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1.
Nature ; 618(7966): 799-807, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37316670

RESUMEN

Plants deploy receptor-like kinases and nucleotide-binding leucine-rich repeat receptors to confer host plant resistance (HPR) to herbivores1. These gene-for-gene interactions between insects and their hosts have been proposed for more than 50 years2. However, the molecular and cellular mechanisms that underlie HPR have been elusive, as the identity and sensing mechanisms of insect avirulence effectors have remained unknown. Here we identify an insect salivary protein perceived by a plant immune receptor. The BPH14-interacting salivary protein (BISP) from the brown planthopper (Nilaparvata lugens Stål) is secreted into rice (Oryza sativa) during feeding. In susceptible plants, BISP targets O. satvia RLCK185 (OsRLCK185; hereafter Os is used to denote O. satvia-related proteins or genes) to suppress basal defences. In resistant plants, the nucleotide-binding leucine-rich repeat receptor BPH14 directly binds BISP to activate HPR. Constitutive activation of Bph14-mediated immunity is detrimental to plant growth and productivity. The fine-tuning of Bph14-mediated HPR is achieved through direct binding of BISP and BPH14 to the selective autophagy cargo receptor OsNBR1, which delivers BISP to OsATG8 for degradation. Autophagy therefore controls BISP levels. In Bph14 plants, autophagy restores cellular homeostasis by downregulating HPR when feeding by brown planthoppers ceases. We identify an insect saliva protein sensed by a plant immune receptor and discover a three-way interaction system that offers opportunities for developing high-yield, insect-resistant crops.


Asunto(s)
Hemípteros , Proteínas de Insectos , Oryza , Defensa de la Planta contra la Herbivoria , Proteínas de Plantas , Animales , Hemípteros/inmunología , Hemípteros/fisiología , Leucina/metabolismo , Nucleótidos/metabolismo , Oryza/crecimiento & desarrollo , Oryza/inmunología , Oryza/metabolismo , Oryza/fisiología , Defensa de la Planta contra la Herbivoria/inmunología , Defensa de la Planta contra la Herbivoria/fisiología , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Proteínas de Insectos/metabolismo , Autofagia
2.
PLoS Biol ; 20(11): e3001856, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36318514

RESUMEN

Feingold syndrome type 1, caused by loss-of-function of MYCN, is characterized by varied phenotypes including esophageal and duodenal atresia. However, no adequate model exists for studying the syndrome's pathological or molecular mechanisms, nor is there a treatment strategy. Here, we developed a zebrafish Feingold syndrome type 1 model with nonfunctional mycn, which had severe intestinal atresia. Single-cell RNA-seq identified a subcluster of intestinal cells that were highly sensitive to Mycn, and impaired cell proliferation decreased the overall number of intestinal cells in the mycn mutant fish. Bulk RNA-seq and metabolomic analysis showed that expression of ribosomal genes was down-regulated and that amino acid metabolism was abnormal. Northern blot and ribosomal profiling analysis showed abnormal rRNA processing and decreases in free 40S, 60S, and 80S ribosome particles, which led to impaired translation in the mutant. Besides, both Ribo-seq and western blot analysis showed that mTOR pathway was impaired in mycn mutant, and blocking mTOR pathway by rapamycin treatment can mimic the intestinal defect, and both L-leucine and Rheb, which can elevate translation via activating TOR pathway, could rescue the intestinal phenotype of mycn mutant. In summary, by this zebrafish Feingold syndrome type 1 model, we found that disturbance of ribosomal biogenesis and blockage of protein synthesis during development are primary causes of the intestinal defect in Feingold syndrome type 1. Importantly, our work suggests that leucine supplementation may be a feasible and easy treatment option for this disease.


