Activation of HCA2 regulates microglial responses to alleviate neurodegeneration in LPS-induced in vivo and in vitro models.

BACKGROUND: Previous studies have shown a close association between an altered immune system and Parkinson's disease (PD). Neuroinflammation inhibition may be an effective measure to prevent PD. Recently, numerous reports have highlighted the potential of hydroxy-carboxylic acid receptor 2 (HCA2) in inflammation-related diseases. Notably, the role of HCA2 in neurodegenerative diseases is also becoming more widely known. However, its role and exact mechanism in PD remain to be investigated. Nicotinic acid (NA) is one of the crucial ligands of HCA2, activating it. Based on such findings, this study aimed to examine the effect of HCA2 on neuroinflammation and the role of NA-activated HCA2 in PD and its underlying mechanisms. METHODS: For in vivo studies, 10-week-old male C57BL/6 and HCA2-/- mice were injected with LPS in the substantia nigra (SN) to construct a PD model. The motor behavior of mice was detected using open field, pole-climbing and rotor experiment. The damage to the mice's dopaminergic neurons was detected using immunohistochemical staining and western blotting methods. In vitro, inflammatory mediators (IL-6, TNF-α, iNOS and COX-2) and anti-inflammatory factors (Arg-1, Ym-1, CD206 and IL-10) were detected using RT-PCR, ELISA and immunofluorescence. Inflammatory pathways (AKT, PPARγ and NF-κB) were delineated by RT-PCR and western blotting. Neuronal damage was detected using CCK8, LDH, and flow cytometry assays. RESULTS: HCA2-/- increases mice susceptibility to dopaminergic neuronal injury, motor deficits, and inflammatory responses. Mechanistically, HCA2 activation in microglia promotes anti-inflammatory microglia and inhibits pro-inflammatory microglia by activating AKT/PPARγ and inhibiting NF-κB signaling pathways. Further, HCA2 activation in microglia attenuates microglial activation-mediated neuronal injury. Moreover, nicotinic acid (NA), a specific agonist of HCA2, alleviated dopaminergic neuronal injury and motor deficits in PD mice by activating HCA2 in microglia in vivo. CONCLUSIONS: Niacin receptor HCA2 modulates microglial phenotype to inhibit neurodegeneration in LPS-induced in vivo and in vitro models.

Efficacy and Related Factors of Artificial Femoral Head Replacement for Femoral Intertrochanteric Fracture and Nonunion: A Systematic Review and Meta-Analysis.

Background: An intertrochanteric fracture can cause ischemic necrosis in the femoral head, leading to negative effects. There are many types of implants for this fracture procedure, including metal-on-metal, metal-on-polyethylene, ceramic-on-ceramic, and ceramic-on-polyethylene, that are currently in use. The current modification is a hybrid prosthetic implant with high functional capacity compared with predecessors. This study aims to determine the procedure's efficacy in recovery, function restoration, complications, and cost-effectiveness. Methods: Our study used a total of 200 patients undergoing total hip arthroplasty and 135 patients undergoing semi-hip arthroplasty to determine the effectiveness of total hip arthroplasty and femoral head arthroplasty From May 2022 to May 2023. Using the RAOSOFT sampling technique, 132 and 101 in the observation and control group, respectively, the sample is obtained with a confidence interval of 95%, an error margin of 1%, and response interval confidence of 50%. This is a descriptive type of research that relies on a meta-analysis of the available data from PubMed, scholarly articles, and the Chinese biomedical database to gather the fundamental data needed to conduct the research. Data obtained is analyzed using SSPS and STATA and presented in tables showing a summary of the objective measured value. Result: In this study, the Harris joint score of patients in the total hip arthroplasty group was significantly higher than that of the control group, indicating that total hip arthroplasty can restore femoral head function, but still lacks absolute strength like half hip arthroplasty. Conclusions: Femoral head replacement is a complex procedure, but the efficacy in restoring the function is better. In conclusion, despite slow healing and regeneration, the efficacy of complete artificial femoral head replacement is higher in restoring function for various fractures.

