The Water Extract of Rhubarb Prevents Ischemic Stroke by Regulating Gut Bacteria and Metabolic Pathways.

Rhubarb (RR), Chinese name Dahuang, is commonly used in the treatment of ischemic stroke (IS). However, its potential mechanism is not fully elucidated. This study intended to verify the effect of RR on IS and investigate the possible mechanism of RR in preventing IS. IS in male rats was induced by embolic middle cerebral artery occlusion (MCAO) surgery, and drug administration was applied half an hour before surgery. RR dramatically decreased the neurological deficit scores, the cerebral infarct volume, and the cerebral edema rate, and improved the regional cerebral blood flow (rCBF) and histopathological changes in the brain of MCAO rats. The 16S rRNA analysis showed the harmful microbes such as Fournierella and Bilophila were decreased, and the beneficial microbes such as Enterorhabdus, Defluviitaleaceae, Christensenellaceae, and Lachnospira were significantly increased, after RR pretreatment. 1H-nuclear magnetic resonance (1H-NMR) was used to detect serum metabolomics, and RR treatment significantly changed the levels of metabolites such as isoleucine, valine, N6-acetyllysine, methionine, 3-aminoisobutyric acid, N, N-dimethylglycine, propylene glycol, trimethylamine N-oxide, myo-inositol, choline, betaine, lactate, glucose, and lipid, and the enrichment analysis of differential metabolites showed that RR may participate in the regulation of amino acid metabolism and energy metabolism. RR exerts the role of anti-IS via regulating gut bacteria and metabolic pathways.

Folic acid-functionalized chitosan nanoparticles with bioenzyme activity for the treatment of spinal cord injury.

Spinal cord injury (SCI) is a central system disease with a high rate of disability. Pathological changes such as ischemia and hypoxia of local tissues, oxidative stress and apoptosis could lead to limb pain, paralysis and even life-threatening. It was reported that catalase (CAT) was the main antioxidant in organisms, which could remove reactive oxygen species (ROS) and release oxygen (O2). However, the efficacy of the drug is largely limited due to its poor stability, low bioavailability and inability to cross the blood spinal cord barrier (BSCB). Therefore, in this study, we prepared folic acid-functionalized chitosan nanoparticles to deliver CAT (FA-CSNCAT) for solving this problem. In vivo small animal imaging results showed that FA-CSN could carry CAT across the BSCB and target to the inflammatory site. In addition, Immunofluorescence, ROS assay and JC-1 probe were used to detect the therapeutic effect of FA-CSNCAT in vitro and in vivo. The results showed that FA-CSNCAT could alleviate the hypoxic environment at the injured site and remove ROS, thereby inhibiting oxidative stress and protecting neurons, which may provide a new idea for clinical medication of SCI.

Circulating exosomal miRNAs as novel biomarkers for acute aortic dissection: A diagnostic accuracy study.

