Edible film preparation by anthocyanin extract addition into acetylated cassava starch/sodium carboxymethyl cellulose matrix for oxidation inhibition of pumpkin seeds.

In this study, an edible film was fabricated by incorporating anthocyanin extract from black rice (AEBR) into acetylated cassava starch (ACS)/carboxymethyl-cellulose (CMC) to enhance the shelf life of pumpkin seeds. The effects of AEBR on the rheological properties of film-forming solutions, as well as the structural characterization and physicochemical properties of the film, were evaluated. Rheological properties of solutions revealed that AEBR was evenly dispersed into polymer matrix and bound by hydrogen bonds, as confirmed by Fourier transform infrared spectroscopy analysis. The appropriate AEBR addition could be compatible with polymer matrix and formed a compact film structure, improving the mechanical properties, barrier properties, and opacity. However, with further addition of AEBR, the tensile strength and water vapor permeability decreased and the tight structure was destroyed. After being stored separately under thermal and UV light accelerated conditions for 20 days, the peroxide value and acid value of roasted pumpkin seeds coated with the AEBR film showed a significant reduction. Moreover, the storage stability of AEBR was improved through the embedding of ACS/CMC biopolymers. These results indicated that AEBR film could effectively delay pumpkin seeds oxidation and prolong their shelf life as an antioxidant material.

The effects of antioxidant supplementation on short-term mortality in sepsis patients.

Background: The occurrence and development of sepsis are related to the excessive production of oxygen free radicals and the weakened natural clearance mechanism. Further dependable evidence is required to clarify the effectiveness of antioxidant therapy, especially its impact on short-term mortality. Objectives: The purpose of this systematic review and meta-analysis was to evaluate the effect of common antioxidant therapy on short-term mortality in patients with sepsis. Methods: According to PRISMA guidelines, a systematic literature search on antioxidants in adults sepsis patients was performed on PubMed/Medline, Embase, and the Cochrane Library from the establishment of the database to November 2023. Antioxidant supplements can be a single-drug or multi-drug combination: HAT (hydrocortisone, ascorbic acid, and thiamine), ascorbic acid, thiamine, N-acetylcysteine and selenium. The primary outcome was the effect of antioxidant treatment on short-term mortality, which included 28-day mortality, in-hospital mortality, intensive care unit mortality, and 30-day mortality. Subgroup analyses of short-term mortality were used to reduce statistical heterogeneity and publication bias. Results: Sixty studies of 130,986 sepsis patients fulfilled the predefined criteria and were quantified and meta-analyzed. Antioxidant therapy reduces the risk of short-term death in sepsis patients by multivariate meta-analysis of current data, including a reduction of in-hospital mortality (OR = 0.81, 95% CI 0.67 to 0.99; P = 0.040) and 28-day mortality (OR = 0.81, 95% CI 0.69 to 0.95]; P = 0.008). Particularly in subgroup analyses, ascorbic acid treatment can reduce in-hospital mortality (OR = 0.66, 95% CI 0.90 to 0.98; P = 0.006) and 28-day mortality (OR = 0.43, 95% CI 0.24 to 0.75; P = 0.003). However, the meta-analysis of RCTs found that antioxidant therapy drugs, especially ascorbic acid, did substantially reduce short-term mortality(OR = 0.78, 95% CI 0.62 to 0.98; P = 0.030; OR = 0.57, 95% CI 0.36 to 0.91; P = 0.020). Conclusions: According to current data of RCTs, antioxidant therapy, especially ascorbic acid, has a trend of improving short-term mortality in patients with sepsis, but the evidence remains to be further demonstrated.

S100A9 exacerbates sepsis-induced acute lung injury via the IL17-NFκB-caspase-3 signaling pathway.

