Interaction Pathways Research Articles

Impact of Hyaluronic Acid and Other Re-Epithelializing Agents in Periodontal Regeneration: A Molecular Perspective

This narrative review delves into the molecular mechanisms of hyaluronic acid (HA) and re-epithelializing agents in the context of periodontal regeneration. Periodontitis, characterized by chronic inflammation and the destruction of tooth-supporting tissues, presents a significant challenge in restorative dentistry. Traditional non-surgical therapies (NSPTs) sometimes fail to fully manage subgingival biofilms and could benefit from adjunctive treatments. HA, with its antibacterial, antifungal, anti-inflammatory, angiogenic, and osteoinductive properties, offers promising therapeutic potential. This review synthesizes the current literature on the bioactive effects of HA and re-epithelializing agents, such as growth factors and biomaterials, in promoting cell migration, proliferation, and extracellular matrix (ECM) synthesis. By modulating signaling pathways like the Wnt/β-catenin, TGF-β, and CD44 interaction pathways, HA enhances wound healing processes and tissue regeneration. Additionally, the role of HA in facilitating cellular crosstalk between epithelial and connective tissues is highlighted, as it impacts the inflammatory response and ECM remodeling. This review also explores the combined use of HA with growth factors and cytokines in wound healing, revealing how these agents interact synergistically to optimize periodontal regeneration. Future perspectives emphasize the need for further clinical trials to evaluate the long-term outcomes of these therapies and their potential integration into periodontal treatment paradigms.

AmiRNA Technology Enhances Tomato Disease Resistance by Suppressing Plant-Pathogen Interaction Pathways through Inhibiting TYLCV Replication.

Tomato yellow leaf curl virus disease has seriously threatened the quality and yield of tomatoes. In this study, we investigated the role of amiRNA technology in disease resistance in tomatoes (cherry tomato and large-fruited tomato) and analyzed the physiological and molecular mechanisms of disease resistance in transgenic plants. TYLCV contains six functional genes, of which the C1, C2, and V1 genes have more phosphorylation sites and glycosylation sites, and the protein structure is more complex. The virus replication was inhibited, the peroxidation of membrane lipids was reduced, and disease resistance was enhanced in all transgenic cherry tomato (J6) plants in which the C1, C2, and V1 genes were silenced, respectively. Similarly, silencing of the C1 gene enhanced disease resistance in large-fruited tomatoes. In conclusion, amiRNA technology hinders viral replication, leading to reduced activity of the tomato plant-pathogen interaction pathway and weakening tomato-virus interactions, thereby improving disease resistance.

Apply the information-motivation-behavioral model to explore the relationship between oral health literacy and oral health behaviors among community-dwelling older adults.

Oral health is a critical area in healthy aging. Oral health literacy (OHL) plays an important role in improving oral health behaviors and oral health status. However, few studies have investigated OHL among community-dwelling older adults and the influential mechanism of OHL on oral health behaviors has not been clarified. The aim of this study is to explore the interaction pathways through which OHL influences oral health behaviors among community-dwelling older adults. This is a cross-sectional study. 429 community-dwelling older adults were recruited by a convenience sampling method from the activity service center in Zhenjiang, Southern China. The data were collected between September and November 2021 using the Oral Health Literacy Adult Questionnaire (OHL-AQ) and other sophisticated scale assessments. A theoretical model based on the information-motivation-behavioral skills model (IMB model) and previous research was developed and then validated using a structural equation model with AMOS v24.0. The proposed model revealed a good fit to the data (χ2/df = 3.349, goodness of fit index = 0.957, adjusted goodness of fit index = 0.921, root mean squared error of approximation = 0.074, comparative fit index = 0.955, normed fit index = 0.938). Oral health information (β = 0.23) and motivation (β = 0.56) positively affected OHL. OHL (β = 0.20) and motivation (β = 0.25) positively affected self-efficacy; self-efficacy (β = 0.98) had a direct effect on oral health behavior. OHL had an indirect effect on oral health behaviors through self-efficacy (β = 0.19). Motivation can both directly influence oral health behavior (β = 0.18) and indirectly influence oral health behavior through OHL and self-efficacy(β = 0.35). The study findings make a valuable contribution to the influential mechanism of OHL on oral health behaviors. OHL improved oral health behaviors through self-efficacy among community-dwelling older adults. Oral health information directly affected OHL. Motivation directly affected oral health behaviors as well as influence oral health behaviors by changing OHL.

