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1.
Mol Carcinog ; 63(7): 1260-1274, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38607240

RESUMEN

DNA methylation, an epigenetic regulatory mechanism dictating gene transcription, plays a critical role in the occurrence and development of cancer. However, the molecular underpinnings of LINC00987 methylation in the regulation of lung adenocarcinoma (LUAD) remain elusive. This study investigated LINC00987 expression in LUAD patients through analysis of The Cancer Genome Atlas data sets. Quantitative real-time polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization assays were used to assess LINC00987 expression in LUAD. The bisulfite genomic sequence PCR (BSP) assay was used to determine the methylation levels of the LINC00987 promoter. The interaction between LINC00987 and SND1 was elucidated via immunoprecipitation and RNA pull-down assays. The functional significance of LINC00987 and SND1 in Calu-3 and NCI-H1688 cells was evaluated in vitro through CCK-8, EdU, Transwell, flow cytometry, and vasculogenic mimicry (VM) tube formation assays. LINC00987 expression decreased in LUAD concomitant with hypermethylation of the promoter region, while hypomethylation of the LINC00987 promoter in LUAD tissues correlated with tumor progression. Treatment with 5-Aza-CdR augmented LINC00987 expression and inhibited tumor growth. Mechanistically, LINC00987 overexpression impeded LUAD progression and VM through direct binding with SND1, thereby facilitating its phosphorylation and subsequent degradation. Additionally, overexpression of SND1 counteracted the adverse effects of LINC00987 downregulation on cell proliferation, apoptosis, cell migration, invasion, and VM in LUAD in vitro. In conclusion, this pioneering study focuses on the expression and function of LINC00987 and reveals that hypermethylation of the LINC00987 gene may contribute to LUAD progression. LINC00987 has emerged as a potential tumor suppressor gene in tumorigenesis through its binding with SND1 to facilitate its phosphorylation and subsequent degradation.


Asunto(s)
Adenocarcinoma del Pulmón , Proliferación Celular , Metilación de ADN , Progresión de la Enfermedad , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , ARN Largo no Codificante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Apoptosis , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Endonucleasas/genética , Endonucleasas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Fosforilación , Regiones Promotoras Genéticas , ARN Largo no Codificante/genética
2.
Clin Exp Immunol ; 215(1): 27-36, 2024 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-37724585

RESUMEN

The overlapping of two or more types of neural autoantibodies in one patient has increasingly been documented in recent years. The coexistence of myelin oligodendrocyte glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) antibodies is most common, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis, clinical manifestations, paraclinical features, and treatment of MNOS. Forty-nine patients with MNOS were included in this study. They were young males with a median onset age of 23 years. No tumors were observed in the patients, and 24 of them reported prodromal symptoms. The most common clinical presentations were psychiatric symptoms (35/49) and seizures (25/49). Abnormalities on magnetic resonance imaging involved the brainstem (11/49), cerebellum (9/49), and parietal lobe (9/49). Most patients mostly responded to immunotherapy and had a good long-term prognosis. However, the overall recurrence rate of MNOS was higher than that of mono antibody-positive diseases. The existence of concurrent NMDAR antibodies should be suspected in patients with MOG antibody-associated disease having psychiatric symptoms, seizures, movement disorders, or autonomic dysfunction. Similarly, serum MOG antibody testing should be performed when patients with anti-NMDAR encephalitis present with atypical clinical manifestations, such as visual impairment and limb weakness, and neuroradiological findings, such as optic nerve, spinal cord, or infratentorial involvement or meningeal enhancement. Early detection of the syndrome and prompt treatment can be beneficial for these patients, and maintenance immunosuppressive therapy is recommended due to the high overall recurrence rate of the syndrome.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Receptores de N-Metil-D-Aspartato , Humanos , Masculino , Adulto Joven , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Autoanticuerpos , Glicoproteína Mielina-Oligodendrócito , Convulsiones/complicaciones , Síndrome
3.
Neuroendocrinology ; 114(3): 223-233, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37827139

