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1.
Opt Express ; 32(3): 3826-3834, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38297595

RESUMO

The critical condition and mechanism of the insulator-to-metal transition (IMT) for the black diamond were studied by the molecular-dynamics-Landauer method. The IMT will occur at sufficiently high contents of vacancies in the diamond. The critical concentration of vacancies for the IMT might be between V:C143 (0.69%) and V:C127 (0.78%). At a low concentration of vacancies (below 0.69%), the intermediate band (IB) consists of a filled band and a separate empty band, which makes the material to be an insulator. The IMT of the black diamond is due to the mergence between the two isolated IBs when the concentration of vacancies is high, and the merged IB is partially filled by electrons. The distribution of vacancies also influences the IMT of the black diamond.

2.
Bioorg Med Chem Lett ; 104: 129729, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38583786

RESUMO

Aptamers have shown significant potential in treating diverse diseases. However, challenges such as stability and drug delivery limited their clinical application. In this paper, the development of AS1411 prodrug-type aptamers for tumor treatment was introduced. A Short oligonucleotide was introduced at the end of the AS1411 sequence with a disulfide bond as responsive switch. The results indicated that the aptamer prodrugs not only enhanced the stability of the aptamer against nuclease activity but also facilitated binding to serum albumin. Furthermore, in the reducing microenvironment of tumor cells, disulfide bonds triggered drug release, resulting in superior therapeutic effects in vitro and in vivo compared to original drugs. This paper proposes a novel approach for optimizing the structure of nucleic acid drugs, that promises to protect other oligonucleotides or secondary structures, thus opening up new possibilities for nucleic acid drug design.


Assuntos
Antineoplásicos , Aptâmeros de Nucleotídeos , Pró-Fármacos , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/farmacologia , Linhagem Celular Tumoral , Dissulfetos/química , Sistemas de Liberação de Medicamentos , Ácidos Nucleicos/química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Estabilidade de Medicamentos
3.
BMC Neurol ; 24(1): 69, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38369500

RESUMO

BACKGROUND: Nummular headache (NH) is categorized as a primary headache in the International Classification of Headache Disorders, Third edition (ICHD-3) diagnostic criteria, but there are secondary etiologies as well. We present a case of secondary NH that associated with vascular lesion. CASE PRESENTATION: We report on a 40-year-old man with a medical history of symptomatic intracranial arterial stenosis who developed a headache after percutaneous transluminal angioplasty and stenting because of Intracranial atherosclerotic stenosis(ICAS). This new-onset headache was a pinprick headache confined to the parietal part of the head and 5 cm in size. This headache most closely resembled the phenotype of a NH. And other causes of secondary headache were excluded. Thus, the diagnosis of NH was highly speculated. This patient represents a rare headache phenomenon after intracranial arterial stent placement. CONCLUSION: This is the first report of NH after stent placement treatment in a patient with ICAS.


Assuntos
Artéria Cerebral Média , Stents , Masculino , Humanos , Adulto , Resultado do Tratamento , Constrição Patológica , Stents/efeitos adversos , Angioplastia , Cefaleia/etiologia
4.
BMC Neurol ; 24(1): 59, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336624

