Antioxidant synergistic anti-inflammatory effect in the MAPK/NF-κB pathway of peptide KGEYNK (KK-6) from giant salamander (Andrias davidianus).

BACKGROUND: Giant salamander protein peptide is a peptide with rich functional properties. Giant salamander protein peptide KGEYNK (KK-6) is a peptide with both antioxidant and anti-inflammatory properties. The antioxidant and anti-inflammatory mechanisms of KK-6 are still unclear. When we studied the functional mechanism of KK-6, we found that the antioxidant property of KK-6 has a synergistic and promoting effect on anti-inflammatory properties. RESULTS: KK-6 enhances cellular resistance to LPS via the MAPK/NF-κB signaling pathway, leading to increased levels of inflammatory factors: interleukin-1ß (764.81 ng mL-1), interleukin-6 (1.06 ng mL-1) and tumor necrosis factor-α (4440.45 ng mL-1). KK-6 demonstrates potent antioxidant properties by activating the Nrf2 signaling pathway, resulting in elevated levels of antioxidant enzymes (glutathione peroxidase: 0.03 µg mL-1; superoxide dismutase: 0.589 µg mL-1) and a reduction in the concentration of the oxidative product malondialdehyde (967.05 µg mL-1). CONCLUSION: Our findings highlight the great potential of KK-6, a peptide extracted from giant salamander protein, as a remedy for intestinal inflammation. Through its dual role as an antioxidant and anti-inflammatory agent, KK-6 offers a promising avenue for alleviating inflammation-related damage and oxidative stress. This study lays the foundation for further exploration of giant salamander products and highlights their importance in health and novel food development. © 2024 Society of Chemical Industry.

Altered leptin level in autism spectrum disorder and meta-analysis of adipokines.

BACKGROUND: Increasing evidence suggests that leptin is involved in the pathology of autism spectrum disorder (ASD). In this study, our objective was to investigate the levels of leptin in the blood of children with ASD and to examine the overall profile of adipokine markers in ASD through meta-analysis. METHODS: Leptin concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) kit, while adipokine profiling, including leptin, was performed via meta-analysis. Original reports that included measurements of peripheral adipokines in ASD patients and healthy controls (HCs) were collected from databases such as Web of Science, PubMed, and Cochrane Library. These studies were collected from September 2022 to September 2023 and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Standardized mean differences were calculated using a random effects model for the meta-analysis. Additionally, we performed meta-regression and explored heterogeneity among studies. RESULTS: Our findings revealed a significant increase in leptin levels in children with ASD compared to HCs (p = 0.0319). This result was consistent with the findings obtained from the meta-analysis (p < 0.001). Furthermore, progranulin concentrations were significantly reduced in children with ASD. However, for the other five adipokines analyzed, there were no significant differences observed between the children with ASD and HCs children. Heterogeneity was found among the studies, and the meta-regression analysis indicated that publication year and latitude might influence the results of the meta-analysis. CONCLUSIONS: These findings provide compelling evidence that leptin levels are increased in children with ASD compared to healthy controls, suggesting a potential mechanism involving adipokines, particularly leptin, in the pathogenesis of ASD. These results contribute to a better understanding of the pathology of ASD and provide new insights for future investigations.

Early blood immune molecular alterations in cynomolgus monkeys with a PSEN1 mutation causing familial Alzheimer's disease.

