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1.
World J Gastrointest Surg ; 16(6): 1558-1570, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38983340

RESUMO

BACKGROUND: Rectal cancer ranks as the second leading cause of cancer-related mortality worldwide, necessitating surgical resection as the sole treatment option. Over the years, there has been a growing adoption of minimally invasive surgical techniques such as robotic and laparoscopic approaches. Robotic surgery represents an innovative modality that effectively addresses the limitations associated with traditional laparoscopic techniques. While previous studies have reported favorable perioperative outcomes for robot-assisted radical resection in rectal cancer patients, further evidence regarding its oncological safety is still warranted. AIM: To conduct a comparative analysis of perioperative and oncological outcomes between robot-assisted and laparoscopic-assisted low anterior resection (LALAR) procedures. METHODS: The clinical data of 125 patients who underwent robot-assisted low anterior resection (RALAR) and 279 patients who underwent LALAR resection at Shandong Provincial Hospital Affiliated to Shandong First Medical University from December 2019 to November 2022 were retrospectively analyzed. After performing a 1:1 propensity score matching, the patients were divided into two groups: The RALAR group and the LALAR group (111 cases in each group). Subsequently, a comparison was made between the short-term outcomes within 30 d after surgery and the 3-year survival outcomes of these two groups. RESULTS: Compared to the LALAR group, the RALAR group exhibited a significantly earlier time to first flatus [2 (2-2) d vs 3 (3-3) d, P = 0.000], as well as a shorter time to first fluid diet [4 (3-4) d vs 5 (4-6) d, P = 0.001]. Additionally, the RALAR group demonstrated reduced postoperative indwelling catheter time [2 (1-3) d vs 4 (3-5) d, P = 0.000] and decreased length of hospital stay after surgery [5 (5-7) d vs 7(6-8) d, P = 0.009]. Moreover, there was an observed increase in total cost of hospitalization for the RALAR group compared to the LALAR group [10777 (10780-11850) dollars vs 10550 (8766-11715) dollars, P = 0.012]. No significant differences were found in terms of conversion rate to laparotomy or incidence of postoperative complications between both groups. Furthermore, no significant disparities were noted regarding the 3-year overall survival rate and 3-year disease-free survival rate between both groups. CONCLUSION: Robotic surgery offers potential advantages in terms of accelerated recovery of gastrointestinal and urologic function compared to LALAR resection, while maintaining similar perioperative and 3-year oncological outcomes.

2.
Phytochemistry ; 225: 114197, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38945281

RESUMO

Five undescribed monoterpene-chalcone conjugates (1-5), one undescribed hypothetical precursor of diarylheptanoid (6), two undescribed diarylheptanoids (7-8), and fourteen known compounds (9-22) were isolated from the seeds of Alpinia katsumadai. Their structures were elucidated through the interpretation of HRESIMS, NMR, ECD, and X-ray diffraction data. MTT assays on human cancer cell lines (HepG2, A549, SGC7901, and SW480) revealed that compounds 3-8, 11, and 13 exhibited broad-spectrum antiproliferative activities with IC50 values ranging from 3.59 to 21.78 µM. B cell lymphoma 2 was predicted as the target of sumadain C (11) by network pharmacology and verified by homogeneous time-resolved fluorescence assay and molecular docking.


Assuntos
Alpinia , Antineoplásicos Fitogênicos , Proliferação de Células , Diarileptanoides , Ensaios de Seleção de Medicamentos Antitumorais , Monoterpenos , Sementes , Alpinia/química , Humanos , Diarileptanoides/química , Diarileptanoides/farmacologia , Diarileptanoides/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Sementes/química , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Monoterpenos/química , Monoterpenos/isolamento & purificação , Monoterpenos/farmacologia , Relação Estrutura-Atividade , Chalconas/química , Chalconas/farmacologia , Chalconas/isolamento & purificação , Chalcona/química , Chalcona/farmacologia , Chalcona/isolamento & purificação , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Simulação de Acoplamento Molecular
3.
Chemistry ; 30(39): e202401400, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38736421

