Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.704
Filtrar
1.
J Control Release ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36706840

RESUMO

Critical-size bone defect repair is in high demand but is difficult to treat. Modern therapies, such as autograft and cell-based treatments, face limitations, including potential immunological rejection and tumorigenesis. Therefore, extracellular vesicle (EV)-based strategies have been proposed as a novel approach for tissue regeneration owing to EVs' complex composition of lipids, proteins, and nucleic acids, as well as their low immunogenicity and congenital cell-targeting features. Despite these remarkable features of EVs, biomimetic synthesis and optimization of natural EVs can lead to enhanced bioactivity, increased cellular uptake, and specific cell targeting, aiming to achieve optimal therapeutic efficacy. To maximize their function, these nanoparticles can be integrated into bone graft biomaterials for superior bone regeneration. Herein, we summarize the role of naturally occurring EVs from distinct cell types in bone regeneration, the current strategies for optimizing biomimetic synthetic EVs in bone regeneration, and discuss the recent advances in applying bone graft biomaterials for the delivery of EVs for bone defect repair. We focused on distinct strategies for optimizing EVs with different functions and the most recent research on achieving time-controlled release of nanoparticles from EV-loaded biomaterials. Furthermore, we thoroughly discuss several current challenges and proposed solutions, aiming to provide insight into current progress, inspiration for future development directions, and incentives for clinical application in this field.

2.
Asian J Androl ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36629158

RESUMO

Reprogramming of metabolism is a hallmark of tumors, which has been explored for therapeutic purposes. Prostate cancer (PCa), particularly advanced and therapy-resistant PCa, displays unique metabolic properties. Targeting metabolic vulnerabilities in PCa may benefit patients who have exhausted currently available treatment options and improve clinical outcomes. Among the many nutrients, glutamine has been shown to play a central role in the metabolic reprogramming of advanced PCa. In addition to amino acid metabolism, glutamine is also widely involved in the synthesis of other macromolecules and biomasses. Targeting glutamine metabolic network by maximally inhibiting glutamine utilization in tumor cells may significantly add to treatment options for many patients. This review summarizes the metabolic landscape of PCa, with a particular focus on recent studies of how glutamine metabolism alterations affect therapeutic resistance and disease progression of PCa, and suggests novel therapeutic strategies.

3.
Biomed Pharmacother ; 159: 114241, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36634587

RESUMO

Ferroptosis is a novel type of programmed cell death, characterized by a dysregulated iron metabolism and accumulation of lipid peroxides. It features the alteration of mitochondria and aberrant accumulation of excessive iron as well as loss of the cysteine-glutathione-GPX4 axis. Eventually, the accumulated lipid peroxides result in lethal damage to the cells. Ferroptosis is induced by the overloading of iron and the accumulation of ROS and can be inhibited by the activation of the GPX4 pathway, FS1-CoQ10 pathway, GCH1-BH4 pathway, and the DHODH pathway, it is also regulated by the oncogenes and tumor suppressors. Ferroptosis involves various physiological and pathological processes, and increasing evidence indicates that ferroptosis play a critical role in cancers and other diseases. It inhibits the proliferation of malignant cells in various types of cancers and inducing ferroptosis may become a new method of cancer treatment. Many inhibitors targeting the key factors of ferroptosis such as SLC7A11, GPX4, and iron overload have been developed. The application of ferroptosis is mainly divided into two directions, i.e. to avoid ferroptosis in healthy cells and selectively induce ferroptosis in cancers. In this review, we provide a critical analysis of the concept, and regulation pathways of ferroptosis and explored its roles in various diseases, we also summarized the compounds targeting ferroptosis, aiming to promote the speed of clinical use of ferroptosis induction in cancer treatment.