BACKGROUND: Sepsis-induced acute lung injury (ALI) is associated with considerable morbidity and mortality in critically ill patients. S100A9, a key endothelial injury factor, is markedly upregulated in sepsis-induced ALI; however, its specific mechanism of action has not been fully elucidated. METHODS: The Gene Expression Omnibus database transcriptome data for sepsis-induced ALI were used to screen for key differentially expressed genes (DEGs). Using bioinformatics analysis methods such as Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network analyses, the pathogenesis of sepsis-induced ALI was revealed. Intratracheal infusion of lipopolysaccharide (LPS, 10 mg/kg) induced ALI in wild-type (WT) and S100A9 knockout mice. Multiomics analyses (transcriptomics and proteomics) were performed to investigate the potential mechanisms by which S100A9 exacerbates acute lung damage. Hematoxylin-eosin, Giemsa, and TUNEL staining were used to evaluate lung injury and cell apoptosis. LPS (10 µg/mL)-induced murine lung epithelial MLE-12 cells were utilized to mimic ALI and were modulated by S100A9 lentiviral transfection. The impact of S100A9 on cell apoptosis and inflammatory responses were identified using flow cytometry and PCR. The expression of interleukin (IL)-17-nuclear factor kappa B (NFκB)-caspase-3 signaling components was identified using western blotting. RESULTS: Six common DEGs (S100A9, S100A8, IFITM6, SAA3, CD177, and MMP9) were identified in the six datasets related to ALI in sepsis. Compared to WT sepsis mice, S100A9 knockout significantly alleviated LPS-induced ALI in mice, with reduced lung structural damage and inflammatory exudation, decreased exfoliated cell and protein content in the lung lavage fluid, and reduced apoptosis and necrosis of pulmonary epithelial cells. Transcriptomic analysis revealed that knocking out S100A9 significantly affected 123 DEGs, which were enriched in immune responses, defense responses against bacteria or lipopolysaccharides, cytokine-cytokine receptor interactions, and the IL-17 signaling pathway. Proteomic analysis revealed that S100A9 knockout alleviated muscle contraction dysfunction and structural remodeling in sepsis-induced ALI. Multiomics analysis revealed that S100A9 may be closely related to interferon-induced proteins with tetratricopeptide repeats and oligoadenylate synthase-like proteins. LPS decreased MLE12 cell activity, accompanied by high expression of S100A9. The expression of IL-17RA, pNFκB, and cleaved-caspase-3 were increased by S100A9 overexpression and reduced by S100A9 knockdown in LPS-stimulated MLE12 cells. S100A9 knockdown decreases transcription of apoptosis-related markers Bax, Bcl and caspase-3, alleviating LPS-induced apoptosis. CONCLUSIONS: S100A9 as a key biomarker of sepsis-induced acute lung injury, and exacerbates lung damage and epithelial cell apoptosis induced by LPS via the IL-17-NFκB-caspase-3 signaling pathway.

Metabolic profiling of peri-implant crevicular fluid in peri-implantitis.

OBJECTS: This study aims to explore the etiology of peri-implantitis by comparing the metabolic profiles in peri-implant crevicular fluid (PICF) from patients with healthy implants (PH) and those with peri-implantitis (PI). MATERIALS AND METHODS: Fifty-six patients were enrolled in this cross-sectional study. PICF samples were collected and analyzed using both non-targeted and targeted metabolomics approaches. The relationship between metabolites and clinical indices including probing depth (PD), bleeding on probing (BOP), and marginal bone loss (MBL) was examined. Additionally, submucosal microbiota was collected and analyzed using 16S rRNA gene sequencing to elucidate the association between the metabolites and microbial communities. RESULTS: Significant differences in metabolic profiles were observed between the PH and PI groups, with 179 distinct metabolites identified. In the PI group, specific amino acids and fatty acids were significantly elevated compared to the PH group. Organic acids including succinic acid, fructose-6-phosphate, and glucose-6-phosphate were markedly higher in the PI group, showing positive correlations with mean PD, BOP, and MBL. Metabolites that increased in the PI group positively correlated with the presence of Porphyromonas and Treponema and negatively with Streptococcus and Haemophilus. CONCLUSIONS: This study establishes a clear association between metabolic compositions and peri-implant condition, highlighting enhanced metabolite activity in peri-implantitis. These findings open avenues for further research into metabolic mechanisms of peri-implantitis and their potential therapeutic implications.