INTRODUCTION: More robust non-human primate models of Alzheimer's disease (AD) will provide new opportunities to better understand the pathogenesis and progression of AD. METHODS: We designed a CRISPR/Cas9 system to achieve precise genomic deletion of exon 9 in cynomolgus monkeys using two guide RNAs targeting the 3' and 5' intron sequences of PSEN1 exon 9. We performed biochemical, transcriptome, proteome, and biomarker analyses to characterize the cellular and molecular dysregulations of this non-human primate model. RESULTS: We observed early changes of AD-related pathological proteins (cerebrospinal fluid Aß42 and phosphorylated tau) in PSEN1 mutant (ie, PSEN1-ΔE9) monkeys. Blood transcriptome and proteome profiling revealed early changes in inflammatory and immune molecules in juvenile PSEN1-ΔE9 cynomolgus monkeys. DISCUSSION: PSEN1 mutant cynomolgus monkeys recapitulate AD-related pathological protein changes, and reveal early alterations in blood immune signaling. Thus, this model might mimic AD-associated pathogenesis and has potential utility for developing early diagnostic and therapeutic interventions. HIGHLIGHTS: A dual-guide CRISPR/Cas9 system successfully mimics AD PSEN1-ΔE9 mutation by genomic excision of exon 9. PSEN1 mutant cynomolgus monkey-derived fibroblasts exhibit disrupted PSEN1 endoproteolysis and increased Aß secretion. Blood transcriptome and proteome profiling implicate early inflammatory and immune molecular dysregulation in juvenile PSEN1 mutant cynomolgus monkeys. Cerebrospinal fluid from juvenile PSEN1 mutant monkeys recapitulates early changes of AD-related pathological proteins (increased Aß42 and phosphorylated tau).

Inhibition of JNK ameliorates rod photoreceptor degeneration in a mouse model of retinitis pigmentosa.

Retinitis pigmentosa (RP) is an inherited eye disease that causes progressive vision loss. Microglial activation and inflammation play essential roles in photoreceptor degeneration in RP, although the underlying mechanisms remain unclear. Here, we examined the progressive degeneration of photoreceptors in rd1 mice, a mouse model of RP. We investigated the molecular changes in various retinal cells in rd1 mice using single-cell RNA sequencing and found that potentiation of JNK signaling is associated with photoreceptor degeneration in RP. Moreover, inflammation-related molecules, which function downstream of JNK, are elevated in RP. Furthermore, inhibiting JNK alleviates microglial activation and rescues photoreceptor degeneration in rd1 mice. Thus, our findings suggest that targeting JNK is a promising approach for slowing RP progression.

Whole-exome sequencing of individuals from an isolated population under extreme conditions implicates rare risk variants of schizophrenia.

Schizophrenia (SCZ), which affects approximately 1% of the world's population, is a global public health concern. It is generally considered that the interplay between genes and the environment is important in the onset and/or development of SCZ. Although several whole-exome sequencing studies have revealed rare risk variants of SCZ, no rare coding variants have been strongly replicated. Assessing isolated populations under extreme conditions might lead to the discovery of variants with a recent origin, which are more likely to have a higher frequency than chance to reflect gene-environment interactions. Following this approach, we examined a unique cohort of Tibetans living at an average altitude above 4500 meters. Whole-exome sequencing of 47 SCZ cases and 53 controls revealed 275 potential novel risk variants and two known variants (12:46244485: A/G and 22:18905934: A/G) associated with SCZ that were found in existing databases. Only one gene (C5orf42) in the gene-based statistics surpassed the exome-wide significance in the cohort. Metascape enrichment analysis suggested that novel risk genes were strongly enriched in pathways relevant to hypoxia, neurodevelopment, and neurotransmission. Additionally, 47 new risk genes were followed up in Han sample of 279 patients with SCZ and 95 controls, only BAI2 variant appearing in one case. Our findings suggest that SCZ patients living at high altitudes may have a unique risk gene signature, which may provide additional information on the underlying biology of SCZ, which can be exploited to identify individuals at greater risk of exposure to hypoxia.

Vancomycin trough concentration in adult patients with periprosthetic joint infection: A machine learning-based covariate model.

AIMS: Although there are various model-based approaches to individualized vancomycin (VCM) administration, few have been reported for adult patients with periprosthetic joint infection (PJI). This work attempted to develop a machine learning (ML)-based model for predicting VCM trough concentration in adult PJI patients. METHODS: The dataset of 287 VCM trough concentrations from 130 adult PJI patients was split into a training set (229) and a testing set (58) at a ratio of 8:2, and an independent external 32 concentrations were collected as a validation set. A total of 13 covariates and the target variable (VCM trough concentration) were included in the dataset. A covariate model was respectively constructed by support vector regression, random forest regression and gradient boosted regression trees and interpreted by SHapley Additive exPlanation (SHAP). RESULTS: The SHAP plots visualized the weight of the covariates in the models, with estimated glomerular filtration rate and VCM daily dose as the 2 most important factors, which were adopted for the model construction. Random forest regression was the optimal ML algorithm with a relative accuracy of 82.8% and absolute accuracy of 67.2% (R2 =.61, mean absolute error = 2.4, mean square error = 10.1), and its prediction performance was verified in the validation set. CONCLUSION: The proposed ML-based model can satisfactorily predict the VCM trough concentration in adult PJI patients. Its construction can be facilitated with only 2 clinical parameters (estimated glomerular filtration rate and VCM daily dose), and prediction accuracy can be rationalized by SHAP values, which highlights a profound practical value for clinical dosing guidance and timely treatment.

