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1.
J Geriatr Cardiol ; 21(8): 779-790, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39308501

RESUMEN

BACKGROUND: Oxidative stress is closely associated with hypertensive outcomes. The oxidative balance score (OBS) measures oxidative stress exposure from dietary and lifestyle elements. The objective of this study was to investigate the association between OBS and mortality in hypertensive patients. METHODS: This study included 7823 hypertensive patients from the National Health and Nutrition Examination Survey (NHANES) 1999-2014. Several models, including Cox regression, restricted cubic splines (RCS), Kaplan‒Meier survival analysis, subgroup, and sensitivity analyses, were exploited to investigate the relationship between OBS and the risk of mortality. RESULTS: Controlling for all potential confounders, a significantly inverse association was observed between elevated OBS and all-cause [hazard ratio (HR) = 0.90, 95% CI: 0.85-0.95] and cardiovascular mortality (HR = 0.85, 95% CI: 0.75-0.95). With adjustment for covariates, significant associations between lifestyle OBS and mortality risks diminished, whereas associations between dietary OBS and these mortality risks remained robust (all-cause mortality: HR = 0.91, 95% CI: 0.86-0.96; cardiovascular mortality: HR = 0.85, 95% CI: 0.76-0.96). RCS demonstrated a linear relationship between OBS and all-cause and cardiovascular mortality risk (P nonlinear = 0.088 and P nonlinear = 0.447, respectively). Kaplan‒Meier curves demonstrated that the mortality rate was lower with a high OBS (P < 0.001). The consistency of the association was demonstrated in subgroup and sensitivity analyses. RCS after stratification showed that among current drinkers, those with higher OBS had a lower risk of mortality compared with former or never drinkers. CONCLUSIONS: In hypertensive individuals, there was a negative association between OBS and all-cause and cardiovascular mortality. Encouraging hypertensive individuals, especially those currently drinking, to maintain high levels of OBS may be beneficial in improving their prognosis.

2.
Curr Probl Cancer ; 52: 101130, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39213785

RESUMEN

Functional neuroendocrine neoplasms (NENs) are those associated with specific symptoms related to the hormonal secretion of the NENs. Although less than 25 % of NENs are functional at diagnosis,1 the associated syndromes significantly increase the patient burden of disease. Management of hormonal NEN symptoms may involve tumor resection or other reduction strategies (e.g., chemotherapy, embolotherapy, etc), but also specific therapies directed at decreasing hormonal synthesis, secretion, or end-organ effects. In this review, we focus on specific symptomatic management of many of the NEN syndromes, which may be pursued in addition to management primarily directed at tumor bulk and growth. A continued focus on symptom management related to the hormonal secretions of NENs, in the context of other efforts to reduce tumor bulk and growth, could significantly improve patient wellbeing.


Asunto(s)
Tumores Neuroendocrinos , Humanos , Tumores Neuroendocrinos/terapia , Tumores Neuroendocrinos/patología , Manejo de la Enfermedad
3.
NPJ Breast Cancer ; 10(1): 60, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39030225

RESUMEN

Triple-negative breast cancers (TNBCs) are a subset of breast cancers that have remained difficult to treat. A proportion of TNBCs arising in non-carriers of BRCA pathogenic variants have genomic features that are similar to BRCA carriers and may also benefit from PARP inhibitor treatment. Using genomic data from 129 TNBC samples from the Malaysian Breast Cancer (MyBrCa) cohort, we developed a gene expression-based machine learning classifier for homologous recombination deficiency (HRD) in TNBCs. The classifier identified samples with HRD mutational signature at an AUROC of 0.93 in MyBrCa validation datasets and 0.84 in TCGA TNBCs. Additionally, the classifier strongly segregated HRD-associated genomic features in TNBCs from TCGA, METABRIC, and ICGC. Thus, our gene expression classifier may identify triple-negative breast cancer patients with homologous recombination deficiency, suggesting an alternative method to identify individuals who may benefit from treatment with PARP inhibitors or platinum chemotherapy.