High-gamma frequency flash stimulation as a possible cognitive facilitator in rat pups.

High-gamma frequency flashes can enhance cognition by synchronizing neural oscillations in mammals. Early flash treatment promotes the development of improved cognitive functions in young children. However, it is unclear whether exposure to high-gamma frequency flashes in preschool-aged individuals affects cognition in preadolescents by regulating neural oscillations in the brain. Here, we aimed to investigate the effects of gamma-frequency flashes on cognitive ability. In this study, the effect of high-frequency flicker on cognitive performance was verified by behavioural experiments such as the open-field test and the water maze, but also proteomics. We found that external 40 Hz and 70 Hz frequency flashes synchronized neural oscillations at the corresponding frequencies in the primary visual cortex (V1) of rats. Rats that underwent 70 Hz flash intervention had better cognitive behavioural performance in the early stages of training. The 70 Hz flash frequency upregulated proteins associated with neuronal growth and differentiation, such as Snapin, FoxO3, Hspa12a, and Penk, and activated the MAPK signalling pathway, signalling pathway regulating stem cell pluripotency, and the neuroactive ligand-receptor interaction pathway. These proteins and pathways play important roles in cognitive functions. Our study revealed that 70 Hz flashes received by young children early in their development substantially promote the growth of cognitive capabilities in the brain. Exposure to 70 Hz flashes may be a new intervention method and a new strategy for improving cognition.

Proteomic signatures of ambient air pollution and risk of non-alcoholic fatty liver disease: A prospective cohort study in the UK Biobank.

Air pollution has been linked with non-alcoholic fatty liver disease (NAFLD), but the underlying mechanisms characterized by perturbations in the circulating proteome profile are largely unknown. Therefore, we included 51,357 participants from the UK Biobank with 2941 plasma proteins measured in blood samples collected between 2006 and 2010, measurements of annual fine particular matter <2.5 μm in diameter (PM2.5) and nitrogen dioxide (NO2), and follow-up data on NAFLD (743 incident cases occurred over a median follow-up of 13.6 years). Multiple linear regression was used to identify proteins associated with PM2.5 and NO2. Cox proportional hazards models were applied to assess associations of PM2.5 and NO2 and identified proteins with incident NAFLD. Mediation analyses were conducted to explore the mediation role of proteins in the associations between air pollution and incident NAFLD. After adjusting for selected covariates, PM2.5 (hazard ratio [HR] = 2.57, 95%CI:1.27, 5.21, per ln increase) and NO2 (HR = 1.43, 95%CI: 1.10, 1.84, per ln increase) were positively associated with incident NAFLD. We identified 138 proteins associated with PM2.5 (92 positively, 46 inversely, FDR <0.05) and 143 with NO2 (100 positively, 43 inversely). Of the proteins that were significantly associated with both PM2.5 and NO2, 93 (79 positively, 14 inversely) and 79 (69 positively, 10 inversely) were significantly associated with incident NAFLD. Furthermore, 84 PM2.5-associated proteins and 66 NO2-associated proteins significantly mediated the corresponding association between air pollutants and incident NAFLD, with the proportion of mediation effects ranging from 3.2 % to 27.3 % for PM2.5 and 2.6 % to 20.8 % for NO2, respectively. Of note, the majority of significant mediating proteins were enriched in pathways of cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor. Our findings suggested that long-term exposure to PM2.5 and NO2 was associated with an increased risk of NAFLD partially by perturbating circulating proteins involved in pathways of inflammation and immunity responses.

Macrophage-Specific Lactate Dehydrogenase Expression Modulates Inflammatory Function In Vitro.

