Bazi Bushen ameliorates age-related energy metabolism dysregulation by targeting the IL-17/TNF inflammatory pathway associated with SASP.

BACKGROUND: Chronic inflammation and metabolic dysfunction are key features of systemic aging, closely associated with the development and progression of age-related metabolic diseases. Bazi Bushen (BZBS), a traditional Chinese medicine used to alleviate frailty, delays biological aging by modulating DNA methylation levels. However, the precise mechanism of its anti-aging effect remains unclear. In this study, we developed the Energy Expenditure Aging Index (EEAI) to estimate biological age. By integrating the EEAI with transcriptome analysis, we aimed to explore the impact of BZBS on age-related metabolic dysregulation and inflammation in naturally aging mice. METHODS: We conducted indirect calorimetry analysis on five groups of mice with different ages and utilized the data to construct EEAI. 12 -month-old C57BL/6 J mice were treated with BZBS or ß-Nicotinamide Mononucleotide (NMN) for 8 months. Micro-CT, Oil Red O staining, indirect calorimetry, RNA sequencing, bioinformatics analysis, and qRT-PCR were performed to investigate the regulatory effects of BZBS on energy metabolism, glycolipid metabolism, and inflammaging. RESULTS: The results revealed that BZBS treatment effectively reversed the age-related decline in energy expenditure and enhanced overall metabolism, as indicated by the aging index of energy expenditure derived from energy metabolism parameters across various ages. Subsequent investigations showed that BZBS reduced age-induced visceral fat accumulation and hepatic lipid droplet aggregation. Transcriptomic analysis of perirenal fat and liver indicated that BZBS effectively enhanced lipid metabolism pathways, such as the PPAR signaling pathway, fatty acid oxidation, and cholesterol metabolism, and improved glycolysis and mitochondrial respiration. Additionally, there was a significant improvement in inhibiting the inflammation-related arachidonic acid-linoleic acid metabolism pathway and restraining the IL-17 and TNF inflammatory pathways activated via senescence associated secretory phenotype (SASP). CONCLUSIONS: BZBS has the potential to alleviate inflammation in metabolic organs of naturally aged mice and maintain metabolic homeostasis. This study presents novel clinical therapeutic approaches for the prevention and treatment of age-related metabolic diseases.

Causal role of immune cells in inflammatory bowel disease: A Mendelian randomization study.

Inflammatory bowel disease (IBD) is characterized by an inflammatory response closely related to the immune system, but the relationship between inflammation and IBD remains unclear. We performed a comprehensive 2-sample Mendelian randomization (MR) analysis to determine the causal relationship between immune cell characteristics and IBD. Using publicly available genetic data, we explored the relationship between 731 immune cell characteristics and IBD risk. Inverse-variance weighting was the primary analytical method. To test the robustness of the results, we used the weighted median-based, MR-Egger, simple mode, and mode-based methods. Finally, we performed a reverse MR analysis to assess the possibility of reverse causality. We identified suggestive associations between 2 immune cell traits and IBD risk (P = 4.18 × 10-5 for human leukocyte antigen-DR on CD14+ monocytes, OR: 0.902; 95% CI: 0.859-0.947; for CD39+ CD4+ T cells, P = 6.24 × 10-5; OR: 1.042; 95% CI: 1.021-1.063). Sensitivity analysis results of these immune cell traits were consistent. In reverse MR analysis, we found no statistically significant association between IBD and these 2 cell traits. Our study demonstrates the close connection between immune cells and IBD using MR, providing guidance for future clinical and basic research.

Sour Jujube (Ziziphus jujuba var. spinosa): A Bibliometric Review of Its Bioactive Profile, Health Benefits and Trends in Food and Medicine Applications.

