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1.
Invest New Drugs ; 2024 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-39432145

RESUMEN

The ongoing research on the role of immunotherapy in advanced ovarian cancer (OC) and current clinical trials indicate that patients shown limited response to immune checkpoint inhibitor (ICI) monotherapy. When combined with other treatments or drugs, the efficacy of immunotherapy will be significantly improved. Biomarkers can be used to identify patients with better responses, thereby improving the precision and efficacy of immunotherapy. Key biomarkers for advanced OC include homologous repair deficiency, programmed death-ligand (PD-L) 1 expression, chemokines, and tumor infiltrating lymphocytes. These biomarkers could be applied in the future to select the most suitable patient populations. This review comprehensively examines the research and development of biomarkers in OC immunotherapy from three omics perspectives: genomics, transcriptomics, and proteomics, which may provide guidance for the effectiveness of OC immunotherapy strategies.

2.
Chin J Nat Med ; 22(9): 822-830, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39326976

RESUMEN

Chemical investigations of the termite-associated Streptomyces tanashiensis BYF-112 resulted in the discovery of four novel alkaloid derivatives: vegfrecines A and B (1 and 2), exfoliazone A (3), and venezueline H (7), in addition to nine known metabolites (4-6, 8-13). The structures of these compounds were elucidated through comprehensive spectroscopic analysis and comparison with existing literature data. Antibacterial assays revealed that viridomycin A (11) exhibited potent antibacterial activity against Staphylococcus aureus, with a zone of inhibition (ZOI) of 12.67 mm, in comparison to a ZOI of 17.67 mm for the positive control gentamicin sulfate. Viridomycin A (11) showed moderate activity against Micrococcus tetragenus and Pseudomonas syringae pv. actinidae, with ZOI values of 15.50 and 14.33 mm, respectively, which were inferior to those of gentamicin sulfate (34.67 and 24.00 mm). Viridomycin F (12) also exhibited moderate antibacterial effects against S. aureus, M. tetragenus, and P. syringae pv. actinidae, with ZOI values of 8.33, 16.50, and 10.83 mm, respectively. Cytotoxicity assays demonstrated that viridobruunine A (5), exfoliazone (6), viridomycin A (11), and X-14881E (13) exhibited significant cytotoxicity against human malignant melanoma (A375), ovarian cancer (SKOV-3), and gastric cancer (MGC-803) cell lines, with IC50 values ranging from 4.61 to 19.28 µmol·L-1. Furthermore, bioinformatic analysis of the complete genome of S. tanashiensis suggested a putative biosynthetic gene cluster (BGC) responsible for the production of compounds 1-12. These findings indicate that the secondary metabolites of insect-associated S. tanashiensis BYF-112 hold promise as potential sources of novel antibacterial and anticancer agents.


Asunto(s)
Antibacterianos , Antineoplásicos , Isópteros , Streptomyces , Streptomyces/química , Streptomyces/metabolismo , Streptomyces/genética , Animales , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Isópteros/microbiología , Antineoplásicos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Estructura Molecular , Alcaloides/farmacología , Alcaloides/química , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos
4.
Medicine (Baltimore) ; 103(26): e38618, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38941435

RESUMEN

RATIONALE: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but serious complication in patients with malignancy; its main manifestation includes acute pulmonary hypertension with severe respiratory distress. More than 200 cases have been reported since it was first identified in 1990. PTTM accounts for approximately 0.9% to 3.3% of deaths due to malignancy, but only a minority of patients are diagnosed ante-mortem, with most patients having a definitive diagnosis after autopsy. PATIENT CONCERNS: Two middle-aged women both died within a short period of time due to progressive dyspnea and severe pulmonary hypertension. DIAGNOSES: One patient was definitively confirmed as a gastrointestinal malignant tumor by liver puncture biopsy pathology. Ultimately, the clinical diagnosis was pulmonary tumor thrombotic microangiopathy. INTERVENTIONS: The patient was treated symptomatically with oxygen, diuresis, and anticoagulation, while a liver puncture was perfected to clarify the cause. OUTCOMES: Two cases of middle-aged female patients with rapidly progressive pulmonary hypertension and respiratory failure resulted in death with malignant neoplasm. LESSONS: PTTM has a rapid onset and a high morbidity and mortality rate. Our clinicians need to be more aware of the need for timely diagnosis through a targeted clinical approach, leading to more targeted treatment and a better prognosis.