In acute kidney injury, macrophages play a major role in regulating inflammation. Classically activated macrophages (M1) undergo drastic metabolic reprogramming during their differentiation and upregulate the aerobic glycolysis pathway to fulfill their pro-inflammatory functions. NAD+ regeneration is crucial for the maintenance of glycolysis and the most direct pathway by which this occurs is via the fermentation of pyruvate to lactate, catalyzed by lactate dehydrogenase A (LDHA). Our previous study determined that LDHA is predominantly expressed in the proximal segments of the nephron in the mouse kidney and increases with hypoxia. This study investigates the potential of LDHA as a therapeutic target for inflammation by exploring its role in macrophage function in vitro. Bone-marrow-derived macrophages (BMDMs) were isolated from myeloid-specific LDHA knockout mice derived from crossbreeding LysM-Cre transgenic mice and LDHA floxed mice. RNA sequencing and LC-MS/MS metabolomics analyses were used in this study to determine the effect of LDHA deletion on BMDM following stimulation with IFN-γ. LDHA deletion in IFN-γ BMDMs resulted in a significant alteration of the macrophage activation and functional pathways, and change in glycolytic, cytokine, and chemokine gene expression. Metabolite concentrations associated with pro-inflammatory macrophage profiles were diminished while anti-inflammatory-associated ones were increased in LDHA KO BMDMs. Glutamate and amino sugars metabolic pathways were significantly affected by the LDHA deletion. A combined muti-omics analysis highlighted changes in Rap1 signaling, cytokine-cytokine receptor interaction, focal adhesion, and MAPK signaling metabolism pathways. Deletion of LDHA in macrophages results in a notable reduction in the pro-inflammatory profile and concurrent upregulation of anti-inflammatory pathways. These findings suggest that LDHA could serve as a promising therapeutic target for inflammation, a key contributor to the pathogenesis of acute kidney injury.

ANGI-04. DISTINCT EXPRESSION OF TARGET MOLECULES BETWEEN TUMOR CELLS IN CEREBROSPINAL FLUID AND LEPTOMENINGES FOR LEPTOMENINGEAL METASTASIS

Abstract PURPOSE Metastatic brain tumor frequently present with leptomeningeal metastasis. The leptomeningeal metastasis is usually diagnosed by cerebrospinal fluid (CSF) cytology and/or contrast enhanced magnetic resonance imaging. However, it remains to be known whether tumor cells from CSF faithfully represent the tumor cells of leptomeniges. Therefore, this study aimed to clarify the transcriptome differences between tumor cells from cerebrospinal fluid, and spinal cords METHODS MDA-MB-231 cells labeled with GFP and luciferase were injected into the right ventricle of immunodeficient mice. Tumor cells from cerebrospinal fluid, and spinal cords were sorted and analyzed the transcriptome differences by RNA sequencing, RESULTS RNA sequencing analysis showed distinct transcriptome profiles between tumor cells from cerebrospinal fluid and spinal cord. Genes related to ECM receptor interaction and PI3K-Akt signaling pathway such as COL1A1, COL1A2, THBS1 were significantly highly upregulated in tumor cells from spinal cord compared to those from CSF CONCLUSIONS Tumor cells from spinal cord had different characteristics in transcriptome from those from CSF. Different therapeutic strategies might be needed to regulate tumor cells from spinal cord and those from CSF.

R-Spondin 1 Suppresses Inflammatory Cytokine Production in Human Cortical Astrocytes

Background/Objectives: Wnt signaling pathways are essential in various biological processes, including embryonic development and tissue homeostasis, and are implicated in many diseases. The R-Spondin (RSpo) family, particularly RSpo1, plays a significant role in modulating Wnt signaling. This study aims to explore how RSpo1 binding to astrocytic LGR6 receptors influences central nervous system (CNS) homeostasis, particularly in the context of inflammation. Methods: Human-induced pluripotent stem cell-derived astrocytes were treated with RSpo1 to assess its impact on inflammatory cytokine release. A proteomic analysis was conducted using a Human Cytokine Array Kit to measure differential protein expression. Pathway enrichment analysis was performed to identify affected signaling pathways. Results: RSpo1 treatment led to a suppression of inflammatory cytokines such as IL-10, IFN-γ, and IL-23 in astrocytes, while TNF-α and CXCL12 levels were increased. Pathway analysis revealed significant alterations in key signaling pathways, including cytokine–cytokine receptor interaction, chemokine signaling, and TNF signaling pathways, suggesting RSpo1’s role in modulating immune responses within the CNS. Conclusions: RSpo1 significantly influences inflammatory responses in astrocytes by modulating cytokine release and altering key signaling pathways. These findings enhance our understanding of the interaction between cell-specific Wnt signaling and CNS inflammation, suggesting potential therapeutic applications of RSpo1 in neuroinflammatory and neurodegenerative diseases.

