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1.
medRxiv ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38853851

ABSTRACT

Importance: The binary classification of spina bifida lesions as myelomeningocele (with sac) or myeloschisis (without sac) belies a spectrum of morphologies, which have not been correlated to clinical characteristics and outcomes. Objective: To characterize spina bifida lesion types and correlate them with preoperative presentation and postoperative outcomes. Design: Secondary analysis of images and videos obtained during fetoscopic spina bifida repair surgery from 2020-2023. Setting: Fetal surgery was performed at a quaternary care center. Participants: A prospective cohort of patients referred for fetal spina bifida underwent fetoscopic repair under an FDA-approved protocol. Of 60 lesions repaired, 57 had available images and were included in the analysis. Interventions or Exposures: We evaluated lesion morphology on high-resolution intraoperative images and videos to categorize lesions based on placode exposure and nerve root stretching. Main Outcomes and Measures: The reproducibility of the lesion classification was assessed via Kappa interrater agreement. Preoperative characteristics analyzed include ventricle size, tonsillar herniation level, lower extremities movement, and lesion dimensions. Outcomes included surgical time, need for patch for skin closure, gestational age at delivery, preterm premature rupture of membranes (PPROM), and neonatal cerebrospinal fluid (CSF) diversion. Results: We distinguished five lesion types that differ across a range of sac sizes, nerve root stretching, and placode exposure, with 93% agreement between examiners (p<0.001). Fetal characteristics at preoperative evaluation differed significantly by lesion type, including lesion volume (p<0.001), largest ventricle size (p=0.008), tonsillar herniation (p=0.005), and head circumference (p=0.03). Lesion level, talipes, and lower extremities movement did not differ by type. Surgical and perinatal outcomes differed by lesion type, including need for patch skin closure (p<0.001), gestational age at delivery (p=0.01), and NICU length of stay (p<0.001). PPROM, CSF leakage at birth, and CSF diversion in the NICU did not differ between lesion groups. Linear regression associated severity of ventriculomegaly with lesion type, but not with tonsillar herniation level. Conclusions and Relevance: There is a distinct phenotypic spectrum in open spina bifida with differential baseline presentation and outcomes. Severity of ventriculomegaly is associated with lesion type, rather than tonsillar herniation level. Our findings expand the classification of spina bifida to reveal a spectrum that warrants further study.

2.
J Hazard Mater ; 472: 134468, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38703680

ABSTRACT

The performance of biochar (BC) in reducing the transport of antibiotics under field conditions has not been sufficiently explored. In repacked sloping boxes of a calcareous soil, the effects of different BC treatments on the discharge of three relatively weakly sorbing antibiotics (sulfadiazine, sulfamethazine, and florfenicol) via runoff and drainage were monitored for three natural rain events. Surface application of 1 % BC (1 %BC-SA) led to the most effective reduction in runoff discharge of the two sulfonamide antibiotics, which can be partly ascribed to the enhanced water infiltration. The construction of 5 % BC amended permeable reactive wall (5 %BC-PRW) at the lower end of soil box was more effective than the 1 %BC-SA treatment in reducing the leaching of the most weakly sorbing antibiotic (florfenicol), which can be mainly ascribed to the much higher plant available and drainable water contents in the 5 %BC-PRW soil than in the unamended soil. The results of this study highlight the importance of BC's ability to regulate flow pattern by modifying soil hydraulic properties, which can make a significant contribution to the achieved reduction in the transport of antibiotics offsite or to groundwater.


Subject(s)
Anti-Bacterial Agents , Charcoal , Soil Pollutants , Soil , Anti-Bacterial Agents/chemistry , Charcoal/chemistry , Adsorption , Soil/chemistry , Soil Pollutants/chemistry , Water Pollutants, Chemical/chemistry , Water Movements , Groundwater/chemistry , Thiamphenicol/analogs & derivatives , Thiamphenicol/chemistry
3.
Zhongguo Zhong Yao Za Zhi ; 49(3): 634-643, 2024 Feb.
Article in Chinese | MEDLINE | ID: mdl-38621867