Asunto(s)
Microangiopatías Trombóticas , Humanos , Femenino , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/diagnóstico , Persona de Mediana Edad , Resultado Fatal , Hipertensión Pulmonar/etiología , Neoplasias Gastrointestinales/complicaciones , Neoplasias Gastrointestinales/patología , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico
5.
Int J Med Sci ; 21(6): 983-993, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38774750

RESUMEN

Previous studies have highlighted the protective effects of pyruvate kinase M2 (PKM2) overexpression in septic cardiomyopathy. In our study, we utilized cardiomyocyte-specific PKM2 knockout mice to further investigate the role of PKM2 in attenuating LPS-induced myocardial dysfunction, focusing on mitochondrial biogenesis and prohibitin 2 (PHB2). Our findings confirmed that the deletion of PKM2 in cardiomyocytes significantly exacerbated LPS-induced myocardial dysfunction, as evidenced by impaired contractile function and relaxation. Additionally, the deletion of PKM2 intensified LPS-induced myocardial inflammation. At the molecular level, LPS triggered mitochondrial dysfunction, characterized by reduced ATP production, compromised mitochondrial respiratory complex I/III activities, and increased ROS production. Intriguingly, the absence of PKM2 further worsened LPS-induced mitochondrial damage. Our molecular investigations revealed that LPS disrupted mitochondrial biogenesis in cardiomyocytes, a disruption that was exacerbated by the absence of PKM2. Given that PHB2 is known as a downstream effector of PKM2, we employed PHB2 adenovirus to restore PHB2 levels. The overexpression of PHB2 normalized mitochondrial biogenesis, restored mitochondrial integrity, and promoted mitochondrial function. Overall, our results underscore the critical role of PKM2 in regulating the progression of septic cardiomyopathy. PKM2 deficiency impeded mitochondrial biogenesis, leading to compromised mitochondrial integrity, increased myocardial inflammation, and impaired cardiac function. The overexpression of PHB2 mitigated the deleterious effects of PKM2 deletion. This discovery offers a novel insight into the molecular mechanisms underlying septic cardiomyopathy and suggests potential therapeutic targets for intervention.


Asunto(s)
Cardiomiopatías , Mitocondrias Cardíacas , Biogénesis de Organelos , Prohibitinas , Piruvato Quinasa , Sepsis , Animales , Humanos , Masculino , Ratones , Cardiomiopatías/inducido químicamente , Cardiomiopatías/genética , Cardiomiopatías/patología , Modelos Animales de Enfermedad , Lipopolisacáridos , Ratones Noqueados , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/patología , Miocitos Cardíacos/patología , Miocitos Cardíacos/metabolismo , Piruvato Quinasa/metabolismo , Piruvato Quinasa/genética , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Sepsis/metabolismo , Sepsis/patología , Sepsis/genética
6.
Int J Med Sci ; 21(5): 809-816, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38617011

RESUMEN

This comprehensive review delves into the pivotal role of mitochondria in doxorubicin-induced cardiotoxicity, a significant complication limiting the clinical use of this potent anthracycline chemotherapeutic agent. Doxorubicin, while effective against various malignancies, is associated with dose-dependent cardiotoxicity, potentially leading to irreversible cardiac damage. The review meticulously dissects the molecular mechanisms underpinning this cardiotoxicity, particularly focusing on mitochondrial dysfunction, a central player in this adverse effect. Central to the discussion is the concept of mitochondrial quality control (MQC), including mitochondrial dynamics (fusion/fission balance) and mitophagy. The review presents evidence linking aberrations in these processes to cardiotoxicity in doxorubicin-treated patients. It elucidates how doxorubicin disrupts mitochondrial dynamics, leading to an imbalance between mitochondrial fission and fusion, and impairs mitophagy, culminating in the accumulation of dysfunctional mitochondria and subsequent cardiac cell damage. Furthermore, the review explores emerging therapeutic strategies targeting mitochondrial dysfunction. It highlights the potential of modulating mitochondrial dynamics and enhancing mitophagy to mitigate doxorubicin-induced cardiac damage. These strategies include pharmacological interventions with mitochondrial fission inhibitors, fusion promoters, and agents that modulate mitophagy. The review underscores the promising results from preclinical studies while advocating for more extensive clinical trials to validate these approaches in human patients. In conclusion, this review offers valuable insights into the intricate relationship between mitochondrial dysfunction and doxorubicin-mediated cardiotoxicity. It underscores the need for continued research into targeted mitochondrial therapies as a means to improve the cardiac safety profile of doxorubicin, thereby enhancing the overall treatment outcomes for cancer patients.