RESUMO

OBJECTIVES: Computed tomographic perfusion (CTP) can play an auxiliary role in the selection of patients with acute ischemic stroke for endovascular treatment. However, data on CTP in non-stroke patients with intracranial arterial stenosis are scarce. We aimed to investigate images in patients with asymptomatic intracranial arterial stenosis to determine the detection accuracy and interpretation time of large/medium-artery stenosis or occlusion when combining computed tomographic angiography (CTA) and CTP images. METHODS: We retrospectively reviewed 39 patients with asymptomatic intracranial arterial stenosis from our hospital database from January 2021 to August 2023 who underwent head CTP, head CTA, and digital subtraction angiography (DSA). Head CTA images were generated from the CTP data, and the diagnostic performance for each artery was assessed. Two readers independently interpreted the CTA images before and after CTP, and the results were analyzed. RESULTS: After adding CTP maps, the accuracy (area under the curve) of diagnosing internal carotid artery (R1: 0.847 vs. 0.907, R2: 0.776 vs. 0.887), middle cerebral artery (R1: 0.934 vs. 0.933, R2: 0.927 vs. 0.981), anterior cerebral artery (R1: 0.625 vs. 0.750, R2: 0.609 vs. 0.750), vertebral artery (R1: 0.743 vs. 0.764, R2: 0.748 vs. 0.846), and posterior cerebral artery (R1: 0.390 vs. 0.575, R2: 0.390 vs. 0.585) occlusions increased for both readers (p < 0.05). Mean interpretation time (R1: 72.4 ± 6.1 s vs. 67.7 ± 6.4 s, R2: 77.7 ± 3.8 s vs. 72.6 ± 4.7 s) decreased when using a combination of both images both readers (p < 0.001). CONCLUSIONS: The addition of CTP images improved the accuracy of interpreting CTA images and reduced the interpretation time in asymptomatic intracranial arterial stenosis. These findings support the use of CTP imaging in patients with asymptomatic intracranial arterial stenosis.


Assuntos
AVC Isquêmico , Humanos , Estudos Retrospectivos , Constrição Patológica/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Angiografia por Tomografia Computadorizada/métodos , Perfusão , Angiografia Cerebral/métodos
5.
J Chem Inf Model ; 64(12): 4835-4849, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38847742

RESUMO

The lymphocyte-specific protein tyrosine kinase (LCK) plays a crucial role in both T-cell development and activation. Dysregulation of LCK signaling has been demonstrated to drive the oncogenesis of T-cell acute lymphoblastic leukemia (T-ALL), thus providing a therapeutic target for leukemia treatment. In this study, we introduced a sophisticated virtual screening strategy combined with biological evaluations to discover potent LCK inhibitors. Our initial approach involved utilizing the PLANET algorithm to assess and contrast various scoring methodologies suitable for LCK inhibitor screening. After effectively evaluating PLANET, we progressed to devise a virtual screening workflow that synergistically combines the strengths of PLANET with the capabilities of Schrödinger's suite. This integrative strategy led to the efficient identification of four potential LCK inhibitors. Among them, compound 1232030-35-1 stood out as the most promising candidate with an IC50 of 0.43 nM. Further in vitro bioassays revealed that 1232030-35-1 exhibited robust antiproliferative effects on T-ALL cells, which was attributed to its ability to suppress the phosphorylations of key molecules in the LCK signaling pathway. More importantly, 1232030-35-1 treatment demonstrated profound in vivo antileukemia efficacy in a human T-ALL xenograft model. In addition, complementary molecular dynamics simulations provided deeper insight into the binding kinetics between 1232030-35-1 and LCK, highlighting the formation of a hydrogen bond with Met319. Collectively, our study established a robust and effective screening strategy that integrates AI-driven and conventional methodologies for the identification of LCK inhibitors, positioning 1232030-35-1 as a highly promising and novel drug-like candidate for potential applications in treating T-ALL.


Assuntos
Aprendizado Profundo , Proteína Tirosina Quinase p56(lck) Linfócito-Específica , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/antagonistas & inibidores , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Humanos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Animais , Descoberta de Drogas , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Camundongos
6.
Phys Chem Chem Phys ; 26(5): 4683-4691, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38251932

RESUMO

The manipulation and regulation of valley characteristics have aroused widespread interest in emerging information fields and fundamental research. Realizing valley polarization is one crucial issue for spintronic and valleytronic applications, the concepts of a half-valley metal (HVM) and ferrovalley (FV) materials have been put forward. Then, to separate electron and hole carriers, a fresh concept of a quasi-HVM (QHVM) has been proposed, in which only one type of carrier is valley polarized for electron and hole carriers. Based on first-principles calculations, we demonstrate that the Janus monolayer VSiGeP4 has QHVM character. To well regulate the QHVM state, strain engineering is utilized to adjust the electronic and valley traits of monolayer VSiGeP4. In the discussed strain range, monolayer VSiGeP4 always favors the ferromagnetic ground state and out-of-plane magnetization, which ensures the appearance of spontaneous valley polarization. It is found that the QHVM state can be induced in different electronic correlations (U), and the strain can effectively tune the valley, magnetic, and electronic features to maintain the QHVM state under various U values. Our work opens up a new research idea in the design of multifunctional spintronic and valleytronic devices.