RESUMO

Coumestan represents a biologically relevant structural motif distributed in a number of natural products, and the rapid construction of related derivatives as well as the characterization of targets would accelerate lead compound discovery in medicinal chemistry. In this work, a general and scalable approach to 8,9-dihydroxycoumestans via two-electrode constant current electrolysis was developed. The application of a two-phase (aqueous/organic) system plays a crucial role for success, protecting the sensitive o-benzoquinone intermediates from over-oxidation. Based on the structurally diverse products, a primary SAR study on coumestan scaffold was completed, and compound 3 r exhibited potent antiproliferative activities and a robust topoisomerase I (Top1) inhibitory activity. Further mechanism studies demonstrates that compound 3 r was a novel Top1 poison, which might open an avenue for the development of Top1-targeted antitumor agent.


Assuntos
Antineoplásicos , Cumarínicos , DNA Topoisomerases Tipo I , Inibidores da Topoisomerase I , Inibidores da Topoisomerase I/química , Inibidores da Topoisomerase I/farmacologia , Inibidores da Topoisomerase I/síntese química , DNA Topoisomerases Tipo I/metabolismo , DNA Topoisomerases Tipo I/química , Humanos , Relação Estrutura-Atividade , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Cumarínicos/química , Cumarínicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Oxirredução , Umbeliferonas/química , Umbeliferonas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais
4.
Leuk Res ; 139: 107483, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38493755

RESUMO

RUNX1 is one of the recurrent mutated genes in newly diagnosed acute myeloid leukemia (AML). Although historically recognized as a provisional distinct entity, the AML subtype with RUNX1 mutations (AML-RUNX1mut) was eliminated from the 2022 WHO classification system. To gain more insight into the characteristics of AML-RUNX1mut, we retrospectively analyzed 1065 newly diagnosed adult AML patients from the First Affiliated Hospital of Soochow University between January 2017 and December 2021. RUNX1 mutations were identified in 112 patients (10.5%). The presence of RUNX1 mutation (RUNX1mut) conferred a lower composite complete remission (CRc) rate (40.2% vs. 58.4%, P<0.001), but no significant difference was observed in the 5-year overall survival (OS) rate (50.2% vs. 53.9%; HR=1.293; P=0.115) and event-free survival (EFS) rate (51.5% vs. 49.4%; HR=1.487, P=0.089), even within the same risk stratification. Multivariate analysis showed that RUNX1mut was not an independent prognostic factor for OS (HR=1.352, P=0.068) or EFS (HR=1.129, P=0.513). When patients were stratified according to induction regimen, RUNX1mut was an unfavorable factor for CRc both on univariate and multivariate analysis in patients receiving conventional chemotherapy, and higher risk stratification predicted worse OS. In those who received venetoclax plus hypomethylating agents, RUNX1mut was not predictive of CRc and comparable OS and EFS were seen between intermediate-risk and adverse-risk groups. The results of this study revealed that the impact of RUNX1mut is limited. Its prognostic value depended more on treatment and co-occurrent abnormalities. VEN-HMA may abrogate the prognostic impact of RUNX1, which merits a larger prospective cohort to illustrate.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Leucemia Mieloide Aguda , Adulto , Humanos , Prognóstico , Estudos Retrospectivos , Estudos Prospectivos , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Mutação , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética
5.
Am J Physiol Endocrinol Metab ; 326(6): E767-E775, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38506752

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with increasing prevalence worldwide. NAFLD could develop from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), NASH-related fibrosis, cirrhosis, and even hepatocellular carcinoma. However, the mechanism of NAFLD development has not yet been fully defined. Recently, emerging evidence shows that the dysregulated iron metabolism marked by elevated serum ferritin, and ferroptosis are involved in the NAFLD. Understanding iron metabolism and ferroptosis can shed light on the mechanisms of NAFLD development. Here, we summarized studies on iron metabolism and the ferroptosis process involved in NAFLD development to highlight potential medications and therapies for treating NAFLD.