Total ginsenosides decrease Aß production through activating PPARγ.

INTRODUCTION: Total ginsenosides (TG), the major active constituents of ginseng, have been proven to be beneficial in treatment of Alzheimer's disease (AD). However, the underlying mechanism of TG remains unclear. METHODS: APP/PS1 mice and N2a/APP695 cells were used as in vivo and in vitro model, respectively. Morris water maze (MWM) was used to investigate behavioral changes of mice; neuronal pathological changes were assessed by hematoxylin and eosin (H&E) and nissl staining; immunofluorescence staining was used to examine amyloid beta (Aß) deposition; Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were used to examine the expression of relative amyloidogenic genes and proteins. Moreover, the antagonist of PPARγ, GW9662, was used to determine whether the effects of TG on Aß production were associated with PPARγ activity. RESULTS: TG treatment increased the spatial learning and memory abilities of APP/PS1 mice while decreasing the Aß accumulation in the cortex and hippocampus. In N2a/APP695 cells, TG treatment attenuated the secretion of Aß1-40 and Aß1-42 acting as an PPARγ agonist by inhibiting the translocation of NF-κB p65. Additionally, TG treatment also decreased the expression of amyloidogenic pathway related gene BACE1, PS1 and PS2. CONCLUSIONS: TG treatment reduced the production of Aß both in vivo and in vitro. Activating PPARγ might be a potential therapeutic target of TG in facilitating Aß clearance and ameliorating cognitive deficiency in APP/PS1 mice.

Mechanisms with network pharmacology approach of Ginsenosides in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss, cognitive disorder, language dysfunction, and mental disability. The main neuropathological changes in AD mainly include amyloid plaque deposition, neurofibrillary tangles, synapse loss, and neuron reduction. However, the current anti-AD drugs do not demonstrate a favorable effect in altering the pathological course of AD. Moreover, long-term use of these drugs is usually accompanied with various side effects. Ginsenosides are the major active constituents of ginseng and have protective effects on AD through various mechanisms in both in vivo and in vitro studies. In this review, we focused on discussing the therapeutic potential effects and the mechanisms of pharmacological activities of ginsenosides in AD, to provide new insight for further research and clinical application of ginsenosides in the future. Recent studies on the pharmacological effects and mechanisms of ginsenosides were retrieved from Chinese National Knowledge Infrastructure, National Science and Technology Library, Wanfang Data, Elsevier, ScienceDirect, PubMed, SpringerLink, and the Web of Science database up to April 2023 using relevant keywords. Network pharmacology and bioinformatics analysis were used to predict the therapeutic effects and mechanisms of ginsenosides against AD. Ginsenosides presented a wide range of therapeutic and biological activities, including alleviating Aß deposition, decreasing tau hyperphosphorylation, regulating the cholinergic system, resisting oxidative stress, modulating Ca2+ homeostasis, as well as anti-inflammation and anti-apoptosis in neurons, respectively. For further developing the therapeutic potential as well as clinical applications, the network pharmacology approach was combined with a summary of published studies.

Clinical relevance of distolingual roots and periodontal status in mandibular first molars: a cross-sectional study employing CBCT analysis. / ä¸‹é¢Œç¬¬ä¸€ç£¨ç‰™è¿œèˆŒæ ¹çš„å­˜åœ¨ä¸Žç‰™å‘¨çŠ¶æ€çš„ä¸´åºŠç›¸å ³æ€§åˆ†æžï¼šä¸€é¡¹é‡‡ç”¨é”¥å½¢å°„æŸç”µè„‘æ–­å±‚æ‰«æåˆ†æžçš„æ¨ªæ–­é¢ç ”ç©¶.

