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1.
Environ Sci Technol ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300776

RESUMO

Brown carbon (BrC) from biomass burning constitutes a significant portion of light-absorbing components in the atmosphere. Although the aging of BrC surrogates from biomass burning has been studied in many laboratory settings, BrC aging behavior in real-world urban environments is not well understood. In this study, through a combination of online dynamic monitoring and offline molecular characterization, the ambient optical aging of BrC was linked to its dynamic changes in molecular composition. Enhanced light absorption by BrC was consistently observed during the periods dominated by oxygenated biomass burning organic aerosol (BBOA), in contrast to periods dominated by primary emissions or secondary formation in aqueous-phase. This enhancement was linked to the formation of nitrogen-containing compounds during the ambient aging of BBOA. Detailed molecular characterization, alongside analysis of environmental parameters, revealed that an increased atmospheric oxidizing capacity, marked by elevated levels of ozone and nighttime NO3 radicals, facilitated the formation of nitrated aromatic BrC chromophores. These chromophores were primarily responsible for the enhanced light absorption during the ambient aging of BBOA. This study elucidates the nitration processes that enhance BrC light absorption for ambient BBOA, and highlights the crucial role of meteorological conditions. Furthermore, our findings shed light on the chemical and optical aging processes of biomass burning BrC in ambient air, offering insights into its environmental behavior and effects.

2.
Drug Des Devel Ther ; 18: 4135-4151, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39308693

RESUMO

Objective: This study aimed to identify the effectiveness and safety of PD-1 blockades among elderly patients with metastatic esophageal squamous cell carcinoma (ESCC) clinically. Methods: A total of 78 elderly patients with previously treated metastatic ESCC aged ≥65 years who received PD-1 blockades monotherapy were included retrospectively. Demographic characteristics, therapeutic effectiveness and adverse reactions of the elderly patients who underwent PD-1 blockade therapy were recorded. Regular follow-up was conducted for all patients. The analysis aimed to identify potential risk factors for OS by examining the correlation between prognosis and subgroups based on baseline characteristics. Results: The median age of the 78 elderly patients was 73 years, ranging from 65 to 87 years. Among the 78 patients, 18 cases showed partial response, 26 cases had stable disease, 29 cases experienced progressive disease and 5 cases were not assessable for response, yielding an ORR of 23.1%, a DCR of 56.4%. The prognostic outcomes indicated that among the 78 patients with metastatic ESCC who received PD-1 blockades, the median PFS was 3.1 months [95% confidence interval (CI): 1.64-4.56], and the median OS was 10.9 months (95% CI: 6.02-15.78), 24-month OS rate was 22.7% (95% CI: 12.8-34.2%). In terms of the safety profile, among the 78 patients with metastatic ESCC during PD-1 blockades single-agent treatment, a total of 61 patients (78.2%) experienced any grade adverse reactions and the incidence of grade ≥3 adverse reactions were 20.5%. Briefly, the common adverse reactions manifested as fatigue (32.1%), gastrointestinal reaction (24.4%), diarrhea (19.2%), anemia (17.9%) and rash (16.7%). Overall tolerability of PD-1 blockade monotherapy in elderly patients with metastatic ESCC was acceptable and manageable. Conclusion: PD-1 blockades single agent demonstrated encouraging effectiveness and acceptable safety profile for elderly patients with previously treated metastatic ESCC in clinical practice. Prospective study should be performed to elucidate the conclusion in this study subsequently.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Estudos de Viabilidade , Receptor de Morte Celular Programada 1 , Humanos , Idoso , Masculino , Idoso de 80 Anos ou mais , Feminino , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Estudos Retrospectivos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Metástase Neoplásica
3.
Artigo em Inglês | MEDLINE | ID: mdl-39263882