4.
Clin Lab ; 69(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36649522

RESUMO

BACKGROUND: The goal was to improve the understanding of mixed phenotypic acute leukemia (MPAL) complicated with plasmacytoid dendritic cell (PDC) proliferation. METHODS: A case of mixed phenotype acute leukemia with plasmacytoid dendritic cell hyperplasia was reported. The clinical characteristics, treatment, and prognosis were analyzed by reviewing relevant literature. RESULTS: The patient was a young female with clinical manifestations of splenomegaly and lymph node enlargement. The bone marrow smear showed hyperactive proliferation, 95% of protoblastic cells. The protoblastic cell body is large, more cell mass, stained gray blue, a small amount of azurophilicgranule can be seen in some cytoplasm, pseudopodia, drag tail, and other phenomena. The nucleus was twisted and folded. Chromatin is fine with nucleoli and Auer rods seen in the cytoplasm. Immune typing: Abnormal primordial cells accounted for 44.75%, and the primordial cells expressed both myeloid markers (CD33, CD13, MPO) and T-series markers (CD7, CD5, Ccd3), which were considered MPAL (M/T) according to WHO diagnostic criteria. In addition, a group of plasmoid dendritic cells occupied an increased proportion of 10.31% of nuclear cells. No obvious phenotypic abnormalities were observed. BCR/ABL fusion genes P190/P210 were negative. NRAS, NOTCH1, and DNMT3A mutations were detected by polymerase chain reaction. Combined with the above results, acute mixed cell leukemia (M/T) with plasmacytoid dendritic cell proliferation was diagnosed. CONCLUSIONS: The diagnosis of mixed phenotype acute leukemia with plasmacytoid dendritic cell proliferation needs to be integrated with clinical manifestations, cytomorphology, immunology, cytogenetics, and molecular biology, etc. Disease should be diagnosed and treated as early as possible.


Assuntos
Leucemia , Feminino , Humanos , Prognóstico , Doença Aguda , Fenótipo , Células Dendríticas , Proliferação de Células
5.
Ophthalmol Ther ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36693992

RESUMO

INTRODUCTION: This study assessed the efficacy and safety of intense pulsed light (IPL) therapy in participants with severe evaporative dry eye disease (DED). METHODS: This randomized, controlled, single-center study included 49 adult participants (≥ 18 years) with severe evaporative DED who received either IPL therapy (n = 56 eyes) or sham therapy (n = 42 eyes) three times. The primary efficacy parameters were ocular surface disease index (OSDI) score, non-invasive tear breakup time (NITBUT), tear film lipid layer (TFLL), conjunctivocorneal staining score (CS), MG Score, meibomian gland (MG) quality, and MG expression score. RESULTS: The mean ages for the IPL group and the control group were 28.05 ± 3.41 years (57.1% female) and 28.14 ± 3.53 years (52.4% female), respectively. Comparison between the IPL group and the control group found significant differences in the mean OSDI score (22.16 ± 6.08 vs. 42.38 ± 6.60; P < 00.01), NITBUT (6.27 ± 0.84 vs. 3.86 ± 0.68; P < 0.001), TFLL (2.14 ± 0.44 vs. 3.45 ± 0.50; P < 0.001), MG Score (1.34 ± 0.55 vs. 1.88 ± 0.33; P < 0.001), MG quality (1.59 ± 0.07 vs. 2.67 ± 0.08), and MG expression (1.54 ± 0.57 vs. 2.45 ± 0.55) at 12 weeks follow-up; however, there was no significant difference in CS (3.32 ± 1.11 vs. 3.74 ± 1.04; P = 0.063). CONCLUSION: The findings suggest that IPL therapy is clinically beneficial in ameliorating the signs and symptoms of severe evaporative dry eye disease.

6.
Artigo em Inglês | MEDLINE | ID: mdl-36652457

RESUMO

BACKGROUND AND AIM: Whether vitamin D3 (VD3) supplementation is associated with improved liver fibrosis is controversial. METHODS: Liver fibrosis models were treated with VD3, active VD (1,25-OH2 Vitamin D3), or collaboration with GSK126 (Ezh2 inhibitor), respectively. Hepatic stellate cells (HSCs) were co-cultured with hepatocytes and then stimulated with TGF-ß. Autophagy of hepatocytes was determined after the intervention of 1,25-OH2 Vitamin D3 and GSK126. Also, the active status of HSCs and the mechanism with 1,25-OH2 Vitamin D3 and GSK126 intervention were detected. RESULTS: 1,25-OH2 Vitamin D3, but not VD3, is involved in anti-fibrosis and partially improves liver function, which might be associated with related enzymes and receptors (especially CYP2R1), leading to decreased of its biotransformation. GSK126 plays a synergistic role in anti-fibrosis. The co-culture system showed increased hepatocyte autophagy after HSCs activation. Supplementation with 1,25-OH2 Vitamin D3 or combined GSK126 reduced these effects. Further studies showed that 1,25-OH2 Vitamin D3 promoted H3K27 methylation of DKK1 promoter through VDR/Ezh2 due to the weakening for HSCs inhibitory signal. CONCLUSIONS: VD3 bioactive form 1,25-OH2 Vitamin D3 is responsible for the anti-fibrosis, which might have bidirectional effects on HSCs by regulating histone modification. The inhibitor of Ezh2 plays a synergistic role in this process.

