Mapping of technological strategies for reducing social isolation in homebound older adults: A scoping review.

BACKGROUND: Homebound older adults (HOAs) are particularly vulnerable to social isolation and loneliness, which engender a poorer physical and mental health, and greater cognitive decline. The purpose of this review is to map the literature to identify potential technological strategies that reduce social isolation in HOAs, and to understand facilitators and barriers for adoption and implementation. METHODS: Six databases including PubMed (MEDLINE), Google Scholar, Cochrane Database, EBSCOHost, National Library ProQuest, Web of Science, and the Journal of Medical Internet Research were searched for relevant articles. Peer-reviewed literature published in English from Jan 2014 to Feb 2024 that employed technological strategies applicable to HOAs and assessed social isolation or connectedness as an outcome measure were included. RESULTS: 107 studies were reviewed and classified into different technological categories based on their functions and features. A social technology framework encompassing delivery, hardware, software, content, training, and support was conceptualized with core characteristics identified from the reviewed technological strategies. Cost and complexity of technology, and resource commitment were identified as barriers while user-friendliness, content curation and a supportive ecosystem may facilitate the adoption of a technological strategy to address social isolation in HOAs. CONCLUSION: There is a need for early and concerted effort to identify HOAs, provide technology training, and empower them to tap on the digital world to complement and/or supplement social interactions. Development of cost-effective and rapid-to-implement technology is vital for HOAs who are at highest risk to social isolation.

Progress on early diagnosing Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects both cognition and non-cognition functions. The disease follows a continuum, starting with preclinical stages, progressing to mild cognitive and behavioral impairment, ultimately leading to dementia. Early detection of AD is crucial for better diagnosis and more effective treatment. However, the current AD diagnostic tests of biomarkers using cerebrospinal fluid and/or brain imaging are invasive or expensive, and mostly are still not able to detect early disease state. Consequently, there is an urgent need to develop new diagnostic techniques with higher sensitivity and specificity during the preclinical stages of AD. Various non-cognitive manifestations, including behavioral abnormalities, sleep disturbances, sensory dysfunctions, and physical changes, have been observed in the preclinical AD stage before occurrence of notable cognitive decline. Recent research advances have identified several biofluid biomarkers as early indicators of AD. This review focuses on these non-cognitive changes and newly discovered biomarkers in AD, specifically addressing the preclinical stages of the disease. Furthermore, it is of importance to explore the potential for developing a predictive system or network to forecast disease onset and progression at the early stage of AD.

A comprehensive meta-analysis on the association of SGLT2is and GLP-1RAs with vascular diseases, digestive diseases and fractures.

AIM: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) are two new classes of antidiabetic agents. We aimed to evaluate the association between these two drug classes and risk of various vascular diseases, digestive diseases and fractures. METHODS: Large randomized trials of SGLT2is and GLP-1RAs were included. Outcomes of interest were the various serious adverse events related to vascular diseases, digestive diseases and fractures. We performed meta-analyses using synthesize risk ratio (RR) and 95% confidence interval (CI) as effect size. RESULTS: We included 27 large trials. SGLT2is had significant association with less hypertension (RR 0.70, 95% CI 0.54-0.91), hypertensive crisis (RR 0.63, 95% CI 0.47-0.84), varicose vein (RR 0.34, 95% CI 0.13-0.92), and vomiting (RR 0.55, 95% CI 0.31-0.97); but more spinal compression fracture (RR 1.73, 95% CI 1.02-2.92) and tibia fracture. GLP-1RAs had significant association with more deep vein thrombosis (RR 1.92, 95% CI 1.23-3.00), pancreatitis (RR 1.54, 95% CI 1.07-2.22), and cholecystitis acute (RR 1.51, 95% CI 1.08-2.09); but less rib fracture (RR 0.59, 95% CI 0.35-0.97). Sensitivity analyses suggested that our findings were robust. CONCLUSIONS: SGLT2is may have protective effects against specific vascular and digestive diseases, whereas they may increase the incidence of site-specific fractures (e.g., spinal compression fracture). GLP-1RAs may have protective effects against site-specific fractures (i.e., rib fracture), whereas they may increase the incidence of specific vascular and digestive diseases. These findings may help to make a choice between SGLT2is and GLP-1RAs in clinical practice.

