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1.
Biochem Pharmacol ; 223: 116193, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38582268

RESUMO

Ovarian aging leads to infertility and birth defects. We aimed to clarify the role of Indole-3-carbinol (I3C) in resistance to oxidative stress, apoptosis, and fibrosis in ovarian aging. I3C was administered via intraperitoneal injection for 3 weeks in young or old mice. Immunohistochemistry; Masson, Sirius red, and TUNEL staining; follicle counting; estrous cycle analysis; and Western blotting were used for validating the protective effect of I3C against ovarian senescence. Human granulosa-like tumor cell line and primary granulosa cells were used for in vitro assay. The results indicated that I3C inhibited ovarian fibrosis and apoptosis while increasing the number of primordial follicles. Mechanistic studies have shown that I3C promoted the nuclear translocation of nuclear factor-erythroid 2-related factor (Nrf2) and upregulated the expression of heme oxygenase 1 (HO-1). Additionally, I3C increased cell viability and decreased lactate dehydrogenase, malondialdehyde, reactive oxygen species and JC-1 levels. Furthermore, the antioxidant effect of I3C was found to be dependent on the activation of Nrf2 and HO-1, as demonstrated by the disappearance of the effect upon inhibition of Nrf2 expression. In conclusion, I3C can alleviate the ovarian damage caused by aging and may be a protective agent to delay ovarian aging.


Assuntos
Heme Oxigenase-1 , Indóis , Fator 2 Relacionado a NF-E2 , Camundongos , Feminino , Humanos , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Heme Oxigenase-1/metabolismo , Estresse Oxidativo , Fibrose , Apoptose
2.
BMC Pregnancy Childbirth ; 24(1): 236, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575874

RESUMO

BACKGROUND: To analyze the impact of the time of natural cessation of the umbilical cord on maternal and infant outcomes in order to explore the time of clamping that would be beneficial to maternal and infant outcomes. METHODS: The study was a cohort study and pregnant women who met the inclusion and exclusion criteria at the Obstetrics and Gynecology Department of Qilu Hospital of Shandong University from September 2020 to September 2021. Analysis using Kruskal-Wallis rank sum test, Pearson's Chi-squared test, generalized linear mixed model (GLMM) and repeated measures ANOVA. If the difference between groups was statistically significant, the Bonferroni test was then performed. A two-sided test of P < 0.05 was considered statistically significant. RESULTS: A total of 345 pregnants were included in this study. The subjects were divided into the ≤60 seconds group (n = 134), the 61-89 seconds group (n = 106) and the ≥90 seconds group (n = 105) according to the time of natural arrest of the umbilical cord. There was no statistically significant difference in the amount of postpartum hemorrhage and the need for iron, medication, or supplements in the postpartum period between the different cord spontaneous arrest time groups for mothers (P > 0.05). The weight of the newborns in the three groups was (3316.27 ± 356.70) g, (3387.26 ± 379.20) g, and (3455.52 ± 363.78) g, respectively, and the number of days of cord detachment was 12.00 (8.00, 15.75) days, 10.00 (7.00, 15.00) days and 9.00 (7.00, 13.00) days, respectively, as the time of natural cessation of the cord increased. The neonatal lymphocyte ratio, erythrocyte pressure, and hemoglobin reached a maximum in the 61-89 s group at (7.41 ± 2.16) %, (61.77 ± 8.17) % and (194.52 ± 25.84) g/L, respectively. Lower incidence of neonatal hyperbilirubinemia in the 61-89 s group compared to the ≥90s group 0 vs 4.8 (P < 0.05). CONCLUSIONS: In full-term singleton vaginal births, maternal and infant outcomes are better when waiting for 61-89 s after birth for the cord to stop pulsating naturally, suggesting that we can wait up to 90s for the cord to stop pulsating naturally, and if the cord does not stop pulsating after 90s, artificial weaning may be more beneficial to maternal and infant outcomes.


