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To investigate the effects of Luhong Yixin Granules on myocardial fibrosis in rats with heart failure and its possible mechanism, a total of 60 male Wistar rats were randomly divided into the control group, model group, and low-, medium-and high-dose Luhong Yixin Granules groups, with 12 rats in each group. Except for those in the control group, rats in the other groups were induced by intraperitoneal injection of doxorubicin(DOX) into a rat model. After the Luhong Yixin Granules were dissolved in the same amount of normal saline, they were given by gavage at low, medium and high doses(2.8, 5.6, 11.2 g·kg~(-1)·d~(-1)), and the control group and the model group were given the same amount of normal saline by gavage for 40 days. After the end of dosing, echocardiography was used to measure left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS). Rat body weight(BW) and heart weight(HW) were calculated as HW/BW. Enzyme-linked immunosorbent assay was used to measure the levels of interleukin-6(IL-6), interleukin-17(IL-17), tumor necrosis factor-α(TNF-α), transforming growth factor-ß1(TGF-ß1), growth stimulation expressed gene 2 protein(ST2), N-terminal pro-B-type natriuretic peptide(NT-proBNP), galectin-3(Gal-3) and creatine kinase isoenzyme(CK-MB) in serum. Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological morphology of myocardial tissue. Western blot and quantitative real-time polymerase chain reaction were used to detect the protein and mRNA expression levels of IL-6, IL-17, TNF-α, TGF-ß1, Smad3, Smad7, α-smooth muscle actin(α-SMA), and collagen â (COL-â ), respectively. RESULTS:: showed that compared with those in the control group, LVEF, LVFS, and HW/BW in the model group were decreased(P<0.05), and the levels of IL-6, IL-17, TNF-α, TGF-ß1, ST2, NT-proBNP, Gal-3, and CK-MB were increased(P<0.05). HE staining showed inflammatory changes in myocardial tissue; Masson staining showed decreases in the cross-sectional area and ventricular cavity area of the heart, and myocardial fibrosis of varying degrees(P<0.05). The protein and mRNA expression of IL-6, IL-17, TNF-α, TGF-ß1, Smad3, α-SMA, and COL-â were increased(P<0.05), and the protein and mRNA expression of Smad7 protein was decreased(P<0.01). Compared with those in the model group, LVEF, LVFS and HW/BW of the low-, medium-and high-dose Luhong Yixin Granules groups were increased(P<0.05), and the levels of IL-6, IL-17, TNF-α, TGF-ß1, ST2, NT-proBNP, Gal-3 and CK-MB were decreased(P<0.05). HE staining showed gradually reduced inflammatory changes of myocardial tissue, and Masson staining showed increased cross-sectional area and ventricular cavity area of the heart and decreased area of myocardial fibrosis(P<0.05). The protein and mRNA expression levels of IL-6, IL-17, TNF-α, TGF-ß1, Smad3, α-SMA, and COL-â were decreased(P<0.05), while the protein and mRNA expression levels of Smad7 were increased(P<0.05). Luhong Yixin Granules may be of great value in the treatment of heart failure by regulating the TGF-ß1/Smads signaling pathway, inhibiting the expression of inflammation-related proteins, reducing the deposition of extracellular matrix, and alleviating myocardial fibrosis.
