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Objective: This study aims to explore the relationship between different endometrial preparations and pregnancy outcomes among patients with regular ovulatory cycles in order to find the best endometrial preparation methods in the freeze-thaw embryo transfer (FET) cycle. Materials and Methods: This is a retrospective study to investigate FET pregnancy outcomes in women who had a regular menstrual cycle, were younger than 35 years old, and underwent a modified natural cycle (mNC), ovulation induction (OI), or a hormone replacement treatment (HRT) cycle. A total of 1071 frozen cycles were included for analysis. Results: The implantation rate and live birth rate (LBR) in the OI group show a significant difference when compared to the mNC and HRT groups (P < 0.01). After adjusting for confounding factors, the logistic regression analysis revealed that the number of embryos transferred, the embryo stage, and quality were significantly associated with clinical pregnancy rate and LBR. The LBR was additionally affected by the mode of the endometrial preparation; the OI cycle could increase LBR. Conclusions: Endometrial preparation methods affect the LBR in women with a regular menstrual cycle. The OI cycle had an advantage in the LBR of FET.
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The binding capacity of ß-Lactoglobulin (BLG) is crucial for delivering polyphenols, influenced by structural changes. High pressure processing (HPP) has the potential to modify BLG's structure and aggregation, but its specific impact on BLG-polyphenol interactions is uncertain. This study used circular dichroism spectroscopy and molecular dynamics simulations to reveal HPP-induced structural changes in BLG, supported by particle size analysis indicating aggregation. Seven structurally diverse polyphenols (quercetin-QR, hesperetin-HSP, dihydromyricetin-DHM, gallic acid-GA, (-)-epicatechin-EC, resveratrol-RES, and secoisolariciresinol diglucoside-SDG) were investigated to comprehensively analyze their binding patterns using fluorescence spectroscopy and molecular docking. HPP reduced BLG's ordered structure and increased its aggregation. Binding affinities peaked at 400 MPa for DHM, QR, HSP, GA, and RES, while SDG and EC exhibited maximum affinities at atmospheric pressure and 600 MPa, respectively. Elevated pressures enhanced BLG-polyphenol interactions, particularly at residues 44GLU and 160CYS, with van der Waals forces dominating the binding free energy.
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Pickering emulsions have attracted much attention as a novel emulsifying technology. This research to explore Zein-Citrus pectin nanoparticles stabilized cinnamon essential oil (CEO) Pickering emulsion (ZCCPEs) for constructing Pickering emulsion edible film (PEF). Unlike traditional research, which focuses on antibacterial and antioxidant activities, our research examined the physical properties of PEF, specifically changes in wettability. The results show that PEF has better transparency and tensile strength than the pectin alone direct emulsion film (PAEF), and the spatial distribution of Pickering emulsion droplets gives different wettability on both sides of PEF. The partially hydrophobic upside has important application value in food packaging. At the same time, the PEF is biodegradable and environmentally non-polluting. The edible film loaded with essential oils, developed based on the Pickering stabilization mechanism in this study, possesses several desirable characteristics for potential used as bioactive packaging films in food applications.