Coronin 2B deficiency induces nucleolar stress and neuronal apoptosis.

In eukaryotes, the nucleolus is the critical non-membranous organelle within nuclei that is responsible for ribosomal DNA (rDNA) transcription and ribosome biogenesis. The transcription of rDNA, a rate-limiting step for ribosome biogenesis, is tightly regulated to meet the demand for global protein synthesis in response to cell physiology, especially in neurons, which undergo rapid changes in morphology and protein composition during development and synaptic plasticity. However, it is unknown how the pre-initiation complex for rDNA transcription is efficiently assembled within the nucleolus in neurons. Here, we report that the nucleolar protein, coronin 2B, regulates rDNA transcription and maintains nucleolar function through direct interaction with upstream binding factor (UBF), an activator of RNA polymerase I transcriptional machinery. We show that coronin 2B knockdown impairs the formation of the transcription initiation complex, inhibits rDNA transcription, destroys nucleolar integrity, and ultimately induces nucleolar stress. In turn, coronin 2B-mediated nucleolar stress leads to p53 stabilization and activation, eventually resulting in neuronal apoptosis. Thus, we identified that coronin 2B coordinates with UBF to regulate rDNA transcription and maintain proper nucleolar function in neurons.

Unraveling the Prefrontal Cortex-Basolateral Amygdala Pathway's Role on Schizophrenia's Cognitive Impairments: A Multimodal Study in Patients and Mouse Models.

BACKGROUND AND HYPOTHESIS: This study investigated the role of the medial prefrontal cortex (mPFC)-basolateral amygdala (BLA) pathway in schizophrenia (SCZ)-related cognitive impairments using various techniques. STUDY DESIGN: This study utilized clinical scales, magnetic resonance imaging, single-cell RNA sequencing, and optogenetics to investigate the mPFC-BLA pathway in SCZ patients. In the mouse model, 6-week-old methylazoxymethanol acetate-induced mice demonstrated significant cognitive deficits, which were addressed through stereotaxic injections of an adeno-associated viral vector to unveil the neural connection between the mPFC and BLA. STUDY RESULTS: Significant disparities in brain volume and neural activity, particularly in the dorsolateral prefrontal cortex (DLPFC) and BLA regions, were found between SCZ patients and healthy controls. Additionally, we observed correlations indicating that reduced volumes of the DLPFC and BLA were associated with lower cognitive function scores. Activation of the mPFC-BLA pathway notably improved cognitive performance in the SCZ model mice, with the targeting of excitatory or inhibitory neurons alone failing to replicate this effect. Single-cell transcriptomic profiling revealed gene expression differences in excitatory and inhibitory neurons in the BLA of SCZ model mice. Notably, genes differentially expressed in the BLA of these model mice were also found in the blood exosomes of SCZ patients. CONCLUSIONS: Our research provides a comprehensive understanding of the role of the PFC-BLA pathway in SCZ, underscoring its significance in cognitive impairment and offering novel diagnostic and therapeutic avenues. Additionally, our research highlights the potential of blood exosomal mRNAs as noninvasive biomarkers for SCZ diagnosis, underscoring the clinical feasibility and utility of this method.

Correlations of dynamic changes in lipid and protein of salted large yellow croaker during storage.