Asunto(s)
Microcefalia , Pez Cebra , Animales , Proteína Proto-Oncogénica N-Myc , Pez Cebra/metabolismo , Microcefalia/genética , Serina-Treonina Quinasas TOR/metabolismo , Leucina
3.
Clin Immunol ; 263: 110232, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38701960

RESUMEN

IgA nephropathy (IgAN), which has been confirmed as a complement mediated autoimmune disease, is also one form of glomerulonephritis associated with COVID-19. Here, we aim to investigate the clinical and immunological characteristics of patients with IgAN after COVID-19. The level of plasma level of C5a (p < 0.001), soluble C5b-9 (p = 0.018), FHR5 (p < 0.001) were all significantly higher in Group CoV (33 patients with renal biopsy-proven IgAN experienced COVID-19) compared with Group non-CoV (44 patients with IgAN without COVID-19), respectively. Compared with Group non-CoV, the intensity of glomerular C4d (p = 0.017) and MAC deposition (p < 0.001) and Gd-IgA1 deposition (p = 0.005) were much stronger in Group CoV. Our finding revealed that for IgAN after COVID-19, mucosal immune responses to SARS-CoV-2 infection may result in the overactivation of systemic and renal local complement system, and increased glomerular deposition of Gd-IgA1, which may lead to renal dysfunction and promote renal progression in IgAN patients.


Asunto(s)
COVID-19 , Glomerulonefritis por IGA , SARS-CoV-2 , Humanos , Glomerulonefritis por IGA/inmunología , Glomerulonefritis por IGA/sangre , COVID-19/inmunología , COVID-19/complicaciones , Femenino , Masculino , Adulto , SARS-CoV-2/inmunología , Persona de Mediana Edad , Activación de Complemento/inmunología , Proteínas del Sistema Complemento/inmunología , Proteínas del Sistema Complemento/metabolismo , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Glomérulos Renales/patología , Glomérulos Renales/inmunología , Complemento C5a/inmunología , Complemento C5a/metabolismo
4.
J Transl Med ; 22(1): 595, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926732

RESUMEN

BACKGROUND: Variations exist in the response of patients with Crohn's disease (CD) to ustekinumab (UST) treatment, but the underlying cause remains unknown. Our objective was to investigate the involvement of immune cells and identify potential biomarkers that could predict the response to interleukin (IL) 12/23 inhibitors in patients with CD. METHODS: The GSE207022 dataset, which consisted of 54 non-responders and 9 responders to UST in a CD cohort, was analyzed. Differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Least absolute shrinkage and selection operator (LASSO) regression was used to screen the most powerful hub genes. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performances of these genes. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used to estimate the proportions of immune cell types. These significantly altered genes were subjected to cluster analysis into immune cell-related infiltration. To validate the reliability of the candidates, patients prescribed UST as a first-line biologic in a prospective cohort were included as an independent validation dataset. RESULTS: A total of 99 DEGs were identified in the integrated dataset. GO and KEGG analyses revealed significant enrichment of immune response pathways in patients with CD. Thirteen genes (SOCS3, CD55, KDM5D, IGFBP5, LCN2, SLC15A1, XPNPEP2, HLA-DQA2, HMGCS2, DDX3Y, ITGB2, CDKN2B and HLA-DQA1), which were primarily associated with the response versus nonresponse patients, were identified and included in the LASSO analysis. These genes accurately predicted treatment response, with an area under the curve (AUC) of 0.938. T helper cell type 1 (Th1) cell polarization was comparatively strong in nonresponse individuals. Positive connections were observed between Th1 cells and the LCN2 and KDM5D genes. Furthermore, we employed an independent validation dataset and early experimental verification to validate the LCN2 and KDM5D genes as effective predictive markers. CONCLUSIONS: Th1 cell polarization is an important cause of nonresponse to UST therapy in patients with CD. LCN2 and KDM5D can be used as predictive markers to effectively identify nonresponse patients. TRIAL REGISTRATION: Trial registration number: NCT05542459; Date of registration: 2022-09-14; URL: https://www. CLINICALTRIALS: gov .