Estimates of PM2.5 concentrations spatiotemporal evolution across China considering aerosol components in the context of the Reform and Opening-up.

With astonishing and rapid development in China since the Reform and Opening-up in 1978, serious air pollution has become a great challenge. A better understanding of the response of PM2.5 pollution to socioeconomic development after the Reform and Opening-up policy is benefit for pollution control. However, heterogeneous influences of biophysical and socioeconomic activities on PM2.5 pollution pose great challenges in statistical simulation of PM2.5. Few statistical model regards aerosol species as the explanatory variables for heterogeneous formation mechanism to retrieve PM2.5 concentration. In this research, monthly PM2.5 concentration in China during 1980-2020 was reconstructed by a novel statistical strategy considering aerosol components (AC-RF). Three cross-validation (CV) methods, sample-based CV, spatial-based CV and temporal-based CV results indicated satisfactory performance of AC-RF model with correlation coefficient (R) of 0.92, 0.90, 0.86, respectively. A three-stage concluded on PM2.5 concentration annual variation in China was drawn as followed: Before 2000, PM2.5 level in China represented smooth evolution and mainly influenced by natural events with polluted region locating in Xinjiang province, North China and Central China. Since 2000, PM2.5 concentration increased to high level in the context of rapid socioeconomic development. Severe air pollution covered Jing-Jin-Ji agglomeration, Central China and Sichuan Basin. During 2012-2020, PM2.5 declined and polluted region shrank, which was benefited by the strictest-ever air pollution control measures. Based on aerosol components analysis, sulfate aerosol exhibited the most significant increase trend in recent 40 years and black aerosol variation is the most closely related to PM2.5 pollution. In conclusion, unsustainable development is the culprit for air quality deterioration. Strict and continuous air pollution control strategies are effective for air quality improvement.

Evodiamine Inhibits Lipopolysaccharide (LPS)-Induced Inflammation in BV-2 Cells via Regulating AKT/Nrf2-HO-1/NF-κB Signaling Axis.

Neuroinflammation is caused by excessive activation of microglia and plays an essential role in neurodegenerative diseases. After activation, microglia produce several kinds of inflammatory mediators, trigger an excessive inflammatory response, and ultimately destroy the surrounding neurons. Therefore, agents that inhibit neuroinflammation may be potential drug candidates for neurodegenerative diseases. Evodiamine (EV) has anti-inflammatory functions in peripheral tissues. However, whether EV exerts the same function in neuroinflammation is not known. In the present study, the aim was to explore whether EV attenuates microglial overactivation and therefore suppresses the development of neuroinflammation in lipopolysaccharide (LPS)-stimulated BV-2 cells. It was found that EV effectively inhibited expression of proinflammatory mediators (cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)) via AKT/Nrf2/HO-1 activation and suppressed NF-κB p65 phosphorylation. In addition, EV could suppress LPS-induced inflammatory response and loss of dopaminergic neuron in mouse mesencephalic neuron--glia cells. Hence, these findings demonstrate that EV suppresses neuroinflammation caused by overactivated microglia via regulating the AKT/Nrf2/HO-1/NF-κB signaling axis.

Investigating the biophysical and socioeconomic determinants of China tropospheric O3 pollution based on a multilevel analysis approach.

Severe tropospheric O3 pollution has swept across China in recent years. Consequently, investigation of tropospheric O3 concentration influencing mechanism is of significance for O3 pollution control in China. Previous studies have rarely detected combined impacts of natural factors and anthropogenic activities behind tropospheric O3 concentration in China at a national scale. Moreover, there is significant spatiotemporal heterogeneity of O3 pollution distribution in China due to the temporal and regional differences of socioeconomic and natural environmental condition in the vast territory. The targeted O3 control recommendations for different regions and seasons should be put forward in terms of the spatiotemporal heterogeneity of O3 concentration determinants. In this context, a three-level regression model integrating multi-scale biophysical and socioeconomic variables was proposed to explore the determinants of O3 pollution in China. The results showed that the tropospheric O3 concentration in the eastern and southeastern regions of China was strongly affected by meteorological conditions. In contrast, tropospheric O3 pollution concentrated in inland areas mainly depended on the emission intensity from anthropogenic sources.

