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1.
Plants (Basel) ; 13(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38592916

RESUMO

'Whangkeumbae' (Pyrus pyrifolia) is a variety of sand pear fruit well-known for its smooth surface and good taste. However, the fruit quality is adversely affected by postharvest ethylene production. Therefore, improving postharvest shelf life by regulating fruit senescence is critical to promoting the 'Whangkeumbae' fruit industry. Here, we investigated the effect of salicylic acid (SA) spray on fruit senescence in sand pears during room temperature shelf life. Exogenous SA reduced polyphenol oxidase (PPO) activity and malondialdehyde (MDA) content during room temperature shelf life. Additionally, SA effectively maintained the fruit skin coloration and increased the activity of antioxidant enzymes, such as superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX). SA treatment inhibited PpPPO1 expression and upregulated PpSOD1, PpAPX6, and PpGST2 expression. Furthermore, SA application downregulated the expression of PpACO2, PpEIN3a, PpNCED1, and PpAOC2, while upregulating PpNPR-1, PpTAR2, and PpCOMT1 during room temperature shelf life. SA treatment also influenced cell wall metabolism and modification genes by inhibiting PpPG1, PpPME2, and PpCEL3 and inducing PpPGIP1 expression. Additionally, SA treatment affected sugar and acid metabolism genes and increased the expression of PpSPS1, PpSUS1, PpSOT1, PpTMT4, PpSWEET15, and PpcyNAD-MDH, but suppressed the expression of PpcyNADP-ME. The Pearson correlation analysis indicated that PPO activity and MDA content were positively correlated with the expression of PpPPO1, PpACO2, PpEIN3a, PpNCED1, PpAOC2, PpPG1, PpPME2, PpCEL3, and PpcyNDA-MDH. Conversely, these factors were negatively associated with the activities of SOD, POD, CAT, and APX, as well as the expression levels of PpSOD1, PpPOD1, PpCAT1, PpAPX6, PpGST2, PpNPR-1, PpTAR2, PpCOMT1, PpPGIP1, PpSPS1, PpSUS1, PpSOT1, PpTMT4, PpSWEET15, and PpcyNAD-MDH. Our results reveal that exogenous SA could delay fruit senescence in sand pear fruit by regulating various biochemical and molecular mechanisms and can be used to effectively extend fruit shelf life during room temperature storage. However, further research is necessary to determine whether the fruits sprayed with SA are suitable for direct human consumption.

2.
Synth Syst Biotechnol ; 9(3): 453-461, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38634001

RESUMO

Vitamin B12 is a complex compound synthesized by microorganisms. The industrial production of vitamin B12 relies on specific microbial fermentation processes. E. coli has been utilized as a host for the de novo biosynthesis of vitamin B12, incorporating approximately 30 heterologous genes. However, a metabolic imbalance in the intricate pathway significantly limits vitamin B12 production. In this study, we employed multivariate modular metabolic engineering to enhance vitamin B12 production in E. coli by manipulating two modules comprising a total of 10 genes within the vitamin B12 biosynthetic pathway. These two modules were integrated into the chromosome of a chassis cell, regulated by T7, J23119, and J23106 promoters to achieve combinatorial pathway optimization. The highest vitamin B12 titer was attained by engineering the two modules controlled by J23119 and T7 promoters. The inclusion of yeast powder to the fermentation medium increased the vitamin B12 titer to 1.52 mg/L. This enhancement was attributed to the effect of yeast powder on elevating the oxygen transfer rate and augmenting the strain's isopropyl-ß-d-1-thiogalactopyranoside (IPTG) tolerance. Ultimately, vitamin B12 titer of 2.89 mg/L was achieved through scaled-up fermentation in a 5-liter fermenter. The strategies reported herein will expedite the development of industry-scale vitamin B12 production utilizing E. coli.