ABSTRACT

This paper aims to study the correlation between the physicochemical properties of raw materials and intermediates and the molding quality and law of traditional Chinese medicine(TCM) gel plaster by using TCM slices and powder as raw materials. 48 TCM compounds are selected as model prescriptions to prepare gel plasters. The rotational rheometer is used to determine the rheological parameters of the plaster, including storage modulus(G'), loss modulus(G″), yield stress(τ), and creep compliance [J(t)]. The molding quality of the prepared TCM gel plaster is evaluated by subjective and objective measures. Clustering and principal component analysis are conducted to evaluate the physical properties of the plaster. By measuring the rheological properties of the plaster, the molding quality of the TCM gel plaster can be predicted, with an accuracy of 83.72% after seven days of modeling and 88.37% after 30 days of modeling. When the parameters such as G' and G″ of the plaster are large, and the [J(t)] is small, the molding quality of the plaster is better. When the plaster coating point is no less than 3, it is difficult to be coated. In addition, when the proportion of metal ions in the prescription is higher, the 30-day forming quality of the plaster is mainly affected, and the viscosity of the plaster is poor. If the prescription contains many acidic chemical components, the 7-day forming quality of the plaster is mainly affected, with many residuals. The results suggest that the rheological properties of the plaster can be used to predict the molding quality of TCM slice and powder gel plaster. It can provide a reference for the development of TCM gel plaster prescriptions.


Subject(s)
Medicine, Chinese Traditional , Prescriptions , Powders , Viscosity , Rheology
4.
Biomed Pharmacother ; 172: 116246, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38359487

ABSTRACT

Azithromycin, a commonly used macrolide antibiotic for treating chlamydial infections during pregnancy, has sparked investigations into its potential effects on offspring development. Despite these inquiries, there remains uncertainty about the specific impact of prenatal azithromycin exposure (PAzE) on offspring ovarian development and the precise "effect window". Pregnant mice, following clinical guidelines for azithromycin dosing, were orally administered azithromycin at different gestational stages [(gestational day, GD) 10-12 or GD 15-17], doses (50, 100, or 200 mg/kg·d), and courses (single or multiple). On GD 18, we collected offspring blood and ovaries to examine changes in fetal serum estradiol (E2) levels, fetal ovarian morphology, pre-granulosa cell function, and oocyte development. Multiple courses of PAzE resulted in abnormal fetal ovarian morphological development, disorganized germ cell nests, enhanced ovarian cell proliferation, and reduced apoptosis. Simultaneously, multiple courses of PAzE significantly increased fetal serum E2 levels, elevated ovarian steroidogenic function (indicated by Star, 3ß-hsd, and Cyp19 expression), disrupted oocyte development (indicated by Figlα and Nobox expression), and led to alterations in the MAPK signal pathway in fetal ovaries, particularly in the high-dose treatment group. In contrast, a single course of PAzE reduced fetal ovarian cell proliferation, decreased steroidogenic function, and inhibited oocyte development, particularly through the downregulation of Mek2 expression in the MAPK signal pathway. These findings suggest that PAzE can influence various aspects of fetal mouse ovarian cell development. Multiple courses enhance pre-granulosa cell estrogen synthesis function and advance germ cell development, while a single terminal gestation dose inhibits germ cell development. These differential effects may be associated with changes in the MAPK signal pathway.


Subject(s)
Azithromycin , Ovary , Pregnancy , Female , Mice , Animals , Azithromycin/toxicity , Granulosa Cells , Reproduction , Germ Cells
5.
J Dairy Sci ; 107(1): 573-592, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37690725

ABSTRACT

The transition period in dairy cows is a critical stage and peripartum oxidative status, negative energy balance (NEB), and inflammation are highly prevalent. Fecal microbial metabolism is closely associated with blood oxidative status and nonesterified fatty acids (NEFA) levels. Here, we investigated dynamic changes in total oxidative status markers and NEFA in blood, fecal microbiome, and metabolome of 30 dairy cows during transition (-21, -7, +7, +21 d relative to calving). Then the Bayesian network and 9 machine-learning algorithms were applied to dismantle their relationship. Our results show that the oxidative status indicator (OSI) of -21, -7, +7 d was higher than +21 d. The plasma concentration of NEFA peaked on +7 d. For fecal microenvironment, a decline in bacterial α diversity was observed at postpartum and in bacterial interactions at +7 d. Conversely, microbial metabolites involved in carbohydrate, lipid, and energy metabolism increased on +7 d. A correlation analysis revealed that 11 and 10 microbial metabolites contributed to OSI and NEFA variations, respectively (arc strength >0.5). The support vector machine (SVM) radial model showed the highest average predictive accuracy (100% and 88.9% in the test and external data sets) for OSI using 1 metabolite and 3 microbiota. The SVM radial model also showed the highest average diagnostic accuracy (100% and 91% in the test and external data sets) for NEFA with 2 metabolites and 3 microbiota. Our results reveal a relationship between variation in the fecal microenvironment and indicators of oxidative status, NEB, and inflammation, which provide a theoretical basis for the prevention and precise regulation of peripartum oxidative status and NEB.