Asunto(s)
Cardiotoxicidad , Enfermedades Mitocondriales , Humanos , Cardiotoxicidad/etiología , Doxorrubicina/efectos adversos , Mitocondrias , Antraciclinas
7.
Cell Stress Chaperones ; 29(2): 349-357, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38485043

RESUMEN

This comprehensive review delves into the pivotal role of mitochondria in doxorubicin-induced cardiotoxicity, a significant complication limiting the clinical use of this potent anthracycline chemotherapeutic agent. Doxorubicin, while effective against various malignancies, is associated with dose-dependent cardiotoxicity, potentially leading to irreversible cardiac damage. The review meticulously dissects the molecular mechanisms underpinning this cardiotoxicity, particularly focusing on mitochondrial dysfunction, a central player in this adverse effect. Central to the discussion is the concept of mitochondrial quality control, including mitochondrial dynamics (fusion/fission balance) and mitophagy. The review presents evidence linking aberrations in these processes to cardiotoxicity in doxorubicin-treated patients. It elucidates how doxorubicin disrupts mitochondrial dynamics, leading to an imbalance between mitochondrial fission and fusion, and impairs mitophagy, culminating in the accumulation of dysfunctional mitochondria and subsequent cardiac cell damage. Furthermore, the review explores emerging therapeutic strategies targeting mitochondrial dysfunction. It highlights the potential of modulating mitochondrial dynamics and enhancing mitophagy to mitigate doxorubicin-induced cardiac damage. These strategies include pharmacological interventions with mitochondrial fission inhibitors, fusion promoters, and agents that modulate mitophagy. The review underscores the promising results from preclinical studies while advocating for more extensive clinical trials to validate these approaches in human patients. In conclusion, this review offers valuable insights into the intricate relationship between mitochondrial dysfunction and doxorubicin-mediated cardiotoxicity. It underscores the need for continued research into targeted mitochondrial therapies as a means to improve the cardiac safety profile of doxorubicin, thereby enhancing the overall treatment outcomes for cancer patients.


Asunto(s)
Cardiotoxicidad , Enfermedades Mitocondriales , Humanos , Cardiotoxicidad/etiología , Cardiotoxicidad/metabolismo , Cardiotoxicidad/patología , Doxorrubicina/efectos adversos , Mitocondrias , Antibióticos Antineoplásicos/efectos adversos , Enfermedades Mitocondriales/complicaciones , Enfermedades Mitocondriales/metabolismo , Enfermedades Mitocondriales/patología , Miocitos Cardíacos
8.
Carbohydr Polym ; 327: 121673, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38171686

RESUMEN

Uncontrolled hemorrhage arising from surgery or trauma may cause morbidity and even mortality. Therefore, facilitating control of severe bleeding is imperative for health care worldwide. Among diverse hemostatic materials, chitosan (CS) is becoming the most promising material owing to its non-toxic feature, as well as inherently hemostatic performance. However, further enhancing hemostatic property of CS-based materials without compromising more beneficial functions remains a challenge. In this review, representative hemostatic mechanisms of CS-based materials are firstly discussed in detail, mostly including red blood cells (RBCs) aggregation, platelet adherence and aggregation, as well as interaction with plasma proteins. Also, various forms (involving powder/particle, sponge, hydrogel, nanofiber, and other forms) of CS-based hemostatic materials are systematically summarized, mainly focusing on their design and preparation, characteristics, and comparative analysis of various forms. In addition, varied hemostatic applications are described in detail, such as skin wound hemostasis, liver hemostasis, artery hemostasis, and heart hemostasis. Finally, current challenges and future directions of functional design of CS-based hemostatic materials in diverse hemostatic applications are proposed to inspire more intensive researches.