Protein and lipid are two major components that undergo significant changes during processing of aquatic products. This study focused on the protein oxidation, protein conformational states, lipid oxidation and lipid molecule profiling of salted large yellow croaker during storage, and their correlations were investigated. The degree of oxidation of protein and lipid was time-dependent, leading to an increase in carbonyl content and surface hydrophobicity, a decrease in sulfhydryl groups, and an increase in conjugated diene, peroxide value and thiobarbituric acid reactive substances value. Oxidation caused protein structure denaturation and aggregation during storage. Lipid composition and content changed dynamically, with polyunsaturated phosphatidylcholine (PC) was preferentially oxidized compared to polyunsaturated triacylglycerol. Correlation analysis showed that the degradation of polyunsaturated key differential lipids (PC 18:2_20:5, PC 16:0_22:6, PC 16:0_20:5, etc.) was closely related to the oxidation of protein and lipid. The changes in protein conformation and the peroxidation of polyunsaturated lipids mutually promote each other's oxidation process.

Identification of blood exosomal metabolomic profiling for high-altitude cerebral edema.

High-altitude cerebral edema (HACE) is a severe neurological condition that can occur at high altitudes. It is characterized by the accumulation of fluid in the brain, leading to a range of symptoms, including severe headache, confusion, loss of coordination, and even coma and death. Exosomes play a crucial role in intercellular communication, and their contents have been found to change in various diseases. This study analyzed the metabolomic characteristics of blood exosomes from HACE patients compared to those from healthy controls (HCs) with the aim of identifying specific metabolites or metabolic pathways associated with the development of HACE conditions. A total of 21 HACE patients and 21 healthy controls were recruited for this study. Comprehensive metabolomic profiling of the serum exosome samples was conducted using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS). Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to identify the metabolic pathways affected in HACE patients. Twenty-six metabolites, including ( +)-camphoric acid, choline, adenosine, adenosine 5'-monophosphate, deoxyguanosine 5'-monophosphate, guanosine, and hypoxanthine-9-ß-D-arabinofuranoside, among others, exhibited significant changes in expression in HACE patients compared to HCs. Additionally, these differentially abundant metabolites were confirmed to be potential biomarkers for HACE. KEGG pathway enrichment analysis revealed several pathways that significantly affect energy metabolism regulation (such as purine metabolism, thermogenesis, and nucleotide metabolism), estrogen-related pathways (the estrogen signaling pathway, GnRH signaling pathway, and GnRH pathway), cyclic nucleotide signaling pathways (the cGMP-PKG signaling pathway and cAMP signaling pathway), and hormone synthesis and secretion pathways (renin secretion, parathyroid hormone synthesis, secretion and action, and aldosterone synthesis and secretion). In patients with HACE, adenosine, guanosine, and hypoxanthine-9-ß-D-arabinofuranoside were negatively correlated with height. Deoxyguanosine 5'-monophosphate is negatively correlated with weight and BMI. Additionally, LPE (18:2/0:0) and pregnanetriol were positively correlated with age. This study identified potential biomarkers for HACE and provided valuable insights into the underlying metabolic mechanisms of this disease. These findings may lead to potential targets for early diagnosis and therapeutic intervention in HACE patients.

Efficacy of natural products in preventing oral mucositis resulting from cancer therapies: A network meta-analysis of randomized controlled trials.

BACKGROUND: Oral mucositis significantly compromises the quality of life for patients undergoing cancer therapies. This study aimed to evaluate the effectiveness of natural products in either preventing or alleviating oral mucositis resulting from cancer treatments. METHODS: A systematic review and network meta-analysis were conducted, sourcing data from the Cochrane Library, PubMed, Embase, Airiti Library, and Wan Fang Data Knowledge Service Platform until August 2023. The study was registered in PROSPERO (CRD42021285433). Confidence in Network Meta-Analysis (CINeMA) and R software 4.1.3 were used for analysis. RESULTS: From 1556 identified articles, 36 randomized controlled trials (RCTs) were analyzed, involving 2083 patients. Honey, notably, was found to significantly reduce the overall incidence of oral mucositis compared to standard care, with a relative risk (RR) of 0.80 (95% CI: 0.67-0.96). It was particularly effective against moderate-to-severe oral mucositis (grade ≥ 2), reducing incidence with RR of 0.48 (95% CI: 0.30-0.75) versus placebo and 0.56 (95% CI: 0.34-0.93) against standard care. Other natural products, including propolis, chamomile, and P. major L., also demonstrated significant efficacy in reducing the incidence of oral mucositis. Regarding pain relief, honey, and P. major L. emerged as effective, significantly reducing pain severity with a mean difference (MD) of -2.96 (95% CI: -3.80 to -1.94) compared to placebo. CONCUSSION: This network meta-analysis supports the use of honey, propolis, chamomile, and P. major L. as effective natural products in the prevention and treatment of oral mucositis among cancer patients. Specifically, honey is highlighted for its significant impact on reducing both the overall incidence and the severity of moderate-to-severe oral mucositis. By leveraging their anti-inflammatory and antioxidant properties, integrating these natural products into the standard care regimen could markedly improve the well-being of individuals undergoing cancer therapy.

