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Gentian, an herb resource known for its antioxidant properties, has garnered significant attention. However, existing methods are time-consuming and destructive for assessing the antioxidant activity in gentian root samples. In this study, we propose a method for swiftly predicting the antioxidant activity of gentian root using FT-IR spectroscopy combined with chemometrics. We employed machine learning and deep learning models to establish the relationship between FT-IR spectra and DPPH free radical scavenging activity. The results of model fitting reveal that the deep learning model outperforms the machine learning model. The model's performance was enhanced by incorporating the Double-Net and residual connection strategy. The enhanced model, named ResD-Net, excels in feature extraction and also avoids gradient vanishing. The ResD-Net model achieves an R2 of 0.933, an RMSE of 0.02, and an RPD of 3.856. These results support the accuracy and applicability of this method for rapidly predicting antioxidant activity in gentian root samples.
Assuntos
Antioxidantes , Gentiana , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Extratos VegetaisRESUMO
Gentian is a traditional Chinese herb with heat-clearing, damp-drying, inflammation-alleviating and digestion-promoting effects, which is widely used in clinical practice. However, there are many species of gentian. According to the pharmacopoeia, Gentiana manshurica Kitag, Gentiana scabra Bge, Gentiana triflora Pall and Gentianarigescens Franch are included. Therefore, accurately identifying the species of gentian is important in clinical use. In recent years, with the advantages of low cost, convenience, fast analysis and high sensitivity, infrared spectroscopy (IR) has been extensively used in herbal identification. Unlike one-dimensional spectroscopy, a two-dimensional correlation spectrum (2D-COS) can improve the resolution of the spectrum and better highlight the details that are difficult to detect. In addition, the residual neural network (ResNet) is an important breakthrough in convolutional neural networks (CNNs) for significant advantages related to image recognition. Herein, we propose a new method for identifying gentian-related species using 2D-COS combined with ResNet. A total of 173 gentian samples from seven different species are collected in this study. In order to eliminate a large amount of redundant information and improve the efficiency of machine learning, the extracted feature band method was used to optimize the model. Four feature bands were selected from the infrared spectrum, namely 3500-3000 cm-1, 3000-2750 cm-1, 1750-1100 cm-1 and 1100-400 cm-1, respectively. The one-dimensional spectral data were converted into synchronous 2D-COS images, asynchronous 2D-COS images, and integrative 2D-COS images using Matlab (R2022a). The identification strategy for these three 2D-COS images was based on ResNet, which analyzes 2D-COS images based on single feature bands and full bands as well as fused feature bands. According to the results, (1) compared with the other two 2D-COS images, synchronous 2D-COS images are more suitable for the ResNet model, and (2) after extracting a single feature band 1750-1100 cm-1 to optimize ResNet, the model has the best convergence performance, the accuracy of training, test and external validation is 1 and the loss value is only 0.155. In summary, 2D-COS combined with ResNet is an effective and accurate method to identify gentian-related species.
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Gentiana , Gentiana/química , Redes Neurais de Computação , Espectrofotometria Infravermelho , Aprendizado de Máquina , Temperatura AltaRESUMO
Identifying the major sources and critical periods of P loss from agricultural fields provides important guidance for reducing P loss. A rice-oilseed rape rotation with no P fertilization (NP, control), medium P fertilization (MP, 90 kg P2O5 ha-1 season-1), and high P fertilization (HP, 180 kg P2O5 ha-1 season-1) was conducted from 2019 to 2021 in the middle Yangtze River Basin. Runoff and leaching P losses were measured simultaneously using runoff event monitoring and a percolation device. Applying P fertilizer increased the P concentration in the field ponding water and percolation water of the rice-oilseed rape rotation. During the rice growing season, total P (TP), dissolved P (DP), and particulate P (PP) concentrations in the field ponding water and percolation water peaked 1 day after P was applied, and then decreased rapidly. After 10 days of fertilization, P concentration in the field ponding water of the MP treatment decreased to a minimum and stabilized, while the HP treatment extended this period to 20 days. The highest P concentration in percolation water was observed at the first sampling during the oilseed rape season, and then it continued to decrease. Inputting P fertilizer increased P loss by 55.0-109.9% compared to the NP treatment, with annual P losses of 0.89-1.10 kg P ha-1, of which runoff loss accounted for 61.7-62.9%. Fertilization and precipitation resulted in varied P loss within and between seasons. Runoff from heavy precipitation during the rice season was the main source of P loss, while PP accounted for 54.7-77.6% of runoff P loss. The strong utilization of soil P by rice resulted in a lower demand for exogenous P fertilizer than oilseed rape. Excessive P input increased the soil P surplus and vertical migration. Therefore, reducing rice season P fertilizer inputs to achieve annual P balance in rice-oilseed rape rotation can effectively reduce soil P surplus and loss while ensuring crop P demand, and the initial 10 d after fertilization in the rice season was a critical period for reducing P runoff loss.
