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Objective: The purpose of this study is to investigate potential associations between osteopenia, osteosarcopenia, and postoperative outcomes in patients with hepatobiliary-pancreatic cancer (HBPC). Methods: Three online databases, including Embase, PubMed, and the Cochrane Library, were thoroughly searched for literature describing the relationship between osteopenia, osteosarcopenia, and outcomes of surgical treatment of HBPC patients from the start of each database to September 29, 2023. The Newcastle-Ottawa Scale was used to rate the quality of the studies. Results: This analysis included a total of 16 articles with a combined patient cohort of 2,599 individuals. The results demonstrated that HBPC patients with osteopenia had significantly inferior OS (HR: 2.27, 95% CI: 1.70-3.03, p < 0.001) and RFS (HR: 1.96, 95% CI: 1.42-2.71, p < 0.001) compared to those without osteopenia. Subgroup analysis demonstrated that these findings were consistent across univariate and multivariate analyses, as well as hepatocellular carcinoma, biliary tract cancer, and pancreatic cancer. The risk of postoperative major complications was significantly higher in patients with osteopenia compared to those without osteopenia (OR: 1.66, 95% CI: 1.19-2.33, p < 0.001). Besides, we also found that the presence of osteosarcopenia in HBPC patients was significantly related to poorer OS (HR: 3.31, 95% CI: 2.00-5.48, p < 0.001) and PFS (HR: 2.50, 95% CI: 1.62-3.84, p < 0.001) in comparison to those without osteosarcopenia. Conclusion: Preoperative osteopenia and osteosarcopenia can predict poorer OS and RFS with HBPC after surgery.
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BACKGROUND: Ethanol gas sensors are widely used in driving safety, security, and clinical respiratory monitoring applications. However, most ethanol sensors are large and exhibit poor stability owing to their integrated controller and high-temperature operation. Moreover, the development of wireless controller-free room-temperature ethanol sensors with long-term reliability is challenging. RESULTS: In this study, a wireless room-temperature ethanol gas antenna sensor was developed by combining a Cu radiation electrode with vertical graphene (VG) embedded with CuO@Cu nanoparticles and a polydimethylsiloxane (PDMS) dielectric substrate filled with cysteine (Cys). In the patch-antenna sensor, changes in the ethanol gas concentration resulted in frequency shift differences in the generation and transmission processes of the synchronized sensing signal. The VG-Cu/Cys-PDMS ethanol gas sensor had a detection range of 50-2100 ppm and a low limit of detection (LOD) of 0.112 ppm, with a response/recovery time of only 20/21 s for 1200 ppm ethanol, thus demonstrating superior long-term stability and satisfactory humidity tolerance. Therefore, the synergistic sensitization mechanism between the VG sensing/radiation layer and Cys-PDMS substrate was investigated. SIGNIFICANCE: This approach effectively addresses the issues of low-temperature operation, miniaturization, and long-term reliability. The proposed patch-antenna gas sensor is suitable for large-scale production owing to its use of industrial chemical vapor deposition technology and could be used to develop Internet-of-Things gas sensor nodes owing to its wireless propagation of electromagnetic waves with sensing information.
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Drug conjugates are obtained from tumor-located vectors connected to cytotoxic agents via linkers, which are designed to deliver hyper-toxic payloads directly to targeted cancer cells. These drug conjugates include antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs), small molecule-drug conjugates (SMDCs), nucleic acid aptamer-drug conjugates (ApDCs), and virus-like drug conjugate (VDCs), which show great therapeutic value in the clinic. Drug conjugates consist of a targeting carrier, a linker, and a payload. Payloads are key therapy components. Cytotoxic molecules and their derivatives derived from natural products are commonly used in the payload portion of conjugates. The ideal payload should have sufficient toxicity, stability, coupling sites, and the ability to be released under specific conditions to kill tumor cells. Microtubule protein inhibitors, DNA damage agents, and RNA inhibitors are common cytotoxic molecules. Among these conjugates, cytotoxic molecules of natural origin are summarized based on their mechanism of action, conformational relationships, and the discovery of new derivatives. This paper also mentions some cytotoxic molecules that have the potential to be payloads. It also summarizes the latest technologies and novel conjugates developed in recent years to overcome the shortcomings of ADCs, PDCs, SMDCs, ApDCs, and VDCs. In addition, this paper summarizes the clinical trials conducted on conjugates of these cytotoxic molecules over the last five years. It provides a reference for designing and developing safer and more efficient conjugates.
