Mechanism of ferroptosis in breast cancer and research progress of natural compounds regulating ferroptosis.

Breast cancer is the most prevalent cancer worldwide and its incidence increases with age, posing a significant threat to women's health globally. Due to the clinical heterogeneity of breast cancer, the majority of patients develop drug resistance and metastasis following treatment. Ferroptosis, a form of programmed cell death dependent on iron, is characterized by the accumulation of lipid peroxides, elevated levels of iron ions and lipid peroxidation. The underlying mechanisms and signalling pathways associated with ferroptosis are intricate and interconnected, involving various proteins and enzymes such as the cystine/glutamate antiporter, glutathione peroxidase 4, ferroptosis inhibitor 1 and dihydroorotate dehydrogenase. Consequently, emerging research suggests that ferroptosis may offer a novel target for breast cancer treatment; however, the mechanisms of ferroptosis in breast cancer urgently require resolution. Additionally, certain natural compounds have been reported to induce ferroptosis, thereby interfering with breast cancer. Therefore, this review not only discusses the molecular mechanisms of multiple signalling pathways that mediate ferroptosis in breast cancer (including metastasis, invasion and proliferation) but also elaborates on the mechanisms by which natural compounds induce ferroptosis in breast cancer. Furthermore, this review summarizes potential compound types that may serve as ferroptosis inducers in future tumour cells, providing lead compounds for the development of ferroptosis-inducing agents. Last, this review proposes the potential synergy of combining natural compounds with traditional breast cancer drugs in the treatment of breast cancer, thereby suggesting future directions and offering new insights.

Efficacy and safety of gut microbiota-based therapies in autoimmune and rheumatic diseases: a systematic review and meta-analysis of 80 randomized controlled trials.

BACKGROUND: Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is lacking. METHODS: Pubmed, EMbase, Sinomed, and other databases were searched for RCTs related to the treatment of autoimmune diseases with probiotics from inception to June 2022. RevMan 5.4 software was used for meta-analysis after 2 investigators independently screened literature, extracted data, and assessed the risk of bias of included studies. RESULTS: A total of 80 RCTs and 14 types of autoimmune disease [celiac sprue, SLE, and lupus nephritis (LN), RA, juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia syndrome, MS, systemic sclerosis, type 1 diabetes mellitus (T1DM), oral lichen planus (OLP), Crohn's disease, ulcerative colitis] were included. The results showed that gut microbiota-based therapies may improve the symptoms and/or inflammatory factor of celiac sprue, SLE and LN, JIA, psoriasis, PSS, MS, systemic sclerosis, Crohn's disease, and ulcerative colitis. However, gut microbiota-based therapies may not improve the symptoms and/or inflammatory factor of spondyloarthritis and RA. Gut microbiota-based therapies may relieve the pain of fibromyalgia syndrome, but the effect on fibromyalgia impact questionnaire score is not significant. Gut microbiota-based therapies may improve HbA1c in T1DM, but its effect on total insulin requirement does not seem to be significant. These RCTs showed that probiotics did not increase the incidence of adverse events. CONCLUSIONS: Gut microbiota-based therapies may improve several autoimmune diseases (celiac sprue, SLE and LN, JIA, psoriasis, fibromyalgia syndrome, PSS, MS, T1DM, Crohn's disease, and ulcerative colitis).

Clinicopathological phenotype and outcomes of NCAM-1+ membranous lupus nephritis.