OBJECTIVES: Distolingual root of the permanent mandibular first molar (PMFM-DLR) has been frequently reported, which may complicate the treatment of periodontitis. This study aimed to assess the morphological features of PMFM-DLR and investigate the correlation between the morphological features of PMFM-DLR and periodontal status in patients with Eastern Chinese ethnic background. MATERIALS AND METHODS: A total of 836 cone beam computed tomography (CBCT) images with 1497 mandibular first molars were analyzed to observe the prevalence of PMFM-DLR at the patients and tooth levels in Eastern China. Among them, complete periodontal charts were available for 69 Chinese patients with 103 teeth. Correlation and regression analyses were used to evaluate the correlation between the morphological features of DLR, bone loss, and periodontal clinical parameters, including clinical attachment loss (CAL), probing pocket depth (PPD), gingival recession (GR), and furcation involvement (FI). RESULTS: The patient-level prevalence and tooth-level prevalence of DLR in mandibular first molars were 29.4% and 26.3%, respectively. Multiple linear regression analysis suggested that bone loss at the lingual site and CAL were negatively affected by the angle of separation between distolingual and mesial roots in the transverse section, while they were significantly influenced by age and the angle of separation between distobuccal and mesial roots in the coronal section. CONCLUSIONS: The prevalence of PMFM-DLR in Eastern China was relatively high in our cohort. The morphological features of DLR were correlated with the periodontal status of mandibular first molars. This study provides critical information on the morphological features of DLR for improved diagnosis and treatment options of mandibular molars with DLR.

Essential elements for spatiotemporal delivery of growth factors within bio-scaffolds: A comprehensive strategy for enhanced tissue regeneration.

The precise delivery of growth factors (GFs) in regenerative medicine is crucial for effective tissue regeneration and wound repair. However, challenges in achieving controlled release, such as limited half-life, potential overdosing risks, and delivery control complexities, currently hinder their clinical implementation. Despite the plethora of studies endeavoring to accomplish effective loading and gradual release of GFs through diverse delivery methods, the nuanced control of spatial and temporal delivery still needs to be elucidated. In response to this pressing clinical imperative, our review predominantly focuses on explaining the prevalent strategies employed for spatiotemporal delivery of GFs over the past five years. This review will systematically summarize critical aspects of spatiotemporal GFs delivery, including judicious bio-scaffold selection, innovative loading techniques, optimization of GFs activity retention, and stimulating responsive release mechanisms. It aims to identify the persisting challenges in spatiotemporal GFs delivery strategies and offer an insightful outlook on their future development. The ultimate objective is to provide an invaluable reference for advancing regenerative medicine and tissue engineering applications.

SARS-CoV-2 and oncolytic EV-D68-encoded proteases differentially regulate pyroptosis.

Pyroptosis, a pro-inflammatory programmed cell death, has been implicated in the pathogenesis of coronavirus disease 2019 and other viral diseases. Gasdermin family proteins (GSDMs), including GSDMD and GSDME, are key regulators of pyroptotic cell death. However, the mechanisms by which virus infection modulates pyroptosis remain unclear. Here, we employed a mCherry-GSDMD fluorescent reporter assay to screen for viral proteins that impede the localization and function of GSDMD in living cells. Our data indicated that the main protease NSP5 of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) blocked GSDMD-mediated pyroptosis via cleaving residues Q29 and Q193 of GSDMD. While another SARS-CoV-2 protease, NSP3, cleaved GSDME at residue G370 but activated GSDME-mediated pyroptosis. Interestingly, respiratory enterovirus EV-D68-encoded proteases 3C and 2A also exhibit similar differential regulation on the functions of GSDMs by inactivating GSDMD but initiating GSDME-mediated pyroptosis. EV-D68 infection exerted oncolytic effects on human cancer cells by inducing pyroptotic cell death. Our findings provide insights into how respiratory viruses manipulate host cell pyroptosis and suggest potential targets for antiviral therapy as well as cancer treatment.IMPORTANCEPyroptosis plays a crucial role in the pathogenesis of coronavirus disease 2019, and comprehending its function may facilitate the development of novel therapeutic strategies. This study aims to explore how viral-encoded proteases modulate pyroptosis. We investigated the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory enterovirus D68 (EV-D68) proteases on host cell pyroptosis. We found that SARS-CoV-2-encoded proteases NSP5 and NSP3 inactivate gasdermin D (GSDMD) but initiate gasdermin E (GSDME)-mediated pyroptosis, respectively. We also discovered that another respiratory virus EV-D68 encodes two distinct proteases 2A and 3C that selectively trigger GSDME-mediated pyroptosis while suppressing the function of GSDMD. Based on these findings, we further noted that EV-D68 infection triggers pyroptosis and produces oncolytic effects in human carcinoma cells. Our study provides new insights into the molecular mechanisms underlying virus-modulated pyroptosis and identifies potential targets for the development of antiviral and cancer therapeutics.