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Medicamentos Herbarios Chinos , Fibrosis , Insuficiencia Cardíaca , Miocardio , Ratas Wistar , Transducción de Señal , Proteínas Smad , Factor de Crecimiento Transformador beta1 , Animales , Masculino , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Ratas , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Transducción de Señal/efectos de los fármacos , Miocardio/patología , Miocardio/metabolismo , Proteínas Smad/metabolismo , Proteínas Smad/genética , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , HumanosRESUMEN
PURPOSE: To compare the morphometry of paraspinal muscles in patients with degenerative spondylolisthesis (DS), isthmic spondylolisthesis (IS), and healthy individuals. METHODS: Thirty-seven pairs of DS patients were selected using propensity score matching with IS patients, while 37 healthy individuals matched for age, sex, and BMI were selected as controls. The relative cross-sectional area (rCSA), and relative functional cross-sectional area (rfCSA) of paraspinal muscles were measured, and the degree of fatty infiltration (FI) was calculated. Based on occupational differences, the patients were also divided into worker and farmer groups, and the same measurements were taken on them. RESULTS: At the L3/L4 level, the multifidus (MF) FI was greater in the DS and IS groups than in the control group, the erector spinae (ES) rfCSA was higher in the IS group than in the DS and control groups. At the L4/L5 level, MF rfCSA was smaller in the DS and IS groups than in the control group; ES rfCSA was higher in the IS group than in the DS and control groups. At the L5/S1 level, MF rfCSA was smaller in the DS and IS groups than in the control group; ES rfCSA was higher in the IS group than in the DS group. At the L3/L4, L4/L5 level, MF rfCSA were higher in the worker group than in the farmer group (p < 0.05). CONCLUSION: The morphological changes in paraspinal muscles in patients with DS were dominated by selective atrophy of the MF, while in patients with IS, the morphological changes in paraspinal muscle showed selective atrophy of the MF accompanied by compensatory hypertrophy of the ES. The surgeon should consider the morphological differences in paraspinal muscle between different types of lumbar spondylolisthesis when establishing the appropriate surgical program.
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Vértebras Lumbares , Músculos Paraespinales , Puntaje de Propensión , Espondilolistesis , Humanos , Espondilolistesis/diagnóstico por imagen , Espondilolistesis/patología , Músculos Paraespinales/patología , Músculos Paraespinales/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Anciano , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/patología , Adulto , Estudios de Casos y Controles , Imagen por Resonancia MagnéticaRESUMEN
[This corrects the article DOI: 10.3389/fnmol.2022.889534.].
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There is inconsistent evidence for an association of obesity with white matter microstructural alterations. Such inconsistent findings may be related to the cumulative effects of obesity and alcohol dependence. This study aimed to investigate the possible interactions between alcohol dependence and overweight/obesity on white matter microstructure in the human brain. A total of 60 inpatients with alcohol dependence during early abstinence (44 normal weight and 16 overweight/obese) and 65 controls (42 normal weight and 23 overweight/obese) were included. The diffusion tensor imaging (DTI) measures [fractional anisotropy (FA) and radial diffusivity (RD)] of the white matter microstructure were compared between groups. We observed significant interactive effects between alcohol dependence and overweight/obesity on DTI measures in several tracts. The DTI measures were not significantly different between the overweight/obese and normal-weight groups (although widespread trends of increased FA and decreased RD were observed) among controls. However, among the alcohol-dependent patients, the overweight/obese group had widespread reductions in FA and widespread increases in RD, most of which significantly differed from the normal-weight group; among those with overweight/obesity, the alcohol-dependent group had widespread reductions in FA and widespread increases in RD, most of which were significantly different from the control group. This study found significant interactive effects between overweight/obesity and alcohol dependence on white matter microstructure, indicating that these two controllable factors may synergistically impact white matter microstructure and disrupt structural connectivity in the human brain.
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Macrocyclic compounds, characterized by cyclic structures, often originate from either modified forms of unicyclic canonical molecules or natural products. Within the field of medicinal chemistry, there has been a growing fascination with drug-like macrocycles in recent years, primarily due to compelling evidence indicating that macrocyclization can significantly influence both the biological and physiochemical properties, as well as the selectivity, when compared to their acyclic counterparts. The approval of contemporary pharmaceutical agents like Lorlatinib underscore the notable clinical relevance of drug-like macrocycles. Nonetheless, the synthesis of these drug-like macrocycles poses substantial challenges, primarily stemming from the complexity of ring-closing reactions, which are inherently dependent on the size and geometry of the bridging linker, impacting overall yields. Nevertheless, macrocycles offer a promising avenue for expanding the synthetic toolkit in medicinal chemistry, enabling the creation of bioactive compounds. To shed light on the subject, we delve into the clinical prowess of established macrocyclic drugs, spanning various therapeutic areas, including oncology, and infectious diseases. Case studies of clinically approved macrocyclic agents illustrate their profound impact on patient care and disease management. As we embark on this journey through the world of macrocyclic pharmaceuticals, we aim to provide a comprehensive overview of their synthesis and clinical applications, shedding light on the pivotal role they play in modern medicine.