Assuntos
Hemorragia Pós-Parto , Cordão Umbilical , Lactente , Recém-Nascido , Gravidez , Humanos , Feminino , Estudos de Coortes , Estudos Prospectivos , Nascimento a Termo
3.
Leuk Res ; 141: 107499, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38640632

RESUMO

Acute myeloid leukemia (AML) is a hematopoietic malignancy with a high relapse rate and progressive drug resistance. Alternative polyadenylation (APA) contributes to post-transcriptional dysregulation, but little is known about the association between APA and AML. The APA quantitative trait locus (apaQTL) is a powerful method to investigate the relationship between APA and single nucleotide polymorphisms (SNPs). We quantified APA usage in 195 Chinese AML patients and identified 4922 cis-apaQTLs related to 1875 genes, most of which were newly reported. Cis-apaQTLs may modulate the APA selection of 115 genes through poly(A) signals. Colocalization analysis revealed that cis-apaQTLs colocalized with cis-eQTLs may regulate gene expression by affecting miRNA binding sites or RNA secondary structures. We discovered 207 cis-apaQTLs related to AML risk by comparing genotype frequency with the East Asian healthy controls from the 1000 Genomes Project. Genes with cis-apaQTLs were associated with hematological phenotypes and tumor incidence according to the PHARMGKB and MGI databases. Collectively, we profiled an atlas of cis-apaQTLs in Asian AML patients and found their association with APA selection, gene expression, AML risk, and complex traits. Cis-apaQTLs may provide insights into the regulatory mechanisms related to APA in AML occurrence, progression, and prognosis.

4.
Materials (Basel) ; 17(7)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38612020

RESUMO

Salt erosion has an adverse impact on the durability of asphalt pavements. Porous asphalt concrete is particularly susceptible to the influence of salt. In this study, a finite element model was developed to investigate the fracture behavior of PAC exposed to salt erosion. The 2D heterogeneous structure of PAC was generated with an image-aided approach to computationally study the fracture behavior of PAC. Laboratory SCB tests were conducted to validate the finite element model. The simulation results of the SCB tests indicate that the peak load of the PAC decreased by 21.8% in dry-wet cycles and 26.1% in freeze-thaw cycles compared to the control group. The salt solution accelerated the degradation of the durability of PAC under both dry-wet cycles and freeze-thaw cycle conditions, which is consistent with laboratory tests. After flushing treatment before the drying phase, the peak load of the PAC in salt environments increased by 5.3% compared to that of the samples with no flushing. Salt erosion also results in a higher average value of scalar stiffness degradation (SDEG), and the damaged elements were primarily the cohesive elements in the fracture of the PAC. Additionally, the influence of crucial factors including the void content, adhesion and cohesion, and loading rate on the fracture behavior of the PAC was analyzed. As the void content increases, the average SDEG value of the cohesive elements increases and surpasses the average SDEG value of the adhesive elements at a void content of approximately 9%. The performance of the fine aggregate matrix (FAM) has a much greater impact than the FAM-aggregate interface on the durability of the PAC. And there were more damaged CZM elements with the increase in the loading rate. Salt erosion results in higher SDEG values and a larger number of cohesive damaged elements at each loading rate.