Asunto(s)
Biología Computacional , Enfermedad de Crohn , ARN Mensajero , Ustekinumab , Adulto , Femenino , Humanos , Masculino , Análisis por Conglomerados , Biología Computacional/métodos , Enfermedad de Crohn/genética , Enfermedad de Crohn/tratamiento farmacológico , Perfilación de la Expresión Génica , Ontología de Genes , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Estudios Prospectivos , Reproducibilidad de los Resultados , ARN Mensajero/genética , ARN Mensajero/metabolismo , Curva ROC , Transcriptoma/genética , Ustekinumab/uso terapéutico , Ustekinumab/farmacología
5.
FASEB J ; 37(11): e23276, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37878291

RESUMEN

Acute kidney injury (AKI) and chronic kidney disease (CKD) are interconnected syndromes that represent a global public health challenge. Here, we identified a specific role of survival of motor neuron (SMN) in ischemia/reperfusion (I/R)-induced kidney injury and progression of CKD. SMN was an essential protein in all cell type and was reported to play important roles in multiple fundamental cellular homeostatic pathways. However, the function of SMN in experimental models of I/R-induced kidney fibrosis has not extensively studied. Genetic ablation of SMN or small interfering RNA-base knockdown of SMN expression aggravated the tubular injury and interstitial fibrosis. Administration of scAAV9-CB-SMN or epithelial cell overexpression of SMN reduced I/R-induced kidney dysfunction and attenuated AKI-to-CKD transition, indicating that SMN is vital for the preservation and recovery of tubular phenotype. Our data showed that the endoplasmic reticulum stress (ERS) induced by I/R was persistent and became progressively more severe in the kidney without SMN. On the contrary, overexpression of SMN prevented against I/R-induced ERS and tubular cell damage. In summary, our data collectively substantiate a critical role of SMN in regulating the ERS activation and phenotype of AKI-to-CKD transition that may contribute to renal pathology during injury and repair.


Asunto(s)
Lesión Renal Aguda , Insuficiencia Renal Crónica , Daño por Reperfusión , Proteína 1 para la Supervivencia de la Neurona Motora , Humanos , Lesión Renal Aguda/genética , Estrés del Retículo Endoplásmico/genética , Fibrosis , Haploinsuficiencia , Isquemia , Riñón , Insuficiencia Renal Crónica/genética , Daño por Reperfusión/genética , Proteína 1 para la Supervivencia de la Neurona Motora/genética
6.
J Org Chem ; 89(17): 12508-12513, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39135492

RESUMEN

Thioesters make up an important class of bioactive compounds. Due to their chemoselectivity, they have been widely used in the synthesis of a wide range of complex bioactive molecules and natural products. At present, chemists have developed a variety of methods for the preparation of thioester compounds. However, these methods usually require the use of transition metal catalysis or harsh reaction conditions. The strategy of synthesizing thioester compounds via visible light-induced electron donor-acceptor (EDA) complex reactions avoids the problems associated with conventional methods through the development of photocatalysis. Here we report a sustainable method for thiocarbonylating aryl sulfonium salts via a visible light-induced EDA complex process without transition metals.

7.
J Org Chem ; 89(11): 7899-7912, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38728220

RESUMEN

An efficient, practical, and metal-free protocol for the synthesis of silicon-containing isoindolin-1-ones and deuterated analogues via the synergistic combination of an organic photoredox and hydrogen atom transfer process is described. This strategy features mild reaction conditions, high atom economy, and excellent functional group compatibility, delivering a myriad of structurally diverse and valuable products with good to excellent yields.

8.
Org Biomol Chem ; 22(34): 6928-6932, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39119751

RESUMEN

A facile synthetic method for direct C(sp2)-H bond trifluoromethylation of 3-methylene-isoindolin-1-ones under visible-light-induced metal-free conditions is presented. This protocol features mild reaction conditions, broad substrate scope and excellent functional group tolerance, resulting in a range of structurally diverse trifluoromethylated products in good to excellent yields.