Impact of thermal ultrasound on enzyme inactivation and flavor improvement of sea cucumber hydrolysates.

In this study, the effects of the thermal ultrasonic enzyme inactivation process on flavor enhancement in sea cucumber hydrolysates (SCHs) and its impact on the inactivation of neutral proteases (NPs) were investigated. The body wall of the sea cucumber was enzymatically hydrolyzed with NPs. On the one hand, the structure of NPs subjected to different enzyme inactivation methods was analyzed using ζ-potential, particle size, and Fourier transform infrared (FT-IR) spectroscopy. On the other hand, the microstructure and flavor changes of SCHs were examined through scanning electron microscopy, E-nose, and gas chromatography-ion mobility spectrometry (GC-IMS). The results indicated that thermal ultrasound treatment at 60 °C could greatly affect the structure of NPs, thereby achieving enzyme inactivation. Furthermore, this treatment generated more pleasant flavor compounds, such as pentanal and (E)-2-nonenal. Hence, thermal ultrasound treatment could serve as an alternative process to traditional heat inactivation of enzymes for improving the flavor of SCHs.

Astrocyte-mediated regulation of BLAWFS1 neurons alleviates risk-assessment deficits in DISC1-N mice.

Assessing and responding to threats is vital in everyday life. Unfortunately, many mental illnesses involve impaired risk assessment, affecting patients, families, and society. The brain processes behind these behaviors are not well understood. We developed a transgenic mouse model (disrupted-in-schizophrenia 1 [DISC1]-N) with a disrupted avoidance response in risky settings. Our study utilized single-nucleus RNA sequencing and path-clamp coupling with real-time RT-PCR to uncover a previously undescribed group of glutamatergic neurons in the basolateral amygdala (BLA) marked by Wolfram syndrome 1 (WFS1) expression, whose activity is modulated by adjacent astrocytes. These neurons in DISC1-N mice exhibited diminished firing ability and impaired communication with the astrocytes. Remarkably, optogenetic activation of these astrocytes reinstated neuronal excitability via D-serine acting on BLAWFS1 neurons' NMDA receptors, leading to improved risk-assessment behavior in the DISC1-N mice. Our findings point to BLA astrocytes as a promising target for treating risk-assessment dysfunctions in mental disorders.

A subunit-based influenza/SARS-CoV-2 Omicron combined vaccine induced potent protective immunity in BALB/c mice.

Infection with influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant risk to human life, health, and the global economy. Vaccination is one of the most effective strategies in the fight against infectious viruses. In this study, we, for the first time, have evaluated the immunogenicity and protective effect of an influenza/SARS-CoV-2 Omicron subunit combined vaccine adjuvanted with MF59 and administered to BALB/c mice. Results showed that the combined vaccine induced high levels of IgG, IgG1 , and IgG2a antibodies, as well as influenza A H1N1/California/2009 virus-specific hemagglutination-inhibiting antibodies in BALB/c mice. Moreover, this subunit combined vaccine induced high titers of neutralization antibodies against SARS-CoV-2 Omicron sublineage BA.5 pseudovirus and effectively reduced the viral load of authentic SARS-CoV-2 Omicron sublineage BA.5.2 in the cell culture supernatants. These results suggested that this subunit combined vaccine achieved protective effect against both H1N1 A/California/07/2009 strain and SARS-CoV-2 Omicron BA.5.2 variant. It is therefore expected that this study will establish the scientific foundation for the next-step development of combined vaccines against other strains or variants of IAV and SARS-CoV-2.