Assuntos
Ferroptose , Ferro , Hepatopatia Gordurosa não Alcoólica , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ferroptose/fisiologia , Humanos , Ferro/metabolismo , Animais , Fígado/metabolismo , Fígado/patologia , Ferritinas/metabolismo
6.
Phytomedicine ; 123: 155227, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38128398

RESUMO

BACKGROUND: Atherosclerosis (AS) is a progressive chronic disease. Currently, cardiovascular diseases (CVDs) caused by AS is responsible for the global increased mortality. Yanshanjiang as miao herb in Guizhou of China is the dried and ripe fruit of Fructus Alpinia zerumbet. Accumulated evidences have confirmed that Yanshanjiang could ameliorate CVDs, including AS. Nevertheless, its effect and mechanism on AS are still largely unknown. PURPOSE: To investigate the role of essential oil from Fructus Alpinia zerumbet (EOFAZ) on AS, and the potential mechanism. METHODS: A high-fat diet (HFD) ApoE-/- mice model of AS and a oxLDL-induced model of macrophage-derived foam cells (MFCs) were reproduced to investigate the pharmacological properties of EOFAZ on AS in vivo and foam cell formation in vitro, respectively. The underlying mechanisms of EOFAZ were investigated using Network pharmacology and molecular docking. EOFAZ effect on PPARγ protein stability was measured using a cellular thermal shift assay (CETSA). Pharmacological agonists and inhibitors and gene interventions were employed for clarifying EOFAZ's potential mechanism. RESULTS: EOFAZ attenuated AS progression in HFD ApoE-/- mice. This attenuation was manifested by the reduced aortic intima plaque development, increased collagen content in aortic plaques, notable improvement in lipid profiles, and decreased levels of inflammatory factors. Moreover, EOFAZ inhibited the formation of MFCs by enhancing cholesterol efflux through activiting the PPARγ-LXRα-ABCA1/G1 pathway. Interestingly, the pharmacological knockdown of PPARγ impaired the beneficial effects of EOFAZ on MFCs. Additionally, our results indicated that EOFAZ reduced the ubiquitination degradation of PPARγ, and the chemical composition of EOFAZ directly bound to the PPARγ protein, thereby increasing its stability. Finally, PPARγ knockdown mitigated the protective effects of EOFAZ on AS in HFD ApoE-/- mice. CONCLUSION: These findings represent the first confirmation of EOFAZ's in vivo anti-atherosclerotic effects in ApoE-/- mice. Mechanistically, its chemical constituents can directly bind to PPARγ protein, enhancing its stability, while reducing PPARγ ubiquitination degradation, thereby inhibiting foam cell formation via activation of the PPARγ-LXRα-ABCA1/G1 pathway. Simultaneously, EOFAZ could ameliorates blood lipid metabolism and inflammatory microenvironment, thus synergistically exerting its anti-atherosclerotic effects.


Assuntos
Alpinia , Aterosclerose , Óleos Voláteis , Placa Aterosclerótica , Animais , Camundongos , PPAR gama/metabolismo , Óleos Voláteis/farmacologia , Frutas , Simulação de Acoplamento Molecular , Transdução de Sinais , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Placa Aterosclerótica/tratamento farmacológico , Apolipoproteínas E , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Receptores X do Fígado/metabolismo
7.
Int J Mol Sci ; 24(18)2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37762645

RESUMO

Surface staining has emerged as a rapid technique for applying external stains to trace cellular identities in diverse populations. In this study, we developed a distinctive aptamer with selective binding to cell surface nucleolin (NCL), bypassing cytoplasmic internalization. Conjugation of the aptamer with a FAM group facilitated NCL visualization on live cell surfaces with laser confocal microscopy. To validate the aptamer-NCL interaction, we employed various methods, including the surface plasmon resonance, IHC-based flow cytometry, and electrophoretic mobility shift assay. The G-quadruplex formations created by aptamers were confirmed with a nuclear magnetic resonance and an electrophoretic mobility shift assay utilizing BG4, a G-quadruplex-specific antibody. Furthermore, the aptamer exhibited discriminatory potential in distinguishing between cancerous and normal cells using flow cytometry. Notably, it functioned as a dynamic probe, allowing real-time monitoring of heightened NCL expression triggered by a respiratory syncytial virus (RSV) on normal cell surfaces. This effect was subsequently counteracted with dsRNA transfection and suppressed the NCL expression; thus, emphasizing the dynamic attributes of the probe. These collective findings highlight the robust versatility of our aptamer as a powerful tool for imaging cell surfaces, holding promising implications for cancer cell identification and the detection of RSV infections.