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Brassica napus , Oryza , Fósforo , Fosfatos , Agricultura/métodos , Fertilizantes/análise , Solo , Nitrogênio/análiseRESUMO
Crop photosynthesis (A) and productivity are often limited by a combination of nutrient stresses, such that changes in the availability of one nutrient may affect the availability of another nutrient, in turn influencing A. In this study, we examined the synergistic effects of phosphorus (P) and potassium (K) on leaf A in a nutrient amendment experiment, in which P and K were added individually or in combination to Brassica napus grown under P and K co-limitation. The data revealed that the addition of P gradually removed the dominant limiting factor (i.e. the limited availability of P) and improved leaf A. Strikingly, the addition of K synergistically improved the overall uptake of P, mainly by boosting plant growth, and compensated for the physiological demand for P by prioritizing investment in metabolic pools of P (P-containing metabolites and inorganic phosphate, Pi). The enlarged pool of metabolically active P was partially associated with the upregulation of Pi regeneration through release from triose phosphates rather than replacement of P-containing lipids. This process mitigated P restrictions on A by maintaining the ATP/NADPH and NADPH/NADP+ ratios and increasing the content and activity of Rubisco. Our findings demonstrate that sufficient K increased Pi-limited A by enhancing metabolic P fractions and Rubisco activity. Thus, ionic synergism may be exploited to mitigate nutrient-limiting factors to improve crop productivity.
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Brassica napus , Fósforo , Fósforo/metabolismo , Fosfatos/metabolismo , Potássio/metabolismo , Brassica napus/metabolismo , Ribulose-Bifosfato Carboxilase/metabolismo , NADP/metabolismo , Fotossíntese/fisiologia , Folhas de Planta/metabolismoRESUMO
Background: The Geriatric Nutritional Index (GNRI) has been indicated as a nutritional index which is highly associated with complications and mortality in older hospitalized patients. Moreover, early studies had suggested that GNRI is a potential prognostic indicator for some malignances. However, the prognostic value of GNRI in esophageal squamous cell carcinoma (ESCC) patients underwent neoadjuvant therapy followed by esophagectomy remains elusive. Materials and methods: This retrospective study incorporated 373 patients with ESCC who had underwent neoadjuvant therapy followed by radical esophagectomy at West China Hospital of Sichuan University between April 2011 and September 2021. The GNRI formula was: 1.489 × albumin (g/dl) + 41.7 × current weight/ideal weight. Patients were classified as GNRI-low (GNRI < 98.7) or GNRI high (GNRI ≥ 98.7). The association between GNRI and clinical survival status were assessed utilizing Kaplan-Meier methods and Cox regression analysis. Results: Three hundred and seventy three patients were retrospectively included in this study. 80 (21.5%) and 293 (78.5%) patients had been divided into the GNRI-low and GNRI-high groups respectively. Pathological T stage and the rate of nodal metastasis were significantly higher in the GNRI low group than in the GNRI high group (P = 0.003 and P = 0.001, respectively) among the examined demographic parameters. Furthermore, GNRI was significantly correlated with postoperative complications, patients with lower GNRI had a higher postoperative complication rate as compared with GNRI high group [Odds ratio: 2.023; 95% confidence interval (CI): 1.208-3.389; P = 0.007]. Univariate analysis of 5-year overall survival (OS) and disease-free survival (DFS) found that the rate of survival was considerably lower in the GNRI-low group than in the GNRI-high group (P < 0.001). However, multivariate analysis demonstrated that GNRI was not an independent risk factor. Conclusion: In patients with ESCC, low GNRI exhibited a poor nutritional indicator and related to postoperative complications after neoadjuvant therapy. Intensive follow-up after surgery should be performed for ESCC patients with low GNRI.
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Gentiana Genus, a herb mainly distributed in Asia and Europe, has been used to treat the damp heat disease of the liver for over 2000 years in China. Previous studies have shown significant differences in the compositional contents of wild Gentiana Genus samples from different geographical origins. Therefore, the traceable geographic locations of the wild Gentiana Genus samples are essential to ensure practical medicinal value. Over the last few years, the developments in chemometrics have facilitated the analysis of the composition of medicinal herbs via spectroscopy. Notably, FT-IR spectroscopy is widely used because of its benefit of allowing rapid, nondestructive measurements. In this paper, we collected wild Gentiana Genus samples from seven different provinces (222 samples in total). Twenty-one different FT-IR spectral pre-processing methods that were used in our experiments. Meanwhile, we also designed a neural network, Double-Net, to predict the geographical locations of wild Gentiana Genus plants via FT-IR spectroscopy. The experiments showed that the accuracy of the neural network structure Double-Net we designed can reach 100%, and the F1_score can reach 1.0.
