The interaction between astrocytes and microglia plays a vital role in the damage and repair of brain lesions due to traumatic brain injury (TBI). Recent studies have shown that exosomes act as ...potent mediators involved in intercellular communication.
In the current study, the expression of inflammatory factors and miR-873a-5p in the lesion area and oedema area was evaluated in 15 patients with traumatic brain injury. Exosomes secreted by astrocytes were detected by immunofluorescence, Western blot and electron microscopy. A mouse model of TBI and an in vitro model of LPS-induced primary microglia were established to study the protective mechanism of exosomes from miR-873a-5p overexpressing in TBI-induced nerve injury.
We discovered that exosomes derived from activated astrocytes promote microglial M2 phenotype transformation following TBI. More than 100 miRNAs were detected in these astrocyte-derived exosomes. miR-873a-5p is a major component that was highly expressed in human traumatic brain tissue. Moreover, miR-873a-5p significantly inhibited LPS-induced microglial M1 phenotype transformation and the subsequent inflammation through decreased phosphorylation of ERK and NF-κB p65. This effect also greatly improved the modified neurological severity score (mNSS) and attenuated brain injury in a strictly controlled cortical impact mouse model.
Taken together, our research indicates that miRNAs in the exosomes derived from activated astrocytes play a key role in the astrocyte-microglia interaction. miR-873a-5p, as one of the main components of these astrocyte-derived exosomes, attenuated microglia-mediated neuroinflammation and improved neurological deficits following TBI by inhibiting the NF-κB signalling pathway. These findings suggest a potential role for miR-873a-5p in treating traumatic brain injury.
Osteoarthritis (OA) is a chronic health condition. MicroRNAs (miRs) are critical in chondrocyte apoptosis in OA. We aimed to investigate the mechanism of miR-130b in OA progression. Bone marrow ...mesenchymal stem cells (BMSCs) and chondrocytes were first extracted. Chondrogenic differentiation of BMSCs was carried out and verified. Chondrocytes were stimulated with interleukin (IL)-1β to imitate OA condition in vitro. The effect of miR-130b on the viability, inflammation, apoptosis, and extracellular matrix of OA chondrocytes was studied. The target gene of miR-130b was predicted and verified. Rescue experiments were performed to further study the underlying downstream mechanism of miR-130b in OA. miR-130b first increased and drastically reduced during chondrogenic differentiation of BMSCs and in OA chondrocytes, respectively, while IL-1β stimulation resulted in increased miR-130b expression in chondrocytes. miR-130b inhibitor promoted chondrogenic differentiation of BMSCs and chondrocyte growth and inhibited the levels of inflammatory factors. miR-130b targeted SOX9. Overexpression of SOX9 facilitated BMSC chondrogenic differentiation and chondrocyte growth, while siRNA-SOX9 contributed to the opposite trends. Silencing of SOX9 significantly attenuated the pro-chondrogenic effects of miR-130b inhibitor on BMSCs. Overall, miR-130b inhibitor induced chondrogenic differentiation of BMSCs and chondrocyte growth by targeting SOX9.
Retinal neovascularization (RNV) is a leading cause of blindness worldwide. Long non-coding RNA (lncRNA) and competing endogenous RNA (ceRNA) regulatory networks play vital roles in angiogenesis. The ...RNA-binding protein galectin-1 (Gal-1) participates in pathological RNV in oxygen-induced retinopathy mouse models. However, the molecular associations between Gal-1 and lncRNAs remain unclear. Herein, we aimed to explore the potential mechanism of action of Gal-1 as an RNA-binding protein.
A comprehensive network of Gal-1, ceRNAs, and neovascularization-related genes was constructed based on transcriptome chip data and bioinformatics analysis of human retinal microvascular endothelial cells (HRMECs). We also conducted functional enrichment and pathway enrichment analyses. Fourteen lncRNAs, twenty-nine miRNAs, and eleven differentially expressed angiogenic genes were included in the Gal-1/ceRNA network. Additionally, the expression of six lncRNAs and eleven differentially expressed angiogenic genes were validated by qPCR in HRMECs with or without siLGALS1. Several hub genes, such as NRIR, ZFPM2-AS1, LINC0121, apelin, claudin-5, and C-X-C motif chemokine ligand 10, were found to potentially interact with Gal-1 via the ceRNA axis. Furthermore, Gal-1 may be involved in regulating biological processes related to chemotaxis, chemokine-mediated signaling, the immune response, and the inflammatory response.
The Gal-1/ceRNA axis identified in this study may play a vital role in RNV. This study provides a foundation for the continued exploration of therapeutic targets and biomarkers associated with RNV.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background:
Phillyrin (Phi) is the main polyphenolic compound found in
Forsythia suspensa
. Recent studies have revealed that Phi has potent antioxidative and anti-inflammatory effects. However, ...whether Phi could relieve blood–brain barrier (BBB) damage following traumatic brain injury (TBI) remains unknown.