Subject(s)
Antineoplastic Agents , Biological Products , Immunoconjugates , Neoplasms , Humans , Neoplasms/drug therapy , Animals , Biological Products/therapeutic use , Biological Products/chemistry , Biological Products/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Immunoconjugates/therapeutic use , Immunoconjugates/chemistry , Immunoconjugates/pharmacologyABSTRACT
Increasing evidence suggests that vitamin D is one of the causes of accelerated development of Insulin Resistance (IR) and islet cell secret dysfunction. Numerous studies have shown that vitamin D can reduce inflammation, activate the transcription of the insulin receptors and related genes, and increase insulin-mediated glucose transport, thereby reducing IR. This article reviews the molecular mechanisms related to vitamin D deficiency and pancreatic ß-cell dysfunction in patients with Type 2 Diabetes (T2D).
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The presence of lincomycin (LIN) residues in food poses significant health risks to humans, necessitating a highly sensitive and specific detection method for LIN. This study used a self-enhancing Ti3C2-TiO2-Ru probe to develop an electrochemiluminescence aptasensor to detect LIN. The Ti3C2-TiO2 was synthesized in situ by harnessing the unique reducibility of Ti3C2, with TiO2 serving as a co-reaction accelerator. Moreover, Ti3C2-TiO2 served as a carrier with an excellent negative charge, allowing for the immobilization of a substantial amount of Ru(bpy)32+ through electrostatic adsorption, thus forming a self-enhancing Ti3C2-TiO2-Ru probe. Furthermore, the specific affinity of LIN toward the aptamer and the chelating interaction between the Ti and phosphate groups ensured highly precise LIN detection. This sensor demonstrated excellent performance, with a detection limit of 0.025 ng mL-1 and a detection range of 1.0 × 10-1-1.0 × 104 ng mL-1. The LIN detection in milk showed commendable recovery rates, ranging from 94.4% to 106.0%.
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Abrin toxin, highly dangerous with an estimated human lethal dose of 0.1-1 µg per kg body weight, has attracted much attention regarding criminal and terroristic misuse over the past decade. Therefore, developing a rapid detection method for abrin toxin is of great significance in the field of biosecurity. In this study, based on the specific dissociation method of an immobilized enzyme reactor, the trypsin immobilized reactor Fe3O4@CTS-GA-Try was prepared to replace free trypsin, and the immobilized enzyme digestion process was systematically investigated and optimized by using bovine serum albumin as the simulant of abrin. After 5 min one-step denaturation and reduction, a satisfactory peptide number and coverage were yielded with only 15 s assisted by an ultrasound probe to identify model proteins. Subsequently, abrin was rapidly digested using the established method, resulting in a stable and highly reproducible characteristic peptide number of 39, which can be analyzed by nanoelectrospray ionization coupled with high-resolution mass spectrometry. With the acquisition mode of full MS scan coupled with PRM, not only MS spectroscopy of total abrin peptides but also the corresponding MS/MS spectroscopy of specific abrin peptides can achieve the characteristic detection of abrin toxin and its different isoforms in less than 10 minutes, with high repeatability. This assay provides a universal platform and has great potential for the development of on-site detection and rapid mass spectrometric analysis techniques for macromolecular protein toxins and can further be applied to the integrated detection of chemical and biological agents.