Assuntos
Gentiana , Plantas Medicinais , China , Gentiana/química , Redes Neurais de Computação , Espectroscopia de Infravermelho com Transformada de Fourier/métodosRESUMO
BACKGROUND: Prospects for the drug treatment of acute lung injury (ALI) is unpromising. Managing inflammation can prevent ALI from progressing and minimize further deterioration. Zedoary turmeric oil injection (ZTOI), a patented traditional Chinese medicine (TCM) that has been used against ALI, has shown significant anti-inflammatory effects. However, the mechanisms underlying these effects remain unclear. PURPOSE: Elucidate the anti-inflammatory mechanism by which ZTOI acts against ALI in rats using an ingredients-targets-pathways (I-T-P) interaction network. STUDY DESIGN AND METHODS: The key ingredients of ZTOI were characterized using UPLC-MS/MS combined with literature mining. The target profiles of each ingredient were established using drug-target databases. The anti-inflammatory activity of ZTOI against lipopolysaccharides (LPS)-induced rat ALI was validated using histopathology and inflammatory factor assessments. The therapeutic targets of ZTOI were screened by integrating transcriptomic results of lung tissues with protein-protein interaction (PPI) expansion. Using KEGG pathway enrichment, an I-T-P network was established to determine the essential interactions among ingredients, targets, and pathways of ZTOI against lung inflammation in ALI. Molecular docking and immunofluorescence staining were utilized to confirm the accuracy of the I-T-P network. RESULTS: A total of 11 sesquiterpenes, whose target profiles may characterize the potential function of ZTOI, were identified as key ingredients. In the ALI rat model, ZTOI can alleviate lung inflammation by decreasing the levels of C-reactive protein, interleukin-6, interleukin-1ß, and tumor necrosis factor α both in serum and lung tissues. Based on our biological samples, transcriptomics, PPI network expansion, and KEGG pathway enrichment, 11 ingredients, 174 targets, and 8 signaling pathways were linked in the I-T-P networks. From these results, ZTOI could be inferred to exert multiple anti-inflammatory effects against ALI through Toll-like receptor, NF-kappa B, RIG-I-like receptor, TNF, NOD-like receptor, IL-17, MAPK, and the Toll and Imd signaling pathways. In addition, two significantly regulated targets in the transcriptome, Usp18 and Map3k7, could be the essential anti-inflammatory targets of ZTOI. CONCLUSION: By integrating network pharmacology with ingredient identification and transcriptomics, we show the multiple anti-inflammatory mechanisms by which ZTOI acts against ALI on an I-T-P level. This work also provides a methodological reference for related research into TCM.
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Lesão Pulmonar Aguda , Medicamentos de Ervas Chinesas , Pneumonia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Proteína C-Reativa , Cromatografia Líquida , Curcuma/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Interleucina-17 , Interleucina-1beta , Interleucina-6 , Lipopolissacarídeos/efeitos adversos , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Proteínas NLR , Farmacologia em Rede , Pneumonia/tratamento farmacológico , Ratos , Receptores do Fator de Necrose Tumoral/uso terapêutico , Espectrometria de Massas em Tandem , Transcriptoma , Fator de Necrose Tumoral alfa/efeitos adversosRESUMO
Pectin, cellulose, and hemicelluloses are major components of primary cell walls in plants. In addition to cell adhesion and expansion, pectin plays a central role in seed mucilage. Seed mucilage contains abundant pectic rhamnogalacturonan-I (RG-I) and lower amounts of homogalacturonan (HG), cellulose, and hemicelluloses. Previously, accumulated evidence has addressed the role of pectin RG-I in mucilage production and adherence. However, less is known about the function of pectin HG in seed coat mucilage formation. In this study, we analyzed a novel mutant, designated things fall apart2 (tfa2), which contains a mutation in HG methyltransferase QUASIMODO2 (QUA2). Etiolated tfa2 seedlings display short hypocotyls and adhesion defects similar to qua2 and tumorous shoot development2 (tsd2) alleles, and show seed mucilage defects. The diminished uronic acid content and methylesterification degree of HG in mutant seed mucilage indicate the role of HG in the formation of seed mucilage. Cellulosic rays in mutant mucilage are collapsed. The epidermal cells of seed coat in tfa2 and tsd2 display deformed columellae and reduced radial wall thickness. Under polyethylene glycol treatment, seeds from these three mutant alleles exhibit reduced germination rates. Together, these data emphasize the requirement of pectic HG biosynthesis for the synthesis of seed mucilage, and the functions of different pectin domains together with cellulose in regulating its formation, expansion, and release.
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Proteínas de Arabidopsis , Arabidopsis , Mucilagem Vegetal , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Parede Celular/metabolismo , Celulose/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Mutação , Pectinas/metabolismo , Sementes/genética , Sementes/metabolismoRESUMO
INTRODUCTION: Oil body (OB), a subcellular organelle that stores oil in plant seeds, is considered a new transdermal drug delivery system. With the increasing understanding of the OB and its main protein (oleosin), numerous studies have been conducted on OB as "carrier" for the expression of exogenous proteins. In our previous study, oil body fused with aFGF (OLAF) was obtained using a plant oil body expression system that had been preliminarily proven to be effective in accelerating the healing of skin wounds. However, no dermal toxicological information on OLAF is available. OBJECTIVE: To ensure the dermal safety of OLAF, a series of tests (the acute dermal toxicity test, 21-day repeat dermal toxicity test, dermal irritation test and skin sensitisation test) were conducted after optimising the extraction protocol of OLAF. MATERIALS AND METHODS: To improve the extraction rate of OLAF, response surface methodology (RSM) was first employed to optimise the extraction conditions. Then, Wistar rats were exposed to OLAF (400 mg·kg-1 body weight) in two different ways (6 hours/time for 24 hours and 1 time/day for 21 days) to evaluate the acute dermal toxicity and 21-day repeated dermal toxicity of OLAF. In the acute dermal toxicity test, clinical observations were conducted to evaluate the toxicity, behaviour, and health of the animals for 14 consecutive days. Similarly, the clinical signs, body weight, haematological and biochemical parameters, histopathological changes and other indicators were also detected during the 21 days administration. For the dermal irritation test, single and multiple doses of OLAF (125 mg·kg-1 body weight) were administered to albino rabbits for 14 days (1 time/day). The irritation reaction on the skin of each albino rabbit was recorded and scored. Meanwhile, skin sensitisation to OLAF was conducted using guinea pigs for a period of 28 days. RESULTS: Suitable extraction conditions for OLAF (PBS concentration 0.01, pH of PBS 8.6, solid-liquid ratio 1:385 g·mL-1) were obtained using RSM. Under these conditions, the extraction rate and particle size of OLAF were 7.29% and 1290 nm, respectively. In the tests of acute dermal toxicity and 21-day repeated dermal toxicity, no mortality or significant differences were observed in terms of clinical signs, body weight, haematological parameters, biochemical parameters and anatomopathological analysis. With respect to the dermal irritation test and skin sensitisation test, no differences in erythema, oedema or other abnormalities were observed between treatment and control groups on gross and histopathological examinations. CONCLUSIONS: The results of this study suggest that OLAF does not cause obvious toxicity, skin sensitisation or irritation in animals.