9.
BMC Gastroenterol ; 24(1): 36, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38229035

RESUMEN

BACKGROUND: Adenosquamous carcinoma is a rare sub-type of colorectal cancer with a poor prognosis. Little is known about its clinicopathological and molecular characteristics in Asian populations. This study aimed to investigate these features in a cohort of patients with adenosquamous carcinoma in the colorectum. METHODS: Tumor cases pathologically diagnosed with colorectal adenosquamous carcinoma were retrieved from the Sixth Affiliated Hospital, Sun Yat-sen University tissue archive between December 2012 and June 2020. Clinicopathological features, molecular characteristics, and oncology outcomes were analyzed. RESULTS: Among 18,139 cases of colorectal cancer, 11 were diagnosed with adenosquamous carcinoma, providing an incidence rate of 0.061%. The median overall survival (OS) was 14 months, and the expected 3-year OS rate was 29.6%. As of October 14, 2022, four cases had local recurrence and five had distant metastasis. KRAS gene mutations were found in four of seven patients (57.1%), and three out of eleven (27.3%) patients had mismatch repair-deficient (dMMR) tumors. CONCLUSIONS: Adenosquamous carcinoma is associated with a poor prognosis. Compared to other sub-types of colorectal cancer, a higher proportion of patients with dMMR and KRAS mutations were observed. These findings suggested that more patients with adenosquamous carcinoma could benefit from targeted therapies, such as immunotherapy.


Asunto(s)
Neoplasias Encefálicas , Carcinoma Adenoescamoso , Neoplasias Colorrectales , Síndromes Neoplásicos Hereditarios , Humanos , Carcinoma Adenoescamoso/genética , Carcinoma Adenoescamoso/patología , Pronóstico , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias Colorrectales/patología , Estudios Retrospectivos
10.
Artículo en Inglés | MEDLINE | ID: mdl-38972728

RESUMEN

BACKGROUND AND AIM: There is a pressing need for non-invasive preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). This study investigates the potential of exosome-derived mRNA in plasma as a biomarker for diagnosing MVI. METHODS: Patients with suspected HCC undergoing hepatectomy were prospectively recruited for preoperative peripheral blood collection. Exosomal RNA profiling was conducted using RNA sequencing in the discovery cohort, followed by differential expression analysis to identify candidate targets. We employed multiplexed droplet digital PCR technology to efficiently validate them in a larger sample size cohort. RESULTS: A total of 131 HCC patients were ultimately enrolled, with 37 in the discovery cohort and 94 in the validation cohort. In the validation cohort, the expression levels of RSAD2, PRPSAP1, and HOXA2 were slightly elevated while CHMP4A showed a slight decrease in patients with MVI compared with those without MVI. These trends were consistent with the findings in the discovery cohort, although they did not reach statistical significance (P > 0.05). Notably, the expression level of exosomal PRPSAP1 in plasma was significantly higher in patients with more than 5 MVI than in those without MVI (0.147 vs 0.070, P = 0.035). CONCLUSION: This study unveils the potential of exosome-derived PRPSAP1 in plasma as a promising indicator for predicting MVI status preoperatively.

11.
Environ Res ; 262(Pt 2): 119922, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39237020

RESUMEN

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) is perceived as an emerging environmental endocrine disruptor, which have been linked to children neurodevelopment. However, the potential mechanisms are not clear. Brain-derived neurotrophic factor (BDNF) is a vital protein in neurodevelopment, and the associations between PFAS exposure and BDNF require exploration. OBJECTIVE: We aimed to explore the relationships between PFAS exposure and the levels of BDNF in cord serum. METHODS: A total of 1,189 mother-infant dyads from the Sheyang Mini Birth Cohort Study (SMBCS) were enrolled. The levels of 12 PFAS and BDNF were measured in cord serum. We utilized generalized linear models (GLMs), quantile-based g-computation (QGC) models, and Bayesian Kernel Machine Regression (BKMR) models to explore the relationships between single and mixed PFAS exposure and BDNF concentration. Additionally, the potential sex differences were explored by sex-stratified analysis. RESULTS: Median concentrations of the included 10 PFAS ranged from 0.04 to 3.97 µg/L. In the single chemical models, four PFAS congeners, namely perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), were negatively associated with BDNF levels in cord serum among females only (ß: -0.116 to -0.062, p < 0.05). In the BKMR models of total mother-infant dyads and female fetuses, the significant negative relationships between PFAS mixtures and BDNF were observed, and PFUnDA was identified as an important contributor (Posterior inclusion probability, PIP = 0.8584 for the total subjects; PIP = 0.8488 for the females). PFOS was another important driver based on the mixture approaches. CONCLUSIONS: We found that PFNA, PFOS, PFDA, and PFUnDA were associated with decreased BDNF concentration in the females, although the causal inference might be limited. PFAS mixtures were also negatively linked with BDNF levels in the total mother-infant pairs and female fetuses. The adverse effect of PFAS exposure on fetal BDNF levels might be sex-specific.