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BACKGROUND: For patients with stage III epithelial ovarian cancer, there are limited studies on the effects of postoperative adjuvant radiotherapy (RT). Here we assessed the therapeutic efficacy and toxicity of postoperative radiotherapy to the abdominal and pelvic lymphatic drainage area for stage III epithelial ovarian cancer patients, who had all received surgery and chemotherapy (CT). METHODS: We retrospectively collected patients with stage III epithelial ovarian cancer after cytoreductive surgery (CRS) and full-course adjuvant CT. The chemoradiotherapy (CRT) group patients were treated with intensity modulated radiotherapy (IMRT) to the abdominal and pelvic lymphatic drainage area in our hospital between 2010 and 2020. A propensity score matching analysis was conducted to compare the results between the CRT and CT groups. Kaplan-Meier analysis estimated overall survival (OS), disease-free survival (DFS), and local control (LC) rates. The log-rank test determined the significance of prognostic factors. RESULTS: A total of 132 patients with median follow-up of 73.9 months (9.1-137.7 months) were included (44 and 88 for the CRT and RT groups, retrospectively). The baseline characteristics of age, histology, level of CA12-5, surgical staging, residual tumour, courses of adjuvant CT, and courses to reduce CA12-5 to normal were all balanced. The median DFS time, 5-year OS, and local recurrence free survival (LRFS) were 100.0 months vs 25.9 months (P = .020), 69.2% vs 49.9% (P = .002), and 85.9% vs 50.5% (P = .020), respectively. The CRT group mainly presented with acute haematological toxicities, with no statistically significant difference compared with grade III intestinal adverse effects (3/44 vs 6/88, P = .480). CONCLUSION: This report demonstrates that long-term DFS could be achieved in stage III epithelial ovarian cancer patients treated with IMRT preventive radiation to the abdominal and pelvic lymphatic area. Compared with the CT group, DFS and OS were significantly prolonged and adverse effects were acceptable.
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Estadiamento de Neoplasias , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/mortalidade , Adulto , Idoso , Carcinoma Epitelial do Ovário/terapia , Carcinoma Epitelial do Ovário/patologia , Procedimentos Cirúrgicos de Citorredução/métodos , Radioterapia de Intensidade Modulada/métodos , Radioterapia Adjuvante/métodosRESUMO
Cisplatin-induced acute kidney injury (AKI) increases the patient mortality dramatically and results in an unfavorable prognosis. A strong correlation between AKI and ferroptosis, which is a notable type of programmed cell death, was found in recent studies. Myricitrin is a natural flavonoid compound with diverse pharmacological properties. To investigate the protective effect of myricitrin against cisplatin induced human tubular epithelium (HK-2) cell injury and the underlying anti-ferroptic mechanism by this study. Firstly, a pharmacology network analysis was proposed to explore the myricitrin's effect. HK-2 cells were employed for in vitro experiments. Ferroptosis was detected by cell viability, quantification of iron, malondialdehyde, glutathione, lipid peroxidation fluorescence, and glutathione peroxidase (GPX4) expression. Ferritinophagy was detected by related protein expression (NCOA4, FTH, LC3II/I, and SQSTM1). In our study, GO enrichment presented that myricitrin might be effective in eliminating ferroptosis. The phenomenon of ferroptosis regulated by ferritinophagy was observed in cisplatin-activated HK-2 cells. Meanwhile, pretreatment with myricitrin significantly rescued HK-2 cells from cell death, reduced iron overload and lipid peroxidation biomarkers, and improved GPX4 expression. In addition, myricitrin downregulated the expression of LC3II/LC3I and NCOA4 and elevated the expression of FTH and SQTM. Furthermore, myricitrin inhibited ROS production and preserved mitochondrial function with a lower percentage of green JC-1 monomers. However, the protection could be reserved by the inducer of ferritinophagy rapamycin. Mechanically, the Hub genes analysis reveals that AKT and NF-κB are indispensable mediators in the anti-ferroptic process. In conclusion, myricitrin ameliorates cisplatin induced HK-2 cells damage by attenuating ferritinophagy mediated ferroptosis.