7.
Fertil Steril ; 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36716811

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of acupuncture in the treatment of endometriosis-associated pain. DESIGN: A multicenter, randomized, single-blind, placebo-controlled trial. INSTITUTIONS: Four tertiary hospitals in Jiangxi and Hainan Provinces. SUBJECTS: Women with endometriosis-associated pain aged between 20 and 40 years. INTERVENTION: Subjects were randomly assigned to receive either acupuncture or sham acupuncture treatment for 12 weeks, starting one week before each expected menstruation and administered as a 30-min session once per day, 3 times a week. During the menstruation period, acupuncture was administered daily when pelvic pain associated with endometriosis occurred. After acupuncture or sham acupuncture treatment, the subjects were followed for another 12 weeks. MAIN OUTCOMES: Changes in maximum pain as assessed with the visual analog scale (VAS) for various pelvic pain, duration of dysmenorrhea, and scores on the Multidimensional Pain Inventory (MPI), Beck Depression Inventory (BDI), Profile of Mood States (POMS), and Endometriosis Health Profile (EHP) from baseline to week 12 and week 24. RESULTS: A total of 106 women were randomly assigned to the acupuncture and sham groups. In the acupuncture group, the reduction in the dysmenorrhea VAS score was significantly greater after treatment, but not at the end of the trial, compared to the sham group. The duration of pain was significantly shorter in the acupuncture group. MPI, BDI, POMS, and EHP scores were improved to a significantly greater extent in the acupuncture group than in the sham group at week 12 but not at week 24. Changes in nonmenstrual pelvic pain and dyspareunia VAS scores were not different between the groups. No severe adverse events or differences in adverse events were recorded. CONCLUSION: Acupuncture is an effective and safe method of relieving dysmenorrhea, shortening the pain duration, and improving wellbeing and quality of life in women with endometriosis-associated pain, although its efficacy fades after treatment is discontinued.

8.
Food Chem ; 410: 135443, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36680882

RESUMO

Botrytis cinerea is a devastating pathogen causing gray mold in fruits and vegetables if not properly managed. Although the mechanisms remain unclear, we previously revealed that the safe food additive calcium propionate (CP) could suppress gray mold development on grapes. The present study reports that sub-lethal dose of CP (0.2 % w/v) could allow growth with substantial reprograming the genome-wide transcripts of B. cinerea. Upon CP treatment, the genes related to fungal methylcitrate cycle (responsible for catabolizing propionate) were upregulated. Meanwhile, CP treatment broadly downregulated the transcript levels of the virulence factors. Further comparative analysis of multiple transcriptomes confirmed that the CP treatment largely suppressed the expression of genes related to development and function of infection cushion. Collectively, these findings indicate that CP can not only reduce fungal growth, but also abrogate fungal virulence factors. Thus, CP has significant potential for the control of gray mold in fruit crops.

9.
Food Chem ; 410: 135451, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36652795

RESUMO

The interaction between 1,3-dimethyltrisulfide and aroma-active compounds in sesame-flavor baijiu was evaluated by Feller's additive model and Odor Activity Value Approach, and the reason for the interaction can promote the release of fruity and caramel aromas of ethyl caproate, ethyl was explored by the Partition Coefficient Approach. The interaction results indicated that 1,3-dimethyltrisulfide caprate and furan-2-ylmethanol. Others showed masking effect. The Partition Coefficient showed that the effect of 1,3-dimethyltrisulfide on the volatility of esters was one of the reasons for the interaction affecting the flavor perception, and the volatility of ethyl esters with longer carbon chains at high phase ratio (PRs) is more likely to be promoted. Besides, the prediction model was initially proposed: y = 2.0112 ln(x) + 0.1461, which indicated that esters with the olfactory threshold lower than 33.80 µg/L are more likely to have positive effects with 1,3-dimethyltrisulfide, the negative effect is more likely to occur conversely.