Subject(s)
Abrin , Enzymes, Immobilized , Serum Albumin, Bovine , Trypsin , Abrin/analysis , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Trypsin/metabolism , Trypsin/chemistry , Serum Albumin, Bovine/chemistry , Animals , Cattle , Tandem Mass Spectrometry/methods , Spectrometry, Mass, Electrospray Ionization/methods , ProteolysisABSTRACT
Inflammatory bowel diseases (IBDs) are prevalent and debilitating diseases with limited clinical treatment strategies. Mesenchymal stem cell (MSCs) are pluripotent stem cells with self-renewal capability and multiple immunomodulatory effects, which make them a promising therapeutic approach for IBDs. Thus, optimization of MSCs regimes is crucial for their further clinical application. Wogonin, a flavonoid-like compound with extensive immunomodulatory and adjuvant effects, has been investigated as a potential pretreatment for MSCs in IBD treatment. In this study, we employed the DSS-induced acute colitis mouse model to compare the therapeutic effectiveness of MSCs in pretreated with or without wogonin and further explore the underlying mechanism. Compared to untreated MSCs, MSCwogonin (pretreated with wogonin) showed greater effectiveness in the treatment of colitis. Further experiments revealed that wogonin treatment activated the AKT signaling pathway, resulting in higher cellular glycolysis. Inhibition of AKT phosphorylation by perifosine not only decreased glycolysis but impaired the therapeutic efficiency of MSCwogonin. Consistent with these results, qPCR data indicated that wogonin treatment induced the expression of immunomodulatory molecules IL-10, IDO, and AGR1, which were reduced by perifosine. Together, our data demonstrated that wogonin preconditioning strategy further augmented the therapeutic efficacy of MSCs via promoting glycolysis, which should be a promising strategy for optimizing MSCs therapy in IBDs.
Subject(s)
Colitis , Flavanones , Glycolysis , Mesenchymal Stem Cells , Mice, Inbred C57BL , Animals , Flavanones/pharmacology , Flavanones/administration & dosage , Mice , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Colitis/drug therapy , Colitis/chemically induced , Glycolysis/drug effects , Disease Models, Animal , Mesenchymal Stem Cell Transplantation/methods , Male , Signal Transduction/drug effects , Dextran SulfateABSTRACT
Currently, the microwave absorbers usually suffer dreadful electromagnetic wave absorption (EMWA) performance damping at elevated temperature due to impedance mismatching induced by increased conduction loss. Consequently, the development of high-performance EMWA materials with good impedance matching and strong loss ability in wide temperature spectrum has emerged as a top priority. Herein, due to the high melting point, good electrical conductivity, excellent environmental stability, EM coupling effect, and abundant interfaces of titanium nitride (TiN) nanotubes, they were designed based on the controlling kinetic diffusion procedure and Ostwald ripening process. Benefiting from boosted heterogeneous interfaces between TiN nanotubes and polydimethylsiloxane (PDMS), enhanced polarization loss relaxations were created, which could not only improve the depletion efficiency of EMWA, but also contribute to the optimized impedance matching at elevated temperature. Therefore, the TiN nanotubes/PDMS composite showed excellent EMWA performances at varied temperature (298-573 K), while achieved an effective absorption bandwidth (EAB) value of 3.23 GHz and a minimum reflection loss (RLmin) value of - 44.15 dB at 423 K. This study not only clarifies the relationship between dielectric loss capacity (conduction loss and polarization loss) and temperature, but also breaks new ground for EM absorbers in wide temperature spectrum based on interface engineering.
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BACKGROUND: This meta-analysis aimed to systematically summarize the association between cancer risks and glutathione s-transferases (GSTs) among smokers and drinkers. METHODS: Literature was searched through PubMed, Web of Science, CNKI, and WANFANG published from 2001 to 2022. Stata was used with fixed-effect model or random-effect model to calculate pooled odds ratios (ORs) and the 95% confidence interval (95% CI). Sensitivity and heterogeneity calculations were performed, and publication bias was analyzed by Begg and Egger's test. Regression analysis was performed on the correlated variables about heterogeneity, and the false-positive report probabilities (FPRP) and the Bayesian False Discovery Probability (BFDP) were calculated to assess the confidence of a statistically significant association. RESULTS: A total of 85 studies were eligible for GSTs and cancer with smoking status (19,604 cases and 23,710 controls), including 14 articles referring to drinking status (4409 cases and 5645 controls). GSTM1-null had significant associations with cancer risks (for smokers: ORâ =â 1.347, 95% CI: 1.196-1.516, Pâ <â .001; for nonsmokers: ORâ =â 1.423, 95% CI: 1.270-1.594, Pâ <â .001; for drinkers: ORâ =â 1.748, 95% CI: 1.093-2.797, Pâ =â .02). GSTT1-null had significant associations with cancer risks (for smokers: ORâ =â 1.356, 95% CI: 1.114-1.651, Pâ =â .002; for nonsmokers: ORâ =â 1.103, 95% CI: 1.011-1.204, Pâ =â .028; for drinkers: ORâ =â 1.423, 95% CI: 1.042-1.942, Pâ =â .026; for nondrinkers: ORâ =â 1.458, 95% CI: 1.014-2.098, Pâ =â .042). Negative associations were found between GSTP1rs1695(AGâ +â GG/AA) and cancer risks among nondrinkers (ORâ =â 0.840, 95% CI: 0.711-0.985, Pâ =â .032). CONCLUSIONS: GSTM1-null and GSTT1-null might be related cancers in combination with smoking or drinking, and GSTP1rs1695 might be associated with cancers among drinkers.