Materials and Methods:
Lipopolysaccharide (LPS) was used to activate primary microglia, which were then treated with different doses of Phi or the peroxisome proliferator–activated receptor-gamma (PPARγ) antagonist (GW9662). CCK-8 assay was used for evaluating cell viability, and the cytokines (including IL-1β, IL-6, TNFα, IL-4, IL-10, and TGFβ), microglial phenotypic markers (iNOS, COX2, and CD86 for “M1” polarization; Arg1, Ym1, and CD206 for “M2” polarization), PPARγ, and NF-κB were determined by RT-PCR, Western blot, or cellular immunofluorescence. Primary cultured mouse brain microvascular endothelial cells (BMECs) were stimulated by the condition medium (CM) from microglia. The cell viability, angiogenesis, and tight junction of BMECs were determined
via
CCK-8 assay, tube formation assay, and Western blot (for detecting MMP3, MMP9, ZO1, claudin-5, and occludin). Furthermore, the mouse TBI model was constructed and treated with Phi and/or GW9662. The BBB integrity was evaluated by H&E staining, Evans blue staining, and tissue immunofluorescence.
Results:
Phi markedly restrained the pro-inflammatory (“M1” state) cytokines and promoted anti-inflammatory (“M2” polarization) cytokines in LPS-mediated microglia. Phi mitigated “M1” polarization and promoted “M2” polarization of microglia
via
enhancing PPARγ and inhibiting the NF-κB pathway. The PPARγ antagonist GW9662 significantly repressed Phi-mediated anti-inflammatory effects. Meanwhile, Phi enhanced the viability, tube formation ability, and cell junction of BMECs. In the TBI mouse model, Phi promoted “M2” polarization, whereas it repressed the “M1” polarization of microglia. In addition, Phi reduced TBI-mediated BBB damage. However, the protective effects of Phi were reversed mainly by GW9662 treatment.
Conclusion:
Phi prevents BBB damage
via
inhibiting the neuroinflammation of microglia through the PPARγ/NF-κB pathway, which provides a potential therapeutic drug against TBI.
Abstract Background Obstructive sleep apnea (OSA) and osteoporosis (OP) are prevalent diseases in the elderly. This study aims to reveal the clinical association between OSA and OP and explore ...potential crosstalk gene targets. Methods Participants diagnosed with OSA in the National Health and Nutrition Examination Survey (NHANES) database (2015–2020) were included, and OP was diagnosed based on bone mineral density (BMD). We explored the association between OSA and OP, and utilized multivariate logistic regression analysis and machine learning algorithms to explore the risk factors for OP in OSA patients. Overlapping genes of comorbidity were explored using differential expression analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and Random Forest (RF) methods. Results In the OSA population, the weighted prevalence of OP was 7.0%. The OP group had more females, lower body mass index (BMI), and more low/middle-income individuals compared to the non-OP group. Female gender and lower BMI were identified as independent risk factors for OP in OSA patients. Gene expression profiling revealed 8 overlapping differentially expressed genes in OP and OSA patients. KCNJ1 , NPR3 and WT1-AS were identified as shared diagnostic biomarkers or OSA and OP, all of which are associated with immune cell infiltration. Conclusion This study pinpointed female gender and lower BMI as OP risk factors in OSA patients, and uncovered three pivotal genes linked to OSA and OP comorbidity, offering fresh perspectives and research targets.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Upgrading of biomass derived 5-hydroxymethylfurfural (HMF) has attracted considerable interest recently. A new highly HMF-tolerant strain of
NJPI-15 was isolated in this study, and the biocatalytic ...reduction of HMF into 2,5-bis(hydroxymethyl)furan (BHMF) using whole cells was reported. Co-substrate was applied to improve the BHMF yield and selectivity of this strain as well as HMF-tolerant level. The catalytic capacity of the cells can be substantially improved by Mn
ion. The strain exhibited good catalytic performance at a pH range of 6.0-9.0 and a temperature range of 25°C-35°C. In addition, 100 mM HMF could be reduced to BHMF by the
NJPI-15 resting cells in presence of 70 mM glutamine and 30 mM sucrose, with a yield of 95%. In the fed-batch strategy, 656 mM BHMF was obtained within 48 h, giving a yield of 93.7%. The reported utilization of HMF to produce BHMF is a promising industrially sound biocatalytic process.
Sedimentary organic matter is an important component of the metabolism of a lake’s ecosystem, and it is generally derived from both the watershed and the primary productivity of a lake. Understanding ...the sources of organic matter in lakes and lake trophic status is important when evaluating the quality of lake ecosystems. We summarize the spatial distribution of total nitrogen (TN), total organic carbon (TOC), TOC/TN (C/N) molar ratios, and organic carbon isotope (δ13Corg) of the surface sediments of Fuxian Lake, Yunnan–Guizhou Plateau, Southwest China, which is the second deepest freshwater oligotrophic lake in China. The results show that the distributions of TN, TOC, C/N, and δ13Corg of the surface sediments are spatially heterogeneous, which is also the case for the trophic conditions of the lake. Compared with the adjacent eutrophic lakes and typical lakes in other areas with strong human activities, the content of organic matter is at a low level. Meanwhile, the autochthonous organic carbon in the surface sediments was characterized by lower δ13Corg (−25.3~−28.5) and C/N (8.7~12.9), suggesting that the biological carbon pump effect plays a significant part in the stability of carbon sinks by coupling with carbonate weathering. Our results emphasize the importance of the carbon sink of coupled carbonate weathering and aquatic photosynthesis in the evolution of the carbon cycle in lakes. Although modern monitoring shows that Fuxian Lake is an oligotrophic lake, there are potential risks of organic nitrogen pollution with respect to surface sediments, especially in northern and southern shallow-water areas. The organic pollution of lakes can be reduced by controlling the discharge of wastewater and reducing the nutrient loading of agricultural runoff.