8.
Biochem Biophys Res Commun ; 671: 246-254, 2023 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-37307708

RESUMO

Vascular dementia (VaD), the second most common type of dementia, is attributed to lower cerebral blood flow. To date, there is still no available clinical treatment for VaD. The phenolic glucoside gastrodin (GAS) is known for its neuroprotective effects, but the role and mechanisms of action on VD remains unclear. In this study, we aim to investigate the neuroprotective role and underlying mechanisms of GAS on chronic cerebral hypoperfusion (CCH)-mediated VaD rats and hypoxia-induced injury of HT22 cells. The study showed that GAS relieved learning and memory deficits, ameliorated hippocampus histological lesions in VaD rats. Additionally, GAS down-regulated LC3II/I, Beclin-1 levels and up-regulated P62 level in VaD rats and hypoxia-injured HT22 cells. Notably, GAS rescued the phosphorylation of PI3K/AKT pathway-related proteins expression, which regulates autophagy. Mechanistic studies verify that YP-740, a PI3K agonist, significantly resulted in inhibition of excessive autophagy and apoptosis with no significant differences were observed in the YP-740 and GAS co-treatment. Meantime, we found that LY294002, a PI3K inhibitor, substantially abolished GAS-mediated neuroprotection. These results revealed that the effects of GAS on VaD are related to stimulating PI3K/AKT pathway-mediated autophagy, suggesting a potentially beneficial therapeutic strategy for VaD.


Assuntos
Disfunção Cognitiva , Demência Vascular , Fármacos Neuroprotetores , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Demência Vascular/tratamento farmacológico , Demência Vascular/patologia , Ratos Sprague-Dawley , Transdução de Sinais , Autofagia , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Disfunção Cognitiva/metabolismo , Hipóxia/tratamento farmacológico
9.
Int J Biol Macromol ; 245: 125443, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37353131

RESUMO

ABCA1 has been found to be critical for cholesterol efflux in macrophages. Understanding the mechanism regulating ABCA1 expression is important for the prevention and treatment of atherosclerosis. In the present study, a G-quadruplex (G4) structure was identified in the ABCA1 promoter region. This G4 was shown to be essential for ABCA1 transcription. Stabilizing the G4 by ligands surprisingly upregulated ABCA1 expression in macrophages. Knocking out the G4 remarkably reduced ABCA1 expression, and abolished the increase of ABCA1 expression induced by the G4 ligand. By pull-down assays, the protein NONO was identified as an ABCA1 G4 binder. Overexpression or repression of NONO significantly induced upregulation and downregulation of ABCA1 expression, respectively. ChIP and EMSA experiments showed that the G4 ligand promoted the binding between the ABCA1 G4 and NONO, which led to more recruitment of NONO to the promoter region and enhanced ABCA1 transcription. Finally, the G4 ligand was shown to significantly reduce the accumulation of cholesterol in macrophages. This study showed a new insight into the regulation of gene expression by G4, and provided a new molecular mechanism regulating ABCA1 expression in macrophages. Furthermore, the study showed a possible novel application of the G4 ligand: preventing and treating atherosclerosis.


Assuntos
Aterosclerose , Macrófagos , Humanos , Ligantes , Macrófagos/metabolismo , Colesterol/metabolismo , Fatores de Transcrição/genética , Aterosclerose/genética , Regiões Promotoras Genéticas/genética , Regulação da Expressão Gênica , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a RNA/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo
10.
Br J Haematol ; 202(3): 539-549, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37246158