BACKGROUND: Acute aortic dissection (AAD) is a serious and life-threatening cardiovascular emergency. This study aim to investigate whether MicroRNAs (miRNAs)in circulating exosomes could serve as novel diagnostic biomarkers for AAD. METHODS: Using miRNA microarray sequencing, the differentially expressed exosomal miRNAs between AAD patients and control subjects were found. In this study, we investigated 8 miRNAs (miR-499a-5p/miR-543/miR-143-3p/miR-4433b-3p/miR-744-5p/miR-4488/miR-202-3p/miR-206), 4 Proteins (Matrix Metalloprotein-9/12)/transforming growth factor-ß/D-Dimer) in AAD (n = 75) and Control (n = 86) expression levels between the 2 groups. The combined diagnostic of exosomal miRNAs and Proteins was performed (area under curve [AUC] > 0.8, R > 0.5 and P < .01). The Receiver Operating Characteristic curve was drawn to evaluate the diagnostic efficacy. Predict the gene targets of differentially expressed miRNAs and analyze the functions and signaling pathways of these targets using online databases. RESULTS: The exosomes isolated from the 2 groups of serum were bilayer membranes with a diameter of about 100 nm. Stably expressed in CD9, CD63 and TSG101. Compared with the control subjects, 8 exosomal miRNAs (miR-499a-5p, miR-543, miR-206, miR-143-3p, miR-4433b-3p, miR-744-5p, miR- 4488, and miR-202-3p) were regulated to varying degrees (P < .05). miR-499a-5p, miR-202-3p, and D-Dimer had higher diagnostic efficacy (AUC > 0.90). Among them, miR-499a-5p had the highest diagnostic accuracy, reaching 95%, AUC = 0.99. Co-diagnosis of positively correlated miRNAs and Proteins improves the diagnostic performance. The combined diagnostic accuracy of miR-499a-5p and miR-202-3p was 98% (AUC = 0.998), and the sensitivity and specificity were 98%. The combined diagnostic accuracy of miR-499a-5p and matrix metalloprotein-9 was 98% (AUC = 0.996), and the sensitivity and specificity were 98%. Gene Ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes signaling pathway analysis, some predicted targets of these miRNAs are involved in the pathophysiological process of AAD. CONCLUSION: Serum exosomal miR-499a-5p, miR-143-3p, and miR-202-3p can be used as potential diagnostic biomarkers for AAD, and the combination of various markers can coordinate and complement each other, and can significantly improve the diagnosis of aortic dissection sensitivity and specificity.

Functionalized Prussian Blue Nanozyme as Dual-Responsive Drug Therapeutic Nanoplatform Against Maxillofacial Infection via Macrophage Polarization.

Purpose: Maxillofacial infection is a common disease in stomatology and is difficult to treat owing to its high potential to spread to vital anatomical structures. Excessive levels of reactive oxygen species (ROS) in infected tissues lead to cellular damage and impede tissue regeneration. However, uncontrollable strategies to remove ROS have limited therapeutic efficacy. Nanoparticle systems for scavenging ROS and remodeling the inflammatory microenvironment offer much promise in the treatment of maxillofacial inflammation. Methods: Here, a novel microenvironment-stimuli-responsive drug delivery nanoplatform (HMPB@Cur@PDA) based on a polydopamine (PDA)-functionalized hollow mesoporous Prussian blue (HMPB) nanozyme was developed for the delivery of curcumin (Cur) in the treatment of maxillofacial infection. Low pH and excess ROS in the inflammatory microenvironment cause degradation of the outer PDA layer of the nanocomplex, exposing the HMPB nanozyme and loaded Cur, which synergistically act as a ROS scavenger and anti-inflammatory agent, respectively, and induce macrophage polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype. Results: Experiments in vitro provided strong evidence for the application of novel nanocomplexes in scavenging multiple ROS and inhibiting lipopolysaccharide-induced inflammation. In addition, in vivo results obtained using a mouse maxillofacial infection model demonstrated that HMPB@Cur@PDA had excellent biocompatibility, significantly attenuated the inflammatory response in periodontal tissue, and improved the repair of damaged tissue. Conclusion: Our results indicate that HMPB@Cur@PDA nanocomposites have great potential for ROS regulation as well as having anti-inflammatory effects, providing new insights for the development of dual-response maxillofacial infection treatments.

A circuit from the ventral subiculum to anterior hypothalamic nucleus GABAergic neurons essential for anxiety-like behavioral avoidance.