INTRODUCTION: No studies explored the long-term outcomes of neural cell adhesion molecule 1 (NCAM1) associated membranous lupus nephritis (MLN) patients. METHOD: We performed immunohistochemical studies on kidney biopsy specimens against NCAM1 in consecutive MLN patients. The clinical and histopathological characteristics and outcomes of cases of NCAM1 associated MLN patients are described and compared with NCAM1 negative patients. In addition, we detected serum circulating anti-NCAM1 antibodies through western blotting and indirect immunofluorescence assays. RESULTS: Among 361 MLN cases, 18 (5.0%) were glomerular NCAM1-positive. NCAM1 positive MLN patients were older [35 years (IQR 27-43) versus 28 (22-37); P = 0.050) and had lower systemic lupus erythematosus disease activity index [11 (IQR 8-12) versus 14 (10-18); P = 0.007], serum creatinine [60 µmol/L (IQR 50-70) versus 70 (54-114); P = 0.029], activity index [3 (IQR 2-6) versus 6 (3-9); P = 0.045] at kidney biopsy compared with NCAM1 negative patients. The percentage of positive anti-Sjogren's syndrome related antigen A antibodies in NCAM1 positive patients was significantly greater (83.3% versus 58.2%; P = 0.035) than in the NCAM1 negative patients. However, no evidence of neuropsychiatric disorders was found in these 18 patients. There were no significant differences in the treatment response and the risk of end stage renal diseases between NCAM1 positive and negative groups (P = 0.668 and P = 0.318, respectively). But the risk of death was much higher in the NCAM1 positive group than the NCAM1 negative group (27.8% vs. 8.1%, P = 0.007). Moreover, the risk of death was also much higher in the NCAM1 positive group than the matched NCAM1 negative group (Log-rank P = 0.013). Additionally, circulating anti-NCAM1 antibodies can be detected in 1/5 (20%) patients who had serum available. CONCLUSION: The prevalence of NCAM1 positivity was 5.0% in our cohort of MLN and the high mortality in these subgroup patients are needed to validate in future studies.

Identification of ion channel-related genes as diagnostic markers and potential therapeutic targets for osteoarthritis through bioinformatics and machine learning-based approaches.

BACKGROUND: Osteoarthritis (OA) is a debilitating joint disorder characterized by the progressive degeneration of articular cartilage. Although the role of ion channels in OA pathogenesis is increasingly recognized, diagnostic markers and targeted therapies remain limited. METHODS: In this study, we analyzed the GSE48556 dataset to identify differentially expressed ion channel-related genes (DEGs) in OA and normal controls. We employed machine learning algorithms, least absolute shrinkage and selection operator(LASSO), and support vector machine recursive feature elimination(SVM-RFE) to select potential diagnostic markers. Then the gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed to explore the potential diagnostic markers' involvement in biological pathways. Finally, weighted gene co-expression network analysis (WGCNA) was used to identify key genes associated with OA. RESULTS: We identified a total of 47 DEGs, with the majority involved in transient receptor potential (TRP) pathways. Seven genes (CHRNA4, GABRE, HTR3B, KCNG2, KCNJ2, LRRC8C, and TRPM5) were identified as the best characteristic genes for distinguishing OA from healthy samples. We performed clustering analysis and identified two distinct subtypes of OA, C1, and C2, with differential gene expression and immune cell infiltration profiles. Then we identified three key genes (PPP1R3D, ZNF101, and LOC651309) associated with OA. We constructed a prediction model using these genes and validated it using the GSE46750 dataset, demonstrating reasonable accuracy and specificity. CONCLUSIONS: Our findings provide novel insights into the role of ion channel-related genes in OA pathogenesis and offer potential diagnostic markers and therapeutic targets for the treatment of OA.

As society ages, the incidence of knee osteoarthritis continues to rise, bringing with it a series of social impacts and medical pressure. Despite the increasing recognition of the role of ion channels in the pathogenesis of OA, diagnostic markers and targeted therapies remain limited.This study investigated the role of TRP as possible diagnostic tools for OA.Seven TRP-related genes were identified as the best traits to distinguish OA from healthy samples, and then we constructed and validated risk scores for three key genes (PPP1R3D, ZNF101, and LOC651309) relevant to OA ion channel gene modules.Our findings provide novel insights into the role of ion channel-related genes in OA pathogenesis and offer a reference for further clinical diagnosis.

Calibration method for a multi-focus microscopic 3D imaging system.

This Letter presents a novel, to the best of our knowledge, method to calibrate multi-focus microscopic structured-light three-dimensional (3D) imaging systems with an electrically adjustable camera focal length. We first leverage the conventional method to calibrate the system with a reference focal length f0. Then we calibrate the system with other discrete focal lengths fi by determining virtual features on a reconstructed white plane using f0. Finally, we fit the polynomial function model using the discrete calibration results for fi. Experimental results demonstrate that our proposed method can calibrate the system consistently and accurately.

Efficacy and safety of total glucosides of paeony in the treatment of 5 types of inflammatory arthritis: A systematic review and meta-analysis.