RESUMO

OBJECT: This study aims to explore the clinical and pathologic characteristics of HPV-related primary thyroid squamous cell carcinoma (PSCCT), a rare tumor classified by WHO-5 as a subtype of anaplastic thyroid carcinoma (ATC). METHODS: Clinical data, histomorphology, immunohistochemistry, HPV detection, and B-raf gene point mutations of 3 PSCCT cases were analyzed. Subsequent follow-up was conducted post-treatment. RESULTS: All 3 cases involved female patients aged between 60 and 76. Microscopic examination revealed squamous cell carcinoma in cases 1 and 3, whereas case 2 exhibited both squamous cell carcinoma and papillary thyroid carcinoma components. Immunohistochemistry demonstrated CK19, PAX8, and TTF1 expression in the papillary thyroid carcinoma component, and CK5/6, p63, p40, and PAX8 expression in the squamous cell carcinoma component. P16 exhibited diffuse positivity in both squamous cell carcinoma and classic papillary carcinoma. HPV analysis identified low-risk type 6 positivity in cases 1 and 3, while both squamous cell carcinoma and papillary carcinoma areas in case 2 were positive for HPV-33. B-raf gene mutation was exclusive to case 2. CONCLUSION: Diagnosis of PSCCT necessitates multidisciplinary assessment, incorporating clinical symptoms, imaging, histomorphology, and immunohistochemistry. This study, for the first time, reveals the presence of HPV DNA in both PTC and PSCCT, occurring concurrently but separately. Given the limited scope of 3 case reports, definitive conclusions cannot be drawn, warranting further investigation.

4.
Front Cell Dev Biol ; 12: 1415258, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39144255

RESUMO

Background: Tuberous sclerosis is a multi-system disorder caused by mutations in either TSC1 or TSC2. The majority of affected patients (85%-90%) have heterozygous variants, and a smaller number (around 5%) have mosaic variants. Despite using various techniques, some patients still have "no mutation identified" (NMI). Methods: We hypothesized that the causal variants of patients with NMI may be structural variants or deep intronic variants. To investigate this, we sequenced the DNA of 26 tuberous sclerosis patients with NMI using targeted long-read sequencing. Results: We identified likely pathogenic/pathogenic variants in 13 of the cases, of which 6 were large deletions, four were InDels, two were deep intronic variants, one had retrotransposon insertion in either TSC1 or TSC2, and one was complex rearrangement. Furthermore, there was a de novo Alu element insertion with a high suspicion of pathogenicity that was classified as a variant of unknown significance. Conclusion: Our findings expand the current knowledge of known pathogenic variants related to tuberous sclerosis, particularly uncovering mosaic complex structural variations and retrotransposon insertions that have not been previously reported in tuberous sclerosis. Our findings suggest a higher prevalence of mosaicism among tuberous sclerosis patients than previously recognized. Our results indicate that long-read sequencing is a valuable approach for tuberous sclerosis cases with no mutation identified (NMI).

5.
World J Clin Cases ; 12(21): 4642-4651, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39070806

RESUMO

BACKGROUND: Studies have revealed that Children's psychological, behavioral, and emotional problems are easily influenced by the family environment. In recent years, the family structure in China has undergone significant changes, with more families having two or three children. AIM: To explore the relationship between emotional behavior and parental job stress in only preschool and non-only preschool children. METHODS: Children aged 3-6 in kindergartens in four main urban areas of Shijiazhuang were selected by stratified sampling for a questionnaire and divided into only and non-only child groups. Their emotional behaviors and parental pressure were compared. Only and non-only children were paired in a 1:1 ratio by class and age (difference less than or equal to 6 months), and the matched data were compared. The relationship between children's emotional behavior and parents' job stress before and after matching was analyzed. RESULTS: Before matching, the mother's occupation, children's personality characteristics, and children's rearing patterns differed between the groups (P < 0.05). After matching 550 pairs, differences in the children's parenting styles remained. There were significant differences in children's gender and parents' attitudes toward children between the two groups. The Strengths and Difficulties Questionnaire (SDQ) scores of children in the only child group and the Parenting Stress Index-Short Form (PSI-SF) scores of parents were significantly lower than those in the non-only child group (P < 0.05). Pearson's correlation analysis showed that after matching, there was a positive correlation between children's parenting style and parents' attitudes toward their children (r = 0.096, P < 0.01), and the PSI-SF score was positively correlated with children's gender, parents' attitudes toward their children, and SDQ scores (r = 0.077, 0.193, 0.172, 0.222). CONCLUSION: Preschool children's emotional behavior and parental pressure were significantly higher in multi-child families. Parental pressure in differently structured families was associated with many factors, and preschool children's emotional behavior was positively correlated with parental pressure.

