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1.
Brain ; 147(4): 1294-1311, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38289861

RESUMEN

Ischaemic stroke causes neuron loss and long-term functional deficits. Unfortunately, effective approaches to preserving neurons and promoting functional recovery remain unavailable. Oligodendrocytes, the myelinating cells in the CNS, are susceptible to oxygen and nutrition deprivation and undergo degeneration after ischaemic stroke. Technically, new oligodendrocytes and myelin can be generated by the differentiation of oligodendrocyte precursor cells (OPCs). However, myelin dynamics and their functional significance after ischaemic stroke remain poorly understood. Here, we report numerous denuded axons accompanied by decreased neuron density in sections from ischaemic stroke lesions in human brain, suggesting that neuron loss correlates with myelin deficits in these lesions. To investigate the longitudinal changes in myelin dynamics after stroke, we labelled and traced pre-existing and newly-formed myelin, respectively, using cell-specific genetic approaches. Our results indicated massive oligodendrocyte death and myelin loss 2 weeks after stroke in the transient middle cerebral artery occlusion (tMCAO) mouse model. In contrast, myelin regeneration remained insufficient 4 and 8 weeks post-stroke. Notably, neuronal loss and functional impairments worsened in aged brains, and new myelin generation was diminished. To analyse the causal relationship between remyelination and neuron survival, we manipulated myelinogenesis by conditional deletion of Olig2 (a positive regulator) or muscarinic receptor 1 (M1R, a negative regulator) in OPCs. Deleting Olig2 inhibited remyelination, reducing neuron survival and functional recovery after tMCAO. Conversely, enhancing remyelination by M1R conditional knockout or treatment with the pro-myelination drug clemastine after tMCAO preserved white matter integrity and neuronal survival, accelerating functional recovery. Together, our findings demonstrate that enhancing myelinogenesis is a promising strategy to preserve neurons and promote functional recovery after ischaemic stroke.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Ratones , Animales , Humanos , Anciano , Vaina de Mielina/patología , Isquemia Encefálica/complicaciones , Isquemia Encefálica/patología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/patología , Oligodendroglía/patología , Neuronas , Diferenciación Celular/fisiología
2.
Drug Resist Updat ; 76: 101113, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39053384

RESUMEN

Gliomas, the most common CNS (central nerve system) tumors, face poor survival due to severe chemoresistance exacerbated by hypoxia. However, studies on whether altered hypoxic conditions benefit for chemo-sensitivity and how gliomas react to increased oxygen stimulation are limited. In this study, we demonstrated that increased oxygen stimulation promotes glioma growth and chemoresistance. Mechanically, increased oxygen stimulation upregulates miR-1290 levels. miR-1290, in turn, downregulates PLCB1, while PLCB1 facilitates the proteasomal degradation of ß-catenin and active-ß-catenin by increasing the proportion of ubiquitinated ß-catenin in a destruction complex-independent mechanism. This process inhibits PLCB1 expression, leads to the accumulation of active-ß-catenin, boosting Wnt signaling through an independent mechanism and ultimately promoting chemoresistance in glioma cells. Pharmacological inhibition of Wnt by WNT974 could partially inhibit glioma volume growth and prolong the shortened survival caused by increased oxygen stimulation in a glioma-bearing mouse model. Moreover, PLCB1, a key molecule regulated by increased oxygen stimulation, shows promising predictive power in survival analysis and has great potential to be a biomarker for grading and prognosis in glioma patients. These results provide preliminary insights into clinical scenarios associated with altered hypoxic conditions in gliomas, and introduce a novel perspective on the role of the hypoxic microenvironment in glioma progression. Furthermore, the outcomes reveal the potential risks of utilizing hyperbaric oxygen treatment (HBOT) in glioma patients, particularly when considering HBOT as a standalone option to ameliorate neuro-dysfunctions or when combining HBOT with a single chemotherapy agent without radiotherapy.