12.
Environ Res ; 261: 119766, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39127330

RESUMEN

BACKGROUND: Environmental phenols were recognized as endocrine disrupting chemicals (EDCs). However, their impact on childhood anthropometric measures and blood pressure (BP) is still inconclusive. Limited studies have simultaneously considered prenatal and childhood exposures in analyzing mixtures of phenols. OBJECTIVE: We investigated the relationships between combined prenatal and childhood exposures (two periodic exposures) to phenol mixtures and anthropometric measure and BP, to further identify the vulnerable periods of phenol exposure and to explore the important individual contribution of each phenol. METHODS: We analyzed 434 mother-child dyads from the Sheyang Mini Birth Cohort Study (SMBCS). The urinary concentrations of 11 phenolic compounds were measured using gas chromatography tandem mass spectrometry. Generalized linear regression models (GLMs) and hierarchical Bayesian Kernel Machine Regression (hBKMR) were used to examine the effects of individual phenolic compounds at each period and of two periodic exposures. RESULTS: In the single-chemical analysis, prenatal or childhood exposure to specific phenols, especially Benzopheone-3 (BP3), 4-tert-Octylphenol (4-tOP), and Benzyl paraben (BePB) were associated with BMI z-scores (BAZ), Waist-to-height ratio (WHtR), and BP. In the hBKMR models, two periodic exposures to phenol mixtures had a U-shaped association with WHtR, primarily driven by childhood BePB exposure. Moreover, among the phenol mixtures analysis, childhood 4-tOP exposure was identified as the primary contributor to the positive association with diastolic BP. Concurrent exposure to phenol mixtures resulted in greater susceptibility. CONCLUSIONS: We found that prenatal and childhood exposure to phenol mixtures might influence childhood obesity and elevate blood pressure levels. Concurrent exposure to 4-tOP may be the primary driver of the positive associations with BP.


Asunto(s)
Presión Sanguínea , Fenoles , Efectos Tardíos de la Exposición Prenatal , Humanos , Fenoles/orina , Fenoles/toxicidad , Fenoles/efectos adversos , Femenino , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Presión Sanguínea/efectos de los fármacos , Embarazo , Masculino , Niño , Contaminantes Ambientales/orina , Disruptores Endocrinos/orina , Disruptores Endocrinos/toxicidad , Disruptores Endocrinos/efectos adversos , Antropometría , Adulto , Preescolar , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Estudios de Cohortes
13.
Skin Res Technol ; 30(6): e13791, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38895902

RESUMEN

BACKGROUND: Hypertrophic scars (HS) are a common disfiguring condition in daily clinical encounters which brings a lot of anxieties and concerns to patients, but the treatment options of HS are limited. Black cloth ointment (BCO), as a cosmetic ointment applicable to facial scars, has shown promising therapeutic effects for facial scarring. However, the molecular mechanisms underlying its therapeutic effects remain unclear. MATERIAL AND METHODS: Network pharmacology was first applied to analyze the major active components of BCO and the related signaling pathways. Subsequently, rabbit ear scar model was successfully established to determine the pharmacological effects of BCO and its active component ß-elemene on HS. Finally, the molecular mechanism of BCO and ß-elemene was analyzed by Western blot. RESULTS: Through the network pharmacology, it showed that ß-elemene was the main active ingredient of BCO, and it could significantly improve the pathological structure of HS and reduce collagen deposition. BCO and ß-elemene could increase the expression of ER stress-related markers and promote the increase of apoptotic proteins in the Western blot experiment and induce the apoptosis of myofibroblasts. CONCLUSIONS: Our findings indicate that the material basis for the scar-improving effects of the BCO is ß-elemene, and cellular apoptosis is the key mechanism through which the BCO and ß-elemene exert their effects.


