Circulating JKAP levels may correlate with postpartum anxiety and depression through its interaction with T helper 17 cells.

Jun N-terminal kinase pathway-associated phosphatase (JKAP) regulates CD4+ T-cell differentiation and immunity, which are linked to mental disorders. This study aimed to explore the relationships between JKAP and T helper 17 (Th17)/regulatory T (Treg) ratio, as well as their associations with anxiety and depression in postpartum women. Serum JKAP were measured by enzyme-linked immunosorbent assay and blood Th17 and Treg cells were measured by flow cytometry in 250 postpartum women. Anxiety and depression were evaluated by the 6-item State-Trait Anxiety Inventory (STAI6) and Edinburgh Postnatal Depression Scale (EPDS). Anxiety and depression rates were 22.0 and 28.4%, respectively, among postpartum women. Notably, JKAP was negatively associated with the STAI6 (P=0.002) and EPDS scores (P<0.001) in postpartum women and was lower in postpartum women with anxiety (P=0.023) or depression (P=0.002) than in those without. Moreover, JKAP was inversely related to Th17 cells and Th17/Treg ratio but positively correlated with Treg cells in postpartum women (all P<0.001). Interestingly, Th17 cells and Th17/Treg ratio were both positively associated with STAI6 and EPDS scores in postpartum women (all P<0.001). Furthermore, Th17 cells and Th17/Treg ratio were lower in postpartum women with anxiety or depression than in those without (all P<0.01). Nevertheless, Treg cells were not linked to anxiety or depression in postpartum women. JKAP was negatively associated with Th17 cells and Th17/Treg ratio; moreover, they all related to anxiety and depression in postpartum women, indicating that JKAP may be involved in postpartum anxiety and depression via interactions with Th17 cells.

Risk Model for Laryngeal Complications Prediction in Chinese PatientGBVs After Coronary Artery Bypass Grafting.

INTRODUCTION: The aim of this study was to identify perioperative risk factors of laryngeal symptoms and to develop an implementable risk prediction model for Chinese hospitalized patients undergoing coronary artery bypass grafting (CABG). METHODS: A total of 1476 Chinese CABG patients admitted to Wuhan Asian Heart Hospital from January 2020 to June 2022 were included and then divided into a modeling cohort and a verification cohort. Univariate analysis was used to identify laryngeal symptoms risk factors, and multivariate logistic regression was applied to construct a prediction model for laryngeal symptoms after CABG. Discrimination and calibration of this model were validated based on the area under the receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow (H-L) test, respectively. RESULTS: The incidence of laryngeal symptoms in patients who underwent CABG was 6.48%. Four independent risk factors were included in the model, and the established aryngeal complications risk calculation formula was Logit (P) = -4.525 + 0.824 × female + 2.09 × body mass index < 18.5 Kg/m2 + 0.793 × transesophageal echocardiogram + 1.218 × intensive care unit intubation time. For laryngeal symptoms, the area under the ROC curve was 0.769 in the derivation cohort (95% confidence interval [CI]: 0.698-0.840) and 0.811 in the validation cohort (95% CI: 0.742-0.879). According to the H-L test, the P-values in the modeling group and the verification group were 0.659 and 0.838, respectively. CONCLUSION: The prediction model developed in this study can be used to identify high-risk patients for laryngealsymptoms undergoing CABG, and help clinicians implement the follow-up treatment.

Gut microbiota, allergic rhinitis, vasomotor rhinitis, Mendelian randomization, causal association.

OBJECTIVE: Continuous research on the structure and function of intestinal microecology has confirmed the association between gut microbiota and the occurrence, development, and outcome of allergic diseases. Here, we explored the genetic causality between gut microbiota and rhinitis. METHODS: We conducted a two-sample Mendelian Randomization (MR) study to investigate the genetic causal relationship between gut microbiota and allergic rhinitis and vasomotor rhinitis. Genetic variations in the human gut microbiota were obtained from the summary statistics of the MiBioGen study. Genome-wide summary statistics of rhinitis were obtained from the FinnGen consortium. The causal effect between gut microbiota and rhinitis was assessed using the inverse variance weighted, MR-Egger regression, and weighted median methods. In addition, sensitivity analyses were conducted using different methods, including maximum likelihood, simple mode, and weighted model methods. RESULTS: The IVW approach revealed a causal association of the genus Ruminococcus gauvreauii group with an increased risk of allergic rhinitis (IVW Odds Ratio [OR = 1.26] [1.04, 1.53], p-value = 0.01645). In addition, the genus Fusicatenibacter (IVW OR = 1.20 [1.02, 1.41], p-value = 0.02868) was causally associated with an increased risk of vasomotor rhinitis. CONCLUSION: Gut microbiota belonging to different genera exert different effects on allergic rhinitis and vasomotor rhinitis, including reducing the risk of rhinitis, and increasing the risk of rhinitis. New insights into the mechanisms of underlying gut microbiota-associated rhinitis are provided. LEVEL OF EVIDENCE: Level 5.