Research on the comprehensive utilization of sour jujube and its beneficial properties to human health has attracted extensive attention. This study aims to conduct a bibliometric analysis of the bioactive profile of sour jujube and future trends in applications. The research advancements within this field from 2000 to 2023 were addressed using the Web of Science database and VOSviewer. Among the 322 results, the most frequent keywords of bioactivity are flavonoids, antioxidants, saponins, insomnia, polyphenols, terpenoids and anti-inflammatory; the most studied parts of sour jujube are seeds, fruits and leaves; the published articles with high citations mainly focus on identification, biological effects and different parts distribution of bioactive compounds. The bioactivity of various parts of sour jujube was reviewed considering their application potential. The seeds, rich in flavonoids, saponins and alkaloids, exhibit strong effects on central nervous system diseases and have been well-developed in pharmacology, healthcare products and functional foods. The pulp has antioxidant properties and is used to develop added-value foods (e.g., juice, vinegar, wine). The leaves can be used to make tea and flowers are good sources of honey; their extracts are rich sources of flavonoids and saponins, which show promising medicinal effects. The branches, roots and bark have healing properties in traditional folk medicine. Overall, this study provides a reference for future applications of sour jujube in food and medicine fields.

Stiffness and BMP-2 Mimetic Peptide Jointly Regulate the Osteogenic Differentiation of Rat Bone Marrow Stromal Cells in a Gelatin Cryogel.

Both biochemical and mechanical cues could regulate the function of stem cells, but the interaction mechanism of their signaling pathway remains unclear, especially in the three-dimensional (3D) culture mode. Higher matrix stiffness promotes osteogenic differentiation of stem cells, and bone morphogenic protein-2 (BMP-2) has been clinically applied to promote bone regeneration. Here, the crosstalk of extracellular mechanical signals on BMP-2 signaling was investigated in rat bone marrow stromal cells (rMSCs) cultured inside cryogels with interconnective pores. Stiff cryogel independently promoted osteogenic differentiation and enhanced the autocrine secretion of BMP-2, thus stimulating increased phosphorylation levels of the Smad1/5/8 complex. BMP-2 mimetic peptide (BMMP) and high cryogel stiffness jointly guided the osteogenic differentiation of rMSCs. Inhibition of rho-associated kinase (ROCK) by Y-27632 or inhibition of nonmuscle myosin II (NM II) by blebbistatin showed that osteogenesis induction by BMP-2 signaling, as well as autocrine secretion of BMP-2 and phosphorylation of the Smad complex, requires the involvement of cytoskeletal tension and ROCK pathway signaling. An interconnective microporous cryogel scaffold promoted rMSC osteogenic differentiation by combining matrix stiffness and BMMP, and it accelerated critical cranial defect repair in the rat model.

Recovery-Based Occluded Face Recognition by Identity-Guided Inpainting.

Occlusion in facial photos poses a significant challenge for machine detection and recognition. Consequently, occluded face recognition for camera-captured images has emerged as a prominent and widely discussed topic in computer vision. The present standard face recognition methods have achieved remarkable performance in unoccluded face recognition but performed poorly when directly applied to occluded face datasets. The main reason lies in the absence of identity cues caused by occlusions. Therefore, a direct idea of recovering the occluded areas through an inpainting model has been proposed. However, existing inpainting models based on an encoder-decoder structure are limited in preserving inherent identity information. To solve the problem, we propose ID-Inpainter, an identity-guided face inpainting model, which preserves the identity information to the greatest extent through a more accurate identity sampling strategy and a GAN-like fusing network. We conduct recognition experiments on the occluded face photographs from the LFW, CFP-FP, and AgeDB-30 datasets, and the results indicate that our method achieves state-of-the-art performance in identity-preserving inpainting, and dramatically improves the accuracy of normal recognizers in occluded face recognition.

MotifHub: Detection of trans-acting DNA motif group with probabilistic modeling algorithm.