Peiminine Protects Dopaminergic Neurons from Inflammation-Induced Cell Death by Inhibiting the ERK1/2 and NF-κB Signalling Pathways.

Neuroinflammation, characterized marked by microglial activation, plays a very important role in the pathogenesis of Parkinson's disease (PD). Upon activation, pro-inflammatory mediators are produced by microglia, triggering excessive inflammatory responses and ultimately damaging dopaminergic neurons. Therefore, the identification of agents that inhibit neuroinflammation may be an effective approach for developing novel treatments for PD. In this study, we sought to investigate whether peiminine protects dopaminergic neurons by inhibiting neuroinflammation. We evaluated the effects of peiminine on behavioural dysfunction, microglial activation and the loss of dopaminergic neurons in a rat model of lipopolysaccharide (LPS)-induced PD. BV-2 cells were pretreated with peiminine for 1 h and then stimulated with LPS for different times. Then, inflammatory responses and the related signalling pathways were analysed. Peiminine markedly attenuated behavioural dysfunction and inhibited the loss of dopaminergic neurons and microglial activation in the LPS-induced PD rat model. In BV-2 cells, peiminine significantly decreased LPS-induced expression of the pro-inflammatory mediators TNF-α, IL-6 and IL-1ß, COX-2 and iNOS by inhibiting the phosphorylation of ERK1/2, AKT and NF-κB p65. Based on these results demonstrated that peiminine has a role in protecting dopaminergic neurons in the LPS-induced PD rat model by inhibiting neuroinflammation.

Tubeimoside I Protects Dopaminergic Neurons Against Inflammation-Mediated Damage in Lipopolysaccharide (LPS)-Evoked Model of Parkinson's Disease in Rats.

Parkinson's disease (PD), a frequent degenerative disease in the elderly, is characterized by dopaminergic neurodegeneration in the substantia nigra pars compacta (SNpc). Neuroinflammation caused by over-activated microglia plays a crucial role in the pathogenesis of PD. Tubeimoside I (TBMS1) has a broad anti-inflammatory effect in peripheral tissues, but the effect on neuroinflammation has not been reported. Therefore, we explored whether TBMS1 could protect dopaminergic neurons by inhibiting the activation of microglia in lipopolysaccharide (LPS)-induced PD rat model. In addition, then, the effect and mechanism of TBMS1 on neuroinflammation were assessed in LPS-exposed murine microglial BV-2 cells. The results in vivo showed that TBMS1 suppressed microglial activation and dopaminergic neurons' reduction in LPS-injected PD rat model. In vitro study found that TBMS1 could inhibit LPS-induced inflammatory responses in BV-2 cells, and this effect was mediated by suppressing the phosphorylation of protein kinase B (AKT), nuclear factor-kappa B (NF-κB p65), p38 and extracellular regulated protein kinases (ERK1/2). Taken together, these results demonstrated for the first time that TBMS1 played a role in protecting dopaminergic neurons by inhibiting neuroinflammation mediated by microglia.

The comparative mitogenomics and phylogenetics of the two grouse-grasshoppers (Insecta, Orthoptera, Tetrigoidea).

OBJECTIVE: This study aimed to reveal the mitochondrial genomes (mtgenomes) of Tetrix japonica and Alulatettix yunnanensis, and the phylogenetics of Orthoptera species. METHODS: The mtgenomes of A. yunnanensis and T. japonica were firstly sequenced and assembled through partial sequences amplification, and then the genome organization and gene arrangement were analyzed. Based on nucleotide/amino acid sequences of 13 protein-coding genes and whole mtgenomes, phylogenetic trees were established on 37 Orthoptera species and 5 outgroups, respectively. RESULTS: Except for a regulation region (A+T rich region), a total of 37 genes were found in mtgenomes of T. japonica and A. yunnanensis, including 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes, which exhibited similar characters with other Orthoptera species. Phylogenetic tree based on 13 concatenated protein-coding nucleotide sequences were considered to be more suitable for phylogenetic reconstruction of Orthoptera species than amino acid sequences and mtgenomes. The phylogenetic relationships of Caelifera species were Acridoidea and Pamphagoidea > Pyrgomorphoidea > Pneumoroidea > Eumastacoidea > Tetrigoidea > Tridactyloidea. Besides, a sister-group relationship between Tettigonioidea and Rhaphidophoroidea was revealed in Ensifera. CONCLUSION: Concatenated protein-coding nucleotide sequences of 13 genes were suitable for reconstruction of phylogenetic relationship in orthopteroid species. Tridactyloidea was a sister group of Tetrigoidea in Caelifera, and Rhaphidophoroidea was a sister group of Tettigonioidea in Ensifera.