4.
RSC Adv ; 14(21): 15167-15177, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38741618

RESUMEN

Significant advancements have been made in catalytic asymmetric α-C-H bond functionalization of ethers via carbenoid insertion over the past decade. Effective asymmetric catalytic systems, featuring a range of chiral metal catalysts, have been established for the enantioselective synthesis of diverse ether substrates. This has led to the generation of various enantioenriched, highly functionalized oxygen-containing structural motifs, facilitating their application in the asymmetric synthesis of bioactive natural products.

5.
Biochemistry ; 63(9): 1225-1233, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38682295

RESUMEN

As plant photoreceptors, phytochromes are capable of detecting red light and far-red light, thereby governing plant growth. All2699 is a photoreceptor found in Nostoc sp. PCC7120 that specifically responds to red light and far-red light. All2699g1g2 is a truncated protein carrying the first and second GAF (cGMP phosphodiesterase/adenylyl cyclase/FhlA) domains of All2699. In this study, we found that, upon exposure to red light, the protein underwent aggregation, resulting in the formation of protein aggregates. Conversely, under far-red light irradiation, these protein aggregates dissociated. We delved into the factors that impact the aggregation of All2699g1g2, focusing on the protein structure. Our findings showed that the GAF2 domain contains a low-complexity (LC) loop region, which plays a crucial role in mediating protein aggregation. Specifically, phenylalanine at position 239 within the LC loop region was identified as a key site for the aggregation process. Furthermore, our research revealed that various factors, including irradiation time, temperature, concentration, NaCl concentration, and pH value, can impact the aggregation of All2699g1g2. The aggregation led to variations in Pfr concentration depending on temperature, NaCl concentration, and pH value. In contrast, ΔLC did not aggregate and therefore lacked responses to these factors. Consequently, the LC loop region of All2699g1g2 extended and enhanced sensory properties.


Asunto(s)
Proteínas Bacterianas , Luz , Nostoc , Nostoc/metabolismo , Nostoc/química , Nostoc/efectos de la radiación , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Dominios Proteicos , Agregado de Proteínas , Fotorreceptores Microbianos/química , Fotorreceptores Microbianos/metabolismo , Pigmentos Biliares/química , Pigmentos Biliares/metabolismo , Concentración de Iones de Hidrógeno , Fitocromo/química , Fitocromo/metabolismo
6.
Sheng Li Xue Bao ; 76(1): 148-160, 2024 Feb 25.
Artículo en Chino | MEDLINE | ID: mdl-38444140

RESUMEN

Mitochondria are dynamically changing organelles that maintain stable mitochondrial morphology, number, and function through constant fusion and division, a process known as mitochondrial dynamics, which is an important mechanism for mitochondrial quality control. Excessive fusion and division of mitochondria can lead to a homeostatic imbalance in mitochondrial dynamics, causing mitochondrial dysfunction, leading to cellular damage, and even death. The physiological functions of the kidney are mainly powered by mitochondria, and homeostatic imbalance in mitochondrial dynamics affects mitochondrial function and is closely related to renal diseases such as acute kidney injury and diabetic nephropathy. This article reviews the regulation of mitochondrial kinetics, how imbalances in mitochondrial kinetic homeostasis affect mitochondrial injury, and the impact of mitochondrial injury on renal pathophysiology, in order to improve understanding and knowledge of the role of mitochondria in renal disease.


Asunto(s)
Lesión Renal Aguda , Nefropatías Diabéticas , Humanos , Dinámicas Mitocondriales , Mitocondrias , Riñón
7.
J Cardiothorac Surg ; 19(1): 155, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38532497

