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Seven new polyketides including three chromone derivatives (1-3) and four linear ones incorporating a tetrahydrofuran ring (4-7), along with three known compounds (8-10), were obtained from the fermentation of an endophytic fungus (Chaetomium sp. UJN-EF006) isolated from the leaves of Vaccinium bracteatum. The structures of these fungal metabolites have been elucidated by spectroscopic means including MS, NMR and electronic circular dichroism. A preliminary anti-inflammatory screening with the lipopolysaccharide (LPS) induced RAW264.7â cell model revealed moderate NO production inhibitory activity for compounds 1 and 4. In addition, the expression of three LPS-induced inflammatory factors IL-6, iNOS and COX-2 was also blocked by 1 and 4.
Subject(s)
Chaetomium , Polyketides , Vaccinium myrtillus , Chaetomium/chemistry , Polyketides/chemistry , Lipopolysaccharides/pharmacology , Molecular StructureABSTRACT
The incidence of thyroid cancer (TC) has been increasing over the last 50 years worldwide. A higher rate of overdiagnosis in indolent thyroid lesions has resulted in unnecessary treatment. An accurate detection of TC at an early stage is highly demanded. We aim to develop an enhanced isobaric labeling-based high-throughput plasma quantitative proteomics to identify biomarkers in a discovery cohort. Selected candidates were tested by enzyme-linked immunosorbent assay (ELISA) in the training cohort and validation cohort. In total, 1063 proteins were quantified, and 129 proteins were differentially expressed between patients and healthy subjects. Serum levels of ISG15 and PLXNB2 were significantly elevated in patients with papillary thyroid cancer (PTC) or thyroid adenoma, compared to healthy subjects (p < 0.001) and patients with nodular goiter (p < 0.001). Receiver operating characteristic (ROC) analysis of combined markers (ISG15 and PLXNB2) significantly distinguished PTC from healthy control (HC) subjects. Similar differentiations were also found between thyroid adenoma and HC subjects. Notably, this combined marker could distinguish stage-I PTC from HC subjects (area under the curve (AUC) = 0.872). Our results revealed that ISG15 and PLXNB2 are independent diagnostic biomarkers for PTC and thyroid adenoma, showing a promising value for the early detection of PTC.
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BACKGROUND: The randomized trials which include ACOSOG Z0011 and IBCSG 23-01 had found that the survival rates were not different in patients with cT1/2N0 and 1-2 sentinel lymph node (SLN)-positive, macro/micrometastases who underwent breast-conserving therapy, and micrometastases who underwent total mastectomy (TM), when axillary lymph node dissection (ALND) was omitted. However, for patients with cT1/2N0 and 1-2 SLN macrometastases who underwent TM; there was still insufficient evidence from clinical studies to support whether ALND can be exempted. This study aimed to investigate the risk factors of non-sentinel lymph node (nSLN) metastasis in breast cancer patients with 1-2 SLN macrometastases undergoing TM. METHODS: The clinicopathological data of 1491 breast cancer patients who underwent TM and SLNB from January 2017 to February 2022 were retrospectively analyzed. Univariate and multivariate analyses were performed to analyze the risk factors for nSLN metastasis. RESULTS: A total of 273 patients with 1-2 SLN macrometastases who underwent TM were enrolled. Postoperative pathological data showed that 35.2% patients had nSLN metastasis. The results of multivariate analysis indicated that tumor size (TS) (P = 0.002; OR: 1.051; 95% CI: 1.019-1.084) and ratio of SLN macrometastases (P = 0.0001; OR: 12.597: 95% CI: 4.302-36.890) were the independent risk factors for nSLN metastasis in breast cancer patients with 1-2 SLN macrometastases that underwent TM. The ROC curve analysis suggested that when TS ≤22 mm and ratio of SLN macrometastases ≤0.33, the incidence of nSLN metastasis could be reduced to 17.1%. CONCLUSIONS: The breast cancer patients with cT1/2N0 stage, undergoing TM and 1-2 SLN macrometastases, when the TS ≤22 mm and macrometastatic SLN does not exceed 1/3 of the total number of detected SLN, the incidence of nSLN metastasis is significantly reduced, but whether ALND can be exempted needs further exploration.