Vascular mimicry (VM) was associated with the prognosis of cancers. The aim of the study was to explore the association between VM and anticancer therapy response in patients with lung ...adenocarcinoma.
This was a single-center retrospective study of patients with lung adenocarcinoma between March 1st, 2013, to April 1st, 2019, at the Second People's Hospital of Taizhou City. All included patients were divided into the VM and no-VM groups according to whether VM was observed or not in the specimen. Vessels with positive PAS and negative CD34 staining were confirmed as VM. The main outcome was progression-free survival (PFS).
Sixty-six (50.4%) patients were male. Eighty-one patients received chemotherapy as the first-line treatment, and 50 patients received TKIs. Forty-five (34.4%) patients were confirmed with VM. There was no difference regarding the first-line treatment between the VM and no-VM groups (P = 0.285). The 86 patients without VM had a median PFS of 279 (range, 90-1095) days, and 45 patients with VM had a median PFS of 167 (range, 90-369) days (P < 0.001). T stage (hazard ratio (HR) = 1.37, 95% confidence interval (CI): 1.10-1.71), N stage (HR = 1.43, 95%CI: 1.09-1.86), M stage (HR = 2.85, 95%CI: 1.76-4.61), differentiation (HR = 1.85, 95%CI: 1.29-2.65), therapy (HR = 0.32, 95%CI: 0.21-0.49), VM (HR = 2.12, 95%CI: 1.33-3.37), and ECOG (HR = 1.41, 95%CI: 1.09-1.84) were independently associated with PFS.
The benefits of first-line TKIs for NSCLC with EGFR mutation are possibly better than those of platinum-based regimens in patients without VM, but there is no difference in the benefit of chemotherapy or target therapy for VM-positive NSCLC harboring EGFR mutations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
New strategies and drugs are urgently needed to improve the treatment of hepatocellular carcinoma (HCC). Vasculogenic mimicry (VM) has been elucidated being associated with the progression of HCC and ...anti-VM could be a promising strategy.
extract (COE), a mixture of 26 compounds isolated from the Chinese Herb
Vine, has been elucidated to be able to disrupt VM formation in HCC. This study aims to dissect and identify the potential targets of COE on anti-VM formation both
and
that are distinct from our previous study. Proteomics analysis was used to identify differential proteins in HCC cells treated with or without COE (Data are available
ProteomeXchange with identifier PXD022203). Cells invasion was examined using Transwell. Matrigel was used to establish a 3-D culture condition for VM formation
. RT-PCR and Western Blot were used to examine changes of mRNA and protein respectively. Clinical resected samples were applied to confirm association between VM formation and identified targets. Subcutaneous xenograft tumor model was established to observe tumor growth and VM formation
. PAS-CD34 dual staining was used to detect VM
. A total of 194 proteins were identified to be differentially expressed in HCC cells treated with or without COE. In the 93 down-regulated proteins EphA2 stood out to be regulated on both RNA and protein level. Disruption EphA2 using COE or NVP inhibited VM formation and decreased VM associated biomarkers. In xenograft mouse model, COE inhibited tumor growth and VM formation via down-regulating EphA2. Taken together, our results indicate that COE could be used in HCC treatment because of its promising anti-VM effect.
We analyzed the economic benefits versus safety risks of sharing anti-vascular endothelial growth factor (VEGF) vials during the coronavirus disease (COVID-19) pandemic. This single-center ...retrospective study analyzed the data of patients with neovascular age-related macular degeneration (nAMD), proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO) who received anti-VEGF between January 2016 and July 2021 at Renmin Hospital, Wuhan University, China. Costs were compared of the two protocols of intravitreal injections (IVIs) of ranibizumab, aflibercept and conbercept after (i) splitting the vial content for use in two patients and after (ii) disposal of the remaining vial content after use in a single patient, with the COVID-19 outbreak considered as the demarcation point. The incidence rates of post-injection endophthalmitis (PIE) pre- and post-outbreak were analyzed. The mean cost of a single IVI increased by 33.3%, from 3917.67?71.69 to 5222.67?84.98 Chinese Yuan during the pandemic. The incidences of IVI-related culture-positive PIE were 0.0134% (3 in 22448) and 0.0223% (1 in 4479), respectively, before and after the pandemic (P=0.6532). We conclude that vial sharing of IVIs in a large clinical institution is not associated with increased PIE risk and can significantly reduce the cost of therapy.
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