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The red panda (Ailurus fulgens) is a distinctive mammal known for its reliance on a diet primarily consisting of bamboo. The gut microbiota and overall health of animals are strongly influenced by diets and environments. Therefore, conducting research to explore the taxonomical and functional variances within the gut microbiota of red pandas exposed to various dietary and environmental conditions could shed light on the dynamic complexities of their microbial communities. In this study, normal fecal samples were obtained from red pandas residing in captive and semi‐free environments under different dietary regimes and used for metabolomic, 16S rRNA, and metagenomic sequencing analysis, with the pandas classified into four distinct cohorts according to diet and environment. In addition, metagenomic sequencing was conducted on mucus fecal samples to elucidate potential etiological agents of disease. Results revealed an increased risk of gastrointestinal diseases in red pandas consuming bamboo shoots due to the heightened presence of pathogenic bacteria, although an increased presence of microbiota‐derived tryptophan metabolites appeared to facilitate intestinal balance. The red pandas fed bamboo leaves also exhibited a decrease in gut microbial diversity, which may be attributed to the antibacterial flavonoids and lower protein levels in leaves. Notably, red pandas residing in semi‐free environments demonstrated an enriched gut microbial diversity. Moreover, the occurrence of mucus secretion may be due to an increased presence of species associated with diarrhea and a reduced level of microbiota‐derived tryptophan metabolites. In summary, our findings substantiate the influential role of diet and environment in modulating the gut microbiota of red pandas, offering potential implications for improved captive breeding practices. [ABSTRACT FROM AUTHOR]

The purpose of this study was to explore the risk factors for renal nonrecovery among elderly and nonelderly patients with acute kidney injury (AKI) in critically ill patients. A multicenter retrospective cohort of 583 critically ill patients with AKI was examined. We found the best cutoff value for predicting renal recovery by age was 63 years old through logistic regression. All patients were divided into two cohorts, age <63 and age ≥63-years old; on the basis of renal recovery at 30 days after AKI, the two patient cohorts were further divided into a renal recovery group and a renal nonrecovery group. Multivariate logistic regression was used to analyze the risk factors affecting renal recovery in the two cohorts. The 30-day renal recovery rate of patients aged <63 years was 70.0% (198/283), multivariate analysis showed that the independent risk factors affecting renal nonrecovery in age <63 years old included AKI stage, blood lactate level and hemoglobin level. The 30-day renal recovery rate of patients aged ≥63 years was 28.7% (86/300), multivariate analysis showed that the independent risk factors for renal nonrecovery in age ≥63-years old included diabetes mellitus, surgery with general anesthesia, AKI stage, APACHE II score, eGFR, and hemoglobin level. The renal nonrecovery after AKI in critically ill patients in patients aged ≥63 years was more strongly affected by multiple risk factors, such as diabetes mellitus, surgery with general anesthesia, eGFR, and APACHE II score, in addition to hemoglobin and AKI stage. [ABSTRACT FROM AUTHOR]

Excessive amyloid beta (Aβ) deposition in brain is mainly responsible for cell damage and blood-brain barrier (BBB) disruption in Alzheimer's disease (AD). Catalpol, an iridoid glucoside extracted from the root of Rehmannia glutinosa Libosch, has neuroprotective effect against AD. It is unclear whether catalpol has a protective effect on Aβ-induced BBB leakage. We employed an immortalized endothelial cell line (bEnd.3) and astrocytes co-culture to mimic a BBB model in vitro and investigated the effect of catalpol on BBB. We found that treatment with catalpol decreased BBB hyperpermeability induced by fibrillar Aβ1-42 . Data from western blotting showed that catalpol prevented fibrillar Aβ1-42 -induced bEnd.3 cell apoptosis through mitochondria-dependent and death receptor pathways; decreased the levels of matrix metalloproteinases (MMPs), MMP-2, MMP-9, and the receptor for advanced glycation end products; and increased the levels of tight junction proteins (ZO-1, occludin, and claudin-5), low-density lipoprotein receptor-related protein 1, and P-glycoprotein in fibrillar Aβ1-42 -treated bEnd.3 cells. Moreover, catalpol also enhanced soluble Aβ efflux across the fibrillar Aβ1-42 -treated bEnd.3 cells BBB monolayer model. Altogether, our results suggest that catalpol alleviate fibrillar Aβ1-42 -induced BBB disruption, enhance soluble Aβ clearance, and offer a feasible therapeutic application in AD treatment. [ABSTRACT FROM AUTHOR]

Cancer development and progression are generally associated with gene dysregulation, often resulting from changes in the transcription factor (TF) sequence or expression. Identifying key TFs involved in cancer gene regulation provides a framework for potential new therapeutics. This study presents a large-scale cancer gene TF-DNA interaction network, as well as an extensive promoter clone resource for future studies. Highly connected TFs bind to promoters of genes associated with either good or poor cancer prognosis, suggesting that strategies aimed at shifting gene expression balance between these two prognostic groups may be inherently complex. However, we identified potential for oncogene-targeted therapeutics, with half of the tested oncogenes being potentially repressed by influencing specific activators or bifunctional TFs. Finally, we investigate the role of intrinsically disordered regions within the key cancer-related TF ESR1 in DNA binding and transcriptional activity, and found that these regions can have complex trade-offs in TF function. Altogether, our study broadens our knowledge of the TFs involved in cancer gene regulation and provides a valuable resource for future studies and therapeutics., (© 2024 Lu et al.)