Efficacy of first-line dual oral pyrotinib plus capetabine therapy in HER2-positive metastatic breast cancer: A real-world retrospective study.

BACKGROUND: The combination of dual-targeted human epidermal growth factor receptor 2 (HER2) therapy and chemotherapy is the standard first-line regimen for recurrent/metastatic breast cancer (mBC). However, the toxicity of such combination therapy can lead to some patients being unable to tolerate adverse events or bear treatment costs. As a novel irreversible pan-ErbB receptor TKI (pyrotinib), can the dual oral administration of pyrotinib plus capetabine (PyroC) provide first-line survival benefits and serve as a more affordable treatment option? METHODS: This real-world retrospective study included patients diagnosed with HER2-positive mBC who received PyroC as a first-line treatment at West China Hospital between May 2018 and July 2023. The survival data and toxicity profiles were reported in this study. RESULTS: A total of 64 patients received PyroC as first-line therapy. The median progression-free survival (PFS) was 19.6 months (95% CI 15.0-27.2), while overall survival (OS) has not yet been reached. Kaplan-Meier analysis indicated that age (≥60, p = 0.03) and metastasis sites (p = 0.004) were related to poor efficacy of PyroC, while there was no relationship between effectiveness and menstrual status, hormone receptor (HR) status or previous treatment with anti-HER2 therapy. Furthermore, the objective response rate (ORR) and disease control rate (DCR) were 79.7% and 98.4%, respectively. Of the patients, 78.1% reported treatment-related adverse events (TRAEs). The predominant adverse events were diarrhea (n = 46, 71.9%) and hand-foot syndrome (n = 10, 15.6%). CONCLUSION: The dual oral administration regimen (PyroC) has a promising ORR or PFS in HER2-positive mBC patients, with an acceptable safety profile and convenience.

Cutaneous manifestations of myelodysplastic syndrome: A systematic review.

Myelodysplastic syndrome (MDS) may present with specific skin lesions, such as leukaemia cutis, which is a well known poor prognostic marker of leukaemia with a high risk of acute leukaemic transformation. However, less is known regarding non-specific cutaneous manifestations of MDS including the prevalence, types and their prognostic and therapeutic significance, which we aimed to determine through this systematic review. We searched electronic databases (PubMed, Medline and EMBASE) from inception up to 26 January 2023 for studies reporting cutaneous manifestations of MDS. Eighty eight articles (case reports n = 67, case series n = 21), consisting of 134 patients were identified. We identified 6 common cutaneous manifestations: neutrophilic dermatoses (n = 64), vasculitis (n = 21), granulomatous (n = 8), connective tissue disease (CTD) (n = 7; composed of dermatomyositis (n = 5), cutaneous lupus erythematosus (n = 1), and systemic sclerosis (n = 1)), panniculitis (n = 4), immunobullous (n = 1), and other (n = 29). Cutaneous features either occurred at time of MDS diagnosis in 25.3%, preceding the diagnosis in 34.7% (range 0.5-216 months), or after diagnosis in 40.0% (range 1-132 months). Prognosis was poor (40.2% death) with 34.1% progressing to acute myeloid leukaemia (AML). 50% of those with MDS who progressed to AML had neutrophilic dermatoses (p = 0.21). Myelodysplastic syndrome was fatal in 39.2% of neutrophilic dermatoses (median time from onset of cutaneous manifestation: 12 months), 50% of vasculitis (7.5 months), 62.5% of granulomatous (15.5 months) and 14.3% of CTD (7 months). Recognition of patterns of cutaneous features in MDS will improve early diagnosis and risk stratification according to subtype and associated prognosis.

MAP2K1 K57N Conferred an Acquired Resistance to Furmonertinib, Dabrafenib and Trametinib Combined Therapy in Advanced Lung Adenocarcinoma with EGFR Mutation and BRAF V600E.