7.
Bioorg Chem ; 142: 106969, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37988784

RESUMO

Nucleolus was an important cellular organelle. The abnormal morphology and number of the nucleolus have been considered as diagnostic biomarkers for some human diseases. However, the imaging agent based on nucleolus was limited. In this manuscript, a series of nucleolar fluorescent probes based on naphthalimide derivatives (NI-1 âˆ¼ NI-5) had been designed and synthesized. NI-1 âˆ¼ NI-5 could penetrate cell membranes and nuclear membranes, achieve clear nucleolar staining in living cells. These results suggested that the presence of amino groups on the side chains of naphthalimide backbone could enhance the targeting to the cell nucleolus. In addition, the molecular docking results showed that NI-1 âˆ¼ NI-5 formed hydrogen bonds and hydrophobic interactions with RNA, and exhibited enhanced fluorescence upon binding with RNA. These results will provide favorable support for the diagnosis and treatment of nucleolus-related diseases in the future.


Assuntos
Nucléolo Celular , Naftalimidas , Humanos , Nucléolo Celular/metabolismo , Simulação de Acoplamento Molecular , RNA/metabolismo
8.
Acta Pharmacol Sin ; 45(5): 914-925, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38253637

RESUMO

Metrnl is a secreted protein involved in neurite outgrowth, insulin sensitivity, immunoinflammatory responses, blood lipids and endothelial protection. In this study, we investigated the role of Metrnl in ischemic stroke. Fifty-eight ischemic stroke patients (28 inpatient patients within 2 weeks of onset and 30 emergency patients within 24 h of onset) and 20 healthy controls were enrolled. Serum Metrnl was measured by enzyme-linked immunosorbent assay. We showed that serum Metrnl levels were significantly reduced in both inpatient and emergency patient groups compared with the controls. Different pathological causes for ischemic stroke such as large artery atherosclerosis and small artery occlusion exhibited similar reduced serum Metrnl levels. Transient ischemic attack caused by large artery atherosclerosis without brain infarction also had lower serum Metrnl levels. Metrnl was correlated with some metabolic, inflammatory and clotting parameters. Reduced serum Metrnl was associated with the severity of intracranial arterial stenosis and the presence of ischemic stroke. In order to elucidate the mechanisms underlying the reduced serum Metrnl levels, we established animal models of ischemic stroke in normal mice, atherosclerotic apolipoprotein E-knockout mice and Metrnl-knockout mice by middle cerebral artery occlusion (MCAO) using intraluminal filament or electrocoagulation. We demonstrated that serum Metrnl levels were significantly lower in atherosclerosis mice than normal mice, whereas acute ischemic stroke injury in normal mice and atherosclerosis mice did not alter serum Metrnl levels. Metrnl knockout did not affect acute ischemic stroke injury and death. We conclude that reduced serum Metrnl levels are attributed to the chronic vascular pathogenesis before the onset of ischemic stroke. Metrnl is a potential target for prevention of ischemic stroke.


