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2.
JMIR Med Inform ; 11: e38590, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36662548

RESUMO

BACKGROUND: In emergency departments (EDs), early diagnosis and timely rescue, which are supported by prediction modes using ED data, can increase patients' chances of survival. Unfortunately, ED data usually contain missing, imbalanced, and sparse features, which makes it challenging to build early identification models for diseases. OBJECTIVE: This study aims to propose a systematic approach to deal with the problems of missing, imbalanced, and sparse features for developing sudden-death prediction models using emergency medicine (or ED) data. METHODS: We proposed a 3-step approach to deal with data quality issues: a random forest (RF) for missing values, k-means for imbalanced data, and principal component analysis (PCA) for sparse features. For continuous and discrete variables, the decision coefficient R2 and the κ coefficient were used to evaluate performance, respectively. The area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC) were used to estimate the model's performance. To further evaluate the proposed approach, we carried out a case study using an ED data set obtained from the Hainan Hospital of Chinese PLA General Hospital. A logistic regression (LR) prediction model for patient condition worsening was built. RESULTS: A total of 1085 patients with rescue records and 17,959 patients without rescue records were selected and significantly imbalanced. We extracted 275, 402, and 891 variables from laboratory tests, medications, and diagnosis, respectively. After data preprocessing, the median R2 of the RF continuous variable interpolation was 0.623 (IQR 0.647), and the median of the κ coefficient for discrete variable interpolation was 0.444 (IQR 0.285). The LR model constructed using the initial diagnostic data showed poor performance and variable separation, which was reflected in the abnormally high odds ratio (OR) values of the 2 variables of cardiac arrest and respiratory arrest (201568034532 and 1211118945, respectively) and an abnormal 95% CI. Using processed data, the recall of the model reached 0.746, the F1-score was 0.73, and the AUROC was 0.708. CONCLUSIONS: The proposed systematic approach is valid for building a prediction model for emergency patients.

3.
Cancer Med ; 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36629131

RESUMO

BACKGROUND: Colposcopy is indispensable for the diagnosis of cervical lesions. However, its diagnosis accuracy for high-grade squamous intraepithelial lesion (HSIL) is at about 50%, and the accuracy is largely dependent on the skill and experience of colposcopists. The advancement in computational power made it possible for the application of artificial intelligence (AI) to clinical problems. Here, we explored the feasibility and accuracy of the application of AI on precancerous and cancerous cervical colposcopic image recognition and classification. METHODS: The images were collected from 6002 colposcopy examinations of normal control, low-grade squamous intraepithelial lesion (LSIL), and HSIL. For each patient, the original, Schiller test, and acetic-acid images were all collected. We built a new neural network classification model based on the hybrid algorithm. EfficientNet-b0 was used as the backbone network for the image feature extraction, and GRU(Gate Recurrent Unit)was applied for feature fusion of the three modes examinations (original, acetic acid, and Schiller test). RESULTS: The connected network classifier achieved an accuracy of 90.61% in distinguishing HSIL from normal and LSIL. Furthermore, the model was applied to "Trichotomy", which reached an accuracy of 91.18% in distinguishing the HSIL, LSIL and normal control at the same time. CONCLUSION: Our results revealed that as shown by the high accuracy of AI in the classification of colposcopic images, AI exhibited great potential to be an effective tool for the accurate diagnosis of cervical disease and for early therapeutic intervention in cervical precancer.

4.
Biosci Rep ; 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36645186

RESUMO

BACKGROUND: Multiple studies have assessed the role of Cassiae semen (CS) in regulating lipid metabolism. However, the mechanism of action of CS on non-alcoholic fatty liver disease (NAFLD) has seen rare scrutiny. OBJECTIVE: To explore the regulatory mechanism of CS on lipid metabolism in NAFLD. METHODS: Components of CS ethanol extract (CSEE) were analyzed and identified using UPLC-Q-Orbirap HRMS. The candidate compounds of CS and its relative targets were extracted from the Traditional Chinese Medicine Systems Pharmacology, Swiss-Target-Prediction, and TargetNet web server. The Therapeutic Target Database, Genecards, Online Mendelian Inheritance in Man, and DisGeNET were searched for NAFLD targets. Binding affinity between potential core components and key targets was established employing molecular docking simulations. After that, free fatty acid (FFA)-induced HepG2 cells were used to further validate part of the network pharmacology results. RESULTS: Six genes, including Caspase 3 (CASP3), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), epidermal growth factor receptor (EGFR), and amyloid beta (A4) precursor protein (APP) were identified as key targets. The mitogen-activated protein kinase (MAPK) signaling pathway was found to associate closely with CS's effect on NAFLD. Per molecular docking findings, toralactone and quinizarin formed the most stable combinations with hub genes. 0.1 (vs. FFA, p <0.01) and 0.2 (vs. FFA, p <0.05) mg/mL CSEE decreased lipid accumulation in vitro by reversing the up-regulation of CASP3, EGFR, and APP and the down-regulation of PIK3CA. CONCLUSION: CSEE can significantly reduce intracellular lipid accumulation by modulating the MAPK signaling pathway to decrease CASP3 and EGFR expression.