Subject(s)
Fatty Acids, Nonesterified , Peripartum Period , Female , Cattle , Animals , Bayes Theorem , Postpartum Period , Inflammation/veterinary , Oxidative Stress , Lactation/physiology , 3-Hydroxybutyric Acid
6.
Transl Cancer Res ; 12(10): 2596-2612, 2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37969374

ABSTRACT

Background: Insulin-like growth factor (IGF) binding proteins (IGFBPs) are involved in tumorigenesis and cancer progression. IGFBP7 has been shown to act as either a tumor suppressive gene or an oncogene in many tumors, including stomach adenocarcinoma (STAD). To provide a more systematic and comprehensive understanding of IGFBP7 gene, we performed an integrative pan-cancer analysis and explored further with the case of STAD. Methods: We compared the expression data of IGFBP7 in various cancer and normal tissues obtained from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database. The TISIDB web portal was used to analyze the associations of IGFBP7 with cancer molecular subtypes and immune subtypes. We also analyzed the predictive ability and prognostic values of IGFBP7 in pan-cancer, as well as explored its targeted binding proteins and their biological functions. Additionally, we examined the relationship between IGFBP7 and the clinical characteristics of STAD, investigated the co-expression genes and biological functions of differentially expressed genes (DEGs), and validated the mRNA and protein expression levels of IGFBP7 using gastric cancer (GC) and adjacent normal tissues in a small self-case-control study. Results: IGFBP7 was found to be overexpressed in STAD and downregulated in many other cancers. The mRNA and protein expression levels of IGFBP7 were also significantly higher in the collected GC tissues compared with adjacent tissues. Expression of IGFBP7 varied significantly across molecular subtypes of nine different cancer types and immune subtypes of eight types, with the highest expression observed in the genomically stable molecular subtype and C3 inflammatory immune subtype in STAD. IGFBP7 demonstrated an area under the curve (AUC) >0.7 for predicting 16 cancer types, and an AUC >0.9 for seven types. Patients in the higher IGFBP7 expression group showed a poorer prognosis for adrenal cortical carcinoma (ACC) and low-grade glioma (LGG), while demonstrating a more favorable prognosis for kidney renal clear cell carcinoma (KIRC). IGFBP7 expression in STAD was significantly associated with T stage, pathological stage, histologic grade, and Helicobacter pylori infection. Conclusions: IGFBP7 showed promise as a biomarker for prediction and prognosis in pan-cancer. IGFBP7 was found to be overexpressed in STAD, and its expression was closely associated with the clinical characteristics of STAD.

7.
Photochem Photobiol ; 2023 Oct 10.
Article in English | MEDLINE | ID: mdl-37814779

ABSTRACT

Although blue light can damage the skin to a certain extent, the pathogenesis of its damage remains still unclear. The available evidence suggests that oxidative stress may be the main cause of its damage. Lycium barbarum polysaccharide (LBP) has antioxidative effects in a variety of cells. In this paper, we investigated the protective role of LBP and its mechanism of action related to mitophagy in blue-light-damaged skin cells. The findings indicated that in HaCaT cells and mouse skin, LBP pretreatment was effective in reducing blue-light-induced apoptosis and ameliorating the elevated level of cellular autophagy/mitophagy caused by excessive blue light exposure. The markers reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) were used to assess oxidative stress. LBP could effectively inhibit blue-light-induced oxidative stress. It was also found that blue light exposure caused mitochondrial dysfunction in HaCaT cells, including increased intracellular calcium ion levels and decreased mitochondrial membrane potential. LBP pretreatment significantly relieved mitochondrial dysfunction in HaCaT cells. These findings imply that LBP pretreatment protects skin cells from damage induced by blue light irradiation and that mitophagy may be a significant factor in skin photodamage.