Assuntos
Adipocinas , AVC Isquêmico , Humanos , Animais , Masculino , AVC Isquêmico/sangue , AVC Isquêmico/genética , Feminino , Pessoa de Meia-Idade , Idoso , Camundongos Endogâmicos C57BL , Camundongos , Infarto da Artéria Cerebral Média/sangue , Camundongos Knockout para ApoE
9.
Acta Pharmacol Sin ; 45(8): 1673-1685, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38641746

RESUMO

Acute kidney injury (AKI) is defined as sudden loss of renal function characterized by increased serum creatinine levels and reduced urinary output with a duration of 7 days. Ferroptosis, an iron-dependent regulated necrotic pathway, has been implicated in the progression of AKI, while ferrostatin-1 (Fer-1), a selective inhibitor of ferroptosis, inhibited renal damage, oxidative stress and tubular cell death in AKI mouse models. However, the clinical translation of Fer-1 is limited due to its lack of efficacy and metabolic instability. In this study we designed and synthesized four Fer-1 analogs (Cpd-A1, Cpd-B1, Cpd-B2, Cpd-B3) with superior plasma stability, and evaluated their therapeutic potential in the treatment of AKI. Compared with Fer-1, all the four analogs displayed a higher distribution in mouse renal tissue in a pharmacokinetic assay and a more effective ferroptosis inhibition in erastin-treated mouse tubular epithelial cells (mTECs) with Cpd-A1 (N-methyl-substituted-tetrazole-Fer-1 analog) being the most efficacious one. In hypoxia/reoxygenation (H/R)- or LPS-treated mTECs, treatment with Cpd-A1 (0.25 µM) effectively attenuated cell damage, reduced inflammatory responses, and inhibited ferroptosis. In ischemia/reperfusion (I/R)- or cecal ligation and puncture (CLP)-induced AKI mouse models, pre-injection of Cpd-A1 (1.25, 2.5, 5 mg·kg-1·d-1, i.p.) dose-dependently improved kidney function, mitigated renal tubular injury, and abrogated inflammation. We conclude that Cpd-A1 may serve as a promising therapeutic agent for the treatment of AKI.


Assuntos
Injúria Renal Aguda , Ferroptose , Camundongos Endogâmicos C57BL , Fenilenodiaminas , Animais , Ferroptose/efeitos dos fármacos , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Camundongos , Masculino , Fenilenodiaminas/farmacologia , Fenilenodiaminas/uso terapêutico , Cicloexilaminas/farmacologia , Cicloexilaminas/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo
10.
J Chem Phys ; 160(18)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38726939

RESUMO

Isotropic materials are required to adhere to various mechanical principles due to their limited thermal stability. For instance, it is essential for Poisson's ratio to be within the range of -1 to 0.5, and the longitudinal wave velocity must exceed the transverse wave velocity. Nevertheless, perfect crystals, as anisotropic materials, have the ability to defy conventional rules. Through the integration of high-throughput processes and first-principles calculations, a comprehensive exploration of known materials was conducted, resulting in the establishment of a database featuring an extreme anisotropic mechanism. This included the identification of abnormal Poisson's ratios (with the directional Poisson's ratio ranging from -3.00 to 3.67), the discovery of extreme negative linear compressibility, the determination of the upper and lower limits of the sound velocity, and other associated properties. Several materials with abnormal Poisson's ratios (<-1 or >0.5) were listed, and their peculiar mechanical behavior, wherein the volume decreased counterintuitively with uniaxial tension, was discussed. Finally, this study focused on the velocities of longitudinal and transverse waves, with specific emphasis on materials exhibiting transverse wave velocities that exceeded the longitudinal wave velocities.