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Portadores de Fármacos/toxicidade , Fator 1 de Crescimento de Fibroblastos/administração & dosagem , Gotículas Lipídicas , Óleos de Plantas/isolamento & purificação , Pele/efeitos dos fármacos , Administração Cutânea , Animais , Feminino , Fator 1 de Crescimento de Fibroblastos/toxicidade , Cobaias , Masculino , Óleos de Plantas/toxicidade , Coelhos , Ratos , Testes Cutâneos , Testes de Toxicidade Aguda , Cicatrização/efeitos dos fármacosRESUMO
Objective: The expression of therapeutic proteins in plant oil body bioreactors has attracted much attention. But its safety is not yet clear. This article determines the risk of safety after using the drug. Methods: The oil body-linked oleosin-hEGF microgel emulsion (OBEME) was prepared by mixing the xanthan gum with suitable concentrations in an appropriate proportion. Skin irritation and sensitization reaction were investigated in rats and guinea pigs using OBEME as test article.Results: The OBEME did not produce dermal erythema/eschar or oedema responses. The dermal subacute and subchronic toxicity of OBEME were evaluated in accordance with OECD guidelines. Compared with the control group, the basic physical signs, such as weight, feed, drinking, excretion, and behaviour of experimental animals, were not abnormal. In addition, no abnormality was found in haematological parameters, biochemical indexes, relative organ weight, and histopathological observation of organs, and there was no significant difference compared with normal saline treatment group. Therefore, we conclude that OBEME has no toxic effects and is safe and reliable to be used for topical application.
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Portadores de Fármacos/toxicidade , Fator de Crescimento Epidérmico/toxicidade , Proteínas de Plantas/toxicidade , Proteínas Recombinantes de Fusão/toxicidade , Pele/efeitos dos fármacos , Administração Cutânea , Animais , Reatores Biológicos/efeitos adversos , Carthamus tinctorius/genética , Dermatite de Contato/diagnóstico , Dermatite de Contato/etiologia , Dermatite de Contato/patologia , Portadores de Fármacos/química , Avaliação Pré-Clínica de Medicamentos , Emulsões , Fator de Crescimento Epidérmico/administração & dosagem , Fator de Crescimento Epidérmico/genética , Eritema/induzido quimicamente , Eritema/diagnóstico , Cobaias , Humanos , Gotículas Lipídicas/química , Masculino , Microgéis , Proteínas de Plantas/administração & dosagem , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Ratos , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/genética , Pele/imunologia , Pele/lesões , Pele/patologia , Testes de Toxicidade Aguda/métodos , Testes de Toxicidade Subaguda/métodos , Testes de Toxicidade Subcrônica/métodos , Cicatrização/efeitos dos fármacosRESUMO
BACKGROUND: In recent years, immunonutrition has been introduced and proposed to have a positive modulatory effect on inflammatory and immune responses and gut function for surgical patients, especially for patients undergoing gastrointestinal cancer resection. We conducted this parallel-group, randomized and double-blind clinical controlled trial to investigate the efficacy of perioperative enteral immunonutrition (EIN) on clinical and immunological outcomes of patients undergoing esophageal resection. METHODS: A randomized, parallel-group, double-blind, clinical trial was conducted between December 1, 2017 and March 1, 2018. This study enrolled 120 patients with esophageal cancer. And 112 patients were divided into two groups randomly: EIN group and enteral nutrition (EN) group. The EIN contained extra immunonutritional substrates, including a consistent combination of arginine, RNA and the omega-3 fatty acids compared with EN. Immune indicators were measured at preoperative day 7, postoperative day (POD) 1, 3, 7 and post-discharge day (PDD) 30. RESULTS: There were 56 participants randomized to each group. Finally, 53 patients in EIN and 50 patients in EN were analyzed. Immune indicator was the primary outcome in this study. EIN yielded a significantly lower rate of CD8/CD3 (%) at POD 3 compared with EN group (P=0.005). The rate of CD4/CD8 (%) in EIN group was higher than that in EN group at POD3 (P=0.004). The serum levels of IgM at POD 3 and 7 were significantly higher in EN group compared with EIN group (P=0.025 and P=0.009, respectively). The rate of NK (%) and the serum level of IgA were significantly higher in EIN group compared with EN group at PDD 30 (P=0.022 and P=0.041, respectively). No significant differences were found in 2-year progressionfree survival and overall survival. CONCLUSIONS: Immunonutrition is a safe and feasible nutritional treatment, which has a positive modulatory impact on immune responses after esophagectomy. Although no significant difference was found in clinical and survival outcomes between EIN and EN groups, immunonutrition could still have a positive effect on immunological function of patients undergoing esophagectomy.