Subject(s)
Breast Neoplasms , Sentinel Lymph Node , Humans , Female , Breast Neoplasms/pathology , Sentinel Lymph Node Biopsy/methods , Lymphatic Metastasis/pathology , Case-Control Studies , Mastectomy, Simple , Retrospective Studies , Neoplasm Micrometastasis/pathology , Mastectomy , Axilla/pathology , Sentinel Lymph Node/surgery , Sentinel Lymph Node/pathology , Lymph Node Excision/methods , Risk Factors , Lymph Nodes/surgery , Lymph Nodes/pathologyABSTRACT
Chemical fractionation of the AcOEt partition, generated from the EtOH extract of the fruits of Schisandra chinensis, afforded a series of sesquiterpenyl constituents including two new cadinanes, a new eudesmane, two new widdranes (a handling artefact and a new natural product), a new bisabolane and two new natural cuparane enantiomers, along with 15 known structurally related analogs. Structures of the new compounds were unambiguously characterized by interpretation of detailed spectroscopic data including ESI-MS and 1D/2D NMR, with their absolute configurations being established by electronic circular dichroism (ECD) calculation and induced ECD experiment. The inhibitory effects of all the isolates against α-glucosidase and lipopolysaccharide (LPS) induced nitric oxide (NO) production in murine RAW264.7 macrophages, as well as their antibacterial and cytotoxic potential, were evaluated, with selective compounds showing moderate α-glucosidase and NO inhibitory activity. Notably, canangaterpene III exhibited the most significant NO inhibitory effect with an IC50 value of 31.50±1.49â µM.
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BACKGROUND: The development of morphine tolerance is a clinical challenge for managing severe pain. Studies have shown that neuroinflammation is a critical aspect for the development of analgesic tolerance. We found that AMPK-autophagy activation could suppress neuroinflammation and improve morphine tolerance via the upregulation of suppressor of cytokine signaling 3 (SOCS3) by inhibiting the processing and maturation of microRNA-30a-5p. METHODS: CD-1 mice were utilized for the tail-flick test to evaluate morphine tolerance. The microglial cell line BV-2 was utilized to investigate the mechanism of AMPK-autophagy-mediated posttranscriptional regulation of SOCS3. Proinflammatory cytokines were measured by western blotting and real-time PCR. The levels of SOCS3 and miRNA-processing enzymes were evaluated by western blotting, real-time PCR and immunofluorescence staining. RESULTS: Based on experimental verification, miRNA-30a-5p could negatively regulate SOCS3. The AMPK activators AICAR, resveratrol and metformin downregulated miRNA-30a-5p. We found that AMPK activators specifically inhibited the processing and maturation of miRNA-30a-5p in microglia by degrading DICER and AGO2 via autophagy. Furthermore, a miRNA-30a-5p inhibitor significantly improved morphine tolerance via upregulation of SCOS3 in mice. It markedly increased the level of SOCS3 in the spinal cord of mice and subsequently inhibited morphine-induced phosphorylation of NF-κB p65. In addition, a miRNA-30a-5p inhibitor decreased the levels of IL-1ß and TNF-α caused by morphine in microglia. CONCLUSION: AMPK-autophagy activation suppresses neuroinflammation and improves morphine tolerance via the upregulation of SOCS3 by inhibiting miRNA-30a-5p.