RESUMEN

INTRODUCTION: Women with epilepsy (WWE) are more likely to develop reproductive endocrine disorders, especially polycystic ovary syndrome (PCOS). This study aimed to explore the genetic factors of PCOS in WWE in hope of improving individual precision diagnosis and treatment. METHODS: WWE registered at West China Hospital between January 2022 and October 2022 were enrolled in this study. Demographic and epilepsy-related characteristics were recorded, and blood samples were collected for hormones, glucose metabolism testing, and whole-genome sequencing. RESULTS: After sample sequencing, quality control, and variants selection, association analyses were performed. Pathway analysis was performed to identify involved biological pathways. The overall and PCOS "burden score" of each individual were calculated to count the deleterious variants. A total of 95 WWE were included in this study and 19 patients were diagnosed with PCOS. WWE with PCOS showed a significantly different hormone profiles and a tendency of impaired glucose metabolism. The most commonly associated genes were ZFYVE28, COL19A1, SIK3, ANKK1, PPIG, and REPIN1. The top 3 canonical pathways are adipogenesis pathway, epoxysqualene biosynthesis signaling, and glutamate degradation signaling. The most significant common variant was rs11914038 located in gene CELSR1 and rs651748 located in gene ZBTB16. In human gene connectome prioritizations, ITGA9, PNPLA2, and DAB2 are the top 3 genes having the shortest distance to known PCOS genes. CONCLUSION: Genetic factors involved in the abnormal regulation of glucose and insulin metabolism are likely to be associated with the comorbidity of PCOS in WWE. Interventions targeting these processes should be given more priority in clinical practice.


Asunto(s)
Epilepsia , Síndrome del Ovario Poliquístico , Femenino , Humanos , Síndrome del Ovario Poliquístico/epidemiología , Síndrome del Ovario Poliquístico/genética , Epilepsia/epidemiología , Epilepsia/genética , Glucosa , China , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/uso terapéutico , Proteínas Adaptadoras Transductoras de Señales/metabolismo
4.
Sensors (Basel) ; 24(5)2024 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-38475020

RESUMEN

A detection and classification machine-learning model to inspect Thin Film Transistor Liquid Crystal Display (TFT-LCD) Mura is proposed in this study. To improve the capability of the machine-learning model to inspect panels' low-contrast grayscale images, piecewise gamma correction and a Selective Search algorithm are applied to detect and optimize the feature regions based on the Semiconductor Equipment and Materials International Mura (SEMU) specifications. In this process, matching the segment proportions to gamma values of piecewise gamma is a task that involves derivative-free optimization which is trained by adaptive particle swarm optimization. The detection accuracy rate (DAR) is approximately 93.75%. An enhanced convolutional neural network model is then applied to classify the Mura type through using the Taguchi experimental design method that identifies the optimal combination of the convolution kernel and the maximum pooling kernel sizes. A remarkable defect classification accuracy rate (CAR) of approximately 96.67% is ultimately achieved. The entire defect detection and classification process can be completed in about 3 milliseconds.

5.
Clin Exp Immunol ; 211(1): 78-83, 2023 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-36539337

RESUMEN

Neuronal surface antibody-mediated autoimmune encephalitis (NSAE) occurs across a wide age range. However, few studies focused on the onset age and their related characteristics. We aimed to explore the age-dependent profile of NSAE. A total of 134 patients with a definite diagnosis of NSAE were retrospectively enrolled from 3 tertiary hospitals between July 2014 and August 2020. Demographic, clinical, therapeutic, and prognostic data were collected and compared between the late- (≥45) and younger-onset (<45) groups. The results showed that 56 (41.8%) patients were classified as late-onset NSAE, and 78 (58.2%) as younger-onset NSAE. There were more males, especially in the late-onset group (P = 0.036). Prodromal symptoms were more common in the younger-onset group (P = 0.004). Among the onset symptoms, more late-onset patients presented as seizures, while more younger-onset patients presented as psychiatric symptoms. Throughout the disease course, the late-onset patients were more likely to have memory dysfunction (P < 0.001), but less likely to have central hypoventilation (P = 0.045). The late-onset patients also had a significantly lower modified Rankin Scale score on admission (P = 0.042), required intensive care unit (ICU) admission less frequently during hospitalization (P = 0.042) and had a shorter hospital stay (P = 0.014). Our study revealed that the late- and younger-onset NSAE had a distinct spectrum of demographic features, presentations, and prognoses. More attention is needed for the younger-onset patients, given a higher disease severity on admission, more frequent requirement for ICU admission and longer length of stay.


Asunto(s)
Enfermedades Autoinmunes del Sistema Nervioso , Hospitalización , Masculino , Humanos , Estudios Retrospectivos , Pronóstico
6.
Bioorg Chem ; 138: 106619, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37253310

RESUMEN

Three new diterpenoids with an unusual carbon skeleton, pedilanins A-C (1-3), and nine new jatrophane diterpenoids, pedilanins D-L (4-12), along with five known ones (13-17), were isolated from Pedilanthus tithymaloides. Compounds 1-3 characterize an unprecedented tricyclo[10.3.0.02,9]pentadecane skeleton. Compounds 4-8 are rare examples of the jatrophanes bearing a cyclic hemiketal substructure. Their structures were determined by an extensive analysis of HRESIMS, NMR, quantum-chemical calculation, DP4+ probability, and X-ray crystallographic data. In the bioassay, compounds 1-12 dramatically reversed multidrug resistance in cancer cells with the fold-reversals ranging from 17.9 to 396.8 at the noncytotoxic concentration of 10 µM. The mechanism results indicated that compounds 2 and 3 inhibited the P-glycoprotein (Pgp) transporter function, thus reversing the drug resistance.