Prevalence and risk factors of significant fibrosis in chronic hepatitis B patients with concurrent metabolic dysfunction-associated steatotic liver disease.

INTRODUCTION AND OBJECTIVES: Significant fibrosis is an indicator of clinical intervention for both chronic hepatitis B (CHB) and metabolic dysfunction-associated steatotic liver disease (MASLD). There remains a paucity of data regarding the clinical impact of biopsy-defined MASLD on significant fibrosis in CHB patients. The current study aims to elucidate whether patients with concomitant MASLD are at higher risk of significant fibrosis in patients with CHB. PATIENTS AND METHODS: This retrospective research of two tertiary hospitals comprised 1818 patients between 2009 and 2021 with CHB and hepatic steatosis who had not received antiviral therapy. Pathologic findings by liver biopsy were contrasted between CHB group (n = 844) and CHB + MASLD (n = 974) group. METAVIR values of F≥2 were used to categorize significant fibrosis. RESULTS: Patients with CHB + MASLD had more significant fibrosis (35.5 % vs. 23.5 %, p < 0.001) than CHB group. The presence of MASLD [adjusted odds ratio (aOR) 2.055, 95 % confidence interval (CI) 1.635-2.584; p < 0.001] was strongly associated with significant fibrosis in all CHB patients. There was a trend for patients with more cardiometabolic risk factors (CMRFs) to have a higher prevalence of significant fibrosis: (25.7 % in CMRF1 subgroup v.s. 34.9 % in CMRF2 subgroup v.s. 53.7 % in CMRF≥ 3 subgroup, p < 0.001). Patients with CMRF≥3 had a three-fold higher significant fibrosis than those with just one CMRF. CONCLUSIONS: MASLD was associated with higher fibrosis stage in patients with CHB. Early detection and intervention are crucial to patients with three or more cardiometabolic risk factors.

A prediction model for coronary artery abnormalities in children with Kawasaki disease older than 5 years

Abstract Objective: Reliably prediction models for coronary artery abnormalities (CAA) in children aged > 5 years with Kawasaki disease (KD) are still lacking. This study aimed to develop a nomogram model for predicting CAA at 4 to 8 weeks of illness in children with KD older than 5 years. Methods: A total of 644 eligible children were randomly assigned to a training cohort (n = 450) and a validation cohort (n = 194). The least absolute shrinkage and selection operator (LASSO) analysis was used for optimal predictors selection, and multivariate logistic regression was used to develop a nomogram model based on the selected predictors. Area under the receiver operating characteristic curve (AUC), calibration curves, Hosmer-Lemeshow test, Brier score, and decision curve analysis (DCA) were used to assess model performance. Results: Neutrophil to lymphocyte ratio, intravenous immunoglobulin resistance, and maximum baseline z-score ≥ 2.5 were identified by LASSO as significant predictors. The model incorporating these variables showed good discrimination and calibration capacities in both training and validation cohorts. The AUC of the training cohort and validation cohort were 0.854 and 0.850, respectively. The DCA confirmed the clinical usefulness of the nomogram model. Conclusions: A novel nomogram model was established to accurately assess the risk of CAA at 4-8 weeks of onset among KD children older than 5 years, which may aid clinical decisionmaking.

Circulating JKAP levels may correlate with postpartum anxiety and depression through its interaction with T helper 17 cells