Gene expression-based modeling of overall survival in Black or African American patients with lung adenocarcinoma

IntroductionLung cancer is a leading cause of cancer-related deaths worldwide. Black/African American (B/AA) populations, in particular, exhibit the highest incidence and mortality rates of lung adenocarcinoma (LUAD) in the United States.MethodsThis study aims to explore gene expression patterns linked to LUAD in B/AA and case-matched white patients, with the goal of developing predictive models for prognosis. Leveraging RNA sequencing data from The Cancer Genome Atlas (TCGA) database, genes and pathways associated with overall survival (OS) were identified.ResultsThe OS-associated genes in B/AA patients were distinct from those in white patients, showing predominant enrichment in immune-related pathways. Furthermore, mRNA co-expression network analysis revealed that OS-associated genes in B/AA patients had higher levels of interaction with various pathways, including those related to immunity, cell-ECM interaction, and specific intracellular signaling pathways. Notably, a potential B/AA-specific biomarker, C9orf64, demonstrated significant correlations with genes involved in immune response. Unsupervised machine learning algorithms stratified B/AA patients into groups with distinct survival outcomes, while supervised algorithms demonstrated a higher accuracy in predicting survival for B/AA LUAD patients compared to white patients.DiscussionIn total, this study explored OS-associated genes and pathways specific for B/AA LUAD patients. Further validation and clinical application of these findings are warranted to address disparities and improve outcomes in diverse patient populations.

SNAP25 as a prognostic marker in transcriptome analysis of meningioma.

Meningiomas are the most common intracranial tumors and their diagnosis relies mostly on neuroimaging and histology. However, the histology grades cannot predict the outcome exactly and some meningiomas tend to recur after resection of even benign tumors. Therefore, it is necessary to explore prognostic and diagnostic molecular targets. Differential expression analysis between meningiomas and meninges was performed based on the merged data of GSE43290 and GSE84263. Next, we performed gene set enrichment analysis (GSEA), immune cell infiltration analysis, protein-protein interaction analysis, and survival analysis using public data. The expression level of Synaptosome-associated-protein-25kDa (SNAP25) was verified by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blotting in meningioma tissues. There were 263 upregulated and 592 downregulated genes identified in meningiomas by differential expression analysis. GSEA results revealed that meningiomas were negatively related to the pathway of soluble N-ethylmaleimide sensitive factor attachment protein receptor interactions in vascular transport and chemokine signaling. SNAP25 was characterized as a hub gene and downregulated in meningiomas. The Kaplan-Meier plot indicated that high expression of SNAP25 is a favorable factor. SNAP25 was downregulated and identified as a potential prognostic marker in meningioma.

Therapeutic Potential of Quercetin Analogous: Prospective and Advances.

The purpose of the article is to investigate the therapeutic potential of quer-cetin and related compounds by elucidating their pharmacological characteristics and molecular mechanisms of action. The potential benefits of quercetin and its analogs for cardiovascular health, disorders of the brain, metabolic disorders, and more are discussed in the discussion part of this page. Concerns about their clinical efficacy due to issues with bioavailability and distribution are also discussed. This region of the paper emphasizes the importance of researchers and clinicians working together to maximize the incorporation of these chemicals into real-world therapeutic approaches. In conclusion, quercetin, along with related substances, shows great potential in a wide range of therapeutic settings. Potentially useful for the management of a wide variety of illnesses, their multiple methods of action include the regulation of pathways for cell signaling and interaction with different enzymes. However, additional clinical tri-als are needed to verify their efficacy and safety.