8.
Environ Sci Pollut Res Int ; 30(40): 93242-93254, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37507564

ABSTRACT

Epidemiological studies in recent years have identified an association between exposure to air pollutants and acute myocardial infarction (AMI); however, the association between short-term ozone (O3) exposure and AMI hospitalization remains unclear, particularly in developing countries. Therefore, this study collected information on 24,489 AMI patients, including daily air pollutant and meteorological data in Henan, China, between 2016 and 2021. A distributed lagged nonlinear model combined with a Poisson regression model was used to estimate the nonlinear lagged effect of O3 on AMI hospitalizations. We also quantified the effects of O3 on the number of AMI hospitalizations, hospitalization days, and hospitalization costs. The results showed that single- and dual-pollution models of O3 at lag0, lag1, and lag (01-07) were risk factors for AMI hospitalizations, with the most significant effect at lag03 (RR = 1.132, 95% CI:1.083-1.182). Further studies showed that males, younger people (15-64 years), warm seasons, and long sunshine duration were more susceptible to O3. Hospitalizations attributable to O3 during the study period accounted for 11.66% of the total hospitalizations, corresponding to 2856 patients, 33,492 hospital days, and 90 million RMB. Maintaining O3 at 10-130 µg/m3 can prevent hundreds of AMI hospitalizations and save millions of RMB per year in Henan, China. In conclusion, we found that short-term exposure to O3 was significantly associated with an increased risk of hospitalization for AMI in Henan, China, and that further reductions in ambient O3 levels may have substantial health and economic benefits for patients and local healthcare facilities.


Subject(s)
Air Pollutants , Air Pollution , Myocardial Infarction , Ozone , Male , Humans , Air Pollution/analysis , Particulate Matter/analysis , Environmental Exposure/analysis , Air Pollutants/analysis , Ozone/analysis , Hospitalization , Myocardial Infarction/epidemiology , Myocardial Infarction/chemically induced , China/epidemiology
9.
PLoS Comput Biol ; 19(6): e1011218, 2023 06.
Article in English | MEDLINE | ID: mdl-37289843

ABSTRACT

Synthetic lethality (SL) occurs when mutations in two genes together lead to cell or organism death, while a single mutation in either gene does not have a significant impact. This concept can also be extended to three or more genes for SL. Computational and experimental methods have been developed to predict and verify SL gene pairs, especially for yeast and Escherichia coli. However, there is currently a lack of a specialized platform to collect microbial SL gene pairs. Therefore, we designed a synthetic interaction database for microbial genetics that collects 13,313 SL and 2,994 Synthetic Rescue (SR) gene pairs that are reported in the literature, as well as 86,981 putative SL pairs got through homologous transfer method in 281 bacterial genomes. Our database website provides multiple functions such as search, browse, visualization, and Blast. Based on the SL interaction data in the S. cerevisiae, we review the issue of duplications' essentiality and observed that the duplicated genes and singletons have a similar ratio of being essential when we consider both individual and SL. The Microbial Synthetic Lethal and Rescue Database (Mslar) is expected to be a useful reference resource for researchers interested in the SL and SR genes of microorganisms. Mslar is open freely to everyone and available on the web at http://guolab.whu.edu.cn/Mslar/.


Subject(s)
Neoplasms , Saccharomyces cerevisiae , Humans , Saccharomyces cerevisiae/genetics , Synthetic Lethal Mutations , Mutation , Genome, Bacterial/genetics , Databases, Genetic , Neoplasms/genetics
11.
Nat Commun ; 14(1): 2390, 2023 04 25.
Article in English | MEDLINE | ID: mdl-37185814

ABSTRACT

A comprehensive understanding of endothelial cell lineage specification will advance cardiovascular regenerative medicine. Recent studies found that unique epigenetic signatures preferentially regulate cell identity genes. We thus systematically investigate the epigenetic landscape of endothelial cell lineage and identify MECOM to be the leading candidate as an endothelial cell lineage regulator. Single-cell RNA-Seq analysis verifies that MECOM-positive cells are exclusively enriched in the cell cluster of bona fide endothelial cells derived from induced pluripotent stem cells. Our experiments demonstrate that MECOM depletion impairs human endothelial cell differentiation, functions, and Zebrafish angiogenesis. Through integrative analysis of Hi-C, DNase-Seq, ChIP-Seq, and RNA-Seq data, we find MECOM binds enhancers that form chromatin loops to regulate endothelial cell identity genes. Further, we identify and verify the VEGF signaling pathway to be a key target of MECOM. Our work provides important insights into epigenetic regulation of cell identity and uncovered MECOM as an endothelial cell lineage regulator.