Subject(s)
MicroRNAs , Morphine , AMP-Activated Protein Kinases/metabolism , Autophagy , Humans , MicroRNAs/metabolism , Morphine/pharmacology , Neuroinflammatory Diseases , Suppressor of Cytokine Signaling 3 Protein/genetics , Suppressor of Cytokine Signaling 3 Protein/metabolismABSTRACT
OBJECTIVE: This study aimed to compare the diagnostic performance of vital touch tissue quantification (VTQ) and virtual touch tissue imaging quantification (VTIQ) in diagnosing infants with biliary atresia (BA) from jaundiced infants. METHODS: In this study, 26 jaundiced infants with BA, 33 jaundiced infants without BA, and 40 normal infants were enrolled. The hepatic shear wave velocity (SWV) of each infant was determined by VTQ and VTIQ examinations, respectively. Then, the receiver operating characteristic (ROC) curves were drawn and the area under the curve (AUC) and optimal cut-off values were calculated to evaluate the sensitivities and specificities of VTIQ and VTQ for BA. RESULTS: The mean values of SWV of the control group measured by VTQ and VTIQ were (1.09 ± 0.18) m/s and (1.36 ± 0.21) m/s, respectively. The mean values of SWV of the non-BA group measured by VTQ and VTIQ were (1.30 ± 0.28) m/s and (1.52 ± 0.29) m/s, respectively. The mean values of SWV of the BA group measured by VTQ and VTIQ were (2.36 ± 0.36) m/s and (2.43 ± 0.29) m/s, respectively. The diagnostic threshold of VTQ and VTIQ to diagnose BA was 1.77 and 1.92 m/s. The sensitivities of VTQ and VTIQ to diagnose BA were 90.9% and 95.5%. The specificities of VTQ and VTIQ to diagnose BA were 68.4% and 78.9%. CONCLUSION: Vital touch tissue quantification and VTIQ could help distinguish infants with BA from jaundiced infants by measuring the liver SWV values. VTIQ has higher sensitivity and specificity than VTQ.
Subject(s)
Biliary Atresia , Elasticity Imaging Techniques , Biliary Atresia/diagnostic imaging , Diagnosis, Differential , Humans , Infant , Liver/diagnostic imaging , ROC Curve , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
Microhaplotype loci (microhaplotype, MHs), defined by two or more closely linked single nucleotide polymorphisms, are a type of molecular marker within a short segment of DNA. As emerging forensic genetic markers, MHs have no stutter artefacts and higher polymorphism, and permit the design of smaller amplicons. In order to identify the markers from a genome wide perspective and explore their potential application further, we constructed the most comprehensive MH dataset to date, based on the whole genome sequencing data of 105 Han individuals in Southern China from 1000 Genomes Project. The results showed that there were 9,490,075 MH loci in the range of 350 bp in the human genome, and the distribution density of microhaplotypes suggests gene variation. Polymorphism analysis of MHs from various base spans showed that the polymorphism of MHs could reach or exceed common short tandem repeat sites. In addition, based on their flexible assembly, a scheme to build the public database of microhaplotypes was proposed.
Subject(s)
DNA Fingerprinting , High-Throughput Nucleotide Sequencing , China , Forensic Genetics , Gene Frequency , Genetics, Population , Genomics , Haplotypes , Humans , Microsatellite Repeats , Polymorphism, Single Nucleotide/geneticsABSTRACT
BACKGROUND: Numerous studies have shown the detrimental effects of overt hyperthyroidism on sexual functioning but a quantitative result has not yet been synthesized. AIM: To conduct a systematic review and meta-analysis that quantifies the association between overt hyperthyroidism and the risk of sexual dysfunction (SD). METHODS: A meta-analysis of studies in the literature published prior to February 1, 2020, from 4 electronic databases (MEDLINE, Embase, Cochrane Library databases, and PsychINFO) was conducted. All analyses were performed using the random-effects model comparing individuals with and without overt hyperthyroidism. OUTCOMES: The strength of the association between overt hyperthyroidism and risk of SD was quantified by calculating the relative risk (RR) and the standard mean difierences with 95% CI. The quality of evidence for the reported outcome was based on the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Of 571 publications, a total of 7 studies involving 323,257 individuals were included. Synthetic results from 7 eligible studies indicated that overt hyperthyroidism led to significant SD in both sexes (pooled RR = 2.59, 95% CI: 1.3-5.17, P = .007; heterogeneity: I2 = 98.8%, P < .001). When we analyzed the data of men and women independently, the pooled results consistently showed that men and women with overt hyperthyroidism were at over 2-fold higher risk of SD than the general populations (RR for males = 2.59, 95% CI: 1.03-6.52, P = .044; RR for females = 2.51, 95% CI: 1.47-4.28, P = .001). Combined standard mean diffierences from those studies providing the Female Sexual Function Index (FSFI) suggested that women with overt hyperthyroidism were associated with a significantly lower FSFI value in FSFI total scores, subscale sexual arousal, lubrication, orgasm, and satisfaction domain (all P < .05). The overall quality of evidence in our study was considered to be moderate. CLINICAL IMPLICATIONS: Clinicians should know the detrimental effects of overt hyperthyroidism on sexual functioning in clinical practice. Measurement of thyroid hormones should be included in the assessment of patients presenting with SD when they show symptoms of clinical hyperthyroidism. STRENGTHS & LIMITATIONS: This is the first meta-analysis quantifying the relationship between overt hyperthyroidism and the risks of SD. However, the combined results were derived from limited retrospective studies along with substantial heterogeneities. CONCLUSION: Our study has confirmed the potentially devastating sexual health consequences caused by overt hyperthyroidism. However, additional rigorous studies with sizable samples are still needed to better elucidate this evidence. Pan Y, Xie Q, Zhang Z, et al. Association Between Overt Hyperthyroidism and Risk of Sexual Dysfunction in Both Sexes: A Systematic Review and Meta-Analysis. J Sex Med 2020;17:2198-2207.