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BACKGROUND: Drug-eluting bead transarterial chemoembolization (DEB-TACE) has shown efficacy for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, whether DEB-TACE is superior to conventional TACE (cTACE) remains unclear. OBJECTIVE: This randomized controlled trial aimed to compare the efficacy and safety of DEB-TACE versus cTACE in treating HCC with PVTT. METHODS: The study was conducted in a tertiary care center in Southeast China. HCC patients with PVTT were randomized at a 1:1 ratio to the DEB-TACE or cTACE groups. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS) and incidence of adverse events (AEs). An independent review committee assessed the radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). AEs were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Systemic therapies were not limited. RESULTS: Between September 2018, and July 2020, 163 patients were randomized to undergo DEB-TACE (n=82) or cTACE (n=81). Nine patients were excluded, and 154 patients were included in the final analysis; the median age was 55 years (range, 24-78 y), and 140 (90.9%) were male. The median PFS in the DEB-TACE group was 6.0 months (95% CI, 5.0 to 10.0) versus 4.0 months (95% CI, 3.0 to 5.0) in the cTACE group (hazard ratio, 0.63; 95% CI, 0.42 to 0.95; P=0.027). The DEB-TACE group showed a higher response rate (51[66.2%] vs. 36 [46.8%]; P=0.0015) and a longer median OS (12.0 months [95% CI, 9.0 to 16.0] vs. 8.0 months [95% CI, 7.0 to 11.0], P=0.039) than the cTACE group. Multivariate analysis showed that the treatment group, ALBI score, distant metastasis and additional TKIs were the four independent prognostic factors correlated with PFS. In addition, the treatment group, PVTT group and combined with surgery were independently correlated with OS. AEs were similar in the two groups, and postembolization syndrome was the most frequent AEs. CONCLUSION: DEB-TACE is superior to cTACE in treating HCC patients with PVTT due to the improved PFS and OS with an acceptable safety profile and may become a promising treatment strategy for HCC patients with PVTT. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800018035.
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Umami peptides are known for enhancing the taste experience by binding to oral umami T1R1 and T1R3 receptors. Among them, small peptides (composed of 2-4 amino acids) constitute nearly 40% of reported umami peptides. Given the diversity in amino acids and peptide sequences, umami small peptides possess tremendous untapped potential. By investigating 168,400 small peptides, we screened candidates binding to T1R1/T1R3 through molecular docking and molecular dynamics simulations, explored bonding types, amino acid characteristics, preferred binding sites, etc. Utilizing three-dimensional molecular descriptors, bonding information, and a back-propagation neural network, we developed a predictive model with 90.3% accuracy, identifying 24,539 potential umami peptides. Clustering revealed three classes with distinct logP (-2.66 ± 1.02, -3.52 ± 0.93, -2.44 ± 1.23) and asphericity (0.28 ± 0.12, 0.26 ± 0.11, 0.25 ± 0.11), indicating significant differences in shape and hydrophobicity (P < 0.05) among potential umami peptides binding to T1R1/T1R3. Following clustering, nine representative peptides (CQ, DP, NN, CSQ, DMC, TGS, DATE, HANR, and STAN) were synthesized and confirmed to possess umami taste through sensory evaluations and electronic tongue analyses. In summary, this study provides insights into exploring small peptide interactions with umami receptors, advancing umami peptide prediction models.
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Simulação de Acoplamento Molecular , Peptídeos , Receptores Acoplados a Proteínas G , Paladar , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Peptídeos/química , Peptídeos/metabolismo , Humanos , Sítios de Ligação , Simulação de Dinâmica Molecular , Ligação Proteica , Sequência de AminoácidosRESUMO
Abdominal aortic aneurysm (AAA) is a serious vascular disease which is associated with vascular remodeling. CD38 is a main NAD+-consuming enzyme in mammals, and our previous results showed that CD38 plays the important roles in many cardiovascular diseases. However, the role of CD38 in AAA has not been explored. Here, we report that smooth-muscle-cell-specific deletion of CD38 (CD38SKO) significantly reduced the morbidity of AngII-induced AAA in CD38SKOApoe-/- mice, which was accompanied with a increases in the aortic diameter, medial thickness, collagen deposition, and elastin degradation of aortas. In addition, CD38SKO significantly suppressed the AngII-induced decreases in α-SMA, SM22α, and MYH11 expression; the increase in Vimentin expression in VSMCs; and the increase in VCAM-1 expression in smooth muscle cells and macrophage infiltration. Furthermore, we demonstrated that the role of CD38SKO in attenuating AAA was associated with the activation of sirtuin signaling pathways. Therefore, we concluded that CD38 plays a pivotal role in AngII-induced AAA through promoting vascular remodeling, suggesting that CD38 may serve as a potential therapeutic target for the prevention of AAA.