Subject(s)
Endothelial Cells , Epigenesis, Genetic , Animals , Humans , Cell Differentiation/genetics , Cell Lineage/genetics , Endothelial Cells/metabolism , MDS1 and EVI1 Complex Locus Protein/genetics , Regulatory Sequences, Nucleic Acid , Transcription Factors/metabolism , Zebrafish/genetics , Zebrafish/metabolism
12.
Methods ; 210: 10-19, 2023 02.
Article in English | MEDLINE | ID: mdl-36621557

ABSTRACT

Proteins encoded by small open reading frames (sORFs) can serve as functional elements playing important roles in vivo. Such sORFs also constitute the potential pool for facilitating the de novo gene birth, driving evolutionary innovation and species diversity. Therefore, their theoretical and experimental identification has become a critical issue. Herein, we proposed a protein-coding sORFs prediction method merely based on integrative sequence-derived features. Our prediction performance is better or comparable compared with other nine prevalent methods, which shows that our method can provide a relatively reliable research tool for the prediction of protein-coding sORFs. Our method allows users to estimate the potential expression of a queried sORF, which has been demonstrated by the correlation analysis between our possibility estimation and codon adaption index (CAI). Based on the features that we used, we demonstrated that the sequence features of the protein-coding sORFs in the two domains have significant differences implying that it might be a relatively hard task in terms of cross-domain prediction, hence domain-specific models were developed, which allowed users to predict protein-coding sORFs both in eukaryotes and prokaryotes. Finally, a web-server was developed and provided to boost and facilitate the study of the related field, which is freely available at http://guolab.whu.edu.cn/codingCapacity/index.html.


Subject(s)
Random Forest , Open Reading Frames/genetics
13.
Environ Technol ; 44(16): 2473-2480, 2023 Jun.
Article in English | MEDLINE | ID: mdl-35084288

ABSTRACT

Modified silica fume powder with oleic acid through coupling agent was prepared based on the in situ utilizing long-chain fatty acids (LCFA) properties of Microthrix parvicella (M. parvicella) in the activated sludge system. The modification was confirmed by XRD and infrared spectrum. The contact angle analysis showed that the modification gave the silica fume powder a hydrophobic surface. The modified silica fume powder had a good combination with M. parvicella from the SEM and Gram staining measurements. The addition of modified silica powder has a certain effect on the settling capacity of sludge, but has little effect on the sludge treatment capacity, while the SVI dropped from 400.1 to 100.0 mL/g. These suggested that the modified silica fume powder could be used as an excellent weight-increasing agent to inhibit sludge bulking.


Subject(s)
Actinobacteria , Sewage , Oleic Acid , Powders , Gases , Waste Disposal, Fluid
14.
Cancer Sci ; 114(4): 1365-1377, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36519789

ABSTRACT

There is increasing evidence that hexokinase is involved in cell proliferation and migration. However, the function of the hexokinase domain containing protein-1 (HKDC1) in gastric cancer (GC) remains unclear. Immunohistochemistry analysis and big data mining were used to evaluate the correlation between HKDC1 expression and clinical features in GC. In addition, the biological function and molecular mechanism of HKDC1 in GC were studied by in vitro and in vivo assays. Our study indicated that HKDC1 expression was upregulated in GC tissues compared with adjacent nontumor tissues. High expression of HKDC1 was associated with worse prognosis. Functional experiments demonstrated that HKDC1 upregulation promoted glycolysis, cell proliferation, and tumorigenesis. In addition, HKDC1 could enhance GC invasion and metastasis by inducing epithelial-mesenchymal transition (EMT). Abrogation of HKDC1 could effectively attenuate its oncogenic and metastatic function. Moreover, HKDC1 promoted GC proliferation and migration in vivo. HKDC1 overexpression conferred chemoresistance to cisplatin, oxaliplatin, and 5-fluorouracil (5-Fu) onto GC cells. Furthermore, nuclear factor kappa-B (NF-κB) inhibitor PS-341 could attenuate tumorigenesis, metastasis, and drug resistance ability induced by HKDC1 overexpression in GC cells. Our results highlight a critical role of HKDC1 in promoting glycolysis, tumorigenesis, and EMT of GC cells via activating the NF-κB pathway. In addition, HKDC1-mediated drug resistance was associated with DNA damage repair, which further activated NF-κB signaling. HKDC1 upregulation may be used as a potential indicator for choosing an effective chemotherapy regimen for GC patients undergoing chemotherapy.


Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , NF-kappa B/metabolism , Up-Regulation , Drug Resistance, Neoplasm/genetics , Hexokinase/genetics , Hexokinase/metabolism , Fluorouracil/pharmacology , Disease Progression , Carcinogenesis/genetics , Epithelial-Mesenchymal Transition/genetics , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Cell Movement/genetics
15.
J Photochem Photobiol B ; 238: 112617, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36495671

ABSTRACT

With the development of technology and electronic products, the problem of light pollution is becoming more and more serious. Blue light, the most energetic light in visible light, is the main culprit of teenage vision problems in the modern environment. As the tissue with the highest oxygen consumption, the retina is vulnerable to oxidative stress. However, the exact way in which blue light-triggered reactive oxygen species (ROS) cause retinal cell death remains unclear. Ferroptosis is a newly defined cell death pathway, whose core molecular mechanism is cell death caused by excessive lipid peroxidation. In this study, the results indicated that blue light-triggered ROS burst in retinal cells, in the meantime, intracellular Fe2+ levels were also significantly up-regulated. Further, deferoxamine (DFO) significantly improved blue light-triggered lipid peroxidation and cell death in ARPE-19 cells, and ferrostatin-1 (Fer-1) alleviated retinal oxidative stress and degeneration in rats. Furthermore, the GSH-GPX4 and FSP1-CoQ10-NADH systems served as key systems for cellular defense against ferroptosis, and interestingly, our results demonstrated that blue light triggered imbalance of the GSH-GPX4 and FSP1-CoQ10-NADH systems in retinal cells. Taken together, these pieces of evidence suggest that ferroptosis may be a crucial pathway for blue light-induced retinal damage and degeneration, which helps us to understand exactly why blue light pollution causes visual impairment in adolescents.


Subject(s)
Ferroptosis , Rats , Animals , Ferroptosis/physiology , Reactive Oxygen Species/metabolism , Light Pollution , NAD , Cell Death
16.
Elife ; 112022 11 15.
Article in English | MEDLINE | ID: mdl-36377439

ABSTRACT

Chronic pain disorders are often associated with negative emotions, including anxiety and depression. The central nucleus of the amygdala (CeA) has emerged as an integrative hub for nociceptive and affective components during central pain development. Prior adverse injuries are precipitating factors thought to transform nociceptors into a primed state for chronic pain. However, the cellular basis underlying the primed state and the subsequent development of chronic pain remains unknown. Here, we investigated the cellular and synaptic alterations of the CeA in a mouse model of chronic muscle pain. In these mice, local infusion of pregabalin, a clinically approved drug for fibromyalgia and other chronic pain disorders, into the CeA or chemogenetic inactivation of the somatostatin-expressing CeA (CeA-SST) neurons during the priming phase prevented the chronification of pain. Further, electrophysiological recording revealed that the CeA-SST neurons had increased excitatory synaptic drive and enhanced neuronal excitability in the chronic pain states. Finally, either chemogenetic inactivation of the CeA-SST neurons or pharmacological suppression of the nociceptive afferents from the brainstem to the CeA-SST neurons alleviated chronic pain and anxio-depressive symptoms. These data raise the possibility of targeting treatments to CeA-SST neurons to prevent central pain sensitization.