Jun N-terminal kinase pathway-associated phosphatase (JKAP) regulates CD4+ T-cell differentiation and immunity, which are linked to mental disorders. This study aimed to explore the relationships between JKAP and T helper 17 (Th17)/regulatory T (Treg) ratio, as well as their associations with anxiety and depression in postpartum women. Serum JKAP were measured by enzyme-linked immunosorbent assay and blood Th17 and Treg cells were measured by flow cytometry in 250 postpartum women. Anxiety and depression were evaluated by the 6-item State-Trait Anxiety Inventory (STAI6) and Edinburgh Postnatal Depression Scale (EPDS). Anxiety and depression rates were 22.0 and 28.4%, respectively, among postpartum women. Notably, JKAP was negatively associated with the STAI6 (P=0.002) and EPDS scores (P<0.001) in postpartum women and was lower in postpartum women with anxiety (P=0.023) or depression (P=0.002) than in those without. Moreover, JKAP was inversely related to Th17 cells and Th17/Treg ratio but positively correlated with Treg cells in postpartum women (all P<0.001). Interestingly, Th17 cells and Th17/Treg ratio were both positively associated with STAI6 and EPDS scores in postpartum women (all P<0.001). Furthermore, Th17 cells and Th17/Treg ratio were lower in postpartum women with anxiety or depression than in those without (all P<0.01). Nevertheless, Treg cells were not linked to anxiety or depression in postpartum women. JKAP was negatively associated with Th17 cells and Th17/Treg ratio; moreover, they all related to anxiety and depression in postpartum women, indicating that JKAP may be involved in postpartum anxiety and depression via interactions with Th17 cells.

A prediction model for coronary artery abnormalities in children with Kawasaki disease older than 5 years.

OBJECTIVE: Reliably prediction models for coronary artery abnormalities (CAA) in children aged >5 years with Kawasaki disease (KD) are still lacking. This study aimed to develop a nomogram model for predicting CAA at 4 to 8 weeks of illness in children with KD older than 5 years. METHODS: A total of 644 eligible children were randomly assigned to a training cohort (n = 450) and a validation cohort (n = 194). The least absolute shrinkage and selection operator (LASSO) analysis was used for optimal predictors selection, and multivariate logistic regression was used to develop a nomogram model based on the selected predictors. Area under the receiver operating characteristic curve (AUC), calibration curves, Hosmer-Lemeshow test, Brier score, and decision curve analysis (DCA) were used to assess model performance. RESULTS: Neutrophil to lymphocyte ratio, intravenous immunoglobulin resistance, and maximum baseline z-score ≥ 2.5 were identified by LASSO as significant predictors. The model incorporating these variables showed good discrimination and calibration capacities in both training and validation cohorts. The AUC of the training cohort and validation cohort were 0.854 and 0.850, respectively. The DCA confirmed the clinical usefulness of the nomogram model. CONCLUSIONS: A novel nomogram model was established to accurately assess the risk of CAA at 4-8 weeks of onset among KD children older than 5 years, which may aid clinical decision-making.

Risk Model for Laryngeal Complications Prediction in Chinese Patients After Coronary Artery Bypass Grafting

ABSTRACT Introduction: The aim of this study was to identify perioperative risk factors of laryngeal symptoms and to develop an implementable risk prediction model for Chinese hospitalized patients undergoing coronary artery bypass grafting (CABG). Methods: A total of 1476 Chinese CABG patients admitted to Wuhan Asian Heart Hospital from January 2020 to June 2022 were included and then divided into a modeling cohort and a verification cohort. Univariate analysis was used to identify laryngeal symptoms risk factors, and multivariate logistic regression was applied to construct a prediction model for laryngeal symptoms after CABG. Discrimination and calibration of this model were validated based on the area under the receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow (H-L) test, respectively. Results: The incidence of laryngeal symptoms in patients who underwent CABG was 6.48%. Four independent risk factors were included in the model, and the established aryngeal complications risk calculation formula was Logit (P) = −4.525 + 0.824 × female + 2.09 × body mass index < 18.5 Kg/m2 + 0.793 × transesophageal echocardiogram + 1.218 × intensive care unit intubation time. For laryngeal symptoms, the area under the ROC curve was 0.769 in the derivation cohort (95% confidence interval [CI]: 0.698-0.840) and 0.811 in the validation cohort (95% CI: 0.742-0.879). According to the H-L test, the P-values in the modeling group and the verification group were 0.659 and 0.838, respectively. Conclusion: The prediction model developed in this study can be used to identify high-risk patients for laryngealsymptoms undergoing CABG, and help clinicians implement the follow-up treatment.

Kindlin-2 in myoepithelium controls luminal progenitor commitment to alveoli in mouse mammary gland.