To investigate the effects of on behavior and blood brain barrier (BBB) in Alzheimer's disease mice. Thirty-eight 4-month-old APP/PS1 double transgenic mice were randomly divided into three groups: model group, low-dose group and high-dose group. Saline, and 12 g·kg·d were given to each group by continuous gavage once a day for respectively. The changes in activities of daily live and fear conditioning memory behavior of mice were examined by nesting behavior test and fear conditioning test, respectively. The β-amyloid protein (Aβ) depositions in cortex and hippocampal CA1 area of mice were detected by thioflavin T staining. The CD34 and activities fibrinogen (Fib) immunofluorescence double staining were used to determine the vascular endothelial integrity and BBB exudation. Compared with model mice, activities of daily live were significantly improved in low-dose and high-dose groups (both <0.01), the fear memory ability was significantly increased in high-dose group (<0.01). The amount of Aβ deposition in cortex and hippocampal CA1 decreased significantly in high-dose group, the area ratio decreased significantly; the area ratio of Aβ deposition in hippocampal CA1 region in low-dose group also decreased (all <0.05). The proportions of CD34 positive area of cortex in low and high dose groups increased, the percentage of fibrinogen positive area decreased (all <0.05). The proportion of CD34 positive area in hippocampal CA1 region in high-dose group was significantly increased, the percentage of fibrinogen positive area decreased significantly (both <0.05). especially high-dose can improve the activities of daily live and fear conditioning memory function of APP/PS1 mice, reduce the deposition of Aβ in brain. The mechanism may be related to the reduction of BBB permeability and the protection of the integrity of BBB.

Amyloid-β peptide (Aβ) plays a causal role in the development and progression of Alzheimer's disease (AD). Oxidative stress and activation of mitogen-activated protein kinase (MAPK) are involved in Aβ-induced neurotoxicity. Morroniside, one active monomer of dry ripe sarcocarp of Cornus officinalis, has shown antioxidant properties in several cell lines. The present study investigated the protective actions of morroniside against the cytotoxicity produced by exposure to H 2 O 2 or Aβ 1-42 in rat pheochromocytoma (PC12) cells. Exposure of PC12 cells to 150 μM H 2 O 2 or 20 μM Aβ 1-42 down-regulated anti-apoptotic protein expression (Bcl-2), up-regulated pro-apoptotic protein expression (Bax, cytochrome C, and cleaved caspase-3), increased JNK and p38 MAPK phosphorylation and finally caused significant cell death. This effect was reversed by pretreatment with morroniside in a dose-dependent manner. Among the selective inhibitors of MAPKs, the JNK inhibitor (SP600125) and p38 MAPK inhibitor (SB203580) showed steady preventive effect against H 2 O 2 or Aβ 1-42 -induced apoptosis. The results suggest that different from the selective inhibitors of MAPKs, morroniside can inhibit H 2 O 2 or Aβ 1-42 -induced apoptotic pathway activation through suppressing its upstream signaling components of JNK and p38 MAPK phosphorylation simultaneously., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Excessive amyloid beta (Aβ) deposition in brain is mainly responsible for cell damage and blood-brain barrier (BBB) disruption in Alzheimer's disease (AD). Catalpol, an iridoid glucoside extracted from the root of Rehmannia glutinosa Libosch, has neuroprotective effect against AD. It is unclear whether catalpol has a protective effect on Aβ-induced BBB leakage. We employed an immortalized endothelial cell line (bEnd.3) and astrocytes co-culture to mimic a BBB model in vitro and investigated the effect of catalpol on BBB. We found that treatment with catalpol decreased BBB hyperpermeability induced by fibrillar Aβ 1-42 . Data from western blotting showed that catalpol prevented fibrillar Aβ 1-42 -induced bEnd.3 cell apoptosis through mitochondria-dependent and death receptor pathways; decreased the levels of matrix metalloproteinases (MMPs), MMP-2, MMP-9, and the receptor for advanced glycation end products; and increased the levels of tight junction proteins (ZO-1, occludin, and claudin-5), low-density lipoprotein receptor-related protein 1, and P-glycoprotein in fibrillar Aβ 1-42 -treated bEnd.3 cells. Moreover, catalpol also enhanced soluble Aβ efflux across the fibrillar Aβ 1-42 -treated bEnd.3 cells BBB monolayer model. Altogether, our results suggest that catalpol alleviate fibrillar Aβ 1-42 -induced BBB disruption, enhance soluble Aβ clearance, and offer a feasible therapeutic application in AD treatment., (Copyright © 2018 John Wiley & Sons, Ltd.)