11.
BMC Pregnancy Childbirth ; 24(1): 109, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317068

RESUMO

BACKGROUND: Hypertensive disorders of pregnancy (HDP) is the most common cause of indicated preterm delivery, but the impact of prenatal steroid exposure on the outcomes of preterm infants born to HDP mothers, who may be at risk for intrauterine hypoxia-ischemia, remains uncertain. The study objective is to evaluate the mortality and morbidities in HDP for very preterm infants (VPIs) exposed to different course of ANS. METHODS: This is a prospective cohort study comprising infants with < 32 weeks gestation born to women with HDP only from 1 Jan. 2019 to 31 Dec. 2021 within 40 participating neonatal intensive care units (NICUs) in Sino-northern network. ANS courses included completed, partial, repeated, and no ANS. Univariate and multivariable analyses were performed on administration of ANS and short-term outcomes before discharge. RESULTS: Among 1917 VPIs born to women with HDP only, 987(51.4%) received a complete course of ANS within 48 h to 7 days before birth, 560(29.2%) received partial ANS within 24 h before delivery, 100(5.2%) received repeat ANS and 270 (14.1%) did not receive any ANS. Compared to infants who received complete ANS, infants unexposed to ANS was associated with higher odds of death (AOR 1.85; 95%CI 1.10, 3.14), Severe Neurological Injury (SNI) or death (AOR 1.68; 95%CI 1.29,3.80) and NEC or death (AOR 1.78; 95%CI 1.55, 2.89), the repeated ANS group exhibits a significant negative correlation with the duration of oxygen therapy days (correlation coefficient - 18.3; 95%CI-39.2, -2.1). However, there were no significant differences observed between the full course and partial course groups in terms of outcomes. We can draw similar conclusions in the non-SGA group, while the differences are not significant in the SGA group. From KM curve, it showed that the repeated group had the highest survival rate, but the statistical analysis did not indicate a significant difference. CONCLUSIONS: Even partial courses of ANS administered within 24 h before delivery proved to be protective against death and other morbidities. The differences mentioned above are more pronounced in the non-SGA group. Repeat courses demonstrate a trend toward protection, but this still needs to be confirmed by larger samples.


Assuntos
Hipertensão Induzida pela Gravidez , Doenças do Prematuro , Pré-Eclâmpsia , Lactente , Recém-Nascido , Gravidez , Humanos , Feminino , Recém-Nascido Prematuro , Estudos Prospectivos , Hipertensão Induzida pela Gravidez/epidemiologia , Corticosteroides/uso terapêutico , Doenças do Prematuro/prevenção & controle , Idade Gestacional , Retardo do Crescimento Fetal , Morbidade
12.
Neoplasma ; 71(3): 266-278, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38958711

RESUMO

Neural invasion underlies the local spread of gastric cancer and is associated with poor prognosis. This process has been receiving increasing attention in recent years. However, the relationship between neural invasion and the malignant phenotypes of gastric cancer cells, as well as the molecular mechanism involved in this process, remain unclear. In this study, bioinformatics analysis was performed using a dataset obtained from The Cancer Genome Atlas-Stomach Adenocarcinoma. The results revealed that high expression of GDNF family receptor alpha 3 (GFRA3) was associated with a poor prognosis of patients with gastric cancer. GFRA3 is a receptor for artemin (ARTN), a glial cell line-derived neurotrophic factor (GDNF). This association was indicated by short overall/disease-free survival, as well as the presence of high-stage and high-grade disease. Gene set enrichment analysis showed that two cancer-associated pathways, namely KRAS signaling and epithelial-mesenchymal transition (EMT), were activated when GFRA3 was highly expressed in gastric cancer. Further studies confirmed that GFRA3 activated KRAS downstream signaling phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) or extracellular signal-regulated kinase (ERK) and induced EMT markers, as well as promoted the migration and invasion of gastric cancer cells. As a ligand of GFRA3, ARTN induced the EMT, migration, and invasion of gastric cancer cells via GFRA3. Notably, the effects of the ARTN-GFRA3 axis were attenuated by treatment with a KRAS inhibitor. The present findings indicated that, during the neural invasion of gastric cancer, ARTN-mediated activation of GFRA3 induces EMT phenotypes, migration, and invasion of gastric cancer cells via KRAS signaling.


Assuntos
Transição Epitelial-Mesenquimal , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial , Invasividade Neoplásica , Transdução de Sinais , Neoplasias Gástricas , Humanos , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Fenótipo , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética
13.
J Obstet Gynaecol Res ; 50(6): 982-990, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38570724