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Neoplasias Esofágicas , Esofagectomia , Assistência ao Convalescente , Nutrição Enteral , Neoplasias Esofágicas/cirurgia , Humanos , Alta do Paciente , Complicações Pós-Operatórias/prevenção & controleRESUMO
The endocrine FGF21 was discovered as a novel metabolic regulator in 2005 with new functions bifurcating from the canonic heparin-binding FGFs that directly promote cell proliferation and growth independent of a co-receptor. Early studies have demonstrated that FGF21 is a stress sensor in the liver and possibly, several other endocrine and metabolic tissues. Hepatic FGF21 signals via endocrine routes to quench episodes of metabolic derangements, promoting metabolic homeostasis. The convergence of mouse and human studies shows that FGF21 promotes lipid catabolism, including lipolysis, fatty acid oxidation, mitochondrial oxidative activity, and thermogenic energy dissipation, rather than directly regulating insulin and appetite. The white and brown adipose tissues and, to some extent, the hypothalamus, all of which host a transmembrane receptor binary complex of FGFR1 and co-receptor KLB, are considered the essential tissue and molecular targets of hepatic or pharmacological FGF21. On the other hand, a growing body of work has revealed that pancreatic acinar cells form a constitutive high-production site for FGF21, which then acts in an autocrine or paracrine mode. Beyond regulation of macronutrient metabolism and physiological energy expenditure, FGF21 appears to function in forestalling the development of fatty pancreas, steato-pancreatitis, fatty liver, and steato-hepatitis, thereby preventing the development of advanced pathologies such as pancreatic ductal adenocarcinoma or hepatocellular carcinoma. This review is intended to provide updates on these new discoveries that illuminate the protective roles of FGF21-FGFR1-KLB signal pathway in metabolic anomalies-associated severe tissue damage and malignancy, and to inform potential new preventive or therapeutic strategies for obesity-inflicted cancer patients via reducing metabolic risks and inflammation.
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Carcinoma Hepatocelular/patologia , Carcinoma Ductal Pancreático/patologia , Fatores de Crescimento de Fibroblastos/metabolismo , Neoplasias Hepáticas/patologia , Obesidade/metabolismo , Neoplasias Pancreáticas/patologia , Tecido Adiposo/metabolismo , Animais , Comunicação Autócrina , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/prevenção & controle , Carcinoma Ductal Pancreático/etiologia , Carcinoma Ductal Pancreático/prevenção & controle , Proliferação de Células , Modelos Animais de Doenças , Metabolismo Energético , Fígado Gorduroso/etiologia , Fígado Gorduroso/patologia , Fatores de Crescimento de Fibroblastos/genética , Humanos , Hipotálamo/metabolismo , Proteínas Klotho , Metabolismo dos Lipídeos , Fígado/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/prevenção & controle , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Transgênicos , Obesidade/complicações , Obesidade/patologia , Pâncreas/patologia , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/prevenção & controle , Comunicação Parácrina , Fatores de Proteção , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de SinaisRESUMO
Importance: Severe acute respiratory syndrome coronavirus 2 has caused a global outbreak of coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 binds angiotensin-converting enzyme 2 of the rennin-angiotensin system, resulting in hypokalemia. Objective: To investigate the prevalence, causes, and clinical implications of hypokalemia, including its possible association with treatment outcomes, among patients with COVID-19. Design, Setting, and Participants: This cohort study was conducted at Wenzhou Central Hospital and Sixth People's Hospital of Wenzhou, Wenzhou, China, from January 11, 2020, to February 15, 2020. Participants included patients who received a diagnosis of COVID-19 according to the criteria issued by the Chinese Health Bureau and were admitted to the hospital. The patients were classified as having severe hypokalemia (plasma potassium <3 mmol/L), hypokalemia (plasma potassium 3-3.5 mmol/L), and normokalemia (plasma potassium >3.5 mmol/L). The clinical features, therapy, and outcomes were compared between the 3 groups. Data analysis was conducted in March 2020. Interventions: The patients were given general support and antiviral therapy. Their epidemiological and clinical features were collected. Main Outcomes and Measures: The prevalence of hypokalemia and response to treatment with potassium supplements were measured by analyzing plasma and urine potassium levels. Results: One hundred seventy-five patients (87 female patients [50%]; mean [SD] age, 45 [14] years) were classified as having severe hypokalemia (31 patients [18%]), hypokalemia (64 patients [37%]), and normokalemia (80 patients [46%]). Patients with severe hypokalemia had statistically significantly higher body temperature (mean [SD], 37.6 °C [0.9 °C]) than the patients with hypokalemia (mean [SD], 37.2 °C [0.7 °C]; difference, 0.4 °C; 95% CI, 0.2-0.6 °C; P = .02) and the patients with normokalemia (mean [SD], 37.1 °C [0.8 °C]; difference, 0.5 °C; 95% CI, 0.3-0.7 °C; P = .005). Patients with higher levels of hypokalemia also had higher creatine kinase levels (severe hypokalemia, mean [SD], 200 [257] U/L [median, 113 U/L; interquartile range {IQR}, 61-242 U/L]; hypokalemia, mean [SD], 97 [85] U/L; and normokalemia, mean [SD], 82 [57] U/L), higher creatine kinase-MB fraction (severe hypokalemia, mean [SD], 32 [39] U/L [median, 14 U/L; IQR, 11-36 U/L]; hypokalemia, mean [SD], 18 [15] U/L; and normokalemia, mean [SD], 15 [8] U/L), higher lactate dehydrogenase levels (mean [SD], severe hypokalemia, 256 [88] U/L; hypokalemia, 212 [59] U/L; and normokalemia, 199 [61] U/L), and higher C-reactive protein levels (severe hypokalemia, mean [SD], 29 [23] mg/L; hypokalemia, mean [SD], 18 [20] mg/L [median, 12, mg/L; IQR, 4-25 mg/L]; and normokalemia, mean [SD], 15 [18] mg/L [median, 6 U/L; IQR, 3-17 U/L]). Of 40 severely and critically ill patients, 34 (85%) had hypokalemia. Patients with severe hypokalemia were given potassium at a dose of 40 mEq per day, for a total mean (SD) of 453 (53) mEq potassium chloride, during the hospital stay. The patients responded well to potassium supplements as they recovered. Conclusions and Relevance: The correction of hypokalemia is challenging because of continuous renal potassium loss resulting from the degradation of angiotensin-converting enzyme 2. The high prevalence of hypokalemia among patients with COVID-19 suggests the presence of disordered rennin-angiotensin system activity, which increases as a result of reduced counteractivity of angiotensin-converting enzyme 2, which is bound by severe acute respiratory syndrome coronavirus 2.
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Betacoronavirus , Infecções por Coronavirus/complicações , Hipopotassemia/sangue , Hipopotassemia/virologia , Pneumonia Viral/complicações , Adulto , Enzima de Conversão de Angiotensina 2 , COVID-19 , China/epidemiologia , Estudos de Coortes , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Feminino , Humanos , Hipopotassemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Peptidil Dipeptidase A/sangue , Pneumonia Viral/sangue , Pneumonia Viral/virologia , Potássio/sangue , Prevalência , SARS-CoV-2RESUMO
OBJECTIVES: In recent years, home enteral nutrition (HEN) has been adopted as a feasible and safe form of nutrition for patients undergoing esophagectomy. The aim of this study was to compare the effects of 4 wk of HEN with standard enteral nutrition (SEN) on immune function, nutritional status, and survival in patients undergoing esophagectomy. METHODS: A parallel-group, randomized, single-blind, clinical trial was conducted between April 1 and August 1, 2017. Eighty patients were enrolled in the study and 62 were eligible for analysis. An enteral feeding pump was used to infuse enteral nutrition via jejunostomy tube postoperatively. Patients in HEN group were instructed to independently administer jejunostomy feeds at home. Immune parameters and nutritional indicators were measured at preoperative day 7 and at postoperative day 30. RESULTS: There were no significant differences in baseline characteristics between the two groups. The levels of immunoglobulin (Ig)A and IgG, which can reflect a patient's immune function, significantly increased in the HEN group compared with those in the SEN group (P = 0.042 and P = 0.003, respectively). Comparing the two groups, 2-y progression-free survival and overall survival had no significant differences in survival curves (P = 0.36 and P = 0.29, respectively). CONCLUSION: Four weeks of HEN is a safe and feasible nutritional strategy to improve immune function and nutritional status after esophagectomy. Although there was no significant difference in survival between the two groups, HEN could still be more effective and beneficial than SEN to patients with defective nutritional and immune status.
Assuntos
Nutrição Enteral , Esofagectomia , Suplementos Nutricionais , Humanos , Imunidade , Método Simples-CegoRESUMO
OBJECTIVES: According to retrospective studies, oesophageal carcinoma is the second deadliest gastrointestinal cancer after gastric cancer. Enteral immunonutrition (EIN) has been increasingly used to enhance host immunity and relieve the inflammatory response of patients undergoing oesophagectomy; however, conclusions across studies remain unclear. We aimed to evaluate the effect of EIN on the clinical and immunological outcomes of patients undergoing oesophagectomy. METHODS: Four electronic databases (MEDLINE, Embase, Web of Science and Cochrane Library) were used to search articles in peer-reviewed, English-language journals. The mean difference, relative risk or standard mean difference with 95% confidence interval were calculated. Heterogeneity was assessed by the Cochran's Q test and I2 statistic combined with the corresponding P-value. The analysis was carried out with RevMan 5.3. RESULTS: Six articles were finally included, with a total of 320 patients with oesophageal cancer. The meta-analysis results showed that EIN did not improve clinical outcomes (such as infectious complications, pneumonia, surgical site infection, anastomotic leak and postoperative hospital stay) or immune indices [referring to C-reactive protein, interleukin (IL)-6, IL-8, tumour necrosis factor-α]. Descriptive analysis suggested that EIN also increased the serum concentrations of IgG and the percentage of the B-cell fraction. Thus, its impact on IL-8 and IL-6 remains inconsistent. CONCLUSIONS: The early-stage impact of EIN on immunological status in patients undergoing oesophagectomy is still unclear. According to the results of this meta-analysis, whether EIN could improve the clinical outcomes or biological status after oesophagectomy compared to standard enteral nutrition is uncertain. Since the impact of EIN is unclear, current guidelines that strongly advise the use of EIN should be changed, as the utility of EIN is very uncertain. More appropriately powered clinical studies are warranted to confirm its effectiveness.