Asunto(s)
Neoplasias Encefálicas , Resistencia a Antineoplásicos , Glioma , MicroARNs , Oxígeno , Fosfolipasa C beta , Vía de Señalización Wnt , beta Catenina , Glioma/tratamiento farmacológico , Glioma/patología , Glioma/genética , Glioma/terapia , Glioma/metabolismo , Animales , Humanos , Resistencia a Antineoplásicos/efectos de los fármacos , Ratones , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/terapia , Vía de Señalización Wnt/efectos de los fármacos , Oxígeno/metabolismo , Fosfolipasa C beta/metabolismo , Fosfolipasa C beta/genética , beta Catenina/metabolismo , beta Catenina/genética , Línea Celular Tumoral , MicroARNs/genética , MicroARNs/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Fenotipo , Ratones Desnudos
3.
J Cell Mol Med ; 28(8): e18290, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38588015

RESUMEN

Growth hormone inducible transmembrane protein (GHITM), one member of Bax inhibitory protein-like family, has been rarely studied, and the clinical importance and biological functions of GHITM in kidney renal clear cell carcinoma (KIRC) still remain unknown. In the present study, we found that GHITM was downregulated in KIRC. Aberrant GHITM downregulation related to clinicopathological feature and unfavourable prognosis of KIRC patients. GHITM overexpression inhibited KIRC cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, GHITM overexpression could induce the downregulation of Notch1, which acts as an oncogene in KIRC. Overexpression of Notch1 effectively rescued the inhibitory effect induced by GHITM upregulation. More importantly, GHITM could regulate PD-L1 protein abundance and ectopic overexpression of GHITM enhanced the antitumour efficiency of PD-1 blockade in KIRC, which provided new insights into antitumour therapy. Furthermore, we also showed that YY1 could decrease GHITM level via binding to its promoter. Taken together, our study revealed that GHITM was a promising therapeutic target for KIRC, which could modulate malignant phenotype and sensitivity to PD-1 blockade of renal cancer cells via Notch signalling pathway.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Riñón , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Fenotipo , Receptor de Muerte Celular Programada 1
4.
Funct Integr Genomics ; 24(4): 125, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38995475

RESUMEN

MDS1 and EVI1 complex locus (MECOM), a transcription factor encoding several variants, has been implicated in progression of ovarian cancer. The function of regulatory regions in regulating MECOM expression in ovarian cancer is not fully understood. In this study, MECOM expression was evaluated in ovarian cancer cell lines treated with bromodomain and extraterminal (BET) inhibitor JQ-1. Oncogenic phenotypes were assayed using assays of CCK-8, colony formation, wound-healing and transwell. Oncogenic phenotypes were estimated in stable sgRNA-transfected OVCAR3 cell lines. Xenograft mouse model was assayed via subcutaneous injection of enhancer-deleted OVCAR3 cell lines. The results displayed that expression of MECOM is downregulated in cell lines treated with JQ-1. Data from published ChIP-sequencing (H3K27Ac) in 3 ovarian cancer cell lines displayed a potential enhancer around the first exon. mRNA and protein expression were downregulated in OVCAR3 cells after deletion of the MECOM enhancer. Similarly, oncogenic phenotypes both in cells and in the xenograft mouse model were significantly attenuated. This study demonstrates that JQ-1 can inhibit the expression of MECOM and tumorigenesis. Deletion of the enhancer activity of MECOM has an indispensable role in inhibiting ovarian cancer progress, which sheds light on a promising opportunity for ovarian cancer treatment through the application of this non-coding DNA deletion.


Asunto(s)
Azepinas , Sistemas CRISPR-Cas , Neoplasias Ováricas , Femenino , Humanos , Animales , Neoplasias Ováricas/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Ratones , Línea Celular Tumoral , Azepinas/farmacología , Elementos de Facilitación Genéticos , Triazoles/farmacología , Proteína del Locus del Complejo MDS1 y EV11/genética , Proteína del Locus del Complejo MDS1 y EV11/metabolismo , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor
5.
Anal Chem ; 96(23): 9424-9429, 2024 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-38825761