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Productos Biológicos , Compuestos Macrocíclicos , Humanos , Compuestos Macrocíclicos/química , Lactamas Macrocíclicas , Química Farmacéutica , Preparaciones FarmacéuticasRESUMEN
PURPOSE: To explore the effects of allicin on insulin resistance and free fatty acids (FFAs) levels in obese rats with periodontitis. METHODS: Forty rats were randomly divided into healthy group, periodontitis group, and low, medium and high dose groups, with 8 rats in each group. The healthy group was healthy rats, and the other groups were induced by sodium glutamate(MSG). After successfully establishing an obesity model, the maxillary molars were ligated and smeared to establish a periodontitis model. Both the periodontitis group and the healthy group were given normal saline, and the allicin low, medium and high dose groups were given allicin 20ï¼40 and 60 mg·kg-1·d-1, mixed with feed for oral administration. After 21 days of treatment, the fasting blood glucose(FPG), fasting insulin (FINS), insulin resistance index (HOMA-IR) scores and FFAs levels of the homeostatic model in rats were detected. The protein expression of TLR4/MyD88 signaling pathway were compared. Statistical analysis was performed with SPSS 22.0 software package. RESULTS: Compared with the healthy group, FPG, FINS levels, HOMA-IR, IL-6 and TNF-α levels of the periodontitis group were significantly increased, and the expression of TLR4 and MyD88 proteins was significantly increased(Pï¼0.05). Compared with the periodontitis group, FPG, FINS levels, HOMA-IR, IL-6 and TNF-α levels of low, medium and high-doses groups were significantly decreased, and the expression of TLR4 and MyD88 proteins was significantly decreased (Pï¼0.05). Compared with the low-dose group, the levels of FPG and FINS, HOMA-IR, IL-6 and TNF-α levels of the middle and high-dose groups were significantly decreased, and the expression of TLR4 and MyD88 proteins was significantly decreased (Pï¼0.05). Compared with the middle-dose group, the levels of FPG and FINS, HOMA-IR, IL-6 and TNF-α levels of the high-dose group were significantly decreased, and the expression of TLR4 and MyD88 proteins was significantly decreased (Pï¼0.05). After treatment, FFAs of the low, medium and high-dose groups were significantly lower than those before treatment(Pï¼0.05). Compared with the healthy group, FFAs levels of the periodontitis group, low-dose and medium-dose groups were significantly increased. Compared with the periodontitis group, FFAs levels of the low, medium and high-dose groups were significantly increased. Compared with the low-dose group, FFAs levels of the high-dose group were significantly increased. Compared with the middle-dose group, FFAs levels of the high-dose group were significantly increased (Pï¼0.05). CONCLUSIONS: Allicin can improve insulin resistance and obesity in obese rats with periodontitis, and its mechanism of action is related to the TLR4/MyD88 signaling pathway.