Previous case reports have demonstrated the effectiveness of combination therapy involving EGFR TKI, BRAF inhibitor dabrafenib, and MEK inhibitor trametinib in metastatic non-small-cell lung cancer (NSCLC) patients with acquired BRAF V600E and EGFR mutations. However, the current literature does not provide any reports on the presence of resistant mutations in response to the administration of three-drug combination therapy. Exploring the resistance mechanism of targeted therapy is helpful to optimize the subsequent treatment strategy of patients. Herein, we report a case of a patient with advanced EGFR positive lung adenocarcinoma harboring an acquired BRAF V600E mutation who responded to the combination of furmonertinib, dabrafenib, and trametinib therapy. Unexpectedly, a MAP2K1 K57N acquired mutation was identified by NGS (Next-generation sequencing) analysis of re-biopsy tumor tissue after the patient was resistant to three-drug therapy. As far as we know, this is the first report demonstrating that the efficacy of using combination of furmonertinib and BRAF/MEK inhibitors and the MAP2K1 K57N mutation serves as a resistant mechanism to the three-drug therapy. This novel finding not only revealed a new resistant mutation but also had important implications for the identification of effective patients to EGFR/BRAF/MEK combination therapy.

Modification, biological activity, applications, and future trends of citrus fiber as a functional component: A comprehensive review.

Citrus fiber, a by-product of citrus processing that has significant nutritional and bioactive properties, has gained attention as a promising raw material with extensive developmental potential in the food, pharmaceutical, and feed industries. However, the lack of in-depth understanding regarding citrus fiber, including its structure, modification, mechanism of action, and potential applications is holding back its development and utilization in functional foods and drugs. This review explores the status of extraction methods and modifications applied to citrus fiber to augment its health benefits. With the aim of introducing readers to the potential health benefits of citrus fibers, we have placed special emphasis on their regulatory mechanisms in the context of various conditions, including type 2 diabetes mellitus, cardiovascular disease, obesity, and cancer. Furthermore, this review highlights the applications and prospects of citrus fiber, aiming to provide a theoretical basis for the utilization and exploration of this valuable resource.

Platelet Exosome-Derived miR-223-3p Regulates Pyroptosis in the Cell Model of Sepsis-Induced Acute Renal Injury by Targeting Mediates NLRP3.

BACKGROUND: The present study investigated the roles and mechanisms of platelet-derived exosomes in sepsis-induced acute renal injury. METHODS: The blood samples of septic patients and healthy controls were collected for clinical examination. The plasma levels of miR-223-3p and NLRP3 mRNA were analyzed by qRT-PCR and the serum IL-1ß and creatinine levels were quantified by enzyme-linked immunosorbent assay (ELISA). C57BL/6 mice injected with LPS (lipopolysaccharide) were employed as the animal model for sepsis-induced acute renal injury. Human coronary artery endothelial cells (HCAECs) were treated with TNF-α as a cellular model for sepsis-induced endothelial damages. RESULTS: The number of PMP (platelet-derived microparticles) in patients with sepsis was increased. The level of miR-223-3p in the platelet exosomes isolated from the serum sample in patients with sepsis was significantly lower than that of the healthy controls. The level of miR-223-3p was also decreased in the platelet exosomes of mouse model with sepsis-induced acute renal injury. Downregulating miR-223-3p promoted sepsis-induced acute renal injury in mice model, while the administration of miR-223-3p reduced the inflammation in endothelial cells of sepsis-induced acute renal injury. NLRP3 (NLR Family Pyrin Domain Containing 3) was identified as one target of miR-223-3p in the platelet exosomes of sepsis-induced acute kidney injury. miR-223-3p attenuated NLRP3-induced pyroptosis in endothelial cell model of sepsis-induced acute kidney injury. CONCLUSION: Our data suggest that platelet exosome-derived miR-223-3p negatively regulates NLRP3-dependent inflammasome to suppress pyroptosis in endothelial cells. Decreased miR-223-3p expression promotes the inflammation in sepsis-induced acute renal injury. Targeting miR-223-3p may be developed into a therapeutic approach for sepsis-induced acute renal injury.

Protective Effect of the Naringin-Chitooligosaccharide Complex on Lipopolysaccharide-Induced Systematic Inflammatory Response Syndrome Model in Mice.