5.
J Nanobiotechnology ; 22(1): 195, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643173

RESUMO

Doxorubicin (DOX) is a chemotherapeutic agent widely used for tumor treatment. Nonetheless its clinical application is heavily limited by its cardiotoxicity. There is accumulated evidence that transplantation of mesenchymal stem cell-derived exosomes (MSC-EXOs) can protect against Dox-induced cardiomyopathy (DIC). This study aimed to examine the cardioprotective effects of EXOs isolated from human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) against DIC and explore the potential mechanisms. EXOs were isolated from the cultural supernatant of human BM-MSCs (BM-MSC-EXOs) and iPSC-MSCs (iPSC-MSC-EXOs) by ultracentrifugation. A mouse model of DIC was induced by intraperitoneal injection of Dox followed by tail vein injection of PBS, BM-MSC-EXOs, or iPSC-MSC-EXOs. Cardiac function, cardiomyocyte senescence and mitochondrial dynamics in each group were assessed. In vitro, neonatal mouse cardiomyocytes (NMCMs) were subjected to Dox and treated with BM-MSC-EXOs or iPSC-MSC-EXOs. The mitochondrial morphology and cellular senescence of NMCMs were examined by Mitotracker staining and senescence-associated-ß-galactosidase assay, respectively. Compared with BM-MSC-EXOs, mice treated with iPSC-MSC-EXOs displayed improved cardiac function and decreased cardiomyocyte mitochondrial fragmentation and senescence. In vitro, iPSC-MSC-EXOs were superior to BM-MSC-EXOs in attenuation of cardiomyocyte mitochondrial fragmentation and senescence caused by DOX. MicroRNA sequencing revealed a higher level of miR-9-5p in iPSC-MSC-EXOs than BM-MSC-EXOs. Mechanistically, iPSC-MSC-EXOs transported miR-9-5p into DOX-treated cardiomyocytes, thereby suppressing cardiomyocyte mitochondrial fragmentation and senescence via regulation of the VPO1/ERK signal pathway. These protective effects and cardioprotection against DIC were largely reversed by knockdown of miR-9-5p in iPSC-MSC-EXOs. Our results showed that miR-9-5p transferred by iPSC-MSC-EXOs protected against DIC by alleviating cardiomyocyte senescence via inhibition of the VPO1/ERK pathway. This study offers new insight into the application of iPSC-MSC-EXOs as a novel therapeutic strategy for DIC treatment.


Assuntos
Cardiomiopatias , Células-Tronco Pluripotentes Induzidas , MicroRNAs , Humanos , Camundongos , Animais , Miócitos Cardíacos/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Cardiomiopatias/induzido quimicamente , Transdução de Sinais , Doxorrubicina
6.
Nano Lett ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647348

RESUMO

Artificial synapses and bionic neurons offer great potential in highly efficient computing paradigms. However, complex requirements for specific electronic devices in neuromorphic computing have made memristors face the challenge of process simplification and universality. Herein, reconfigurable Ag/HfO2/NiO/Pt memristors are designed for feasible switching between volatile and nonvolatile modes by compliance current controlled Ag filaments, which enables stable and reconfigurable synaptic and neuronal functions. A neuromorphic computing system effectively replicates the biological synaptic weight alteration and continuously accomplishes excitation and reset of artificial neurons, which consist of bionic synapses and artificial neurons based on isotype Ag/HfO2/NiO/Pt memristors. This reconfigurable electrical performance of the Ag/HfO2/NiO/Pt memristors takes advantage of simplified hardware design and delivers integrated circuits with high density, which exhibits great potency for future neural networks.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38626346

RESUMO

Background: The incidence of chronic obstructive pulmonary disease (COPD) and osteoporosis are rising worldwide. Observational studies showed that COPD is associated with increased risk of osteoporosis. We performed the Mendelian randomization (MR) study to genetically investigate the causality of COPD on osteoporosis. Methods: We explored the causal effect of COPD on osteoporosis by the MR analysis. A total of 108 genetic loci single nucleotide polymorphisms were related to COPD. The primary approach in this MR analysis was the inverse variance-weighted (IVW) method. Simple median, weighted median, MR Egger and penalized weighted median analyzed the sensitivity. Results: The study found that genetically predicted COPD is causally linked to an increased risk of osteoporosis, as evidenced by both the fixed-effect IVW model and random-effect IVW model (odds ratio [OR], 1.010; 95% CI, 1.001-1.019, P=0.021; OR, 1.010; 95% CI, 1.001-1.020, P=0.039). This association was also observed in other methods, including the simple median, weighted median, Penalised weighted median, MR-Egger method, and MR Egger (bootstrap) method. The results of the IVW and MR-Egger analyses showed no heterogeneity (Q=131.374, P=0.061 and Q=128.895, P=0.069, respectively). Additionally, MR-Egger regression did not reveal any pleiotropic influence through genetic variants (intercept, -0.004; P=0.101). Lastly, the leave-one-out sensitivity analysis did not identify any individual SNP that significantly influenced the association between COPD and osteoporosis. Conclusion: The Mendelian randomization analysis showed a significant detrimental effect of COPD on the risk of osteoporosis.