Seasonal drought promotes citrate accumulation in citrus fruit through the CsABF3-activated CsAN1-CsPH8 pathway.

Plenty of rainfall but unevenly seasonal distribution happens regularly in southern China. Seasonal drought from summer to early autumn leads to citrus fruit acidification, but how seasonal drought regulates citrate accumulation remains unknown. Herein, we employed a set of physiological, biochemical, and molecular approaches to reveal that CsABF3 responds to seasonal drought stress and modulates citrate accumulation in citrus fruits by directly regulating CsAN1 and CsPH8. Here, we demonstrated that irreversible acidification of citrus fruits is caused by drought lasting for > 30 d during the fruit enlargement stage. We investigated the transcriptome characteristics of fruits affected by drought and corroborated the pivotal roles of a bHLH transcription factor (CsAN1) and a P3A-ATPase gene (CsPH8) in regulating citrate accumulation in response to drought. Abscisic acid (ABA)-responsive element binding factor 3 (CsABF3) was upregulated by drought in an ABA-dependent manner. CsABF3 activated CsAN1 and CsPH8 expression by directly and specifically binding to the ABA-responsive elements (ABREs) in the promoters and positively regulated citrate accumulation. Taken together, this study sheds new light on the regulatory module ABA-CsABF3-CsAN1-CsPH8 responsible for citrate accumulation under drought stress, which advances our understanding of quality formation of citrus fruit.

Gut microbiota-driven metabolic alterations reveal gut-brain communication in Alzheimer's disease model mice.

The gut microbiota (GM) and its metabolites affect the host nervous system and are involved in the pathogeneses of various neurological diseases. However, the specific GM alterations under pathogenetic pressure and their contributions to the "microbiota - metabolite - brain axis" in Alzheimer's disease (AD) remain unclear. Here, we investigated the GM and the fecal, serum, cortical metabolomes in APP/PS1 and wild-type (WT) mice, revealing distinct hub bacteria in AD mice within scale-free GM networks shared by both groups. Moreover, we identified diverse peripheral - central metabolic landscapes between AD and WT mice that featured bile acids (e.g. deoxycholic and isodeoxycholic acid) and unsaturated fatty acids (e.g. 11Z-eicosenoic and palmitoleic acid). Machine-learning models revealed the relationships between the differential/hub bacteria and these metabolic signatures from the periphery to the brain. Notably, AD-enriched Dubosiella affected AD occurrence via cortical palmitoleic acid and vice versa. Considering the transgenic background of the AD mice, we propose that Dubosiella enrichment impedes AD progression via the synthesis of palmitoleic acid, which has protective properties against inflammation and metabolic disorders. We identified another association involving fecal deoxycholic acid-mediated interactions between the AD hub bacteria Erysipelatoclostridium and AD occurrence, which was corroborated by the correlation between deoxycholate levels and cognitive scores in humans. Overall, this study elucidated the GM network alterations, contributions of the GM to peripheral - central metabolic landscapes, and mediatory roles of metabolites between the GM and AD occurrence, thus revealing the critical roles of bacteria in AD pathogenesis and gut - brain communications under pathogenetic pressure.

The role of exosomal circular RNA ZNF292 in intermittent hypoxia-induced AC16 cardiomyocytes injury.