Asunto(s)
Diterpenos , Euphorbia , Estructura Molecular , Euphorbia/química , Resistencia a Múltiples Medicamentos , Radiofármacos/farmacología , Diterpenos/farmacología , Diterpenos/química
7.
Antonie Van Leeuwenhoek ; 116(8): 801-815, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37231142

RESUMEN

A novel moderately halophilic bacterial strain, designated Z330T, was isolated from the egg of a marine invertebrate of the genus Onchidium collected in the South China Sea. The 16S rRNA gene sequence of strain Z330T exhibited the highest similarity value to that of the type strain Paracoccus fistulariae KCTC 22803T (97.6%), Paracoccus seriniphilus NBRC 100798T (97.6%) and Paracoccus aestuarii DSM 19484T (97.6%). Phylogenomic and 16S rRNA phylogenetic analysis showed that strain Z330T was most closely related to P. seriniphilus NBRC 100798T and P. fistulariae KCTC 22803T. Strain Z330T grew optimally at 28-30 °C, pH 7.0-8.0 with the presence of 5.0-7.0% (w/v) NaCl. In addition, growth of strain Z330T occurred at 0.5-16% NaCl, indicated strain Z330T was a moderately halophilic and halotolerant bacterium of genus Paracoccus. The predominant respiratory quinone in strain Z330T was identified as ubiquinone-10. The major polar lipids of strain Z330T were phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, glycolipid and six unidentified polar lipids. The major fatty acids of strain Z330T was summed feature 8 (C18:1 ω6c and/or C18:1 ω7c). The draft genome sequence of strain Z330T includes 4,084,570 bp in total (N50 = 174,985 bp) with a medium read coverage of 463.6 × and 83 scaffolds. The DNA G + C content of strain Z330T was 60.5%. In silico DNA-DNA hybridization with the four type strains showed 20.5, 22.3, 20.1 and 20.1% relatedness to Paracoccus fistulariae KCTC 22803T, Paracoccus seriniphilus NBRC 100798T, Paracoccus aestuarii DSM 19484T and Paracoccus denitrificans 1A10901T, respectively. And the average nucleotide identity (ANIb) values between strain Z330T and these four type strains were 76.2, 80.0, 75.8 and 73.8%, respectively, lower than the 95-96% threshold value for dividing prokaryotic species. On the basis of the phenotypic, phylogenetic, phylogenomic and chemotaxonomic properties, a novel species of the genus Paracoccus, Paracoccus onchidii sp. nov. is proposed with the type strain Z330T (= KCTC 92727T = MCCC 1K08325T).


Asunto(s)
Paracoccus , Fosfolípidos , Animales , Fosfolípidos/química , Filogenia , ARN Ribosómico 16S/genética , Cloruro de Sodio , ADN Bacteriano/genética , Ácidos Grasos/química , Invertebrados , China , Análisis de Secuencia de ADN , Técnicas de Tipificación Bacteriana
8.
Neurol Sci ; 44(10): 3711-3715, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37389732

RESUMEN

INTRODUCTION: Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy that affects the brain, spinal cord, leptomeninges, or eyes, in the absence of systemic diffusion. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a newly identified benign immune-mediated CNS inflammatory disorder with specific anti-MOG antibody seropositivity. These two seemingly unrelated nosological entities both have abundant clinical and radiological manifestations, and whether there is a potential link between them is unclear. CASE REPORT: We describe a 49-year-old man who presented progressive headache, dizziness, and unsteady gait with multifocal scattered T2 hyperintensities with contrast enhancement. The serum anti-MOG antibody test was positive, and a brain biopsy showed inflammatory infiltration. Initially, he was diagnosed with MOGAD and his condition improved after corticosteroid therapy. The patient relapsed with exacerbation of symptoms and neuroimaging showed new mass-forming lesions four months later. A second brain biopsy confirmed PCNSL. DISCUSSION: This is the first report of histologically confirmed successive MOGAD and PCNSL. Our case broadens the phenotypic spectrum of sentinel lesions in PCNSL. Though rare, PCNSL should be considered in patients diagnosed with benign CNS inflammatory disorder and responding well to steroid treatment when their clinical symptoms worsen and the imaging deteriorates. A timely biopsy is critical for accurate diagnosis and appropriate therapy.


