Search

Highlights • Larger neutrophils were found in the peritoneal of septic mice infected with E.coli. • The cells consumed massive E.coli than regular neutrophils. • Their presence were correlated with severity of septic mice. Abstract Neutrophils, classified as professional phagocytes, are crucial in killing bacteria and preventing inflammation. When studying the roles of neutrophils in the development of the septic peritonitis induced by E. coli , we noticed some of the larger cells existed among peritoneal lavage fluid cells (PLCs). Besides the large size, their nuclei are segmented and flat, and squeezed to the marginal zone of the inner membrane. The cells, therefore, were designated as E. coli induced larger neutrophils (e-Neus). Further studies showed that, the e-Neus were ly6G positive, indicating the e-Neus were a type of neutrophils. The enlarged cell size and marginal nucleus of the e-Neus were caused by engulfing abundant of E. coli , marking the active participation of the e-Neus in clearance of E. coli. Functionally, the e-Neus generated reactive oxygen species (ROS) and IL-10. Furthermore, the occurrence and accumulation of the e-Neus were closely correlated with the severity of septic peritonitis and mortality of the mice. Overall, the e-Neus presented here may enrich the understandings on neutrophil transitions in response to various insults, and could be used to evaluate the severity of septic peritonitis induced by E. coli. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), which is a prevailing type of dementia, presents a significant global health concern. The current therapies do not meet clinical expectations. Amyloid-beta (Aβ) has been found to induce endogenous formaldehyde (FA) accumulation by inactivating FA dehydrogenase (FDH); in turn, excessive FA triggers Aβ aggregation that eventually leads to AD onset. Hence, scavenging FA by astaxanthin (ATX, a strong exogenous antioxidant) may be pursued as a promising disease-modifying approach. Here, we report that liposomal nanoparticles coupled with PEG (PEG-ATX@NPs) could enhance water-solubility of ATX and alleviate cognitive impairments by scavenging FA and reducing Aβ deposition. To enable drug delivery to the brain, liposomes were used to encapsulate ATX and then coupled with PEG, which produced liposomal nanoparticles (PEGATX@NPs) with a diameter of <100 nm. The PEG-ATX@NPs reduced Aβ neurotoxicity by both degrading FA and reducing FA-induced Aβ assembly in vitro. Intraperitoneal administration of PEG-ATX@NPs in APPswe/PS1dE9 mice (APP/PS1, a familial model of AD), not only decreased the levels of brain FA and malondialdehyde (MDA, a typical product of oxidative stress), but also attenuated both intracellular Aβ oligomerization and extracellular Aβ-related senile plaque (SP) formation. These pathological changes were accompanied by rescued ability of spatial learning and memory. Collectively, PEG-ATX@NPs improved the water-solubility, bioavailability, and effectiveness of ATX. Thus, it has the potential to be developed as a safe and effective strategy for treating AD. [Display omitted] • Liposomal NPs of ATX with PEG enhances its bioavailability and drug delivery. • Scavenging FA by PEG-ATX@NPs decreases Aβ oligomerization and deposition. • PEG-ATX@NPs more than ATX reduce Aβ neurotoxicity by scavenging FA. • PEG-ATX@NPs may be a promising strategy for treating Alzheimer's disease. [ABSTRACT FROM AUTHOR]