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Resistencia a la Insulina , Periodontitis , Ratas , Animales , Ácidos Grasos no Esterificados , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Receptor Toll-Like 4/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Obesidad/metabolismo , Insulina/metabolismoRESUMEN
The relationships of KRAS, NRAS, BRAF and PIK3CA gene mutations with the clinicopathological features and prognosis of colorectal cancer (CRC) in patient are lacking. Furthermore, the role of ring finger protein 215 (RNF215) in CRC patients with KRAS, NRAS, BRAF and PIK3CA mutations remains unclear. In the present study, 182 surgical resection specimens from patients with primary CRC for retrospective analysis, were collected. KRAS/NRAS/BRAF/PIK3CA gene mutations were confirmed by an amplification-refractory mutation system. Immunohistochemistry (IHC) was conducted to confirm KRAS, NRAS, BRAF and PIK3CA protein expression. RNF215 expression in patients with CRC was evaluated using TIMER 2.0 database and IHC. The individual mutation rates of KRAS, NRAS, BRAF and PIK3CA were 40.7% (74/182), 4.4% (8/182), 4.4% (8/182) and 3.3% (6/182), respectively. The KRAS exon 2 mutation rate was the highest (61.5%, 64/104), and these mutations mainly occurred at codons 12 and 13. KRAS/NRAS/BRAF/PIK3CA wild-type CRC patients had significantly longer overall survival and disease-free survival than mutated KRAS/NRAS/BRAF/PIK3CA CRC patients (P<0.05). Overall, 45.4% (5/11) of patients with PIK3CA mutations had concomitant KRAS mutations. The KRAS/NRAS/BRAF/PIK3CA gene mutation rate in patients with lymph node metastasis (76.1%, 35/46) was significantly higher than that in patients without lymph node metastasis (50.8%, 69/136) (P=0.0027). There were no significant differences in IHC expression between patients with and without KRAS, NRAS, BRAF and PIK3CA mutations (P>0.05). The TIMER 2.0 analysis showed that RNF215 expression was significantly higher in the mutated BRAF group than in the wild-type BRAF group in CRC (P<0.05). In conclusion, KRAS is the most commonly mutated gene, and KRAS mutations may be a poor prognostic factor for patients with CRC. KRAS wild-type patient resistance may be related to PIK3CA gene mutations, although this needs further verification in larger cohorts. BRAF mutations may be associated with RNF215 expression in patients with CRC.
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Gastrointestinal (GI) cancers encompass a group of malignancies affecting the digestive system, including the stomach, esophagus, liver, colon, rectum and pancreas. These cancers represent a significant global health burden, necessitating effective treatment strategies. Small-molecule drugs have emerged as crucial therapeutic options in the fight against GI cancers due to their oral bioavailability, targeted mechanisms of action, and well-established safety profiles. The review then elucidates the clinical applications and synthetic methods of clinically approved small-molecule drugs for the treatment of GI cancer, shedding light on their mechanisms of action and their potential in mitigating GI cancer progression. The review also discusses future prospects and the evolving landscape of small-molecule drug development in GI oncology, highlighting the potential for personalized medicine. In summary, this review provides valuable insights into cutting-edge strategies for harnessing clinically approved small-molecule drugs to combat GI cancer effectively.
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Neoplasias Gastrointestinales , Humanos , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/patología , Resultado del TratamientoRESUMEN
Fertilizer-based biofortification is a strategy for combating worldwide malnutrition of zinc (Zn), iron (Fe) and selenium (Se). Field experiments were conducted to investigate the effects of foliar treatments on concentrations of Zn, Fe, Se, N and bioavailability of Zn and Fe in grains of three maize cultivars grown at three locations. We compared the efficacy of ZnO nanoparticles (ZnO-NPs), Zn complexed chitosan nanoparticles (Zn-CNPs), conventional ZnSO4 and a cocktail solution (containing Zn, Fe and Se). All treatments were foliar-applied at rate of 452 mg Zn L-1, plus urea. Applying ten-fold less Zn (at rate of 45.2 mg Zn L-1) plus urea in the form of ZnO-NPs, Zn-CNPs, or ZnSO4 resulted in no increase, or a negligible increase, in grain Zn concentration compared with deionized water. By contrast, among the different Zn sources plus urea applied by foliar sprays, conventional ZnSO4 was the most efficient in improving grain Zn concentration. Furthermore, foliar application of a cocktail solution effectively improved grain concentrations of Zn, Fe, Se and N simultaneously, without a grain yield trade-off. For example, the average grain concentrations were simultaneously increased from 13.8 to 22.1 mg kg-1 for Zn, from 17.2 to 22.1 mg kg-1for Fe, from 21.4 to 413.5 ug kg-1 for Se and from 13.8 to 14.7 g kg-1 for N by foliar application of a cocktail solution. Because grain yield was significantly negatively correlated with grain nutrient concentrations, the magnitude of increase in grain concentrations of Zn and Fe was most pronounced in the maize cultivar with the lowest grain yield (Zhengdan958 grown in Linyi). Foliar application of a cocktail solution also significantly decreased the phytic acid (PA) concentration, ratios of PA/Fe and PA/Zn in grains, indicating an increased bioavailability of Fe and Zn for human health. In conclusion, we found that a foliar application of a cocktail solution including Zn, Fe, Se and N was most effective for biofortification, but that the grains with the lowest yield contained the greatest concentration of these elements. This finding highlights the need to breed maize varieties that are capable of achieving both high grain yield and high grain nutritional quality to address food security and human health challenges.