Exploring the potential pharmacological mechanism of aripiprazole against hyperprolactinemia based on network pharmacology and molecular docking

The current primary therapeutic approach for schizophrenia is antipsychotic medication, and antipsychotic-induced hyperprolactinemia occurs in 40–80% of patients with schizophrenia. Aripiprazole, an atypical antipsychotic belonging to the quinolinone derivative class, can reduce the likelihood of developing hyperprolactinemia, but the pharmacological mechanisms of this reduction are unknown. This study aimed to explore the molecular mechanism of action of aripiprazole in treating hyperprolactinemia based on network pharmacology and molecular docking techniques. This study identified a total of 151 potential targets for aripiprazole from the DrugBank, TCMSP, BATMAN-TCM, TargetNet, and SwissTargetPrediction databases. Additionally, 71 hyperprolactinemia targets were obtained from the PharmGKB, DrugBank, TTD, GeneCards, OMIM, and DisGENET databases. Utilizing Venny 2.1.0 software, an intersection of 27 genes was identified between aripiprazole and hyperprolactinemia. To construct a common target protein–protein interaction (PPI) network, the common targets obtained from both sources were input into the STRING database. The resulting PPI network was then imported into Cytoscape 3.7.2 software, which identified eight core targets associated with aripiprazole’s treatment of hyperprolactinemia. Subsequently, a PPI network was established for these targets. Enrichment analysis of the key targets was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes in the DAVID database. Additionally, molecular docking verification of the interaction between aripiprazole and the core targets was performed using AutoDock Vina software. Aripiprazole’s intervention in hyperprolactinemia primarily targets the following core proteins: Solute Carrier Family 6 Member 3 (SLC6A3), monoamine oxidase (MAO-B), Dopamine D2 receptor (DRD2), 5-hydroxytryptamine (serotonin) receptor 2A (HTR2A), 5-hydroxytryptamine (serotonin) receptor 2C (HTR2C), cytochrome P450 2D6 (CYP2D6), Dopamine D1 receptor (DRD1), Dopamine D4 receptor (DRD4). These targets are predominantly involved in biological processes such as the adenylate cyclase-activating adrenergic receptor signaling pathway, G-protein coupled receptor signaling pathway coupled to cyclic nucleotide second messenger, phospholipase C-activating G-protein coupled receptor signaling pathway, chemical synaptic transmission, and response to xenobiotic stimulus. Primary enrichment occurs in signaling pathways such as the neuroactive ligand-receptor interaction and serotonergic synapse pathways. Molecular docking results demonstrate a favorable affinity between aripiprazole and the core target proteins MAO-B, DRD2, SLC6A3, HTR2C, HTR2A, CYP2D6, DRD4, and DRD1. Network pharmacology predicted potential targets and signaling pathways for aripiprazole’s intervention in hyperprolactinemia, offering theoretical support and a reference basis for optimizing clinical strategies and drug development involving aripiprazole.

A NETWORK PHARMACOLOGY-BASED DRUG REPURPOSING STUDY OF LEVETIRACETAM UNCOVERS ITS INTERACTION WITH MULTI-DRUG TARGETS IN PARKINSON'S DISEASE