Asunto(s)
Encéfalo , Linfoma , Humanos , Masculino , Autoanticuerpos , Encéfalo/patología , Linfoma/complicaciones , Glicoproteína Mielina-Oligodendrócito , Neuroimagen , Médula Espinal , Persona de Mediana Edad
9.
Clin Immunol ; 241: 109074, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35809856

RESUMEN

The Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome (KLHL 11-PNS) was first identified in 2019. This novel antibody, targeting the intracellular KLHL 11 antigen, can be detected in serum and cerebrospinal fluid using tissue-based and cell-based assays. It is thought to be a biomarker for a T-cell autoimmunity response. The most likely immunopathogenesis of KLHL 11-PNS appears to be linked to cytotoxic T-cell-mediated neuronal injury and loss. Patients have adult-male predilection, rhombencephalitis (brainstem and / or cerebellar involvement), and a robust oncological correlation with testicular germ cell tumors (predominately seminoma). Brain magnetic resonance imaging demonstrated T2 / fluid-attenuated inversion recovery hyperintensities and atrophy of the temporal lobe, cerebellum, and brainstem. Most patients responded poorly to immunotherapy and oncotherapy and thus had a poor long-term prognosis. We review the literature and provide an update of current knowledge regarding KLHL 11-PNS, including epidemiology, underlying mechanism, clinical presentations, paraclinical and oncological findings, diagnostic workup, and treatment approaches.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Síndromes Paraneoplásicos del Sistema Nervioso , Síndromes Paraneoplásicos , Neoplasias Testiculares , Adulto , Autoanticuerpos , Humanos , Masculino , Síndromes Paraneoplásicos del Sistema Nervioso/diagnóstico , Síndromes Paraneoplásicos del Sistema Nervioso/terapia
10.
Epilepsia ; 63(9): 2173-2191, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35652436

RESUMEN

Seizure is one of the manifestations of central nervous system inflammatory demyelinating diseases, which mainly include multiple sclerosis (MS), aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Acute symptomatic seizures secondary to MS/AQP4-NMOSD/MOGAD occur in the acute phase of the diseases, and are more frequent in MOGAD. In contrast, recurrent nonprovoked seizures, mainly attributed to autoimmune-associated epilepsy, occur in the nonacute phase of the diseases. Seizures in MS/AQP4-NMOSD/MOGAD mostly have a focal onset. MS patients with concomitant systemic infections, earlier onset, and greater disease activity are more likely to have seizures, whereas factors such as greater MS severity, the presence of status epilepticus, and cortical damage indicate a greater risk of developing epilepsy. In MOGAD, cerebral cortical encephalitis and acute disseminated encephalomyelitis (ADEM)-like phenotypes (predominately ADEM and multiphasic disseminated encephalomyelitis) indicate a greater seizure risk. Multiple relapses with ADEM-like phenotypes predict epilepsy in pediatrics with MOGAD. Pathophysiologically, acute symptomatic seizures in MS are associated with neuronal hyperexcitability secondary to inflammation and demyelination. Chronic epilepsy in MS is largely due to gliosis, neuronal dysfunction, and synaptic abnormalities. The mainstay of treatment for seizures secondary to MS/AQP4-NMOSD/MOGAD consists of immunotherapy along with antiseizure medications. This critical review discusses the most-updated evidence on epidemiology, clinical correlates, and inflammatory mechanisms underlying seizures and epilepsy in MS/AQP4-NMOSD/MOGAD. Treatment cautions including drug-drug interactions and the impact of treatments on the diseases are outlined. We also highlight pitfalls and challenges in managing such patients and future research perspectives to address unsolved questions.


Asunto(s)
Epilepsia , Esclerosis Múltiple , Neuromielitis Óptica , Acuaporina 4 , Autoanticuerpos , Niño , Epilepsia/etiología , Humanos , Esclerosis Múltiple/complicaciones , Glicoproteína Mielina-Oligodendrócito/metabolismo , Neuromielitis Óptica/complicaciones , Convulsiones
11.
J Endovasc Ther ; : 15266028221136434, 2022 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-36382889