BACKGROUND: Trans-acting factors are of special importance in transcription regulation, which is a group of proteins that can directly or indirectly recognize or bind to the 8-12 bp core sequence of cis-acting elements and regulate the transcription efficiency of target genes. The progressive development in high-throughput chromatin capture technology (e.g., Hi-C) enables the identification of chromatin-interacting sequence groups where trans-acting DNA motif groups can be discovered. The problem difficulty lies in the combinatorial nature of DNA sequence pattern matching and its underlying sequence pattern search space. METHOD: Here, we propose to develop MotifHub for trans-acting DNA motif group discovery on grouped sequences. Specifically, the main approach is to develop probabilistic modeling for accommodating the stochastic nature of DNA motif patterns. RESULTS: Based on the modeling, we develop global sampling techniques based on EM and Gibbs sampling to address the global optimization challenge for model fitting with latent variables. The results reflect that our proposed approaches demonstrate promising performance with linear time complexities. CONCLUSION: MotifHub is a novel algorithm considering the identification of both DNA co-binding motif groups and trans-acting TFs. Our study paves the way for identifying hub TFs of stem cell development (OCT4 and SOX2) and determining potential therapeutic targets of prostate cancer (FOXA1 and MYC). To ensure scientific reproducibility and long-term impact, its matrix-algebra-optimized source code is released at http://bioinfo.cs.cityu.edu.hk/MotifHub.

Sex differences in abdominal visceral fat composition and metabolism as predictors of DLBCL prognosis: A retrospective cohort study.

PURPOSE: We aimed to determine if sex differences in abdominal visceral fat composition and metabolism can help predict the prognosis of diffuse large B-cell lymphoma (DLBCL) patients. METHODS: This retrospective cohort study included 117 DLBCL patients. The area and metabolic activity of subcutaneous adipose tissue and visceral adipose tissue were measured using CT and PET imaging. Kaplan-Meier survival analysis was employed to evaluate the effect of these parameters on progression-free survival. Multivariate Cox proportional hazard regression models were used to determine the effects of relative visceral fat area (rVFA) on sex-specific survival. RESULTS: Females with an rVFA greater than the optimal threshold of 35 % and a visceral-to-subcutaneous adipose tissue ratio (V/S) >3.24 had worse progression-free survival (p = 0.01, 0.001, respectively). No rVFA or V/S were identified in significantly stratified males with DLBCL (p = 0.249 and 0.895, respectively). Combining the changes in rVFA and V/S identified a subgroup of females with high rVFA and V/S values and exceptionally poor outcomes. The rVFA was a significant predictor of DLBCL progression in females alone. CONCLUSION: Once female DLBCL patients accumulate fat over the tolerable range in the visceral area, they might be at an increased risk of progression (hazard ratio, 3.87; 95 % CI, 1.81-12.69, p = 0.02). Sex differences in visceral fat composition and metabolism may provide a new risk stratification system for patients with DLBCL.

Wavelength-Controlled Photoconductance Polarity Switching via Harnessing Defects in Doped PdSe2 for Artificial Synaptic Features.

Optoelectronic synapses are currently drawing significant attention as fundamental building blocks of neuromorphic computing to mimic brain functions. In this study, a two-terminal synaptic device based on a doped PdSe2 flake is proposed to imitate the key neural functions in an optical pathway. Due to the wavelength-dependent desorption of oxygen clusters near the intrinsic selenide vacancy defects, the doped PdSe2 photodetector achieves a high negative photoresponsivity of -7.8 × 103 A W-1 at 473 nm and a positive photoresponsivity of 181 A W-1 at 1064 nm. This wavelength-selective bi-direction photoresponse endows an all-optical pathway to imitate the fundamental functions of artificial synapses on a device level, such as psychological learning and forgetting capability, as well as dynamic logic functions. The underpinning photoresponse is further demonstrated on a flexible platform, providing a viable technology for neuromorphic computing in wearable electronics. Furthermore, the p-type doping results in an effective increase of the channel's electrical conductivity and a significant reduction in power consumption. Such low-power-consuming optical synapses with simple device architecture and low-dimensional features demonstrate tremendous promise for building multifunctional artificial neuromorphic systems in the future.

Predicting diffuse large B-cell lymphoma outcomes with lesion-to-liver maximum standardized uptake value for interim-treatment and end-of-treatment positron emission tomography-computed tomography.