SARS-CoV-2 Nsp8 suppresses MDA5 antiviral immune responses by impairing TRIM4-mediated K63-linked polyubiquitination.

Melanoma differentiation-associated gene-5 (MDA5) acts as a cytoplasmic RNA sensor to detect viral dsRNA and mediates antiviral innate immune responses to infection by RNA viruses. Upon recognition of viral dsRNA, MDA5 is activated with K63-linked polyubiquitination and then triggers the recruitment of MAVS and activation of TBK1 and IKKα/ß, subsequently leading to IRF3 and NF-κB phosphorylation. However, the specific E3 ubiquitin ligase for MDA5 K63-polyubiquitination has not been well characterized. Great numbers of symptomatic and severe infections of SARS-CoV-2 are spreading worldwide, and the poor efficacy of treatment with type I interferon and antiviral immune agents indicates that SARS-CoV-2 escapes from antiviral immune responses via several unknown mechanisms. Here, we report that SARS-CoV-2 nonstructural protein 8 (nsp8) acts as a suppressor of antiviral innate immune and inflammatory responses to promote infection of SARS-CoV-2. It downregulates the expression of type I interferon, IFN-stimulated genes and proinflammatory cytokines by binding to MDA5 and TRIM4 and impairing TRIM4-mediated MDA5 K63-linked polyubiquitination. Our findings reveal that nsp8 mediates innate immune evasion during SARS-CoV-2 infection and may serve as a potential target for future therapeutics for SARS-CoV-2 infectious diseases.

Detection of NPM1 Mutations in Acute Myeloid Leukemia by using Drop-Off Droplet Digital PCR and its Clinical Application.

BACKGROUND: Nucleophosmin 1 (NPM1) mutations, which occur in 25 - 30% of acute myeloid leukemia (AML) and 50 - 60% of AML with normal karyotype, have been identified as an important marker for stratification of prog-nosis in AML. This study aimed to establish a new quantitative polymerase chain reaction (PCR) technique, the drop-off droplet digital PCR (ddPCR), for rapid and sensitive detection of NPM1 mutations in AML. METHODS: We established the drop-off ddPCR system and verified its performance. NPM1 mutations were screened in 130 AML patients by drop-off ddPCR and were validated by Sanger sequencing and next-generation sequencing (NGS). Then, the NPM1 mutation burden was dynamically monitored in five patients. RESULTS: The limit of blank (LOB) of drop-off ddPCR established for NPM1 mutation was 3.36 copies/µL, and the limit of detection (LOD) was 5.00 - 5.37 copies/µL in 50 ng DNA, and the sensitivity was about 0.05%, which had good linearity. Drop-off ddPCR identified 33/130 (25.4%) NPM1 mutated cases, consistent with Sanger sequencing. In 18 NPM1 positive cases selected randomly, NGS identified fourteen with type A mutation, two with type D mutation, and two with rare type mutations. The mutation burden of NPM1 mutation analyzed by NGS was consistent with the drop-off ddPCR. The sequential samples were detected for measurable residual disease (MRD) monitoring in 5 patients showed that the NPM1 mutation burden was consistent with clinical remission and recurrence. Compared with traditional ddPCR, drop-off ddPCR was also suitable for MRD monitoring. CONCLUSIONS: In this study, we established a drop-off ddPCR method for detecting three common mutations in AML with good sensitivity and repeatability, which can be used to screen mutations in newly diagnosed AML patients and for MRD monitoring after remission to guide treatment.