Myoepithelium plays an important role in mammary gland development, but less is known about the molecular mechanism underlying how myoepithelium controls acinus differentiation during gestation. Herein, we found that loss of Kindlin-2 in myoepithelial cells impaired mammary morphogenesis, alveologenesis, and lactation. Using five genetically modified mouse lines combined with single-cell RNA sequencing, we found a Kindlin-2-Stat3-Dll1 signaling cascade in myoepithelial cells that inactivates Notch signaling in luminal cells and consequently drives luminal progenitor commitment to alveolar cells identity. Single-cell profiling revealed that Kindlin-2 loss significantly reduces the proportion of matured alveolar cells. Mechanistically, Kindlin-2 depletion in myoepithelial cells promotes Stat3 activation and upregulates Dll1, which activates the Notch pathway in luminal cells and inhibits luminal progenitor differentiation and maturation during gestation. Inhibition of Notch1 with tangeretin allowed luminal progenitors to regain commitment ability in the pregnant mice with Kindlin-2 depletion in myoepithelium. Taken together, we demonstrated that Kindlin-2 is essential to myoepithelium-controlled luminal progenitors to alveoli transition during gestation.

Lessons from the genomic analysis of Hesperiidae (Lepidoptera) holotypes in the MIZA collection (Maracay, Venezuela).

Genomic sequencing and analysis of holotypes from the MIZA collection (Maracay, Venezuela) and their comparison with other species and their type specimens advances our understanding of their taxonomy. Jemadia demarmelsi Orellana, [2010] is confirmed as a species-level taxon and its female is genetically verified. The following are species-level taxa, not subspecies: Amenis pedro O. Mielke & Casagrande, 2022, stat. nov. (not Amenis pionia (Hewitson, 1857)) and Jemasonia sosia (Mabille, 1878), stat. rest. (not Jemasonia hewitsonii (Mabille, 1878)). Amenis ponina rogeri Orellana, [2010], stat. nov. and Jemasonia pater ortizi (Orellana, [2010]), stat. nov. are subspecies, not species. Jemadia pseudognetus imitator (Mabille, 1891), comb. nov. (not Jemadia hospita (Butler, 1877)) and Damas cervelina Orellana & Costa, 2019, comb. nov. (not Megaleas Godman, 1901) are new combinations.

Analysis and therapeutic targeting of the IL-1R pathway in anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL), a subgroup of mature T-cell neoplasms with an aggressive clinical course, is characterized by elevated expression of CD30 and anaplastic cytology. To achieve a comprehensive understanding of the molecular characteristics of ALCL pathology and to identify therapeutic vulnerabilities, we applied genome-wide CRISPR library screenings to both anaplastic lymphoma kinase positive (ALK+) and primary cutaneous (pC) ALK- ALCLs and identified an unexpected role of the interleukin-1R (IL-1R) inflammatory pathway in supporting the viability of pC ALK- ALCL. Importantly, this pathway is activated by IL-1α in an autocrine manner, which is essential for the induction and maintenance of protumorigenic inflammatory responses in pC-ALCL cell lines and primary cases. Hyperactivation of the IL-1R pathway is promoted by the A20 loss-of-function mutation in the pC-ALCL lines we analyze and is regulated by the nonproteolytic protein ubiquitination network. Furthermore, the IL-1R pathway promotes JAK-STAT3 signaling activation in ALCLs lacking STAT3 gain-of-function mutation or ALK translocation and enhances the sensitivity of JAK inhibitors in these tumors in vitro and in vivo. Finally, the JAK2/IRAK1 dual inhibitor, pacritinib, exhibited strong activities against pC ALK- ALCL, where the IL-1R pathway is hyperactivated in the cell line and xenograft mouse model. Thus, our studies revealed critical insights into the essential roles of the IL-1R pathway in pC-ALCL and provided opportunities for developing novel therapeutic strategies.

Novel PAX9 compound heterozygous variants in a Chinese family with non-syndromic oligodontia and genotype-phenotype analysis of PAX9 variants.

OBJECTIVE: Studies have reported that >91.9% of non-syndromic tooth agenesis cases are caused by seven pathogenic genes. To report novel heterozygous PAX9 variants in a Chinese family with non-syndromic oligodontia and summarize the reported genotype-phenotype relationship of PAX9 variants. METHODOLOGY: We recruited 28 patients with non-syndromic oligodontia who were admitted to the Hospital of Stomatology Hebei Medical University (China) from 2018 to 2021. Peripheral blood was collected from the probands and their core family members for whole-exome sequencing (WES) and variants were verified by Sanger sequencing. Bioinformatics tools were used to predict the pathogenicity of the variants. SWISS-MODEL homology modeling was used to analyze the three-dimensional structural changes of variant proteins. We also analyzed the genotype-phenotype relationships of PAX9 variants. RESULTS: We identified novel compound heterozygous PAX9 variants (reference sequence NM_001372076.1) in a Chinese family with non-syndromic oligodontia: a new missense variant c.1010C>A (p.T337K) in exon 4 and a new frameshift variant c.330_331insGT (p.D113Afs*9) in exon 2, which was identified as the pathogenic variant in this family. This discovery expands the known variant spectrum of PAX9; then, we summarized the phenotypes of non-syndromic oligodontia with PAX9 variants. CONCLUSION: We found that PAX9 variants commonly lead to loss of the second molars.