RESUMEN

BACKGROUND: To demonstrate the effectiveness and feasibility of robotic portal resection (RPR) for mediastinal tumour using a prospectively collected database. METHODS: Data from 73 consecutive patients with mediastinal tumours who underwent RPRs were prospectively collected from August 2018 to April 2023. All patients underwent chest and abdominal enhanced computed tomography (CT) and preoperative multidisciplinary team (MDT) discussion. The patients were stratified into two groups based on tumour size: Group A (tumour size < 4 cm) and Group B (tumour size ≥ 4 cm). General clinical characteristics, surgical procedures, and short outcomes were promptly recorded. RESULTS: All of the cases were scheduled for RPRs. One patient (1/73, 1.4%) was switched to a small utility incision approach because of extensive pleural adhesion. Two patients (2.8%) converted to sternotomy, however, no perioperative deaths occurred. Most of the tumours were located in the anterior mediastinum (51/73, 69.9%). Thymoma (27/73, 37.0%) and thymic cyst (16/73, 21.9%) were the most common diagnoses. The median diameter of tumours was 3.2 cm (IQR, 2.4-4.5 cm). The median total operative time was 61.0 min (IQR, 50.0-90.0 min). The median intraoperative blood loss was 20 mL (IQR, 5.0-30.0 ml), and only one patient (1.4%) experienced an intraoperative complication. The median length of hospital stay was 3 days (IQR, 2-4 days). Compared with Group A, the median total operative time and console time of Group B were significantly longer (P = 0.006 and P = 0.003, respectively). The volume of drainage on the first postoperative day was greater in group B than in group A (P = 0.013). CONCLUSION: RPR is a safe and effective technique for mediastinal tumour treatment, which can expand the application of minimally invasive surgery for the removal of complicated mediastinal tumours.


Asunto(s)
Neoplasias del Mediastino , Procedimientos Quirúrgicos Robotizados , Robótica , Timoma , Neoplasias del Timo , Humanos , Neoplasias del Mediastino/cirugía , Robótica/métodos , Neoplasias del Timo/cirugía , Timoma/cirugía , Resultado del Tratamiento , Estudios Retrospectivos
8.
Biomed Pharmacother ; 171: 116140, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38211425

RESUMEN

Stroke is a prevalent cerebrovascular condition with a global impact, causing significant rates of illness and death. Despite extensive research, the available treatment options for stroke remain restricted. Hence, it is crucial to gain a deeper understanding of the molecular mechanisms associated with the onset and advancement of stroke in order to establish a theoretical foundation for novel preventive and therapeutic approaches. NF-κB, also known as nuclear factor κB, is a transcription factor responsible for controlling the expression of numerous genes and plays a crucial role in diverse physiological processes. NF-κB is triggered and regulates neuroinflammation and other processes after stroke, promoting the generation of cytokine storms and contributing to the advancement of ischemic stroke (IS). Therefore, NF-κB could potentially play a vital role in stroke by regulating diverse pathophysiological processes. This review provides an overview of the functions of NF-κB in stroke and its governing mechanisms. In addition, our attention is directed towards various potential therapies that aim to inhibit the NF-κB signaling pathway in order to offer valuable insights for the advancement of innovative treatment approaches for stroke.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , FN-kappa B , Accidente Cerebrovascular , Humanos , Isquemia Encefálica/tratamiento farmacológico , FN-kappa B/metabolismo , Transducción de Señal/fisiología , Accidente Cerebrovascular/tratamiento farmacológico
9.
J Microbiol Immunol Infect ; 57(2): 225-237, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38262772

RESUMEN

BACKGROUND: The COVID-19 pandemic is spreading rapidly around the world, causing countries to impose lockdowns and efforts to develop vaccines on a global scale. However, human-to-animal and animal-to-human transmission cannot be ignored, as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can spread rapidly in farmed and wild animals. This could create a worrying cycle of SARS-CoV-2 spillover from humans to animals and spillback of new strains back into humans, rendering vaccines ineffective. METHOD: This study provides a key indicator of animals that may be potential susceptible hosts for SARS-CoV-2 and coronavirus infections by analysing the phylogenetic distance between host angiotensin-converting enzyme 2 and the coronavirus spike protein. Crucially, our analysis identifies animals that are at elevated risk from a spillover and spillback incident. RESULTS: One group of animals has been identified as potentially susceptible to SARS-CoV-2 by harbouring a parasitic coronavirus spike protein similar to the SARS-CoV-2 spike protein. These animals may serve as amplification hosts in spillover events from zoonotic reservoirs. This group consists of a mixture of animals infected internally and naturally: minks, dogs, cats, tigers. Additionally, no internal or natural infections have been found in masked palm civet. CONCLUSION: Tracing interspecies transmission in multi-host environments based solely on in vitro and in vivo examinations of animal susceptibility or serology is a time-consuming task. This approach allows rapid identification of high-risk animals to prioritize research and assessment of the risk of zoonotic disease transmission in the environment. It is a tool to rapidly identify zoonotic species that may cause outbreaks or participate in expansion cycles of coexistence with their hosts. This prevents the spread of coronavirus infections between species, preventing spillover and spillback incidents from occurring.