Background: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) has been used in response evaluation systems for malignant lymphomas and is an important tool for determining efficacy and prognosis. The Deauville 5-point scale (D-5PS) is an 18F-FDG PET-CT image-interpretation protocol for patients with lymphoma. Nevertheless, a number of limitations in visual image interpretation, such as interobserver disagreement and the increase of false-positive results, suggests that new parameters are needed. In this study, we aimed to evaluate the prognostic values of interim-treatment (I-) and end-of-treatment (EOT) PET-CT by comparing D-5PS to the semiquantitative lesion-to-liver maximum standardized uptake value ratio (RLL). Methods: A total of 90 patients with diffuse large B-cell lymphoma (DLBCL) (45 I-PET and 45 EOT-PET) were analyzed, and the RLL was calculated. Patients were additionally evaluated using the D-5PS system. We determined the optimal cutoff value of RLL using receiver operating characteristic (ROC) analysis. Kaplan-Meier survival analysis was used to compare the outcome predictions, while multivariate Cox regression analysis was used to identify the predictive factors. Results: Among the patients examined, 41 (20 I-PET and 21 EOT-PET) experienced progression, and 49 (25 I-PET, 24 EOT-PET) did not. The optimal cutoff values of the RLL for predicting disease progression were 1.37 for I-PET (sensitivity 75%, specificity 88%) and 2.03 for EOT-PET (sensitivity 45.5%, specificity 100%), while the cutoffs of the D-5PS were scores 4 for I-PET (sensitivity 80%, specificity 72%) and 5 for EOT-PET (sensitivity 40.9%, specificity 100%). The prognostic efficacy was higher for the RLL at interim than for the D-5PS [area under the curve (AUC) =0.848 vs. 0.741]. The EOT prognostic efficacy of both evaluation methods was essentially equivalent (AUC =0.785 vs. 0.725). Univariate and multivariate analyses showed that RLL and D-5PS were independent factors affecting DLBCL outcomes for both interim and EOT assessment. Conclusions: RLL and D-5PS have independent predictive values for the interim and EOT evaluation of outcomes in patients with DLBCL. The RLL has better interim predictive ability than does D-5PS and can optimize D-5PS interpretation, thus improving interim outcome prediction.

Mixed solvent-assisted synthesis of high mass loading amorphous NiCo-MOF as a promising electrode material for supercapacitors.

The pursuit of high mass loading metal-organic framework (MOF) materials via a simple method is crucial to achieve high-performance supercapacitors. Herein, an amorphous NiCo-MOF material with a high mass loading of up to 10.3 mg cm-2 was successfully prepared using a mixed solvent system of ethanol and water. In addition, by adjusting the volume ratio of ethanol to water, amorphous NiCo-MOFs with three different morphologies including nanospheres, nanopores, and ultra-thick plates were obtained. It was found that the different solvent systems not only affected the growth rate of MOFs, but also controlled their nucleation rate by changing the coordination environment of the metal ions, and thus achieved morphology and mass loading regulation, thereby influencing their energy storage behavior. Notably, the optimum NiCo-MOF exhibited the superior specific capacitance of up to 9.7 F cm-2 (941.8 F g-1) at a current density of 5 mA cm-2 and high-rate capability of 71.1% even at 20 mA cm-2. Moreover, the corresponding assembled solid-state supercapacitor exhibited an excellent energy density of 0.65 mW h cm-2 at a power density of 2 mW cm-2 and capacity retention of 84.7% after 8000 cycles at 30 mA cm-2. Overall, this work proposes a feasible and effective strategy to achieve high mass loading NiCo-MOFs, impacting their ultimate electrochemical performance, which can possibly be further extended to other MOFs with superior capacitance.

Ligand-Controlled Electroreduction of CO2 to Formate over Facet-Defined Bimetallic Sulfide Nanoplates.