6.
Brain Behav Immun ; 120: 256-274, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38852761

RESUMO

Major depressive disorder (MDD) is a global health burden characterized by persistent low mood, deprivation of pleasure, recurrent thoughts of death, and physical and cognitive deficits. The current understanding of the pathophysiology of MDD is lacking, resulting in few rapid and effective antidepressant therapies. Recent studies have pointed to the sigma-1 (σ-1) receptor as a potential rapid antidepressant target; σ-1 agonists have shown promise in a variety of preclinical depression models. Hypidone hydrochloride (YL-0919), an independently developed antidepressant by our institute with faster onset of action and low rate of side effects, has recently emerged as a highly selective σ-1 receptor agonist; however, its underlying astrocyte-specific mechanism is unknown. In this study, we investigated the effect of YL-0919 treatment on gene expression in the prefrontal cortex of depressive-like mice by single-cell RNA sequencing. Furthermore, we knocked down σ-1 receptors on astrocytes in the medial prefrontal cortex of mice to explore the effects of YL-0919 on depressive-like behavior and neuroinflammation in mice. Our results demonstrated that astrocyte-specific knockdown of σ-1 receptor resulted in depressive-like behavior in mice, which was reversed by YL-0919 administration. In addition, astrocytic σ-1 receptor deficiency led to activation of the NF-κB inflammatory pathway, and crosstalk between reactive astrocytes and activated microglia amplified neuroinflammation, exacerbating stress-induced neuronal apoptosis. Furthermore, the depressive-like behavior induced by astrocyte-specific knockdown of the σ-1 receptor was improved by a selective NF-κB inhibitor, JSH-23, in mice. Our study not only reaffirms the σ-1 receptor as a key target of the faster antidepressant effect of YL-0919, but also contributes to the development of astrocytic σ-1 receptor-based novel drugs.


Assuntos
Antidepressivos , Astrócitos , Transtorno Depressivo Maior , Camundongos Endogâmicos C57BL , NF-kappa B , Córtex Pré-Frontal , Receptores sigma , Receptor Sigma-1 , Receptores sigma/metabolismo , Receptores sigma/agonistas , Animais , Astrócitos/metabolismo , Astrócitos/efeitos dos fármacos , Camundongos , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Antidepressivos/farmacologia , NF-kappa B/metabolismo , Masculino , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Modelos Animais de Doenças , Depressão/metabolismo , Depressão/tratamento farmacológico
7.
Biochem Pharmacol ; 226: 116392, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38942091

RESUMO

Bitter taste receptors (TAS2Rs) Tas2r108 gene possesses a high abundance in mouse kidney; however, the biological functions of Tas2r108 encoded receptor TAS2Rs member 4 (TAS2R4) are still unknown. In the present study, we found that mouse TAS2R4 (mTAS2R4) signaling was inactivated in chronic high glucose-stimulated mouse podocyte cell line MPC, evidenced by the decreased protein expressions of mTAS2R4 and phospholipase C ß2 (PLCß2), a key downstream molecule of mTAS2R4 signaling. Nonetheless, agonism of mTAS2R4 by quinine recovered mTAS2R4 and PLCß2 levels, and increased podocyte cell viability as well as protein expressions of ZO-1 and nephrin, biomarkers of podocyte slit diaphragm, in high glucose-cultured MPC cells. However, blockage of mTAS2R4 signaling with mTAS2R4 blockers γ-aminobutyric acid and abscisic acid, a Gßγ inhibitor Gallein, or a PLCß2 inhibitor U73122 all abolished the effects of quinine on NLRP3 inflammasome and p-NF-κB p65 as well as the functional podocyte proteins in MPC cells in a high glucose condition. Furthermore, knockdown of mTAS2R4 with lentivirus-carrying Tas2r108 shRNA also ablated the effect of quinine on the key molecules of the above inflammatory signalings and podocyte functions in high glucose-cultured MPC cells. In summary, we demonstrated that activation of TAS2R4 signaling alleviated the podocyte injury caused by chronic high glucose, and inhibition of NF-κB p65 and NLRP3 inflammasome mediated the protective effects of TAS2R4 activation on podocytes. Moreover, activation of TAS2R4 signaling could be an important strategy for prevention and treatment of diabetic kidney disease.