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ADP-Ribosil Ciclase 1 , Angiotensina II , Aneurisma da Aorta Abdominal , Camundongos Knockout , Miócitos de Músculo Liso , Remodelação Vascular , Animais , Masculino , Camundongos , ADP-Ribosil Ciclase 1/metabolismo , ADP-Ribosil Ciclase 1/genética , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/patologia , Modelos Animais de Doenças , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Cadeias Pesadas de Miosina/metabolismo , Cadeias Pesadas de Miosina/genética , Transdução de Sinais , Remodelação Vascular/genéticaRESUMO
We investigated the contamination of the operator and the surrounding environment during wound debridement through simulated operations using fluorescent labelling. On-site simulated operation assessment was performed before and after the training. Oranges and square towels were used to simulate wounds and the inpatient units, respectively. Fluorescent powder was applied to the surfaces. Operations on oranges simulated bedside debridement, and the postoperative distribution of the fluorescent powder was employed to reflect the contamination of the operator and the surrounding environment. During the pre-training assessment, contamination was observed in 28 of the 29 trainees. The commonly contaminated parts were the extensor side of the forearm, middle abdomen, upper abdomen, and hands. The right side of the operating area was contaminated in 24 trainees. During the post-training assessment, contamination was observed in 13 of the 15 trainees. The commonly parts were the hands, extensor side of the forearm, and the lower abdomen. The front, back, left, and right sides of the operating area were contaminated in 12, 9, 11, and 14 trainees, respectively. Contamination of the treatment cart was observed in 5 trainees. Operator and the surrounding environment can be contaminated during wound debridement. Attention should be paid to hand hygiene, wearing and changing of work clothes, and disinfection of the surrounding environment. Moreover, regular training is recommended.
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Mãos , Extremidade Superior , Humanos , Desbridamento , Pós , Antebraço , CorantesRESUMO
Objective: Diabetic nephropathy (DN) represents the principal cause of end-stage renal diseases worldwide, lacking effective therapies. Fatty acid (FA) serves as the primary energy source in the kidney and its dysregulation is frequently observed in DN. Nevertheless, the roles of FA metabolism in the occurrence and progression of DN have not been fully elucidated. Methods: Three DN datasets (GSE96804/GSE30528/GSE104948) were obtained and combined. Differentially expressed FA metabolism-related genes were identified and subjected to DN classification using "ConsensusClusterPlus". DN subtypes-associated modules were discovered by "WGCNA", and module genes underwent functional enrichment analysis. The immune landscapes and potential drugs were analyzed using "CIBERSORT" and "CMAP", respectively. Candidate diagnostic biomarkers of DN were screened using machine learning algorithms. A prediction model was constructed, and the performance was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The online tool "Nephroseq v5" was conducted to reveal the clinical significance of the candidate diagnostic biomarkers in patients with DN. A DN mouse model was established to verify the biomarkers' expression. Results: According to 39 dysregulated FA metabolism-related genes, DN samples were divided into two molecular subtypes. Patients in Cluster B exhibited worse outcomes with a different immune landscape compared with those in Cluster A. Ten potential small-molecular drugs were predicted to treat DN in Cluster B. The diagnostic model based on PRKAR2B/ANXA1 was created with ideal predictive values in early and advanced stages of DN. The correlation analysis revealed significant association between PRKAR2B/ANXA1 and clinical characteristics. The DN mouse model validated the expression patterns of PRKAR2B/ANXA1. Conclusion: Our study provides new insights into the role of FA metabolism in the classification, immunological pathogenesis, early diagnosis, and precise therapy of DN.