10.
World J Clin Cases ; 11(2): 268-291, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36686358

RESUMO

As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient's conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and post-transplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.

11.
World J Clin Cases ; 11(1): 233-241, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36687187

RESUMO

BACKGROUND: Bronchiolar adenoma (BA) and ciliated muconodular papillary tumor are rare tumors that have bilayered cell proliferation and continuous expression of p40 and CK5/6 in the basal cell layer. Diagnosis is difficult because of the limited knowledge of these tumors and their morphological similarities to malignant tumors, including invasive mucinous adenocarcinoma, especially based on the histopathology of intraoperative frozen sections. These tumors are now considered to be benign neoplasms, with malignant transformation reported in only a few cases. CASE SUMMARY: A 57-year-old woman presented with a 17.0 mm × 7.0 mm nodule in the lower lobe of the left lung. Hematoxylin-eosin staining and immunohistochemistry of a surgical specimen were performed. The tumor consisted of a BA area and a mucinous adenocarcinoma (MA) area. In the BA area, the tumor had a bilayered structure of luminal cells and basal cells. The basal cells were positive for CK5/6 and p40, but the MA area was negative for these biomarkers. The Ki-67 proliferation index was low (1%-2%). The patient was diagnosed with BA accompanied by MA, and had a favorable outcome. CONCLUSION: The present study indicated that BA may be carcinogenic, and suggests that clinicians should be aware of its potential for malignant transformation.

12.
Artigo em Inglês | MEDLINE | ID: mdl-36689360

RESUMO

Context: The persistent use of anticancer medicines can cause multidrug resistance in many tumors and serious cytotoxicity for healthy cells, including adriamycin (ADR), a treatment for breast cancer (BC). Cell resistance to ADR in patients with recurrent advanced BC can occur. Creating effective treatments that can grapple with multidrug resistance is still challenging. Traditional Chinese medicine (TCM) may offer a solution in D Rhamnose beta-hederin (DRß-H), an oleanane type of triterpenoid saponin. Objective: The study intended to assess the ability of DRß-H to inhibit the ADR resistance of two BC-lineage cell lines, MCF-7 and SUM-1315, and to explore the causal link between DRß-H and the reversal of chemoresistance. Design: The research team performed a cell biology study. Setting: The study took place at laboratory in China. Outcome Measures: The research team: (1) assessed cell viability and the migration and invasion the cell lines; (2) investigated the molecular mechanism and identified the downstream targets of DRß-H, and (3) comprehensively examined the expression pattern, underlying functions, and evident prognostic significance of NAP1L5 in BC by gathering the online information available. Results: DRß-H can inhibit the viability of the MCF-7/ADR and SUM-1315/ADR cancer cells in a dosage-dependent manner. NAP1L5 might be the main target of DRß-H in reversing ADR resistance. Its expression decreased in BC cells, and the more advanced the BC was, the lower the NAP1L5 expression was. Conclusion: DRß-H at nontoxic concentrations was related to ADR resistance in BC through its downstream target NAP1L5. NAP1L5 is potentially a preferable prognostic marker for BC.

13.
Nanotechnology ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36649652

RESUMO

Solid-state lithium-metal batteries using inorganic solid-state electrolyte (SSE) instead of liquid-electrolyte, especially lithium-oxygen (Li-O2) battery, have attracted much more attention due to their high-energy density and safety. However, the poor interface contact between electrodes and SSEs makes these batteries lose most of their capacity and power during cycling. Here we report that by coating a heterogeneous silicon carbide on lithium metal anode and LAGP-SSE, a good interface contact is created between the electrode and electrolyte that can effectively reduce the interface impedance and improve the cycle performance of the assembled battery. As a result, the solid-sate Li-O2 battery demonstrates a cycle lifespan of ~78 cycles being at least 3-times higher than the solid-state Li-O2 battery without silicon carbide with a capacity limitation of 1000 mAhg-1 at 250 mA g-1. The characterization of discharge products indicates a typical two-electron convention of oxygen-to-lithium oxide for the solid-state Li-O2 battery system. This work paves a way for developing high-energy long-cycle solid-state lithium-metal battery. The work provides insights into the interface between the Li-metal and SSE to develop high-energy long-cycle all solid-state Li-metal batteries.