Behavioral observations suggest a connection between anxiety and predator defense, but the underlying neural mechanisms remain unclear. Here we examine the role of the anterior hypothalamic nucleus (AHN), a node in the predator defense network, in anxiety-like behaviors. By in vivo recordings in male mice, we find that activity of AHN GABAergic (AHNVgat+) neurons shows individually stable increases when animals approach unfamiliar objects in an open field (OF) or when they explore the open-arm of an elevated plus-maze (EPM). Moreover, object-evoked AHN activity overlap with predator cue responses and correlate with the object and open-arm avoidance. Crucially, exploration-triggered optogenetic inhibition of AHNVgat+ neurons reduces object and open-arm avoidance. Furthermore, retrograde viral tracing identifies the ventral subiculum (vSub) of the hippocampal formation as a significant input to AHNVgat+ neurons in driving avoidance behaviors in anxiogenic situations. Thus, convergent activation of AHNVgat+ neurons serves as a shared mechanism between anxiety and predator defense to promote behavioral avoidance.

Genipin modified lyophilized platelet-rich fibrin scaffold for sustained release of growth factors to promote bone regeneration.

Lyophilized platelet-rich fibrin (L-PRF) was shown to further activate resident platelets in platelet-rich fibrin causing a higher amount of growth factors release. However, it still required further experimental studies to resolve the uncontrolled degradation and burst release problem. In this study, the nature crosslinker genipin is introduced to improve the performance of L-PRF scaffold. We used a series of gradient concentration genipin solutions to react with L-PRF. The crosslinking degree, micro morphology, mean pore size, water absorption and mechanical properties of the crosslinked scaffold were evaluated. In order to study the effect of genipin modification on the release kinetics of growth factors from L-PRF, we detected the release of platelet-derived growth factor, vascular endothelial growth factor and transforming growth factor in vitro by ELISA. To investigate the biodegradability of the crosslinked L-PRF in vivo, the scaffolds were transplanted subcutaneously into backs of rats, and the materials were recovered at 1, 2 and 4 weeks after implantation. The biodegradation, inflammatory reaction and biocompatibility of the scaffolds were examined by histological staining. Finally, the genipin crosslinked/uncrosslinked L- Platelet-rich fibrin scaffolds were implanted with freshly prepared SHED cell sheets into rat critical size calvarial defects and the skull samples were recovered to examine the treatment efficacy of genipin crosslinked L-PRF by histologic and radiographic approaches. Results of this study indicated that genipin can be used to modify L-PRF at room temperature at a very low concentration. Genipin-modified L-PRF shows better biomechanical performance, slower biodegradation, good bioavailable and sustained release of growth factors. The 0.01% w/v and 0.1% w/v genipin crosslinked L-PRF have good porous structure and significantly promote cell proliferation and enhance the expression of key genes in osteogenesis in vitro, and work best in promoting bone regeneration in vivo.

Musashi-1 and miR-147 Precursor Interaction Mediates Synergistic Oncogenicity Induced by Co-Infection of Two Avian Retroviruses.

Synergism between avian leukosis virus subgroup J (ALV-J) and reticuloendotheliosis virus (REV) has been reported frequently in co-infected chicken flocks. Although significant progress has been made in understanding the tumorigenesis mechanisms of ALV and REV, how these two simple oncogenic retroviruses induce synergistic oncogenicity remains unclear. In this study, we found that ALV-J and REV synergistically promoted mutual replication, suppressed cellular senescence, and activated epithelial-mesenchymal transition (EMT) in vitro. Mechanistically, structural proteins from ALV-J and REV synergistically activated the expression of Musashi-1(MSI1), which directly targeted pri-miR-147 through its RNA binding site. This inhibited the maturation of miR-147, which relieved the inhibition of NF-κB/KIAA1199/EGFR signaling, thereby suppressing cellular senescence and activating EMT. We revealed a synergistic oncogenicity mechanism induced by ALV-J and REV in vitro. The elucidation of the synergistic oncogenicity of these two simple retroviruses could help in understanding the mechanism of tumorigenesis in ALV-J and REV co-infection and help identify promising molecular targets and key obstacles for the joint control of ALV-J and REV and the development of clinical technologies.

Therapeutic mechanisms of mulberry leaves in type 2 diabetes based on metabolomics.