Identification and validation of necroptosis-related gene signatures to predict clinical outcomes and therapeutic responses in acute myeloid leukemia.

BACKGROUND: Necroptosis is a tightly regulated form of necrotic cell death that promotes inflammation and contributes to disease development. However, the potential roles of necroptosis-related genes (NRGs) in acute myeloid leukemia (AML) have not been elucidated fully. METHODS: We conducted a study to identify a robust biomarker signature for predicting the prognosis and immunotherapy efficacy based on NRGs in AML. We analyzed the genetic and transcriptional alterations of NRGs in 151 patients with AML. Then, we identified three necroptosis clusters. Moreover, a necroptosis score was constructed and assessed based on the differentially expressed genes (DEGs) between the three necroptosis clusters. RESULTS: Three necroptosis clusters were correlated with clinical characteristics, prognosis, the tumor microenvironment, and infiltration of immune cells. A high necroptosis score was positively associated with a poor prognosis, immune-cell infiltration, expression of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1), immune score, stromal score, interferon-gamma (IFNG), merck18, T-cell dysfunction-score signatures, and cluster of differentiation-86, but negatively correlated with tumor immune dysfunction and exclusion score, myeloid-derived suppressor cells, and M2-type tumor-associated macrophages. Our observations indicated that a high necroptosis score might contribute to immune evasion. More interestingly, AML patients with a high necroptosis score may benefit from treatment based on immune checkpoint blockade. CONCLUSIONS: Consequently, our findings may contribute to deeper understanding of NRGs in AML, and facilitate assessment of the prognosis and treatment strategies.

Collagen-based scaffolds with high wet-state cyclic compressibility for potential oral application.

Soft tissue substitutes have been developed to treat gingival recessions to avoid a second surgical site. However, products of pure collagen for clinical application lack their original mechanical strengths and tend to degrade fast in vivo. In this study, a collagen-based scaffold crosslinked with oxidized sodium alginate (OSA-Col) was developed to promote mechanical properties. Compared with commercial products collagen matrix (CM) and collagen sponge (CS), OSA-Col scaffolds presented higher wet-state cyclic compressibility, early anti-degradation ability, similar hemocompatibility and cytocompatibility. Furthermore, in the subcutaneous implantation experiment, OSA2-Col3 scaffolds showed better anti-degradation performance than CS scaffolds and superior neovascularization than CM scaffolds. These results demonstrated that OSA2-Col3 scaffolds had potential as a new soft tissue substitute for the treatment of gingival recessions.

Identification of module genes and functional pathway analysis in septic shock subtypes by integrated bioinformatics analysis.