3.
J Cosmet Dermatol ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654514

RESUMO

BACKGROUND: Facial cutaneous sporotrichosis presents with diverse clinical manifestations, often leading to misdiagnosis. OBJECTIVE: This study aims to present the clinical characteristics of five misdiagnosed cases of facial cutaneous sporotrichosis, aiming to enhance understanding of this disease and prevent misdiagnosis and mistreatment. METHODS: Clinical data, histopathology, and fungal culture results of these five cases were comprehensively analyzed. RESULTS: Among these five patients, three presented with lymphocutaneous sporotrichosis, while two had the fixed cutaneous type. Due to misdiagnosis, initial treatments were ineffective for all patients. Upon histopathological examination and fungal culture confirming sporotrichosis, treatment with itraconazole for 3 months led to complete resolution of lesions. While one patient experienced a relapse due to noncompliance with the prescribed medication. CONCLUSION: Facial sporotrichosis, with its diverse clinical manifestations and obscure trauma history, is prone to misdiagnosis. Timely and thorough examinations are crucial for precise diagnosis and management. Itraconazole treatment demonstrated notable efficacy, and patient compliance is also essential for favorable outcomes.

4.
Sci Total Environ ; 929: 172332, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615776

RESUMO

Nanobiotechnology and the engineering of nanomaterials are currently the main focus of many researches. Seafood waste carbon nanomaterials (SWCNs) are a renewable resource with large surface area, porous structure, high reactivity, and abundant active sites. They efficiently adsorb food contaminants through π-π conjugated, ion exchange, and electrostatic interaction. Furthermore, SWCNs prepared from seafood waste are rich in N and O functional groups. They have high quantum yield (QY) and excellent fluorescence properties, making them promising materials for the removal and detection of pollutants. It provides an opportunity by which solutions to the long-term challenges of the food industry in assessing food safety, maintaining food quality, detecting contaminants and pretreating samples can be found. In addition, carbon nanomaterials can be used as adsorbents to reduce environmental pollutants and prevent food safety problems from the source. In this paper, the types of SWCNs are reviewed; the synthesis, properties and applications of SWCNs are reviewed and the raw material selection, preparation methods, reaction conditions and formation mechanisms of biomass-based carbon materials are studied in depth. Finally, the advantages of seafood waste carbon and its composite materials in pollutant removal and detection were discussed, and existing problems were pointed out, which provided ideas for the future development and research directions of this interesting and versatile material. Based on the concept of waste pricing and a recycling economy, the aim of this paper is to outline current trends and the future potential to transform residues from the seafood waste sector into valuable biological (nano) materials, and to apply them to food safety.

5.
ACS Omega ; 9(14): 16322-16333, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38617635

RESUMO

Coronary heart disease remains a major global health challenge, with a clear need for enhanced early risk assessment. This study aimed to elucidate metabolic signatures across various stages of coronary heart disease and develop an effective multiclass diagnostic model. Using metabolomic approaches, gas chromatography-mass and liquid chromatography-tandem mass spectrometry were used to analyze plasma samples from healthy controls, patients with stable angina pectoris, and those with acute myocardial infarction. Pathway enrichment analysis was conducted on metabolites exhibiting significant differences. The key metabolites were identified using Random Forest and Recursive Feature Elimination strategies to construct a multiclass diagnostic model. The performance of the model was validated through 10-fold cross-validation and evaluated using confusion matrices, receiver operating characteristic curves, and calibration curves. Metabolomics was used to identify 1491 metabolites, with 216, 567, and 295 distinctly present among the healthy controls, patients with stable angina pectoris, and those with acute myocardial infarction, respectively. This implicated pathways such as the glucagon signaling pathway, d-amino acid metabolism, pyruvate metabolism, and amoebiasis across various stages of coronary heart disease. After selection, testosterone isobutyrate, N-acetyl-tryptophan, d-fructose, l-glutamic acid, erythritol, and gluconic acid were identified as core metabolites in the multiclass diagnostic model. Evaluating the diagnostic model demonstrated its high discriminative ability and accuracy. This study revealed metabolic pathway perturbations at different stages of coronary heart disease, and a precise multiclass diagnostic model was established based on these findings. This study provides new insights and tools for the early diagnosis and treatment of coronary heart disease.