RESUMEN

PURPOSE: This study aims to evaluate the long-term outcome and prognostic factors of a "mother-child" coaxial dual-catheter technique for percutaneous transluminal angioplasty (PTA) in the treatment of central vein stenosis (CVS) or central vein occlusion (CVO). MATERIALS AND METHODS: During September 2017 to August 2020, totally, 76 hemodialysis patients with symptomatic CVS or CVO were treated with PTA using the mother-child technique. The success rate, complications, and follow-up information were collected. Cox proportional hazard analysis was used to explore the predicting factors of primary patency. Primary patency rates of different subgroups were generated with the Kaplan-Meier analysis and compared using the log-rank (Mantel-Cox) test. RESULTS: There were 31 CVS patients and 45 CVO patients who presented with 114 PTAs. The initial procedure success rate was 98.25%. By the end of the follow-up, 57 patients (75%) had maintained functioning fistula after initial or repeated PTAs. The primary patency rates were 88.75% at 3 months, 73.36% at 6 months, 55.83% at 12 months, and 50.75% at 18 months. The secondary patency rates were 97.14% at 6 months, 87.66% at 12 months, and 82.18% at 24 months. The predictors for primary patency were history diabetes mellitus (hazard ratio [HR] = 3.1, 95% confidence interval [CI]: 1.31-7.30, P = .010), abnormal white blood cell count (HR = 1.44, 95% CI: 1.18-1.75, P < .001), lesion at subclavian-innominate vein (HR=2.75, 95% CI: 1.34-5.63, P = .006), and occlusion (HR=0.33, 95% CI: 0.14-0.76, P = .010). The primary patency was significantly lower in the subclavian-innominate vein subgroup, with a median primary patency of 4.5 (3-12.75) months, than in the nonsubclavian-innominate vein subgroup (8.5 [5-13] months; P = .005). The median duration of each PTA was 8 months for the first PTA, 7.5 months for the second PTA, and 5 months for the third PTA. There was no significant difference in the patency duration of repeated PTAs and the primary PTA (P = .389). CONCLUSIONS: The mother-child coaxial dual-catheter technique has a good success rate and acceptable primary patency in the treatment of hemodialysis patients with CVS or CVO. Repeated PTA is as effective as the primary PTA. CLINICAL IMPACT: This is the follow up report on the "Mother-Child" coaxial dual-catheter technique for percutaneous transluminal angioplasty of central vein stenosis or occlusion in hemodialysis patients since we first presented it in 2019. In this paper, we can see that the long-term patency rate of this technique for central venous disease is satisfactory, and repeated use of this technique does not affect the patency time. Compared with other literature reports, the surgical success rate of this technique is significantly improved. Therefore, this technique is worth popularizing in the treatment of central venous disease.

12.
Neurol Sci ; 43(12): 6961-6965, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36152072

RESUMEN

INTRODUCTION: Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma that diffusely involves throughout the brain. In recent years, increasingly reported cases have notably broadened the spectrum of clinical and radiological features; however, it remains a great diagnostic challenge. CASE REPORT: We reported an atypical case of LC presented with subacute onset of focal neurological deficits and diffuse T2 hyperintensities without contrast enhancement on magnetic resonance imaging. He was initially considered as inflammatory leukoencephalopathy and received empirical corticosteroids, showing a dramatically clinical response. Three months later, the patient relapsed with deteriorating symptoms and enlarged brain lesions with mass-like enhancement. A diagnosis of LC was finally established according to the radiological and pathological findings. DISCUSSION: Though rare, LC should always be kept as a differential diagnosis of diffuse leukoencephalopathy. Neurologists should be aware of every detailed information about LC to avoid a delay of diagnostic biopsy in clinical practice.


Asunto(s)
Neoplasias Encefálicas , Leucoencefalopatías , Humanos , Masculino , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/patología , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/diagnóstico por imagen , Biopsia/métodos
13.
Chem Biodivers ; 19(4): e202200028, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35194947

RESUMEN

Mesophotic coral ecosystems (MCEs) represent an underexplored source of intriguing natural products. Efforts to discover bioactive metabolites from sponge-associated fungi in MCEs identified a new steroid, acremocholone (1) and its three known analogs (2-4), from Acremonium sp. NBUF150. The Acremonium sp. NBUF150 was isolated from a Ciocalypta sponge located 70 m deep within the South China Sea. The planar structures and absolute configuration of 1-4 were determined from NMR-derived spectroscopic data, HR-ESI-MS, and X-ray crystallography. Compound 1 exhibited antimicrobial inhibition against Vibrio scophthalmi, V. shilonii and V. brasiliensis at minimum inhibitory concentrations of 8 µg/mL; compound 2 inhibited V. shilonii and V. brasiliensis at 8 and 32 µg/mL, respectively, and compound 4 inhibited growth of V. brasiliensis at 16 µg/mL. Sponge associated fungi from MCEs represent a promising resource of anti-Vibrio drug leads for aquaculture use.