Asunto(s)
Cicatriz Hipertrófica , Modelos Animales de Enfermedad , Farmacología en Red , Pomadas , Sesquiterpenos , Cicatriz Hipertrófica/tratamiento farmacológico , Cicatriz Hipertrófica/patología , Cicatriz Hipertrófica/metabolismo , Conejos , Animales , Farmacología en Red/métodos , Sesquiterpenos/farmacología , Humanos , Apoptosis/efectos de los fármacos , Femenino , Masculino
14.
Knee Surg Sports Traumatol Arthrosc ; 32(6): 1622-1630, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38586974

RESUMEN

PURPOSE: Both the arthroscopic Broström-Gould and Lasso-loop stitch techniques are commonly used to treat chronic lateral ankle instability (CLAI). The purpose of this study is to introduce an arthroscopic one-step outside-in Broström-Gould (AOBG) technique and compare the mid-term outcomes of the AOBG technique and Lasso-loop stitch technique. METHODS: All CLAI patients who underwent arthroscopic lateral ankle stabilization surgery in our department from 2018 to 2019 were retrospectively enrolled. The patients were divided into two groups according to the surgical methods employed: the AOBG technique (Group A) and the Lasso-loop technique (Group B). The visual analogue scale pain score, American Orthopaedic Foot and Ankle Society ankle hindfoot score, Tegner activity score and Karlsson-Peterson score were evaluated preoperatively and during the follow-up from June to December 2022. The surgical duration, return to sports, sprain recurrence and surgical complications were also recorded and compared. RESULTS: A total of 74 patients (Group A, n = 42; Group B, n = 32) were included in this study with a mean follow-up of 39 months. No statistically significant differences were observed in demographic parameters or follow-up time between the two groups. Postoperative clinical scores indicated a significant improvement (all with p < 0.001) with no significant difference between the two groups (not significant [n.s.]). There was no significant difference in the surgical duration (46.1 vs. 49.7 min, n.s.), return to sports (92.9% vs. 93.8%, n.s.), or sprain recurrence (4.8% vs. 6.3%, n.s.). Only two cases in Group A reported knot irritation (4.8% vs. 0, n.s.), and one case in Group A experienced local skin numbness (0 vs. 3.1%, n.s.), with no significant difference. CONCLUSION: Both the AOBG and Lasso-loop stitch techniques yielded comparable favourable mid-term outcomes and return to sports with a low rate of surgical complications. Both procedures could be feasible strategies for CLAI patients. LEVEL OF EVIDENCE: Level III.


Asunto(s)
Artroscopía , Inestabilidad de la Articulación , Técnicas de Sutura , Humanos , Inestabilidad de la Articulación/cirugía , Artroscopía/métodos , Masculino , Femenino , Estudios Retrospectivos , Adulto , Enfermedad Crónica , Resultado del Tratamiento , Recurrencia , Ligamentos Laterales del Tobillo/cirugía , Volver al Deporte , Articulación del Tobillo/cirugía , Tempo Operativo , Dimensión del Dolor , Adulto Joven
15.
J Clin Rheumatol ; 30(4): 138-144, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38351510

RESUMEN

BACKGROUND: Although observational studies have revealed associations between idiopathic inflammatory myopathies (IIMs) and lung cancer (LC), they have not established a causal relationship between these 2 conditions. METHODS: We used a 2-sample Mendelian randomization approach to examine the bidirectional causal associations between IIMs and LC, using single-nucleotide polymorphisms selected from high-quality genome-wide association studies in the FinnGen database. Sensitivity analyses were conducted to assess potential heterogeneity and pleiotropy impacts on the Mendelian randomization results. RESULTS: Our analysis demonstrated a positive causal effect of genetically increased IIM risk on LC (odds ratio, 1.114; 95% confidence interval, 1.057-1.173; p = 5.63 × 10 -5 ), particularly on the lung squamous cell carcinoma subtype (odds ratio, 1.168, 95% confidence interval, 1.049-1.300, p = 0.00451), but not on lung adenocarcinoma or small cell lung cancer. No causal effect of LC on IIMs was identified. Sensitivity analyses indicated that horizontal pleiotropy was unlikely to influence causality, and leave-one-out analysis confirmed that the observed associations were not driven by a single-nucleotide polymorphism. CONCLUSION: Our findings offer compelling evidence of a positive causal relationship between IIMs and LC, particularly with regard to lung squamous cell carcinoma, in the European population. Conversely, there is no evidence of LC causing IIMs. We recommend that LC diagnosis consider the specific characteristics of IIMs.