Licochalcone A Prevents the Loss of Dopaminergic Neurons by Inhibiting Microglial Activation in Lipopolysaccharide (LPS)-Induced Parkinson's Disease Models.

The neuroprotective effects of Licochalcone A (Lico.A), a flavonoid isolated from the herb licorice, in Parkinson's disease (PD) have not been elucidated. The prominent pathological feature of PD is the loss of dopaminergic neurons. The crucial role of neuroinflammation induced by activated microglia in dopaminergic neurodegeneration has been validated. In this study, we explore the therapeutic effects of Lico.A in lipopolysaccharide (LPS)-induced PD models in vivo and in vitro. We find that Lico.A significantly inhibits LPS-stimulated production of pro-inflammatory mediators and microglial activation by blocking the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and nuclear factor κB (NF-κB) p65 in BV-2 cells. In addition, through cultured primary mesencephalic neuron-glia cell experiments, we illustrate that Lico.A attenuates the decrease in [³H] dopamine (DA) uptake and the loss of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in LPS-induced PD models in vitro. Furthermore, LPS intoxication in rats results in microglial activation, dopaminergic neurodegeneration and significant behavioral deficits in vivo. Lico.A treatment prevents microglial activation and reduction of dopaminergic neuron and ameliorates PD-like behavioral impairments. Thus, these results demonstrate for the first time that the neuroprotective effects of Lico.A are associated with microglia and anti-inflammatory effects in PD models.

Vanillin Protects Dopaminergic Neurons against Inflammation-Mediated Cell Death by Inhibiting ERK1/2, P38 and the NF-κB Signaling Pathway.

Neuroinflammation plays a very important role in the pathogenesis of Parkinson's disease (PD). After activation, microglia produce pro-inflammatory mediators that damage surrounding neurons. Consequently, the inhibition of microglial activation might represent a new therapeutic approach of PD. Vanillin has been shown to protect dopaminergic neurons, but the mechanism is still unclear. Herein, we further study the underlying mechanisms in lipopolysaccharide (LPS)-induced PD models. In vivo, we firstly established rat models of PD by unilateral injection of LPS into substantia nigra (SN), and then examined the role of vanillin in motor dysfunction, microglial activation and degeneration of dopaminergic neurons. In vitro, murine microglial BV-2 cells were treated with vanillin prior to the incubation of LPS, and then the inflammatory responses and the related signaling pathways were analyzed. The in vivo results showed that vanillin markedly improved the motor dysfunction, suppressed degeneration of dopaminergic neurons and inhibited microglial over-activation induced by LPS intranigral injection. The in vitro studies demonstrated that vanillin reduces LPS-induced expression of inducible nitric oxide (iNOS), cyclooxygenase-2 (COX-2), IL-1ß, and IL-6 through regulating ERK1/2, p38 and NF-κB signaling. Collectively, these data indicated that vanillin has a role in protecting dopaminergic neurons via inhibiting inflammatory activation.

DNA methylation modulates H19 and IGF2 expression in porcine female eye.

