A novel 25-ferroptosis-related gene signature for the prognosis of gliomas

BackgroundFerroptosis is closely associated with cancer and is of great importance in the immune evasion of cancer. However, the relationship between ferroptosis and glioma is unclear.MethodsWe downloaded the expression profiles and clinical data of glioma from the GlioVis database and obtained the expression profiles of ferroptosis genes. A ferroptosis-related gene signature was developed for the prognosis of gliomas.ResultsWe screened out prognostic ferroptosis genes, named ferroptosis-related genes, by the Cox regression method. Based on these genes, we used unsupervised clustering to obtain two different clusters; the principal component analysis algorithm was applied to determine the gene score of each patient, and then all the patients were classified into two subgroups. Results showed that there exist obvious differences in survival between different clusters and different gene score subgroups. The prognostic model constructed by the 25 ferroptosis-related genes was then evaluated to predict the clinicopathological features of immune activity in gliomas.ConclusionThe ferroptosis-related genes play an important role in the malignant process of gliomas, potentially contributing to the development of prognostic stratification and treatment strategies

Sialylation: An alternative to designing long-acting and targeted drug delivery system

Long-acting and specific targeting are two important properties of excellent drug delivery systems. Currently, the long-acting strategies based on polyethylene glycol (PEG) are controversial, and PEGylation is incapable of simultaneously possessing targeting ability. Thus, it is crucial to identify and develop approaches to produce long-acting and targeted drug delivery systems. Sialic acid (SA) is an endogenous, negatively charged, nine-carbon monosaccharide. SA not only mediates immune escape in the body but also binds to numerous disease related targets. This suggests a potential strategy, namely “sialylation,” for preparing long-acting and targeted drug delivery systems. This review focuses on the application status of SA-based long-acting and targeted agents as a reference for subsequent research

Combined application of microbial inoculant and kelp-soaking wastewater promotes wheat seedlings growth and improves structural diversity of rhizosphere microbial community

Abstract Industrial processing of kelp generates large amounts of kelp-soaking wastewater (KSW), which contains a large amount of nutrient-containing substances. The plant growth-promoting effect might be further improved by combined application of growth-promoting bacteria and the nutrient-containing KSW. Here, a greenhouse experiment was conducted to determine the effect of the mixture of KSW and Bacillus methylotrophicus M4-1 (MS) vs. KSW alone (SE) on wheat seedlings, soil properties and the microbial community structure in wheat rhizosphere soil. The available potassium, available nitrogen, organic matter content and urease activity of MS soil as well as the available potassium of the SE soil were significantly different (p < 0.05) from those of the CK with water only added, increased by 39.51%, 36.25%, 41.61%, 80.56% and 32.99%, respectively. The dry and fresh weight of wheat seedlings from MS plants increased by 166.17% and 50.62%, respectively, while plant height increased by 16.99%, compared with CK. Moreover, the abundance and diversity of fungi in the wheat rhizosphere soil were significantly increased (p < 0.05), the relative abundance of Ascomycetes and Fusarium spp. decreased, while the relative abundance of Bacillus and Mortierella increased. Collectively, the combination of KSW and the plant growth-promoting strain M4-1 can promote wheat seedlings growth and improve the microecology of rhizosphere microorganisms, thereby solving the problems of resource waste and environmental pollution, ultimately turning waste into economic gain

Biocontrol of Two Bacterial Inoculant Strains and Their Effects on the Rhizosphere Microbial Community of Field-Grown Wheat

Biocontrol by inoculation with beneficial microbes is a proven strategy for reducing the negative effect of soil-borne pathogens. We evaluated the effects of microbial inoculants BIO-1 and BIO-2 in reducing soil-borne wheat diseases and in influencing wheat rhizosphere microbial community composition in a plot test. The experimental design consisted of three treatments: (1) Fusarium graminearum F0609 (CK), (2) F. graminearum + BIO-1 (T1), and (3) F. graminearum F0609 + BIO-2 (T2). The results of the wheat disease investigation showed that the relative efficacies of BIO-1 and BIO-2 were up to 82.5% and 83.9%, respectively. Illumina MiSeq sequencing revealed that bacterial abundance and diversity were significantly higher (P<0.05) in the treatment groups (T1 and T2) than in the control, with significantly decreased fungal diversity in the T2 group. Principal coordinates and hierarchical clustering analyses revealed that the bacterial and fungal communities were distinctly separated between the treatment and control groups. Bacterial community composition analysis demonstrated that beneficial microbes, such as Sphingomonas, Bacillus, Nocardioides, Rhizobium, Streptomyces, Pseudomonas, and Microbacterium, were more abundant in the treatment groups than in the control group. Fungal community composition analysis revealed that the relative abundance of the phytopathogenic fungi Fusarium and Gibberella decreased and that the well-known beneficial fungi Chaetomium, Penicillium, and Humicola were more abundant in the treatment groups than in the control group. Overall, these results confirm that beneficial microbes accumulate more easily in the wheat rhizosphere following application of BIO-1 and BIO-2 and that the relative abundance of phytopathogenic fungi decreased compared with that in the control group