7.
Biochem Pharmacol ; 222: 116104, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428826

RESUMO

Adipose tissues (AT) are an important endocrine organ that secretes various functional adipokines, peptides, non-coding RNAs, and acts on AT themselves or other distant tissues or organs through autocrine, paracrine, or endocrine manners. An accumulating body of evidence has suggested that many adipokines play an important role in liver metabolism. Besides the traditional adipokines such as adiponectin and leptin, many novel adipokines have recently been identified to have regulatory effects on the liver. Additionally, AT can produce extracellular vesicles (EVs) that act on peripheral tissues. However, under pathological conditions, such as obesity and diabetes, dysregulation of adipokines is associated with functional changes in AT, which may cause liver diseases. In this review, we focus on the newly discovered adipokines and EVs secreted by AT and highlight their actions on the liver under the context of obesity, nonalcoholic fatty liver diseases (NAFLD), and some other liver diseases. Clarifying the action of adipokines and adipose tissue-derived EVs on the liver would help to identify novel therapeutic targets or biomarkers for metabolic diseases.


Assuntos
Adipocinas , Hepatopatia Gordurosa não Alcoólica , Humanos , Adipocinas/metabolismo , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Adiponectina , Hepatopatia Gordurosa não Alcoólica/metabolismo
8.
Sci Total Environ ; 927: 171888, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38531442

RESUMO

Lignocellulosic biomass is a pivotal renewable resource in biorefinery process, requiring pretreatment, primarily chemical pretreatment, for effective depolymerization and subsequent transformation. This process yields solid residue for saccharification and lignocellulosic pretreatment wastewater (LPW), which comprises sugars and inhibitors such as phenols and furans. This study explored the microalgal capacity to treat LPW, focusing on two key hydrolysate inhibitors: furfural and vanillin, which impact the growth of six green microalgae. Chlorella sorokiniana exhibited higher tolerance to furfural and vanillin. However, both inhibitors hindered the growth of C. sorokiniana and disrupted algal photosynthetic system, with vanillin displaying superior inhibition. A synergistic inhibitory effect (Q < 0.85) was observed with furfural and vanillin on algal growth. Furfural transformation to low-toxic furfuryl alcohol was rapid, yet the addition of vanillin hindered this process. Vanillin stimulated carbohydrate accumulation, with 50.48 % observed in the 0.1 g/L furfural + 0.1 g/L vanillin group. Additionally, vanillin enhanced the accumulation of C16: 0 and C18: 2, reaching 21.71 % and 40.36 %, respectively, with 0.1 g/L vanillin. This study proposed a microalgae-based detoxification and resource utilization approach for LPW, enhancing the comprehensive utilization of lignocellulosic components. The observed biomass modifications also suggested potential applications for biofuel production, contributing to the evolving landscape of sustainable biorefinery processes.


Assuntos
Lignina , Microalgas , Eliminação de Resíduos Líquidos , Águas Residuárias , Águas Residuárias/química , Lignina/metabolismo , Eliminação de Resíduos Líquidos/métodos , Benzaldeídos/metabolismo , Furaldeído/metabolismo , Biomassa , Poluentes Químicos da Água , Chlorella/metabolismo
9.
Int J Gen Med ; 17: 863-870, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38463441