RESUMEN

Candida auris (C. auris) was first discovered in Japan in 2009 and has since spread worldwide. It exhibits strong transmission ability, high multidrug resistance, blood infectivity, and mortality rates. Traditional diagnostic techniques for C. auris have shortcomings, leading to difficulty in its timely diagnosis and identification. Therefore, timely and accurate diagnostic assays for clinical samples are crucial. We developed a novel, rapid recombinase-aided amplification (RAA) assay targeting the 18S rRNA, ITS1, 5.8S rRNA, ITS2, and 28S rRNA genes for C. auris identification. This assay can rapidly amplify DNA at 39 °C in 20 min. The analytical sensitivity and specificity were evaluated. From 241 clinical samples collected from pediatric inpatients, none were detected as C. auris-positive. We then prepared simulated clinical samples by adding 10-fold serial dilutions of C. auris into the samples to test the RAA assay's efficacy and compared it with that of real-time PCR. The assay demonstrated an analytical sensitivity of 10 copies/µL and an analytical specificity of 100%. The lower detection limit of the RAA assay for simulated clinical samples was 101 CFU/mL, which was better than that of real-time PCR (102-103 CFU/mL), demonstrating that the RAA assay may have a better detection efficacy for clinical samples. In summary, the RAA assay has high sensitivity, specificity, and detection efficacy. This assay is a potential new method for detecting C. auris, with simple reaction condition requirements, thus helping to manage C. auris epidemics.


Asunto(s)
Candida auris , Técnicas de Amplificación de Ácido Nucleico , Recombinasas , Técnicas de Amplificación de Ácido Nucleico/métodos , Humanos , Recombinasas/metabolismo , Candida auris/genética , Candidiasis/diagnóstico , Candidiasis/microbiología , Límite de Detección , ADN de Hongos/genética , ADN de Hongos/análisis
6.
BMC Med ; 22(1): 167, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38637815

RESUMEN

BACKGROUND: The prevalence of depression among people with chronic pain remains unclear due to the heterogeneity of study samples and definitions of depression. We aimed to identify sources of variation in the prevalence of depression among people with chronic pain and generate clinical prediction models to estimate the probability of depression among individuals with chronic pain. METHODS: Participants were from the UK Biobank. The primary outcome was a "lifetime" history of depression. The model's performance was evaluated using discrimination (optimism-corrected C statistic) and calibration (calibration plot). RESULTS: Analyses included 24,405 patients with chronic pain (mean age 64.1 years). Among participants with chronic widespread pain, the prevalence of having a "lifetime" history of depression was 45.7% and varied (25.0-66.7%) depending on patient characteristics. The final clinical prediction model (optimism-corrected C statistic: 0.66; good calibration on the calibration plot) included age, BMI, smoking status, physical activity, socioeconomic status, gender, history of asthma, history of heart failure, and history of peripheral artery disease. Among participants with chronic regional pain, the prevalence of having a "lifetime" history of depression was 30.2% and varied (21.4-70.6%) depending on patient characteristics. The final clinical prediction model (optimism-corrected C statistic: 0.65; good calibration on the calibration plot) included age, gender, nature of pain, smoking status, regular opioid use, history of asthma, pain location that bothers you most, and BMI. CONCLUSIONS: There was substantial variability in the prevalence of depression among patients with chronic pain. Clinically relevant factors were selected to develop prediction models. Clinicians can use these models to assess patients' treatment needs. These predictors are convenient to collect during daily practice, making it easy for busy clinicians to use them.


Asunto(s)
Asma , Dolor Crónico , Adulto , Humanos , Persona de Mediana Edad , Dolor Crónico/epidemiología , Modelos Estadísticos , Prevalencia , Depresión/epidemiología , Bancos de Muestras Biológicas , Biobanco del Reino Unido , Pronóstico
7.
J Neuroinflammation ; 21(1): 102, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637850

RESUMEN

The notion that the central nervous system is an immunologically immune-exempt organ has changed over the past two decades, with increasing evidence of strong links and interactions between the central nervous system and the peripheral immune system, both in the healthy state and after ischemic and hemorrhagic stroke. Although primary injury after stroke is certainly important, the limited therapeutic efficacy, poor neurological prognosis and high mortality have led researchers to realize that secondary injury and damage may also play important roles in influencing long-term neurological prognosis and mortality and that the neuroinflammatory process in secondary injury is one of the most important influences on disease progression. Here, we summarize the interactions of the central nervous system with the peripheral immune system after ischemic and hemorrhagic stroke, in particular, how the central nervous system activates and recruits peripheral immune components, and we review recent advances in corresponding therapeutic approaches and clinical studies, emphasizing the importance of the role of the peripheral immune system in ischemic and hemorrhagic stroke.