Asunto(s)
COVID-19 , Vacunas , Animales , Humanos , Perros , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/metabolismo , COVID-19/epidemiología , Filogenia , Pandemias/prevención & control , Control de Enfermedades Transmisibles
10.
J Asian Nat Prod Res ; 26(4): 534-540, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37639617

RESUMEN

Based on the One Strain-Many Compounds (OSMAC) strategy, the secondary metabolites of Phomopsis lithocarpus FS508 were investigated. As a result, a new secondary metabolite, 4-methoxy-3-[4-(acetyloxy)-3-methyl-2-butenyl]benzoic acid (1) as well as eleven known compounds were isolated from the fermentation product of the strain FS508. Their structures were determined by NMR, IR, UV, and MS spectroscopic data analyses. All the isolated compounds were evaluated for cytotoxic and anti-inflammatory activities. Among them, compounds 3 and 9 displayed potent cytotoxicity against HepG-2 cell line, and compounds 2, 3 and 12 showed significant anti-inflammatory activities.


Asunto(s)
Antineoplásicos , Ascomicetos , Phomopsis , Ascomicetos/química , Línea Celular Tumoral , Antineoplásicos/química , Antiinflamatorios/farmacología , Estructura Molecular
11.
Front Neurol ; 14: 1266167, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38145123

RESUMEN

Objective: Functional magnetic resonance imaging (fMRI) has been used for evaluating residual brain function and predicting the prognosis of patients with severe traumatic brain injury (sTBI). This study aimed to integrate the fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) to investigate the mechanism and prognosis of patients with sTBI. Methods: Sixty-five patients with sTBI were included and underwent fMRI scanning within 14 days after brain injury. The patient's outcome was assessed using the Glasgow Outcome Scale-Extended (GOSE) at 6 months post-injury. Of the 63 patients who met fMRI data analysis standards, the prognosis of 18 patients was good (GOSE scores ≥ 5), and the prognosis of 45 patients was poor (GOSE scores ≤ 4). First, we apply fALFF to identify residual brain functional differences in patients who present different prognoses and conjoined it in regions of interest (ROI)-based FC analysis to investigate the residual brain function of sTBI at the acute phase of sTBI. Then, the area under the curve (AUC) was used to evaluate the predictive ability of the brain regions with the difference of fALFF and FC values. Results: Patients who present good outcomes at 6 months post-injury have increased fALFF values in the Brodmann area (7, 18, 31, 13, 39 40, 42, 19, 23) and decreased FC values in the Brodmann area (28, 34, 35, 36, 20, 28, 34, 35, 36, 38, 1, 2, 3, 4, 6, 13, 40, 41, 43, 44, 20, 28 35, 36, 38) at the acute phase of sTBI. The parameters of these alterations can be used for predicting the long-term outcomes of patients with sTBI, of which the fALFF increase in the temporal lobe, occipital lobe, precuneus, and middle temporal gyrus showed the highest predictive ability (AUC = 0.883). Conclusion: We provide a compensatory mechanism that several regions of the brain can be spontaneously activated at the acute phase of sTBI in those who present with a good prognosis in the 6-month follow-up, that is, a destructive mode that increases its fALFF in the local regions and weakens its FC to the whole brain. These findings provide a theoretical basis for developing early intervention targets for sTBI patients.