RESUMO

Purpose: To investigate the predictive value of hemoglobin (Hb) to red blood cell distribution width (RDW) (Hb/RDW) ratio in combination with serum sodium for major adverse cardiovascular events (MACE) in elderly acute heart failure patients with preserved ejection fraction at 30 days after discharge. Methods: 130 elderly acute heart failure patients with preserved ejection fraction were enrolled and followed up at 30 days after discharge. They were classified into the MACE group (n=11) and none-MACE group (n=119). On the day of admission, clinical baseline characteristics were measured and results from laboratory tests were gathered. The correlation and predictive value of Hb/RDW and serum sodium with the occurrence of MACE at 30 days after discharge in acute heart failure patients with preserved ejection fraction in the elderly were analyzed. Results: Spearman correlation analysis showed that the occurrence of MACE was negatively correlated with Hb/RDW, serum sodium (r=-0.209, r=0.291, p<0.05) and Hb/RDW (OR=0.484, 95% CI:0.254, 0.922), serum sodium (OR=0.779, 95% CI:0.646,0.939) were independent risk factors (p<0.05) analyzed by multifactorial logistic. Receiver operating characteristic curves (ROC) analysis showed that the area under the curve (AUC) for the prediction of MACE by Hb/RDW was 0.73, with an optimal threshold of 9.28, sensitivity 81.80%, specificity 70.60%, positive predictive value (PPV) 20.50%, negative predictive value (NPV) 97.70%; the AUC of serum sodium for predicting the occurrence of MACE was 0.76, with an optimal threshold of 140.35 mmol/L, sensitivity 90.90%, specificity 57.10%, PPV 16.40%, NPV 98.60%; and the AUC of Hb/RDW combined serum sodium to predict the occurrence of MACE was 0.83, with sensitivity 90.90%, specificity 78.20%, PPV 27.80% and NPV 98.90%. Conclusion: Hb/RDW and serum sodium had negative correlation with MACE and were independent risk factors of 30-day MACE; Hb/RDW combined with serum sodium can predict 30-day MACE occurrence in elderly acute heart failure patients with preserved ejection fraction.

10.
Behav Brain Res ; 465: 114962, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38499157

RESUMO

BACKGROUND: Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP1) is upregulated in the hippocampus of patients with depression, while pharmacological inhibition of hippocampal MKP1 can mitigate depression-like behaviors in rodents. In addition, MAPK signaling regulates autophagy, and antidepressants were recently shown to target autophagic signaling pathways. We speculated that MKP1 contributes to depression by enhancing hippocampal autophagy through dephosphorylation of the MAPK isoform ERK1/2. METHODS: We established a rat depression model by exposure to chronic unpredictable mild stress (CUMS), and then examined depression-like behaviors in the sucrose preference test (SPT) and forced swimming test (FST) as well as expression changes in hippocampal MKP1, ERK1/2, phosphorylated ERK1/2, and autophagy-related proteins LC3II by Western blotting and immunostaining. These same measurements were repeated in rats exposed to CUMS following hippocampal infusion of a MKP1-targeted shRNA. Finally, the effects of MKP1 expression level on autophagy we examined in rat GMI-R1 microglia. RESULTS: CUMS-exposed rats demonstrated anhedonia in the SPT and helplessness in the FST, two core depression-like behaviors. Expression levels of MKP1 and LC3II were upregulated in the hippocampus of CUMS rats, suggesting enhanced autophagy, while pERK/ERK was downregulated. Knockdown of hippocampal MKP1 mitigated depression-like behaviors, downregulated hippocampal LC3II expression, and upregulated hippocampal pERK/ERK. Similarly, MKP1 knockdown in GMI-R1 cells upregulated pERK/ERK and reduced the number of LC3II autophagosomes, while MKP1 overexpression had the opposite effects. CONCLUSION: Enhanced hippocampal autophagy via MKP1-mediated ERK dephosphorylation may contribute to the development of depression.