8.
Geroscience ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38499958

RESUMO

Di-(2-ethylhexyl) phthalate (DEHP), a prevalent plasticizer, is known to have endocrine-disrupting effects on males and cause reproductive toxicity. There were causal effects of DEHP on testosterone levels in the real world by Mendelian randomization analysis. Exposure to DEHP during the preadult stage might lead to premature testicular senescence, but the mechanisms responsible for this have yet to be determined. In this study, we administered DEHP (300 mg/kg/day) to male C57BL/6 mice from postnatal days 21 to 49. The mice were kept for 6 months without DEHP. RNA sequencing was conducted on testicular tissue at PNM6. The results indicated that DEHP hindered testicular development, lowered serum testosterone levels in male mice, and induced premature testicular senescence. TM3 Leydig cells were exposed to 300 µM of mono(2-ethylhexyl) phthalate (MEHP), the bioactive metabolite of DEHP, for 72 h. The results also found that DEHP/MEHP induced senescence in vivo and in vitro. The mitochondrial respiratory chain was disrupted in Leydig cells. The expression and stability of STAT5B were elevated by MEHP treatment in TM3 cells. Furthermore, p-ERK1/2 was significantly decreased by STAT5B, and mitochondria-STAT3 (p-STAT3 ser727) was significantly decreased due to the decrease of p-ERK1/2. Additionally, the senescence level of TM3 cells was decreased and treated with 5 mM NAC for 1 h after MEHP treatment. In conclusion, these findings provided a novel mechanistic understanding of Leydig cells by disrupting the mitochondrial respiratory chain through STAT5B-mitoSTAT3.

9.
Clin Respir J ; 18(3): e13743, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38529681

RESUMO

BACKGROUND: This study aimed to investigate the radiological, pathological, and prognostic characteristics of large consolidative-type pulmonary invasive mucinous adenocarcinomas (IMA). METHODS: We retrospectively reviewed 738 patients who confirmed IMA between January 2010 and August 2022, and two radiologists reviewed imaging data to determine subtypes. We included 41 patients with pathologically large consolidative-type IMA. We analyzed their radiological, pathological, and prognostic characteristics. The recurrence-free survival (RFS) and overall survival (OS) were determined using the Kaplan-Meier method. RESULTS: Most lesions were located in the lower lobe, with 46.3% patients showing multiple lesions. Halo, angiogram, vacuole, air bronchogram, and dead branch sign were observed in 97.6%, 73.2%, 63.4%, 61.0%, and 61.0% of the cases, respectively. Unevenly low enhancement was observed in 88.89% of patients. T3 and T4 pathological stages were observed in 50.0% and 30.6% of patients, respectively. Lymph node metastasis was observed in 16.7% patients, with no distant metastasis. Spread-through air spaces and intrapulmonary dissemination were observed in 27.8% and 19.4% patients, respectively. Moreover, Kirsten rat sarcoma viral oncogene mutations were found in 68.6% of cases, and no epidermal growth factor receptor mutations were seen. Among all mutation sites, G12V mutation is the most common, accounting for 40%. The average RFS and OS were 19.4 and 66.4 months, respectively, with 3-year RFS and OS rates of 30.0% and 75.0%, respectively. Pleural invasion and lymph node metastasis were independent risk factors for diagnosis. CONCLUSION: Halo, vacuole, angiogram, and dead branch signs were frequently observed in consolidative-type IMA. Kirsten rat sarcoma viral oncogene mutations are common in consolidative-type IMA, especially site G12V, whereas epidermal growth factor receptor mutations were rare; therefore, gene immunotherapy was more difficult. Most patients were in stage T3-T4; however, lymph node metastasis was rare.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma Mucinoso , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Adenocarcinoma/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Metástase Linfática , Estudos Retrospectivos , Proteínas Proto-Oncogênicas p21(ras)/genética , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Prognóstico , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/tratamento farmacológico , Estadiamento de Neoplasias
11.
Drug Des Devel Ther ; 18: 685-697, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38445065