Naringin is one of the common flavonoids in grapefruit, which has anti-cancer, antioxidant, and anti-inflammatory activities. However, its poor solubility limits its wide application. Therefore, the aim of this study is to investigate the anti-inflammatory effect of naringin combined with chitooligosaccharides with good biocompatibility by constructing a mouse model of systemic inflammatory response syndrome (SIRS). The results showed that the naringin-chitooligosaccharide (NG-COS) complex significantly inhibited lipopolysaccharide (LPS)-induced weight loss, reduced food intake, tissue inflammatory infiltration, and proinflammatory cytokines IL-6, TNF-α, INF-γ, and IL-1ß levels. The complex also significantly affected the content of malondialdehyde and the activities of MPO, SOD, and GSH in the liver, spleen, lungs, and serum of mice with systemic inflammation. In addition, NG-COS significantly inhibited the mRNA expression of inflammatory factors in the TLR4/NF-κB signaling pathway. Principal component analysis showed that the complexes could inhibit LPS-induced systemic inflammation in mice, and the effect was significantly better than that of naringin and chitooligosaccharides alone. This study explored the synergistic effects of chitosan and naringin in reducing inflammation and could contribute to the development of novel biomedical interventions.

Space-time cube uncovers spatiotemporal patterns of basin ecological quality and their relationship with water eutrophication.

Maintaining an optimal eco-environment is important for sustainable regional development. However, existing methods are inadequate for examining both spatial and temporal dimensions. Here, we propose a systematic procedure for spatiotemporal examination of the eco-environment using the space-time cube (STC) model and describe a preliminary investigation of the coupling relationships between basin ecological quality and water eutrophication in upstream of the Han River basin between 2000 and 2020. The STC model considers the temporal dimension as the third dimension in calculations. We first categorized the basin into three sub-watershed types: forest, cultivated land, and artificial surface. Subsequently, the ecological quality and driving factors were assessed and identified using the remote sensing ecological index (RSEI) and Geodetector method, respectively. The findings indicated that the forest basin and artificial surface basin had the highest and lowest ecological quality, respectively. The spatiotemporal cold spots of ecological quality during the past 20 years were mostly located in the vicinity of reservoirs, rivers, and artificial surface areas. Human activity, precipitation, and the percentage of cultivated land were other important driving factors in the artificial surface, forest, and cultivated land sub-watersheds, respectively, in addition to the dominant factors of elevation and temperature. The results also indicated that when the ecological quality degraded to a certain extent, water eutrophication was significantly coupled with the ecological quality of the catchments. The findings of this study are useful for ecological restoration and sustainable river basin development.

Antihyperlipidemic drug rosuvastatin suppressed tumor progression and potentiated chemosensitivity by downregulating CCNA2 in lung adenocarcinoma.

Rosuvastatin (RSV) is widely used to treat hyperlipidemia and hypercholesterolemia and is recommended for the primary and secondary prevention of cardiovascular diseases (CVD). In this study, we aimed to explore its action and mechanism in lung adenocarcinoma (LUAD) therapy. Lewis and CMT64 cell-based murine subcutaneous LUAD models were employed to explore the effects of RSV monotherapy combined with cisplatin and gemcitabine. Human lung fibroblasts and human LUAD cell lines were used to assess the effects of RSV on normal and LUAD cells. Bioinformatics and RNA interference were used to observe the contribution of cyclin A2 (CCNA2) knockdown to RSV inhibition and to improve chemosensitivity in LUAD. RSV significantly suppressed grafted tumor growth in a murine subcutaneous LUAD model and exhibited synergistic anti-tumor activity with cisplatin and gemcitabine. In vitro and in vivo experiments demonstrated that RSV impaired the proliferation and migration of cancer cells while showing little inhibition of normal lung cells. RNA interference and CCK8 detection preliminarily indicated that RSV inhibited tumor growth and enhanced the chemosensitivity to cisplatin and gemcitabine by downregulating CCNA2. RSV suppressed LUAD progression and enhanced chemosensitivity to cisplatin and gemcitabine by downregulating CCNA2, which should be prior consideration for the treatment of LUAD, especially for patients co-diagnosed with hyperlipidemia and hypercholesterolemia.