RESUMO

PURPOSE: This study analyzes the relationship between human papillomavirus (HPV) infection, vaginal microecology, and cervical lesions to provide a basis for the prevention and treatment of cervical cancer (CC) in the Xinjiang region. METHODS: Real-time quantitative PCR was used for HPV genotyping and viral load. The Gram staining and dry biochemical enzyme kit were utilized to diagnose vaginal secretions. The χ2 test and Logistic regression analysis were used for statistical analysis. RESULTS: The HPV infection rate among women in the Xinjiang region was 30.29%, of which the single HPV infection accounts for 77%. HPV16 and HPV52 were the main infection types. There was significant differences in the HPV infection rate and infection types among the Han, Uighur, Hui, and Kazakh ethnic groups. The viral load of HPV16 and HPV52 increases with the upgrade of cervical lesions. There were significant differences in vaginal microecology evaluation indicators H2O2, SNA, LE, GUS, trichomonas, clue cells, and lactobacilli among different ethnic groups. HPV negative patients with varying grades of cervical lesions exhibit a notable variance in H2O2 and LE, which is statistically significant. Single HPV infection and high viral load HPV significantly increase the risk of CC. CONCLUSIONS: This study indicates that HPV infection and vaginal microecology differ among ethnic groups, which have a strong correlation with the progression of CC, offering guidance on CC screening and interventions in the Xinjiang area.


Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Vagina , Humanos , Feminino , China/epidemiologia , Infecções por Papillomavirus/virologia , Adulto , Pessoa de Meia-Idade , Displasia do Colo do Útero/virologia , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/etnologia , Neoplasias do Colo do Útero/virologia , Vagina/virologia , Adulto Jovem , Carga Viral
14.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2385-2392, 2024 May.
Artigo em Zh | MEDLINE | ID: mdl-38812139

RESUMO

This study aims to investigate the mechanism of total saponins of Paridis Rhizoma in inducing the ferroptosis of MCF-7 cells and provide a theoretical basis for the clinical treatment of breast cancer with total saponins of Paridis Rhizoma. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the effects of different concentrations of total saponins of Paridis Rhizoma on the proliferation of MCF-7 cells. A phase contrast inverted microscope was used to observe the morphological changes of MCF-7 cells. The colony formation assay was employed to test the colony formation of MCF-7 cells. The lactate dehydrogenase(LDH) release test was conducted to determine the cell membrane integrity of MCF-7 cells. The cell scratch assay was employed to examine the migration of MCF-7 cells. After that, the level of reactive oxygen species(ROS) in MCF-7 cells was observed by an inverted fluorescence microscope, and the content of Fe~(2+) in MCF-7 cells was detected by the corresponding kit. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of MCF-7 cells. Western blot was employed to determine the expression of ferroptosis-related proteins, such as p53, solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long-chain family member 4(ACSL4), and transferrin receptor protein 1(TFR1) in MCF-7 cells. The results showed that 1.5, 3, 4.5, 6, 7.5, and 9 µg·mL~(-1) total saponins of Paridis Rhizoma significantly inhibited the proliferation of MCF-7 cells, with the IC_(50) of 4.12 µg·mL~(-1). Total saponins of Paridis Rhizoma significantly damaged the morphology of MCF-7 cells, leading to the formation of vacuoles and the gradual shrinkage and detachment of cells. Meanwhile, total saponins of Paridis Rhizoma inhibited the colony formation of MCF-7 cells, destroyed the cell membrane(leading to the release of LDH), and shortened the migration distance of MCF-7 cells. Total saponins of Paridis Rhizoma treatment significantly increased the content of ROS, induced oxidative damage, and led to the accumulation of Fe~(2+) in MCF-7 cells. Furthermore, total saponins of Paridis Rhizoma changed the mitochondrial structure, increased the mitochondrial membrane density, led to the decrease or even disappear of ridges, promoted the expression of p53 protein, down-regulated the expression of SLC7A11 and GPX4, and up-regulated the expression of ACSL4 and TFR1. In summary, total saponins of Paridis Rhizoma can significantly inhibit the proliferation and migration of MCF-7 cells and destroy the cell structure by inducing ferroptosis.