BACKGROUND: The present study aimed to identify the module genes and key gene functions and biological pathways of septic shock (SS) through integrated bioinformatics analysis. METHODS: In the study, we performed batch correction and principal component analysis on 282 SS samples and 79 normal control samples in three datasets, GSE26440, GSE95233 and GSE57065, to obtain a combined corrected gene expression matrix containing 21,654 transcripts. Patients with SS were then divided into three molecular subtypes according to sample subtyping analysis. RESULTS: By analyzing the demographic characteristics of the different subtypes, we found no statistically significant differences in gender ratio and age composition among the three groups. Then, three subtypes of differentially expressed genes (DEGs) and specific upregulated DEGs (SDEGs) were identified by differential gene expression analysis. We found 7361 DEGs in the type I group, 5594 DEGs in the type II group, and 7159 DEGs in the type III group. There were 1698 SDEGs in the type I group, 2443 in the type II group, and 1831 in the type III group. In addition, we analyzed the correlation between the expression data of 5972 SDEGs in the three subtypes and the gender and age of 227 patients, constructed a weighted gene co-expression network, and identified 11 gene modules, among which the module with the highest correlation with gender ratio was MEgrey. The modules with the highest correlation with age composition were MEgrey60 and MElightyellow. Then, by analyzing the differences in module genes among different subgroups of SS, we obtained the differential expression of 11 module genes in four groups: type I, type II, type III and the control group. Finally, we analyzed the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment of all module DEGs, and the GO function and KEGG pathway enrichment of different module genes were different. CONCLUSIONS: Our findings aim to identify the specific genes and intrinsic molecular functional pathways of SS subtypes, as well as further explore the genetic and molecular pathophysiological mechanisms of SS.

Traditional Chinese medicine for the treatment of Alzheimer's disease: A focus on the microbiota-gut-brain axis.

Alzheimer's disease (AD), the most frequent cause of dementia, is a neurodegenerative disorder characterised by a progressive decline in cognitive function that is associated with the formation of amyloid beta plaques and neurofibrillary tangles. Gut microbiota comprises of a complex community of microorganisms residing in the gastrointestinal ecosystem. These microorganisms can participate in gut-brain axis activities, thereby affecting cognitive function and associated behaviours. Increasing evidence has indicated that gut dysbiosis can jeopardise host immune responses and promote inflammation, which may be an initiating factor for the onset and evolution of AD. Traditional Chinese medicine (TCM) is a promising resource which encompasses immense chemical diversity and multiple-target characteristics for the treatment of AD. Many TCMs regulate the gut microbiota during treatment of diseases, indicating that gut microbiota may be an important target for TCM efficacy. In this review, we summarised the role of the microbiota-gut-brain axis in the development of AD and the effects of TCM in treating AD by regulating the gut microbiota. We anticipate that this review will provide novel perspectives and strategies for future AD research and treatments.

Focusing on scRNA-seq-Derived T Cell-Associated Genes to Identify Prognostic Signature and Immune Microenvironment Status in Low-Grade Glioma.

Background: The clinical outcomes of low-grade glioma (LGG) are associated with T cell infiltration, but the specific contribution of heterogeneous T cell types remains unclear. Method: To study the different functions of T cells in LGG, we mapped the single-cell RNA sequencing results of 10 LGG samples to obtain T cell marker genes. In addition, bulk RNA data of 975 LGG samples were collected for model construction. Algorithms such as TIMER, CIBERSORT, QUANTISEQ, MCPCOUTER, XCELL, and EPIC were used to depict the tumor microenvironment landscape. Subsequently, three immunotherapy cohorts, PRJEB23709, GSE78820, and IMvigor210, were used to explore the efficacy of immunotherapy. Results: The Human Primary Cell Atlas was used as a reference dataset to identify each cell cluster; a total of 15 cell clusters were defined and cells in cluster 12 were defined as T cells. According to the distribution of T cell subsets (CD4+ T cell, CD8+ T cell, Naïve T cell, and Treg cell), we selected the differentially expressed genes. Among the CD4+ T cell subsets, we screened 3 T cell-related genes, and the rest were 28, 4, and 13, respectively. Subsequently, according to the T cell marker genes, we screened six genes for constructing the model, namely, RTN1, HERPUD1, MX1, SEC61G, HOPX, and CHI3L1. The ROC curve showed that the predictive ability of the prognostic model for 1, 3, and 5 years was 0.881, 0.817, and 0.749 in the TCGA cohort, respectively. In addition, we found that risk scores were positively correlated with immune infiltration and immune checkpoints. To this end, we obtained three immunotherapy cohorts to verify their predictive ability of immunotherapy effects and found that high-risk patients had better clinical effects of immunotherapy. Conclusion: This single-cell RNA sequencing combined with bulk RNA sequencing may elucidate the composition of the tumor microenvironment and pave the way for the treatment of low-grade gliomas.