• DEK was overexpressed in neutrophilic asthma. • miR-181b-5p was decreased in neutrophilic asthma. • miR-181b-5p attenuate neutrophilic asthma through DEK/p-GSK-3βSer9/β-catenin/MMP-9 and DEK/Wnt/DRP1/MMP-9 axis. We investigated the regulatory role of miR-181b-5p in neutrophilic asthma and its mechanisms by targeting DEK. DEK, matrix metalloproteinase (MMP)-2, and MMP-9 were overexpressed and the miR-181b-5p was decreased in mice with neutrophilic asthma. DEK was a direct target of miR-181b-5p. In mouse model, miR-181b-5p agomir had an inhibitory effect on airway inflammation and remodeling. miR-181b-5p inhibited DEK/p-GSK-3βSer9/β-catenin/MMP-9 pathway activation by regulating Wnt ligands in BEAS-2B and 16HBE cells. The ability of supernatants from human bronchial epithelial cells (hBECs) co-stimulated with CXCL8 (IL-8) and miR-181b-5p to induce NETs was weaker than that of IL-8 alone. Moreover, DEK overexpression led to excessive mitochondrial dysfunction, including DRP1 up-regulation, p-DRP1ser637 and MFN2 down-regulation, mitochondrial membrane potential loss, excessive mtROS generation and mitochondrial incompleteness. Interestingly, all these phenotypes were rescued by Wnt inhibitor DKK-1 and miR-181b-5p agomir. Additionally, inhibition of DRP1 with Mdivi-1 decreased MMP-9 on BEAS-2B cells. Overall, miR-181b-5p could attenuate neutrophilic asthma through inhibition of NETs release, DEK/p-GSK-3βSer9/β-catenin/MMP-9 pathway, DEK/Wnt/DRP1/MMP-9 and mitochondria damage. It may become a new therapeutic target for neutrophilic asthma. [ABSTRACT FROM AUTHOR]

[Display omitted] We investigated whether Panax notoginseng saponin (PNS-R1) attenuates allergic rhinitis (AR) through AMPK/Drp1-mediated mitochondrial fission. AR model was established in mice by Ovalbumin (OVA). In vitro , human nasal epithelial cells (HNEpCs) were stimulated using recombinant human interleukin 13 (IL-13). PNS-R1 was administrated in vivo and in vitro. Then, HE staining of nasal tissue, ELISA detection of immunoglobulin E (IgE) and proinflammatory cytokine levels in serum and nasal lavage fluid, flow cytometry analysis of Th1/Th2 ratio and apoptosis, TUNEL staining, Western blot, detection of reactive oxygen species (ROS) and mitochondrial ROS, immunofluorescence analysis of Tom20 and mitochondrial fission protein Drp1 co-localization, and mitochondrial membrane potential detection, were performed. PNS-R1 attenuated allergic symptoms in AR mice, decreased OVA-specific IgE, IL-4, IL-6, IL-8, IL-13, and TNF-α levels, and restored the Th1/Th2 imbalance. Meanwhile, we found that PNS-R1 treatment significantly reduced apoptosis, ROS production, and co-localization of Tom20 and Drp1 in the nasal epithelium of AR mice. In vitro , we found that PNS-R1 upregulated mitochondrial membrane potential and reduced ROS and mitochondrial ROS production as well as Cleaved-caspase-3/9, Bax, Cyt-c, Apaf-1 expression and mitochondrial fission. Mechanistically, we found that PNS-R1 downregulated Drp1 phosphorylation (Ser 616) and Drp1 translocation in an AMPK-dependent manner, promoted MFN2 expression, and reduced TXNIP, NLRP3, Caspase-1, and IL-1β expression. PNS-R1 may protect mitochondrial integrity by inhibiting AMPK/Drp1 and TXNIP/NLRP3 signaling pathway, thereby alleviating AR symptoms in mice. PNS-R1 may have great potential as a therapeutic agent for AR. [ABSTRACT FROM AUTHOR]

• miR-128-3p alleviates OVA-induced pulmonary inflammation in asthmatic mice. • miR-128-3p adjusts mitochondrial kinetics and inhibits mitochondrial dysfunction. • SIX1 regulates mitochondrial kinetics and maintains mitochondrial function. Bronchial asthma is known for airway inflammation, hyperresponsiveness, and remodeling.MicroRNAs (MiRNAs) have been involved in the development of asthma, whereas, the mechanism of various MiRNAs in asthma remains to be elucidated. In this study, we aim to explore the mechanism of miR-128-3p in asthma-related airway inflammation by targeting sine oculis homeobox homolog 1 (SIX1) to regulate the mitochondrial function. In an ovalbumin (OVA) asthma mouse model, miR-128-3p levels were found to be significantly diminished. Administration of miR-128-3p agomir decreased peribronchial inflammatory cell infiltration and improved airway inflammation. Afterwards, we used the luciferase reporter assay to predict and confirmed that SIX1 is a target gene of miR-128-3p. Overexpression of miR-128-3p attenuated IL-13-induced cellular inflammation and ROS production in bronchial epithelial cells (BEAS-2B). In vitro , overexpression of miR-128-3p and SIX1 knockdown mitigated mitochondrial fragmentation, reduced Drp1-mediated mitochondrial division, and upregulated mitochondrial membrane potential. Moreover, led to decreased production of ROS/mitochondrial ROS, P-Drp1(6 1 6) and Fis1 expression, while enhancing P-Drp1(6 3 7), MFN1, caspase-3/9, and Bax–mediated apoptosis. Our findings demonstrated that miR-128-3p could alleviate airway inflammation by downregulating SIX1 and improving mitochondrial function, positioning the miR-128-3p/SIX1/Drp1 signaling as a potential therapeutic target for asthma. [ABSTRACT FROM AUTHOR]