Assuntos
Glucose , Podócitos , Receptores Acoplados a Proteínas G , Transdução de Sinais , Podócitos/metabolismo , Podócitos/efeitos dos fármacos , Podócitos/patologia , Animais , Camundongos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Glucose/toxicidade , Glucose/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Linhagem Celular
8.
Phytomedicine ; 128: 155521, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38489891

RESUMO

BACKGROUND: The ancient Chinese herb Salvia miltiorrhiza Bunge (Danshen), plays the important role in cardiovascular and cerebrovascular disease. Furthermore, Danshen could also be used for curing carcinogenesis. Up to now, the anti-tumor effects of the main active constituents of Danshen have made great progress. However, the bioavailability of the active constituents of Danshen were restricted by their unique physical characteristics, like low oral bioavailability, rapid degradation in vivo and so on. PURPOSE: With the leap development of nano-delivery systems, the shortcomings of the active constituents of Danshen have been greatly ameliorated. This review tried to summarize the recent progress of the active constituents of Danshen based delivery systems used for anti-tumor therapeutics. METHODS: A systematic literature search was conducted using 5 databases (Embase, Google scholar, PubMed, Scopus and Web of Science databases) for the identification of relevant data published before September 2023. The words "Danshen", "Salvia miltiorrhiza", "Tanshinone", "Salvianolic acid", "Rosmarinic acid", "tumor", "delivery", "nanomedicine" and other active ingredients contained in Danshen were searched in the above databases to gather information about pharmaceutical decoration for the active constituents of Danshen used for anti-tumor therapeutics. RESULTS: The main extracts of Danshen could inhibit the proliferation of tumor cells effectively and a great deal of studies were conducted to design drug delivery systems to ameliorate the anti-tumor effect of the active contents of Danshen through different ways, like improving bioavailability, increasing tumor targeting ability, enhancing biological barrier permeability and co-delivering with other active agents. CONCLUSION: This review systematically represented recent progress of pharmaceutical decorations for the active constituents of Danshen used for anti-tumor therapeutics, revealing the diversity of nano-decoration skills and trying to inspire more designs of Danshen based nanodelivery systems, with the hope that bringing the nanomedicine of the active constituents of Danshen for anti-tumor therapeutics from bench to bedside in the near future.


Assuntos
Antineoplásicos Fitogênicos , Medicamentos de Ervas Chinesas , Salvia miltiorrhiza , Salvia miltiorrhiza/química , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Humanos , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Sistemas de Liberação de Medicamentos , Animais , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Fármacos por Nanopartículas/química , Nanopartículas/química
9.
J Pharmacol Sci ; 154(4): 236-245, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38485341

RESUMO

Postpartum depression (PPD) is a significant contributor to maternal morbidity and mortality. The Sigma-1 (σ-1) receptor has received increasing attention in recent years because of its ability to link different signaling systems and exert its function in the brain through chaperone actions, especially in neuropsychiatric disorders. YL-0919, a novel σ-1 receptor agonist developed by our institute, has shown antidepressive and anxiolytic effects in a variety of animal models, but effects on PPD have not been revealed. In the present study, excitatory/inhibitory signaling in the hippocampus was reflected by GABA and glutamate and their associated excitatory-inhibitory receptor proteins, the HPA axis hormones in the hippocampus were assessed by ELISA. Finally, immunofluorescence for markers of newborn neuron were undertaken in the dentate gyri, along with dendritic spine staining and dendritic arborization tracing. YL-0919 rapidly improves anxiety and depressive-like behavior in PPD-like mice within one week, along with normalizing the excitation/inhibition signaling as well as the HPA axis activity. YL-0919 rescued the decrease in hippocampal dendritic complexity and spine density induced by estrogen withdrawal. The study results suggest that YL-0919 elicits a therapeutic effect on PPD-like mice; therefore, the σ-1 receptor may be a novel promising target for PPD treatment in the future.


Assuntos
Ácido Glutâmico , Receptor Sigma-1 , Feminino , Camundongos , Animais , Ácido Glutâmico/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Hipocampo/metabolismo , Ansiedade/tratamento farmacológico , Ansiedade/metabolismo , Estrogênios , Plasticidade Neuronal , Ácido gama-Aminobutírico/metabolismo
10.
Heliyon ; 10(5): e27115, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38444513