Subject(s)
Chronic Pain , Neuralgia , Rats , Mice , Animals , Central Nervous System Sensitization , Rats, Sprague-Dawley , Chronic Pain/complications , Myalgia , Amygdala , Disease Models, Animal
17.
Nucleic Acids Res ; 50(21): 12186-12201, 2022 11 28.
Article in English | MEDLINE | ID: mdl-36408932

ABSTRACT

Despite being a member of the chromodomain helicase DNA-binding protein family, little is known about the exact role of CHD6 in chromatin remodeling or cancer disease. Here we show that CHD6 binds to chromatin to promote broad nucleosome eviction for transcriptional activation of many cancer pathways. By integrating multiple patient cohorts for bioinformatics analysis of over a thousand prostate cancer datasets, we found CHD6 expression elevated in prostate cancer and associated with poor prognosis. Further comprehensive experiments demonstrated that CHD6 regulates oncogenicity of prostate cancer cells and tumor development in a murine xenograft model. ChIP-Seq for CHD6, along with MNase-Seq and RNA-Seq, revealed that CHD6 binds on chromatin to evict nucleosomes from promoters and gene bodies for transcriptional activation of oncogenic pathways. These results demonstrated a key function of CHD6 in evicting nucleosomes from chromatin for transcriptional activation of prostate cancer pathways.


Subject(s)
Nucleosomes , Prostatic Neoplasms , Male , Humans , Mice , Animals , Transcriptional Activation , Chromatin Assembly and Disassembly/genetics , Chromatin/genetics , Prostatic Neoplasms/genetics , DNA Helicases/genetics , DNA Helicases/metabolism , Nerve Tissue Proteins/genetics
18.
Free Radic Res ; 56(5-6): 398-410, 2022.
Article in English | MEDLINE | ID: mdl-36194238

ABSTRACT

Melittin is a natural polypeptide present in bee venom, with significant anti-tumor activity. Melittin has been reported to induce cell death in lung carcinoma cell line A549 cells, suggesting an excellent potential for treating lung cancer. However, the core mechanism underlying melittin-induced cell death in A549 cells remains unclear. This work reports that melittin induces reactive oxygen species (ROS) burst, upregulates intracellular Fe2+ levels, disrupts the glutathione-glutathione peroxidase 4 antioxidant system, and increases lipid peroxide accumulation, eventually inducing cell death, indicating that ferroptosis may be involved in the antitumor effects of melittin in A549 cells. Furthermore, A549 cells treated with the ferroptosis inhibitors ferrostatin-1 and deferoxamine demonstrated that these inhibitors could reverse the cell death induced by melittin, further confirming that melittin induces A549 cell death via ferroptosis. Furthermore, the results also illustrated that melittin activated the endoplasmic reticulum (ER) stress-CHOP (C/EBP homologous protein) apoptotic signal, closely associated with high-level intracellular ROS. The ER stress inhibitor, 4-Phenylbutyric acid, was used to confirm that ER stress-CHOP apoptotic signaling is another molecular mechanism of melittin-induced A549 cell death. Thus, our results demonstrate that ferroptosis and ER stress-CHOP signaling are key molecular mechanisms of melittin-induced cell death in lung cancer.KEY POLICY HIGHLIGHTSMelittin upregulates intracellular Fe2+ levels, leading to the accumulation of lipid peroxides in A549 cells.Melittin disrupts the glutathione-glutathione peroxidase 4 antioxidant system in A549 cells.Melittin induces activation of endoplasmic reticulum stress-C/EBP homologous protein apoptosis signal.Ferroptosis and ER stress are the core molecular mechanisms underlying melittin-induced cell death in A549 cells.


Subject(s)
Antineoplastic Agents , Ferroptosis , Lung Neoplasms , Humans , Endoplasmic Reticulum Stress , A549 Cells , Reactive Oxygen Species/metabolism , Melitten/pharmacology , Melitten/therapeutic use , Antioxidants/pharmacology , Phospholipid Hydroperoxide Glutathione Peroxidase , Antineoplastic Agents/pharmacology , Transcription Factor CHOP/metabolism , Apoptosis , Lung Neoplasms/pathology , Glutathione/pharmacology , Cell Line, Tumor
19.
Sensors (Basel) ; 22(20)2022 Oct 19.
Article in English | MEDLINE | ID: mdl-36298303

ABSTRACT

In recent years, hazardous wastewater treatment has been a complex and global problem. In this work, by considering the antimicrobial activity of Ag nanoparticles (AgNPs) and reduced graphene oxide (rGO), we constructed an antibacterial device (G-AgNP) with AgNPs conformably deposited onto a 3D scaffold of reduced graphene oxide in situ. The major limitation, which is difficult to recycle, of two-dimensional graphene-silver composite materials in previous studies is improved. Characterization techniques, SEM, TEM, XRD, and XPS, confirmed the synthesis of nanocomposites. Attributed to its larger specific area, more active sites, and synergistic enhancement, the G-AgNP device demonstrated the best bacterial removal capacity, with an antibacterial rate for both E. coli and S. aureus as high as 100% at quite low AgNP contents. The reported G-AgNP has potential application as a wearable sewage treatment device and for the protection of wearable sensors as a promising sterilizing candidate based on its high and stable antibacterial efficiency.