OBJECTIVE: To evaluate efficacy and safety of total glucosides of paeony in the treatment of 5 types of inflammatory arthritis METHODS: Databases such as Pubmed, Cochran Library, Embase were searched to collect RCTs about TGP in the treatment of inflammatory arthritis. Then, the RCTs were assessed for risk of bias and RCT data were extracted. Finally, RevMan 5.4 was used for the meta-analysis. RESULTS: A total of 63 RCTs were finally included, involving 5293 participants and 5 types of types of inflammatory arthritis: rheumatoid arthritis (RA), ankylosing spondylitis (AS), osteoarthritis (OA), juvenile idiopathic arthritis (JIA), psoriatic arthritis. For AS, TGP may improve AS disease activity score (ASDAS), decrease erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tumor necrosis factor (TNF)- α and interleukin (IL)- 6; for RA, TGP may improve disease activity of 28 joints (DAS28), decrease ESR, CRP, rheumatoid factor (RF), TNF-α and IL-6; for psoriatic arthritis, TGP may improve psoriasis area and severity index (PASI) and decrease ESR; for OA, TGP may improve visual analogue scale (VAS) and decrease nitric oxide (NO); for JIA, TGP may increase total efficiency rate, decrease ESR, CRP and TNF-α. For safety, RCTs showed that the addition of TGP did not increase adverse events, and may even reduce adverse events. CONCLUSION: TGP may improve symptoms and inflammation levels in patients with inflammatory arthritis. However, due to the low quality and small number of RCTs, large-sample, multi-center clinical trials are still needed for revision or validation.

Geometric-feature-based approach to human face reconstruction with high measurement speed.

This paper presents a method based on geometry for three-dimensional (3D) face reconstruction without the need for additional images, hardware components, or objects. In our proposed method, we consider part of the nose as the feature region because its shape remains almost constant during the measurement. The geometry of this region was used to provide cues for phase unwrapping. We first spatially unwrap the phase and determine the integer multiple of 2π to be added by comparing the recovered result of the feature region and its actual shape. Then, the face can be reconstructed with the acquired absolute phase. Experimental results demonstrated that our method is capable of reconstructing a dynamic face with high measurement speed, and only three phase-shifted fringes are required per frame.

Recovery of driving skills after endoscopy under propofol sedation: a prospective pilot study to assess the driving skills after endoscopic sedation using driving simulation.

BACKGROUND: Patients are recommended not to drive for at least the first 24 h after endoscopy with propofol sedation. However, the evidence underlying these recommendations is scarce. We hypothesized that after endoscopic procedures performed under propofol sedation, the subject's driving ability was restored in less than 24 h. METHODS: We prospectively enrolled thirty patients between 20 and 70 years possessing a legitimate driver's license scheduled for endoscopy at our hospital. The sample chosen was a convenience sample. Gastroscopy or colonoscopy was performed with propofol sedation. Before and after endoscopy, the investigator drove the subjects to the laboratory to assess their driving skills using a driving simulation system, which employs 3 driving scenarios designed by professional transportation researchers. The blood propofol concentration was estimated before endoscopy, and 2 and 4 h after endoscopy. The primary outcome was the time required for subjects to recover their driving ability after propofol sedation. The secondary outcome was the blood propofol concentration before and after endoscopic procedures under propofol anesthesia. RESULTS: Thirty volunteers participated in the study and 18 of them completed all the interventions. In the low-risk S-curve scene, the mean acceleration, lane deviation, and number of deviations from the path at baseline (0.016 cm/s2, 42.50 cm, and 0.83, respectively) were significantly less than that at post-2 h (0.029 cm/s2, P = 0.001; 53.80 cm, P = 0.014; 2.06, P = 0.022). In the moderate-(overtaking) and high-risk (emergency collision avoidance) scenes, the tested parameters at baseline and post-2 h were statistically comparable. In the low-, moderate-, and high-risk scenes the tested parameters at baseline and post-4 h were statistically comparable. The total range of propofol was 120-280 mg.The mean blood concentration of propofol at post-2 h was 0.81 ± 0.40 µg/mL, and at post-4 h was below the limit of detection. CONCLUSION: After endoscopy performed under propofol sedation, subjects' driving abilities were completely restored at 4 h when tested on a simulator.

Comparison and verification of two deep learning models for the detection of chest CT rib fractures.