Background: Type 2 diabetes (T2D) is considered as one of the most significant metabolic syndromes worldwide, and the long-term use of the drugs already on the market for T2D often gives rise to some side effects. The mulberry leaf (ML), Morus alba L., has advantages in terms of its comprehensive therapeutic efficacy, which are characterized as multicomponent, multitarget, multipathway, and matching with the complex pathological mechanisms of diabetes. Methods: T2D rats were established by a high-fat diet combined with an intraperitoneal injection of streptozotocin; an evaluation of the hypoglycemic effects of the ML in combination with fasting blood glucose and other indicators, in addition to the utilization of metabolomics technology, was performed to analysis the metabolite changes in serum of rats. Results: MLs significantly reduced the fasting blood glucose of T2D rats, while improving the symptoms of polyphagia and polyuria. ML treatment altered the levels of various metabolites in the serum of T2D rats, which are involved in multiple metabolic pathways (amino acid metabolism, carbohydrate metabolism, and lipid metabolism), played a role in antioxidative stress and anti-inflammation, modulated immune and gluconeogenesis processes, and improved obesity as well as insulin resistance (IR). Conclusion: The ML contains a variety of chemical components, and metabolomic results have shown that MLs regulate multiple metabolic pathways to exert hypoglycemic effects, suggesting that MLs may have great promise in the development of new hypoglycemic drugs.

Epimedium koreanum Nakai-Induced Liver Injury-A Mechanistic Study Using Untargeted Metabolomics.

Epimedii Folium is widely used worldwide as an herbal supplement, and the risk of its induced liver damage has emerged in recent years. Our preliminary study has found that, among several Epimedii Folium species specified in the Chinese Pharmacopoeia, Epimedium koreanum Nakai has a more severe propensity for hepatotoxicity. However, the mechanism of hepatotoxicity of Epimedium koreanum Nakai is still unclear. In this study, untargeted metabolomics was performed to analyze the serum and liver tissue to explore the mechanism of hepatotoxicity of Epimedium koreanum Nakai. The results of experiments in vivo showed that, after 28 days of exposure to Epimedium koreanum Nakai ethanol extract (EEE), the liver weight, levels of AST, ALP, TBIL, etc. in serum of rats in the EEE group were significantly increased, as well as severe cytoplasmic vacuolation appeared in the liver tissue, which suggested that EEE has significant hepatotoxicity. Subsequently, the results of metabolomics revealed significant changes in the metabolic profile in the liver and serum of rats after EEE exposure, in which metabolites in serum such as flavin mononucleotide, phenylacetylglycine, glutathione, l-tryptophan, and sphingomyelin were able to accurately identify liver injury caused by EEE and could be used as serum markers to reflect EEE-induced liver injury. The KEGG pathway enrichment analysis revealed that EEE caused extensive effects on rats' metabolic pathways. Some of the most affected pathways included glutathione metabolism, glutamate metabolism pathway, primary bile acid biosynthesis pathway, and sphingolipid metabolism pathway, which were all directed to the biological process of ferroptosis. Then, the main markers related to ferroptosis in the liver were examined, and the results demonstrated that the content of malondialdehyde was significantly increased, the activity of superoxide dismutase was significantly reduced, the ferroptosis inhibitory proteins GPX4 and System xc - were significantly downregulated, and the ferroptosis-promoting protein ACSL4 was significantly up-regulated. Judging from these results, we concluded that the mechanism of hepatotoxicity of Epimedium koreanum Nakai was probably related to the induction of ferroptosis in hepatocytes.

Xiongshao Zhitong Recipe Attenuates Nitroglycerin-Induced Migraine-Like Behaviors via the Inhibition of Inflammation Mediated by Nitric Oxide Synthase.