The sexually dimorphic expression of H19/IGF2 is evolutionarily conserved. To investigate whether the expression of H19/IGF2 in the female porcine eye is sex-dependent, gene expression and methylation status were evaluated using quantitative real-time PCR (qPCR) and bisulfite sequencing PCR (BSP). We hypothesized that H19/IGF2 might exhibit a different DNA methylation status in the female eye. In order to evaluate our hypothesis, parthenogenetic (PA) cells were used for analysis by qPCR and BSP. Our results showed that H19 and IGF2 were over-expressed in the female eye compared with the male eye (3-fold and 2-fold, respectively). We observed a normal monoallelic methylation pattern for H19 differentially methylated regions (DMRs). Compared with H19 DMRs, IGF2 DMRs showed a different methylation pattern in the eye. Taken together, these results suggest that elevated expression of H19/IGF2 is caused by a specific chromatin structure that is regulated by the DNA methylation status of IGF2 DMRs in the female eye.

GLP-2 Attenuates LPS-Induced Inflammation in BV-2 Cells by Inhibiting ERK1/2, JNK1/2 and NF-κB Signaling Pathways.

The pathogenesis of Parkinson's disease (PD) often involves the over-activation of microglia. Over-activated microglia could produce several inflammatory mediators, which trigger excessive inflammation and ultimately cause dopaminergic neuron damage. Anti-inflammatory effects of glucagon-like peptide-2 (GLP-2) in the periphery have been shown. Nonetheless, it has not been illustrated in the brain. Thus, in this study, we aimed to understand the role of GLP-2 in microglia activation and to elucidate the underlying mechanisms. BV-2 cells were pretreated with GLP-2 and then stimulated by lipopolysaccharide (LPS). Cells were assessed for the responses of pro-inflammatory enzymes (iNOS and COX-2) and pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α); the related signaling pathways were evaluated by Western blotting. The rescue effect of GLP-2 on microglia-mediated neurotoxicity was also examined. The results showed that GLP-2 significantly reduced LPS-induced production of inducible nitric oxide synthase (iNOS), cyclooxygenase-s (COX-2), IL-1ß, IL-6 and TNF-α. Blocking of Gαs by NF449 resulted in a loss of this anti-inflammatory effect in BV-2 cells. Analyses in signaling pathways demonstrated that GLP-2 reduced LPS-induced phosphorylation of ERK1/2, JNK1/2 and p65, while no effect was observed on p38 phosphorylation. In addition, GLP-2 could suppress microglia-mediated neurotoxicity. All results imply that GLP-2 inhibits LPS-induced microglia activation by collectively regulating ERK1/2, JNK1/2 and p65.

Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn's Disease Mouse Model.

Mycophenolate mofetil (MMF) is an alternative immunosuppressive agent that has been reported to be effective and well tolerated for the treatment of refractory inflammatory bowel disease (IBD). The aim of this study was to investigate the therapeutic effect of MMF on intestinal injury and tissue inflammation, which were caused by Crohn's disease (CD). Here, trinitrobenzene sulfonic acid-relapsing (TNBS) colitis was induced in mice; then, we measured the differentiation of Th1/Th2 cells in mouse splenocytes by flow cytometry and the secretion of cytokines in mice with TNBS-induced colitis by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay (RT-PCR/ELISA). The results show that MMF significantly inhibited mRNA expression of pro-inflammatory cytokines IFN-γ, TNF-α, IL-12, IL-6, and IL-1ß in mice with TNBS-induced colitis; however, MMF did not inhibit the expression of IL-10 mRNA. Additionally, ELISA showed that the serum levels of IFN-γ, TNF-α, IL-12, IL-6, and IL-1ß were down-regulated in a TNBS model of colitis. Flow cytometric analysis showed MMF markedly reduced the percentages of Th1 and Th2 splenocytes in the CD mouse model. Mycophenolic acid (MPA) also significantly decreased the percentages of splenic Th1 and Th2 cells in vitro. Furthermore, MMF treatment not only significantly ameliorated diarrhea, and loss of body weight but also abrogated the histopathologic severity and inflammatory response of inflammatory colitis, and increased the survival rate of TNBS-induced colitic mice. These results suggest that treatment with MMF may improve experimental colitis and induce inflammatory response remission of CD by down-regulation of pro-inflammatory cytokines via modulation of the differentiation of Th1/Th2 cells.

GLP-2 suppresses LPS-induced inflammation in macrophages by inhibiting ERK phosphorylation and NF-κB activation.