Asunto(s)
Quitosano , Hemostáticos , Humanos , Hemostáticos/farmacología , Hemostáticos/uso terapéutico , Quitosano/farmacología , Coagulación Sanguínea , Hemostasis , Hemorragia/tratamiento farmacológico
9.
Sci Adv ; 10(4): eadi5300, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38266085

RESUMEN

The constant interplay and information exchange between cells and the microenvironment are essential to their survival and ability to execute biological functions. To date, a few leading technologies such as traction force microscopy, optical/magnetic tweezers, and molecular tension-based fluorescence microscopy are broadly used in measuring cellular forces. However, the considerable limitations, regarding the sensitivity and ambiguities in data interpretation, are hindering our thorough understanding of mechanobiology. Here, we propose an innovative approach, namely, quantum-enhanced diamond molecular tension microscopy (QDMTM), to precisely quantify the integrin-based cell adhesive forces. Specifically, we construct a force-sensing platform by conjugating the magnetic nanotags labeled, force-responsive polymer to the surface of a diamond membrane containing nitrogen-vacancy centers. Notably, the cellular forces will be converted into detectable magnetic variations in QDMTM. After careful validation, we achieved the quantitative cellular force mapping by correlating measurement with the established theoretical model. We anticipate our method can be routinely used in studies like cell-cell or cell-material interactions and mechanotransduction.


Asunto(s)
Comunicación Celular , Mecanotransducción Celular , Microscopía de Fuerza Atómica , Microscopía Fluorescente , Diamante
10.
Pest Manag Sci ; 80(4): 2011-2020, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38105413

RESUMEN

BACKGROUND: Wheat powdery mildew, caused by the biotrophic pathogen Blumeria graminis f. sp. tritici (Bgt) is a serious fungal disease. Natural metabolites produced by microorganisms are beneficial biological control agents to inhibit Bgt. In the present study, we investigated the effects of Aspergillus chevalieri BYST01 on wheat powdery mildew. RESULTS: A strain isolated from the termite was identified as A. chevalieri BYST01 by morphological characteristics and phylogenetic analysis. The fermentation broth of BYST01 showed good biocontrol effect on the Bgt in vivo with the control efficiencies of 81.59% and 71.34% under the protective and therapeutic tests, respectively. Four known metabolites, including the main compound physcion (30 mg/L), were isolated from the fermentation broth of BYST01 extracted with ethyl acetate. Importantly, under a concentration of 0.1 mM, physcion repressed conidial germination of Bgt with an inhibition rate of 77.04% in vitro and showed important control efficiencies of 80.36% and 74.64% in vivo under the protective and therapeutic tests, respectively. Hence, the BYST01 showed important potential as a microbial cell factory for the high yield of the green natural fungicide physcion. Finally, the biosynthetic gene clusters responsible for physicon production in BYST01 was predicted by analyzing a chromosome-scale genome obtained using a combination of Illumina, PacBio, and Hi-C sequencing technologies. CONCLUSION: Aspergillus chevalieri BYST01 and its main metabolite physcion had a significant control effect on wheat powdery mildew. The biosynthesis pathway of physcion in BYST01 was predicted. © 2023 Society of Chemical Industry.