5.
Physiol Behav ; 258: 114023, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36336146

RESUMO

Akkermansia muciniphila is present in the mucus layer of its host gut, and its outer membrane protein Amuc_1100 has a significant ameliorative effect on metabolic disorders and emotional memory aspects of enteritis, obesity, depression, and anxiety in the host. Antibiotics affect gut microbial composition, leading to imbalance and behavioral changes in the gut-brain axis, while probiotics have a protective effect against behavioral changes caused by gut flora disorders. In the present study, a depressed mouse model using a broad-spectrum cocktail mixture resulted in increased anxiety and depression-like behavior, decreased serum and hippocampal levels of 5-hydroxytryptamine (5-HT), and increased serum corticosterone (cort) levels. After application of A. muciniphila and Amuc_1100, anxiety and depression-like behavior in antibiotic-treated mice were significantly alleviated. In addition, the brain derived neurotrophic factor / Tropomyosin receptor kinase B (BDNF/TrkB) signaling pathway was altered, glial fibrillary acidic protein (GFAP) expression increased, and c-Fos protein expression decreased in the hippocampus of antibiotic-treated mice. After treatment with A. muciniphila and Amuc_1100, BDNF and TrkB levels were restored in the hippocampus and cortex. These results suggest that A. muciniphila and Amuc_1100 may alleviate antibiotic-induced anxiety and depression by affecting the BDNF/TrkB signaling pathway.


Assuntos
Ansiedade , Proteínas da Membrana Bacteriana Externa , Depressão , Animais , Camundongos , Antibacterianos/efeitos adversos , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Depressão/metabolismo , Serotonina/metabolismo , Akkermansia/metabolismo , Proteínas da Membrana Bacteriana Externa/farmacologia
6.
Int Immunopharmacol ; 114: 109487, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36493694

RESUMO

Systemic lupus erythematosus (SLE) is a multisystemic, inflammatory autoimmune disease. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells participated in the pathogenesis of SLE. MDSCs has been considered a potential therapeutic target for lupus. As traditional Chinese medicine, Halofuginone (HF) has the extensive immunomodulatory effects on some autoimmune disorders. Our research was dedicated to discovering therapeutic efficacy of HF for lupus to explore novel mechanisms on MDSCs. We found that HF prominently alleviated the systemic symptoms especially nephritis in Imiquimod-induced lupus mice, and simultaneously repaired the immune system, reflected in the alteration of autoantibodies. HF diminished the quantity of MDSCs in lupus mice, and induced apoptosis of MDSCs. Through RNA sequencing performed on the sorted MDSC from lupus mice and HF-treated lupus mice, B lymphoid tyrosine kinase (Blk, a non-receptor cytoplasmic tyrosine kinase) was screened as the target molecule of HF. It's proven that HF had two independent effects on Blk. On the one hand, HF increased the mRNA expression of Blk in MDSCs by inhibiting the nuclear translocation of p65/p50 heterodimer. On the other hand, HF enhanced the kinase activity of Blk in MDSCs through direct molecular binding. We further investigated that Blk suppressed the phosphorylation of downstream ERK signaling pathway to increase the apoptosis of MDSCs. In conclusion, our study illustrated that HF alleviated the disease progression of lupus mice by targeting Blk to promote the apoptosis of MDSCs, which indicated the immunotherapeutic potential of HF to treat lupus.