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Identifying biomarkers to predict lapse of alcohol-dependence (AD) is essential for treatment and prevention strategies, but remains remarkably challenging. With an aim to identify neuroimaging features for predicting AD lapse, 66 male AD patients during early-abstinence (baseline) after hospitalized detoxification underwent resting-state functional magnetic resonance imaging and were then followed-up for 6 months. The relevance-vector-machine (RVM) analysis on baseline large-scale brain networks yielded an elegant model for differentiating relapsing patients (n = 38) from abstainers, with the area under the curve of 0.912 and the accuracy by leave-one-out cross-validation of 0.833. This model captured key information about neuro-connectome biomarkers for predicting AD lapse.
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Alcoholismo , Humanos , Masculino , Alcoholismo/terapia , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Neuroimagen , BiomarcadoresRESUMEN
OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.
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In recent years, the contamination of antibiotics and their resistance genes (ARGs) has attracted the extensive attention of researchers at home and abroad. Soil is an important sink for the migration and transformation of antibiotics and ARGs, which pose a threat to soil organisms and human health. According to the relevant investigations in the past 15 years, the soil has been polluted by antibiotics to varying degrees in China. Bioremediation is a green and environment-friendly remediation technology, which has great potential in the remediation of antibiotic-contaminated soil. This review summarized the spatial and temporal characteristics of antibiotic pollution of soils in China in the past 15 years and the application of plants, animals, and microorganisms in the remediation of antibiotic-contaminated soil. In particular, the recent research advances of microbial electrochemical systems in removing antibiotics and ARGs in soil were reviewed, and the unaddressed issues of relevant research and the direction of future development were proposed, in order to provide a scientific basis for soil pollution remediation.
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Restauración y Remediación Ambiental , Animales , Humanos , Biodegradación Ambiental , China , Antibacterianos , SueloRESUMEN
The prognostic value of ring finger protein 215 (RNF215) in colorectal cancer (CRC) is unclear. Herein, the present study aimed to investigate the precise value of RNF215 based on CRC datasets from The Cancer Genome Atlas (TCGA) and clinical cases. CRC patient data was collected from TCGA and clinical samples from the Department of Pathology, Shanghai Fifth People's Hospital, Fudan University (Shanghai, China). Logistic regression analysis was used to investigate the correlations between RNF215 and clinicopathological characteristics. The predictive value of RNF215 for the clinical outcome of CRC was determined using Kaplan-Meier curves and Cox regression. Gene set enrichment analysis (GSEA), single-sample GSEA (ssGSEA), and angiogenesis analysis were also conducted to investigate the biological role of RNF215. Immunohistochemistry was conducted to validate the results. The results of the present study confirmed that RNF215 protein expression was significantly associated with age, lymphatic invasion, and overall survival (OS). Univariate analysis showed that upregulation of RNF215 in CRC was significantly associated with age and lymphatic invasion. Kaplan-Meier survival analysis revealed that high RNF215 expression predicted poorer OS and disease-specific survival. A total of nine experimentally detected RNF215-binding proteins were identified with the STRING tool and Cytoscape software. GSEA suggested that RNF215 was associated with several important pathways involved in tumor occurrence, including the Kyoto Encyclopedia of Genes and Genomes MAPK signaling pathway and the WikiPathway RAS signaling pathway. ssGSEA confirmed that RNF215 was significantly expressed in natural killer cells, CD8 T cells and T helper cells. Angiogenesis analysis revealed that numerous angiogenesis-related genes had the same expression trend as RNF215 in CRC. The immunostaining results indicated that RNF215 expression was significantly higher in CRC tissues than in corresponding normal tissues. In conclusion, increased RNF215 expression may be a potential molecular marker predictive of poor survival and a treatment target in CRC. In addition, RNF215 may participate in the formation of CRC through a variety of signaling pathways.