14.
J Alzheimers Dis ; 91(2): 877-893, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36502323

RESUMO

BACKGROUND: Alzheimer's disease (AD) is the most common form of neurodegenerative dementia among the elderly. Excitotoxicity has been implicated as playing a dominant role in AD, especially related to the hyperactivation of excitatory neurons. Death-associated protein kinase 1 (DAPK1) is a calcium/calmodulin-dependent kinase and involved in the pathogenesis of AD, but the roles and mechanisms of DAPK1 in excitotoxicity in AD are still uncertain. OBJECTIVE: We mainly explored the underlying mechanisms of DAPK1 involved in the excitotoxicity of AD and its clinical relevance. METHODS: Differentiated SH-SY5Y human neuroblastoma cells, PS1 V97 L transgenic mice, and human plasma samples were used. Protein expression was assayed by immunoblotting, and intracellular calcium and neuronal damage were analyzed by flow cytometry. Plasma DAPK1 was measured by ELISA. RESULTS: We found that DAPK1 was activated after amyloid-ß oligomers (AßOs) exposure in differentiated SH-SY5Y cells. Besides, we found the phosphorylation of GluN2B subunit at Ser1303 was increased, which contributing to excitotoxicity and Ca2+ overload in SH-SY5Y cells. Inhibiting DAPK1 activity, knockdown of DAPK1 expression, and antagonizing GluN2B subunits could effectively prevent AßOs-induced activation of GluN2B subunit, Ca2+ overload, and neuronal apoptosis. Additionally, we found that DAPK1 was elevated in the brain of AD transgenic mouse and in the plasma of AD patients. CONCLUSION: Our finding will help to understand the mechanism of DAPK1 in the excitotoxicity in AD and provide a reference for the diagnosis and therapy of AD.


Assuntos
Doença de Alzheimer , Neuroblastoma , Idoso , Animais , Humanos , Camundongos , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Cálcio/metabolismo , Proteínas Quinases Associadas com Morte Celular/genética , Camundongos Transgênicos , Receptores de N-Metil-D-Aspartato/metabolismo
15.
Inorg Chem ; 62(2): 1007-1017, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36584325

RESUMO

Quinolinic acid (QA) is an index for some diseases, whose detection is of importance. This work presents a samarium metal-organic framework (Sm-MOF) containing 5-sulfoisophthalate ligand (SIP3-). The fluorescence of Sm-MOF integrates the emission at 339 nm from the SIP3- ligand and four characteristic 4G5/2 → 4Hj (j = 5/2, 7/2, 9/2, and 11/2) transitions at 559, 596, 642, and 701 nm from Sm(III). Sm-MOF as a turn-off fluorescence sensor to QA exhibits high sensitivity, selectivity, and durability. The fluorescence quenching response to QA shows a linear relationship of I0/I = 0.00496·CQA + 1.12474 in the QA concentration of 0-500 µM and a limit of detection calculated as 4.11 µM. Sm-MOF shows the structural and fluorescent stabilities in five quenching-recovery cycles. The recoveries of close to 100% in human urine and serum indicate high reliability. The paper-based Sm-MOF sensor displays a rough QA quantitative analysis by recognizing red values in the on-site QA detection.


Assuntos
Estruturas Metalorgânicas , Samário , Humanos , Samário/química , Ácido Quinolínico , Ligantes , Reprodutibilidade dos Testes , Corantes Fluorescentes/química , Limite de Detecção , Estruturas Metalorgânicas/química
16.
Front Genet ; 13: 1038274, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36468023