RESUMO

Purpose: We designed this study to investigate the effect of intravenous use of penehyclidine on postoperative nausea and vomiting (PONV) after gynecological laparoscopic surgery. Patients and Methods: Ninety-two Women Patients (Aged ≥ 18) Scheduled for Elective Gynecologic Laparoscopy Were Enrolled in the Current Study. Patients Were Equally Randomized Assigned Into Penehyclidine group (PHC group: received a bolus of penehyclidine 10 µg/kg during the induction of anesthesia, then followed by a continuous infusion of 10 µg/kg penehyclidine at a fixed rate of 2.0 mL/h in postoperative intravenous analgesia pump over 48h, 0.5 mg upper limit respectively) or Control group (received 0.9% saline in replace of penehyclidine at the same time points). The primary outcome measure was the incidence of postoperative nausea and vomiting in the postanesthesia care unit and ward area. Quality of Recovery-15 (QoR-15) scores and general comfort questionnaire (GCQ) scores were assessed on postoperative day (POD) 1, 2. Results: Patients between two groups had comparable baseline characteristics. Compared with the Control group, the incidence and severity of PONV, postoperative nausea (PON), and postoperative vomiting (POV) were significantly lower in the PHC group at 2h (PONV: P = 0.002, P = 0.004, respectively; PON: P = 0.018, P = 0.038, respectively; POV: P = 0.011, P = 0.072, respectively), 24h (PONV: P = 0.003, P = 0.001, respectively; PON: P = 0.010, P = 0.032, respectively; POV: P = 0.006, P = 0.044, respectively), and 48h (PONV: P = 0.003, P = 0.002, respectively; PON: P = 0.007, P = 0.019, respectively; POV: P = 0.002, P = 0.013, respectively) after surgery. The QoR-15 and GCQ scores of the PHC group were significantly higher than those of the Control group at POD 1, 2 (P < 0.001; P < 0.001, respectively). Conclusion: Our findings suggest that perioperative intravenous application of penehyclidine can effectively prevent postoperative nausea and vomiting in gynecological laparoscopic surgery patients and improve postoperative recovery.


Assuntos
Náusea e Vômito Pós-Operatórios , Quinuclidinas , Feminino , Humanos , Anestesia por Inalação , Laparoscopia/efeitos adversos , Náusea e Vômito Pós-Operatórios/prevenção & controle , Quinuclidinas/uso terapêutico , Adolescente , Adulto , Método Duplo-Cego
12.
Heliyon ; 10(5): e27107, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38434265