Assuntos
Lúpus Eritematoso Sistêmico , Células Supressoras Mieloides , Camundongos , Animais , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Quinazolinonas/farmacologia , Quinazolinonas/uso terapêutico
7.
Front Genet ; 13: 938250, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36561319

RESUMO

Background: Necroptosis has been demonstrated to play a crucial role in the prognosis prediction and assessment of treatment outcome in cancers, including cervical cancer. The purpose of this study was to explore the potential prognostic value of necroptosis-related lncRNAs and their relationship with immune microenvironment and response to treatment in cervical cancer. Methods: Data from The Cancer Genome Atlas (TCGA) were collected to obtain synthetic data matrices. Necroptosis-related lncRNAs were identified by Pearson Correlation analysis. Univariate Cox and multivariate Cox regression analysis and Lasso regression were used to construct a necroptosis-related LncRNAs signature. Kaplan-Meier analysis, univariate and multivariate Cox regression analyses, receiver operating characteristic (ROC) curve, nomogram, and calibration curves analysis were performed to validate this signature. Gene set enrichment analyses (GSEA), immunoassays, and the half-maximal inhibitory concentration (IC50) were also analyzed. Results: Initially, 119 necroptosis-related lncRNAs were identified based on necroptosis-related genes and differentially expressed lncRNAs between normal and cervical cancer samples. Then, a prognostic risk signature consisting of five necroptosis-related lncRNAs (DDN-AS1, DLEU1, RGS5, RUSC1-AS1, TMPO-AS1) was established by Cox regression analysis, and LASSO regression techniques. Based on this signature, patients with cervical cancer were classified into a low- or high-risk group. Cox regression confirmed this signature as an independent prognostic predictor with an AUC value of 0.789 for predicting 1-year OS. A nomogram including signature, age, and TNM stage grade was then established, and showed an AUC of 0.82 for predicting 1-year OS. Moreover, GSEA analysis showed that immune-related pathways were enriched in the low-risk group; immunoassays showed that most immune cells, ESTIMAT scores and immune scores were negatively correlated with risk score and that the expression of immune checkpoint-proteins (CD27, CD48, CD200, and TNFRSF14) were higher in the low-risk group. In addition, patients in the low-risk group were more sensitive to Rucaparib, Navitoclax and Crizotinib than those in the high-risk group. Conclusion: We established a novel necroptosis-related lncRNA based signature to predict prognosis, tumor microenvironment and response to treatment in cervical cancer. Our study provides clues to tailor prognosis prediction and individualized immunization/targeted therapy strategies.

8.
Chin J Nat Med ; 20(12): 914-924, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36549805

RESUMO

Houttuynia cordata is traditionally used as phytoantibiotics for treating lung disease in China. Houttuynia cordata polysaccharides (HCPs) have been reported to alleviate influenza virus-induced intestinal and lung immune injury by regulating the gut-lung axis. The present study aims to investigate the effects and mechanisms of HCPs on ulcerative colitis (UC). Male C57BL/6 mice were induced by dextran sodium sulfate (DSS) to establish the UC animal model. Our results showed that HCPs significantly reduced the weight loss and the shortening of colon length in colitis mice, and relieved the pathological damage of colon mucosa and inhibited the expression of pro-inflammatory cytokines such as TNF-α, IL-1ß, IL-6, etc. It was suggested that HCPs could significantly improve DSS-induced colitis in mice. HCPs directly protected intestinal epithelial cells, ameliorated epithelial barrier dysfunction and cell apoptosis, which was also proved in H2O2 stimulated cell apoptosis model. HCPs inhibited inflammation in the colon, which was related to suppressing the infiltration of macrophages, inhibiting the expression of pro-inflammatory cytokines and proteins (TLR4, NF-κB), and restoring the dysfunction of Th17 and Treg cells. HCPs also restored the alteration of intestinal flora induced by DSS, increased the abundance ofFirmicutes and Bacteroides, and reduced the abundance of Proteobacteria. This study confirmed the protective effect of Houttuynia cordata polysaccharide extracted from traditional Chinese medicine on ulcerative colitis, of which the mechanism was closely related to the maintenance of intestinal homeostasis (intestinal barrier, immune cells, and intestinal bacteria).