Asunto(s)
Lesiones Encefálicas , Isquemia Encefálica , Neoplasias Encefálicas , Accidente Cerebrovascular Hemorrágico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Hemorrágico/complicaciones , Isquemia Encefálica/complicaciones , Encéfalo , Accidente Cerebrovascular/complicaciones , Lesiones Encefálicas/complicaciones , Neoplasias Encefálicas/complicaciones
8.
Small ; 20(19): e2307308, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38126576

RESUMEN

Reaction kinetics can be improved by the enhanced electrical contact between different components growing symbiotically. But so far, due to the necessity for material synthesis conditions match, the component structures of cooperative growth are similar, and the materials are of the same type. The collaborative growth of high-reaction kinetics composite homogeneous core-shell heterostructure between various materials is innovatively proposed with different structures in one step. The NiCo-LDH and PPy successfully symbiotically grow on activated carbon fiber fabric in one step. The open channel structure of the NiCo-LDH nanosheets is preserved while PPy effectively wrapped around the NiCo-LDH. The well-defined nanostructure with abundant active sites and convenient ion diffusion paths is favorable for electrolyte entry into the entire nanoarrays. In addition, owing to the enhanced electronic interaction between different components through XPS analysis, the NiCo-LDH@PPy electrode shows outstanding reaction kinetics and structural stability. The as-synthesized NiCo-LDH@PPy exhibited excellent super-capacitive storage capabilities, robust capacitive activity, and good rate survival. Furthermore, an asymmetric supercapacitor (ASC) device made of NiCo-LDH@PPy and activated carbon (AC) is able to maintain a long cycle life while achieving high power and energy densities.

9.
Ann Surg Oncol ; 31(7): 4250-4260, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38334847

RESUMEN

BACKGROUND: The prognosis of limited-stage small cell lung cancer (LS-SCLC) after surgery usually is estimated at diagnosis, but how the prognosis actually evolves over time for patients who survived for a predefined time is unknown. METHODS: Data on patients with a diagnosis of LS-SCLC after surgery between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The 5-year conditional cancer-specific survival (CCSS) and conditional overall survival (COS) were calculated. RESULTS: This study analyzed 997 patients (555 women, 55.7%) with a median age, of 67 years (interquartile range [IQR], 60-73 years). The 5-year CCSS and COS increased from 44.7% and 38.3%, respectively, at diagnosis to 83.7% and 67.9% at 5 years after diagnosis. Although there were large differences with different stages (stages I, II, and III) at diagnosis (respectively 59.5%, 28.4%; 28.1% for CCSS and 50.6%, 24.8%, and 23.6% for COS), the gap decreased with time, and the rates were similar after 5 years (respectively 85.0%, 80.3%, and 79.4% for CCSS; 65.6%, 56.9%, and 61.3% for COS). The 5-year conditional survival for the patients who received lobectomy was better than for those who received sublobectomy or pneumonectomy. Multivariable analyses showed that only age and resection type were independent predictors for CCSS and COS, respectively, throughout the period. CONCLUSION: Conditional survival estimates for LS-SCLC generally increased over time, with the most significant improvement in patients with advanced stage of disease. Resection type and old age represented extremely important determinants of prognosis after a lengthy event-free follow-up period.


Asunto(s)
Neoplasias Pulmonares , Estadificación de Neoplasias , Programa de VERF , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Femenino , Carcinoma Pulmonar de Células Pequeñas/cirugía , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/patología , Persona de Mediana Edad , Masculino , Tasa de Supervivencia , Anciano , Pronóstico , Estudios de Seguimiento , Neumonectomía/mortalidad , Estudios de Cohortes
10.
Clin Genet ; 105(4): 397-405, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38173219