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BACKGROUND: Stomach diseases have become global health concerns. Protoberberine alkaloids (PBAs) are a group of quaternary isoquinoline alkaloids from abundant natural sources and have been shown to improve gastric disorders in preclinical and clinical studies. The finding that PBAs exhibit low oral bioavailability but potent pharmacological activity has attracted great interest. PURPOSE: This review aims to provide a systematic review of the molecular mechanisms of PBAs in the treatment of gastric disorders and to discuss the current understanding of the pharmacokinetics and toxicity of PBAs. METHODS: The articles related to PBAs were collected from the Web of Science, Pubmed, and China National Knowledge Infrastructure databases using relevant keywords. The collected articles were screened and categorized according to their research content to focus on the gastroprotective effects, pharmacokinetics, and toxicity of PBAs. RESULTS: Based on the results of preclinical studies, PBAs have demonstrated therapeutic effects on chronic atrophic gastritis and gastric cancer by activating interleukin-4 (IL-4)/signal transducer and activator of transcription 6 (STAT6) pathway and suppressing transforming growth factor-beta 1 (TGF-ß1)/phosphoinositide 3-kinase (PI3K), Janus kinase-2 (JAK2)/signal transducers and activators of transcription 3 (STAT3), and mitogen-activated protein kinase (MAPK) pathways. The major PBAs exhibit similar pharmacokinetic properties, including rapid absorption, slow elimination, and low bioavailability. Notably, the natural organ-targeting property of PBAs may account for the finding of their low blood levels and high pharmacological activity. PBAs interact with other compounds, including conventional drugs and natural products, by modulation of metabolic enzymes and transporters. The potential tissue toxicity of PBAs should be emphasized due to their high tissue accumulation. CONCLUSION: This review highlights the gastroprotective effects, pharmacokinetics, and toxicity of PBAs and will contribute to the evaluation of drug properties and clinical translational studies of PBAs, accelerating their transfer from the laboratory to the bedside.
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Alcaloides de Berberina , Alcaloides de Berberina/farmacologia , Alcaloides de Berberina/farmacocinética , Humanos , Animais , Neoplasias Gástricas/tratamento farmacológico , Gastrite Atrófica/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacosRESUMO
Aim: To investigate the mechanism of doxorubicin (DOX)-induced immunogenic cell death (ICD) and to improve immunotherapy efficacy. Materials & methods: In this study, hybrid vesicles containing DOX (HV-DOX) were prepared by thin-film hydration with extrusion, and the formulated nanoparticles were characterized physically. Furthermore, in vitro experiments and animal models were used to investigate the efficacy and new mechanisms of chemotherapy combined with immunotherapy. Results: DOX improved tumor immunogenicity by alkalinizing lysosomes, inhibiting tumor cell autophagy and inducing ICD. HVs could activate dendritic cell maturation, synergistically enhancing chemotherapeutic immunity. Conclusion: The mechanism of DOX-induced ICD was explored, and antitumor immunity was synergistically activated by HV-DOX to improve chemotherapeutic drug loading and provide relevant antigenic information.
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Neoplasias Colorretais , Nanopartículas , Animais , Calefação , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Imunoterapia , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
INTRODUCTION: Oxidative stress is one of the major contributors to acute alcoholic liver injury (AALI), which is a common alcoholic liver disease. Quercetin and catechin are flavonoid antioxidants present in plant foods and possess chemopreventive and chemotherapeutic activities. Quercetin and catechin are often included in the same meal and ingested together. While they show cooperative actions against oxidative damage, the underlying mechanisms behind their counteracting effects against oxidative stress-induced AALI remain poorly understood. OBJECTIVES: The aim of this study was to understand the mechanism underlying the enhanced antioxidant effect of quercetin-catechin combination to alleviate AALI in rats. METHODS: The ethanol (EtOH)-treated rats and H2O2-treated liver cells were used to demonstrate the enhanced antioxidant effect of quercetin and catechin. Then we used RNA-sequencing to compare quercetin alone, catechin alone and quercetin-catechin combination and then identified the critical role of IKKα combining with gene silencing and overexpression techniques. Its transcription factor, FOXO3 was found through yeast one-hybrid assay, luciferase reporter assay, EMSA and ChIP assay. Finally, the interaction between quercetin, catechin and FOXO3 was verified through molecular docking, UV-Vis absorption spectroscopy, fluorescence spectroscopy, and CD spectroscopy. RESULTS: The study demonstrated the enhanced antioxidant effect of a quercetin-catechin combination in EtOH-treated rats and in H2O2-treated liver cells. Quercetin and catechin cooperatively inhibited IKKα/p53 pathway and activated Nrf2 signaling pathway. IKKα was a critical negative regulator in their joint action. FOXO3 bound to IKKα promoter to regulate IKKα transcription. Quercetin and catechin influenced FOXO3-IKKα binding through attaching directly to FOXO3 at different sites and altering FOXO3's secondary structures. CONCLUSION: Our study revealed the mechanism of quercetin and catechin against oxidative stress-induced AALI through jointly interacting with transcription factor. This research opens new vistas for examining the joint effect of therapeutics towards functional proteins and confirms the chemopreventive effects of multiple flavonoids via co-regulation.