Asunto(s)
Ascomicetos , Aspergillus , Emodina/análogos & derivados , Isópteros , Animales , Ascomicetos/fisiología , Triticum/genética , Filogenia , Enfermedades de las Plantas/prevención & control , Enfermedades de las Plantas/microbiología , Resistencia a la Enfermedad/genética
11.
Cell Stress Chaperones ; 28(6): 675-688, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37755621

RESUMEN

Myocardial microvessels are composed of a monolayer of endothelial cells, which play a crucial role in maintaining vascular barrier function, luminal latency, vascular tone, and myocardial perfusion. Endothelial dysfunction is a key factor in the development of cardiac microvascular injury and diabetic cardiomyopathy. In addition to their role in glucose oxidation and energy metabolism, mitochondria also participate in non-metabolic processes such as apoptosis, intracellular ion handling, and redox balancing. Mitochondrial dynamics and mitophagy are responsible for regulating the quality and quantity of mitochondria in response to hyperglycemia. However, these endogenous homeostatic mechanisms can both preserve and/or disrupt non-metabolic mitochondrial functions during diabetic endothelial damage and cardiac microvascular injury. This review provides an overview of the molecular features and regulatory mechanisms of mitochondrial dynamics and mitophagy. Furthermore, we summarize findings from various investigations that suggest abnormal mitochondrial dynamics and defective mitophagy contribute to the development of diabetic endothelial dysfunction and myocardial microvascular injury. Finally, we discuss different therapeutic strategies aimed at improving endothelial homeostasis and cardiac microvascular function through the enhancement of mitochondrial dynamics and mitophagy.


Asunto(s)
Diabetes Mellitus , Mitofagia , Humanos , Mitofagia/fisiología , Células Endoteliales , Dinámicas Mitocondriales , Miocardio
12.
Medicine (Baltimore) ; 102(32): e34540, 2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37565908

RESUMEN

Hyperuricemia nephropathy, also known as gouty nephropathy, refers to renal damage induced by hyperuricemia caused by excessive production of serum uric acid or low excretion of uric acid. the persistence of symptoms will lead to changes in renal tubular phenotype and accelerate the progress of renal fibrosis. The existence and progressive aggravation of symptoms will bring a heavy burden to patients, their families and society, affect their quality of life and reduce their well-being. With the increase of reports on hyperuricemia nephropathy, the importance of related signal pathways in the pathogenesis of hyperuricemia nephropathy is becoming more and more obvious, but most studies are limited to the upper and lower mediating relationship between 1 or 2 signal pathways. The research on the comprehensiveness of signal pathways and the breadth of crosstalk between signal pathways is limited. By synthesizing the research results of signal pathways related to hyperuricemia nephropathy in recent years, this paper will explore the specific mechanism of hyperuricemia nephropathy, and provide new ideas and methods for the treatment of hyperuricemia nephropathy based on a variety of signal pathway crosstalk and personal prospects.


Asunto(s)
Hiperuricemia , Cálculos Renales , Humanos , Ácido Úrico , Hiperuricemia/complicaciones , Calidad de Vida , Transducción de Señal , Cálculos Renales/complicaciones
13.
J Nat Prod ; 86(8): 1891-1900, 2023 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-37506055

RESUMEN

Streptomyces spp. are well-known symbiotic microorganisms that produce antimicrobial metabolites against various pathogens. We isolated actinomycetes from the body surface of the termite Odontotermes formosanus and identified it as Streptomyces neopeptinius BYF101 based on 16S rRNA phylogenetic analysis. Chemical analysis of the cultures of termite-associated S. neopeptinius BYF101 via HR-MS2 and GNPS analyses enabled the isolation and identification of 20 metabolites, including the unreported obscurolide-type metabolites (1-3). The chemical structures of unreported compounds (1-3) were elucidated using HR-ESI-MS and 1D and 2D NMR analysis, and their absolute configurations were determined via chemical reactions followed by the application of competing enantioselective acylation (CEA) and computational methods for ECD and DP4+ probability calculation. The isolated compounds (1-20) were tested to determine their antifungal activity against two human fungal pathogens, Candida albicans and Cryptococcus neoformans. Among the compounds tested, indole-3-carboxylic acid (9) displayed antifungal activity against C. neoformans, with an MIC value of 12 µg/mL.