Objective: The current study utilized network pharmacology to examine how Levetiracetam interacts with specific drug targets associated with Parkinson's Disease (PD) treatment. Methods: We used information from Kyoto Encyclopedia of Genes and Genome (KEGG) studies and Protein-Protein Interaction (PPI) pathway analysis to create a network that depicts the relationships between Levetiracetam and PD targets. Further investigation involved PPI analysis, molecular docking, and Molecular Dynamics (MD) simulation studies, ultimately pinpointing five protein targets. Their participation in pathways such as Ribonucleic acid Polymerase II-specific Deoxyribonucleic acid binding Transcription Factor Binding (Gene Ontology [GO]:0061629), Axon (GO: 0030424), and Excitatory Postsynaptic Potential was emphasized by GO and KEGG pathway enrichment. Additionally, Dopamine Receptor D2 (DRD2), Solute Carrier Family 6 Member 3 (SLC6A3), Glycogen Synthase Kinase 3 Beta (GSK3B), Poly (ADP-ribose) Polymerase 1 (PARP1) and Myeloperoxidase (MPO) were identified as protein targets through PPI and molecular docking analysis. Results: The results of molecular docking showed that protein targets, SLC6A3, have highest binding affinity with Levetiracetam. The MD Simulation result of Levetiracetam-SLC6A3 docked complex represented the complex to be quite stable with few conformational changes in the SLC6A3 structure. DRD2, SLC6A3, GSK3B, PARP1, MPO were recognized as the likely protein targets of Levetiracetam for treating PD. SLC6A3 was considered as a target of Levetiracetam in PD. Conclusion: Our study revealed the mechanism of Levetiracetam in the treatment of PD and can contribute to more effective treatment for the same. By identifying key protein targets, this research lays the groundwork for future studies that could further explore Levetiracetam’s efficacy.

The role of mesenchymal cells in cholangiocarcinoma.

The tumour microenvironment (TME) significantly influences tumour formation and progression through dynamic interactions. Cholangiocarcinoma (CCA), a highly desmoplastic tumour, lacks early diagnostic biomarkers and has limited effective treatments due to an incomplete understanding of its molecular pathogenesis. Investigating the TME's role in CCA progression could lead to better therapies. RNA sequencing was performed on seven CCA PDXs and their corresponding patient samples. Differential expression analysis was conducted, and Qiagen Ingenuity Pathway Analysis (IPA) was used to predict dysregulated pathways and upstream regulators. PDX and cell line-derived spheroids, with and without immortalised mesenchymal stem cells, were grown and analysed for morphology, growth, and viability. Histological analysis confirmed biliary phenotypes. RNA sequencing indicated upregulation of ECM-receptor interaction and PI3K-Akt pathways in the presence of MSCs, with several genes linked to poor survival. MSCs restored the activity of inhibited cancer-associated kinases (ICAKs). This study shows that adding MSCs to CCA spheroid models restores key paracrine signalling pathways lost in PDXs, enhancing tumour growth and viability. These findings highlight the importance of including stromal components in cancer models to improve pre-clinical studies.

Combining Mendelian Randomization analysis and Network toxicology strategy to identify causality and underlying mechanisms of environmental pollutants with glioblastoma: A study of Methyl-4-hydroxybenzoate

BackgroundAn increasing number of environmental pollutants are associated with human diseases. We explored the mechanisms by which an aromatic small molecule -- Methyl-4-hydroxybenzoate (MEP) contribute to the development of glioblastoma (GBM). MethodsThe causality of MEP and GBM were identified via the Mendelian Randomization (MR) analysis. We identified the key targets by integrating the targets of GBM, differential expressed genes (DEGs) from GEO and target genes of MEP. The network of hub genes was obtained from STRING and Cytoscape tools and GO, KEGG enrichment analysis were conducted by clusterProfiler R package. These hub targets were executed molecular docking via Autodock software. ResultsMEP had a causal association with GBM as risk factors (P < 0.05, OR > 1). 46 key targets were derived, in which CASP3, MMP2 and CDK4 were screened as the hub targets. MEP might play a role in the GBM by affecting the pathways of neuroactive ligand-receptor interaction, Molecular docking analysis showed a good binding ability of between MEP and CASP3, MMP2, CDK4, CASP8 and MCL1. ConclusionsA causal relationship between MEP and GBM exists. CASP3, MMP2, CDK4, CASP8 and MCL1 have been identified as the crucial targets correlating with GBM. This discovery may provide an important insight into how environmental pollutants contribute to the development of GBM.

The Italian guideline on diagnosis and treatment of dementia and mild cognitive impairment.