BACKGROUND: A high false-positive rate remains a technical glitch hindering the broad spectrum of application of deep-learning-based diagnostic tools in routine radiological practice from assisting in diagnosing rib fractures. PURPOSE: To examine the performance of two versions of deep-learning-based software tools in aiding radiologists in diagnosing rib fractures on chest computed tomography (CT) images. MATERIAL AND METHODS: In total, 123 patients (708 rib fractures) were included in this retrospective study. Two groups of radiologists with different experience levels retrospectively reviewed images for rib fractures in the concurrent mode aided with RibFrac-High Sensitivity (HS) and RibFrac-High Precision (HP). We compared their diagnostic performance against the reference standard in terms of sensitivity and positive predictive value (PPV). RESULTS: On a per-patient basis, RibFrac-HS exhibited a higher sensitivity compared with RibFrac-HP (mean difference=0.051, 95% CI=0.012-0.090; P = 0.011), whereas the latter significantly outperformed the former in terms of the PPV (mean difference=0.273, 95% CI=0.238-0.308; P < 0.0001). The use of RibFrac-HP significantly improved the junior and the senior groups' sensitivities respectively by 0.058 (95% CI=0.033-0.083; P < 0.0001) and 0.058 (95% CI=0.034-0.081; P < 0.0001), and decreased the diagnosis time by 206 s (95% CI=191-220; P < 0.0001) and 79 s (95% CI=67-92; P < 0.0001), respectively, when compared to no software assistance. CONCLUSION: The sensitivity and efficiency of radiologists in identifying rib fractures can be improved by using RibFrac-HS and/or RibFrac-HP. With an added module for false-positive suppression, RibFrac-HP maintains the sensitivity and increases the PPV in fracture detection compared to Rib-Frac-HS.

NRF1 Alleviated Oxidative Stress of Glioblastoma Cells by Regulating NOR1.

Oxidored-nitro domain-containing protein 1 (NOR1) is a critical tumour suppressor gene, though its regulatory mechanism in oxidative stress of glioblastoma (GBM) remains unclear. Hence, further study is needed to unravel the function of NOR1 in the progression of oxidative stress in GBM. In this study, we evaluated the expression of NOR1 and nuclear respiratory factor 1 (NRF1) in GBM tissue and normal brain tissue (NBT) using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB), and investigated their relationship. We then induced oxidative stress in U251 cells through H2O2 treatment and conducted Cell Count-ing Kit-8, Transwell and wound healing assays to analyse cell proliferation, invasion and migration. Cell apoptosis was assessed by flow cytometry and TUNEL staining. We also measured the activities of superoxide dismutase and catalase, as well as the level of reactive oxygen species (ROS) using biochemical techniques. Via qRT-PCR and WB, the mRNA and protein expression levels of NOR1 and NRF1 were determined. Chromatin immunoprecipitation (ChIP) assays were applied to validate NRF1's interaction with NOR1. Our results showed that the expression of NOR1 and NRF1 was low in GBM, and their expression levels were positively correlated. H2O2-induced oxidative stress reduced NRF1 and NOR1 expression levels and increased the ROS level. The ChIP assay confirmed the binding of NRF1 to NOR1. Over-expression of NRF1 attenuated the inhibitory effect of oxidative stress on the proliferation, migration and invasion of U251 cells, which was reversed by knockdown of NOR1.

The impact of traffic control measures on the spread of COVID-19 within urban agglomerations based on a modified epidemic model.

With the spatial structure of urban agglomerations, well-developed transportation networks and close economic ties can increase the risk of intercity transmission of infectious diseases. To reveal the epidemic transmission mechanism in urban agglomerations and to explore the effectiveness of traffic control measures, this study proposes an Urban-Agglomeration-based Epidemic and Mobility Model (UAEMM) based on the reality of urban transportation networks and population mobility factors. Since the model considers the urban population inflow, along with the active intracity population, it can be used to estimate the composition of urban cases. The model was applied to the Chang-Zhu-Tan urban agglomeration, and the results show that the model can better simulate the transmission process of the urban agglomeration for a certain scale of epidemic. The number of cases within the urban agglomeration is higher than the number of cases imported into the urban agglomeration from external cities. The composition of cases in the core cities of the urban agglomeration changes with the adjustment of prevention and control measures. In contrast, the number of cases imported into the secondary cities is consistently greater than the number of cases transmitted within the cities. A traffic control measures discount factor is introduced to simulate the development of the epidemic in the urban agglomeration under the traffic control measures of the first-level response to major public health emergency, traffic blockades in infected areas, and public transportation shutdowns. If none of those traffic control measures had been taken after the outbreak of COVID-19, the number of cases in the urban agglomeration would theoretically have increased to 3879, which is 11.61 times the actual number of cases that occurred. If only one traffic control measure had been used alone, each of the three measures would have reduced the number of cases in the urban agglomeration to 30.19 %-57.44 % of the theoretical values of infection cases, with the best blocking effect coming from the first-level response to major public health emergency. Traffic control measures have a significant effect in interrupting the spread of COVID-19 in urban agglomerations. The methodology and main findings presented in this paper are of general interest and can also be used in studies in other countries for similar purposes to help understand the spread of COVID-19 in urban agglomerations.