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Viral infections have led to many public health crises and pandemics in the last few centuries. Neurotropic virus infection-induced viral encephalitis (VE), especially the symptomatic inflammation of the meninges and brain parenchyma, has attracted growing attention due to its high mortality and disability rates. Understanding the infectious routes of neurotropic viruses and the mechanism underlying the host immune response is critical to reduce viral spread and improve antiviral therapy outcomes. In this review, we summarize the common categories of neurotropic viruses, viral transmission routes in the body, host immune responses, and experimental animal models used for VE study to gain a deeper understanding of recent progress in the pathogenic and immunological mechanisms under neurotropic viral infection. This review should provide valuable resources and perspectives on how to cope with pandemic infections.
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Encefalitis Viral , Virosis , Virus , Animales , Encefalitis Viral/veterinaria , Virosis/veterinaria , Encéfalo , Modelos Animales de EnfermedadRESUMEN
To understand the mitigation effects of melatonin on the chilling-induced photoinhibition in tomato, four groups of seedlings were labelled: NW (normal temperature + water), NM (normal temperature + melatonin), CW (chilling + water) and CM (chilling+ melatonin). We measured chlorophyll fluorescence, key photosynthetic parameters and the cycle efficiency for chloroplast ascorbic acid-glutathione (AsA-GSH). The results showed that, compared with the NW control, photosynthesis rate in CW was decreased by 50.3%-72.6%, chloroplast malondialdehyde content was decreased by 17.5%-132.7%, superoxide anion production was increased by 86.5%-235.9%, and H2O2 was increased by 96.6%-208.4%. These trends were significantly alleviated by exogenous melatonin, with photosynthetic rates in CM being increased by 22.7%-24.7% compared with in CW, malondialdehyde content being decreased by 16.6%-29.0%, the rate of superoxide anion production being decreased by 14.9%-22.7%, H2O2 content being decreased by 10.7%-27.1%. Compared with CW, the quantum yield of photochemical energy in PS â ¡ was increased by 15.8% in CM, the quantum yield of regulated non-photochemical energy loss was increased by 7.2%, the quantum yield of non-regulated non-photochemical energy loss was decreased by 24.7%, and the activities of key metabolic enzymes in the AsA-GSH cycle were increased to different degrees. We concluded that exogenous melatonin application could alleviate photoinhibition in tomato seedlings under chilling by balancing the partitioning of absorption energy in PS â ¡ and by enhancing the ROS scavenging efficiency of the AsA-GSH cycle in the chloroplast.
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Melatonina , Solanum lycopersicum , Melatonina/farmacología , Plantones/fisiología , Superóxidos/metabolismo , Superóxidos/farmacología , Peróxido de Hidrógeno , Fotosíntesis , Ácido Ascórbico/farmacología , Ácido Ascórbico/metabolismo , Glutatión/metabolismo , Glutatión/farmacología , Malondialdehído/metabolismoRESUMEN
Using hyaluronic acid (HA) as macromolecular drug carriers, a glutathione-responsive imaging drug delivery system HA-SS-a-Gd-DOTA was formed by conjugating gadolinium chelates and cytarabine. This system exhibited T1-reflexivity (21.9 mmol-1 L s-1, 0.5 T) that was higher than that of gadoterate meglumine. In an acidic environment, in vitro drug release reached 63.4% in 24 h. Low cytotoxicity indicated that this system has good biocompatibility. In vivo mouse imaging studies showed that tumor signaling was significantly enhanced. About 58% of the signal enhancement was obtained 50 min after injection of the drug. The degradation of the hyaluronic acid macromolecular chains in vivo makes it an ideal tumor imaging diagnostic agent because it did not cause damage to important organs of the mice.