Approximately 2 million people in Italy are currently living with dementia or mild cognitive impairment (MCI), and 4 million are involved as family members or caregivers. Considering the significant impact of dementia, the Italian Ministry of Health entrusted the Italian National Institute of Health (Istituto Superiore di Sanità) with the development of a guideline within the Italian National Guideline System (Sistema Nazionale Linee Guida, SNLG) on the diagnosis and treatment of dementia and MCI. The main objective was to provide evidence-based recommendations aimed at reducing the variability and ensuring the appropriateness of clinical practices throughout the whole care process from identification and diagnosis to the end of life for people with dementia (PwD) or MCI and their families/caregivers. The GRADE-ADOLOPMENT approach was used to adopt, adapt and update the guideline developed by the National Institute for Health and Care Excellence in 2018 (NG97). The methodology was based on the Methodological Handbook produced by the SNLG. A multidisciplinary panel of 29 experts and four representatives of family members/caregivers discussed and approved 47 review questions. Of these, 34 questions were adopted from the NG97, and 13 were new questions, including 10 questions referring to MCI. Systematic literature reviews were performed for each question, and a team of methodological and clinical experts qualitatively assessed and summarised results from included studies based on the GRADE approach. To facilitate the implementation and dissemination of the contents of this guideline, a care pathway and a leaflet dedicated to PwD or MCI and their families/caregivers were also developed. The literature review for this guideline included studies published up to November 2023. More than 1000 peer-reviewed publications were included, covering the following areas: (i) identification, diagnosis and post-diagnostic support; (ii) care models and care coordination; (iii) pharmacological interventions for cognitive symptoms; (iv) non-pharmacological interventions for cognitive symptoms; (v) non-cognitive symptoms, intercurrent illnesses and palliative care. The multidisciplinary panel discussed and approved 167 clinical practice recommendations and 39 research recommendations. Italy's first National Guideline on dementia and MCI addresses diagnosis, treatment and care within the National Healthcare System. It includes recommendations on pharmacological and non-pharmacological approaches, and emphasises tailored interventions, comprehensive cognitive assessment, staff training and palliative care. The guideline also underlines the need to involve PwD in decision-making and supporting caregivers throughout the entire course of the disease. Structured strategies for the dissemination and implementation of the guideline will be defined within the Italian Fund for Alzheimer and other Dementias 2024-2026. An interactive care pathway and a leaflet dedicated to PwD and their carers are already available. The guideline will be updated starting January 2027, but early updates may be planned in case of breakthrough advancements.

Inhibiting dipeptidyl peptidase 4 positive fibroblasts using zinc sulfide cellulose nanofiber scaffolds to achieve scarless healing

Wound regeneration with integral function and cutaneous appendages remains challenging in wound dressing applications. Cellulose nanofibers (CNF) exhibit remarkable characteristics in wound dressing applications; however, their utility in the wound healing process is limited by insufficient scar inhibition and regenerative healing. Herein, inspired by fibroblast heterogeneity mediating wound healing and skin regeneration, we developed a CNF scaffold designed to block Dipeptidyl Peptidase 4 positive (DPP4+) fibroblasts for regenerative healing. CNF encapsulated sitagliptin (SITA) and zinc sulfide nanoparticles (NZnS), namely CNF@SITA@NZnS, to fabricate a novel biomaterial for scar reduction and regenerative healing. The scaffold promoted scarless healing and hair follicle regeneration in rats. In vivo experiments, the wounds in the scaffold showed less skin fibrosis, a better collagen ratio and more new hair follicles. In vitro experiments showed that the scaffold material promoted scarless healing, possibly by inhibiting the secretion of extracellular matrix and fibroblast-to-myofibroblast conversion. The promotion of hair follicle regeneration by the scaffold material may be due to promotion of the migration and proliferation of human hair follicle papilla cells. RNA sequencing is performed to explore the underlying mechanisms, which can activate ECM-receptor interaction pathway in favor of the wound healing process. The inhibiting effect of CNF@SITA@NZnS scaffold on DPP4+ fibroblasts can be a potential target to reduce scarring and promote skin regeneration.