RESUMO

Fms-like tyrosine kinase 3 (FLT3) is frequently mutated in haematological malignancies. Although canonical FLT3 mutations including internal tandem duplications (ITDs) and tyrosine kinase domains (TKDs) have been extensively studied, little is known about the clinical significance of non-canonical FLT3 mutations. Here, we first profiled the spectrum of FLT3 mutations in 869 consecutively newly diagnosed acute myeloid leukaemia (AML), myelodysplastic syndrome and acute lymphoblastic leukaemia patients. Our results showed four types of non-canonical FLT3 mutations depending on the affected protein structure: namely non-canonical point mutations (NCPMs) (19.2%), deletion (0.7%), frameshift (0.8%) and ITD outside the juxtamembrane domain (JMD) and TKD1 regions (0.5%). Furthermore, we found that the survival of patients with high-frequency (>1%) FLT3-NCPM in AML was comparable to those with canonical TKD. In vitro studies using seven representative FLT3-deletion or frameshift mutant constructs showed that the deletion mutants of TKD1 and the FLT3-ITD mutant of TKD2 had significantly higher kinase activity than wild-type FLT3, whereas the deletion mutants of JMD had phosphorylation levels comparable with wild-type FLT3. All tested deletion mutations and ITD were sensitive to AC220 and sorafenib. Collectively, these data enrich our understanding of FLT3 non-canonical mutations in haematological malignancies. Our results may also facilitate prognostic stratification and targeted therapy of AML with FLT3 non-canonical mutations.


Assuntos
Neoplasias Hematológicas , Leucemia Mieloide Aguda , Humanos , Tirosina Quinase 3 Semelhante a fms/genética , Mutação , Leucemia Mieloide Aguda/genética , Mutação Puntual
11.
J Biol Chem ; 299(7): 104856, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37230388

RESUMO

Neuroblastoma (NB) is one of the most common extracranial solid tumors in children. MYCN gene amplification is highly associated with poor prognosis in high-risk NB patients. In non-MYCN-amplified high-risk NB patients, the expression of c-MYC (MYCC) and its target genes is highly elevated. USP28 as a deubiquitinase is known to regulate the stability of MYCC. We show here USP28 also regulates the stability of MYCN. Genetic depletion or pharmacologic inhibition of the deubiquitinase strongly destabilizes MYCN and stops the growth of NB cells that overexpress MYCN. In addition, MYCC could be similarly destabilized in non-MYCN NB cells by compromising USP28 function. Our results strongly suggest USP28 as a therapeutic target for NB with or without MYCN amplification/overexpression.


Assuntos
Células-Tronco Neurais , Neuroblastoma , Criança , Humanos , Linhagem Celular Tumoral , Enzimas Desubiquitinantes/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteína Proto-Oncogênica N-Myc/genética , Proteína Proto-Oncogênica N-Myc/metabolismo , Proteína Proto-Oncogênica N-Myc/uso terapêutico , Células-Tronco Neurais/metabolismo , Neuroblastoma/patologia , Fatores de Transcrição/metabolismo , Ubiquitina Tiolesterase/metabolismo
12.
Clin Case Rep ; 11(1): e6688, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36619491

RESUMO

Philadelphia chromosome-positive acute myeloid leukemia (Ph + AML) is a rare type of AML with a low survival rate and poor prognosis. We first report a Ph + AML patient who remained in long-term remission after the combination of flumatinib and venetoclax, which could provide corresponding treatment ideas for clinical practice.