Subject(s)
Hyperthyroidism , Sexual Dysfunction, Physiological , Female , Humans , Hyperthyroidism/complications , Hyperthyroidism/epidemiology , Male , Orgasm , Retrospective Studies , Sexual Behavior , Sexual Dysfunction, Physiological/epidemiology , Sexual Dysfunction, Physiological/etiologyABSTRACT
This meta-analysis aims to determine whether autologous fat grafting (AFG) affects the risk of local-regional recurrence (LRR) in breast cancer patients. In pooled analyses of 11 eligible studies, AFG was not associated with increased LRR. Subgroup analyses showed that AFG did not increase the risk of LRR in patients undergoing breast-conserving surgery or mastectomy, in patients with in situ carcinomas or invasive carcinomas, or in patients undergoing postoperative radiotherapy.
Subject(s)
Adipose Tissue/transplantation , Breast Neoplasms/surgery , Neoplasm Recurrence, Local/etiology , Postoperative Complications , Female , Humans , Transplantation, AutologousABSTRACT
Fluoride (sodium fluoride) is thought to be essential in the development of tooth, and research shows that fluoride can modulate the differentiation of dental stem cells. However, the effects of fluoride on the committed differentiation of stem cells from apical papilla (SCAPs) and the underlying mechanisms remain unclear. Here, SCAPs were isolated from healthy extracted human third molars with immature roots and then were cultured with NaF conditioned media. Cell Counting Kit-8, EdU staining, and flow cytometry were performed to detected the proliferation activity. Alkaline phosphatase (ALP) activity, Alizarin Red staining, Western blot assay, and real-time reverse-transcription polymerase chain reaction were applied to assess the osteo/odontogenic differentiation NaF-treated SCAPs. Western blot assay and transmission electron microscope were used to evaluate the autophagy involved in the differentiation of SCAPs. ALP activity, ALP protein, and messenger RNA (mRNA) expression showed that 0.5 mM was the optimal concentration for the induction of SCAPs by NaF. 0.5 mM NaF-treated SCAPs induced more mineralized nodules as compared with untreated cells. Moreover, the osteo/odontogenic markers (RUNX2, OSX, DSP, and OCN) in mRNA levels were upregulated while the protein levels of these markers increased considerably in 0.5 mM NaF-treated SCAPs. Furthermore, the autophagy-related proteins (LC3, ATG5, and Beclin1) increased in NaF-treated SCAPs, and the osteo/odontogenic makers significantly decreased while silencing ATG5 to block autophagy. In all, sodium fluoride can regulate the osteo/odontogenic differentiation of SCAPs by modulating autophagy.
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A new triphenanthrene compound named 2,2',2'',7,7',7''-hexahydroxy-4,4',4''-trimethoxy-[9,9',9'',10,10',10'']-hexahydro-1,8,1',6''-triphenanthrene (1), together with eleven known compounds (2ï¼12), were isolated from tubers of Bletilla striata. Their structures were determined by analysis of spectroscopic data.