RESUMO

In recent years, extensive research has been conducted on bismuth tungstate (Bi2WO6) in the field of photocatalysis owing to its unique crystal structure and favorable bandgap. This study offers a comprehensive review of the research on Bi2WO6-based photocatalysts from 2007 to 2022 using bibliometric analysis. The analysis utilized the Web of Science Core Collection Database and encompassed a dataset of 2064 publications. The bibliometric analysis and science mapping were carried out using the bibliometix R-package and CiteSpace software. This analysis examined and discussed the network of relationships among countries, journals, organizations, authors, and keywords pertaining to the topic and subtopics under investigation. The findings demonstrate that China has played a significant role in this research area and has formed close collaborations with other countries. The identification of highly-cited emerging terms suggests that enhancing the photocatalytic performance of Bi2WO6-based nanomaterials is a primary research focus. Moreover, there has been increasing interest in exploring the synergistic effects of photocatalysis and adsorption as a means to improve catalytic efficiency. This study provides valuable insights for researchers seeking a deeper understanding of Bi2WO6-based photocatalysts.

11.
Front Endocrinol (Lausanne) ; 15: 1346605, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38419955

RESUMO

Background: Evidence of vitamin D status and cardiometabolic health in adults with type 2 diabetes mellitus (T2DM) is still limited. This study aimed to investigate the association between vitamin D status and cardiometabolic risk factors among adults with T2DM in Shenzhen, China. Methods: This cross-sectional study included 164 adults (aged ≥18 years) with T2DM who were hospitalized at Peking University Shenzhen Hospital from March 1, 2023, to May 31, 2023. Serum 25-hydroxyvitamin D [25(OH)D] concentration, the active marker of vitamin D, and three major cardiometabolic risk factors including blood pressure (BP), glucose metabolism-related indicators, and blood lipid profiles were collected. Vitamin D deficiency (VDD) was defined as 25(OH)D < 20 ng/mL. Correlation, Regression, and Logistic analysis were applied to verify the association among serum 25(OH)D concentration, VDD, and 11 cardiometabolic risk factors. Results: Median 25(OH)D concentration was 21.78 [interquartile range (IQR)=17.51-28.05] ng/mL. The prevalence of VDD was 40.24%. Serum 25(OH)D concentration was significantly negatively correlated with diastolic BP (DBP) and glycated hemoglobin A1c (HbA1c) rather than systolic BP, plasma glucose, plasma C-peptide, and blood lipid profiles among adults with T2DM in both correlation and linear regression analysis. Furthermore, the adjusted odd ratio for poor DBP control (≥90 mmHg) of T2DM patients with VDD was 3.164 (95% confidence interval=1.303, 7.683; P=0.011) compared to those without VDD. Conclusion: In China, VDD was highly prevalent among adults with T2DM and associated with greater cardiovascular risk factors, especially with increased chances of uncontrolled DBP. These findings suggest that vitamin D levels should be monitored in T2DM patients, especially those with high DBP.


Assuntos
Diabetes Mellitus Tipo 2 , Deficiência de Vitamina D , Adulto , Humanos , Adolescente , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Fatores de Risco Cardiometabólico , Estudos Transversais , Vitamina D , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Vitaminas , China/epidemiologia , Lipídeos
13.
World J Clin Cases ; 11(31): 7656-7662, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-38078131

RESUMO

BACKGROUND: This report delves into the diagnostic and therapeutic journey undertaken by a patient with Sneddon's syndrome (SS) and cerebral venous sinus thrombosis (CVST). Particular emphasis is placed on the comprehensive elucidation of SS's clinical manifestations, the intricate path to diagnosis, and the exploration of potential underlying mechanisms. CASE SUMMARY: A 26-year-old woman presented with recurrent episodes of paroxysmal unilateral limb weakness accompanied by skin mottling, seizures, and cognitive impairment. Digital subtraction angiography revealed CVST. Despite negative antiphospholipid antibody results, skin biopsy indicated chronic inflammatory cell infiltration. The patient was treated using anticoagulation, antiepileptic therapy, and supportive care, which resulted in symptom improvement. The coexistence of SS and CVST is rare and the underlying pathophysiology remains uncertain. This case underscores the challenge in diagnosis and highlights the need for early clinical differentiation to facilitate accurate assessment and prompt intervention. CONCLUSION: This article has reported and analyzed the clinical data, diagnosis, treatment, and prognosis of a case of SS with CVST and reviewed the relevant literature to improve the clinical understanding of this rare condition.