Asunto(s)
Cryptococcus neoformans , Isópteros , Streptomyces , Animales , Humanos , Antifúngicos/química , Isópteros/microbiología , ARN Ribosómico 16S/genética , Filogenia , Streptomyces/química , Pruebas de Sensibilidad Microbiana , Candida albicans
14.
Materials (Basel) ; 16(12)2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37374474

RESUMEN

Natural river sand resources are facing depletion, and large-scale mining pollutes the environment and harms humans. To utilize fly ash fully, this study used low-grade fly ash as a substitute for natural river sand in mortar. This has great potential to alleviate the shortage of natural river sand resources, reduce pollution, and improve the utilization of solid waste resources. Six types of green mortars were prepared by replacing different amounts of river sand (0, 20, 40, 60, 80, and 100%) with fly ash and other volumes. Their compressive strength, flexural strength, ultrasonic wave velocity, drying shrinkage, and high-temperature resistance were also investigated. Research has shown that fly ash can be used as a fine aggregate in the preparation of building mortar, thereby ensuring that green-building mortar has sufficient mechanical properties and better durability. The replacement rate for optimal strength and high-temperature performance was determined to be 80%.

15.
Pest Manag Sci ; 79(5): 1800-1808, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36640042

RESUMEN

BACKGROUND: Insect-associated Streptomyces is a valuable resource for development of compounds with antibacterial potential. However, relatively little is known of the secondary metabolites produced by termite-associated Streptomyces. RESULTS: Here, seven compounds including o-acetaminophenol (1), phenazine-1,6-dicarboxylic acid (2), phenylacetic acid (3), phenazinolin D (4), izumiphenazine A (5), izumiphenazine B (6) and phenazinolin E (7) were obtained from the fermentation broth of a termite-associated Streptomyces showdoensis BYF17, which was isolated from the body surfaces of Odontotermes formosanus. Two additional novel derivative compounds (6a and 6b) were synthesized via acetylation and methylation, respectively. The structures of these compounds were elucidated by spectroscopic analyses. The antibacterial bioassay showed that compound 6a displayed strong inhibitory effects against Pseudomonas syringae pv. actinidiae (Psa), with a zone of inhibition (ZOI) diameter of 20.6 mm, which was comparable to that of positive gentamicin sulfate with a ZOI value of 25.6 mm. Furthermore, the Day 5 curative activities of both compounds 6 and 6a against kiwifruit bacterial canker were 71.5%, which was higher than those of referred oxine-copper (55.0%) and ethylicin (46.8%) at a concentration of 200 µg mL-1 . In addition, the mechanism analysis based on scanning electron microscopic observation revealed that both compounds 6 and 6a destroyed the integrity of the Psa cell membrane. CONCLUSION: The results of biological tests showed that these bioactive compounds exhibit potent antimicrobial activities, which have the potential to be developed into new antibacterial agents. © 2023 Society of Chemical Industry.


Asunto(s)
Isópteros , Streptomyces , Animales , Antibacterianos/farmacología , Streptomyces/química , Pseudomonas syringae , Enfermedades de las Plantas/microbiología
16.
Molecules ; 28(2)2023 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-36677710

RESUMEN

Endometriosis is a common gynecological illness in women of reproductive age that significantly decreases life quality and fertility. Paeonol has been shown to play an important part in endometriosis treatments. Understanding the mechanism is critical for treating endometriosis. In this study, autologous transplantation combined with a 28 day ice water bath was used to create a rat model of endometriosis with cold clotting and blood stagnation. The levels of estradiol and progesterone in plasma were detected by ELISA, and the pathological changes of ectopic endometrial tissue were examined by H&E staining, which proved the efficacy of paeonol. For metabolomic analysis of plasma samples, UPLC-Q/TOF-MS was combined with multivariate statistical analysis to identify the influence of paeonol on small molecule metabolites relevant to endometriosis. Finally, the key targets were screened using a combination of network pharmacology and molecular docking approaches. The results showed that the pathological indexes of rats were improved and returned to normal levels after treatment with paeonol, which was the basis for confirming the efficacy of paeonol. Metabolomics results identified 13 potential biomarkers, and paeonol callbacks 7 of them, involving six metabolic pathways. Finally, four key genes were found for paeonol therapy of endometriosis, and the results of molecular docking revealed a significant interaction between paeonol and the four key genes. This study was successful in establishing a rat model of endometriosis with cold coagulation and blood stagnation. GCH1, RPL8, PKLR, and MAOA were the key targets of paeonol in the treatment of endometriosis. It is also demonstrated that metabolomic techniques give the potential and environment for comprehensively understanding drug onset processes.