12.
Ying Yong Sheng Tai Xue Bao ; 34(11): 3135-3143, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37997425

RESUMEN

One of the effective ways to improve the productivity of mixed forests is enhancing resource use efficiency based on the biological characteristics of afforestation tree species. Resource use efficiency is affected by tree species interactions and environmental conditions through applying appropriate cultivation patterns. In this study, we evaluated two estimating methods for the productivity of mixed forest, analyzed the internal mechanism of interspecific tree competition and complementary effects on mixed forest productivity, clarified external factors of growth space and habitat factors control over productivity of mixed forest, discussed the effects of tree species composition, stand density and site quality on productivity, and illustrated the productivity trajectory during the development of mixed forests. Finally, based on the knowledge of the internal mechanism and habitat factors affecting the formation of mixed forest productivity, we focused on the key scientific issues that urgently need to be solved in the construction of the current mixed forests cultivation patterns, and put forward future research directions, including improving the productivity estimation system, establishing long-term mixed forest observation field, enhancing the research on the comprehensive effect of various cultivation measures, and reinforcing research of the growth and development dynamics in mixed forests.


Asunto(s)
Bosques , Árboles , Ecosistema , Eficiencia
13.
J Am Chem Soc ; 145(46): 25033-25042, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37864571

RESUMEN

Programmable biomolecule-mediated computing is a new computing paradigm as compared to contemporary electronic computing. It employs nucleic acids and analogous biomolecular structures as information-storing and -processing substrates to tackle computational problems. It is of great significance to investigate the various issues of programmable biomolecule-mediated processors that are capable of automatically processing, storing, and displaying information. This Perspective provides several conceptual designs of programmable biomolecule-mediated processors and provides some insights into potential future research directions for programmable biomolecule-mediated processors.

14.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(8): 843-848, 2023 Aug 15.
Artículo en Chino | MEDLINE | ID: mdl-37668033

RESUMEN

OBJECTIVES: To explore the etiology composition and outcomes of pediatric chronic critical illness (PCCI) in the pediatric intensive care unit (PICU). METHODS: The children who were hospitalized in the PICU of Dongguan Children's Hospital Affiliated to Guangdong Medical University and met the diagnostic criteria for PCCI from January 2017 to December 2022 were included in the study. The etiology of the children was classified based on their medical records and discharge diagnoses. Relevant clinical data during hospitalization were collected and analyzed. RESULTS: Among the 3 955 hospitalized children in the PICU from January 2017 to December 2022, 321 cases (8.12%) met the diagnostic criteria for PCCI. Among the 321 cases, the most common etiology was infection (71.3%, 229 cases), followed by unintentional injury (12.8%, 41 cases), postoperation (5.9%, 19 cases), tumors/immune system diseases (5.0%, 16 cases), and genetic and chromosomal diseases (5.0%, 16 cases). Among the 321 cases, 249 cases (77.6%) were discharged after improvement, 37 cases (11.5%) were discharged at the request of the family, and 35 cases (10.9%) died in the hospital. Among the deaths, infection accounted for 74% (26/35), unintentional injury accounted for 17% (6/35), tumors/immune system diseases accounted for 6% (2/35), and genetic and chromosomal diseases accounted for 3% (1/35). From 2017 to 2022, the proportion of PCCI in PICU diseases showed an increasing trend year by year (P<0.05). Among the 321 children with PCCI, there were 148 infants and young children (46.1%), 57 preschool children (17.8%), 54 school-aged children (16.8%), and 62 adolescents (19.3%), with the highest proportion in the infant and young children group (P<0.05). The in-hospital mortality rates of the four age groups were 14.9% (22/148), 8.8% (5/57), 5.6% (3/54), and 8.1% (5/62), respectively. The infant and young children group had the highest mortality rate, but there was no statistically significant difference among the four groups (P>0.05). CONCLUSIONS: The proportion of PCCI in PICU diseases is increasing, and the main causes are infection and unintentional injury. The most common cause of death in children with PCCI is infection. The PCCI patient population is mainly infants and young children, and the in-hospital mortality rate of infant and young children with PCCI is relatively high.