Assuntos
Colite Ulcerativa , Colite , Houttuynia , Masculino , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Peróxido de Hidrogênio/farmacologia , Camundongos Endogâmicos C57BL , Colo/metabolismo , Colo/patologia , NF-kappa B/metabolismo , Citocinas/metabolismo , Polissacarídeos/farmacologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças
9.
Front Cardiovasc Med ; 9: 991503, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36440047

RESUMO

Sick sinus syndrome (SSS) is a refractory arrhythmia disease caused by the pathological changes of sinoatrial node and its adjacent tissues. 2,251 publications related to SSS were retrieved from Web of Science database from 2000 to 2022 and analyzed by using VOS viewer and CiteSpace software. The results showed the United States dominated the field, followed by Japan, Germany, and China. SSS was closely related to risk factors such as atrial fibrillation and aging. Sick sinus syndrome, atrial fibrillation and sinus node dysfunction were the top three keywords that had the strongest correlation with the study. Pacemaker implantation, differentiation and mutation are research hotspots currently. Clinical studies on SSS found that sick sinus syndrome, atrial fibrillation, and pacemakers were the top three keywords that had the largest nodes and the highest frequency. In the field of basic applied research and basic research, atrial fibrillation and pacemaker cells were the focus of research. In conclusion, bibliometric analysis provided valuable information for the prevention, treatment and future research trends of SSS.

10.
World J Clin Cases ; 10(30): 11155-11161, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36338236

RESUMO

BACKGROUND: Struma ovarii is a type of monodermal mature teratoma composed entirely or mainly of thyroid tissue, accounting for 1% to 3% of all ovarian teratomas and 0.3% to 1.0% of all ovarian tumors. Of which, struma ovarii with ascites and pleural effusion, called pseudo-Meigs'syndrome and raised cancer antigen-125 levels (CA 125) is even rarer. CASE SUMMARY: This paper reports the diagnosis and treatment of a patient of struma ovarii with pseudo-Meigs'syndrome, presenting with the clinical features of ovarian carcinoma: Complex pelvic mass, gross ascites, right pleural effusion and markedly elevated serum CA 125 levels. During the operation, a cystic-solid mass about 20 cm × 10 cm × 5 cm in the right adnexa and a solid mass with the size of 3 cm × 2 cm × 0.1 cm in the left ovary were observed. She underwent right adnexectomy and resection of the left ovarian mass and histopathology revealed a mature left-sided ovarian teratoma and struma ovarii of right adnexal mass. During 1-year follow-up, the patient recovered well, tumor markers and other indicators returned to normal. CONCLUSION: The diagnosis and treatment process of this case suggests that the clinical symptoms of struma ovarii with pseudo-Meigs'syndrome are lack specificity, which is easily misdiagnosed. Clinicians should improve the understanding of this disease, enhance the awareness of early screening, and improve the level of diagnosis and treatment.

11.
Front Oncol ; 12: 955150, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353544

RESUMO

Although vaginal microbiota (VM) may interact with human papillomavirus (HPV) infection and clearance, longitudinal data remain very limited. We aimed to investigate the association between VM at baseline and the clearance of high-risk HPV (HR-HPV) infection within 12 months. Cervical swabs were collected at diagnosis from 85 patients with HR-HPV infection and histologically confirmed cervical lesions, including cervicitis, low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion. Microbiome analysis was performed using 16S rRNA gene sequencing. Among the 73 women included in the analyses, HPV clearance was observed in 58.9% of the patients within 12 months. No significant difference was observed between the HPV-cleared and HPV-uncleared groups regarding age, disease stage, HPV subtype, VM community state types, and VM diversity (α and ß). Women with the depletion of enterococcus ASV_62 and enrichment in Lactobacillus iners at baseline were less likely to have HPV clearance at month 12. Further analysis revealed a significant negative association between high abundance of L. iners and HPV clearance in patients who received non-operative treatment (OR = 3.94, p = 0.041), but not in those who received operative treatment (OR = 1.86, p = 0.660). Our findings provide new evidence for the potential role of VM in the persistent HR-HPV infections.