Asunto(s)
Medicamentos Herbarios Chinos , Endometriosis , Humanos , Ratas , Femenino , Animales , Endometriosis/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Metabolómica/métodos , Acetofenonas/análisis , Medicamentos Herbarios Chinos/farmacología , Cromatografía Líquida de Alta Presión/métodos
17.
Front Public Health ; 10: 1023797, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36582384

RESUMEN

Objective: This study aimed to provide a basis for epidemic prevention and control measures as well as the management of re-positive personnel by analyzing and summarizing the characteristics of re-positive patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infections discharged from a hospital in the Ningxia Hui Autonomous Region in 2021. Methods: This case-control study included a total of 45 patients with Delta variant infections diagnosed in the Fourth People's Hospital of the Ningxia Hui Autonomous Region between October 17 and November 28, 2021. Based on the nucleic acid test results post-discharge, the patients were dichotomized into re-positive and non-re-positive groups. Based on the time of the first re-positive test, the re-positive group was further divided into <7 and ≥7 days groups to compare their clinical characteristics and explore the possible influencing factors of this re-positivity. Results: Of the 45 total patients, 16 were re-positive (re-positivity rate: 35.6%), including four patients who were re-positive after 2 weeks (re-positivity rate: 8.8%). The median time of the first re-positive after discharge was 7 days (IQR: 14-3). The re-positive group was younger than the non-re-positive group (35 vs. 53, P < 0.05), had a higher proportion of patients who were not receiving antiviral therapy (56.2 vs. 17.2%, P < 0.05). The median CT value of nucleic acid in the re-positive group was considerably greater than that at admission (36.7 vs. 22.6 P < 0.05). The findings demonstrated that neutralizing antibody treatment significantly raised the average IgG antibody level in patients, particularly in those who had not received COVID-19 vaccine (P < 0.05). The median lowest nucleic acid CT value of the ≥7 days group during the re-positive period and the immunoglobulin G (IgG) antibody level at discharge were lower than those in the <7 days group (P < 0.05). When compared to the non-positive group, patients in the ≥7 days group had a higher median virus nucleic acid CT value (27.1 vs. 19.2, P < 0.05) and absolute number of lymphocytes at admission (1,360 vs. 952, P < 0.05), and a lower IgG antibody level at discharge (P < 0.05). Conclusions: In conclusion, this study found that: (1) The re-positivity rate of SARS-CoV-2 Delta variant infection in this group was 35.6%, while the re-positivity rate was the same as that of the original strain 2 weeks after discharge (8.0%). (2) Young people, patients who did not use antiviral therapy or had low IgG antibody levels at discharge were more likely to have re-positive. And the CT value of nucleic acid at the time of initial infection was higher in re-positive group. We speculated that the higher the CT value of nucleic acid at the time of initial infection, the longer the intermittent shedding time of the virus. (3) Re-positive patients were asymptomatic. The median CT value of nucleic acid was > 35 at the re-positive time, and the close contacts were not detected as positive. The overall transmission risk of re-positive patients is low.


Asunto(s)
COVID-19 , Ácidos Nucleicos , Humanos , Adolescente , SARS-CoV-2/genética , Estudios de Casos y Controles , Cuidados Posteriores , Vacunas contra la COVID-19 , Alta del Paciente , Antivirales , Inmunoglobulina G
18.
Mol Clin Oncol ; 16(6): 108, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35620207

RESUMEN

The aim of this retrospective study was to identify the perioperative incidence and risk factors of venous thromboembolism (VTE) in patients undergoing surgery for cervical cancer. The retrospective medical records of consecutive patients with cervical cancer were collected at the Qianfoshan Hospital affiliated with Shandong University from July 2014 to July 2017. Basic information regarding the patients, as well as tumor and surgery-related factors were compared between the cervical cancer patients with and without VTE. In the present study, a total of 338 patients undergoing surgery for cervical cancer were included. Ten (3.0%) patients were diagnosed with preoperative VTE and 18 (5.5%) with postoperative VTE. Multivariate analyses found that high levels of D-dimer and a larger size of the cervical tumor were independent risk factors for preoperative VTE, whereas the length of surgery and use of chemotherapy were independently associated with VTE development within 30 days after surgery. In conclusion, the major findings of the present study was a significant incidence of VTE in patients with cervical cancer. We also identified the clinical characteristics which can cause cervical cancer patients to have an increased risk for VTE.