RESUMO

TTMV::RARA is a recently reported fusion gene associated with acute promyelocytic leukemia (APL), caused by the integration of torque teno mini virus (TTMV) genomic fragments into the second intron of the RARA gene. Currently, there have been only six documented cases, with clinical presentations showing significant variability. Although initial responses to all-trans retinoic acid (ATRA) treatment may be observed in patients with TTMV::RARA-APL, the overall prognosis remains unfavorable among infrequent reported cases. This article presents a pediatric case that manifested as PML::RARA-negative APL with central nervous system involvement at onset. The patient experienced both intramedullary and extramedullary relapse one year after undergoing allogeneic hematopoietic stem cell transplantation. Upon identification as TTMV::RARA-APL and subsequent administration of two rounds of ATRA-based treatment, the patient rapidly developed multiple RARA ligand-binding domain mutations and demonstrated extensive resistance to ATRA and various other therapeutic interventions. Additionally, the patient experienced ARID1A mutant clone expansion and progressed MYC-targeted gene activation. This case represents the first documentation of extramedullary involvement at both the initial diagnosis and relapse stages, emphasizing the intricate clinical features and challenges associated with the rapid accumulation of multiple ATRA-resistant mutations in TTMV::RARA-APL, characterizing it as a distinct and complex sub-entity of atypical APL.

13.
J Clin Rheumatol ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427830

RESUMO

OBJECTIVE: The aim of the study was to examine the factors influencing the therapeutic effect of patients with systemic lupus erythematosus combined with immune thrombocytopenia (SLE-ITP) and develop a prediction model to predict the therapeutic effect of SLE-ITP. METHODS: Three hundred twenty-four SLE-ITP patients were retrieved from the electronic health record database of SLE patients in Jiangsu Province according to the latest treatment response criteria for ITP. We adopted the Cox model based on the least absolute shrinkage and selection operator to explore the impact factors affecting patient therapeutic effect, and we developed neural network model to predict therapeutic effect, and in prediction model, cost-sensitivity was introduced to address data category imbalance, and variational autoencoder was used to achieve data augmentation. The performance of each model was evaluated by accuracy and the area under the receiver operator curve. RESULTS: The results showed that B-lymphocyte count, H-cholesterol level, complement-3 level, anticardiolipin antibody, and so on could be used as predictors of SLE-ITP curative effect, and abnormal levels of alanine transaminase, immunoglobulin A, and apolipoprotein B predicted adverse treatment response. The neural network treatment effect prediction model based on cost-sensitivity and variational autoencoder was better than the traditional classifiers, with an overall accuracy rate closed to 0.9 and a specificity of more than 0.9, which was useful for clinical practice to identify patients at risk of ineffective treatment response and to achieve better individualized management. CONCLUSIONS: By predicting the curative effect of SLE-ITP, the severity of patients can be determined, and then the best treatment strategy can be planned to avoid ineffective treatment.

14.
Am J Hematol ; 99(5): 824-835, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38321864

RESUMO

Two recent guidelines, the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) and the International Consensus Classification (ICC), were published to refine the diagnostic criteria of acute myeloid leukemia (AML). They both consider genomic features more extensively and expand molecularly defined AML subtypes. In this study, we compared the classifications of 1135 AML cases under both criteria. According to WHO-HAEM5 and ICC, the integration of whole transcriptome sequencing, targeted gene mutation screening, and conventional cytogenetic analysis identified defining genetic abnormalities in 89% and 90% of AML patients, respectively. The classifications displayed discrepancies in 16% of AML cases after being classified using the two guidelines, respectively. Both new criteria significantly reduce the number of cases defined by morphology and differentiation. However, their clinical implementation heavily relies on comprehensive and sophisticated genomic analysis, including genome and transcriptome levels, alongside the assessment of pathogenetic somatic and germline variations. Discrepancies between WHO-HAEM5 and ICC, such as the assignment of RUNX1 mutations, the rationality of designating AML with mutated TP53 as a unique entity, and the scope of rare genetic fusions, along with the priority of concurrent AML-defining genetic abnormalities, are still pending questions requiring further research for more elucidated insights.