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Neoplasias , Compuestos Organometálicos , Ratones , Animales , Ácido Hialurónico , Imagen por Resonancia Magnética/métodos , Medios de Contraste , Sustancias MacromolecularesRESUMEN
BACKGROUND: Crouzon syndrome (CS; OMIM 123500) is an autosomal dominant inherited craniofacial disorder caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. CS is characterized by craniofacial dysostosis, exophthalmos, and facial anomalies with hypoplastic maxilla and relative mandibular prognathism. CASE SUMMARY: Our report involves a 6-year-old fraternal twin boy with many caries in the oral cavity who presented with characteristic features of CS based on clinical and radiographic examinations along with Sanger sequencing. The fraternal girl did not show any abnormalities indicating CS. Carious teeth and poor oral hygiene were managed promptly through administering appropriate behavior guidance, orthodontic treatment was planned, and preventive procedures were described. CONCLUSION: CS could occur in a fraternal twin caused by a de novo mutation of the FGFR2 gene. Oral hygiene instruction, preventive programs on oral hygiene, orthodontic treatment, and maxillary osteotomy were required for treatment.
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Purpose: To identify novel genetic causes of febrile seizures (FS) and epilepsy with febrile seizures plus (EFS+). Methods: We performed whole-exome sequencing in a cohort of 32 families, in which at least two individuals were affected by FS or EFS+. The probands, their parents, and available family members were recruited to ascertain whether the genetic variants were co-segregation. Genes with repetitively identified variants with segregations were selected for further studies to define the gene-disease association. Results: We identified two heterozygous ATP6V0C mutations (c.64G > A/p.Ala22Thr and c.361_373del/p.Thr121Profs*7) in two unrelated families with six individuals affected by FS or EFS+. The missense mutation was located in the proteolipid c-ring that cooperated with a-subunit forming the hemichannel for proton transferring. It also affected the hydrogen bonds with surround residues and the protein stability, implying a damaging effect. The frameshift mutation resulted in a loss of function by yielding a premature termination of 28 residues at the C-terminus of the protein. The frequencies of ATP6V0C mutations identified in this cohort were significantly higher than that in the control populations. All the six affected individuals suffered from their first FS at the age of 7-8 months. The two probands later manifested afebrile seizures including myoclonic seizures that responded well to lamotrigine. They all displayed favorable outcomes without intellectual or developmental abnormalities, although afebrile seizures or frequent seizures occurred. Conclusion: This study suggests that ATP6V0C is potentially a candidate pathogenic gene of FS and EFS+. Screening for ATP6V0C mutations would help differentiating patients with Dravet syndrome caused by SCN1A mutations, which presented similar clinical manifestation but different responses to antiepileptic treatment.
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BACKGROUND: Alcohol dependence is a mental disorder with a high relapse rate. However, specific neuroimaging biomarkers have not been determined for alcohol dependence and its relapse. We conducted data-driven research to investigate resting-state functional magnetic resonance imaging (rs-fMRI) during early abstinence from alcohol dependence and its potential ability to predict relapse. METHODS: Participants included 68 alcohol-dependent patients and 68 healthy controls (HCs). The regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF) were compared between the alcohol dependence group and the HCs and between the relapse group and the nonrelapse group. The brain regions that presented significantly different ReHo and/or fALFF between the alcohol-dependent patients and HCs and/or between the relapsed and nonrelapsed patients were selected as the seeds to calculate the functional connectivities (FCs). RESULTS: During a 6-month follow-up period, 52.24% of alcohol-dependent patients relapsed. A regression model for differentiating alcohol-dependent patients and HCs showed that reductions in ReHo in the left postcentral region, fALFF in the right fusiform region, and FC in the right fusiform region to the right middle cingulum were independently associated with alcohol dependence, with an area under the receiver operating characteristic curve (AUC) of 0.841. The baseline FC of the left precentral to the left cerebellum of the relapse group was significantly lower than that of the nonrelapse group. The AUC of this FC to predict relapse was 0.774. CONCLUSIONS: Our findings contribute to advancing research on the neurobiological etiology and predictive biomarkers for relapse associated with alcohol dependence.