RESUMO

Prenatal imaging phenotypes and genotypes were analyzed in 13 cases prenatally diagnosed with Joubert syndrome (JS), all of which underwent magnetic resonance imaging (MRI), ultrasound, and genetic testing. Prenatal MRI diagnosed 10 cases as JS with a typical molar tooth sign (MTS), while prenatal ultrasound diagnosed or suspiciously diagnosed 11 cases as JS with typical or mild MTS in 10 cases. Mutations in JS-related genes and other prenatal JS imaging phenotypes were identified in 10 cases, including OFD1 in two cases [cerebellar vermis (CV) absence, posterior fossa dilation, ventriculomegaly, polydactyly, malformations of cortical development (MCD), and persistent left superior vena cava], TMEM67 in two cases (CV absence, polydactyly, hyperechoic kidneys or polycystic kidneys, posterior fossa dilation, and ventriculomegaly), CC2D2A in two cases (CV absence, polydactyly, MCD, agenesis of the corpus callosum, encephalocele and hydrocephalus, ventriculomegaly, and posterior fossa dilation), RPGRIP1L in one case (CV absence), TCTN3 in one case (CV absence, polydactyly, MCD, and posterior fossa dilation), CEP290 in one case (CV absence and polycystic kidney), and NPHP1 in one case (CV absence). The prenatal diagnosis of JS presents a number of challenges, including the variants of unknown significance, the lack of functional assessment in prenatal imaging, unclear phenotype-genotype relationships in prenatal evaluation, and the incorrect identification of the JS hallmark, the MTS, in prenatal imaging, especially on ultrasound. Although combined MRI, ultrasound, and exome sequencing could help improve the prenatal diagnosis of JS, there still exist significant challenges.

17.
Chemistry ; 2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36479740

RESUMO

m-Benziporphyrin(1.1.0.0) and m-pyreniporphyrin(1.1.0.0) were prepared as ring-contracted carbaporphyrins. While m-Benziporphyrin(1.1.0.0) was unstable, m-pyreniporphyrin(1.1.0.0) was fairly stable. Both of their PdII complexes showed distorted coordination structures with extremely short Pd-C bonds. As compared with the reported m-benziporphyrin PdII complexes, these PdII complexes showed considerably small HOMO-LUMO gaps, despite their smaller molecular size.PdII metalation of m-pyreniporphyrin(1.1.0.0) dimer gave corresponding PdII complex, which showed the similar distorted coordination and a smaller HOMO-LUMO gap. Finally, PdII metalation of a pyrene-sharing formal p-benziporphyrin(1.1.1.1) dimer gave a nonaromatic PdII dimer, which rearranged to an aromatic PdII complex upon treatment with alumina.

18.
Front Genet ; 13: 993322, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36506331

RESUMO

The purpose of this study was to explore platinum resistance-related biomarkers and mechanisms in lung adenocarcinoma. Through the analysis of gene expression data of lung adenocarcinoma patients and normal patients from The Cancer Genome Atlas, Gene Expression Omnibus database, and A database of genes related to platinum resistance, platinum resistance genes in lung adenocarcinoma and platinum resistance-related differentially expressed genes were obtained. After screening by a statistical significance threshold, a total of 252 genes were defined as platinum resistance genes with significant differential expression, of which 161 were up-regulated and 91 were down-regulated. The enrichment results of up-regulated gene Gene Ontology (GO) showed that TOP3 entries related to biological processes (BP) were double-strand break repair, DNA recombination, DNA replication, the down-regulated gene GO enriches the TOP3 items about biological processes (BP) as a response to lipopolysaccharide, muscle cell proliferation, response to molecule of bacterial origin. Gene Set Enrichment Analysis showed that the top three were e2f targets, g2m checkpoint, and rgf beta signaling. A prognostic model based on non-negative matrix factorization classification showed the characteristics of high- and low-risk groups. The prognostic model established by least absolute shrinkage and selection operator regression and risk factor analysis showed that genes such as HOXB7, NT5E, and KRT18 were positively correlated with risk score. By analyzing the differences in m6A regulatory factors between high- and low-risk groups, it was found that FTO, GPM6A, METTL3, and YTHDC2 were higher in the low-risk group, while HNRNPA2B1, HNRNPC, TGF2BP1, IGF2BP2, IGF2BP3, and RBM15B were higher in the high-risk group. Immune infiltration and drug sensitivity analysis also showed the gene characteristics of the platinum-resistant population in lung adenocarcinoma. ceRNA analysis showed that has-miR-374a-5p and RP6-24A23.7 were lower in the tumor expression group, and that the survival of the low expression group was worse than that of the high expression group. In conclusion, the results of this study show that platinum resistance-related differentially expressed genes in lung adenocarcinoma are mainly concentrated in biological processes such as DNA recombination and response to lipopolysaccharide. The validation set proved that the high-risk group of our prognostic model had poor survival. M6A regulatory factor analysis, immune infiltration, and drug sensitivity analysis all showed differences between high and low-risk groups. ceRNA analysis showed that has-miR-374a-5p and RP6-24A23.7 could be protective factors. Further exploration of the potential impact of these genes on the risk and prognosis of drug-resistant patients with lung adenocarcinoma would provide theoretical support for future research.