Assuntos
Leucemia Mieloide Aguda , Humanos , Consenso , Mutação , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Genômica , Organização Mundial da Saúde
15.
Adv Mater ; : e2310443, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372054

RESUMO

Liver fibrosis represents a reversible stage of various chronic liver diseases that progresses to cirrhosis. This condition is characterized by an imbalance between tissue damage and repair, and the production of fibers in the liver exceeds their degradation. Oxidative stress (OS) resulting from tissue injury and endoplasmic reticulum stress (ERS) triggered by the overproduction of proteins are pivotal factors in liver fibrosis. Melatonin demonstrates the capability to neutralize free radicals, shielding cells from oxidative harm. It is also a specific inhibitor of the ERS receptor transcription activating factor 6 (ATF6), indicating its great potential in ameliorating liver fibrosis. However, its limited water solubility and oral bioavailability of under 15% present hurdles in achieving therapeutic blood concentrations for treating liver fibrosis. The PLGA@Melatonin is constructed by loading melatonin with poly (lactic-co-glycolic acid) (PLGA). Platelet membranes (PM) and activated hepatic stellate cell membranes (HSCM) with high expression of the platelet-derived growth factor receptor (PDGFR) are extracted to successfully construct PM@PLGA@Melatonin and HSCM@PLGA@Melatonin, which are subsequently utilized to treat mice with liver fibrosis. The results illustrated the remarkable therapeutic effects of the two nanoparticles on liver fibrosis, along with their excellent targeting and biosafety properties.

16.
J Asian Nat Prod Res ; 26(1): 69-77, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38305031

RESUMO

Two new depside derivatives 1 and 2 as well as a new pair of rosmarinic acid enantiomers 3a/b were isolated from the leaves of Perilla frutescens (L.) britt. The chemical structures of these compounds were identified based on detailed spectroscopic and physicochemical analyses (HR-ESI-MS, NMR) and comparison of literature data. Compounds 3a/b were obtained by chiral separation, and their absolute configurations were determined by comparison of experimental and calculated ECD spectra. Compounds 3a/b exhibited potential inhibitory activity on nitric oxide (NO) production induced by lipopolysaccharide in RAW264.7 cells with IC50 values of 15.92 ± 3.32 µM and 48.72 ± 4.12 µM.


Assuntos
Perilla frutescens , Perilla frutescens/química , 60556 , Extratos Vegetais/química , Folhas de Planta/química , Anti-Inflamatórios/farmacologia
17.
Sci Data ; 11(1): 244, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413596

RESUMO

Infectious disease outbreaks transcend the medical and public health realms, triggering widespread panic and impeding socio-economic development. Considering that self-limiting diarrhoea of sporadic cases is usually underreported, the Salmonella outbreak (SO) study offers a unique opportunity for source tracing, spatiotemporal correlation, and outbreak prediction. To summarize the pattern of SO and estimate observational epidemiological indicators, 1,134 qualitative reports screened from 1949 to 2023 were included in the systematic review dataset, which contained a 506-study meta-analysis dataset. In addition to the dataset comprising over 50 columns with a total of 46,494 entries eligible for inclusion in systematic reviews or input into prediction models, we also provide initial literature collection datasets and datasets containing socio-economic and climate information for relevant regions. This study has a broad impact on advancing knowledge regarding epidemic trends and prevention priorities in diverse salmonellosis outbreaks and guiding rational policy-making or predictive modeling to mitigate the infringement upon the right to life imposed by significant epidemics.


Assuntos
Surtos de Doenças , Intoxicação Alimentar por Salmonella , Infecções por Salmonella , Humanos , China/epidemiologia , Coleta de Dados , Salmonella , Intoxicação Alimentar por Salmonella/epidemiologia , Infecções por Salmonella/epidemiologia , Revisões Sistemáticas como Assunto , Metanálise como Assunto
18.
Phytochemistry ; 220: 113995, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38307313