Brain diseases present a significant obstacle to both global health and economic progress, owing to their elusive pathogenesis and the limited effectiveness of pharmaceutical interventions. Phototherapy has emerged as a promising non-invasive therapeutic modality for addressing age-related brain disorders, including stroke, Alzheimer's disease (AD), and Parkinson's disease (PD), among others. This review examines the recent progressions in phototherapeutic interventions. Firstly, the article elucidates the various wavelengths of visible light that possess the capability to penetrate the skin and skull, as well as the pathways of light stimulation, encompassing the eyes, skin, veins, and skull. Secondly, it deliberates on the molecular mechanisms of visible light on photosensitive proteins, within the context of brain disorders and other molecular pathways of light modulation. Lastly, the practical application of phototherapy in diverse clinical neurological disorders is indicated. Additionally, this review presents novel approaches that combine phototherapy and pharmacological interventions. Moreover, it outlines the limitations of phototherapeutics and proposes innovative strategies to improve the treatment of cerebral disorders. [Display omitted] ● Medicines targeting age-related diseases have not approached clinical expectations. ● Novel and non-invasive phototherapy has been rapidly developed in recent decades. ● Transocular flicker with 40 Hz white light can improve sleep and cognitive ability. ● Transcranial light activates photo-sensitive proteins and alleviates brain diseases. [ABSTRACT FROM AUTHOR]

Excessive application of synthetic nitrogen fertilizer and discharge of organic wastes were the primary sources of greenhouse gas (GHG) emissions in agricultural system. Synthetic nitrogen fertilizer substitution (NSS) practice by organic amendments was considered as a possible strategy to decrease the on-field N 2 O emission and simultaneously increase the soil organic carbon (SOC) and yield in cropping system. The effects of NSS practice on the trade-offs between crop yield and net greenhouse (NGHG) emissions have been still uncertain at a global level at present. This study carried out a joint use of meta-analysis, NGHG balance assessment and carbon footprint (CF) to quantitatively assess the effects of the NSS practices from multi-points. Results showed the NSS practice improved crop yield by 2.00 %, showing a positive effect at a global level, especially in rice and maize production systems. Meanwhile, the NSS practice significantly increased SOC storage by 23.97 %. For the on-field N 2 O and CH 4 emissions, the effect sizes varied large under different factors, without significant difference. The general trends were that the NSS practice decreased the average effect sizes of N 2 O emission and increased the average effect sizes of CH 4 emission. Standing at a farmland and system levels, the NSS practice increased the NGHGs and CFs both at the area and yield scales for paddy system. For upland cropping system, both of the yield-based and area-based CFs were reduced under the NSS practice due to the improved yields of wheat and maize. In conclusion, the NSS practice showed positive effects on improving crop yield and SOC storage at the global level but negative effect on decreasing the on-field GHG emissions. Crop type was the primary influencing factor. According to the current results, we assumed that the NSS would be an effective practice for upland cropping systems because it would generate the less NGHG emission and CF when producing unit mass of grain products. However, the NSS would not be a good practice for the rice production system. The results provided valuable information for the development of sustainable agricultural production in the world. • Effect of substituting synthetic N fertilizer by organic wastes (NSS) was analyzed. • A global meta-analysis, NGHG balance and carbon footprint were jointly used. • NSS practice showed positive effects on improving crop yield and SOC stock. • NSS practice showed negative effect on decreasing the on-field GHG emissions. • NSS was an effective practice for upland cropping system but not for rice system. [ABSTRACT FROM AUTHOR]