Asunto(s)
Niño Hospitalizado , Enfermedad Crítica , Adolescente , Lactante , Preescolar , Humanos , Niño , Pronóstico , Enfermedad Crónica , Unidades de Cuidado Intensivo Pediátrico
16.
Biochemistry ; 62(13): 2021-2028, 2023 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-37319348

RESUMEN

Liquid-liquid phase separation (LLPS) plays a key role in the regulation of life activities. Here, we reported a protein from Synechocystis sp. PCC 6803 and annotated as Slr0280. To obtain a water-soluble protein, we deleted the N-terminus transmembrane domain and named it Slr0280Δ. Slr0280Δ with high concentration can undergo LLPS at a low temperature in vitro. It belongs to the phosphodiester glycosidase family of proteins and has a segment of a low-complexity sequence region (LCR), which is thought to regulate the LLPS. Our results show that electrostatic interactions impact the LLPS of Slr0280Δ. We also acquired the structure of Slr0280Δ, which has many grooves on the surface with a large distribution of positive and negative charges. This may be advantageous for the LLPS of Slr0280Δ through electrostatic interactions. Furthermore, the conserved amino acid (arginine at position 531) located on the LCR is important for maintaining the stability of Slr0280Δ as well as LLPS. Our research indicated that the LLPS of proteins can be transformed into aggregation by changing the surface charge distribution.


Asunto(s)
Dominios Proteicos
17.
Clin Lung Cancer ; 24(6): e226-e235, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37263866

RESUMEN

BACKGROUND: We aimed to investigate the impact of the number of harvested lymph nodes (LNs) on the overall survival (OS) and disease-free survival (DFS) of patients with clinical node-negative (cN0) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 2247 patients with cN0 NSCLC between 2001 and 2014 were included. Scatter plots of hazard ratios from Cox proportional hazards models against the number of harvested LNs were created, and curves were fitted using a LOWESS smoother. Chow test was used to determine the cut-off points for the optimal number of harvested LNs. Long-term survival was compared between groups divided by the cut-off points. RESULTS: The increasing numbers of harvested LNs and N2 level LNs were independent factors favoring OS and DFS. Seventeen LNs and 10 N2 level LNs were determined as the optimal cut-off points. The patients with ≥17 harvested LNs had a better OS (P = .001) and DFS (P = .002), while the patients with ≥10 harvested N2 level LNs also had a better OS (P < .001) and DFS (P = .001). The increasing numbers of harvested LNs and N2 level LNs were independent prognostic factors associated with prolonged OS and DFS only in patients with clinical T2 (cT2) NSCLC. CONCLUSIONS: The increasing numbers of harvested LNs and N2 level LNs were associated with better OS and DFS in cN0 NSCLC patients that were suitable for lobectomies. At least 17 LNs and 10 N2 level LNs were required to be harvested, especially in cT2 patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , Ganglios Linfáticos/patología , Escisión del Ganglio Linfático , Pronóstico , Estudios Retrospectivos
18.
J Ethnopharmacol ; 317: 116706, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37301305