Subject(s)
Orchidaceae , Molecular Structure , Plant TubersABSTRACT
BACKGROUND: The development of antinociceptive tolerance following repetitive administration of opioid analgesics significantly hinders their clinical use. Evidence has accumulated indicating that microglia within the spinal cord plays a critical role in morphine tolerance. The inhibitor of microglia is effective to attenuate the tolerance; however, the mechanism is not fully understood. Our present study investigated the effects and possible mechanism of a natural product procyanidins in improving morphine tolerance via its specific inhibition on NOD-like receptor protein3 (NLRP3) inflammasome in microglia. METHODS: CD-1 mice were used for tail-flick test to evaluate the degree of pain. The microglial cell line BV-2 was used to investigate the effects and the mechanism of procyanidins. Reactive oxygen species (ROS) produced from BV-2 cells was evaluated by flow cytometry. Cell signaling was measured by western blot assay and immunofluorescence assay. RESULTS: Co-administration of procyanidins with morphine potentiated its antinociception effect and attenuated the development of acute and chronic morphine tolerance. Procyanidins also inhibited morphine-induced increase of interleukin-1ß and activation of NOD-like receptor protein3 (NLRP3) inflammasome. Furthermore, procyanidins decreased the phosphorylation of p38 mitogen-activated protein kinase, inhibited the translocation of nuclear factor-κB (NF-κB), and suppressed the level of reactive oxygen species in microglia. CONCLUSIONS: Procyanidins suppresses morphine-induced activation of NLRP3 inflammasome and inflammatory responses in microglia, and thus resulting in significant attenuation of morphine antinociceptive tolerance.
Subject(s)
Analgesics, Opioid/pharmacology , Inflammasomes/genetics , Microglia/metabolism , Morphine/pharmacology , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , Proanthocyanidins/pharmacology , Activation, Metabolic/drug effects , Animals , Behavior, Animal/drug effects , Drug Synergism , Drug Tolerance , Interleukin-1beta/biosynthesis , Interleukin-1beta/genetics , Mice , Microglia/drug effects , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pain Measurement/drug effects , p38 Mitogen-Activated Protein Kinases/biosynthesisABSTRACT
BACKGROUND: The aim of this study was to detect the expression of hypoxia-inducible factor (HIF)-1α and HIF-2α in papillary thyroid carcinoma (PTC) compared with normal thyroid tissues. METHODS: The mRNA levels and protein levels of HIF-1α and HIF-2α were detected by real-time PCR and Western blot separately in 30 pairs of PTCs and normal thyroid cases. The protein levels were also detected by immunohistochemistry (IHC) using 92 samples of PTC group and 46 normal samples as control group for analyzing the biological and clinical significance of the expression of HIF-1α/HIF-2α. RESULTS: Real-time PCR results showed the mRNA level of HIF-1α and HIF-2α were significantly higher in PTC than normal group (P<0.001). Also, significantly higher positive rates (73%/65%) of HIF-1α and HIF-2α were observed in PTC compared with the control group (27%/35%) by IHC (P<0.01); the consistent results were gotten with Western blot. Although we did not find a significant correlation between the expression of HIF-1α and HIF-2α with gender, age, calcification, or Hashimoto's disease in the present study (P>0.05), both of their expressions were correlated to lymph node metastasis (P<0.05), capsular invasion (P<0.05), and TNM stage (P<0.05). CONCLUSIONS: Overexpression of HIF-1α and HIF-2α are associated with the carcinogenesis of PTC, served as potential biomarkers of PTC.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Papillary/secondary , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Thyroid Neoplasms/pathology , Adult , Aged , Basic Helix-Loop-Helix Transcription Factors/genetics , Biomarkers, Tumor/genetics , Blotting, Western , Carcinoma, Papillary/genetics , Carcinoma, Papillary/metabolism , Carcinoma, Papillary/surgery , Female , Follow-Up Studies , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Immunoenzyme Techniques , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Thyroid Neoplasms/genetics , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/surgery , Young AdultABSTRACT
Propofol is a widely used intravenous anesthetic agent with antioxidant/antiapoptotic properties. Aldose reductase (AR) has been implicated in oxidative stress and apoptosis in endothelial cells. AR inhibition may protect cells from cardiovascular injury. Although the cytoprotective effect of propofol against hydrogen peroxide (H2O2)-induced injury has been widely studied, there is no information about the effects of propofol on AR. We therefore investigated the effect of propofol on H2O2-mediated injury and on aldose reductase expression. We found that propofol protected HUVECs against H2O2-induced damage and apoptosis and ameliorated AR expression induced by H2O2. Propofol also inhibited H2O2-induced p38 MAPK, JNK and Akt phosphorylation. Epalrestat (an AR inhibitor) or ablation of AR siRNA had a similar effect to propofol. The results suggest that propofol may be a preemptive anesthetic in patients with cardiovascular disease and inhibition of AR might be a new cytoprotective pathway for propofol.