13.
Eur J Hosp Pharm ; 30(1): 3-8, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-34497128

RESUMO

PURPOSE: To investigate the efficacy and safety of programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) plus cytotoxic T lymphocyte antigen-4 (CTLA-4) antibodies ± other therapies in patients with advanced lung cancer. METHODS: In accordance with the retrieval strategy, we searched electronic databases for randomised controlled trials testing PD-1/PD-L1 plus CTLA-4 antibodies in patients with lung cancer; RR (for objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and immune-related adverse events (irAEs)) from individual studies were calculated and pooled by using random-effects models or fixed-effects models; heterogeneity and publication bias analyses were also performed, using Review Manager 5.3 and Stata 15.1 for statistical analysis. RESULTS: We included six studies. Four different immune checkpoint inhibitors (nivolumab, pembrolizumab, durvalumab, tremelimumab) were used. Dual checkpoint inhibitors ± other therapies for advanced lung cancer showed significant improvements in ORR (RR 1.49, 95% CI 1.11 to 1.98; p=0.007), OS (HR 0.72, 95% CI 0.63 to 0.83; p<0.00001), and PFS (HR 0.72, 95% CI 0.63 to 0.82; p<0.00001). The subgroup analyses were consistent with the pooled results. The PD-L1 ≥1% (HR 0.67, 95% CI 0.54 to 0.82; p<0.0001) subgroup differences indicated a statistically significant subgroup effect, but the PD-L1 <1% subgroup (HR 0.88, 95% CI 0.75 to 1.05; p=0.15) was not statistically significant. The incidence of adverse events (grade ≥3) was lower than that of the control group (RR 0.90, 95% CI 0.80 to 1.02; p=0.09), but was not significant. CONCLUSIONS: PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors ± other therapies can improve the ORR, OS and PFS of patients with advanced or metastatic lung cancer, but the incidence of adverse reactions is high although generally tolerable. PROSPERO REGISTRATION: CRD42020149216.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Receptor de Morte Celular Programada 1 , Antígeno CTLA-4 , Antígeno B7-H1 , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia
14.
Cornea ; 41(12): 1553-1558, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36343168

RESUMO

PURPOSE: The purpose of this study was to assess the effect of a second povidone-iodine (PVP-I) application at the time of donor tissue recovery on overall tissue quality and to analyze the rate of positive fungal and bacterial rim cultures before and after implementing increased PVP-I exposure. METHODS: The left cornea was recovered after a single application of PVP-I, while the right cornea was recovered after double PVP-I application in research-consented donors. The epithelial cell death rate was estimated using viability assay in corneal whole mounts under 10× objective (n = 5). Clinical characteristics of epithelium, stroma, and endothelium; positive rim culture rate; and incidences of infectious postoperative adverse reactions were compared for a period of 14 months before and after implementation of increased PVP-I protocol. RESULTS: The average epithelial cell death rate was unaltered between single and double PVP-I exposure groups. We observed a modest 10% increase in the number of tissues with mild edema after implementation of increased PVP-I exposure. Nonetheless, the percentage of tissues with moderate or severe edema was unaltered. The average positive rim culture rate decreased from 1.17% to 0.88% (P = 0.075) after implementation of the double PVP-I soak procedure. There has been only one report of infectious postoperative adverse reactions since this procedure change. By contrast, there were 5 reports for a period of 14 months before implementation of this protocol. CONCLUSIONS: These results indicate that new donor preparation methods with an additional 5 minutes of PVP-I exposure do not affect tissue quality, reduce positive rim cultures, and lead to lower incidence of postoperative infection.


Assuntos
Epitélio Corneano , Povidona-Iodo , Humanos , Povidona , Córnea/microbiologia , Edema
15.
Int J Mol Sci ; 23(19)2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36232805

RESUMO

Ocular surface exposure to nitrogen mustard (NM) leads to severe ocular toxicity which includes the separation of epithelial and stromal layers, loss of endothelial cells, cell death, and severe loss of tissue function. No definitive treatment for mustard gas-induced ocular surface disorders is currently available. The research was conducted to investigate the therapeutic potential of mesenchymal stem cell-conditioned media (MSC-CM) in NM-induced corneal wounds. NM was added to different types of corneal cells, the ocular surface of porcine, and the ocular surface of mice, followed by MSC-CM treatment. NM significantly induced apoptotic cell death, cellular ROS (Reactive oxygen species), and reduced cell viability, metabolic gene expression, and mitochondrial function, and, in turn, delayed wound healing. The application of MSC-CM post NM exposure partially restored mitochondrial function and decreased intracellular ROS generation which promoted cell survival. MSC-CM therapy enhanced wound healing process. MSC-CM inhibited NM-induced apoptotic cell death in murine and porcine corneal tissue. The application of MSC-CM following a chemical insult led to significant improvements in the preservation of corneal structure and wound healing. In vitro, ex vivo, and in vivo results suggest that MSC-CM can potentially provide targeted therapy for the treatment of chemical eye injuries, including mustard gas keratopathy (MGK) which presents with significant loss of vision alongside numerous corneal pathologies.