Effect of high mobility group box 1 pathway inhibition on gene expression in the prefrontal cortex of mice exposed to alcohol

The high mobility group box 1 (HMGB1) pathway plays a pivotal role in the development of alcohol-induced brain injury. Glycyrrhizinic acid (GlyA) is widely regarded as an inhibitor of HMGB1. The objective is to investigate the impact on gene expression in the prefrontal cortex,we sequenced the transcriptome in control, alcohol-exposed, and HMGB1-inhibited groups of mice. We verified our findings by real-time quantitative PCR (qRT-PCR). An alcohol exposure model was established in mice by intraperitoneal injection of alcohol. Transcriptome sequencing and bioinformatics analyses were performed on prefrontal cortex tissue. Kyoto Encyclopedia of Genes and Genomes analysis was performed to identify pivotal pathways of differentially expressed genes. The role of relevant genes was verified by qRT-PCR. Expression of genes involved in the neuroactive ligand-receptor interaction pathway exhibited an increase in mice from the alcohol-exposed group.However, there were no significant differences observed in the expression of these genes between control and those receiving an intraperitoneal injection of alcohol along with a HMGB1 inhibitor. Mice in the alcohol-exposed group showed increased gene expression of Cysltr2, Chrna6, Chrna3, Chrnb4, and Pmch. Expression of these genes was decreased in mice injected with HMGB1 inhibitor. Our study demonstrates that alcohol primarily influences gene expression in the prefrontal cortex of mice through the neuroactive ligand-receptor interaction pathway. HMGB1 inhibitor effectively inhibited the expression of this pathway. This study provides a novel route for drug development in alcohol-induced brain injury.

Unraveling the impact of intervention strategies and oxygen disparity in humification during domestic waste composting.

This study constructs three different photovoltaic assisted composting systems to treat rural domestic waste, and explores the interaction pathways between biomacromolecules and other factors under oxygen disparity at gradient heights of the compost. The optimized mode of regular turning and ventilation-dehydration significantly reduced the moisture content by 53.6% and increased the seed germination index by 35.6%. The oxygen content at different heights under the optimized mode significantly affects the physicochemical properties of the compost, and the degradation of cellulose, hemicellulose, and protein in the middle is higher than other parts. The structural equation model shows that the physicochemical properties at the bottom are affected by biomacromolecules, which may be related to volatile fatty acids(VFAs) produced under low oxygen conditions.The research results show that using manual turning and ventilation-dehydration as the optimized process can promote compost maturity, and oxygen concentration has an important impact on the humification process of the compost.

Mechanistic insights into antihypertensive activity of mushroom-derived protein-peptides via metabolomic and proteomic approaches

Stropharia rugosoannulata mushroom peptides have well-defined sequences, specific structures, and excellent antihypertensive activity. In this study, metabolomic and proteomic analyses revealed the antihypertensive mechanism of mushroom-derived protein-peptides, GQEDYDRLRPL (GL-11P) and KSWDDFFTR (KR-9P), to demonstrate their potential antihypertensive buck-regulation systems and pathways. Protein-peptides were predominantly down-regulated expression of endogenous metabolites in antihypertensive regulation, and bile acid analogs were key endogenous differentially expressed metabolic markers. Antihypertensive treatment with protein-peptides activated the immune and signal transduction systems, affected extracellular regions, metal ion binding, and receptor binding ability. The ECM-receptor interaction pathway, with differentially expressed proteins in antihypertensive treatment, distinguished the protein-peptides from blank control and was also a critical pathway that distinguished the two protein-peptides. Up-regulatory pathways of protein expression dominated by GL-11P's antihypertensive regulation, while down-regulatory pathways of protein expression dominated by KR-9P's antihypertensive regulation. Protein-peptides exerted antihypertensive regulatory effects by enhancing immune responses, up-regulating protein and enzyme binding capacity, and down-regulating inflammatory mediator release. Differentially expressed protein interactions produced in protein-peptides antihypertensive therapy mostly up-regulated the Reactome pathway and were dominated by immune system regulation. This study provided data support for utilizing mushroom-derived protein-peptides in antihypertensive therapy, and enriched the theoretical basis of protein-peptides' antihypertensive regulation mechanisms.