Asunto(s)
Estudio de Asociación del Genoma Completo , Neoplasias Pulmonares , Análisis de la Aleatorización Mendeliana , Miositis , Polimorfismo de Nucleótido Simple , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/etiología , Miositis/genética , Miositis/epidemiología , Miositis/diagnóstico , Predisposición Genética a la Enfermedad , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/etiología , Causalidad
16.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(4): 878-885, 2024 Jul 20.
Artículo en Zh | MEDLINE | ID: mdl-39170014

RESUMEN

Objective: To investigate the ameliorative effect of tanshinone ⅡA (Tan) on osteoarticular degeneration in ovariectomized rats (a postmenopausal estrogen deficiency model) and the mechanisms involved. Methods: Eight-week-old female Sprague Dawley (SD) rats were randomly allocated to 5 groups (n=10 each), including a Sham operation group (Sham), an ovariectomy group (OVX), and low, medium, and high-dose Tan groups. Eight weeks after bilateral ovariectomy, the rats in the low, medium, and high-dose Tan groups were treated with Tan at the doses of 5, 10, and 20 mg/kg for a duration of 28 days. Evaluation of the rat articular cartilage was performed using X-ray imaging, anatomical observation, hematoxylin and eosin (H&E) staining, and toluidine blue staining. Immunohistochemistry was performed to assess the expression levels of transforming growth factor ß1 (TGF-ß1), phosphorylated-smad2 (p-Smad2), type Ⅱ collagen (CⅡ), matrix metalloproteinase 9 (MMP-9), and MMP-13 in the cartilage tissue. Results: The knee joints of the OVX rats exhibited narrowed joint spaces, osteophyte formation, cartilage erosion or even localized cartilage cracks, faded methylene blue staining on the cartilage surface, disordered arrangement of chondrocytes, unclear or interrupted tidal line, and increased Kellgren-Lawrence grading, Pelletier grading, Mankin grading, and OARSI scores compared to those of the Sham group (P<0.01), as revealed by X-ray imaging, anatomical observation, and histological examination results. Tan ameliorated the degenerative changes in the knee joint caused by OVX in a dose-dependent manner while improving Kellgren-Lawrence grading, Pelletier grading, Mankin grading, and OARSI scores. Immunohistochemistry findings showed that TGF-ß1, p-Smad2, and CⅡ expression levels were significantly increased (P<0.01), while MMP-9 and MMP-13 expression levels were significantly decreased (P<0.01) in the articular cartilage of the Tan group compared to those of the OVX group, with all these effects being dose-dependent. Conclusion: Tan mitigates articular cartilage degeneration in ovariectomized rats, which may be related to the regulation of TGF-ß1/Smad2/MMPs signaling pathway.


Asunto(s)
Abietanos , Cartílago Articular , Ovariectomía , Ratas Sprague-Dawley , Transducción de Señal , Proteína Smad2 , Factor de Crecimiento Transformador beta1 , Animales , Femenino , Factor de Crecimiento Transformador beta1/metabolismo , Ratas , Abietanos/farmacología , Abietanos/uso terapéutico , Transducción de Señal/efectos de los fármacos , Proteína Smad2/metabolismo , Cartílago Articular/metabolismo , Cartílago Articular/efectos de los fármacos , Cartílago Articular/patología , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , Colágeno Tipo II/metabolismo
17.
Eur J Immunol ; 52(12): 2010-2012, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36153835

RESUMEN

We found an elevation of circulating TFH13 cell subset in asthmatic children and the frequency of TFH13 cells positively correlated with the plasma dust mite-specific IgE levels. These results indicated that TFH13 cell subset may be responsible for the immunopathogenesis of excessive IgE accumulation in children with allergic asthma.