14.
Molecules ; 28(15)2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37570813

RESUMO

In recent years, the use of magnetic biochar in wastewater treatment has shown significant effects and attracted scholars' attention. However, due to the relatively short research time and the lack of systematic summaries, it is difficult to provide a more in-depth analysis. This study utilizes RStudio and CiteSpace software to comprehensively analyze the research trends and progress of magnetic biochar in wastewater treatment. The analysis of bibliometrics is performed on 551 relevant papers retrieved from the Web of Science, spanning the period between 2011 and 2022. The most influential countries, institutions, journals, disciplinary distribution, and top 10 authors and papers in this field have been identified. The latest dataset has been used for keyword clustering and burst analysis. The results indicated that: (1) Bin Gao is the most influential author in this field, and high-level journals such as Bioresource Technology are more inclined to publish articles in the field of magnetic biochar. (2) Research in this field has predominantly focused on the removal of heavy metals and organic compounds. Keyword burst analysis shows a shift in research direction towards the removal of complex organic pollutants recently. (3) For the future development of magnetic biochar, an environment-friendly approach, economic viability, and joint technology are the directions that need more exploration. Finally, this paper provides a summary of the various adsorption mechanisms of magnetic biochar and several common modification methods, aiming to assist scholars in their research endeavors.


Assuntos
Poluentes Ambientais , Águas Residuárias , Fenômenos Físicos , Fenômenos Magnéticos
15.
Respir Res ; 24(1): 204, 2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-37598171

RESUMO

BACKGROUND: Pulmonary hypertension (PH) is a lethal vascular disease with limited therapeutic options. The mechanistic connections between alveolar hypoxia and PH are not well understood. The aim of this study was to investigate the role of mitotic regulator Polo-like kinase 1 (PLK1) in PH development. METHODS: Mouse lungs along with human pulmonary arterial smooth muscle cells and endothelial cells were used to investigate the effects of hypoxia on PLK1. Hypoxia- or Sugen5416/hypoxia was applied to induce PH in mice. Plk1 heterozygous knockout mice and PLK1 inhibitors (BI 2536 and BI 6727)-treated mice were checked for the significance of PLK1 in the development of PH. RESULTS: Hypoxia stimulated PLK1 expression through induction of HIF1α and RELA. Mice with heterozygous deletion of Plk1 were partially resistant to hypoxia-induced PH. PLK1 inhibitors ameliorated PH in mice. CONCLUSIONS: Augmented PLK1 is essential for the development of PH and is a druggable target for PH.


Assuntos
Hipertensão Pulmonar , Humanos , Animais , Camundongos , Hipertensão Pulmonar/genética , Células Endoteliais , Proteínas de Ciclo Celular/genética , Hipóxia , Camundongos Knockout , Quinase 1 Polo-Like
16.
Heliyon ; 9(7): e17340, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37501950

RESUMO

The number of centenarians with cancer is increasing as the global population ages. The diagnosis and treatment for centenarians with tumor sometimes are specific, and there are currently less appropriate guidelines as references. We report a 104-year-old man with asymptomatic primary liver cancer (PLC) whose family decided to receive conservative and palliative care. The patient has been followed up for 27 months. He has been mainly received Chinese herbal medicine (CHM), nutritional support and thymalfasin injection intermittently, etc. During the 27-month follow-up, the patient has showed good compliance and tolerance without any complications of the tumor. Conclusion: Individualized palliative care and complementary medicine, based on multidisciplinary evaluation, traditional Chinese medicine, consultation with patients and their families about treatment options, etc., may help improve the life quality of centenarians with end-stage tumors.