CO2 reduction (CO2R) catalyzed by an efficient, stable, and earth-abundant electrocatalyst offers an attractive means to store energy derived from renewable sources. Here, we describe the synthesis of facet-defined Cu2SnS3 nanoplates and the ligand-controlled CO2R property. We show that thiocyanate-capped Cu2SnS3 nanoplates possess excellent selectivity toward formate over a wide range of potentials and current densities, attaining a maximum formate Faradaic efficiency of 92% and partial current densities as high as 181 mA cm-2 when tested using a flow cell with gas-diffusion electrode. In situ spectroscopic measurements and theoretical calculations reveal that the high formate selectivity originates from favorable adsorption of HCOO* intermediates on cationic Sn sites that are electronically modulated by thiocyanates bound to adjacent Cu sites. Our work illustrates that well-defined multimetallic sulfide nanocrystals with tailored surface chemistries could provide a new avenue for future CO2R electrocatalyst design.

Changes in the salivary metabolome in patients with chronic erosive gastritis.

INTRODUCTION: Chronic erosive gastritis (CEG) is closely related to gastric cancer, which requires early diagnosis and intervention. The invasiveness and discomfort of electronic gastroscope have limited its application in the large-scale screening of CEG. Therefore, a simple and noninvasive screening method is needed in the clinic. OBJECTIVES: The aim of this study is to screen potential biomarkers that can identify diseases from the saliva samples of CEG patients using metabolomics. METHODS: Saliva samples from 64 CEG patients and 30 healthy volunteers were collected, and metabolomic analysis was performed using UHPLC-Q-TOF/MS in the positive and negative ion modes. Statistical analysis was performed using both univariate (Student's t-test) and multivariate (orthogonal partial least squares discriminant analysis) tests. Receiver operating characteristic (ROC) analysis was conducted to determine significant predictors in the saliva of CEG patients. RESULTS: By comparing the saliva samples from CEG patients and healthy volunteers, 45 differentially expressed metabolites were identified, of which 37 were up-regulated and 8 were down-regulated. These differential metabolites were related to amino acid, lipid, phenylalanine metabolism, protein digestion and absorption, and mTOR signaling pathway. In the ROC analysis, the AUC values of 7 metabolites were greater than 0.8, among which the AUC values of 1,2-dioleoyl-sn-glycoro-3-phosphodylcholine and 1-stearoyl-2-oleoyl-sn-glycoro-3-phospholine (SOPC) were greater than 0.9. CONCLUSIONS: In summary, a total of 45 metabolites were identified in the saliva of CEG patients. Among them, 1,2-dioleoyl-sn-glycoro-3-phosphorylcholine and 1-stearoyl-2-oleoyl-sn-glycoro-3-phosphorine (SOPC) might have potential clinical application value.

Silver Nanocoating of LiNi0.8Co0.1Mn0.1O2 Cathode Material for Lithium-Ion Batteries.

Surface coating has become an effective approach to improve the electrochemical performance of Ni-rich cathode materials. In this study, we investigated the nature of an Ag coating layer and its effect on electrochemical properties of the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode material, which was synthesized using 3 mol.% of silver nanoparticles by a facile, cost-effective, scalable and convenient method. We conducted structural analyses using X-ray diffraction, Raman spectroscopy, and X-ray photoelectron spectroscopy, which revealed that the Ag nanoparticle coating did not affect the layered structure of NCM811. The Ag-coated sample had less cation mixing compared to the pristine NMC811, which could be attributed to the surface protection of Ag coating from air contamination. The Ag-coated NCM811 exhibited better kinetics than the pristine one, which is attributed to the higher electronic conductivity and better layered structure provided by the Ag nanoparticle coating. The Ag-coated NCM811 delivered a discharge capacity of 185 mAh·g-1 at the first cycle and 120 mAh·g-1 at the 100th cycle, respectively, which is better than the pristine NMC811.

Efficient Generation of Paired Single-Cell Multiomics Profiles by Deep Learning.