Comparison of nitrogen removal performance and mechanism from low-polluted wastewater by constructed wetlands with two oxygen supply strategies: Tidal flow and intermittent aeration.

Due to dissolved oxygen (DO) limited nitrogen removal efficiency in constructed wetlands (CWs), two representative oxygen-suppling CWs, i.e., tidal flow constructed wetlands (TFCWs) and intermittently aerated constructed wetlands (IACWs) were proposed to compare the effect of oxygen supply strategies on the nitrogen removal performance and mechanism. Results showed that the removal efficiencies of NH4+-N and COD in IACWs were as high as 90.35-97.14% and 91.14-92.44%, respectively. In terms of TN, TFCWs (83.82%) showed a significantly higher removal efficiency than IACWs, and this result was derived with the flooded/drained phase (FP/DP) ratio of 21 h:3 h in TFCWs, because rhythmic FP and DP formed a high oxygen gradient at different depths of the system, which intensified the nitrification and denitrification simultaneously. The potential nitrifying and denitrifying bacteria (e.g., Nitrospira, Azospira, Haliangium, Bradyrhizobium and Arenimonas) were enriched more significantly in TFCWs compared with IACWs, as well as Bacillus for simultaneous nitrification and denitrification, which promoted nitrogen transformation together. Also, the results of molecular ecological network analysis showed that bacterial community structure in IACWs was more complex and robust than in TFCWs, because there were obviously more nodes and links as well as a higher proportion of negative interference. However, the relationship between genera in TFCWs was closer depending on shorter path distances, and the keystone genus (Nitrosomonas) in related to nitrification was considered to play an important role in nitrogen transformation performance.

Novel PAX9 compound heterozygous variants in a Chinese family with non-syndromic oligodontia and genotype-phenotype analysis of PAX9 variants

Abstract Studies have reported that >91.9% of non-syndromic tooth agenesis cases are caused by seven pathogenic genes. Objective To report novel heterozygous PAX9 variants in a Chinese family with non-syndromic oligodontia and summarize the reported genotype-phenotype relationship of PAX9 variants. Methodology We recruited 28 patients with non-syndromic oligodontia who were admitted to the Hospital of Stomatology Hebei Medical University (China) from 2018 to 2021. Peripheral blood was collected from the probands and their core family members for whole-exome sequencing (WES) and variants were verified by Sanger sequencing. Bioinformatics tools were used to predict the pathogenicity of the variants. SWISS-MODEL homology modeling was used to analyze the three-dimensional structural changes of variant proteins. We also analyzed the genotype-phenotype relationships of PAX9 variants. Results We identified novel compound heterozygous PAX9 variants (reference sequence NM_001372076.1) in a Chinese family with non-syndromic oligodontia: a new missense variant c.1010C>A (p.T337K) in exon 4 and a new frameshift variant c.330_331insGT (p.D113Afs*9) in exon 2, which was identified as the pathogenic variant in this family. This discovery expands the known variant spectrum of PAX9; then, we summarized the phenotypes of non-syndromic oligodontia with PAX9 variants. Conclusion We found that PAX9 variants commonly lead to loss of the second molars.

Simulated weightlessness led to the transformation of glycolipid metabolism in the livers of mice / La antigravedad simulada provocó la transformación del metabolismo de los glicolípidos en el hígado de ratones / Antigravidade simulada levou à transformação do metabolismo de glicolipídios no fígado de camundongos