Assuntos
Nutrição Enteral/métodos , Neoplasias Esofágicas/secundário , Esofagectomia , Imunossupressores/uso terapêutico , Imunoterapia/métodos , Cuidados Pré-Operatórios/métodos , HumanosRESUMO
Combined application of nitrogen (N) and potassium (K) fertilizer could significantly enhance crop yield. Crop yield and photosynthesis are inseparable. However, the influence of N and K interaction on photosynthesis is still not fully understood. Field and hydroponic experiments were conducted to examine the effects of N and K interaction on leaf photosynthesis characteristics and to explore the mechanisms in the hydroponic experiment. CO2 conductance and carboxylation characteristic parameters of oilseed leaves were measured under different N and K supplies. Results indicated that detectable increases in leaf area, biomass and net photosynthetic rate (An ) were observed under optimal N and K supply in field and hydroponic experiments. The ratio of total CO2 diffusion conductance to the maximum carboxylation rate (gtot /Vcmax ) and An presented a linear-plateau relationship. Under insufficient N, increased K contributed to the CO2 transmission capacity and improved the proportion of N used for carboxylation, promoting gtot /Vcmax . However, the low Vcmax associated with N insufficiency limited the An . High N supply obviously accelerated Vcmax , yet K deficiency led to a reduction of gtot , which restricted Vcmax . Synchronous increases in N and K supplementation ensured the appropriate ratio of N to K content in leaves, which simultaneously facilitated gtot and Vcmax and preserved a gtot /Vcmax suitable for guaranteeing CO2 transmission and carboxylation coordination; the overall effect was increased An and leaf area. These results highlight the suitable N and K nutrients to coordinate CO2 diffusion and carboxylation, thereby enhancing photosynthetic capacity and area to obtain high crop yield.
Assuntos
Dióxido de Carbono/metabolismo , Nitrogênio/metabolismo , Folhas de Planta/metabolismo , Potássio/metabolismo , Fotossíntese/fisiologia , Folhas de Planta/fisiologiaRESUMO
Three new glycosides (1-3), together with six known ones (4-9), were isolated from the root bark of Lycium chinense. Their structures were elucidated on the basis of MS and NMR spectroscopic data. Five compounds (3, 5, 6, 8, and 9) exhibited potent antihyperlipidemic activities in HepG2 cells as assessed by Oil Red O staining and significant inhibition of intracellular triglyceride (TG) levels, whereas two compounds (5 and 9) significantly reduced total cholesterol (TC) levels.
Assuntos
Glicosídeos/química , Glicosídeos/farmacologia , Hipolipemiantes/farmacologia , Lycium/química , Colesterol/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Células Hep G2 , Humanos , Hipolipemiantes/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Casca de Planta/química , Extratos Vegetais/química , Espectrometria de Massas por Ionização por Electrospray , Triglicerídeos/metabolismoRESUMO
BACKGROUND: Epidermal growth factor (EGF) can promote cell proliferation as well as migration, which is feasible in tissue wound healing. Oil bodies have been exploited as an important platform to produce exogenous proteins. The exogenous proteins were expressed in oil bodies from plant seeds. The process can reduce purification steps, thereby significantly reducing the purification cost. Mostly, the diameter of oil body particle ranges between 1.0 and 1.5 µm in the safflower seeds, however, it reduces to 700-1000 nm in the transgenic safflower seeds. The significant reduction of particle size in transgenic seeds is extremely beneficial to skin absorption. RESULTS: The diameter of oil body in the transgenic safflower seeds was recorded in the range of 700-1000 nm. The smaller particle size improved their skin absorption. The expression level of oleosin-hEGF-hEGF in T3 transgenic seeds was highest at 69.32 mg/g of seeds. The oil body expressing oleosin-hEGF-hEGF had significant proliferative activity on NIH/3T3 cells and improved skin regeneration thereby accelerating wound healing in rats. The wound coverage rate exceeded 98% after treatment for 14 days with oil body expressing oleosin-hEGF-hEGF, while the saline without EGF group and wild type oil body group both showed less than 80%. The neonatal fibroblast and collagen were found to be increased in the safflower oil body expressing oleosin-hEGF-hEGF treatment group. TGF-ß1, bFGF and VEGF were noted as important growth factors in the repair of cutaneous wounds. Their expression level increased after 4 and 7 day treatment, but decreased after 14 days. Therefore, it can promote skin regeneration to accelerate wounds healing. CONCLUSIONS: The expression of oleosin-hEGF-hEGF in T3 transgenic seeds was 80.43 ng/µL oil body. It had significant proliferative activity on NIH/3T3 cells and improved skin regeneration to accelerate wound healing in rats. The expression process of TGF-ß1, bFGF and VEGF increased at first and then gradually declined.