BACKGROUND/AIMS: GLP-2 has been shown to exert anti-inflammatory effects, but the underlying molecular mechanisms remained undefined. As macrophages are important in the development and maintenance of inflammation, we investigated whether exogenous GLP-2 modulates the expression of pro-inflammatory proteins in LPS stimulated murine peritoneal macrophages. METHODS: Macrophages were pretreated with various concentrations of GLP-2 for 1 h and then stimulated with LPS. The effects on pro-inflammatory enzymes (iNOS and COX-2), and pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) were analysed by Western blotting, ELISA and qRT-PCR. We also examined whether NF-κB or MAPK signaling was involved in the effects of GLP-2. RESULTS: In macrophages, GLP-2 blunted the effect of LPS on protein and mRNA expression levels of iNOS, COX-2, TNF-α, IL-1ß and IL-6. Pre-incubation of macrophages with GLP-2 also blunted LPS-induced IκB-α degradation, IκB-α phosphorylation and NF-κB translocation. In the presence of GLP-2, the effect of LPS treatment on ERK phosphorylation was also profoundly blunted. GLP-2 did, however, not significantly modify the effects of LPS on p38 and JNK activities. CONCLUSIONS: These findings demonstrate that in LPS primed macrophages, GLP-2 reduced pro-inflammatory enzymes and cytokine production via mechanisms involving the suppression of NF-κB activity and ERK phosphorylation.

Arbutin alleviates intestinal colitis by regulating neutrophil extracellular traps formation and microbiota composition.

BACKGROUND: Ulcerative colitis (UC) is a chronic recurrent intestinal disease lacking effective treatments. ß-arbutin, a glycoside extracted from the Arctostaphylos uva-ursi leaves, that can regulate many pathological processes. However, the effects of ß-arbutin on UC remain unknown. PURPOSE: In this study, we investigated the role of ß-arbutin in relieving colitis and explored its potential mechanisms in a mouse model of dextran sulfate sodium (DSS)-induced colitis. METHODS: In C75BL/6 J mice, DSS was used to induce colitis and concomitantly ß-arbutin (50 and 100 mg/kg) was taken orally to evaluate its curative effect by evaluating disease activity index (DAI) score, colon length and histopathology. Alcian blue periodic acid schiff (AB-PAS) staining, immunohistochemistry (IHC), immunofluorescence (IF) and TdT-mediated dUTP Nick-End Labeling (Tunel) staining were used to assess intestinal barrier function. Flow cytometry, double-IF and western blotting (WB) were performed to verify the regulatory mechanism of ß-arbutin on neutrophil extracellular traps (NETs) in vivo and in vitro. NETs depletion experiments were used to demonstrate the role of NETs in UC. Subsequently, the 16S rRNA gene sequencing was used to analyze the intestinal microflora of mouse. RESULTS: Our results showed that ß-arbutin can protect mice from DSS-induced colitis characterized by a lower DAI score and intestinal pathological damage. ß-arbutin reduced inflammatory factors secretion, notably regulated neutrophil functions, and inhibited NETs formation in an ErK-dependent pathway, contributing to the resistance to colitis as demonstrated by in vivo and in vitro experiments. Meanwhile, remodeled the intestinal flora structure and increased the diversity and richness of intestinal microbiota, especially the abundance of probiotics and butyric acid-producing bacteria. It further promoted the protective effect in the resistance of colitis. CONCLUSION: ß-arbutin promoted the maintenance of intestinal homeostasis by inhibiting NETs formation, maintaining mucosal-barrier integrity, and shaping gut-microbiota composition, thereby alleviating DSS-induced colitis. This study provided a scientific basis for the rational use of ß-arbutin in preventing colitis and other related diseases.

Orally administered neohesperidin attenuates MPTP-induced neurodegeneration by inhibiting inflammatory responses and regulating intestinal flora in mice.