12.
Molecules ; 27(22)2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36431955

RESUMO

Qingdai-Mabo (QM), a traditional Chinese herbal formula composed of medicinal herb and fungus, has been used for treatment of cough and viral pneumonia. However, the underlying mechanism and bioactive components against anti-influenza A virus remain unclear. In the present study, ethyl acetate (EA) extract of QM decoctions was tested for its biological activity against acute lung injury (ALI) and its main components were identified using UPLC-MS/MS. In total, 18 bioactive components were identified, including 2-Methylquinaozlin-4(3H)-one (C1), which showed significant antiviral activity in vitro with an IC50 of 23.8 µg/mL. Furthermore, we validated the efficacy of C1 in ameliorating ALI lesions and inflammation in influenza A virus-infected mice. The results showed that C1 significantly reduced the lung index, downregulated neuraminidase (NA) and nucleoprotein (NP), and decreased the expression of pro-inflammatory molecules IFN-α, TNF-α, MCP-1, IL-6, and IL-8; however, they enhanced levels of IL-10 and IFN-γ in lung homogenate from mice infected by influenza A virus. In addition, C1 inhibited the recruitment of macrophages. These in vitro and in vivo studies suggested that the significant anti-influenza A virus activity contributed to its curative effect on lesions and inflammation of viral pneumonia in mice. Given its potential antiviral activity against influenza A virus, C1 is determined to be a main active component in the EA extract of QM. Taken together, the antiviral activity of C1 suggests its potential as an effective treatment against viral pneumonia via the inhibition of virus replication, but the mechanism C1 on antiviral research needs to be explored further.


Assuntos
Lesão Pulmonar Aguda , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Pneumonia Viral , Camundongos , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Cromatografia Líquida , Espectrometria de Massas em Tandem , Lesão Pulmonar Aguda/tratamento farmacológico , Inflamação/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Extratos Vegetais/farmacologia
13.
Nanomaterials (Basel) ; 12(22)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36432388

RESUMO

In this paper, the micropyramid structure was transferred to the TiO2 substrate by soft imprinting. Then, the PPy nanobowls were assembled onto the surface of the TiO2 micropyramids through the induction of the PS template. Finally, a layer of Ag nanoparticles was deposited on the surface of PPy nanobowls to form a novel Ag nanoparticle/PPy nanobowl/TiO2 micropyramid SERS substrate. Its structure is similar to the bioinspired compound eyes. This substrate exhibited excellent antireflection, ultra-sensitivity, excellent uniformity, and recyclability. The concentration of R6G molecules can be detected as low as 10-9 mol/L, and the Raman enhancement factor can reach 3.4 × 105. In addition, the excellent catalytic degradation performance of the substrate ensures recyclability. This work proves that the micropyramid structure can be applied to other SERS materials besides silicon by the above methods, which broadens the selection range of composite SERS materials.

14.
J Mol Histol ; 53(6): 947-954, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36260151

RESUMO

This article investigated the effect of Insm1 on RPC differentiation in mice and the underlying mechanism. The retinal tissues of mouse embryo at 12.5 days (E12.5) and postnatal 14 days (P14) were collected, following by the detection of Insm1 and corresponding markers by immunofluorescent staining. RPCs isolated from retinal tissues at P1 were cultured in culture medium for 7 days. The differentiation of photoreceptor and glial cells was assessed after RPCs transferred to the differentiation medium for 20 days. Next, the effect of Insm1 overexpression on the differentiation of RPCs toward rod photoreceptor and glial cells were assessed. Insm1 was highly expressed in RPCs of retinal tissues and decline in photoreceptor cells, while hardly expressed in glial cells. Based on the results of Pax-6 positive immunofluorescent staining and flow cytometry detection, RPCs were successfully isolated from retinal tissues. After the culture in differentiation medium, RPCs showed positive staining of Rhodopsin and glial fibrillary acidic protein (GFAP). Further results showed that overexpression of Insm1 significantly increased the percentage of Rhodopsin positive cells, and up-regulated Sonic Hedgehog (SHH), hairy and enhancer of split homolog-1(Hes1), S-opsin and Rhodopsin levels, while decreased the percentage of Glutamine synthetase positive cells, and reduced Glutamine synthetase and GFAP levels. Whereas, the effect of Insm1 overexpression on these protein levels were partly abolished by the knockdown of SHH or Hes1. We conclude that Insm1 promotes the differentiation of RPCs into photoreceptor cells in the developing retina through up-regulation of SHH.