Assuntos
Depressão , Hipocampo , Animais , Ratos , Antidepressivos/farmacologia , Autofagia , Depressão/metabolismo , Modelos Animais de Doenças , Hipocampo/metabolismo , Transdução de Sinais , Estresse Psicológico/metabolismo
11.
Clin Cosmet Investig Dermatol ; 17: 477-481, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435842

RESUMO

A 43-year-old male was diagnosed with vitiligo and had been treated with topical nitrogen mustard at the age of 13. Following two years of treatment, eruptive cherry angiomas developed and presented as widely distributed red papules throughout his trunk and proximal limbs. Ceasing the use of nitrogen mustard slowed the emergence of lesions. This case highlights the potential adverse effects associated with nitrogen mustard treatment in individuals with susceptibility, as it may lead to the onset of eruptive cherry angiomas.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38430163

RESUMO

Background: A traditional Chinese medicine (TCM) formula, containing Astragalus membranaceus (Fisch.) Bunge, Aconitum wilsonii Stapf ex Veitch, Curcuma longa L., and Radix ophiopogonis (AACO), has therapeutic value for the treatment of chronic heart failure (CHF). Objective: This study intends to explore the pharmacological mechanism underlying the activity of the AACO formula against CHF. Materials and Methods: Using the TCM Systems Pharmacology database and Bioinformatics Analysis Tool for Molecular Mechanism of TCM, the active ingredients contained in the herbs of the AACO formula were screened. Meanwhile, the target genes related to these active ingredients were identified and genes correlated with CHF were screened. Protein-protein interaction networks were built to elucidate the relationships between the AACO formula and CHF. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment analysis were carried out using the DAVID database. A "drug-component-target-disease" network was constructed with Cytoscape 3.7.0. The therapeutic effect of the AACO formula was proven by hemodynamic study, echocardiography evaluation, and histological analysis in transverse aortic constriction-induced CHF mice and was validated in vitro. Results: A total of 105 active ingredients and 1026 related targets were screened and identified, and 240 related targets overlapping with CHF were selected. According to GO analysis, the enriched genes participated in gene expression and cardiac contraction regulation by Ca2+ regulation. From KEGG analysis, the calcium axis was identified as one of the main mechanisms through which the AACO formula exerts an anti-CHF effect. AACO was validated to significantly improve cardiac diastolic and systolic functions in vivo via an increase in the rate of Ca2+ reuptake of the myocardial sarcoplasmic reticulum and improved myocardial contractility in vitro. Conclusions: Network pharmacology is a convenient method to study the complex pharmacological mechanisms of TCM. The calcium axis likely participates in the anti-CHF mechanism of AACO.

13.
Chest ; 165(3): e71-e74, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38461021

RESUMO

CASE PRESENTATION: An 8-year-old girl presented with a 34-day history of cough, fatigue, and impaired exercise tolerance. She experienced cyanosis on exertion but denied fever, hemoptysis, hematuria, or seizures. Her perinatal and family histories were unremarkable, and she had no history of exposure to TB. A chest radiogram from a local clinic showed diffuse pulmonary lesions. Tuberculin skin test, interferon-γ release assay, and HIV antibody test results were all negative. Immunoglobulin levels and lymphocyte subsets were normal. The patient did not respond to IV azithromycin for 1 week for community-acquired pneumonia. She was transferred to our hospital because of progressive respiratory distress and hypoxemia.


Assuntos
Azitromicina , Tosse , Humanos , Feminino , Criança , Tosse/etiologia , Hemoptise , Dispneia , Hipóxia/complicações
14.
Front Immunol ; 15: 1281741, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38420126

