their immune genes expression, respiratory burst, chemotaxis, proliferation, acid phosphatase activity, and phagocytic activity. Additionally, rPoIL8-L induce neutrophils to extrude neutrophil extracellular traps. In vivo, rPoIL8-L could promote host resistance to E. tarda infection. In summary, these findings provide fresh perspectives on the immunological antibacterial properties of IL-8 in teleost.

Assuntos

Edwardsiella tarda , Infecções por Enterobacteriaceae , Doenças dos Peixes , Proteínas de Peixes , Linguados , Imunidade Inata , Interleucina-8 , Leucócitos , Animais , Doenças dos Peixes/imunologia , Proteínas de Peixes/imunologia , Proteínas de Peixes/genética , Edwardsiella tarda/fisiologia , Leucócitos/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Linguados/imunologia , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/veterinária , Regulação da Expressão Gênica/imunologia , Vibrio/fisiologia , Sequência de Aminoácidos , Filogenia , Iridoviridae/fisiologia , Alinhamento de Sequência/veterinária , Perfilação da Expressão Gênica/veterinária

RESUMO

In this work, carbon-coated bimetallic tin-nickel selenide heterostructures loaded on reduced graphene oxide composites were prepared through a metal-organic framework-assisted strategy. The carbon coating mitigates the volume expansion and maintains the structural stability, while the introduction of reduced graphene oxide and heterojunction enhances electrical conductivity and reaction kinetics, thereby together contributing to the enhanced lithium-ion storage performance. As expected, the optimal material delivers excellent lithium-ion storage performance in terms of a high reversible capacity of 1033.4 mAh g-1 at 0.2 A g-1, outstanding rate capability, and long-term cyclability with the capacity of 726.2 mAh g-1 after 500 cycles at 1.0 A g-1 and 452.4 mAh g-1 after 1000 cycles at 2.0 A g-1. Furthermore, the electrochemical reaction mechanism of the composite is analyzed.

RESUMO

[This corrects the article DOI: 10.3389/fcell.2021.646575.].

RESUMO

BACKGROUND: This study reported the safety and efficacy of a phase 2, open-label, single-arm, exploratory clinical trial of induction immunochemotherapy in patients with initially unresectable advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Patients underwent three cycles of induction therapy with tislelizumab, cisplatin, and 5-fluorouracil. The primary endpoints were the safety, major pathological response (MPR), and pathological complete response (pCR). Secondary endpoints included the R0 resection rate, disease-free survival (DFS), and overall survival (OS). Genomic data and immune microenvironment data were analyzed exploratively. RESULTS: The treatment was safe, with a grade 3 or higher adverse event rate of 14.9% (7/47). Of the total 47 patients enrolled in the study, 19 (40.4%) achieved MPR, 12 (25.5%) achieved pCR, 4 (8.5%) achieved complete clinical response (cCR) and declined surgery, and 23 (48.94%) underwent successful resection. Median follow-up was 18 months, with a median DFS of 24 months, a median OS of 36 months. A high tumor mutation burden was associated with a better prognosis for patients who underwent surgery. Patients who achieved pCR had higher levels of immune cell infiltration and a greater proportion and concentration of tertiary lymphoid structures compared with those who experienced a major pathological response. CONCLUSIONS: Tislelizumab combined with chemotherapy is effective for ESCC, yielding high cCR, pCR, surgical conversion, and R0 resection rates, and tolerable adverse events. TRIAL REGISTRATION: NCT05469061.