17.
BMC Public Health ; 23(1): 1293, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37407916

RESUMO

BACKGROUND: Adverse childhood experiences are critical factors in depression and cognitive decrease, but the effect of adverse childhood health experiences (ACHEs) on cognitive function and the role of depression have not been fully studied. METHODS: Data were taken from the China Health and Retirement Longitudinal Study (CHARLS) of 2014 and 2018. This study used indicators of situational memory ability and mental status to measure cognitive capacity. Besides analyzing the different types of ACHEs, scores for ACHEs were calculated to represent the severity of ACHEs. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess depression. The analysis of this study employed two different analytical strategies in order to examine the mediated effects of depression. We used Sobel's test and Baron and Kenny's causal step approach, which utilized a generalized least squares regression model. Furthermore, a logistic regression model was used to evaluate the robustness of the Karlson-Holm-Breen (KHB) approach. RESULTS: In this study, 6301 individuals who met the requirements of the study were included. We found that being confined to bed (ACHE3) (ß=-0.3846, p = 0.022) in childhood had a negative impact on cognitive function. Similarly, ACHEs had a negative effect on cognitive function (ß=-0.0819, p = 0.090). And after the depression had been introduced into the model, the regression coefficient of ACHEs on cognitive function was no longer significant (ß=-0.0170, p = 0.727). The Sobel test showed that for ACHE3, the mediated proportion of the total effect of depression was 36.92%. While for ACHEs, the proportion of the mediated effect of depression was 70.11%. Finally, a robustness test of the mediating effect using the KHB method revealed that the mediating effect still existed. Further, based on different gender, age, and educational levels, the heterogeneity test indicated that the relationship between ACHEs and cognitive function and mediating effects of the depression were different as well as passing the robustness test of the interaction. CONCLUSION: The decline in cognition had been shown to be correlated with ACHEs and depression mediated this relationship. Positive interventions might help to improve cognitive performance in individuals suffering from ACHEs and depression.


Assuntos
Experiências Adversas da Infância , Pessoa de Meia-Idade , Humanos , Idoso , Estudos Longitudinais , Depressão/epidemiologia , Depressão/psicologia , População do Leste Asiático , Cognição , China/epidemiologia , Dor
18.
Huan Jing Ke Xue ; 44(7): 3902-3912, 2023 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-37438289

RESUMO

The intensity of crop farming fertilizer input is generally high in the Taihu Lake Region, with chemical fertilizer as the main form. Due to inappropriate fertilizer application, nitrogen and phosphorus loss have occurred, causing serious agricultural non-point source pollution. The Ministry of Agriculture and Rural Affairs of China has launched the "zero-growth action for chemical fertilizer use" and "replacement action with organic fertilizer" ("two actions" for short) campaigns since 2015. Local agricultural sectors adjusted fertilizer application strategies of crop farming to respond to the call of two actions. However, the current research is still focusing on reducing the total amount of fertilizer application and increasing the area of organic fertilizer application, which is mainly based on grain crops. The study of agricultural environment problems is still lacking, especially in vegetable, orchard, and tea systems. Therefore, a study was carried out in the typical agricultural area of Suzhou City Wuzhong District from 2019 to 2021. Based on the data of the amount of nitrogen and phosphorus removal by harvest crops and soil nitrogen and phosphorus residual in paddy, vegetable, orchard, and tea systems, the loss was estimated. The responses of nitrogen and phosphorus loss from typical crop systems to fertilizer application strategy adjustments were studied through analysis of different factors. The results showed that fertilizer application rate was the key to control nitrogen and phosphorus loss. Additionally, the suitable replacement ratio of organic fertilizer could further reduce the loss risk. It should be noted that the urgent demand for nutrients in crop growth should be considered to determine the timing of organic fertilizer application, and agricultural machinery should be used to assist organic fertilizer application to reduce labor output if possible. Fertilizer efficiency was the core of environmental friendliness and economic benefits of crop farming. Hence, improving fertilizer efficiency should be the guidance of fertilizer application strategy adjustment. Our suggestions on the adjustment of fertilizer application strategy in different crop systems in the study area are as follows:attention should be paid to the nitrogen, phosphorus, and potassium input ratio in paddy systems to further reduce nitrogen and phosphorus loss. Planting structure adjustment should be emphasized in vegetable systems to promote fertilizer efficiency. The strategy to satisfy both tea and orchard growth from a composite system perspective would help to build crop systems that meet the needs of green agricultural development.


Assuntos
Fertilizantes , Lagos , Produtos Agrícolas , Nitrogênio , Fósforo , Chá
19.
Huan Jing Ke Xue ; 44(6): 3063-3070, 2023 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-37309925