Citrus p-Synephrine Improves Energy Homeostasis by Regulating Amino Acid Metabolism in HFD-Induced Mice.

p-Synephrine is a common alkaloid widely distributed in citrus fruits. However, the effects of p-synephrine on the metabolic profiles of individuals with energy abnormalities are still unclear. In the study, we investigated the effect of p-synephrine on energy homeostasis and metabolic profiles using a high fat diet (HFD)-induced mouse model. We found that p-synephrine inhibited the gain in body weight, liver weight and white adipose tissues weight induced by HFD. p-Synephrine supplementation also reduced levels of serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) but not to a statistically significant degree. Histological analysis showed that HFD induced excessive lipid accumulation and glycogen loss in the liver and adipocyte enlargement in perirenal fat tissue, while p-synephrine supplementation reversed the changes induced by HFD. Moreover, HFD feeding significantly increased mRNA expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) and reduced the mRNA expression level of interleukin-10 (IL-10) compared to the control group, while p-synephrine supplementation significantly reversed these HFD-induced changes. Liver and serum metabolomic analysis showed that p-synephrine supplementation significantly altered small molecule metabolites in liver and serum in HFD mice and that the changes were closely associated with improvement of energy homeostasis. Notably, amino acid metabolism pathways, both in liver and serum samples, were significantly enriched. Our study suggests that p-synephrine improves energy homeostasis probably by regulating amino acid metabolism in HFD mice, which provides a novel insight into the action mechanism of p-synephrine modulating energy homeostasis.

Elevated brain temperature under severe heat exposure impairs cortical motor activity and executive function.

BACKGROUND: Excessive heat exposure can lead to hyperthermia in humans, which impairs physical performance and disrupts cognitive function. While heat is a known physiological stressor, it is unclear how severe heat stress affects brain physiology and function. METHODS: Eleven healthy participants were subjected to heat stress from prolonged exercise or warm water immersion until their rectal temperatures (Tre) attained 39.5°C, inducing exertional or passive hyperthermia, respectively. In a separate trial, blended ice was ingested before and during exercise as a cooling strategy. Data were compared to a control condition with seated rest (normothermic). Brain temperature (Tbr), cerebral perfusion, and task-based brain activity were assessed using magnetic resonance imaging techniques. RESULTS: Tbr in motor cortex was found to be tightly regulated at rest (37.3°C ± 0.4°C (mean ± SD)) despite fluctuations in Tre. With the development of hyperthermia, Tbr increases and dovetails with the rising Tre. Bilateral motor cortical activity was suppressed during high-intensity plantarflexion tasks, implying a reduced central motor drive in hyperthermic participants (Tre = 38.5°C ± 0.1°C). Global gray matter perfusion and regional perfusion in sensorimotor cortex were reduced with passive hyperthermia. Executive function was poorer under a passive hyperthermic state, and this could relate to compromised visual processing as indicated by the reduced activation of left lateral-occipital cortex. Conversely, ingestion of blended ice before and during exercise alleviated the rise in both Tre and Tbr and mitigated heat-related neural perturbations. CONCLUSION: Severe heat exposure elevates Tbr, disrupts motor cortical activity and executive function, and this can lead to impairment of physical and cognitive performance.

Eutrophication and loss of riparian shading influence food quality and trophic relation in stream food webs.

Eutrophication induced by excessive inputs of nutrient is one of the main stressors in aquatic ecosystems. Deforestation in riparian zones alter riparian shading, which together with eutrophication is expected to exert a complex control over stream food webs. We manipulated two levels of riparian shading (open canopy vs. shading canopy) and nutrient supply (ambient vs. nutrient addition) in three headwater streams to investigate the individual and combined effects of eutrophication and loss of riparian shading on carbon sources and nutritional quality of biofilms, and the subsequent trophic effects on macroinvertebrate grazers. Nutrient enrichment increased the autochthonous carbon (i.e., algae especially diatoms) indicated by fatty acid (FA) biomarkers within biofilms and grazers. The nutritional quality indicated by eicosapentaenoic acid (EPA) content of biofilms was increased with nutrient enrichment and more so with the combined effect of an increase in riparian shading, consequently leading to an increase in the nutritional quality, density, and biomass of grazers. In particular, the trophic linkages between biofilms and grazers were mainly influenced by EPA concentration in the biofilms, and strengthened with the combined effects of riparian shading and additional nutrients. Our study emphasizes the nutritional significance of EPA for consumers at higher trophic levels and proposes its potential as an indicator for monitoring the health of aquatic ecosystems.

Targeting PRSS23 with tipranavir induces gastric cancer stem cell apoptosis and inhibits growth of gastric cancer via the MKK3/p38 MAPK-IL24 pathway.