RESUMO

Allergic diseases in children are major public health concerns due to their widespread and rising prevalence. Food-specific immunoglobulin G4(FS-IgG4) has been detected in patients with allergic diseases, but its clinical significance is still debated. In the present study, 407 children with allergic diseases were recruited and categorized into three groups according to the different systems involved: the respiratory system group, the skin system group, and a multiple system group, with the collection of clinical symptoms and serum antibodies, including total immunoglobulin E (IgE), house dust mite (HDM) IgE, food-specific IgE (FS-IgE), and FS-IgG4. Part of these patients were followed up with the intervention of FS-IgG4-guided diet elimination with or without add-on probiotics supplement. The analysis at baseline revealed distinct serum levels of different antibodies. The positive rate of FS-IgG4 in all groups was more than 80%, and the proportion of total IgE and FS-IgG4 both positive in the multi-system group was the highest (p=0.039). Egg and milk were the foods with the highest positive rate of FS-IgG4 in all groups. After diet elimination for more than 3 months, serum FS-IgG4 in children significantly decreased (P<0.05) along with the improvement of clinical symptoms, regardless of the add-on of probiotics. However, the intervention did not impact the serum levels of total IgE, FS-IgE, and HDM IgE. There was no further decrease of serum FS-IgG4 level in children followed up for more than 1 year, which may be related to noncompliance with diet elimination. Multivariate regression analysis revealed that the decline of serum FS-IgG4 was an independent predictable factor for the improvement of clinical symptoms (adjusted OR:1.412,95%CI 1.017-1.96, p=0.039). The add-on of probiotics showed less efficiency in reducing the FS-IgG4 level in more patients with relief of clinical symptoms. Our results confirmed the correlation between FS-IgG4 and allergic diseases, and the decreased FS-IgG4 could be a useful predictor for the improvement of allergic symptoms. FS-IgG4-guided diet elimination is an efficient treatment for allergic diseases. Our study adds solid data to the clinical significance of FS-IgG4 in allergic diseases.


Assuntos
Hipersensibilidade , Imunoglobulina G , Criança , Animais , Humanos , Alérgenos , Imunoglobulina E , Dieta , Pyroglyphidae , Dermatophagoides pteronyssinus , Leite
15.
Cell Biochem Biophys ; 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300374

RESUMO

This investigation delves into the structural foundation of human dermal telocytes (TCs) with the aim of elucidating their role in signal transmission. Dermal TCs were isolated from human foreskins via enzymatic digestion and flow cytometric sorting, and identified by immunohistochemical staining with an antibody against CD34. The ultrastructure of TCs was examined using transmission electron microscopy (TEM). The proliferation rates of sorted TCs and CD34-negative fibroblasts were compared using the MTS assay (Cell Proliferation Assay). Images of viable cultured TCs were analyzed using atomic force microscopy (AFM) under normal atmospheric pressure and temperature. Results demonstrated that dermal TCs were positive for CD34 and vimentin, predominantly distributed in the reticular dermis and subcutaneous tissue, forming interwoven networks. Each TC had a small body with a high nuclear-plasma ratio and two or three extremely long and thin telopodes (TPs), exhibiting a typical 'moniliform' appearance. Compared with CD34-negative fibroblasts, dermal TCs exhibited significantly lower proliferation rates. Cultured TCs displayed typical moniliform projections (namely, TPs) in the AFM images. The distal ends of TPs were enlarged, shaped like a broom, and extended multiple pseudopods to contact other cell bodies. Slender filamentary pseudopodia and thick, short cone-like structures were observed on the surfaces of the dilated segments and terminals of TPs. These structures are assumed to be evidence of the secretion and release of endosomes, such as exosomes, and the communication between cells. TCs form interstitial networks in the reticular dermis and subcutaneous tissue, providing a structural basis for contacts between cells and the secretion of signal-carrying substances, involving intercellular connections and communication.

17.
Small ; : e2308850, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38366271

RESUMO

Personalized radiotherapy strategies enabled by the construction of hypoxia-guided biological target volumes (BTVs) can overcome hypoxia-induced radioresistance by delivering high-dose radiotherapy to targeted hypoxic areas of the tumor. However, the construction of hypoxia-guided BTVs is difficult owing to lack of precise visualization of hypoxic areas. This study synthesizes a hypoxia-responsive T1 , T2 , T2 mapping tri-modal MRI molecular nanoprobe (SPION@ND) and provides precise imaging of hypoxic tumor areas by utilizing the advantageous features of tri-modal magnetic resonance imaging (MRI). SPION@ND exhibits hypoxia-triggered dispersion-aggregation structural transformation. Dispersed SPION@ND can be used for routine clinical BTV construction using T1 -contrast MRI. Conversely, aggregated SPION@ND can be used for tumor hypoxia imaging assessment using T2 -contrast MRI. Moreover, by introducing T2 mapping, this work designs a novel method (adjustable threshold-based hypoxia assessment) for the precise assessment of tumor hypoxia confidence area and hypoxia level. Eventually this work successfully obtains hypoxia tumor target and accurates hypoxia tumor target, and achieves a one-stop hypoxia-guided BTV construction. Compared to the positron emission tomography-based hypoxia assessment, SPION@ND provides a new method that allows safe and convenient imaging of hypoxic tumor areas in clinical settings.