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Disulfidptosis, a recently identified mode of cellular demise marked by excess SLC7A11-reliant cystine, has been proved to affect the development and resilience of tumor cells through the production of glutathione from cystine. Glutathione synthesis plays a crucial role in chemotherapy resistance and the survival of liver cancer cells. Thus, understanding the relationship between disulfidptosis and hepatocellular carcinoma (HCC) is imperative. A molecular typing approach was employed to classify patients with HCC into two distinct subtypes, namely disulfidptosis and disulfide-homeostasis, based on the expression of genes associated with disulfidptosis. Patients with disulfidptosis exhibited a longer survival time, improved immune status, and heightened sensitivity to conventional chemotherapeutic drugs and immunotherapy. Patients with disulfide-homeostasis demonstrated an immunosuppressive microenvironment, drug resistance, and unfavorable prognosis. A prognostic model was constructed utilizing the significant prognostic variables of the disulfidptosis-regulated genes. A real-world cohort was subjected to multiplex immunofluorescence to validate the clinical outcomes and immune context. Ultimately, our study delved into the prognostic relevance of disulfidptosis in HCC and provides insights into potential avenues for future research.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Cistina , Microambiente Tumoral/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Dissulfetos , GlutationaRESUMO
BACKGROUND: The glymphatic system is reportedly involved in Parkinson's disease (PD). Based on previous studies, we aimed to confirm the correlation between the glymphatic system and PD progression by combining two imaging parameters, diffusion tensor image analysis along the perivascular space (DTI-ALPS), and enlarged perivascular spaces (EPVS). METHODS: Fifty-one PD patients and fifty healthy control (HC) were included. Based on the Hoehn-Yahr scale, the PD group was divided into early-stage and medium-to late-stage. All PD patients were scored using the Unified PD Rating Scale (UPDRS). We assessed the DTI-ALPS indices in the bilateral hemispheres and EPVS numbers in bilateral centrum semiovale (CSO), basal ganglia (BG), and midbrain. RESULTS: The DTI-ALPS indices were significantly lower bilaterally in PD patients than in the HC group, and EPVS numbers in any of the bilateral CSO, BG, and midbrain were significantly higher, especially for the medium- to late-stage group and the BG region. In PD patients, the DTI-ALPS index was significantly negatively correlated with age, while the BG-EPVS numbers were significantly positively correlated with age. Furthermore, the DTI-ALPS index was negatively correlated with UPDRS II and III scores, while the BG-EPVS numbers were positively correlated with UPDRS II and III scores. Similarly, the correlation was more pronounced in the medium- to late-stage group. CONCLUSION: The DTI-ALPS index and EPVS numbers (especially in the BG region) are closely related to age and PD progression and can serve as non-invasive assessments for glymphatic dysfunction and its interventions in clinical studies.