Parkinson's disease (PD), a neurodegenerative disease, is the leading cause of movement disorders. Neuroinflammation plays a critical role in PD pathogenesis. Neohesperidin (Neo), a natural flavonoid extracted from citric fruits exhibits anti-inflammatory effects. However, the effect of Neo on PD progression is unclear. This study aimed to investigate the effects of Neo on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in mice and its underlying mechanism. Our results indicated that Neo administration ameliorated motor impairment and neural damage in MPTP-injected mice, by inhibiting neuroinflammation and regulating gut microbial imbalance. Additionally, Neo administration reduced colonic inflammation and tissue damage. Mechanistic studies revealed that Neo suppressed the MPTP-induced inflammatory response by inhibiting excessive activation of NF-κB and MAPK pathways. In summary, the present study demonstrated that Neo administration attenuates neurodegeneration in MPTP-injected mice by inhibiting inflammatory responses and regulating the gut microbial composition. This study may provide the scientific basis for the use of Neo in the treatment of PD and other related diseases.

Allantoin ameliorates dopaminergic neuronal damage in MPTP-induced Parkinson's disease mice via regulating oxidative damage, inflammation, and gut microbiota disorder.

Parkinson's disease (PD) is a chronic progressive neurodegenerative disease that often occurs in older people. Neuroinflammation and oxidative stress are important factors in the development of PD. Gastrointestinal dysfunction is the most common non-motor symptom, and inflammation of the gut, which activates the gut-brain axis, maybe a pathogenic factor. Previous studies have attributed anti-inflammatory and antioxidant effects to Allantoin, but its function and mechanism of action in PD are unclear. This study aimed to investigate the effect and mechanism of Allantoin on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in mice. Our results showed that Allantoin administration ameliorated motor dysfunction and neuronal damage in mice injected with MPTP by inhibiting neuroinflammation and oxidative damage. Mechanistic studies showed that Allantoin suppresses inflammatory responses by inhibiting the overactivation of the NF-κB and MAPK signaling pathways, as well as oxidative stress by regulating the AKT/Nrf2/HO-1 signaling pathway. Notably, Allantoin also restored intestinal barrier function by modulating the gut microbiota and improving antioxidant and anti-inflammatory capacities to alleviate MPTP-induced motor deficits. In conclusion, the present study shows that the administration of Allantoin attenuated neurodegeneration in mice injected with MPTP by inhibiting neuroinflammation and oxidative stress and modulating the composition of the gut microbiome.

Narirutin mitigates dextrose sodium sulfate-induced colitis in mice by modulating intestinal flora.

BACKGROUND: Ulcerative colitis (UC) is a prolonged inflammatory disease of the gastrointestinal tract. Current therapeutic options remain limited, underscoring the imperative to explore novel therapeutic strategies. Narirutin (NR), a flavonoid naturally present in citrus fruits, exhibits excellent anti-inflammatory effects in vitro, yet its in vivo efficacy, especially in UC, remains underexplored. OBJECTIVE: This work examined the effect of NR on dextrose sodium sulfate (DSS)-induced UC in mice in vivo, with a specific focus on the role of gut flora in it. METHODS: The effects of NR (10, 20, and 40 mg/kg) on DSS-induced UC in mice were investigated by monitoring changes in body weight, disease activity index (DAI) scores, colon length, and histological damage. Colonic levels of pro-inflammatory mediators, tight junction (TJ) proteins, and inflammation-related signaling pathway proteins were analyzed via enzyme-linked immunosorbent assay, western blot, and immunofluorescence. The role of gut microbiota in NR against colitis was analyzed through 16S rRNA sequencing, flora clearance assays, and fecal microbiota transplantation (FMT) assays. RESULTS: NR administration suppressed DSS-induced colitis as reflected in a decrease in body weight loss, DAI score, colon length shortening, and histological score. Furthermore, NR administration preserved the integrity of the DSS-induced intestinal barrier by inhibiting the reduction of TJ proteins (claudin3, occludin, and zonula occludens-1). Moreover, NR administration markedly repressed the activation of the toll-like receptor 4-mitogen-activated protein kinase/nuclear factor-κB pathway and reduced the amount of pro-inflammatory mediators in the colon. Importantly, the results of 16S rRNA sequencing showed that the intestinal flora of mice with colitis exhibited richer microbial diversity following NR administration, with elevated abundance of Lactobacillaceae (Lactobacillus) and decreased abundance of Bacteroidaceae (Bacteroides) and Shigella. In addition, the anti-colitis effect of NR almost disappeared after gut flora clearance. Further FMT assay also validated this gut flora-dependent protective mechanism of NR. CONCLUSION: Our findings suggest that NR is a prospective natural compound for the management of UC by modulating intestinal flora.