Toxicological Effects of Secondary Air Pollutants.

Secondary air pollutants, originating from gaseous pollutants and primary particulate matter emitted by natural sources and human activities, undergo complex atmospheric chemical reactions and multiphase processes. Secondary gaseous pollutants represented by ozone and secondary particulate matter, including sulfates, nitrates, ammonium salts, and secondary organic aerosols, are formed in the atmosphere, affecting air quality and human health. This paper summarizes the formation pathways and mechanisms of important atmospheric secondary pollutants. Meanwhile, different secondary pollutants' toxicological effects and corresponding health risks are evaluated. Studies have shown that secondary pollutants are generally more toxic than primary ones. However, due to their diverse source and complex generation mechanism, the study of the toxicological effects of secondary pollutants is still in its early stages. Therefore, this paper first introduces the formation mechanism of secondary gaseous pollutants and focuses mainly on ozone's toxicological effects. In terms of particulate matter, secondary inorganic and organic particulate matters are summarized separately, then the contribution and toxicological effects of secondary components formed from primary carbonaceous aerosols are discussed. Finally, secondary pollutants generated in the indoor environment are briefly introduced. Overall, a comprehensive review of secondary air pollutants may shed light on the future toxicological and health effects research of secondary air pollutants.

Structure-guided discovery of novel potent and efficacious proteolysis targeting chimera (PROTAC) degrader of BRD4.

Bromodomain-containing protein 4 (BRD4) has been identified as a potential target in the treatment of many cancers and several BRD4 inhibitors have entered clinical studies. Previous studies have shown that BRD4 degraders have potential to overcome resistance to BRD4 inhibitors. However, most of the BRD4 degraders have poor solubility and bioavailability, one of which the reason is large molecular weight. Here, we describe the design, synthesis, and evaluation studies of a BRD4 degrader based on the proteolysis targeting chimeras (PROTAC) concept. Our efforts have led to the discovery of compound 15, which is a weak inhibitor and potent BRD4 degrader with a molecular weight of 821.8. In vitro, 15 can completely degrade BRD4 at nanomolar concentration, with DC50 = 0.25 and 3.15 nM in MV4-11 and RS4-11 cell lines, respectively. Further optimization of compound 15 may reduce its molecular weight and improve druggabillity, and provide a new choice for the treatment of cancer.

Peptides derived from small mitochondrial open reading frames: Genomic, biological, and therapeutic implications.

Mitochondrial-derived peptides (MDPs) are a novel class of bioactive microproteins that modify cell metabolism. The the eight MDPs that been characterized (e.g., humanin, MOTS-c, SHLPs1-6) attenuate disease pathology including Alzheimer's disease, prostate cancer, macular degeneration, cardiovascular disease, and diabetes. The association between disease and human genetic variation in MDPs is underexplored, although two polymorphisms in humanin and MOTS-c associate with cognitive decline and diabetes, respectively, suggesting a precise role for MDPs in disease-modification. There could be hundreds of additional MDPs that have yet to be discovered. Altogether, MDPs could explain unanswered biological and metabolic questions and are part of a growing field of novel microproteins encoded by small open reading frames. In this review, the current state of MDPs are summarized with an emphasis on biological and therapeutic implications.

Total Flavonoids of Bidens pilosa Ameliorates Bone Destruction in Collagen-Induced Arthritis.