Assuntos
Glutamato-Amônia Ligase , Rodopsina , Camundongos , Animais , Rodopsina/genética , Rodopsina/metabolismo , Rodopsina/farmacologia , Regulação para Cima , Glutamato-Amônia Ligase/metabolismo , Glutamato-Amônia Ligase/farmacologia , Proteínas Hedgehog/metabolismo , Células-Tronco , Diferenciação Celular , Retina/metabolismo , Células Fotorreceptoras/metabolismo , Proteínas Repressoras/metabolismo , Proteínas Repressoras/farmacologia
15.
Int J Biol Macromol ; 222(Pt B): 2414-2425, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36252625

RESUMO

Previous studies showed that crude Houttuynia cordata polysaccharides (CHCP) exerted therapeutic effects on acute lung injury induced by influenza A virus (IAV) in mice. Here, an acidic heteropolysaccharide from H. cordata, named HCPM (Mw, 19.1 kDa), was obtained directly from CHCP using sequential ultrafiltration membrane columns. The backbone of HCPM was consisted of 1, 3, 6-ß-Manp, 1, 4-α-GalpA, 1, 2-α-Rhap, and 1, 2, 4-α-Rhap, with main branches of glucan, arabinan, and galactan substituted at C-3 of 1, 3, 6-ß-Manp or C-4 of 1, 2, 4-α-Rhap. The structural information was further validated by oligosaccharide sequencing analysis using UPLC-ESI-MS. Furthermore, HCPM exhibited a potent anti-complementary activity with CH50 value of 254.1 ± 7.8 µg/mL in vitro and significantly attenuated IAV-induced lung and gut injuries in vivo by inhibiting viral replication, reducing inflammatory responses, and suppressing complement overactivation. These results suggested that HCPM might be a key H. cordata substance for pulmonary infection treatment.


Assuntos
Lesão Pulmonar Aguda , Houttuynia , Vírus da Influenza A Subtipo H1N1 , Camundongos , Animais , Houttuynia/química , Ultrafiltração , Lesão Pulmonar Aguda/tratamento farmacológico , Pulmão
16.
Tomography ; 8(5): 2565-2573, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-36287813

RESUMO

BACKGROUND: To investigate the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy on brain glucose metabolism in patients with diffuse large B cell lymphoma (DLBCL). METHODS: Seventy-two patients with newly diagnosed DLBCL underwent FDG PET/CT brain and whole-body scans at baseline (PET0), in the interim of chemotherapy (PET2), and at the end (PET6) of chemotherapy. All three brain scans of each patient were analyzed using statistical parametric mapping software. RESULTS: Compared with the PET0 scan, the PET2 and PET6 scans revealed a significantly higher glucose metabolism throughout the whole brain, with the PET6 scan revealing a higher metabolism than the PET2 scan. Patients with a complete response (CR) displayed decreased glucose metabolism in the lingual gyrus and increased glucose metabolism in the pons after chemotherapy compared with the findings in patients with partial responses or progressive disease. CONCLUSIONS: Brain glucose metabolism was affected by R-CHOP treatment throughout the entire chemotherapy protocol.


Assuntos
Linfoma Difuso de Grandes Células B , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Vincristina/uso terapêutico , Rituximab/uso terapêutico , Prednisona/uso terapêutico , Fluordesoxiglucose F18 , Glucose , Anticorpos Monoclonais Murinos/uso terapêutico , Tomografia Computadorizada por Raios X/métodos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Encéfalo/diagnóstico por imagem
17.
Acta Pharmacol Sin ; 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36216897

RESUMO

Neuronal loss is a primary factor in determining the outcome of ischemic stroke. Oridonin (Ori), a natural diterpenoid compound extracted from the Chinese herb Rabdosia rubescens, has been shown to exert anti-inflammatory and neuroregulatory effects in various models of neurological diseases. In this study we investigated whether Ori exerted a protective effect against reperfusion injury-induced neuronal loss and the underlying mechanisms. Mice were subjected to transient middle cerebral artery occlusion (tMCAO), and were injected with Ori (5, 10, 20 mg/kg, i.p.) at the beginning of reperfusion. We showed that Ori treatment rescued neuronal loss in a dose-dependent manner by specifically inhibiting caspase-9-mediated neuronal apoptosis and exerted neuroprotective effects against reperfusion injury. Furthermore, we found that Ori treatment reversed neuronal mitochondrial damage and loss after reperfusion injury. In N2a cells and primary neurons, Ori (1, 3, 6 µM) exerted similar protective effects against oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury. We then conducted an RNA-sequencing assay of the ipsilateral brain tissue of tMCAO mice, and identified receptor-interacting protein kinase-3 (RIPK3) as the most significantly changed apoptosis-associated gene. In N2a cells after OGD/R and in the ipsilateral brain region, we found that RIPK3 mediated excessive neuronal mitophagy by activating AMPK mitophagy signaling, which was inhibited by Ori or 3-MA. Using in vitro and in vivo RIPK3 knockdown models, we demonstrated that the anti-apoptotic and neuroprotective effects of Ori were RIPK3-dependent. Collectively, our results show that Ori effectively inhibits RIPK3-induced excessive mitophagy and thereby rescues the neuronal loss in the early stage of ischemic stroke.