Assuntos
Neoplasias da Mama , Ferroptose , Espécies Reativas de Oxigênio , Rizoma , Saponinas , Humanos , Saponinas/farmacologia , Saponinas/química , Ferroptose/efeitos dos fármacos , Células MCF-7 , Rizoma/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Espécies Reativas de Oxigênio/metabolismo , Feminino , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Proliferação de Células/efeitos dos fármacos , Primulaceae/química
15.
Zhongguo Zhong Yao Za Zhi ; 49(14): 3971-3976, 2024 Jul.
Artigo em Zh | MEDLINE | ID: mdl-39099370

RESUMO

The development of traditional Chinese medicine(TCM) preparations as an incubator for new drugs in medical institutions has flourished, while an evaluation index system remains to be established for comprehensively assessing the development value of these prescriptions. This study established an item pool through literature research, employed the Delphi method to determine the content of evaluation indexes, and adopted the superiority chart to determine the weight of each index. Two-level evaluation index system for the development value of TCM preparations in medical institutions was established, which included 7 first-level items and 36 se-cond-level items, demonstrating scientific validity. The first-level items(weight) were inheritance(10.61%), effectiveness(23.22%), safety(22.71%), innovation(13.21%), economy(10.00%), suitability(8.57%), and accessibility(11.68%). The top three second-level items in terms of weight distribution were adverse reaction monitoring(6.73%), evidence of therapeutic effect(5.71%), and clinical response rate(4.75%). The bottom three second-level items were production advantages(0.86%), medicinal dosage(0.48%), and medicinal smell or taste(0.18%). The content validity of the established system was assessed, which revealed that the index system was reliable, with the overall and average content validity indexes of 0.47 and 0.90, respectively. Furthermore, the established evaluation index system was used to evaluate six TCM preparations in a city-level hospital of TCM in Sichuan Province, which demonstrated that the system had operability. The results indicate that the evaluation index system is scientific, reliable, and operable, providing a reference for developers to selectively develop TCM preparations in medical institutions. In practical application, the system can be adjusted regarding the index weights according to actual conditions.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicina Tradicional Chinesa/normas , Medicamentos de Ervas Chinesas/normas , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Humanos
16.
Angew Chem Int Ed Engl ; : e202407612, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007237

RESUMO

The synthesis of multicarbon (C2+) products remains a substantial challenge in sustainable CO2 electroreduction owing to the need for sufficient current density and faradaic efficiency alongside carbon efficiency. Herein, we demonstrate ampere-level high-efficiency CO2 electroreduction to C2+ products in both neutral and strongly acidic (pH = 1) electrolytes using a hierarchical Cu hollow-fiber penetration electrode (HPE). High concentration of K+ could concurrently suppress hydrogen evolution reaction and facilitate C-C coupling, thereby promoting C2+ production in strong acid. By optimizing the K+ and H+ concentration and CO2 flow rate, a faradaic efficiency of 84.5% and a partial current density as high as 3.1 A cm-2 for C2+ products, alongside a single-pass carbon efficiency of 81.5% and stable electrolysis for 240 h were demonstrated in a strong acidic solution of H2SO4 and KCl (pH = 1). Experimental measurements and density functional theory simulations suggested that tensile-strained Cu HPE enhances the asymmetric C-C coupling to steer the selectivity and activity of C2+ products.

17.
Angew Chem Int Ed Engl ; : e202411173, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39109442

RESUMO

The electrochemical propylene epoxidation reaction (PER) provides a promising route for ecofriendly propylene oxide (PO) production, instantly generating active halogen/oxygen species to alleviate chloride contamination inherent in traditional PER. However, the complex processes and unsatisfactory PO yield for current electrochemical PER falls short of meeting industrial application requirements. Herein, a spatial-coupling strategy over RuO2/Ti hollow-fiber penetration electrode (HPE) is adopted to facilitate efficient PO production, significantly improving PER performance to the ampere level (achieving over 80% PO faradaic efficiency and a maximum PO current density of 859 mA cm-2). The synergetic combination of the penetration effect of HPE and the spatial-coupled reaction sequence, enables the realization of ampere-level PO production with high specificity, exhibiting significant potentials for economically viable PER applications.