Rheumatoid arthritis is a chronic autoimmune disease characterized by the infiltration of synovial inflammatory cells and progressive joint destruction. Total flavonoids of Bidens pilosa have been used against inflammation in rheumatoid arthritis, but its role in bone destruction remains to be explored. The aim of this paper was to study whether total flavonoids of B. pilosa relieve the severity of collagen-induced arthritis in rats, particularly whether it regulates the production of proinflammatory cytokines and the receptor activator of nuclear factor-κB/receptor activator of nuclear factor-κB ligand/osteoprotegerin signaling pathway. In this research, a collagen-induced disease model was induced in adult rats by subcutaneous injection of collagen II. Total flavonoids of B. pilosa at different doses (40, 80, and 160 mg/kg/d) were administered intragastrically, while methotrexate (1 mg/kg/w) was injected intraperitoneally as a positive control. Paw swelling, arthritis score, and body weight were assessed and evaluated. The severity of joint damage was determined using X-ray and confirmed by histopathology. The expression levels of receptor activator of nuclear factor-κB ligand, osteoprotegerin, IL-1ß, IL-17, and TNF in the serum and tissue were assayed using ELISA and immunohistochemistry. We found that total flavonoids of B. pilosa attenuated collagen-induced arthritis at the macroscopic level, and total flavonoids of B. pilosa-treated rats showed reduced paw swelling, arthritis scores, and X-ray appearance of collagen-induced arthritis in addition to improved histopathological results. These findings were consistent with reduced serum and tissue receptor activator of nuclear factor-κB ligand, TNF, IL-1ß, and IL-17 levels but increased osteoprotegerin levels. Our data suggest that total flavonoids of B. pilosa attenuate collagen-induced arthritis by suppressing the receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factor-κB/osteoprotegerin pathway and the subsequent production of proinflammatory cytokines. In addition, total flavonoids of B. pilosa may be a promising therapeutic candidate for the management of rheumatoid arthritis.

Research Progress on Molecular Markers Related to Unexplained Sudden Cardiac Death and Its Forensic Application. / ä¸æ˜ŽåŽŸå› å¿ƒè„æ€§çŒæ­»ç›¸å ³åˆ†å­æ ‡å¿—ç‰©ç ”ç©¶è¿›å±•åŠæ³•åŒ»å­¦åº”ç”¨.

Routine pathological examination of unexplained sudden cardiac death (USCD) lacks significant morphological characteristics. In the field of forensic medicine, molecular biology methods have been used to find the cause of death by detecting genes and research related to the mechanism of sudden cardiac death has been carried out. From the molecular pathology point of view, the application of multiple levels of biomarkers to resolve the causes of USCD has already shown potential and provides an important path for forensic identification of USCD. This article reviews the latest research progress on USCD-related genes, RNA, proteins and USCD, and summarizes forensic application.

Exploring the Mechanism of Icariin in Osteoporosis Based on a Network Pharmacology Strategy.

BACKGROUND With the aging of the world's population, the incidence of osteoporosis (OP) has become a public health problem of worldwide concern. Research shows that icariin may have a therapeutic effect on OP. MATERIAL AND METHODS PharmMapper was utilized to predict the potential targets of icariin. GeneCards and Online Mendelian Inheritance in Man (OMIM) were used for the collection of OP genes. The STRING database was utilized to obtain the protein-protein interaction (PPI) data. We used Cytoscape 3.7.2 to construct and analyze the networks. The genes and targets in the networks were input into the Database for Annotation, Visualization and Integrated Discovery (DAVID) to undergo Gene Ontology (GO) and pathway enrichment analysis. Finally, animal experiments were performed to verify the prediction results of this study. RESULTS A total of 297 icariin potential targets and 262 OP genes were obtained, and an icariin-OP PPI network was constructed and analyzed. The results of the GO enrichment analysis showed that icariin can regulate the steroid hormone-mediated signaling pathway, skeletal system development, extracellular space, cytosol, and steroid hormone receptor activity. The results of the pathway enrichment analysis showed that icariin can regulate osteoclast differentiation, FoxO, estrogen, and PPAR signaling pathways. The results of the experiments showed that icariin can increase estradiol, ß-catenin, and Receptor Activator of Nuclear Factor-к B Ligand (RANKL)/osteoprotegerin (OPG) ratio in postmenopausal OP rats (P<0.05). CONCLUSIONS This research found that the icariin can regulate OP-related biological processes, cell components, molecular functions, and signaling pathways.

[Establishment of concentration process and physical property parameter model of Carthami Flos extract based on quality by design].