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used clinically to treat inflammatory diseases clinically. However, the adverse effects of NSAIDs cannot be ignored. Therefore, it is critical for us to find alternative anti-inflammatory drugs that can reduce adverse reactions to herbal medicine, such as Iris tectorum Maxim., which has therapeutic effects and can treat inflammatory diseases and liver-related diseases. AIM OF THE STUDY: This study aimed to isolate active compounds from I. tectorum and investigate their anti-inflammatory effects and action mechanisms. MATERIALS AND METHODS: Fourteen compounds were isolated from I. tectorum using silica gel column chromatography, Sephadex LH-20, ODS and high performance liquid chromatography, and their structures were identified by examining physicochemical properties, ultraviolet spectroscopy, infrared spectroscopy, mass spectrometry, and nuclear magnetic resonance spectroscopy. Classical inflammatory cell models were established using lipopolysaccharide (LPS)-stimulated RAW264.7 cells and rat primary peritoneal macrophages to examine the effect of these compounds. To examine the action mechanisms, the nitric oxide (NO) levels were measured by Griess reagent and the levels of inflammatory cytokines in the supernatant were measured by ELISA; The expressions of major proteins in prostaglandin E2 (PGE2) synthesis and the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were examined by Western blotting, and the mRNA expression levels were measured by quantitative real-time polymerase chain reaction; and the nuclear translocation of p65 was examined by high content imaging. Molecular docking was used to predict the binding of active compound to target protein. RESULTS: Our findings revealed that Iristectorigenin C (IT24) significantly inhibited the levels of NO and PGE2 without affecting cyclooxygenase (COX)-1/COX-2 expression in LPS-induced RAW264.7 cells and rat peritoneal macrophages. Furthermore, IT24 was shown to decrease the expression of microsomal prostaglandin synthetase-1 (mPGES-1) in LPS-induced rat peritoneal macrophages. IT24 did not suppress the phosphorylation and nuclear translocation of proteins in the NF-κB pathway, but it inhibited the phosphorylation of p38/JNK in LPS-stimulated RAW264.7 cells. Additionally, molecular docking analysis indicated that IT24 may directly bind to the mPGES-1 protein. CONCLUSION: IT24 might inhibit mPGES-1 and the p38/JNK pathway to exert its anti-inflammatory effects and could be also developed as an inhibitor of mPGES-1 to prevent and treat mPGES-1-related diseases, such as inflammatory diseases, and holds promise for further research and drug development.


Asunto(s)
Lipopolisacáridos , Sistema de Señalización de MAP Quinasas , Ratas , Animales , Lipopolisacáridos/farmacología , FN-kappa B/metabolismo , Simulación del Acoplamiento Molecular , Antiinflamatorios/farmacología , Antiinflamatorios no Esteroideos/farmacología , Macrófagos Peritoneales , Ciclooxigenasa 2/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo
20.
Malays J Med Sci ; 30(1): 107-115, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36875199

RESUMEN

Background: Hypopituitarism following traumatic brain injury (TBI) is not rare however most patients were left undiagnosed and untreated. Association of post TBI hypopituitarism causing neurobehavioural and quality of life impairment. The aim of the study is to determine the incidence of the chronic anterior pituitary deficiency in patients with traumatic brain injury. Subsequently determine the risk factor and the outcome of the patient with chronic anterior pituitary dysfunction. Methods: This is single centre cross-sectional study involved 105 traumatic head injury patients under the Neurosurgical Department Hospital Sultanah Aminah, Johor Bahru, Malaysia. The primary investigator will do an interview and the patients will be asked question to complete a questioner from SF-36 (36 questions). Subsequently, consent for participation will be taken and blood sampling will be done. Results: Thirty-three patients were noted to have anterior pituitary dysfunction. The mean age was 36.97 ± 12.96 years old. Twenty-seven patients (32.5%) were male and six patients were female (27.3%). Chronic anterior pituitary dysfunction in patients with a severe traumatic head injury around 47.1% (23 patients), as compared to a moderate head injury (8 patients, 38.1%) and 2 sustained mild head injury (5.6%). The mean duration after the onset of trauma was 10.3 ± 1.79 months. All patient with anterior pituitary dysfunction had positive CT brain findings with 22 had subarachnoid haemorrhage (SAH) at the basal cistern and 27 patients had a base of skull fracture, where 52.1% of the patient underwent surgical intervention, 84.8% involved one axis and another 5 patients had two axes involved. Severity of the head injury (P < 0.001), prolonged duration of hospital stay (P = 0.014), radiological findings of a base of skull fracture (P < 0.001) and presence of SAH at basal cistern (P < 0.001) was significantly associated with pituitary dysfunction. The patient with anterior pituitary dysfunction has the lower 36-item Short Form Survey (SF-36) marks 56.3 ± 10.3. Conclusion: The prevalence of hypopituitarism was 31%. Indicators are increased TBI severity, prolonged hospitalisation and positive finding in radiological assessment. Post-traumatic chronic anterior pituitary dysfunction also related with poor quality of life as showed by low SF-36 marks.

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