RESUMEN

CCDC88C gene, which encodes coiled-coil domain containing 88C, is essential for cell communication during neural development. Variants in the CCDC88C caused congenital hydrocephalus, some accompanied by seizures. In patients with epilepsy without acquired etiologies, we performed whole-exome sequencing (trio-based). Two de novo and two biallelic CCDC88C variants were identified in four cases with focal (partial) epilepsy. These variants did not present or had low frequencies in the gnomAD populations and were predicted to be damaging by multiple computational algorithms. Patients with de novo variants presented with adult-onset epilepsy, whereas patients with biallelic variants displayed infant-onset epilepsy. They all responded well to anti-seizure medications and were seizure-free. Further analysis showed that de novo variants were located at crucial domains, whereas one paired biallelic variants were located outside the crucial domains, and the other paired variant had a non-classical splicing and a variant located at crucial domain, suggesting a sub-molecular effect. CCDC88C variants associated with congenital hydrocephalus were all truncated, whereas epilepsy-associated variants were mainly missense, the proportion of which was significantly higher than that of congenital hydrocephalus-associated variants. CCDC88C is potentially associated with focal epilepsy with favorable outcome. The underlying mechanisms of phenotypic variation may correlation between genotype and phenotype.


Asunto(s)
Epilepsias Parciales , Epilepsia , Hidrocefalia , Lactante , Adulto , Humanos , Epilepsias Parciales/genética , Epilepsia/genética , Hidrocefalia/genética , Genotipo , Estudios de Asociación Genética , Proteínas de Microfilamentos/genética , Péptidos y Proteínas de Señalización Intracelular/genética
11.
Opt Lett ; 49(11): 3006-3009, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824314

RESUMEN

In analogy to a wavelength selective switch in wavelength-division multiplexing (WDM) optical fiber communication systems, a spatial and optical mode selective switch (SMSS) would be an important component in future ultrahigh capacity optical fiber communication systems based on space and mode division multiplexing. In this work, a free-space SMSS for orbital angular momentum (OAM) mode-division multiplexing (MDM) is proposed and experimentally demonstrated. The SMSS consists of a separating part for transforming OAM modes to spatial modes and a recombining part for selecting and recombining the modes to any spatial channel. The SMSS is able to implement strictly non-blocking switching between a total of 36 SDM/MDM channels configured as four spatial channels each supporting nine OAM mode channels.

12.
Opt Lett ; 49(4): 887-890, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38359208

RESUMEN

The multiplication of orbital angular momentum (OAM) modes using optical coordinate transformation is useful for OAM optical networks, but the scalability of this scheme is limited by the ray model. Here, we propose an alternative scheme for the scalable multiplication of OAM modes based on modified multi-plane light conversion (MPLC) that can extend azimuthal and radial indices of OAM modes supported by the multipliers and unlock a new degree of freedom for radial high-order OAM states that has been restricted in the zero order. The multiplication for 20 OAM modes with radial index p = 0 and 10 OAM modes with radial index p = 1 is performed in simulation and experiment. The 3-dB optical bandwidth corresponding to the purity of OAM modes covers the entire C-band experimentally. This novel, to the best of our knowledge, approach to manipulating OAM states provides valuable insights and flexible strategies for high-capacity OAM optical communication and high-dimensional optical quantum information processing.

13.
Cell Mol Neurobiol ; 44(1): 33, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38625414

RESUMEN

Subarachnoid hemorrhage (SAH) is associated with high mortality and disability rates, and secondary white matter injury is an important cause of poor prognosis. However, whether brain capillary pericytes can directly affect the differentiation and maturation of oligodendrocyte precursor cells (OPCs) and subsequently affect white matter injury repair has still been revealed. This study was designed to investigate the effect of tissue inhibitor of metalloproteinase-3 (TIMP-3) for OPC differentiation and maturation. PDGFRßret/ret and wild-type C57B6J male mice were used to construct a mouse model of SAH via endovascular perforation in this study. Mice were also treated with vehicle, TIMP-3 RNAi or TIMP-3 RNAi + TIMP-3 after SAH. The effect of TIMP-3 on the differentiation and maturation of OPCs was determined using behavioral score, ELISA, transmission electron microscopy, immunofluorescence staining and cell culture. We found that TIMP-3 was secreted mainly by pericytes and that SAH and TIMP-3 RNAi caused a significant decrease in the TIMP-3 content, reaching a nadir at 24 h, followed by gradual recovery. In vitro, the myelin basic protein content of oligodendrocytes after oxyhemoglobin treatment was increased by TIMP-3 overexpression. The data indicates TIMP-3 could promote the differentiation and maturation of OPCs and subsequently improve neurological outcomes after SAH. Therefore, TIMP-3 could be beneficial for repair after white matter injury and could be a potential therapeutic target in SAH.