Migraine is a major cause of disability worldwide, particularly in young adults and middle-aged women. Xiongshao Zhitong Recipe (XZR) is a traditional Chinese medicine prescription used for treating migraine, but its bioactive components and therapeutic mechanisms remain unclear. We aimed to confirm the therapeutic effect of XZR on migraine and to determine the possible mechanism and bioactive components of XZR. Here, a sensitive UHPLC-LTQ-Orbitrap MS assay was carried out to analyze the ingredients of XZR, and a total of 62 components were identified, including coumarins, phenolic acids, phthalides, flavonoids, and terpenoids; among them, 15 components were identified in the serum samples after XZR treatment. We established a rat model of migraine via nitroglycerin (NTG) injection. The in vivo experiments demonstrated that XZR attenuated allodynia and photophobia in rats with NTG-induced migraine, and XZR also demonstrated analgesic effects. XZR reversed the abnormal levels of nitric oxide, 5-hydroxytryptamine (5-HT), calcitonin gene-related peptide (CGRP), and substance P (SP) to normal levels. XZR also downregulated inflammatory reactions, including mast cell degranulation and serum IL-1ß, IL-6, and TNF-α levels. In terms of mechanism, we revealed that XZR treated NTG-induced migraine through the inhibition of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) expression in both the trigeminal nucleus caudalis (TNC) and periaqueductal gray matter (PAG), as well as the total NOS enzyme activity, which regulated the NF-κB signaling pathway. Additionally, imperatorin and xanthotoxin, two major ingredients of XZR, showed a high binding affinity to nNOS (Gly468-Leu616). In vitro, XZR, imperatorin, and xanthotoxin inhibited the nNOS expression and the NF-κB signaling pathway in lipopolysaccharide (LPS)-stimulated PC12 cells. In conclusion, we demonstrated the therapeutic effects of XZR and provided evidence that XZR played a critical anti-inflammatory role by suppressing NOS and NF-κB signaling pathway activation. Imperatorin and xanthotoxin were potential bioactive components of XZR. The findings from this study supported that XZR was a candidate herbal drug for migraine therapy.

TiO2 nanosheet supported MnCeOx: a remarkable catalyst with enhanced low-temperature catalytic activity in o-DCB oxidation.

Morphology engineering was an effective strategy for 1,2-dichlorobenzene (o-DCB) oxidation. Herein, TiO2 nanosheet supported MnCeOx (TiMn15Ce30-NS) showed excellent catalytic activity with T50% = 156 °C and T90% = 238 °C, which was better than the T50% = 213 °C and T90% = 247 °C for TiO2 nano truncated octahedron supported MnCeOx (TiMn15Ce30-NTO). TiMn15Ce30-NS also exhibited enhanced water resistance (T50% = 179 °C, T90% = 240 °C), and good stability with the o-DCB conversion retained at 98.9% for 12 h at 350 °C. The excellent catalytic activity of TiMn15Ce30-NS could be mainly ascribed to the preferentially exposed {001} crystal plane and Ce addition which favored the higher concentration of Mn4+ and surface active oxygen, along with stronger interaction between MnOx and CeOx. The present results deepen the understanding of the morphology-dependent effect on o-DCB oxidation.

MoS2/MXene pillared nanocomposite for ultrafast photonics applications.

In this work, we used nanocomposite saturable absorbers (SAs) in order to precisely design and modulate the process of compositing the light absorption by band gap engineering. Due to the higher absorption intensity of our MoS2/MXene nanocomposite, we have successfully shortened the pulse duration (1.2µs) of SA with enhancing saturable absorption intensity (7.22 MW cm-2), and the ultra-fast fiber laser based on this nanocomposite SA has shown wider Q-switching stable range in the case of high pump power. This strategy can efficiently improve the performance of SA and shows the potential application prospect of nanocomposites in nonlinear optics.

Downregulated Expression of RIPOR3 Correlated with Immune Infiltrates Predicts Poor Prognosis in Oral Tongue Cancer.