Subject(s)
Aldehyde Reductase/metabolism , Anesthetics, Intravenous/pharmacology , Free Radical Scavengers/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Hydrogen Peroxide/antagonists & inhibitors , Hydrogen Peroxide/toxicity , Oxidants/toxicity , Propofol/pharmacology , Aldehyde Reductase/biosynthesis , Apoptosis/drug effects , Human Umbilical Vein Endothelial Cells/enzymology , Humans , MAP Kinase Kinase 4/metabolism , Malondialdehyde/metabolism , Oncogene Protein v-akt/metabolism , RNA, Small Interfering/pharmacology , Rhodanine/analogs & derivatives , Rhodanine/pharmacology , Signal Transduction/drug effects , Thiazolidines/pharmacology , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Photocatalysis is an effective technique to remove antibiotic residues from aquatic environments. Typical metal sulfides like Zn3 In2 S6 have been applied to a wide range of photocatalytic applications. However, there are currently no readily accessible methods to increase its antibiotic-degrading activity. Here, a facile hydrothermal approach is developed for the preparation of flower-like Zn3 In2 S6 with tunable sulfur lattice defects. Photogenerated carriers can be separated and transferred more easily when there is an adequate amount of lattice defects. Moreover, lattice defect-induced electronic modulation enhances light utilization and adsorption properties. The modified Zn3 In2 S6 demonstrates outstanding photocatalytic degradation activity for levofloxacin, ofloxacin, and tetracycline. This work sheds light on exploring metal sulfides with sulfur lattice defects for enhancing photocatalytic activity.
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Two heterodimers including a clovane-phenylpropanoid hybrid (1) and a clovane-menthane hybrid (2), five linear sesquiterpenoids incorporating a tetrahydrofuran ring (3-6 & 8), and four steroids (7 & 9-11), were separated from the ethanolic extract of a well-known aromatic and medicinal herb Eupatorium fortunei. Their structures were characterised by detailed analyses of spectroscopic data and comparison with known analogues, with seven (1-7) of them being described for the first time. The hybrids 1 and 2 represent the first examples of clovane type sesquiterpenoids hybridising with other class of natural products, and compounds 3-6 and 8 are first linear sesquiterpenyl constituents reported from the title species. All the isolates were evaluated for their inhibitory effect on the NO production induced by LPS in murine RAW264.7 macrophage cells, and 1, 7, 10 and 11 exhibited moderate activity with IC50 values in the range of 24.4-43.5 µM.
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The high prevalence of prediabetes and diabetes globally has led to the widespread occurrence of severe complications, such as diabetic neuropathy, which is a result of chronic hyperglycemia. Studies have demonstrated that maternal diabetes can lead to neural tube defects by suppressing neurogenesis during neuroepithelium development. While aberrant autophagy has been associated with abnormal neuronal differentiation, the mechanism by which high glucose suppresses neural differentiation in stem cells remains unclear. Therefore, we developed a neuronal cell differentiation model of retinoic acid induced P19 cells to investigate the impact of high glucose on neuronal differentiation in vitro. Our findings indicate that high glucose (HG) hinders neuronal differentiation and triggers excessive. Furthermore, HG treatment significantly reduces the expression of markers for neurons (Tuj1) and glia (GFAP), while enhancing autophagic activity mediated by peroxisome proliferator-activated receptor gamma (PPARγ). By manipulating PPARγ activity through pharmacological approaches and genetically knocking it down using shRNA, we discovered that altering PPARγ activity affects the differentiation of neural stem cells exposed to HG. Our study reveals that PPARγ acts as a downstream mediator in high glucose-suppressed neural stem cell differentiation and that refining autophagic activity via PPARγ at an appropriate level could improve neuronal differentiation efficiency. Our data provide novel insights and potential therapeutic targets for the clinical management of gestational diabetes mellitus.