Asunto(s)
Células Precursoras de Oligodendrocitos , Hemorragia Subaracnoidea , Sustancia Blanca , Masculino , Animales , Ratones , Inhibidor Tisular de Metaloproteinasa-3 , Encéfalo
14.
Eur J Neurol ; 31(1): e16096, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37877685

RESUMEN

BACKGROUND AND PURPOSE: The aim was to investigate the neurological complications associated with coronavirus disease 19 (COVID-19) during the 2022 Omicron wave. METHODS AND ANALYSIS: The medical records of a cohort of people admitted to neurological wards of three participating tertiary centres in Sichuan from 12 December 2022 to 12 January 2023 were reviewed. Demographics and clinical data were obtained and analysed with an interest in COVID-19-related new-onset or worse neurological symptoms. The current data were also compared in two centres with similar data from the same period 12 months earlier. RESULTS: In all, 790 people were enrolled, of whom 436 were positive for COVID-19. Ninety-nine had new onset COVID-related neurological problems, or their known neurological condition deteriorated during the wave. There was a significant difference in demographics from the findings amongst admissions 12 months earlier as there was an increase in the average age, the incidence of encephalitis and encephalopathy, and mortality rates. One hundred and one received COVID-specific antivirals, intravenous glucocorticoids and intravenous immunoglobulin therapy. No differences were seen between these and those who did not use them. CONCLUSION: New-onset neurological conditions, particularly encephalitis and encephalopathy, increased significantly during this period. Deterioration of existing neurological conditions, such as seizure exacerbation, was also observed. A large-scale treatment trial of people with COVID-19 infection presenting with neurological disorders is still needed.


Asunto(s)
Encefalopatías , COVID-19 , Encefalitis , Humanos , Estudios de Cohortes , COVID-19/complicaciones , COVID-19/epidemiología , China/epidemiología , Convulsiones
15.
Cell Biol Int ; 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38973665

RESUMEN

Neonatal necrotizing enterocolitis (NEC) is a critical digestive disorder frequently affecting premature infants. Characterized by intestinal inflammation caused by activated M1 macrophages, modulation of macrophage polarization is considered a promising therapeutic strategy for NEC. It has been demonstrated that the growth factor-like protein progranulin (PGRN), which plays roles in a number of physiological and pathological processes, can influence macrophage polarization and exhibit anti-inflammatory characteristics in a number of illnesses. However, its role in NEC is yet to be investigated. Our research showed that the levels of PGRN were markedly elevated in both human and animal models of NEC. PGRN deletion in mice worsens NEC by encouraging M1 polarization of macrophages and escalating intestinal damage and inflammation. Intravenous administration of recombinant PGRN to NEC mice showed significant survival benefits and protective effects, likely due to PGRN's ability to inhibit M1 polarization and reduce the release of pro-inflammatory factors. Our findings shed new light on PGRN's biological role in NEC and demonstrate its potential as a therapeutic target for the disease.

16.
Environ Sci Technol ; 58(23): 9980-9990, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38819024

RESUMEN

Exposure to fine particulate matter (PM2.5) during pregnancy has been inversely associated with neonatal neurological development. However, the associations of exposure to specific PM2.5 constituents with neonatal neurological development remain unclear. We investigated these associations and examined the mediating role of meconium metabolites in a Chinese birth cohort consisting of 294 mother-infant pairs. Our results revealed that exposure to PM2.5 and its specific constituents (i.e., organic matter, black carbon, sulfate, nitrate, and ammonium) in the second trimester, but not in the first or third trimester, was inversely associated with the total neonatal behavioral neurological assessment (NBNA) scores. The PM2.5 constituent mixture in the second trimester was also inversely associated with NBNA scores, and sulfate was identified as the largest contributor. Furthermore, meconium metabolome analysis identified four metabolites, namely, threonine, lysine, leucine, and saccharopine, that were associated with both PM2.5 constituents and NBNA scores. Threonine was identified as an important mediator, accounting for a considerable proportion (14.53-15.33%) of the observed inverse associations. Our findings suggest that maternal exposure to PM2.5 and specific constituents may adversely affect neonatal behavioral development, in which meconium metabolites may play a mediating role.