Subject(s)
Glutathione S-Transferase pi , Neoplasms , Humans , Glutathione S-Transferase pi/genetics , Bayes Theorem , Genetic Predisposition to Disease , Glutathione Transferase/genetics , Smoking/adverse effects , Neoplasms/etiology , Neoplasms/genetics , Glutathione , Risk Factors , Genotype , Case-Control StudiesABSTRACT
BACKGROUND: Mogroside V (MV), a triterpene glycoside, exhibits diverse biological functions. However, its ability to promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) under diabetic conditions is yet to be elucidated. OBJECTIVE: To study the regulation of osteogenic differentiation of BMSCs in diabetic mice by MV and determine the potential mechanism. METHODS: BMSCs were isolated from both normal (referred to as N-BMSCs) and diabetic (referred to as DM-BMSCs) C57BL/6 mice. DM-BMSCs were treated with different concentrations of MV for varying durations, and cell viability was detected using the cell counting kit-8 assay. Following 2 weeks of osteogenic induction, osteogenic differentiation capability was evaluated using alizarin red S staining, alkaline phosphatase (ALP) activity analysis, and quantitative real-time reverse transcription polymerase chain reaction. Furthermore, the microRNA (miRNA) expression profiles of N-BMSCs, DM-BMSCs, and DM-BMSCs treated with MV were tested using high-throughput sequencing. RESULTS: Treatment with MV enhanced the viability of DM-BMSCs and mitigated the reduction of calcium nodule deposition, ALP activity, and mRNA expression of ALP, osteocalcin, and runt-related transcription factor 2. Of the analyzed miRNAs, miR-10b-5p was the only one that exhibited differential expression in N-BMSCs, DM-BMSCs, and DM-BMSCs treated with MV. An analysis of the top four protein clusters based on KEGG suggested that the target genes of differentially expressed miRNAs were closely linked to the PI3K/AKT pathway. CONCLUSION: MV significantly enhances the viability and osteogenic differentiation of BMSCs under diabetic conditions. The alteration of miRNA profiles provides a foundation for further research into the regulatory role of miRNAs and MV in this process.
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Ultrasound tomography is an emerging imaging modality that uses the transmission of ultrasound through tissue to reconstruct images of its mechanical properties. Initially, ray-based methods were used to reconstruct these images, but their inability to account for diffraction often resulted in poor resolution. Waveform inversion overcame this limitation, providing high-resolution images of the tissue. Most clinical implementations, often directed at breast cancer imaging, currently rely on a frequency-domain waveform inversion to reduce computation time. For ring arrays, ray tomography was long considered a necessary step prior to waveform inversion in order to avoid cycle skipping. However, in this paper, we demonstrate that frequency-domain waveform inversion can reliably reconstruct high-resolution images of sound speed and attenuation without relying on ray tomography to provide an initial model. We provide a detailed description of our frequency-domain waveform inversion algorithm with open-source code and data that we make publicly available.