BACKGROUND: Exosomes are involved in cell-to-cell communication in numerous diseases including cardiovascular diseases, neurological diseases. Little attention has been dedicated to exosomal circular RNAs in obstructive sleep apnea (OSA)-related cardiovascular diseases. The aim of this study was to explore the role of exosomal circular RNA ZNF292 (circZNF292) on AC16 cells exposure to intermittent hypoxia (IH). METHODS: Exosome release inhibitor GW4869 was used to examine the effect of exosomes on IH-induced AC16 cells apoptosis. The expression of exosomal circZNF292 was detected by qRT-PCR in AC16 cells exposure to IH, and a luciferase reporter assay was conducted to confirm the connection between circZNF292 and miR-146a-5p. Exosomal circZNF292 was stably transfected with short hairpin RNAs (shRNAs) against circZNF292 and co-cultured with AC16 cells. The expression of miR-146a-5p and apoptosis-related protein was then measured to evaluate the effect of exosomal circZNF292. RESULTS: We found that IH contributed to the AC16 cells apoptosis, and the administration of GW4869 increased the apoptosis of cardiomyocytes when exposed to IH. The expression of exosomal circZNF292 decreased and miR-146a-5p increased significantly in AC16 cells exposed to IH compared to normoxic conditions. Bioinformatics analysis predicted a circZNF292/miR-146a-5p axis in IH-induced cardiomyocytes apoptosis. The dual-luciferase reporter system validated the direct interaction of circZNF292 and miR-146a-5p. Knockdown of circZNF292 increased the expressions of miR-146a-5p and accelerated the AC16 cardiomyocytes apoptosis. CONCLUSIONS: The findings of this study suggested a novel mechanism by which exosomes transmit intrinsic regulatory signals to the myocardium through the exosomal circZNF292/miR-146a-5p axis. This finding highlights the potential of targeting this pathway as a therapeutic approach for treating cardiovascular diseases associated with OSA.

Physicochemical and functional characteristics of glycated collagen protein from giant salamander skin induced by ultrasound Maillard reaction.

Chinese giant salamander skin collagen (CGSSC) was successfully conjugated with glucose (Glu)/xylose (Xy) by ultrasound Maillard reaction (MR) in nature deep eutectic solvents (NADES). The effects of ultrasound and reducing sugar types on the degree graft (DG) of MR products (MRPs), as well as the influence of DG on the structure and functional properties of MRPs were investigated. The results indicated that the ultrasound assisted could markedly enhance the MR of CGSSC, and low molecular weight reducing sugars were more reactive in MR. The ultrasound MR significantly changed the microstructure, secondary and tertiary structures of CGSSC. Moreover, the free sulfhydryl content of MRPs were increased, thus enhancing the surface hydrophobicity, emulsifying properties and antioxidant activity, which were positively correlated with DG. These findings provided theoretical insights into the effects of ultrasound assisted and different sugar types on the functional properties of collagen induced by MR.

Unlocking the Therapeutic Potential of Exosomes Derived From Nasal Olfactory Mucosal Mesenchymal Stem Cells: Restoring Synaptic Plasticity, Neurogenesis, and Neuroinflammation in Schizophrenia.

BACKGROUND AND HYPOTHESIS: Schizophrenia (SCZ) is a multifaceted mental disorder marked by a spectrum of symptoms, including hallucinations, delusions, cognitive deficits, and negative symptoms. Its etiology involves intricate interactions between genetic and environmental factors, posing significant challenges for effective treatment. We hypothesized that intranasal administration of exosomes derived from nasal olfactory mucosal mesenchymal stem cells (OM-MSCs-exos) could alleviate SCZ-like behaviors in a murine model induced by methylazoxymethanol (MAM). STUDY DESIGN: We conducted a comprehensive investigation to assess the impact of intranasally delivered OM-MSC-exos on SCZ-like behaviors in MAM-induced mice. This study encompassed behavioral assessments, neuroinflammatory markers, glial activation, synaptic protein expression, and neurogenesis within the hippocampus. STUDY RESULTS: Our findings demonstrated that intranasal administration of OM-MSC-exos effectively ameliorated SCZ-like behaviors, specifically addressing social withdrawal and sensory gating deficits in the MAM-induced murine model. Furthermore, OM-MSC-exos intervention yielded a reduction in neuroinflammatory markers and a suppression of microglial activation within the hippocampus. Simultaneously, we observed an upregulation of key synaptic protein expression, including PSD95 and TH, the rate-limiting enzyme for dopamine biosynthesis. CONCLUSIONS: Our study underscores the therapeutic potential of OM-MSC-exos in mitigating SCZ-like behavior. The OM-MSC-exos have the capacity to modulate glial cell activation, diminish neuroinflammation, and promote BDNF-associated synaptic plasticity and neurogenesis, thus ameliorating SCZ-like behaviors. In summary, intranasal administration of OM-MSC-exos offers a multifaceted approach to address SCZ mechanisms, promising innovative treatments for this intricate disorder.