19.
J Nurs Manag ; 30(7): 2670-2680, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35580873

RESUMEN

AIM: The purpose of this study was to explore the effect of authentic leadership on nurses' innovation behaviour and the mediating role of work engagement. BACKGROUND: Encouraging nurses to generate more innovation behaviours has become an important development direction for improving the quality of nursing services. METHOD: We employed a self-report questionnaire to collect data in Jinan City, China. A total of 2018 valid surveys were obtained. Hierarchical multiple regression model analysis was conducted to test the study hypothesis. RESULT: The mean values of authentic leadership were 55.72 and 35.29, respectively. It shows that nurses can perceive the authenticity of managers, and their innovation behaviours need to be improved. Work engagement was found to have partially mediating effect on the relationship between authentic leadership and innovation behaviour. CONCLUSION: Results suggest the importance of developing nurse managers' authentic leadership to foster nurses' work engagement and innovation behaviour. IMPLICATIONS FOR NURSING MANAGEMENT: Hospitals should enhance authentic leadership by designing leadership training programmes and establishing authentic culture. In addition, nursing managers can also foster nursing innovation through improvements in work engagement. The study data were collected via questionnaires, and we sent out questionnaires with informed consent forms to the study subjects. All valid subjects signed the consent forms and agreed to join this study. In addition, the questionnaires were collected anonymously, and all the subjects' information is strictly confidential. More importantly, the data are only used for research and do not involve any commercial interests.


Asunto(s)
Enfermeras Administradoras , Enfermeras y Enfermeros , Humanos , Liderazgo , Compromiso Laboral , Negociación , Creatividad , Encuestas y Cuestionarios
20.
Plant J ; 111(1): 117-133, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35437852

RESUMEN

Serine carboxypeptidase-like acyltransferases (SCPL-ATs) play a vital role in the diversification of plant metabolites. Galloylated flavan-3-ols highly accumulate in tea (Camellia sinensis), grape (Vitis vinifera), and persimmon (Diospyros kaki). To date, the biosynthetic mechanism of these compounds remains unknown. Herein, we report that two SCPL-AT paralogs are involved in galloylation of flavan-3-ols: CsSCPL4, which contains the conserved catalytic triad S-D-H, and CsSCPL5, which has the alternative triad T-D-Y. Integrated data from transgenic plants, recombinant enzymes, and gene mutations showed that CsSCPL4 is a catalytic acyltransferase, while CsSCPL5 is a non-catalytic companion paralog (NCCP). Co-expression of CsSCPL4 and CsSCPL5 is likely responsible for the galloylation. Furthermore, pull-down and co-immunoprecipitation assays showed that CsSCPL4 and CsSCPL5 interact, increasing protein stability and promoting post-translational processing. Moreover, phylogenetic analyses revealed that their homologs co-exist in galloylated flavan-3-ol- or hydrolyzable tannin-rich plant species. Enzymatic assays further revealed the necessity of co-expression of those homologs for acyltransferase activity. Evolution analysis revealed that the mutations of the CsSCPL5 catalytic residues may have taken place about 10 million years ago. These findings show that the co-expression of SCPL-ATs and their NCCPs contributes to the acylation of flavan-3-ols in the plant kingdom.


Asunto(s)
Diospyros , Vitis , Acilación , Aciltransferasas/metabolismo , Carboxipeptidasas/genética , Carboxipeptidasas/metabolismo , Flavonoides , Filogenia , Plantas/metabolismo , Polifenoles , Vitis/metabolismo
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