BACKGROUND Tongue cancer is the most prevalent of head and neck squamous cell carcinomas, including base of tongue cancer (BOT) and oral squamous cell carcinoma of the mobile tongue (OTSCC). We aimed to investigate the role of RIPOR3 in tumorigenesis and its development as a potential prognostic biomarker for tongue cancer, especially OTSCC. MATERIAL AND METHODS Associations of expression, clinical pathologic features, and overall survival were analyzed by logistic regression, multivariate Cox analysis, and Kaplan-Meier methods. Gene set enrichment analysis (GSEA) and the CIBERSORT algorithm were performed to determine the correlation between RIPOR3 and tumor immune infiltration. cBioPortal was used for methylation and copy number variation (CNV) analysis. The Human Protein Atlas (HPA) and GSE31056 dataset were used for further external validation. RESULTS RIPOR3 expression in OTSCC was significantly associated with various clinicopathological parameters. Kaplan-Meier survival analysis showed that OTSCC with low RIPOR3 expression had a worse prognosis than that with high RIPOR3 expression. Multivariate analysis revealed that lower RIPOR3 expression was an independent prognostic factor for poor prognosis. GSEA and Neighbor Gene Network analysis showed RIPOR3 expression was related with the modulation and function of the immune-related pathway. Methylation level and CNV analysis showed that the downregulated expression of RIPOR3 was significantly related to hypermethylation but not to CNV. Finally, high RIPOR3 expression was validated at the protein level using the HPA database and GSE31056 dataset. CONCLUSIONS These findings suggested that RIPOR3 might serve as a promising prognostic biomarker and is related to the immune cell infiltration of OTSCC.

Sodium alginate and naloxone loaded macrophage-derived nanovesicles for the treatment of spinal cord injury.

Spinal cord injury (SCI) causes Ca2+ overload, which can lead to inflammation and neuronal apoptosis. In this study, we prepared a nanovesicle derived from macrophage membrane (MVs), which encapsulated sodium alginate (SA) and naloxone (NAL) to inhibit inflammation and protect neurons by reducing the free Ca2+concentration at the SCI site. Based on the transmission electron microscopy (TEM) image, the encapsulated sample (NAL-SA-MVs) had a particle size of approximately 134 ±â€¯11 nm and exhibited a sustained release effect. The encapsulation rate of NAL and SA was 82.07% ± 3.27% and 72.13% ± 2.61% in NAL-SA-MVs, respectively. Targeting tests showed that the NAL-SA-MVs could accumulate in large quantities and enhance the concentration of SA and NAL at the lesion sites. In vivo and in vitro studies indicated that the NAL-SA-MVs could decrease the concentration of free Ca2+, which should further alleviate the inflammatory response and neuronal apoptosis. Anti-inflammation results demonstrated that the NAL-SA-MVs could reduce the pro-inflammation factors (iNOS, TNF-α, IL-1ß, IL-6) and increase the expression of anti-inflammation factors (IL-10) at the cell and animal level. Concurrently, fluorescence, flow cytometry and western blot characterization showed that the apoptotic condition of the neurons was significantly inhibited. In addition, the motor function of C57 mice were significantly improved after NAL-SA-MVs treatment. In conclusion, it is suggested that the NAL-SA-MVs has tremendous potential in the treatment of SCI.

The effect and mechanism of gene Fam20a on the development and function of salivary glands in mice.