Assuntos
Lesões da Córnea , Células-Tronco Mesenquimais , Gás de Mostarda , Animais , Lesões da Córnea/induzido quimicamente , Lesões da Córnea/metabolismo , Lesões da Córnea/terapia , Meios de Cultivo Condicionados/farmacologia , Células Endoteliais/metabolismo , Mecloretamina/toxicidade , Células-Tronco Mesenquimais/metabolismo , Camundongos , Gás de Mostarda/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Fator de Células-Tronco/metabolismo , Suínos , Cicatrização
16.
ACS Omega ; 7(42): 37304-37314, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36312389

RESUMO

Malus crabapple has high ornamental and ecological value. Here, the flavonoids in the petals of three pink Malus crabapple cultivars, Malus 'Strawberry Parfait' (GD), M. 'Pink Spire' (FY), and M. 'Hongyi' (HY), at the bud stage (flower buds are swollen, and the pistils and stamens are about to appear; L), full bloom stage (the flowers are fully open, and the stigma and anthers have recently appeared; S), and end bloom stage (the stigma and anthers are dry; M) were identified, and their abundances were determined. First, Kodak Color Control Patches were used to describe the colors of petals, and a colorimeter was used to determine the phenotypic values of flower colors. Flavonoids were determined using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In all three crabapple cultivars, the red and yellow hues of the petals gradually disappeared, the color of the flowers changed from bright to dull, and the petals gradually faded. The extent of fading of the red hue of the petals was highest in GD, followed by FY and HY. A total of 302 metabolites were detected in the three cultivars. The content of total flavonoids in the three cultivars significantly differed, but there were no significant differences among species. The total flavonoid content of the three crabapple varieties was highest in HY, followed by FY and GD. The content of the anthocyanins delphinidin-3-O-sophoricoside-5-O-glucoside, pelargonidin-3-O-(6″-O-malonyl)glucoside, pelargonidin-3-O-glucoside, peonidin-3-O-glucoside, and cyanidin-3-O-arabinoside decreased significantly, which resulted in the discoloration of GD petals from L to M. The flavonoids and flavonols in FY might interact with anthocyanins in metabolic pathways. The content of these five anthocyanins decreased slowly, which resulted in the weaker discoloration of FY and HY compared with GD. The content of the five anthocyanins in HY did not decrease significantly, but the content of chalcone increased significantly, which might facilitate the production of anthocyanin auxiliary pigments and result in less pronounced fading of the petals. Cyanidin-3-O-arabinoside and pelargonidin-3-O-glucoside were the key flavonoids of the three crabapple cultivars. The total content and changes in anthocyanins were the key factors affecting petal color development and fading. Nonanthocyanin polyphenols, such as flavonoids, flavonols, and chalcone, are auxiliary pigments that affect petal fading. Overall, the results of this study provide new insights into the mechanism underlying the fading of the color of Malus crabapple flowers, and these new insights could aid the breeding of cultivars with different flower colors.

17.
Front Surg ; 9: 904928, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35662821

RESUMO

Objective: To compare the clinical effect of hip arthroplasty and closed reduction intramedullary nailing of proximal femur in the treatment of elderly hip fracture patients. Methods: There are 90 elderly hip fracture patients being recruited in the present study. Fifty patients in Group A received closed reduction intramedullary nailing of proximal femur, and 40 patients in Group B received hip arthroplasty. All patients were followed up for 12 months after surgery, clinical outcomes included surgical indicators, visual analog scale (VAS) score, Harris score, quality of life, mental status, and complications. Results: The surgery time, bleeding volume, infusion volume of patients in Group A are all significantly lower than those in Group B (p < 0.05), while the weight-bearing activity time and first workout time of Group A are all significantly higher than those in Group B (p < 0.05). The VAS score in patients of Group A at 1 week postoperative is significantly lower than that in patients of Group B (p < 0.05). The Harris score in patients of Group A at 3, 6, and 12 months postoperative are all significantly higher than those in patients of Group B (p < 0.05), and the excellent and good rate of hip function recovery at 12 months postoperative in patient of Group A is significantly lower than that in patients of Group B (80% vs. 95%, p < 0.05). Furthermore, The score of SF-36 standardized physical component, SF-36 standardized mental component and Barthel in patients of Group A at 6 months postoperative are significantly lower than those in patients of Group B (p < 0.05), and the score of mini-mental state examination is significantly higher (p < 0.05), while there are not significantly different at 12 months postoperative (p > 0.05). The incidence of postoperative complications in Group A was significantly lower than that in Group B (10% vs. 27.5%, p < 0.05). Conclusion: Elderly hip fracture patients treated with closed reduction intramedullary nailing of proximal femur has less surgical trauma and lower complication rates, but slower postoperative recovery compared with hip arthroplasty.