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Sistema Glinfático , Doença de Parkinson , Humanos , Imageamento por Ressonância Magnética , Doença de Parkinson/diagnóstico por imagem , Sistema Glinfático/diagnóstico por imagem , Gânglios da Base , Progressão da DoençaRESUMO
Excessive apoptosis can kill normal cells and lead to liver damage, heart failure and neurodegenerative diseases. Polyphenols are secondary metabolites of plants that can interact with proteins to inhibit toxins and disease-related apoptosis. Bax is the major pro-apoptotic protein that disrupts the outer mitochondrial membrane to induce apoptosis, but limited studies have focused on the interaction between polyphenols and Bax and the associated anti-apoptotic mechanisms, especially at the atomic level. In this article, we collected 69 common polyphenols for active ingredient screening targeting Bax. Polyphenols with better and worse molecular docking scores were selected, and their anti-apoptosis effects were compared using the H2O2-induced HepG2 cell model. The interactions between the selected polyphenols and Bax protein were analyzed using molecular dynamics simulation to explore the molecular mechanism underlying the anti-apoptosis effect. Secoisolariciresinol diglucoside (SDG) and Epigallocatechin-3-gallate (EGCG) with the best affinity for Bax (-6.76 and -6.52 kcal/mol) reduced the expression of cytochrome c and caspase 3, decreasing the apoptosis rate from 52 to 11% and 12%. Molecular dynamics simulation results showed that Bim unfolded the α1-α2 loop of Bax, and disrupted the non-bond interactions between the loop (Pro-43, Glu-44 and Leu-45) and surface (Ile-133, Arg-134 and Met-137) residues, with binding free energy changed from -15.0 to 0 kJ/mol. The hydrogen bonds and van der Waals interactions formed between polyphenols and Bax prevented the unfolding of the loop. Taken together, our results proved that polyphenols can inhibit apoptosis by maintaining the unactivated conformation of Bax to reduce outer mitochondrial membrane damage.Communicated by Ramaswamy H. Sarma.
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Peróxido de Hidrogênio , Polifenóis , Proteína X Associada a bcl-2/química , Simulação de Acoplamento Molecular , Polifenóis/química , Peróxido de Hidrogênio/farmacologia , Proteínas Reguladoras de Apoptose/química , ApoptoseRESUMO
The 3-succinate-30-stearyl glycyrrhetinic acid(18-GA-Suc) was inserted into glycyrrhetinic acid(GA)-tanshinone â ¡_A(TSN)-salvianolic acid B(Sal B) liposome(GTS-lip) to prepare liver targeting compound liposome(Suc-GTS-lip) mediated by GA receptors. Next, pharmacokinetics and tissue distribution of Suc-GTS-lip and GTS-lip were compared by UPLC, and in vivo imaging tracking of Suc-GTS-lip was conducted. The authors investigated the effect of Suc-GTS-lip on the proliferation inhibition of hepatic stellate cells(HSC) and explored their molecular mechanism of improving liver fibrosis. Pharmacokinetic results showed that the AUC_(Sal B) decreased from(636.06±27.73) µg·h·mL~(-1) to(550.39±12.34) µg·h·mL~(-1), and the AUC_(TSN) decreased from(1.08±0.72) µg·h·mL~(-1) to(0.65±0.04) µg·h·mL~(-1), but the AUC_(GA) increased from(43.64±3.10) µg·h·mL~(-1) to(96.21±3.75) µg·h·mL~(-1). The results of tissue distribution showed that the AUC_(Sal B) and C_(max) of Sal B in the liver of the Suc-GTS-lip group were 10.21 and 4.44 times those of the GTS-lip group, respectively. The liver targeting efficiency of Sal B, TSN, and GA in the Suc-GTS-lip group was 40.66%, 3.06%, and 22.08%, respectively. In vivo imaging studies showed that the modified liposomes tended to accumulate in the liver. MTT results showed that Suc-GTS-lip could significantly inhibit the proliferation of HSC, and RT-PCR results showed that the expression of MMP-1 was significantly increased in all groups, but that of TIMP-1 and TIMP-2 was significantly decreased. The mRNA expressions of collagen-I and collagen-â ¢ were significantly decreased in all groups. The experimental results showed that Suc-GTS-lip had liver targeting, and it could inhibit the proliferation of HSC and induce their apoptosis, which provided the experimental basis for the targeted treatment of liver fibrosis by Suc-GTS-lip.