RESUMO

To find structurally previously undescribed compounds with pharmacological effects from Prismatomeris tetrandra (Roxb.) K. Schum (Rubiaceae), thirteen undescribed tetrahydroanthraquinones (1⎼13) named prisconnatanones J⎼V and seven known anthraquinones (14⎼20) were isolated and characterized. The structures of these compounds were elucidated by detailed spectroscopic analyses, and their absolute configurations were established by modified Mosher's method and ECD calculations. The antitumor cell proliferative activities of prisconnatanones J⎼V were determined. Among them, prisconnatanones J possessed high antitumor cell proliferation in HGC27 cells (IC50, 0.792 µM) by blocking HGC27 cells in the S phase and significantly inducing apoptosis in HGC27 cells. Prisconnatanone J has no cytotoxicity to normal gastric cells line (GES-1) at 10 µM and showed a considerable selectivity for HGC27 cells. Prisconnatanone J can potentially inhibit tumor cell proliferation and should be further investigated.


Assuntos
Rubiaceae , Proliferação de Células , Linhagem Celular Tumoral , Rubiaceae/química , Apoptose , Estrutura Molecular
19.
Drug Des Devel Ther ; 18: 341-350, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38344258

RESUMO

Background: Emergence agitation (EA) is one of the most common complications in clinical general anesthesia during recovery in adults. Remifentanil and propofol can reduce the incidence of EA, but with no randomized controlled trial to evaluate their effectiveness for treating EA. This study aims to compare the effectiveness of remifentanil and propofol for treating EA following general anesthesia. Patients and methods: Among 152 randomized patients with a mean of 49.5 years, and 99 (65.1%) of them being male, 149 were divided into two groups for subsequent analysis. The remifentanil group (Group R, n = 74) received a 0.5µg kg-1 remifentanil infusion followed by a 0.05µg kg-1 min-1 infusion until 15 minutes, after the onset of agitation. The propofol group (Group P, n = 75) received a 1mg kg-1 propofol infusion once agitation occurred. Emergence agitation was assessed using the Riker Sedation Agitation Score, with a score of ≥5 defining emergence agitation. During the post-anesthesia care unit (PACU), the recurrence of emergence agitation, time to extubation, and discharge from PACU were evaluated. Results: The incidence of reoccurring emergence agitation was lower in Group R (29.7%) compared with Group P (49.3%), with an odds ratio of 0.44 (95% CI 0.22-0.85; P=0.014). The time to extubation was shorter in Group R (mean 12min, range 8-15 min) compared with Group P (mean 17min, range 13-21 min) (P<0.001), as was the time discharge from the PACU (mean 30.5 min, range 25-40 min) vs Group P (mean 37.5 min, range 31-50 min) (P=0.001). Conclusion: Treatment of emergence agitation in adults with remifentanil infusion is more effective than propofol, with a shorter time to extubation and discharge from PACU.


Assuntos
Delírio do Despertar , Propofol , Adulto , Humanos , Masculino , Feminino , Propofol/efeitos adversos , Remifentanil/uso terapêutico , Delírio do Despertar/tratamento farmacológico , Anestesia Geral/efeitos adversos , Incidência , Período de Recuperação da Anestesia , Anestésicos Intravenosos/efeitos adversos
20.
iScience ; 27(2): 108993, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38327786

RESUMO

The rapid development of nuclear energy posed a great threat to the environment and human health. Herein, two hydroxyl-functionalized hyper-crosslinked polymers (PIHCP-1 and PIHCP-2) containing different electron active sites have been synthesized via Friedel-Crafts alkylation reaction of the polyimides. The resulting polymers showed a micro/mesoporous morphology and good thermal and chemical stability. Rely on the high porosity and multi-active sites, the PIHCPs show an ultrahigh iodine uptake capacity reached 6.73 g g-1 and the iodine removal efficiency from aqueous solution also reaches 99.7%. Kinetic analysis demonstrates that the iodine adsorption on PIHCPs was happened on the heterogeneous surfaces in the form of multilayer chemisorption. Electrostatic potential (ESP) calculation proves the great contribution of hydroxyl groups on the iodine capture performance. In addition, the iodine capture efficiency of both adsorbents can be maintained over 91% after four cyclic experiments which ensures their good recyclability for further practical applications.

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