Subject(s)
Algorithms , Image Processing, Computer-Assisted , Phantoms, Imaging , Ultrasonography , Ultrasonography/methods , Image Processing, Computer-Assisted/methods , Humans , Tomography/methodsABSTRACT
In this study, a microelectrode array sensor based on boron and nitrogen co-doped vertical graphene (BNVG) was assembled to quantify salicylic acid (SA) in living plants. The influence of B and N contents on the electrochemical reaction kinetics and SA response signal was investigated. A microneedle sensor with three optimized BNVG microelectrodes (3.57 at.% B and 3.27 at.% N) was used to quantitatively analyze SA in the 0.5-100 µM concentration range and pH 4.0-9.0, with limits of detection of 0.14-0.18 µM. Additionally, a quantitative electrochemical model database based on the BNVG microelectrode sensor was constructed to monitor the growth of cucumbers and cauliflowers, which confirmed that the SA level and plant growth rate were positively correlated. Moreover, the SA levels in various vegetables and fruits purchased from the market were measured to demonstrate the practical application prospects for on-site inspection and evaluation.
Subject(s)
Boron , Electrochemical Techniques , Fruit , Graphite , Microelectrodes , Nitrogen , Salicylic Acid , Vegetables , Graphite/chemistry , Salicylic Acid/analysis , Vegetables/chemistry , Fruit/chemistry , Electrochemical Techniques/instrumentation , Boron/chemistry , Nitrogen/analysis , Needles , Cucumis sativus/chemistry , Biosensing Techniques/instrumentation , Limit of DetectionABSTRACT
Gestational Diabetes Mellitus (GDM) is a common endocrine condition associated with adverse pregnancy outcomes. In recent years, a growing number of risk factors associated with gestational diabetes mellitus have been defined. GDM poses a serious threat to maternal health. The etiology is complex and multifactorial and can be divided into inherent and modifiable factors. The inherent factors have been described in other literature, while the modifiable factors are mainly the risk of lifestyle habits. In this study, we performed a narrative review of the progress of risk factors associated with gestational diabetes mellitus.
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Detoxification of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) with high efficiency and dynamic performance is challenging for a polymeric catalyst. Herein, a series of conjugated microporous polyanilines (CMPAs), capable of efficiently catalytically reducing 4-NP, were synthesized based on the Buchwald-Hartwig cross-coupling reaction mechanism. By adjusting the types of linkers and the molar ratios of linker to core, CMPAs with different Brunauer-Emmett-Teller (BET) specific surface areas and reduction degrees were obtained and used as the catalysts in reducing 4-NP. The ultrahigh catalytic reduction efficiency (K = 141.32 s-1 g-1, kapp = 0.00353 s-1) was achieved when using CMPA-3-0.7 as the catalyst (prepared with 4,4'-diaminodiphenylamine as the linker and a 0.7:1 molar ratio of linker to core). The catalytic reduction performance exhibited a strong correlation with the reduction degree and BET specific surface area of CMPAs. Furthermore, they also exhibit excellent cycling stability and dynamic performance. The coexistence of a microporous structure and high BET specific surface area endowed CMPAs with an increased number of catalytic active centers. The reversible redox transformation of CMPAs in the presence of NaBH4 and air enabled self-healing (the oxidation units in CMPAs were reduced to reduction units by NaBH4, and the newly generated reduction unit in CMPAs was subsequently oxidized to its original state by the O2 in the air), leading to the reduction reaction of 4-NP proceeded continuously and stably. The aforementioned factors resulted in the high efficiency of CMPAs for reducing 4-NP to 4-AP, enhancing the practical application prospects of CMPAs in the detoxification of 4-NP wastewater.
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Rapid and accurate on-site detection of chemical warfare agents (CWAs) could defend military and civilian populations against current and emerging chemical weapons. With the development of ambient ionization and linear ion trap technology, the rapid and accurate quantitative determination method of CWAs based on direct ionization and multistage mass spectrometry has attracted widespread attention. In this study, a microliter electrospray ionization-miniature linear ion trap mass spectrometry (LIT-MS) instrument was designed and constructed, and the effects of quadrupole enhanced dipole resonance excitation on the resolution and sensitivity were investigated; consequently, the parameters of CWAs detection were optimized. Based on the broad time-frequency ion excitation technology, accurate multiple reaction monitoring (MRM) quantitative analysis of DMMP (G-series agent simulants, m/z 125 â m/z 93) was obtained. The linear correlation coefficient in the concentration range of 1 to 20 µg/mL could reach 99.02%, and the relative standard deviations (RSD) of continuous repeatability, interday repeatability, and intraday repeatability were all less than 10%. The results showed that the accurate pseudo-MRM detection method based on miniature linear ion trap mass spectrometry for CWAs detection was feasible.