18.
Transl Psychiatry ; 14(1): 130, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38424085

RESUMO

Chronic stress is the primary environmental risk factor for major depressive disorder (MDD), and there is compelling evidence that neuroinflammation is the major pathomechanism linking chronic stress to MDD. Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is a negative regulator of MAPK signaling pathways involved in cellular stress responses, survival, and neuroinflammation. We examined the possible contributions of MKP-1 to stress-induced MDD by comparing depression-like behaviors (anhedonia, motor retardation, behavioral despair), neuroinflammatory marker expression, and MAPK signaling pathways among rats exposed to chronic unpredictable mild stress (CUMS), overexpressing MKP-1 in the hippocampus, and CUMS-exposed rats underexpressing MKP-1 in the hippocampus. Rats exposed to CUMS exhibited MKP-1 overexpression, greater numbers of activated microglia, and enhanced expressions of neuroinflammatory markers (interleukin [IL]-6, [IL]-1ß, tumor necrosis factor [TNF]-ɑ, and decreased phosphorylation levels of ERK and p38 in the hippocampus as well as anhedonia in the sucrose preference test, motor retardation in the open field, and greater immobility (despair) in the forced swimming tests. These signs of neuroinflammation and depression-like behaviors and phosphorylation levels of ERK and p38 were also observed in rats overexpressing MKP-1 without CUMS exposure, while CUMS-induced neuroinflammation, microglial activation, phosphorylation levels of ERK and p38, and depression-like behaviors were significantly reversed by MKP-1 knockdown. Moreover, MKP-1 knockdown promoted the activation of the MAPK isoform ERK, implying that the antidepressant-like effects of MKP-1 knockdown may be mediated by the ERK pathway disinhibition. These findings suggested that hippocampal MKP-1 is an essential regulator of stress-induced neuroinflammation and a promising target for antidepressant development.


Assuntos
Depressão , Transtorno Depressivo Maior , Animais , Ratos , Anedonia , Antidepressivos/uso terapêutico , Depressão/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Modelos Animais de Doenças , Regulação para Baixo , Hipocampo/metabolismo , Interleucina-6/metabolismo , Doenças Neuroinflamatórias , Estresse Psicológico/complicações , Estresse Psicológico/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
19.
Heliyon ; 10(4): e25616, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38375275

RESUMO

Pigs are natural host to various zoonotic pathogens including viruses. In this study, we analyzed the viral communities in the feces of 89 piglets with diarrhea under one month old which were collected from six farms in Jiangsu Province of the Eastern China, using the unbiased virus metagenomic method. A total of 89 libraries were constructed, and 46937894 unique sequence reads were generated by Illumina sequencing. Overall, the family Picornaviridae accounted for the majority of the total reads of putative mammalian viruses. Ten novel virus genomes from different family members were discovered, including Parvoviridae (n = 2), Picobirnaviridae (n = 4) and CRESS DNA viruses (n = 4). A large number of phages were identified, which mainly belonged to the order Caudovirales and the family Microviridae. Moreover, some identified viruses were closely related to viruses found in non-porcine hosts, highlighting the potential for cross-species virus dissemination. This study increased our understanding of the fecal virus communities of diarrhea piglets and provided valuable information for virus monitoring and preventing.

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