To explore the potential of "physical property model" based on the concept of quality by design(QbD),during the application of process analysis technology(PAT) in the concentration process. The Carthami Flos was used as a model drug. Firstly, the total flavonoid retention rate and the hydroxysafflor yellow A(HSYA) retention rate of the concentrated solution were used as indicators to determine the concentration temperature range of the Carthami Flos extract. Then different concentrations were prepared at the optimal concentration temperature, and the corresponding viscosity(η) and electrical conductivity(σ) at different concentrations and temperatures were measured. Data processing software such as Excel, 1 stOpt, SPSS, and MATLAB were used to establish Carthami Flos extract's mathematical model of physical parameters: ρ-C, η-C, η-T, η-C-T, σ-T, σ-C-T. The results showed that the best concentration temperature of the Carthami Flos extract should not exceed 60 ℃, and the R~2 of the exponential equation and Arrhenius equation established based on physical parameters was all greater than 0.9, indicating that such model had better predictive ability. The mathematical model:η=14.465 1 exp(-0.019 8T+ 0.771 1C-0.058 3C~2), σ=4.061 0 + 0.004 3T +(-1.104 1 +0.950 9T)C-0.556 9TC~2 can be used to reflect the comprehensive effect of concentration and temperature on viscosity or conductance, laying foundation for the establishment of an online monitoring system for the viscosity or conductivity of the extraction liquid in the concentration step, rapid prediction of the concentration status, and control of the concentration endpoint. This study has initially proved the feasibility of using the physical property model as the core of the research idea in application of PAT for intelligent quality control of traditional Chinese medicine concentration links, providing a reference for the online intelligent monitoring of concentration steps of traditional Chinese medicine extracts.

Analyzing the interactions of mRNAs, miRNAs, lncRNAs and circRNAs to predict competing endogenous RNA networks in glioblastoma.

Cross-talk between competitive endogenous RNAs (ceRNAs) may play a critical role in revealing potential mechanisms of tumor development and physiology. Glioblastoma is the most common type of malignant primary brain tumor, and the mechanisms of tumor genesis and development in glioblastoma are unclear. Here, to investigate the role of non-coding RNAs and the ceRNA network in glioblastoma, we performed paired-end RNA sequencing and microarray analyses to obtain the expression profiles of mRNAs, lncRNAs, circRNAs and miRNAs. We identified that the expression of 501 lncRNAs, 1999 mRNAs, 2038 circRNAs and 143 miRNAs were often altered between glioblastoma and matched normal brain tissue. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed on these differentially expressed mRNAs and miRNA-mediated target genes of lncRNAs and circRNAs. Furthermore, we used a multi-step computational framework and several bioinformatics methods to construct a ceRNA network combining mRNAs, miRNAs, lncRNAs and circRNA, based on co-expression analysis between the differentially expressed RNAs. We identified that plenty of lncRNAs, CircRNAs and their downstream target genes in the ceRNA network are related to glutamatergic synapse, suggesting that glutamate metabolism is involved in glioma biological functions. Our results will accelerate the understanding of tumorigenesis, cancer progression and even therapeutic targeting in glioblastoma.

Activation of the mTOR signaling pathway in peritumoral tissues can cause glioma-associated seizures.

Epileptic seizures, the most common symptom accompanying glioma, are closely associated with tumor growth and patient quality of life. However, the association between glioma and glioma-related epilepsy is poorly understood. In fact, findings related to the location of epileptogenicity have been inconsistent in previous studies. We investigated seizure foci in patients with glioma and the corresponding association between glioma-related epilepsy and the tumoral and peritumoral microenvironment. Clinical characteristics, extracellular electrophysiology, immunohistochemistry, and western blots were conducted on 12 patients with glioma; nine patients had histories of preoperative seizures while three did not. Samples from included patients were used to identify seizure foci and mTOR pathway status. Electrophysiological recordings were conducted on 36 samples (tumor, peritumoral, and normal brain tissues) from 12 patients. Interictal-like discharges (ILDs) were observed in seven of nine peritumoral tissues obtained from patients with glioma that had experienced perioperative seizures. No ILDs were observed in any other sample groups. Western blots and immunohistochemistry for mTOR pathway proteins (mTOR and S6k) suggested that the mTOR pathway was activated in peritumoral tissues of patients with seizure history, but inactivated in patients without seizure history. Our results suggest that mTOR pathway expression in peritumoral tissues is associated with tumor-related seizures, thus providing a potential target for therapeutics aimed at simultaneously controlling gliomas and seizures.