Asunto(s)
Exposición Materna , Meconio , Material Particulado , Humanos , Femenino , Meconio/química , Embarazo , Estudios de Cohortes , Recién Nacido , Adulto , Contaminantes Atmosféricos
17.
Thromb J ; 22(1): 11, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38229151

RESUMEN

INTRODUCTION: Sepsis is a global public health burden. Deep vein thrombosis (DVT) is the third most common cause of death from cardiovascular disease after heart attacks and strokes. We designed this experiment to investigate the factors influencing DVT formation in patients with sepsis. METHODS: In this survey, 918 septic patients admitted to Peking Union Medical College Hospital, who underwent DVT screening were enrolled. The data were collected from June 8, 2013 to October 12, 2022. The differences between septic patients with and without DVT were studied from following aspects: basic information, comorbidities, inflammatory cytokines, albumin, source of infection, sequential organ failure assessment (SOFA) score, coagulation and prognosis. MAIN RESULTS: In this study, the prevalence of DVT in patients with sepsis was 0.23. Elderly patients with sepsis were prone to DVT (p value < 0.001). In terms of comorbidities, septic patients with hypertension and atrial fibrillation were prone to DVT (p value 0.045 and 0.048). Inflammatory cytokines, such as procalcitonin (PCT), C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, had no significant correlation with DVT in patients with sepsis (p value 0.364, 0.882, 0.912, 0.789, 0.245, and 0.780). Levels of serum albumin correlated with DVT in patients with sepsis (p value 0.003). The SOFA total score had no relationship with DVT formation (p value 0.254). Coagulation and respiration function were negatively correlated with DVT (p value 0.018). Liver function was positively correlated with DVT (p value 0.020). Patients in the DVT group had longer duration of mechanical ventilation and longer intensive care unit (ICU) stays (p value < 0.001 and 0.006). There was no significant difference in survival in septic patients with and without DVT (p value 0.868). CONCLUSIONS: The SOFA total score had no relationship with DVT formation. The function of each organ had different effects on DVT formation. Better coagulation and respiration function, easier DVT formation. Poorer liver function, easier DVT formation. DVT was associated with longer duration of mechanical ventilation and longer ICU stays.

18.
Appl Microbiol Biotechnol ; 108(1): 45, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38175238

RESUMEN

Veillonella spp. are Gram-negative opportunistic pathogens present in the respiratory, digestive, and reproductive tracts of mammals. An abnormal increase in Veillonella relative abundance in the body is closely associated with periodontitis, inflammatory bowel disease, urinary tract infections, and many other diseases. We designed a pair of primers and a probe based on the 16S rRNA gene sequences of Veillonella and conducted real-time quantitative PCR (qPCR) and droplet digital PCR (ddPCR) to quantify the abundance of Veillonella in fecal samples. These two methods were tested for specificity and sensitivity using simulated clinical samples. The sensitivity of qPCR was 100 copies/µL, allowing for the accurate detection of a wide range of Veillonella concentrations from 103 to 108 CFU/mL. The sensitivity of ddPCR was 11.3 copies/µL, only allowing for the accurate detection of Veillonella concentrations from 101 to 104 CFU/mL because of the limited number of droplets generated by ddPCR. ddPCR is therefore more suitable for the detection of low-abundance Veillonella samples. To characterize the validity of the assay system, clinical samples from children with inflammatory bowel disease were collected and analyzed, and the results were verified using isolation methods. We conclude that molecular assays targeting the 16S rRNA gene provides an important tool for the rapid diagnosis of chronic and infectious diseases caused by Veillonella and also supports the isolation and identification of Veillonella for research purposes. KEY POINTS: • With suitable primer sets, the qPCR has a wider detection range than ddPCR. • ddPCR is suitable for the detection of low-abundance samples. • Methods successfully guided the isolation of Veillonella in clinical sample.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Veillonella , Niño , Humanos , Bioensayo , Enfermedades Inflamatorias del Intestino/diagnóstico , Mamíferos , Reacción en Cadena en Tiempo Real de la Polimerasa , ARN Ribosómico 16S/genética
19.
BMC Public Health ; 24(1): 2064, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39085819