18.
Ultrason Sonochem ; 90: 106183, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36201933

RESUMO

Nisin, a peptide used as a natural food preservative, is employed in this work for the development of a novel nanocarrier system. Stable and uniform nisin-shelled nanoemulsions (NSNE) with a diameter of 100 ± 20 nm were successfully prepared using 20 kHz flow-through ultrasonication technique. The NSNE showed limited toxicity, high bactericidal activity and high drug loading capacity (EE 65 % w/w). In addition, the nisin shell was exploited for the site-specific attachment of a recombinantly produced cancer targeting ligand (αHER2LPETG IgG). Employing a unique two phases (bio-click) approach which involved both Sortase A mediated Azide Bioconjugation (SMAB) and Strain Promoted Azide Alkyne Cycloaddition (SPAAC) reactions, targeted NSNE (NSNEDOX-αHER2 IgG) were successfully assembled and loaded with the chemotherapeutic drug Doxorubicin (DOX). Finally, NSNEDOX-αHER2 IgG showed cancer-specific binding and augmented cytotoxicity to HER2 expressing tumour cells.


Assuntos
Neoplasias , Nisina , Humanos , Azidas , Nisina/farmacologia , Doxorrubicina/farmacologia , Imunoglobulina G
19.
Front Endocrinol (Lausanne) ; 13: 860261, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36187124

RESUMO

Recurrent pregnancy loss (RPL) is a severe complication of pregnancy that is caused by genetic abnormalities, immune dysfunction, aberrant cell biology, and tissue structure destruction. Among which, placental dysfunction is crucial in the pathogenetic progression of RPL. Although some regulatory factors associated with RPL have been reported, the placental changes correlated with RPL still need to be elucidated. Here, we found that a portion of RPL patients presented with low serum and placental S100P expression. Using a human trophoblast stem cell model, we demonstrated that S100P was exclusively expressed in syncytiotrophoblast (ST)-like syncytia (ST(2D)-TSCT) and that loss of S100P expression in ST(2D)-TSCT cells impaired ß-hCG secretion, leading to syncytialization failure during early placental development. Moreover, we found that S100P is involved in regulating trophoblast syncytialization by downregulating the protein level of Yes-associated protein 1 (YAP1), which plays a pivotal role in maintaining trophoblast stemness. Together, our findings suggest that S100P plays an essential role in regulating trophoblast syncytialization during early placental development in humans via YAP1. Additionally, lower serum S100P levels may predict poor pregnancy outcomes and represent a potentially useful marker for evaluating placental biological function during early pregnancy.


Assuntos
Placentação , Trofoblastos , Proteínas de Ligação ao Cálcio/metabolismo , Gonadotropina Coriônica Humana Subunidade beta/genética , Gonadotropina Coriônica Humana Subunidade beta/metabolismo , Feminino , Humanos , Proteínas de Neoplasias , Placenta/metabolismo , Gravidez , Trofoblastos/metabolismo , Proteínas de Sinalização YAP
20.
Comput Intell Neurosci ; 2022: 1300068, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36188681

RESUMO

In order to further improve the evaluation quality of enterprise operating efficiency, reduce the error items and invalid items of partition, and improve the objectivity of operating condition evaluation, this study takes listed enterprises as an example and proposes an evaluation method of operating efficiency based on association rule algorithm and data set. In this method, the results of operating efficiency are scientifically analyzed from horizontal and vertical dimensions. The operating cost of total assets of listed companies is taken as indicators, and the correlation test is carried out by Kendall's tau_b. From the longitudinal comparison results, it can be seen that only 12 of the 19 enterprises in the study have small-scale changes and increase year by year, accounting for 63.16%. At the same time, there are also 6 enterprises with an overall trend of decline, which objectively reflects the reasonable operation status and operation scale of enterprises in the study.


Assuntos
Algoritmos , China
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