Gastric cancer stem cells (GCSCs) contribute to the refractory features of gastric cancer (GC) and are responsible for metastasis, relapse, and drug resistance. The key factors drive GCSC function and affect the clinical outcome of GC patients remain poorly understood. PRSS23 is a novel serine protease that is significantly up-regulated in several types of cancers and cancer stem cells, and related to tumor progression and drug resistance. In this study, we investigated the role of PRSS23 in GCSCs as well as the mechanism by which PRSS23 regulated the GCSC functions. We demonstrated that PRSS23 was critical for sustaining GCSC survival. By screening a collection of human immunodeficiency virus (HIV) protease inhibitors (PIs), we identified tipranavir as a PRSS23-targeting drug, which effectively killed both GCSC and GC cell lines (its IC50 values were 4.7 and 6.4 µM in GCSC1 cells and GCSC2 cells, respectively). Administration of tipranavir (25 mg·kg-1·d-1, i.p., for 8 days) in GCSC-derived xenograft mice markedly inhibited the growth of subcutaneous GCSC tumors without apparent toxicity. In contrast, combined treatment with 5-FU plus cisplatin did not affect the tumor growth but causing significant weight loss. Furthermore, we revealed that tipranavir induced GCSC cell apoptosis by suppressing PRSS23 expression, releasing MKK3 from the PRSS23/MKK3 complex to activate p38 MAPK, and thereby activating the IL24-mediated Bax/Bak mitochondrial apoptotic pathway. In addition, tipranavir was found to kill other types of cancer cell lines and drug-resistant cell lines. Collectively, this study demonstrates that by targeting both GCSCs and GC cells, tipranavir is a promising anti-cancer drug, and the clinical development of tipranavir or other drugs specifically targeting the PRSS23/MKK3/p38MAPK-IL24 mitochondrial apoptotic pathway may offer an effective approach to combat gastric and other cancers.

Primary pulmonary adenoid cystic carcinoma: A clinicopathological study of 64 patients.

BACKGROUND: This study aimed to investigate the clinicopathological features and prognostic indicators of primary pulmonary adenoid cystic carcinoma (PACC). METHODS: Clinical data were collected from 64 primary PACC patients and analyzed retrospectively at the Tianjin Medical University General Hospital, the West China Hospital of Sichuan University, the First Affiliated Hospital of Guangxi Medical University, and the Bishan Hospital of Chongqing Medical University from January 2003 to August 2023. The 64 patients (28 males and 36 females) were aged from 20 to 73 years, with a median age of 49 years and an average age of 49.3 years. RESULTS: Immunohistochemical staining showed that the tumors expressed CK7, S-100 protein, CK5/6, CD117, and p63. Seven patients underwent fluorescence in situ hybridization (FISH) testing and three were found to have myeloblastosis (MYB) gene translocation. In total, 53 patients underwent surgery, among whom 31 received only surgery and 22 received both surgery and postoperative chemoradiotherapy. In addition, 10 patients received chemoradiotherapy only, while one patient underwent treatment with traditional Chinese medicine. The overall survival rates in the first, third, and fifth years were 98.4%, 95.3%, and 87.5%, respectively. CONCLUSION: Prognostic analysis revealed that age, tumor size, lymph node metastasis status, margin status, and choice of treatment modality significantly influenced the patients' prognosis.

The role of Nurr1-miR-30e-5p-NLRP3 axis in inflammation-mediated neurodegeneration: insights from mouse models and patients' studies in Parkinson's disease.