RESUMEN

The association between ambient temperature and mental health has been explored previously. However, research on the psychological effect of temperature in vulnerable groups and neighborhood scales have been scarce. Based on the survey and temperature data collected from 20 neighborhoods in Guangzhou, China, this study estimated the association between ambient temperature and community mental health among the elderly, adopting a fixed-effects methodology. According to this empirical analysis, compared to a comfortable temperature range of 20℃-25℃, measures of worse mental health among elderly were significant in high and low temperatures with increases in negative outcomes observable at both ends of the temperature range, leading to the U-shaped relationship. Second, the association between ambient temperature and worse mental health was found in the subcategories of gender, income, and symptom events. Specifically, from the hot temperature aspect, elderly males were more sensitive than elderly females. The effect on the low was far more than on the middle-high income group, and the probability of each symptom of the elderly's mental health significantly increased. From the cool temperature aspect, the temperature in the range of 5ºC-10ºC was significantly associated with the probability of some symptoms (feeling down, not calm, downheartedness, and unhappiness) and the middle-high income group. Our research enriches the empirical research on ambient temperature and mental health from a multidisciplinary perspective and suggests the need for healthy aging and age-friendly planning in Chinese settings.


Asunto(s)
Salud Mental , Humanos , Masculino , China/epidemiología , Femenino , Anciano , Salud Mental/estadística & datos numéricos , Persona de Mediana Edad , Características de la Residencia/estadística & datos numéricos , Anciano de 80 o más Años , Dinámicas no Lineales , Temperatura , Calor/efectos adversos
20.
Food Microbiol ; 122: 104557, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38839221

RESUMEN

To investigate the potential antifungal mechanisms of rhizosphere Actinobacteria against Ceratocystis fimbriata in sweet potato, a comprehensive approach combining biochemical analyses and multi-omics techniques was employed in this study. A total of 163 bacterial strains were isolated from the rhizosphere soil of sweet potato. Among them, strain MEPS155, identified as Streptomyces djakartensis, exhibited robust and consistent inhibition of C. fimbriata mycelial growth in in vitro dual culture assays, attributed to both cell-free supernatant and volatile organic compounds. Moreover, strain MEPS155 demonstrated diverse plant growth-promoting attributes, including the production of indole-3-acetic acid, 1-aminocyclopropane-1-carboxylate deaminase, phosphorus solubilization, nitrogen fixation, and enzymatic activities such as cellulase, chitinase, and protease. Notably, strain MEPS155 exhibited efficacy against various sweet potato pathogenic fungi. Following the inoculation of strain MEPS155, a significant reduction (P < 0.05) in malondialdehyde content was observed in sweet potato slices, indicating a potential protective effect. The whole genome of MEPS155 was characterized by a size of 8,030,375 bp, encompassing 7234 coding DNA sequences and 32 secondary metabolite biosynthetic gene clusters. Transcriptomic analysis revealed 1869 differentially expressed genes in the treated group that cultured with C. fimbriata, notably influencing pathways associated with porphyrin metabolism, fatty acid biosynthesis, and biosynthesis of type II polyketide products. These alterations in gene expression are hypothesized to be linked to the production of secondary metabolites contributing to the inhibition of C. fimbriata. Metabolomic analysis identified 1469 potential differently accumulated metabolites (PDAMs) when comparing MEPS155 and the control group. The up-regulated PDAMs were predominantly associated with the biosynthesis of various secondary metabolites, including vanillin, myristic acid, and protocatechuic acid, suggesting potential inhibitory effects on plant pathogenic fungi. Our study underscores the ability of strain S. djakartensis MEPS155 to inhibit C. fimbriata growth through the production of secretory enzymes or secondary metabolites. The findings contribute to a theoretical foundation for future investigations into the role of MEPS155 in postharvest black rot prevention in sweet potato.


Asunto(s)
Ascomicetos , Ipomoea batatas , Enfermedades de las Plantas , Rizosfera , Streptomyces , Ipomoea batatas/microbiología , Streptomyces/genética , Streptomyces/metabolismo , Streptomyces/aislamiento & purificación , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Ascomicetos/crecimiento & desarrollo , Ascomicetos/metabolismo , Ascomicetos/genética , Microbiología del Suelo , Antifúngicos/farmacología , Antifúngicos/metabolismo , Multiómica
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