Asunto(s)
Acremonium , Antozoos , Poríferos , Animales , Ecosistema , Hongos , Esteroides/farmacología
14.
Angew Chem Int Ed Engl ; 61(26): e202202855, 2022 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-35419921

RESUMEN

Transition-metal catalysts exhibit great potential as therapeutic agents to inhibit tumor growth. However, the precise delivery and in situ catalysis are challenging in catalytic medicine. Herein, we report an anti-HER2 affibody-ruthenium catalyst hybrid, named Ru-HER2 for selective and effective killing of cancer cells. Ru-HER2 binds to the HER2 receptor on a tumor cell and in situ catalyzes the activation of gemcitabine prodrug, resulting in enhanced selectivity in suppression of tumor growth and reduction of side effects. Immunoblotting reveals that Ru-HER2 in combination with gemcitabine prodrug can not only induce DNA damage, but also effectively block the HER2 signaling pathway in cancer cells. Therefore, the HER2-targeted chemotherapy exhibits substantially high anticancer activity toward HER2-positive cancer cells in vitro and in vivo. In a word, we report the first affibody-ruthenium catalyst hybrid and reveal its potential for effective HER2-targeted cancer chemotherapy.


Asunto(s)
Neoplasias , Profármacos , Rutenio , Catálisis , Humanos , Profármacos/farmacología , Rutenio/farmacología
15.
J Cell Mol Med ; 25(21): 10126-10139, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34651433

RESUMEN

Osteoporosis is an age-related disease characterized by low mineral density, compromised bone strength and increased risk of fragility fracture. Most agents for treating osteoporosis focus primarily on anti-resorption by inhibiting osteoclast activity. Bisphosphonate (BP) is a potent anti-resorptive agent that has been used clinically for decades and is proven to be effective. However, BP has a variety of side effects and is far from being an ideal anti-osteoporosis agent. BP selectively binds to calcium crystals, which are subsequently taken up or released by osteoclasts. Based on the action of BP, we previously demonstrated the inhibitory effect of a novel bone-targeting BP derivative, bisphosphonate-enoxacin (BE). In the current study, we used bone marrow-derived osteoclast cultures to further assess the inhibitory effect of BE on osteoclastogenesis and employed reverse transcription PCR and real-time PCR to examine expression of osteoclast-specific genes. Additionally, we used bone resorption and F-actin immunofluorescence assays to evaluate the effect of BE on osteoclast function and investigated the potential mechanisms affecting osteoclast differentiation and function in vitro. Furthermore, an ovariectomized (OVX) rat model was established to evaluate the therapeutic effects of BE on preventing bone loss. Results showed that BE exerted potent inhibitory effects on osteoclast formation and bone resorption by specifically abrogating RANKL-induced JNK signalling, and that it preserved OVX rat bone mass in vivo without any notable side effects. Collectively, these results indicated that the BP derivative BE may have significant potential as a treatment for osteoporosis and other osteolytic diseases.


Asunto(s)
Difosfonatos/farmacología , Enoxacino/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoporosis/metabolismo , Ligando RANK/metabolismo , Actinas/metabolismo , Animales , Biomarcadores , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/etiología , Resorción Ósea/metabolismo , Resorción Ósea/patología , Huesos/diagnóstico por imagen , Huesos/efectos de los fármacos , Huesos/metabolismo , Huesos/patología , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Regulación de la Expresión Génica , Ratones , Osteogénesis/efectos de los fármacos , Osteoporosis/diagnóstico , Osteoporosis/tratamiento farmacológico , Osteoporosis/etiología , Ligando RANK/genética , Células RAW 264.7 , Resultado del Tratamiento , Microtomografía por Rayos X
16.
J Vasc Surg ; 74(1): 217-224, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33340700

RESUMEN

OBJECTIVE: Arteriovenous fistula (AVF) is the preferred access for hemodialysis. Percutaneous transluminal angioplasty (PTA) has become a choice for AVF stenosis, and ultrasound has been used in PTA more frequently. METHODS: This single-center retrospective cohort study analyzed 129 patients who underwent PTA in the First Affiliated Hospital of Chongqing Medical University from January 2016 to December 2016. Angioplasty was performed using a noncompliant high-pressure balloon. The process was visualized by duplex scan. Our inclusion criteria were as follows: (1) stenoses or occlusions were located at the juxta-anastomosis site: the first 5 cm of the vein distal to the anastomosis; (2) stenosis was confirmed with the following conditions: (a) flow rates are <500 mL/min in the brachial artery and <200 mL/min in the fistula during dialysis, and (b) the stenosis diameter is <1.7 mm. We used the Kaplan-Meier curve to show the postintervention primary and secondary patency rates of patients with stenosis and occlusion. RESULTS: Altogether, 129 patients with 76 males were analyzed. Moreover, 104 have AVFs on the left arm, and only one patient had an ulnar-basilic AVF, whereas others had a radial-cephalic AVF. The postintervention primary patency rates are better in occlusion cases (P < .05), whereas secondary patency rates have no difference. The postintervention primary patency rates are better in patients without diabetes mellitus (P < .05), whereas the secondary patency rates had no difference. CONCLUSIONS: For juxta-anastomosis site stenosis or occlusion, PTA can be used to obtain satisfactory results.