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Ácido Glicirretínico , Lipossomos , Humanos , Células Estreladas do Fígado , Ácido Glicirretínico/farmacologia , Fígado , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/genética , Colágeno/farmacologiaRESUMO
Purpose: Fruits have been identified as the primary triggers of anaphylaxis in older children in the Chinese population, especially among individuals with pollen sensitization. To date, no allergies have been reported after blueberry ingestion in the Chinese population. Case Report: A 12-year-old girl experienced one episode of anaphylaxis within 30 minutes of having breakfast (including milk, egg, wheat bread, and blueberry) while walking to school. She menstruated during this episode. Prompt treatment with epinephrine and fluid therapy led to full recovery within 24 h. Specific IgE was conducted using ImmunoCAP, and the patient exhibited sensitization to several pollens, mainly Japanese hop (74.3 kUa/L) and mugwort (26.5 kUa/L). Regarding specific IgE to allergen components, the patient showed sensitization primarily to lipid transfer protein (LTP) components from mugwort Art v 3 (79.7 kUa/L), wheat Tri a 14 (12.4 kUa/L) and peach Pru p 3 (2.15 kUa/L), but tested negative for omega-5 gliadin. The prick test results were positive for blueberries (wheal size 9.5 mm), cherries (wheal size 6.5 mm), kiwifruits (wheal size 6 mm), and pears (wheal size 4.5 mm). Our patient was provided with an epi-pen and was advised to avoid consuming relevant fruits. After four months of follow-up, the patient had not experienced any episodes of anaphylaxis since these recommendations were implemented. Conclusion: We report for the first time a Chinese child with severe IgE-mediated immediate-type anaphylactic reaction to blueberries, in whom we identified LTP as the suspected allergen component.
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AIM: To identify subtypes of competence in managing workplace violence (WPV) among nursing interns and to assess between-group differences. BACKGROUND: Nursing interns are reported to be a vulnerable population for experiencing workplace violence during their clinical placement. Although WPV could have a negative impact on nursing interns' health and attitudes towards the nursing profession, little is known about nursing interns' competence in workplace violence management or its influencing factors. DESIGN: A cross-sectional study. METHODS: Between March to April 2023, nursing interns at three tertiary general hospitals in Anhui Province, China, completed questionnaires including a general information questionnaire, the Management of Workplace Violence Competence Scale (MWVCS), the Utrecht Work Engagement Scale (UWES-9), the Emotional Labour Scale for Nurses (ELSN) and were classified into subtypes by latent class analysis. Subsequently, univariate analysis and multivariate logistic regression were performed to identify the influencing factors by subtypes. RESULTS: A total of 264 questionnaires were valid and the overall mean age of the participants was 21.06 ±1.41 years. Four classes were identified: low competency group (15.5%), low cognition-low coping competency group (18.2%), low cognition-medium to high competency group (21.6%) and high competency group (44.7%). The results of multinomial logistic regression analysis showed that placement hospitals with a WPV management department, emotional control effort in profession dimension and emotional pretense by norms dimension in the Emotional Labour Scale for Nurses, pursuing further education and vigour dimension in the Utrecht Work Engagement Scale were influencing factors of the potential categories of WPV management competence. CONCLUSIONS: Four classes were identified and there was competence variability among nursing interns. More attention should be given to nursing interns who did not receive WPV-related training in their school or placement hospital.
Assuntos
Violência no Trabalho , Humanos , Adulto Jovem , Adulto , Violência no Trabalho/prevenção & controle , Estudos Transversais , Análise de Classes Latentes , Inquéritos e Questionários , Hospitais , Local de Trabalho/psicologiaRESUMO
A high-performance optical sensor with a vertical cavity structure comprising high-contrast gratings (HCGs) and a distributed Bragg reflector was designed. The structure has two peaks with different mechanisms, among which the first peak is formed by breaking the symmetry of the structure and coupling between the incident wave and the symmetric protection mode. The joint action of the HCG resonance and Fabry-Perot resonance formed a second peak. Moreover, changing the structural parameters, such as the grating width, period, and cavity length, can tune the spectral reflection dips. The sensitivity of the designed structure was as high as 674â nm/RIU, and the corresponding figure of merit was approximately 34741. The presented gas sensor provides a method for applying a vertical cavity structure to the sensing domain.