Nuclear receptor related-1 (Nurr1), a ligand-activated transcription factor, is considered a potential susceptibility gene for Parkinson's disease (PD), and has been demonstrated to possess protective effects against inflammation-induced neuronal damage. Despite the evidence showing decreased NURR1 level and increased pro-inflammatory cytokines in cell and animal models as well as in PD patients' peripheral blood mononuclear cells (PBMCs), the underlying mechanism remains elusive. In this study, we investigated the molecular mechanism of Nurr1 in PD-related inflammation. Through the miRNA-sequencing and verification in PBMCs from a cohort of 450 individuals, we identified a significant change of a Nurr1-dependent miRNA miR-30e-5p in PD patients compared to healthy controls (HC). Additionally, PD patients exhibited an elevated plasma interleukin-1ß (IL-1ß) level and increased nucleotide-binding domain-like receptor protein 3 (NLRP3) expression in PBMCs compared to HC. Statistical analyses revealed significant correlations among NURR1, miR-30e-5p, and NLRP3 levels in the PBMCs of PD patients. To further explore the involvement of Nurr1-miR-30e-5p-NLRP3 axis in the inflammation-mediated PD pathology, we developed a mouse model (Nurr1flox+/Cd11b-cre+, Nurr1cKO) conditionally knocking out Nurr1 in Cd11b-expressing cells. Our investigations in Nurr1cKO mice unveiled significant dopaminergic neurodegeneration following lipopolysaccharide-induced inflammation. Remarkably, Nurr1 deficiency triggered microglial activation and activated NLRP3 inflammasome, resulting in increased IL-1ß secretion. Coincidently, we found that miR-30e-5p level was significantly decreased in the PBMCs and primary microglia of Nurr1cKO mice compared to the controls. Furthermore, our in vitro experiments demonstrated that miR-30e-5p specifically targeted NLRP3. In Nurr1-knockdown microglia, NLRP3 expression was upregulated via miR-30e-5p. In summary, our findings highlight the involvement of Nurr1-miR-30e-5p-NLRP3 axis in the inflammation-mediated neurodegeneration in PD, the results of which may offer promising prospects for developing PD biomarkers and targeted therapeutic interventions.

Regulatory effect of lactulose on intestinal flora and serum metabolites in colitis mice: In vitro and in vivo evaluation.

Lactulose is a common component in foods. However, the effect of lactulose on intestinal flora and overall metabolic levels remains unclear. Therefore, this study aims to explore the regulative role of lactulose on intestinal flora and serum metabolites via in vitro simulated colonic fermentation model and in vivo colitis mouse model. The results showed that lactulose significantly enriched beneficial bacteria including Dubosiella and Bifidobacterium, and reduced pathogenic bacteria such as Fusobacterium. Moreover, lactulose significantly inhibited dextran sodium sulfate-induced body weight loss, colon shortening, colonic inflammatory infiltration, and pro-inflammatory cytokines IL-6, TNF-α, IL-17, and IL-1ß. Lactulose significantly affected serum metabolome in colitis mice and total 24 metabolites representing a high inter-group difference were obtained. Correlation analysis revealed that the changes in serum metabolites were closely associated with the role of intestinal flora, and thus affected phenotypic indicators. Our study provides a reference for nutritional characteristics and application scenarios of dietary lactulose.

Propionic Acid Driven by the Lactobacillus johnsonii Culture Supernatant Alleviates Colitis by Inhibiting M1 Macrophage Polarization by Modulating the MAPK Pathway in Mice.

In this study, we investigated the effects of Lactobacillus johnsonii on the mouse colitis model. The results showed that the supernatant of the L. johnsonii culture alleviated colitis and remodeled gut microbiota, represented by an increased abundance of bacteria producing short-chain fatty acids, leading to an increased concentration of propionic acid in the intestine. Further studies revealed that propionic acid inhibited activation of the MAPK signaling pathway and polarization of M1 macrophages. Macrophage clearance assays confirmed that macrophages are indispensable for alleviating colitis through propionic acid. In vitro experiments showed that propionic acid directly inhibited the MAPK signaling pathway in macrophages and reduced M1 macrophage polarization, thereby inhibiting the secretion of pro-inflammatory cytokines. These findings improve our understanding of how L. johnsonii attenuates inflammatory bowel disease (IBD) and provide valuable insights for identifying molecular targets for IBD treatment in the future.

Modification methods, biological activities and applications of pectin: A review.

Pectin is a complex and functionally rich natural plant polysaccharide that is widely used in food, medical, and cosmetic industries. It can be modified to improve its properties and expand its applications. Modification methods for natural pectin can be divided into physical, chemical, enzymatic, and compound methods. Different modification methods can result in modified pectins (MPs) exhibiting different physicochemical properties and biological activities. The objectives of this paper were to review the various pectin modification methods explored over the last decade, compare their differences, summarize the impact of different modification methods on the biological activity and physicochemical properties of pectin, and describe the applications of MPs in food and pharmaceutical fields. Finally, suggestions and perspectives for the development of MPs are discussed. This review offers a theoretical reference for the rational and efficient processing of pectin and the expansion of its applications.