OBJECTIVE: The influence of the knockout of gene Fam20a on mice salivary glands was studied in this research, to provide a potential gene therapeutic target for salivary gland dysfunction. DESIGN: The control group with genotype Fam20af/f and conditional knockout (cKO) group with Fam20af/f;K14-Cre were constructed with Cre-Loxp. The influence of Fam20a on the salivary glands was studied in terms of morphology, functionality and molecular mechanism. RESULTS: In terms of morphology, the cross-sectional area ratio of ductal to the total was reduced in the cKO mice, while that of extracellular matrix to the total was increased. At the sub-microscopic level, the knockout of Fam20a led to abnormal sub-microscopic structure of the duct cells. Functionally, saliva flow rate was significantly reduced in cKO mice. The result was consistent with the change of acinar cell marker Aquaporin 5 which was abnormally diffusely expressed in the cytoplasm of acinar cells. Meanwhile, the expression of ductal cell markers Cytokeratin 7 and nerve growth factor ß were significantly decreased, suggesting the abnormal development and function of the duct cells. The research on the mechanism reveals that the loss of Fam20a led to the decreased expression and varied localization of bone morphogenetic protein 4 (BMP4), and a significant decrease of the proportion of phosphorylated extracellular signal-regulated protein1/2 (ERK1/2) to total ERK1/2. These changes suggested that the loss of Fam20a attenuated the activity of the BMP/ERK signaling pathway. CONCLUSIONS: Fam20a affects the morphology and function of salivary glands, probably by attenuating the activity of the BMP/ERK signaling pathway.

Characterization of transcriptional landscape in bone marrow-derived mesenchymal stromal cells treated with aspirin by RNA-seq.

INTRODUCTION: Aspirin is a common antipyretic, analgesic, and anti-inflammatory drug, which has been reported to extend life in animal models and application in the treatment of aging-related diseases. However, it remains unclear about the effects of aspirin on bone marrow-derived mesenchymal stromal cells (BM-MSCs). Here, we aimed to analyze the influence of aspirin on senescence and young BM-MSCs. METHODS: BM-MSCs were serially passaged to construct a replicative senescence model. SA-ß-gal staining, PCR, western blot, and RNA-sequencing were performed on BM-MSCs with or without aspirin treatment, to examine aspirin's impact on bone marrow-derived mesenchymal stem cells. RESULTS: SA-ß-gal staining, PCR, and western blot revealed that aspirin could alleviate the cellular expression of senescence-related indicators of BM-MSCs, including a decrease of SA-ß-gal-positive cells and staining intensity, and downregulation of p16, p21, and p53 expression after aspirin treatment. RNA-sequencing results shown in the biological processes related to aging, aspirin could influence cellular immune response and lipid metabolism. CONCLUSION: The efficacy of aspirin for retarding senescence of BM-MSCs was demonstrated. Our study indicated that the mechanisms of this delay might involve influencing immune response and lipid metabolism.

Glutathione-modified macrophage-derived cell membranes encapsulated metformin nanogels for the treatment of spinal cord injury.

Spinal cord injury (SCI) causes a range of pathological responses, including oxidative stress, inflammation and apoptosis. In SCI treatment, whether an effective drug preparation can cross the blood-spinal cord barrier (BSCB) to the injury site is closely related to its therapeutic effect. Metformin (Met) is a glucose-lowering drug that shows a good effect for the treatment of SCI. However, it cannot cross the BSCB, which limits its application. In this study, we prepared glutathione-modified macrophage-derived cell membranes encapsulating metformin nanogels (Met-CNG-GSH) to solve this problem. Drug release and pharmacokinetics study results indicated that Met-CNG-GSH exhibits a slow release effect, and in vivo imaging demonstrated that Met-CNG-GSHs accumulated at the injury site, indicating that it has a good targeting effect. Animal experiments demonstrated that Met-CNG-GSH has a good therapeutic effect in alleviating oxidative stress, inflammation, and apoptosis. Therefore, Met-CNG-GSH represents a potential treatment for SCI.

Folate-functionalized SMMC-7721 liver cancer cell membrane-cloaked paclitaxel nanocrystals for targeted chemotherapy of hepatoma.