Attenuation of allergic airway inflammation in a murine model of asthma by Licochalcone A.

CONTEXT: Licochalcone A (Lico A) is a major and biogenetically characteristic chalcone isolated from the root of Xinjiang liquorice, Glycyrrhiza inflata. OBJECTIVE: We focused on investigating whether Lico A possesses distinct anti-inflammatory activity on a non-infectious mouse model of asthma, and we aimed to elucidate its involvement with the mitogen-activated protein kinases pathway. METHODS: BALB/c mice that were sensitized and challenged to ovalbumin (OVA) were treated with Lico A (50 mg/kg) 1 h before they were challenged with OVA. RESULTS: Our study demonstrated that Lico A may effectively inhibit the increase in T-helper type 2 cytokines, such as interleukin (IL)-4, IL-5 and IL-13 in bronchoalveolar lavage fluid, and reduced serum levels of OVA-specific IgE and IgG. Furthermore, Lico A substantially inhibited OVA-induced eosinophilia in lung tissue and mucus hyper-secretion by goblet cells in the airway. Meanwhile, pretreatment with Lico A resulted in a significant reduction in mRNA expression of acidic mammalian chitinase, chitinase 3-like protein 4 (Ym2), E-selectin, Muc5ac, CCL11 and CCR3 in lung tissues and airway hyper-responsiveness to methacholine. CONCLUSIONS: These findings suggest that Lico A may effectively delay the progression of airway inflammation and could be used as a therapy for patients with allergic airway inflammation.

[Study on anti-aging effect of ginsenoside Rg1 in serial transplantation of hematopoietic stem cells and progenitor cells].

OBJECTIVE: To investigate the anti-aging effect of ginsenoside R1 in serial transplantation of hematopoietic stem cells and progenitor cells. METHOD: HSC/HPC aging model in vivo was established through the Sca-1 (+) HSC/HPC serial transplantation of male donor mice that had been separated and purified by the magnetic-activated cell sorting method. The female recipient mice that had been radiated with lethal dose of 60Co gamma ray were divided into four groups: the control group, the aging group, the Rg1-treated aging group and the Rg1 anti-aging group. The expression of Sry genes in bone marrow cells of recipient mice was analyzed by fluorescence quantitative PCR, in order to determine the source of hematopoietic reconstruction cells, observe the survival time and the recovery of the hematology of peripheral blood, and study the reconstruction of the hematopoietic function of recipient mice, the hematopoietic recovery promoted by Rg1, the culture of CFU-Mix of hemopoietic progenitor cells, the cell cycle analysis and aging-related SA-beta-Gal staining analysis on biological characteristics of Sca-1 (+) HSC/HPC aging, and the effect of Rg1 in vivo regulation on Sca-1 + HSC/HPC aging. RESULT: The hematopoietic reconstruction cells of female recipient mice were derived from male donor mice. With the serial transplantation, the 30-day survival rate and the hematology in peripheral blood of recipient mice decreased. Sca-1 (+) HSC/HPC showed aging characteristics: the ratio of cells in G0/G1 phase and the positive rate of SA-beta-gal staining increased, whereas the number of CFU-Mix decreased. Compared with the aging group of the same generation, Rg1 -treated aging group and Rg1 anti-aging group showed higher 30-day survival rate and WBC, HCT, PLT and CFU-Mix, and lower cell ratio in Sca-1 (+) HSC/HPC G0/G1 stage and positive rate of SA-beta-gal staining. The Rg1 anti-aging group showed more significant changes than the Rg1 -treated aging group. CONCLUSION: Ginsenoside Rg1 has the effect of delaying and treating Sca-1 (+) HSC/HPC aging during the serial transplantation. Rg1 's anti-aging effect is superior to its effect of treating aging.