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BACKGROUND AND PURPOSE: To develop a computed tomography (CT)-based deep learning model to predict overall survival (OS) among small-cell lung cancer (SCLC) patients and identify patients who could benefit from prophylactic cranial irradiation (PCI) based on OS signature risk stratification. MATERIALS AND METHODS: This study retrospectively included 556 SCLC patients from three medical centers. The training, internal validation, and external validation cohorts comprised 309, 133, and 114 patients, respectively. The OS signature was built using a unified fully connected neural network. A deep learning model was developed based on the OS signature. Clinical and combined models were developed and compared with a deep learning model. Additionally, the benefits of PCI were evaluated after stratification using an OS signature. RESULTS: Within the internal and external validation cohorts, the deep learning model (concordance index [C-index] 0.745, 0.733) was far superior to the clinical model (C-index: 0.635, 0.630) in predicting OS, but slightly worse than the combined model (C-index: 0.771, 0.770). Additionally, the deep learning model had excellent calibration, clinical usefulness, and improved accuracy in classifying survival outcomes. Remarkably, patients at high risk had a survival benefit from PCI in both the limited and extensive stages (all P < 0.05), whereas no significant association was observed in patients at low risk. CONCLUSIONS: The CT-based deep learning model exhibited promising performance in predicting the OS of SCLC patients. The OS signature may aid in individualized treatment planning to select patients who may benefit from PCI.
Subject(s)
Cranial Irradiation , Deep Learning , Lung Neoplasms , Small Cell Lung Carcinoma , Tomography, X-Ray Computed , Humans , Small Cell Lung Carcinoma/radiotherapy , Small Cell Lung Carcinoma/mortality , Small Cell Lung Carcinoma/diagnostic imaging , Small Cell Lung Carcinoma/pathology , Lung Neoplasms/radiotherapy , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/diagnostic imaging , Retrospective Studies , Male , Female , Tomography, X-Ray Computed/methods , Middle Aged , Cranial Irradiation/methods , Aged , Survival RateABSTRACT
Polysaccharides are employed to modify proteins, forming complexes that enhance the functional properties of proteins, such as emulsification and stability. In this study, myofibrillar protein (MP)-chitosan (CS) complexes were formed between CS and MP under acidic conditions (pH 3.0-6.0). Results showed that CS can improve the solubility and emulsifying properties of MP, and the MP-CS complexes at pH 3.0 and 6.0 had better emulsifying properties. Concurrently, the particle size results indicated that better the emulsifying properties of the complex, the smaller the particle size. Consequently, the characteristics of the MP-CS complexes (at pH 3.0 and 6.0) were investigated. Our analysis using Fourier transform infrared spectroscopy revealed that the amide I band of MP was blue-shifted with the addition of CS, signifying a decrease in hydrogen bonding within MP. The endogenous fluorescence spectra showcased that the hydrophobicity surrounding the tryptophan residues in the protein changed, leading to enhanced polarity. Thermogravimetric analysis and differential scanning calorimetry further confirmed that the addition of CS improved the thermal stability of MP. These findings provide valuable insights into the interactions between MP and CS. Furthermore, the MP-CS complex can be leveraged to create a Pickering emulsion system for the efficient delivery of bioactive substances.