Assuntos
Fator de Crescimento Epidérmico/química , Gotículas Lipídicas/química , Proteínas de Plantas/química , Pele/metabolismo , Cicatrização/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Células NIH 3T3 , Tamanho da Partícula , Óleos de Plantas/química , Ratos , Ratos Wistar , Regeneração/efeitos dos fármacos , Sementes/química , Propriedades de Superfície , Distribuição Tecidual/efeitos dos fármacos , Distribuição Tecidual/imunologiaRESUMO
Severe fever with thrombocytopenia syndrome (SFTS) caused by a recently identified bunyavirus, SFTSV, is an emerging infectious disease with extensive geographical distribution and high mortality. Progressive viral replication and severe thrombocytopenia are key features of SFTSV infection and fatal outcome, whereas the underlying mechanisms are unknown. We revealed arginine deficiency in SFTS cases by performing metabolomics analysis on two independent patient cohorts, suggesting that arginine metabolism by nitric oxide synthase and arginase is a key pathway in SFTSV infection and consequential death. Arginine deficiency was associated with decreased intraplatelet nitric oxide (Plt-NO) concentration, platelet activation, and thrombocytopenia. An expansion of arginase-expressing granulocytic myeloid-derived suppressor cells was observed, which was related to T cell CD3-ζ chain down-regulation and virus clearance disturbance, implicating a role of arginase activity and arginine depletion in the impaired anti-SFTSV T cell function. Moreover, a comprehensive measurement of arginine bioavailability, global arginine bioavailability ratio, was shown to be a good prognostic marker for fatal prediction in early infection. A randomized controlled trial demonstrated that arginine administration was correlated with enhanced Plt-NO concentration, suppressed platelet activation, and elevated CD3-ζ chain expression and eventually associated with an accelerated virus clearance and thrombocytopenia recovery. Together, our findings revealed the arginine catabolism pathway-associated regulation of platelet homeostasis and T cell dysregulation after SFTSV infection, which not only provided a functional mechanism underlying SFTS pathogenesis but also offered an alternative therapy choice for SFTS.
Assuntos
Arginina/deficiência , Infecções por Bunyaviridae/complicações , Infecções por Bunyaviridae/imunologia , Terapia de Imunossupressão , Phlebovirus/fisiologia , Trombocitopenia/complicações , Trombocitopenia/virologia , Arginina/uso terapêutico , Plaquetas/metabolismo , Infecções por Bunyaviridae/sangue , Infecções por Bunyaviridae/tratamento farmacológico , Complexo CD3/metabolismo , Suplementos Nutricionais , Humanos , Imunidade , Metaboloma , Metabolômica , Células Supressoras Mieloides/metabolismo , Óxido Nítrico/metabolismo , Linfócitos T/imunologia , Trombocitopenia/sangue , Trombocitopenia/tratamento farmacológicoRESUMO
The expression of fibroblast growth factor 9 (FGF9) recombinant fusion protein in Carthamus tinctorius was used to identify its effect on hair regrowth and wound repair system in mice, providing a basis for C. tinctorius as a plant bioreactor, and establishing a foundation for commercial applications of FGF9 fusion protein in hair regrowth and wound repair. The identified pOTBar-oleosin-rhFGF9 plasmid was transformed into Agrobacterium tumefaciens EHA105 by freeze-thaw method, and the oleosin-rhFGF9 gene was transformed into safflower leaves by A. tumefaciens mediated method. Transgenic safflower seedlings were then obtained by tissue culture. After basta screening, transgenic T3 safflower seeds were obtained by grafting method, PCR verification and propagation. The expression of oleosin-rhFGF9 was detected by Western blot, and the content of oleosin-rhFGF9 fusion protein was 0.09% by using ELISA quantitative method. It was observed that 60 µg·L⻹ transgenic safflower oil had better effect on promoting NIH/3T3 cells proliferation in a certain dose-dependent manner. Sixty C57BL/6 mice were used to establish alopecia model and wound model respectively, and then were randomly divided into control group (treated with PBS or saline), negative group (treated with wild type safflower seed oil bodies, 60 g·L⻹), positive group (treated with FGF9, 0.054 g·L⻹), low dose group (treated with transgenic safflower oil bodies, 10 g·L⻹) and high dose group (treated with transgenic safflower oil bodies, 60 g·L⻹). The skin of all above-mentioned mice models were coated with soft adhesive manner every other day, 100 µL/time. After 15 days, the mice skin was cut and embedded for histological analysis. The hair regrowth experimental results showed that the hair of mice grew well, and the mice in high dose group had bushy hair, with significant effect on regeneration hair number as compared with the positive group. The healing was obvious in wound experiment, with significant healing effect in positive group, high dose group and low dose group as compared to blank control group. Furthermore, high dose group remarkably showed a better and higher healing effect than the positive group at day 5. Oleosin-rhFGF9 was successfully transformed into safflower, and T3 transgenic safflower oil bodies expressed oleosin-rhFGF9 fusion protein were obtained, with the role of promoting hair regeneration and wound repair in mice.