ABSTRACT Objectives: The effects of weightlessness on the liver were studied using a tail suspension (TS) male mouse model. Methods: The effects of 0-, 2- and 4-week TS (CON, TS2 and TS4 groups) on glycogen and lipid content, as well as on the molecular processes of the synthesis and degradation pathways, were examined. Results: (1) The number of glycogenosomes under ultrastructure and the glycogen content were considerably larger in the TS4 group than in the other two groups. (2) In the TS4 group, glycogen synthase activity remained constant while glycogen phosphorylase activity dropped, indicating that glycogen breakdown was reduced. (3) The livers of the TS2 group had the highest lipid and triglyceride content, indicating lipid buildup in the liver at this time. (4) In the TS2 group, the activities of the fatty acid synthesis-related factors acetyl-CoA carboxylase and fatty acid synthase increased, while hepatic lipase decreased, indicating that lipid synthesis increased, while decomposition decreased. (5) In the TS2 group, the protein expression of glucose transporters 1 and 2 increased. Conclusions: From TS2 weeks to TS4 weeks, the main energy consumption mode in the livers of mice transitioned from glucose metabolism to lipid metabolism as glucose use decreased. Level of evidence II; Comparative prospective study.

RESUMEN Objetivos: Se estudiaron los efectos de la antigravedad en el hígado utilizando un modelo de ratón macho en prueba de suspensión de la cola (TS, tail suspension). Métodos: Se examinaron los efectos de la TS a las 0, 2 y 4 semanas (grupos CON, TS2 y TS4) sobre el contenido de glucógeno y lípidos, así como sobre los procesos moleculares de las vías de síntesis y degradación. Resultados: (1) El número de glucogenosomas ultraestructurales y el contenido de glucógeno fueron expresivamente más altos en el grupo TS4 que en los otros dos grupos. (2) En el grupo TS4, la actividad de la glucógeno sintasa se mantuvo constante, mientras que la actividad de la glucógeno fosforilasa disminuyó, lo que indica que la degradación del glucógeno se redujo. (3) Los hígados del grupo TS2 presentaron el mayor contenido de lípidos y triglicéridos, lo que indica la acumulación de lípidos en el hígado en ese momento. (4) En el grupo TS2, la actividad de los factores relacionados con la síntesis de ácidos grasos acetil-CoA carboxilasa y ácido graso sintasa aumentó, mientras que la lipasa hepática disminuyó, indicando que la síntesis de lípidos aumentó mientras que la descomposición disminuyó. (5) En el grupo TS2, la expresión proteica de los transportadores de glucosa 1 y 2 aumentó. Conclusiones: Desde la semana TS2 hasta la semana TS4, el principal modo de consumo de energía en el hígado de los ratones pasó del metabolismo de la glucosa al metabolismo de los lípidos a medida que disminuía el uso de la glucosa. Nivel de Evidencia II, Estudio retrospectivo comparativo.

RESUMO Objetivos: Os efeitos da antigravidade no fígado foram estudados usando um modelo de camundongo macho com a suspensão pela cauda (TS, tail suspension). Métodos: Foram examinados os efeitos da TS em 0, 2 e 4 semanas (grupos CON, TS2 e TS4) sobre o conteúdo de glicogênio e lipídios, bem como nos processos moleculares das vias de síntese e degradação. Resultados: (1) O número de glicogenossomos ultraestruturais e o teor de glicogênio foram expressivamente maiores no grupo TS4 do que nos outros dois grupos. (2) No grupo TS4, a atividade de glicogênio sintase permaneceu constante, enquanto a atividade de glicogênio fosforilase caiu, indicando que a degradação do glicogênio foi reduzida. (3) Os fígados do grupo TS2 tiveram o maior teor lipídico e de triglicérides, indicando acúmulo de lipídios no fígado no momento. (4) No grupo TS2, a atividade dos fatores relacionados com a síntese de ácidos graxos acetil-CoA carboxilase e ácido graxo sintase aumentaram, enquanto a lipase hepática diminuiu, indicando que a síntese de lipídios aumentou, enquanto a decomposição diminuiu. (5) No grupo TS2, a expressão proteica dos transportadores de glicose 1 e 2 aumentou. Conclusões: De TS2 semanas para TS4 semanas, o principal modo de consumo de energia no fígado de camundongos passou do metabolismo da glicose para o metabolismo lipídico, à medida que o uso de glicose diminuiu. Nível de evidência II, Estudo retrospectivo comparativo.

Using wild yeasts to modulate the aroma profile of low-alcoholic meads.