Asunto(s)
Linfocitos T Colaboradores-Inductores , Humanos , Niño
18.
Biochem Biophys Res Commun ; 683: 149114, 2023 11 26.
Artículo en Inglés | MEDLINE | ID: mdl-37857164

RESUMEN

Long noncoding RNA (lncRNA) is implicated in both cancer development and pain process. However, the role of lncRNA in the development of cancer-induced bone pain (CIBP) is unclear. LncRNA NONRATT014888.2 is highly expressed in tibia related dorsal root ganglions (DRGs) in CIBP rats which function is unknown. CIBP was induced by injection of Walker 256 mammary gland tumor cells into the tibia canal of female SD rats. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) of rats were measured. Down-regulation of NONRATT014888.2 by siRNA in CIBP rats markedly attenuated hind-paw mechanical pain hypersensitivity. LncRNA-predicted target mRNAs analysis and mRNA sequencing results cued Socs3, Npr3 were related with NONRATT014888.2. Intrathecal injection of NONRATT014888.2-siR206 upregulated Npr3 both in mRNA and protein level. Npr3 was co-expressed in NONRATT014888.2-positive DRGs neurons and mainly located in cytoplasm, but not in Glial fibrillary acidic protein (GFAP)-positive cells. Intrathecal injection of ADV-Npr3 upregulated Npr3 expression and enhanced the PWT of CIBP rats. Our results suggest that upregulated lncRNA NONRATT014888.2 contributed to hyperalgesia in CIBP rats, and the mechanism may through downregulation of Npr3.


Asunto(s)
Neoplasias Óseas , Dolor en Cáncer , Neoplasias , ARN Largo no Codificante , Ratas , Femenino , Animales , ARN Largo no Codificante/genética , Regulación hacia Abajo , Ratas Sprague-Dawley , Dolor/genética , Dolor/metabolismo , Dolor en Cáncer/genética , Dolor en Cáncer/patología , Hiperalgesia/genética , ARN Mensajero/metabolismo , Péptidos Natriuréticos/metabolismo , Neoplasias Óseas/complicaciones , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo
19.
J Org Chem ; 88(20): 14351-14356, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37802501

RESUMEN

Herein, we present a decarboxylative thiocarbonylation of aryl and alkenyl sulfonium salts with oxalic acid monothioethers (OAMs), which can be achieved by visible light-accelerated palladium catalysis. Sulfonium salts are widely available, and OAM is an easily accessible and stored reagent; this mild reaction method can also be used for the synthesis of different types of thioester compounds. The reaction represents a new application of visible light-accelerated palladium catalysis in catalytic decarboxylative cross-couplings.

20.
Microb Ecol ; 85(4): 1288-1299, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-35522265

RESUMEN

Microbial co-culture simulates the natural ecosystem through the combination of artificial microbes. This approach has been widely applied in the study of activating silent genes to reveal novel secondary metabolites. However, there are still challenges in determining the biosynthetic pathways. In this study, the effects of microbial co-culture on the morphology of the microbes were verified by the morphological observation. Subsequently, through the strategy combining substrate feeding, stable isotope labeling, and gene expression analysis, the biosynthetic pathways of five benzoic acid derivatives N1-N4 and N7 were demonstrated: the secondary metabolite 10-deoxygerfelin of A. sydowii acted as an inducer to induce B. subtilis to produce benzoic acid, which was further converted into 3-OH-benzoic acid by A. sydowii. Subsequently, A. sydowii used 3-OH-benzoic acid as the substrate to synthesize the new compound N2, and then N1, N3, N4, and N7 were biosynthesized upon the upregulation of hydrolase, hydroxylase, and acyltransferase during co-culture. The plate zone analysis suggested that the biosynthesis of the newly induced compounds N1-N4 was mainly attributed to A. sydowii, and both A. sydowii and B. subtilis were indispensable for the biosynthesis of N7. This study provides an important basis for a better understanding of the interactions among microorganisms, providing new ideas for studying the biosynthetic pathways of the newly induced secondary metabolites in co-culture.


Asunto(s)
Bacillus subtilis , Ecosistema , Bacillus subtilis/genética , Técnicas de Cocultivo , Ácido Benzoico
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