Subject(s)
Neurons , PPAR gamma , Autophagy , Cell Differentiation , Glucose/pharmacology , Glucose/metabolism , Neurons/metabolism , PPAR gamma/metabolism , Animals , MiceABSTRACT
Clarifying the antibacterial mechanism of silver (Ag)-based materials is of great significance for the rational design, synthesis, and evaluation of antimicrobials. Herein, detailed description of the antibacterial mechanism of a synthesized silver deposited fullerene material (Ag(I)-C60) towards Staphylococcus aureus was surveyed from the point of view of DNA damage by ultraviolet-visible spectroscopy (UV-vis), inductively coupled plasma mass spectrometry (ICP-MS), and liquid chromatography-mass spectrometry (LC-MS). The model material, Ag(I)-C60, was prepared by liquid-liquid interfacial precipitation method, and characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), thermos-gravimetric analysis (TGA), and nitrogen adsorption/desorption analysis. Ultra-efficient bacteriostatic rate of Ag(I)-C60 was found to be 88.98% under light irradiation for 20 min. UV-vis measurement of the composition changes of four DNA bases showed that they changed in the presence of Ag(I)-C60 under light irradiation, suggesting Ag(I)-C60 could destroy the cells and genetic material of Staphylococcus aureus and thereby inhibit its growth and reproduction. ICP-MS analysis demonstrated the releasing behavior of Ag+ from Ag-based materials. Finally, the transformation pathway of G, A, C, and T were measured by LC-MS, demonstrating the conversion of Adenine (m/z 136.06) to 8-OH-Ade (m/z 174.04). These collective results suggested that Ag(I)-C60 was a new ultra-efficient antibacterial by slowly releasing Ag+ in water and producing a large amount of ROS under light.
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Recycled aggregate concrete (RAC) has become a popular building material due to its eco-friendly features, but the difficulty in predicting the crack resistance of RAC is increasingly impeding its application. In this study, splitting tensile strength is adopted to describe the crack resistance ability of RAC, and physics-assisted machine learning (ML) methods are used to construct the predictive models for the splitting tensile strength of RAC. The results show that the AdaBoost model has excellent predictive performance with the help of the Firefly algorithm, and physical assistance plays a remarkable role in selecting features and verifying the ML models. Due to the limit in data size and the generalizability of the model, the dataset should be supplemented with more representative data, and an algorithm for small sample sizes could be studied in the future.
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Opioids, such as morphine, are the most potent drugs used to treat pain. Long-term use results in high tolerance to morphine. High mobility group box-1 (HMGB1) has been shown to participate in neuropathic or inflammatory pain, but its role in morphine tolerance is unclear. In this study, we established rat and mouse models of morphine tolerance by intrathecal injection of morphine for 7 consecutive days. We found that morphine induced rat spinal cord neurons to release a large amount of HMGB1. HMGB1 regulated nuclear factor κB p65 phosphorylation and interleukin-1ß production by increasing Toll-like receptor 4 receptor expression in microglia, thereby inducing morphine tolerance. Glycyrrhizin, an HMGB1 inhibitor, markedly attenuated chronic morphine tolerance in the mouse model. Finally, compound C (adenosine 5'-monophosphate-activated protein kinase inhibitor) and zinc protoporphyrin (heme oxygenase-1 inhibitor) alleviated the morphine-induced release of HMGB1 and reduced nuclear factor κB p65 phosphorylation and interleukin-1ß production in a mouse model of morphine tolerance and an SH-SY5Y cell model of morphine tolerance, and alleviated morphine tolerance in the mouse model. These findings suggest that morphine induces HMGB1 release via the adenosine 5'-monophosphate-activated protein kinase/heme oxygenase-1 signaling pathway, and that inhibiting this signaling pathway can effectively reduce morphine tolerance.