Subject(s)
Graphite , Metal Nanoparticles , Graphite/pharmacology , Graphite/chemistry , Staphylococcus aureus , Escherichia coli , Metal Nanoparticles/chemistry , Sewage , Silver , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry
20.
Zhen Ci Yan Jiu ; 47(10): 907-13, 2022 Oct 25.
Article in Chinese | MEDLINE | ID: mdl-36301169

ABSTRACT

OBJECTIVE: To investigate the therapeutic effect of acupuncture stimulation combined with administration of"Gushen Zhuyu Tang"(decoction for consolidating kidney to eliminate blood stasis, DCKEBS) in the treatment of lumbar disc herniation (LDH) patients. METHODS: A total of 147 patients with LDH were randomly divided into DCKEBS, acupuncture and DCKEBS+acupuncture groups (n= 49 cases in each group). The patients of the acupuncture group received a) acupuncture stimulation of Dazhui (GV14), Ganshu (BL18), Shenshu (BL23), Tianshu (ST25), Yanglingquan (GB34), etc., b) fire needle pricking of the topical tendons, cord-like points, tender-points, c) row-needles stimulation of the attachment sites of muscles of the sacroiliac joint or crista iliaca, and d) acupotomy-debonding of the topical high-tension muscles, twice a week for 4 weeks. Those patients of the DCKEBS group were ordered to take DCKEBS [containing fried Yiyiren (Semen Coicis), Shanzhuyu (Fructus Corni), fried Baizhu (Rhizoma Astractylodis), Sangjisheng (Ramulus Loranthi), Duzhong (Cortex Eucommiae), Buguzhi (Fructus Psoraieae), etc.] 150 mL, twice daily, continuously for 4 weeks, and those of the DCKEBS+acupuncture group received the combined treatment mentioned above in the acupuncture and DCKEBS groups. The pain severity was assessed by using visual ana-logue scale (VAS, 0-10 points) and the modified Japan Orthopaedic Association questionnaire (M-JOA) score (0-30 points), separately, and the lumbar range of motion (ROM) and lumbar muscle strength were tested to evaluate the lumbar motor function. The levels of serum tumor necrosis factor α(TNF-α), matrix metalloproteinase-2 (MMP-2), and apoptosis related factors Caspase-3 and Caspase-9 were assayed using ELISA. The total effective rates of the three groups were compared. RESULTS: After the treatment, the VAS and M-JOA scores, contents of serum TNF-α, MMP-2, Caspase-3 and Caspase-9 were significantly decreased (P<0.01), and the myodynamia of lumbar muscular flexor and extensor was considerably increased (P<0.01) in the three groups, and the ROM angles of lumbar extending and buckling were increased (P<0.01) in the DCKEBS+acupuncture group compared with pretreatment. Comparison among the 3 groups showed that the VAS and M-JOA scores, and serum TNF-α, MMP-2, Caspase-3 and Caspase-9 contents of the DCKEBS+acupuncture group were significantly lower than those of both DCKEBS and acupuncture groups (P<0.01), while the ROM angles of lumbar extending and buckling, and the myodynamia of lumbar muscular flexor and extensor were obviously higher in the DCKEBS+acupuncture group than those of the DCKEBS and acupuncture groups (P<0.01). The total effective rate was 93.88%(46/49) in the DCKEBS+acupuncture group, higher than 75.51%(37/49) in the DCKEBS group and 71.43%(35/49) in the acupuncture group (P<0.05). CONCLUSION: Acupuncture combined with DCKEBS can relieve pain, improve lumbar muscle strength and lumbar movement function, and reduce serum TNF-α, MMP-2, Caspase-3 and Caspase-9 levels in LDH patients.


Subject(s)
Acupuncture Therapy , Intervertebral Disc Displacement , Humans , Intervertebral Disc Displacement/therapy , Matrix Metalloproteinase 2 , Caspase 9 , Caspase 3 , Tumor Necrosis Factor-alpha , Treatment Outcome , Acupuncture Points
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