RESUMO

In order to study the effects of clean heating measures on the concentration and source of carbonaceous aerosols in PM2.5 in Baoding, we collected PM2.5 samples in Baoding during the winter heating periods of 2014 and 2019. The concentrations of OC and EC in the samples were determined by using a DRI Model 2001A thermo-optical carbon analyzer.The results showed that the average values of ρ(OC) and ρ(EC) in the heating period in 2014 were 60.92 µg·m-3 and 18.15 µg·m-3, and the average values of ρ(OC) and ρ(EC) in the heating period in 2019 were 36.63 µg·m-3 and 6.07 µg·m-3. Compared with those in 2014, the concentrations of OC and EC decreased by 39.87% and 66.56%, respectively, in 2019; the decrease in EC was larger than that in OC, and the meteorological conditions in 2019 were more severe than those in 2014, which was not conducive to the spread of pollutants.The correlation analysis and SOC estimation of OC and EC indicated that the correlation R2 of OC and EC in Baoding in 2014 and 2019 were 0.874 and 0.811, respectively, indicating that OC and EC in Baoding had relatively consistent sources. The average values of ρ(SOC) in 2014 and 2019 were 16.59 µg·m-3 and 11.31 µg·m-3, respectively, and the contribution rates to OC were 27.23% and 30.87%, respectively. This showed that in 2019, compared with that in 2014, the primary pollution decreased, but the secondary pollution increased, and the atmospheric oxidation increased.The analysis of the pollution sources of carbonaceous aerosols revealed that in 2014 and 2019 before and after the implementation of clean heating, the carbonaceous aerosols in the atmosphere were mainly from biomass combustion, coal combustion, and vehicle exhaust emissions. However, the contribution from biomass burning and coal burning decreased in 2019 compared to that in 2014. The decrease in OC and EC concentrations was attributed to the control of coal-fired and biomass-fired sources by clean heating. At the same time, the implementation of clean heating measures reduced the contribution of primary emissions to carbonaceous aerosols in PM2.5 in Baoding City.

20.
ESC Heart Fail ; 10(4): 2510-2523, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37290760

RESUMO

AIMS: Diabetic cardiomyopathy (DC) is one of serious complications of diabetic patients. This study investigated the biological function of activating transcription factor 4 (ATF4) in DC. METHODS AND RESULTS: Streptozotocin-treated mice and high glucose (HG)-exposed HL-1 cells were used as the in vivo and in vitro models of DC. Myocardial infarction (MI) was induced by left coronary artery ligation in mice. Cardiac functional parameters were detected by echocardiography. Target molecule expression was determined by real time quantitative PCR and western blotting. Cardiac fibrosis was observed by haematoxylin and eosin and Masson's staining. Cardiac apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labelling. Activities of superoxide dismutase, glutathione peroxidase, and levels of malonic dialdehyde and reactive oxygen species were used to assess oxidative stress damage. Molecular mechanisms were evaluated by chromatin immunoprecipitation, dual luciferase assay, and co-immunoprecipitation. ATF4 was up-regulated in the DC and MI mice (P < 0.01). Down-regulation of ATF4 improved cardiac function as evidenced by changes in cardiac functional parameters (P < 0.01), inhibited myocardial collagen I (P < 0.001) and collagen III (P < 0.001) expression, apoptosis (P < 0.001), and oxidative stress (P < 0.001) in diabetic mice. Collagen I (P < 0.01) and collagen III (P < 0.01) expression was increased in MI mice, which was reversed by ATF4 silencing (P < 0.05). ATF4 depletion enhanced viability (P < 0.01), repressed apoptosis (P < 0.001), oxidative damage (P < 0.001), and collagen I (P < 0.001), and collagen III (P < 0.001) expression of HG-stimulated HL-1 cells. ATF4 transcriptionally activated Smad ubiquitin regulatory factor 2 (Smurf2, P < 0.001) to promote ubiquitination and degradation of homeodomain interacting protein kinase-2 (P < 0.001) and subsequently caused inactivation of nuclear factor erythroid 2-related factor 2/heme oxygenase 1 pathway (P < 0.001). The inhibitory effects of ATF4 silencing on HG-induced apoptosis (P < 0.01), oxidative injury (P < 0.01), collagen I (P < 0.001), and collagen III (P < 0.001) expression were reversed by Smurf2 overexpression. CONCLUSIONS: ATF4 facilitates diabetic cardiac fibrosis and oxidative stress by promoting Smurf2-mediated ubiquitination and degradation of homeodomain interacting protein kinase-2 and then inactivation of nuclear factor erythroid 2-related factor 2/heme oxygenase 1 pathway, suggesting ATF4 as a treatment target for DC.


Assuntos
Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Infarto do Miocárdio , Animais , Camundongos , Fator 4 Ativador da Transcrição/genética , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/metabolismo , Fibrose , Heme Oxigenase-1 , Proteínas Quinases
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