Recent advances in single-cell sequencing technology have made it possible to measure multiple paired omics simultaneously in a single cell such as cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-nucleus chromatin accessibility and mRNA expression sequencing (SNARE-seq). However, the widespread application of these single-cell multiomics profiling technologies has been limited by their experimental complexity, noise in nature, and high cost. In addition, single-omics sequencing technologies have generated tremendous and high-quality single-cell datasets but have yet to be fully utilized. Here, single-cell multiomics generation (scMOG), a deep learning-based framework to generate single-cell assay for transposase-accessible chromatin (ATAC) data in silico is developed from experimentally available single-cell RNA-seq measurements and vice versa. The results demonstrate that scMOG can accurately perform cross-omics generation between RNA and ATAC, and generate paired multiomics data with biological meanings when one omics is experimentally unavailable and out of training datasets. The generated ATAC, either alone or in combination with measured RNA, exhibits equivalent or superior performance to that of the experimentally measured counterparts throughout multiple downstream analyses. scMOG is also applied to human lymphoma data, which proves to be more effective in identifying tumor samples than the experimentally measured ATAC data. Finally, the performance of scMOG is investigated in other omics such as proteomics and it still shows robust performance on surface protein generation.

Review of single-cell RNA-seq data clustering for cell-type identification and characterization.

In recent years, the advances in single-cell RNA-seq techniques have enabled us to perform large-scale transcriptomic profiling at single-cell resolution in a high-throughput manner. Unsupervised learning such as data clustering has become the central component to identify and characterize novel cell types and gene expression patterns. In this study, we review the existing single-cell RNA-seq data clustering methods with critical insights into the related advantages and limitations. In addition, we also review the upstream single-cell RNA-seq data processing techniques such as quality control, normalization, and dimension reduction. We conduct performance comparison experiments to evaluate several popular single-cell RNA-seq clustering approaches on simulated and multiple single-cell transcriptomic data sets.

Bazi Bushen mitigates epigenetic aging and extends healthspan in naturally aging mice.

Bazi Bushen (BZBS), a traditional Chinese medicine, has been proven effective in the treatment of age-related disease in mouse models. However, whether its therapeutic effects are due to antiaging mechanism has not yet been explored. In the present study, we investigated the antiaging effects of BZBS in naturally aging mice by using behavioral tests, liver DNA methylome sequencing, methylation age estimation, and frailty index assessment. The methylome analysis revealed a decrease of mCpG levels in the aged mouse liver. BZBS treatment tended to restore age-associated methylation decline and prune the methylation pattern toward that of young mice. More importantly, BZBS significantly rejuvenated methylation age of the aged mice, which was computed by an upgraded DNA methylation clock. These results were consistent with enhanced memory and muscular endurance, as well as decreased frailty score and liver pathological changes. KEGG analysis together with aging-related database screening identified methylation-targeted pathways upon BZBS treatment, including oxidative stress, DNA repair, MAPK signaling, and inflammation. Upregulation of key effectors and their downstream effects on elevating Sod2 expression and diminishing DNA damage were further investigated. Finally, in vitro experiments with senescent HUVECs proved a direct effect of BZBS extracts on the regulation of methylation enzymes during cellular aging. In summary, our work has revealed for the first time the antiaging effects of BZBS by slowing the methylation aging. These results suggest that BZBS might have great potential to extend healthspan and also explored the mechanism of BZBS action in the treatment of age-related diseases.

Topological identification and interpretation for single-cell gene regulation elucidation across multiple platforms using scMGCA.

Single-cell RNA sequencing provides high-throughput gene expression information to explore cellular heterogeneity at the individual cell level. A major challenge in characterizing high-throughput gene expression data arises from challenges related to dimensionality, and the prevalence of dropout events. To address these concerns, we develop a deep graph learning method, scMGCA, for single-cell data analysis. scMGCA is based on a graph-embedding autoencoder that simultaneously learns cell-cell topology representation and cluster assignments. We show that scMGCA is accurate and effective for cell segregation and batch effect correction, outperforming other state-of-the-art models across multiple platforms. In addition, we perform genomic interpretation on the key compressed transcriptomic space of the graph-embedding autoencoder to demonstrate the underlying gene regulation mechanism. We demonstrate that in a pancreatic ductal adenocarcinoma dataset, scMGCA successfully provides annotations on the specific cell types and reveals differential gene expression levels across multiple tumor-associated and cell signalling pathways.