In recent years, ample research has focused on applying wild (especially non-Saccharomyces) yeasts in producing alcoholic beverages. Common characteristics of wild yeast strains include simultaneous high production of fruity and floral aroma compounds and low ethanol production. In this study, mead starter cultures were selected based on preliminary screening of wild yeast strains from a Brazilian culture collection (n = 63) for their ability to produce aroma-active compounds. The selected strains included one strain of Saccharomyces cerevisiae and three non-Saccharomyces strains (Pichia jadinii, Torulaspora delbrueckii, and Kluyveromyces lactis). These strains were used to ferment honey must prepared with Aroeira honey, adjusted to 24°Brix, which took 36 days to complete. Single culture fermentations and co-fermentations with S. cerevisiae and non-Saccharomyces strains were carried out. The quality of the produced beverages was evaluated by sugar consumption and production of alcohols and organic acids, analyzed with high-performance liquid chromatography. The volatile organic compound composition was analyzed with gas chromatography-mass spectrometry. Meads with various ethanol amounts (4.7-11.0% v/v) and residual sugar contents (70.81-160.25 g l-1) were produced. In addition, in both single-strain fermentation and co-fermentation with S. cerevisiae, meads produced with either Torulaspora delbrueckii or Kluyveromyces lactis had a roughly three-fold higher content of honey-aroma compound phenethyl acetate and a higher hedonic impression score than meads produced with only S. cerevisiae. These results demonstrated non-Saccharomyces yeasts' ability to increase aroma complexity and improve the sensory quality of low-alcoholic meads.

Ulinastatin alleviates early brain injury after intracerebral hemorrhage by inhibiting oxidative stress and neuroinflammation via ROS/MAPK/Nrf2 signaling pathway.

PURPOSE: Spontaneous intracerebral hemorrhage (ICH) is still a major public health problem, with high mortality and disability. Ulinastatin (UTI) was purified from human urine and has been reported to be anti-inflammatory, organ protective, and antioxidative stress. However, the neuroprotection of UTI in ICH has not been confirmed, and the potential mechanism is unclear. In the present study, we aimed to investigate the neuroprotection and potential molecular mechanisms of UTI in ICH-induced early brain injury in a C57BL/6 mouse model. METHODS: The neurological score, brain water content, neuroinflammatory cytokine levels, oxidative stress levels, and neuronal damage were evaluated. RESULTS: UTI treatment markedly increased the neurological score, alleviated brain edema, decreased the levels of the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, and NF-κB, decreased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and upregulated the levels of glutathione (GSH), superoxide dismutase (SOD), and Nrf2. This finding indicated that UTI-mediated inhibition of neuroinflammation and oxidative stress alleviated neuronal damage after ICH. The neuroprotective capacity of UTI is partly dependent on the ROS/MAPK/Nrf2 signaling pathway. CONCLUSIONS: UTI improves neurological outcomes in mice and reduces neuronal death by protecting against neural neuroinflammation and oxidative stress.

The ethanol extract of Periplaneta Americana L. improves ulcerative colitis induced by a combination of chronic stress and TNBS in rats.

PURPOSE: To investigate the effects of Periplaneta americana L. on ulcerative colitis (UC) induced by a combination of chronic stress (CS) and 2,4,6-trinitrobenzene sulfonic acid enema (TNBS) in rats. METHODS: The experiment UC model with CS was established in rats by a combination of chronic restraint stress, excess failure, improper, and TNBS. The body weight, disease activity index (DAI), colonic mucosal injury index (CMDI), histopathological score (HS) and pro-inflammatory mediators were measured. The content of corticotropin-releasing hormone (CRH) in hypothalamus or adrenocorticotropic hormone (ACTH) and corticosteroids (CORT) in plasma were evaluated by enzyme-linked immunosorbent assay. The proportion of T lymphocyte subsets was detected by flow cytometry, and gut microbiota was detected by 16S rDNA amplicon sequencing. RESULTS: Weight loss, DAI, CMDI, HS and proinflammatory mediators were reversed in rats by P. americana L. treatment after UC with CS. Increased epidermal growth factor (EGF) was observed in P. americana L. groups. In addition, P. americana L. could reduce the content of CRH and ACTH and regulate the ratio of CD3+, CD3+CD8+ and CD3+CD4+CD25+/CD4+ in spleen. Comparably, P. americana L. changes composition of gut microbiota. CONCLUSIONS: The ethanol extract of Periplaneta Americana L. improves UC induced by a combination of CS and TNBS in rats.

Ulinastatin alleviates early brain injury after intracerebral hemorrhage by inhibiting necroptosis and neuroinflammation via MAPK/NF-κB signaling pathway.