19.
J Pers Med ; 12(12)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36556209

RESUMO

(1) Background: Hormone receptor positive breast cancer is a subtype of breast cancer with relatively good prognosis, but luminal B (HER-2 negative) breast cancer has a higher risk of recurrence and metastasis. Patients with endocrine therapy resistance and chemotherapy insensitivity have poor prognosis. Androgen receptor (AR) is widely expressed in breast cancer, but there is no clear conclusion about its function and correlation with prognosis in luminal B breast cancer. Further research is needed to reveal the role of AR in luminal B (HER-2 negative) breast cancer. (2) Methods: Retrospectively analyzed patients with early-stage luminal B breast cancer. The correlation between AR and its associated indexes with long-term survival was determined. (3) Results: A total of 985 patients were included with 143 treated by neoadjuvant therapy. Of these, 83.5% of the patients had AR expression ≥65%. High AR expression was associated with good disease-free survival (DFS) and overall survival (OS). In the neoadjuvant population, AR/estrogen receptor (ER) > 1.06 and residual tumor Ki67 > 23% had significantly worse DFS. (4) Conclusion: Low AR (<65%) expression is associated with poor prognosis in luminal B (HER-2 negative) breast cancer patients. High AR/ER and residual tumor Ki67 were associated with poor DFS in neoadjuvant group with a cutoff value of AR/ER > 1.06 and residual tumor Ki67 > 23%.

20.
J Hepatol ; 2022 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-36574921

RESUMO

BACKGROUND & AIMS: Hepatitis E virus (HEV) is a globally prevalent pathogen, annually resulting in 20 million infections, 3 million cases of clinical disease, and 60,000 fatalities worldwide, significantly endangering pregnant women and immunocompromised individuals. HEV-related research has been considerably delayed, and no HEV-specific therapeutics have yet been developed. We aimed to discover efficient anti-HEV drugs through high throughput screening that could be validated in vitro and in a preclinical animal study in vivo, and elucidate the underlying antiviral mechanism. METHODS: Using appropriate cellular and rodent HEV infection models, we studied a critical pathway for host-HEV interaction and performed a preclinical study of the corresponding antivirals by targeting proteostasis of the HEV replicase. RESULTS: We found 17 inhibitors that target HEV-HSP90 interactions by an unbiased compound library screening on human hepatocytes harboring an HEV replicon. Inhibitors of HSP90 (iHSP90) markedly suppressed HEV replication with efficacy exceeding that of conventional antivirals (IFNα and ribavirin) in vitro. Mechanistically, iHSP90 treatment released the viral replicase ORF1 protein from the ORF1-HSP90 complex and triggered ORF1 for rapid ubiquitin/proteasome-mediated degradation, resulting in abrogated HEV replication. Furthermore, a preclinical trial in a Mongolian gerbil HEV infection model showed this novel anti-HEV strategy to be safe, efficient, and able to prevent HEV-induced liver damage. CONCLUSIONS: This study collectively illustrates a critical proteostasis pathway for host-HEV interaction and paves the way for translating the new understanding of the HEV life cycle into clinically promising antivirals. IMPACT AND IMPLICATIONS: Appropriate treatment options for HEV-infected pregnant women as well as immunocompromised patients are lacking, creating an urgent need for developing safe HEV-specific therapies. This study identified new antivirals (inhibitors of HSP90) that significantly decrease the HEV infection by targeting viral replicase for degradation. Moreover, these anti-HEV drugs were validated in an HEV rodent model and found to be safe and efficient for prevention of HEV-induced liver injury in preclinical experiments. Our findings substantially promote the understanding of HEV pathobiology and the pace of antiviral development.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...