Subject(s)
Chitosan , Chitosan/chemistry , Polysaccharides , Emulsions/chemistry , Particle SizeABSTRACT
BACKGROUND: Mogroside V (MV) has anti-inflammatory properties. However, its impact on macrophage polarization under diabetic condition is yet unclear. This study aimed to investigate effects and underlying mechanisms of MV on inflammatory response and M1 polarization of bone marrow-derived macrophages (BMDMs) from diabetic mice. METHODS: BMDMs were isolated from normal and diabetic C57BL/6 mice. LPS and IFN-γwere used to produce M1-polarized BMDMs. MV treatment was administered throughout the M1 polarization process with or without SB203580 or PDTC. Surface markers CD11b, F4/80 and CD86 of macrophages were identified using flow cytometry or immunofluorescence staining. Inflammatory cytokines IL-1ß and IL-6 and phosphorylation levels of p65 and p38 were examined by western blot. RESULTS: High glucose increased proportion of CD11b+F4/80+CD86+ cells, protein levels of inflammatory cytokines IL-1ß and IL-6 and phosphorylation levels of p65 and p38 in LPS+IFN-γ-induced BMDMs, while they were decreased upon MV treatment. Additionally, these effects were further downregulated when MV was co-added with SB203580 or PDTC. CONCLUSIONS: MV suppressed M1 macrophage polarization and inflammatory response, which was partially through NF-κB and p38 MAPK in LPS+IFN-γ induced BMDMs under high glucose condition, implying the potential of MV in treatment for inflammatory complications of diabetes.
Subject(s)
Diabetes Mellitus, Experimental , Macrophages , Mice, Inbred C57BL , NF-kappa B , Signal Transduction , p38 Mitogen-Activated Protein Kinases , Animals , p38 Mitogen-Activated Protein Kinases/metabolism , Macrophages/immunology , Macrophages/metabolism , Macrophages/drug effects , Mice , NF-kappa B/metabolism , Signal Transduction/drug effects , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Male , Triterpenes/pharmacology , Anti-Inflammatory Agents/pharmacology , Cells, Cultured , Inflammation/drug therapy , Inflammation/metabolism , Macrophage Activation/drug effects , Cytokines/metabolism , Lipopolysaccharides/immunologyABSTRACT
BACKGROUND: Long non-coding RNAs (lncRNAs) play a critical role in the development of ovarian cancer (OC). OBJECTIVE: The study aimed to determine the role of LncRNA LINC01123 in OC bio-progression, which is upregulated in OC tissues during OC progression. METHODS: Bioinformatics methods, GEPIA, and qRT-PCR were used to reveal the level and correlation of LINC01123, hsa-miR-516b-5p, and VEGFA, in OC cell lines. MTT, EdU, TUNEL, and Transwell assays were performed to assess the bioactivity of OC cell. Target sites of LINC01123 and hsa-miR-516b-5p were predicted using Starbase, and the potential linkage points of VEGFA and hsa-miR-516b-5p were predicted using TargetScan. These sites and linkage points were confirmed by double luciferase reporter assay. RESULTS: LINC01123 was upregulated in OC cell lines and LINC01123 silencing suppressed the proliferation and metastasis of OC cells, but promoted cell apoptosis. hsa-miR-516b-5p was linked to LINC01123 and. VEGFA was downstream of hsa-miR-516b-5p. Importantly, silencing of hsa-miR-516b-5p reversed the inhibitory impact of si-LINC01123. The result of hsa-miR-516b-5p inhibitor + si-LINC01123 co-transfection were rescued by si-VEGFA. CONCLUSION: LINC01123 promotes OC development by dampening miR-516b-5p function, and may be a novel target for treating OC.
Subject(s)
MicroRNAs , Ovarian Neoplasms , RNA, Long Noncoding , Female , Humans , RNA, Long Noncoding/genetics , Ovarian Neoplasms/genetics , Apoptosis/genetics , Cell Line , MicroRNAs/genetics , Vascular Endothelial Growth Factor A/geneticsABSTRACT
Ferroptosis is an iron-dependent death mode mediated by the aggregation of lipid peroxides and lipid-reactive oxygen species. It is characterized by iron-dependent lipid peroxide accumulation accompanied by oxidoreductase deficiency. Pancreatic beta cell dysfunction and insulin resistance are two major causes of type 2 diabetes mellitus (T2DM). Iron accumulation and metabolism may play a role in the development of T2DM. The molecular mechanism of ß cell apoptosis and iron death in T2DM were reviewed. In addition, we discuss recent insights on the relationship between the trace element iron and apoptosis of ß cells in T2DM.