Asunto(s)
Angioplastia de Balón , Derivación Arteriovenosa Quirúrgica/efectos adversos , Oclusión de Injerto Vascular/terapia , Diálisis Renal , Ultrasonografía Doppler Dúplex , Ultrasonografía Intervencional , Extremidad Superior/irrigación sanguínea , Grado de Desobstrucción Vascular , Adulto , Anciano , Angioplastia de Balón/efectos adversos , Femenino , Estudios de Seguimiento , Oclusión de Injerto Vascular/diagnóstico por imagen , Oclusión de Injerto Vascular/etiología , Oclusión de Injerto Vascular/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
17.
Artículo en Inglés | MEDLINE | ID: mdl-33406030

RESUMEN

A novel sulphate-reducing, Gram-stain-negative, anaerobic strain, isolate XJ01T, recovered from production fluid at the LiaoHe oilfield, PR China, was the subject of a polyphasic study. The isolate together with Desulfovibrio oxamicus NCIMB 9442T and Desulfovibrio termitidis DSM 5308T formed a distinct, well-supported clade in the Desulfovibrionaceae 16S rRNA gene tree. The taxonomic status of the clade was underscored by complementary phenotypic data. The three isolates comprising the clade formed distinct phyletic branches and were distinguished using a combination of physiological features and by low average nucleotide identity and digital DNA-DNA hybridization values. Consequently, it is proposed that isolate XJ01T represents a novel genus and species for which the name Cupidesulfovibrio liaohensis gen. nov., sp. nov. is proposed with the type strain XJ01T (=CGMCC 1.5227T=DSM 107637T). It is also proposed that D. oxamicus and D. termitidis be reclassified as Cupidesulfovibrio oxamicus comb. nov. and Cupidesulfovibrio termitidis comb. nov., respectively.


Asunto(s)
Desulfovibrionaceae/clasificación , Yacimiento de Petróleo y Gas/microbiología , Filogenia , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Desulfovibrio/clasificación , Desulfovibrionaceae/aislamiento & purificación , Ácidos Grasos/química , Hibridación de Ácido Nucleico , Oxidación-Reducción , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Sulfatos/metabolismo , Bacterias Reductoras del Azufre/clasificación , Bacterias Reductoras del Azufre/aislamiento & purificación
18.
Biochem Biophys Res Commun ; 525(2): 326-333, 2020 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-32093887

RESUMEN

Spexin (SPX) acts as a neuropeptide with pleiotropic functions that can participate in anxiety regulation. Corticotropin releasing factor (CRF) is widely expressed in brain tissues and associated with depression and anxiety and addiction. With the anxious mice under chronic unpredictable stress, we found SPX mRNA expression level in the hippocampus of the brain was significantly reduced, while local CRF mRNA expression level was increased. Furthermore, CRF injection in the hippocampus could also decrease SPX mRNA expression levels in hippocampus and other brain tissues, including pituitary and hypothalamus. With the primary mouse hippocampal cell model, CRF treatment could decrease SPX mRNA expression at hippocampal cell level and this inhibitory effect was mediated only by corticotropin releasing factor receptor 2 (CRFR2) but not corticotropin releasing factor receptor 1 (CRFR1). In HEK293 cells with CRFR2 over-expression, CRF could also inhibit SPX promoter activity coupling with AC/cAMP/PKA and MEK1/2/Erk1/2 cascades. In addition, Epac was also involved with the CRF-repressed SPX promoter activity and cross-talked with MEK1/2/Erk1/2 pathway. CRF could inhibit SPX gene expression in mouse hippocampus via transcriptional activation at the promoter level with coupling of AC/cAMP and MEK1/2/Erk1/2 signaling, which will be relevant to the anxiety response mediated by SPX in central nervous system.