PURPOSE: Spontaneous intracerebral hemorrhage (ICH) is a major public health problem with a huge economic burden worldwide. Ulinastatin (UTI), a serine protease inhibitor, has been reported to be anti-inflammatory, immune regulation, and organ protection by reducing reactive oxygen species production, and inflammation. Necroptosis is a programmed cell death mechanism that plays a vital role in neuronal cell death after ICH. However, the neuroprotection of UTI in ICH has not been confirmed, and the potential mechanism is unclear. The present study aimed to investigate the neuroprotection and potential molecular mechanisms of UTI in ICH-induced EBI in a C57BL/6 mouse model. METHODS: The neurological score, brain water content, neuroinflammatory cytokine levels, and neuronal damage were evaluated. The anti-inflammation effectiveness of UTI in ICH patients also was evaluated. RESULTS: UTI treatment markedly increased the neurological score, alleviate the brain edema, decreased the inflammatory cytokine TNF-α, interleukin­1ß (IL­1ß), IL­6, NF­κB levels, and RIP1/RIP3, which indicated that UTI-mediated inhibition of neuroinflammation, and necroptosis alleviated neuronal damage after ICH. UTI also can decrease the inflammatory cytokine of ICH patients. The neuroprotective capacity of UTI is partly dependent on the MAPK/NF-κB signaling pathway. CONCLUSIONS: UTI improves neurological outcomes in mice and reduces neuronal death by protecting against neural neuroinflammation, and necroptosis.

The increased ratio of Treg/Th2 in promoting metastasis of hepatocellular carcinoma.

OBJECTIVE: Liver cancer is the fifth most common cancer in the world. Research on the pathogenesis and detailed molecular mechanisms of liver cancer is very important. The immune system plays an important role in regulating the incidence and metastasis of liver cancer. MATERIALS AND METHODS: This work collected 20 blood samples from patients with clinical hepatocellular carcinoma without metastasis, 20 blood samples from patients with metastatic hepatocellular carcinoma, and 20 blood samples from healthy subjects. Flow cytometry was used to analyze the content of Treg and Th2 cells in the three groups of blood samples. Immunofluorescence was applied to analyze the relative expression of CTLA-4 and CD28 in lymphocytes of each group of blood samples. Western blot was used to analyze the T cell surface protein CTLA-4, CD28, GATA3, and FOXP3 expression in each group of blood samples. RESULTS: The expression of CD28 and GATA3 in the blood of patients with hepatocellular carcinoma without metastasis was obviously higher than that of patients with metastasis of hepatocellular carcinoma, which is contrary to the expression trend of CTLA-4 and FOXP3, and corresponds to the content ratio of Treg and Th2 cells, thus verifying the relationship between Treg/Th2 ratio and metastasis of hepatocellular carcinoma. CONCLUSIONS: In the microenvironment of liver cancer, the ratio of Treg/Th2 will increase significantly, thereby promoting the metastasis of hepatocellular carcinoma.

OBJETIVO: El cáncer de hígado es el quinto cáncer más común en el mundo. La investigación sobre la patogenia y los mecanismos moleculares detallados del cáncer de hígado es muy importante. El sistema inmunológico juega un papel importante en la regulación de la incidencia y metástasis del cáncer de hígado. MATERIAL Y MÉTODOS: Este trabajo recogió 20 muestras de sangre de pacientes con carcinoma hepatocelular clínico sin metástasis, 20 muestras de sangre de pacientes con carcinoma hepatocelular metastásico y 20 muestras de sangre de sujetos sanos. Se utilizó citometría de flujo para analizar el contenido de células Treg y Th2 en los tres grupos de muestras de sangre. Se aplicó inmunofluorescencia para analizar la expresión relativa de CTLA-4 y CD28 en linfocitos de cada grupo de muestras de sangre. Se utilizó Western blot para analizar la expresión de la proteína de superficie de células T CTLA-4, CD28, GATA3, FOXP3 en cada grupo de muestras de sangre. RESULTADOS: La expresión de CD28 y GATA3 en la sangre de pacientes con carcinoma hepatocelular sin metástasis fue obviamente mayor que la de pacientes con metástasis de carcinoma hepatocelular, lo cual es contrario a la tendencia de expresión de CTLA-4 y FOXP3, y corresponde al contenido relación de células Treg y Th2, verificando así la relación entre la relación Treg/Th2 y la metástasis del carcinoma hepatocelular. CONCLUSIONES: En el microambiente del cáncer de hígado, la proporción de Treg/Th2 aumentará significativamente, promoviendo así la metástasis del carcinoma hepatocelular.