C1q and central nervous system disorders.

C1q is a crucial component of the complement system, which is activated through the classical pathway to perform non-specific immune functions, serving as the first line of defense against pathogens. C1q can also bind to specific receptors to carry out immune and other functions, playing a vital role in maintaining immune homeostasis and normal physiological functions. In the developing central nervous system (CNS), C1q functions in synapse formation and pruning, serving as a key player in the development and homeostasis of neuronal networks in the CNS. C1q has a close relationship with microglia and astrocytes, and under their influence, C1q may contribute to the development of CNS disorders. Furthermore, C1q can also have independent effects on neurological disorders, producing either beneficial or detrimental outcomes. Most of the evidence for these functions comes from animal models, with some also from human specimen studies. C1q is now emerging as a promising target for the treatment of a variety of diseases, and clinical trials are already underway for CNS disorders. This article highlights the role of C1q in CNS diseases, offering new directions for the diagnosis and treatment of these conditions.

Comparison of Yizhiqingxin formula extraction methods and their pharmacodynamic differences.

Objectives: This study compared different extraction methods of Yizhiqingxin formula (YQF) and its neuroprotective effects based on pharmacodynamic indices such as learning and memory ability, brain tissue histopathology and morphology, and inflammatory factor expression in a mouse model of Alzheimer's disease (AD). Methods: The pharmaceutical components of YQF were extracted using three extraction processes, and the components were analyzed by high performance liquid chromatography. Donepezil hydrochloride was used as a positive control drug. Fifty 7-8-month-old 3 × Tg AD mice were randomly divided into three YQF groups (YQF-1, YQF-2, and YQF-3), a donepezil group, and a model group. Ten age-matched C57/BL6 mice were used as normal controls. YQF and Donepezil were administered by gavage at a clinically equivalent dose of 2.6 and 1.3 mg⋅kg-1⋅d-1, respectively, with a gavage volume of 0.1 ml/10 g. Control and model groups received equal volumes of distilled water by gavage. After 2 months, the efficacy was evaluated using behavioral experiments, histopathology, immunohistochemistry, and serum assays. Results: The main components in YQF are ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, epiberberine, coptisine chloride, palmatine, berberine, and ferulic acid. YQF-3 (alcohol extraction) has the highest content of active compounds, followed by YQF-2 (water extraction and alcohol precipitation method). Compared to the model group, the three YQF groups showed alleviated histopathological changes and improved spatial learning and memory, with the effect in YQF-2 being the most significant. YQF showed protection of hippocampal neurons, most significantly in the YQF-1 group. YQF significantly reduced Aß pathology and tau hyperphosphorylation, decreased expressions of serum pro-inflammatory factors interleukin-2 and interleukin-6 as well as serum chemokines MCP-1 and MIG. Conclusion: YQF prepared by three different processes showed differences in pharmacodynamics in an AD mouse model. YQF-2 was significantly better than the other extraction processes in improving memory.

The contribution of mitochondria-associated endoplasmic reticulum membranes (MAMs) dysfunction in Alzheimer's disease and the potential countermeasure.

Alzheimer's disease (AD) is the most common neurodegenerative disease. There are many studies targeting extracellular deposits of amyloid ß-peptide (Aß) and intracellular neurofibrillary tangles (NFTs), however, there are no effective treatments to halt the progression. Mitochondria-associated endoplasmic reticulum membranes (MAMs) have long been found to be associated with various pathogenesis hypotheses of AD, such as Aß deposition, mitochondrial dysfunction, and calcium homeostasis. However, there is a lack of literature summarizing recent advances in the mechanism and treatment studies. Accordingly, this article reviews the latest research involving the roles of MAM structure and tethering proteins in the pathogenesis of AD and summarizes potential strategies targeting MAMs to dissect treatment perspectives for AD.