In this study, we prepared a folic acid-functionalized SMMC-7721 liver cancer cell membrane (CM)-encapsulated paclitaxel nanocrystals system (FCPN) for hepatoma treatment. Transmission electron microscopy (TEM) characterization showed that FCPN was irregular spherical shapes with a particle size larger than 200 nm and a coated thickness of approximately 20 nm. In an in vitro release experiment, FCPN indicated a slowly release effect of paclitaxel (PTX). Cell experiments demonstrated that FCPN was taken up by SMMC-7721 cells and significantly inhibited the proliferation of SMMC-7721 cells, which illustrated that FCPN had good targeting ability compared with PN and CPN. According to the results of in vivo animal experiments, FCPN significantly inhibited tumor growth. Tissue distribution experiments proved that FCPN could accumulate significantly in tumor tissues, which further explained why FCPN had good targeting ability. These results clearly suggested that folate-functionalized homotypic CM bionic nanosystems might represent a very valuable method for liver cancer treatment in the future.

Functional resveratrol-biodegradable manganese doped silica nanoparticles for the spinal cord injury treatment.

Spinal cord injury (SCI) causes secondary injury, accompanied by pathological changes such as oxidative stress, inflammation and neuronal apoptosis. This leads to permanent disabilities such as paralysis and loss of movement or sensation. Due to the ineffectiveness of drugs passing through the blood spinal cord barrier (BSCB), there is currently no effective treatment for SCI. The aim of this experiment was to design plasma complex component functionalized manganese-doped silica nanoparticles (PMMSN) with a redox response as a targeted drug carrier for resveratrol (RES), which effectively transports insoluble drugs to cross the BSCB. RES was adsorbed into PMMSN with a particle size of approximately 110 â€‹nm by the adsorption method, and the drug loading reached 32.61 â€‹± â€‹3.38%. The RES release results for the loaded sample (PMMSN-RES) showed that the PMMSN-RES exhibited a release slowly effect. In vitro and vivo experiments demonstrated that PMMSN-RES decreased reactive oxygen species (ROS) and malondialdehyde (MDA), increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, reduced the expression of inflammatory (TNF-α, IL-1ß and IL-6) and apoptotic cytokines (cleaved caspase-3) in spinal cord tissue after SCI. In summary, PMMSN-RES may be a potential pharmaceutical preparation for the treatment of SCI by reducing neuronal apoptosis and inhibiting inflammation caused by reducing oxidative stress to promote the recovery of mouse motor function.

Prognostic and immunological role of Fam20C in pan-cancer.

BACKGROUND: The family with sequence similarity 20-member C (Fam20C) kinase plays important roles in physiopathological process and is responsible for majority of the secreted phosphoproteome, including substrates associated with tumor cell migration. However, it remains unclear whether Fam20C plays a role in cancers. Here, we aimed to analyze the expression and prognostic value of Fam20C in pan-cancer and to gain insights into the association between Fam20C and immune infiltration. METHODS: We analyzed Fam20C expression patterns and the associations between Fam20C expression levels and prognosis in pan-cancer via the ONCOMINE, TIMER (Tumor Immune Estimation Resource), PrognoScan, GEPIA (Gene Expression Profiling Interactive Analysis), and Kaplan-Meier Plotter databases. After that, GEPIA and TIMER databases were applied to investigate the relations between Fam20C expression and immune infiltration across different cancer types, especially BLCA (bladder urothelial carcinoma), LGG (brain lower grade glioma), and STAD (stomach adenocarcinoma). RESULTS: Compared with adjacent normal tissues, Fam20C was widely expressed across many cancers. In general, Fam20C showed a detrimental role in pan-cancer, it was positively associated with poor survival of BLCA, LGG, and STAD patients. Specifically, based on TCGA (The Cancer Genome Atlas) database, a high expression level of Fam20C was associated with worse prognostic value in stages T2-T4 and stages N0-N2 in the cohort of STAD patients. Moreover, Fam20C expression had positive associations with immune infiltration, including CD4+ T cells, macrophages, neutrophils, and dendritic cells, and other diverse immune cells in BLCA, LGG, and STAD. CONCLUSION: Fam20C may serve as a promising prognostic biomarker in pan-cancer and has positive associations with immune infiltrates.