Impaired face recognition is associated with abnormal gray matter volume in the posterior cingulate cortex in congenital amusia

Congenital amusia is as a neurodevelopment disorder primarily defined by impairment in pitch discrimination and pitch memory. Interestingly, it has been reported that individuals with congenital amusia also exhibit deficits in face recognition (prosopagnosia). One explanation of such comorbidity is that the neural substrates of pitch recognition and face recognition may be similar. To test this hypothesis, face recognition ability was assessed using the Cambridge Face Memory Test (CFMT) and gray matter volume was determined through voxelbased morphometry (VBM) among participants with and without congenital amusia. As expected, participants with amusia performed worse on the CFMT test and showed reduced gray matter volume (GMV) in the middle temporal gyrus (MTG), the superior temporal gyrus (STG), and the posterior cingulate cortex (PCC) in the right hemisphere, when compared with matched controls. Furthermore, correlation analyses demonstrated that the CFMT score was positively related to MTG, STG, and PCC GMV in all participants, while separate analyses of each group found a positive correlation of CFMT score and PCC GMV in amusics. These findings suggest that face recognition is associated with a widely distributed microstructural network in the human brain and the PCC plays an important role in both pitch recognition and face recognition in amusics. In addition, neurodevelopmental disorders such as congenital amusia and prosopagnosia may share a common neural substrate

A systematic review and meta-analysis of inflammatory biomarkers in Parkinson’s disease

Abstract Neuroinflammation plays a crucial role in the pathogenesis of Parkinson’s disease (PD), but controversies persist. Studies reporting concentrations of blood or cerebrospinal fluid (CSF) markers for patients with PD and controls were included and extracted. Pooled Hedges’g was adopted to illustrate comparisons, and covariates were used to explore sources of heterogeneity. Finally, 152 studies were included. Increased IL-6, TNF-α, IL-1β, STNFR1, CRP, CCL2, CX3CL1, and CXCL12 levels and decreased INF-γ and IL-4 levels were noted in the PD group. In addition, increased CSF levels of IL-6, TNF-α, IL-1β, CRP and CCL2 were revealed in patients with PD compared to controls. Consequently, significantly altered levels of inflammatory markers were verified between PD group and control, suggesting that PD is accompanied by inflammatory responses in both the peripheral blood and CSF. This study was registered with PROSPERO, CRD42022349182

Network-Based Elaboration of the Efficacy of the Dachangshu (BL25) and Tianshu (ST25) Points in the Treatment of Functional Constipation in Children through Inflammation, Adipocytokine, or Leptin Pathways

Constipation commonly occurs during childhood, and more than 95% of cases are classified as functional constipation. If not effectively treated, 20% of patients with childhood constipation can continue to exhibit symptoms into adulthood, which seriously affects their mental health and quality of life. The main feature of acupuncture or acupoint stimulation, a special branch of traditional Chinese medicine, is the selection of different acupoints for different diseases, and many worthy guidelines have been established for matching acupoints. The back-shu and front-mu point combination adheres to an important acupoint compatibility law that has been used since its proposal 2,500 years ago but has not yet been verified by the modern evidence-based experiments. This study focused on the back-shu and front-mu point combination using the Dachangshu (BL25) and Tianshu (ST25) points as examples to explore possible research methods for network acupoint-based stimulation based on existing evidence and to elucidate the mechanisms induced by BL25 and ST25 in the treatment of functional constipation in children (FCC). The study found that BL25 and ST25 have 20 common targets, namely, AQP8, DRD2, VIP, TAC1, IL6R, TNF, FOS, KIT, CHAT, HTR3A, GAS8, SOD3, TRPV1, MPO, CALCA, IL1B, P2RX7, NPY2R, IL10RA, and TPH1, and these targets may provide a strategy for the combined usage of BL25 and ST25. In addition, BL25 and ST25 can affect FCC treatment through inflammation-relatedTh17-cell differentiation, the NF-kappa B signaling pathway, and the Toll-like receptor signaling pathway. Adipocytokines or leptin may also comprise the mechanism through which BL25 and ST25 regulate FCC. In addition, BL25 and ST25 regulate FCC through 13 core targets, namely, NFKBIA, RELA, TNF, IKBKB, IRAK1, TLR4, MYD88, TNFRSF1A, IL1R1, TLR2, IL1B, TRAF6, and TNFRSF1B. In short, this study provides new ideas and methods for studying the mechanism of acupuncture points

α-Asarone Attenuates Cognitive Deficit in a Pilocarpine-Induced Status Epilepticus Rat Model via a Decrease in the Nuclear Factor-κB Activation and Reduction in Microglia Neuroinflammation