Enhanced Electron Correlation and Significantly Suppressed Thermal Conductivity in Dirac Nodal-Line Metal Nanowires by Chemical Doping.

Enhancing electron correlation in a weakly interacting topological system has great potential to promote correlated topological states of matter with extraordinary quantum properties. Here, the enhancement of electron correlation in a prototypical topological metal, namely iridium dioxide (IrO2 ), via doping with 3d transition metal vanadium is demonstrated. Single-crystalline vanadium-doped IrO2 nanowires are synthesized through chemical vapor deposition where the nanowire yield and morphology are improved by creating rough surfaces on substrates. Vanadium doping leads to a dramatic decrease in Raman intensity without notable peak broadening, signifying the enhancement of electron correlation. The enhanced electron correlation is further evidenced by transport studies where the electrical resistivity is greatly increased and follows an unusual T $\sqrt T $ dependence on the temperature (T). The lattice thermal conductivity is suppressed by an order of magnitude via doping even at room temperature where phonon-impurity scattering becomes less important. Density functional theory calculations suggest that the remarkable reduction of thermal conductivity arises from the complex phonon dispersion and reduced energy gap between phonon branches, which greatly enhances phase space for phonon-phonon Umklapp scattering. This work demonstrates a unique system combining 3d and 5d transition metals in isostructural materials to enrich the system with various types of interactions.

Bazi Bushen capsule improves the deterioration of the intestinal barrier function by inhibiting NLRP3 inflammasome-mediated pyroptosis through microbiota-gut-brain axis.

Purpose: The senescence-accelerated prone mouse 8 (SAMP8) is a widely used model for accelerating aging, especially in central aging. Mounting evidence indicates that the microbiota-gut-brain axis may be involved in the pathogenesis and progression of central aging-related diseases. This study aims to investigate whether Bazi Bushen capsule (BZBS) attenuates the deterioration of the intestinal function in the central aging animal model. Methods: In our study, the SAMP8 mice were randomly divided into the model group, the BZ-low group (0.5 g/kg/d BZBS), the BZ-high group (1 g/kg/d BZBS) and the RAPA group (2 mg/kg/d rapamycin). Age-matched SAMR1 mice were used as the control group. Next, cognitive function was detected through Nissl staining and two-photon microscopy. The gut microbiota composition of fecal samples was analyzed by 16S rRNA gene sequencing. The Ileum tissue morphology was observed by hematoxylin and eosin staining, and the intestinal barrier function was observed by immunofluorescence. The expression of senescence-associated secretory phenotype (SASP) factors, including P53, TNF-α, NF-κB, IL-4, IL-6, and IL-10 was measured by real-time quantitative PCR. Macrophage infiltration and the proliferation and differentiation of intestinal cells were assessed by immunohistochemistry. We also detected the inflammasome and pyroptosis levels in ileum tissue by western blotting. Results: BZBS improved the cognitive function and neuronal density of SAMP8 mice. BZBS also restored the intestinal villus structure and barrier function, which were damaged in SAMP8 mice. BZBS reduced the expression of SASP factors and the infiltration of macrophages in the ileum tissues, indicating a lower level of inflammation. BZBS enhanced the proliferation and differentiation of intestinal cells, which are essential for maintaining intestinal homeostasis. BZBS modulated the gut microbiota composition, by which BZBS inhibited the activation of inflammasomes and pyroptosis in the intestine. Conclusion: BZBS could restore the dysbiosis of the gut microbiota and prevent the deterioration of intestinal barrier function by inhibiting NLRP3 inflammasome-mediated pyroptosis. These results suggested that BZBS attenuated the cognitive aging of SAMP8 mice, at least partially, by targeting the microbiota-gut-brain axis.