Asunto(s)
Ansiedad , Hormona Liberadora de Corticotropina/farmacología , Hipocampo/metabolismo , Hormonas Peptídicas/fisiología , Animales , Regulación de la Expresión Génica/efectos de los fármacos , Células HEK293 , Humanos , Ratones , Hormonas Peptídicas/efectos de los fármacos , Hormonas Peptídicas/genética , Regiones Promotoras Genéticas/efectos de los fármacos , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Receptores de Hormona Liberadora de Corticotropina , Transducción de Señal
19.
Environ Res ; 190: 109991, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32768725

RESUMEN

Tefluthrin was the first pyrethroid developed for soil treatment. There was no report about the toxicity to terrestrial invertebrates at the enantiomer level. The main objective of the present study was to investigate the enantiomer-specific acute toxicity to the earthworm Eisenia fetida and potential mechanism via multilevel response. The filter paper contact and the artificial soil method were used to detect the acute toxicity of tefluthrin enantiomers to earthworms. Histopathological examination (H&E), biochemical criterion, and comet assay were used to identify the effects and potential mechanism of toxicity. The order of acute toxicity was Z-cis-(1S,3S)-(-)-tefluthrin < Rac-tefluthrin < Z-cis-(1R,3R)-(+)-tefluthrin. H&E stained images showed that intestinal cells were suffered seriously damaged after exposed to Rac-tefluthrin, and the Z-cis-(1R,3R)-(+)-isomer. Tefluthrin and enantiomers also enantioselectively disturbed reactive oxygen species (ROS) level and enzymatic activity. Additionally, Z-cis-(1R,3R)-(+)-tefluthrin significantly increased the olive tail moment (OTM) and Trail DNA% compared with the control and other treatment groups at the concentration of 0.1 mg/kg was observed. It can be concluded that intestinal damage, body weight changes, DNA damage caused by oxidative stress that might be the primary mechanisms of tefluthrin toxicity to earthworms. The results indicated the rational use of chiral compounds in agriculture to avoid damage to the soil ecosystem.


Asunto(s)
Insecticidas , Oligoquetos , Piretrinas , Contaminantes del Suelo , Animales , Ciclopropanos , Ecosistema , Hidrocarburos Fluorados , Insecticidas/toxicidad , Piretrinas/toxicidad , Suelo , Contaminantes del Suelo/análisis , Contaminantes del Suelo/toxicidad
20.
BMC Nephrol ; 21(1): 234, 2020 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-32571240

RESUMEN

BACKGROUND: Previous studies have not described the relationship between reducing radial artery diameter as well as increasing age and functional maturation of the radio-cephalic arteriovenous fistula (RCAVF) and no data identify these as linear relationship. The objective of this study was to perform trend analysis to assess these aspects. METHODS: Our retrospective cohort study enrolled and analyzed 353 follow-up cases that underwent first AVF creation. The artery and vein sizes were measured by ultrasound. We performed follow-up, a minimum of 3 months after surgery. Multivariable logistic regression analysis was used to identify independent risk factors inmaturation. Participant age was categorized into four groups (age ≤ 29, 30-49, 50-69, and 70-90 years). Radial artery diameter was categorized into four groups (≤ 1.9, >1.9 and ≤ 2.1, >2.1 and ≤ 2.4, >2.4 mm) according to median and interquartile ranges. We adjusted for confounders in four logistic models, and primary analyses were based on building ordered category models and tested P values for trends to estimate the relationship of radial artery diameter and each 20-year increase in age with risk of maturation. RESULTS: The mature RCAVF group included 301 cases, and the immature group included 52 cases. Radial artery diameter, age, and diabetes were independent risk factors of maturation. Odds ratios (ORs) associated with maturation reduced with increasing age, while ORs increased with increasing radial artery diameter. P values for trends(<0.05) were observed in all four models. A reduction in radial artery diameter and higher age were significantly associated with a higher incidence of immaturity after adjusting the multivariate models. The risks of immaturation were increased by more than 1.54 fold for each 20-year increase and increased by more than 1.34 fold for the smaller radial artery diameter group. CONCLUSION: Our findings suggest that a significantly higher immaturity risk of RCAVF was associated with increasing age and a reduction in radial artery diameter. Our study identified a linear exposure-response relationship of age and radial artery diameter with immaturity incident. A careful selection of patients will be helpful in improving AVF functional maturation.


Asunto(s)
Derivación Arteriovenosa Quirúrgica , Fallo Renal Crónico/terapia , Arteria Radial/diagnóstico por imagen , Diálisis Renal , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Mano/irrigación sanguínea , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Tamaño de los Órganos , Arteria Radial/patología , Estudios Retrospectivos , Ultrasonografía
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