18.
Front Genet ; 13: 846877, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571028

RESUMO

Polycystic liver disease (PLD) is a rare autosomal dominant disorder including two genetically and clinically distinct forms: autosomal dominant polycystic kidney disease (ADPKD) and isolated polycystic liver disease (PCLD). The main manifestation of ADPKD is kidney cysts, while PCLD has predominantly liver presentations with mild or absent kidney cysts. Over the past decade, PRKCSH, SEC63, ALG8, and LRP5 have been candidate genes of PCLD. Recently, more candidate genes such as GANAB, SEC61B, and ALR9 were also reported in PCLD patients. This review focused on all candidate genes of PCLD, including the newly established novel candidate genes. In addition, we also discussed some other genes which might also contribute to the disease.

19.
Front Surg ; 9: 859269, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402483

RESUMO

Objective: The objective of this study was to explore the nursing effect and negative psychological stress response of elderly patients with femoral neck fracture by applying the high-quality nursing mode of medical care. Methods: A total of 130 elderly patients with femoral neck fractures hospitalized in our hospital from January 2020 to June 2021 were randomly divided into the control group and observation group, with 65 patients in each group. The control group adopted the conventional nursing mode, while the observation group adopted the high-quality nursing mode of medical care. The observation indexes selected in this study are nursing satisfaction, hip flexion activity on the 1, 15, and 30 days after the operation, the time when the affected limb was lifted off the bed actively, and the anxiety and depression of patients. Results: On the 1, 15, and 30 days after the operation, there were statistically significant differences between the two groups in hip flexion activity and the time when the affected limb was lifted off the bed (P < 0.05). The nursing satisfaction of the observation group was 95.38%, which was statistically significant compared with the 80.00% of the control group (P < 0.05). After treatment, the self rating depression scale (SDS) and self rating anxiety scale (SAS) scores in the observation group were lower than those in the control group (P < 0.05). Conclusion: The high-quality nursing model of medical care can effectively promote the rehabilitation of elderly patients with femoral neck fracture, reduce the negative psychological stress reaction of patients, and improve nursing satisfaction, which has important application value and guiding significance for the nursing of patients with femoral neck fracture.

20.
Front Surg ; 9: 865238, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402487

RESUMO

Purpose: To explore the intervention effect of psychological support therapy (PST) on elderly patients with femoral neck fracture. Methods: A total of 82 elderly patients with femoral neck fractures admitted to our hospital from July 2020 to June 2021 were selected. Patients were randomly divided into conventional group (n = 41) and intervention group (n = 41). The conventional group received routine nursing care. The intervention group was given PST on the basis of the conventional group. The joint function, psychological state, pain, quality of life, and nursing satisfaction of both groups were observed. Results: Compared with before intervention, the Harris hip joint score and the General Quality-of-Life Inventory-74 scores of both groups increased after the intervention, and the increase was more obvious in the intervention group (p < 0.05). Compared with before intervention, the self-rating anxiety scale, the self-rating depression scale scores, and the visual analog scales score in both groups decreased after the intervention, and the decrease was more obvious in the intervention group (p < 0.05). The total satisfaction of the intervention group (92.68%) was higher than that of the conventional group (75.61%) (p < 0.05). Conclusion: Psychological support therapy has a certain intervention effect on elderly patients with femoral neck fracture, which can improve psychological state, reduce pain, improve quality of life, and improve nursing satisfaction.

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