BackgroundTemporal lobe epilepsy (TLE) is one of the most drug-resistant types of epilepsy with about 80% of TLE patients falling into this category. Increasing evidence suggests that neuroinflammation, which has a critical role in the epileptogenesis of TLE, is associated with microglial activation. Therefore, agents that act toward the alleviation in microglial activation and the attenuation of neuroinflammation are promising candidates to treat TLE. α-Asarone is a major active ingredient of the Acori Graminei Rhizoma used in Traditional Chinese Medicine, which has been used to improve various disease conditions including stroke and convulsions. In addition, an increasing number of studies suggested that α-asarone can attenuate microglia-mediated neuroinflammation. Thus, we hypothesized that α-asarone is a promising neuroprotective agent for the treatment of the TLE.MethodsThe present study evaluated the therapeutic effects of α-asarone on microglia-mediated neuroinflammation and neuroprotection in vitro and in vivo, using an untreated control group, a status epilepticus (SE)-induced group, and an SE-induced α-asarone pretreated group. A pilocarpine-induced rat model of TLE was established to investigate the neuroprotective effects of α-asarone in vivo. For the in vitro study, lipopolysaccharide (LPS)-stimulated primary cultured microglial cells were used.ResultsThe results indicated that the brain microglial activation in the rats of the SE rat model led to important learning and memory deficit. Preventive treatment with α-asarone restrained microglial activation and reduced learning and memory deficit. In the in vitro studies, α-asarone significantly suppressed proinflammatory cytokine production in primary cultured microglial cells and attenuated the LPS-stimulated neuroinflammatory responses. Our mechanistic study revealed that α-asarone inhibited inflammatory processes by regulation the transcription levels of kappa-B, by blocking the degradation pathway of kappa B-alpha [inhibitor kappa B-alpha (IκB-α)] and kappa B-beta (IκB-β) kinase in both the SE rats and in primary cultured microglial cells.ConclusionTaken together, these data demonstrate that α-asarone is a promising neuroprotective agent for the prevention and treatment of microglia-mediated neuroinflammatory conditions including TLE, for which further assessment studies are pertinent

DataSheet_1_A novel 25-ferroptosis-related gene signature for the prognosis of gliomas.docx

BackgroundFerroptosis is closely associated with cancer and is of great importance in the immune evasion of cancer. However, the relationship between ferroptosis and glioma is unclear.MethodsWe downloaded the expression profiles and clinical data of glioma from the GlioVis database and obtained the expression profiles of ferroptosis genes. A ferroptosis-related gene signature was developed for the prognosis of gliomas.ResultsWe screened out prognostic ferroptosis genes, named ferroptosis-related genes, by the Cox regression method. Based on these genes, we used unsupervised clustering to obtain two different clusters; the principal component analysis algorithm was applied to determine the gene score of each patient, and then all the patients were classified into two subgroups. Results showed that there exist obvious differences in survival between different clusters and different gene score subgroups. The prognostic model constructed by the 25 ferroptosis-related genes was then evaluated to predict the clinicopathological features of immune activity in gliomas.ConclusionThe ferroptosis-related genes play an important role in the malignant process of gliomas, potentially contributing to the development of prognostic stratification and treatment strategies.</p

Structure–Property Correlations of Reactive Oxygen Species-Responsive and Hydrogen Peroxide-Eliminating Materials with Anti-Oxidant and Anti-Inflammatory Activities

To develop reactive oxygen species (ROS)-responsive anti-inflammatory materials and establish their structure–property correlations, a series of H₂O₂-eliminating materials (OxbCDs) were designed and synthesized by conjugating different phenylboronic acid pinacol ester (PBAP) groups onto a biocompatible scaffold compound β-cyclodextrin via varied linker groups. Both the H₂O₂-triggered hydrolysis profiles and H₂O₂-eliminating capacities of these materials were dependent on the chemical structure of the PBAP moieties. Together with the elucidation of hydrolysis mechanisms, we established structure–property correlations of these OxbCD materials. Extensive in vitro experiments revealed nanoparticles (NPs) based on OxbCDs showed no adverse biological effects on normal cells. OxbCD NPs could effectively inhibit inflammatory responses and oxidative stress in stimulated macrophages. Consistently, OxbCD NPs efficaciously alleviated the symptoms of peritonitis in mice, with respect to reducing the counts of neutrophils and macrophages as well as inhibiting the secretion of pro-inflammatory cytokines, chemokines, and oxidative mediators. Similarly, OxbCD NPs loaded with anti-inflammatory drugs displayed superior efficacy in an acute inflammation model of peritonitis in mice. More importantly, OxbCD NPs showed good biocompatibility after administration via different routes. Consequently, besides serving as anti-inflammatory materials, the newly developed H₂O₂-eliminating materials may be utilized as pharmacologically functional carriers for targeted therapy of many diseases associated with inflammation and oxidative stress