18.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(5): 437-443, 2024 May 15.
Artigo em Zh | MEDLINE | ID: mdl-38802901

RESUMO

The UK screening and treatment of retinopathy of prematurity (ROP) updated 2022 guidelines were developed by a multidisciplinary guideline development group from the Royal College of Paediatrics and Child Health and the Royal College of Ophthalmologists, following the standards of the National Institute for Health and Care Excellence. They were published on the websites of the Royal College of Paediatrics and Child Health and the Royal College of Ophthalmologists in March 2022, and formally published in Early Human Development in March 2023. The guidelines provide evidence-based recommendations for the screening and treatment of ROP. The most significant change in the 2022 updated version compared to the previous guidelines is the lowering of the gestational age screening criterion to below 31 weeks. The treatment section covers treatment indications, timing, methods, and follow-up visits of ROP. This article interprets the guidelines and compares them with ROP guidelines/consensus in China, providing a reference for domestic peers.


Assuntos
Guias de Prática Clínica como Assunto , Retinopatia da Prematuridade , Humanos , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/terapia , Recém-Nascido , Reino Unido , Triagem Neonatal , Idade Gestacional
19.
J Transl Med ; 21(1): 911, 2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-38098005

RESUMO

OBJECTIVE: Pancreatic cancer is an aggressive malignancy with high mortality, and cancer cell stemness and related drug resistance are considered important contributors to its poor prognosis. The objective of this study was to identify regulatory targets associated with the maintenance of pancreatic cancer stemness. MATERIALS AND METHODS: Pancreatic tumor samples were collected from patients at Sun Yat-sen University Cancer Center, followed by immunofluorescence analysis. Pancreatic cancer cell lines with Interleukin-20 receptor subunit beta (IL20RB) overexpression and knockdown were established, and clonal formation, spheroid formation and side population cell analysis were conducted. The effects of IL20RB knockdown on the tumor-forming ability of pancreatic cancer cells and chemotherapy resistance in vivo were explored. RESULTS: IL20RB expression was significantly upregulated in pancreatic cancer tissues, and was correlated with unfavorable prognosis. The IL20RB receptor promotes stemness and chemoresistance in both in vitro and in vivo models of pancreatic cancer. Mechanistically, IL20RB enhances the stemness and chemoresistance of pancreatic cancer by promoting STAT3 phosphorylation, an effect that can be counteracted by a STAT3 phosphorylation inhibitors. Additionally, Interleukin-19 derived from the microenvironment is identified as the primary ligand for IL20RB in mediating these effects. CONCLUSION: Our findings demonstrate that IL20RB plays a crucial role in promoting stemness in pancreatic cancer. This discovery provides a potential therapeutic target for this lethal disease.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias Pancreáticas , Humanos , Linhagem Celular Tumoral , Transdução de Sinais , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Prognóstico , Células-Tronco Neoplásicas/patologia , Microambiente Tumoral
20.
Phys Rev Lett ; 131(26): 266101, 2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38215382

RESUMO

The Grüneisen parameter (γ) is crucial for determining many thermal properties, including the anharmonic effect, thermostatistics, and equation of state of materials. However, the isentropic adiabatic compression conditions required to measure the Grüneisen parameter under high pressure are difficult to achieve. Thus, direct experimental Grüneisen parameter data in a wide range of pressures is sparse. In this work, we developed a new device that can apply pressure (up to tens of GPa) with an extremely short time of about 0.5 ms, confidently achieving isentropic adiabatic compression. Then, we applied our new technique to sodium chloride and measured its Grüneisen parameter, which conforms to previous theoretical predictions. According to our obtained sodium chloride Grüneisen parameters, the calculated Hugoniot curve of the NaCl B1 phase appears up to 20 GPa and 960 K, which compares very well with the shock compression experimental data by Fritz et al. and other calculation works. Our results suggest that this new method can reliably measure the Grüneisen parameter of even more materials, which is significant for researching the equation of state in substances.

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