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1.
Aging (Albany NY) ; 162024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38613801

RESUMO

INTRODUCTION: Ulcerative colitis (UC) is a refractory disease with complex pathogenesis, and its pathogenesis is not clear. The present study aimed to investigate the potential target and related mechanism of Compound Sophora Decoction (CSD) in treating UC. METHODS: A network pharmacology approach predicted the components and targets of CSD to treat UC, and cell and animal experiments confirmed the findings of the approach and a new target for CSD treatment of UC. RESULTS: A total of 155 potential targets were identified for CSD treatment of UC, with some related to macrophage polarization, such as nitric oxide synthase (NOS2), also known as inducible nitric oxide synthase (iNOS). GO and KEGG enrichment analysis indicated that oxidative stress response and multiple inflammatory signaling pathways such as TNF-α may play a significant role. In vitro experiments revealed that Interferon-stimulated DNA (ISD) interference can cause polarization imbalances in Raw 264.7 and bone marrow-derived macrophages (BMDMs). Flow cytometry demonstrated that polarization of macrophages in the intestine, spleen, and lymph nodes in vivo was also unbalanced after dextran sulfate sodium (DSS) modeling with pathological intestinal injury. Both in vitro and in vivo studies indicated that after inducing inflammation, the levels of macrophage polarization-related markers (iNOS and Arg1) and inflammation-related factors (CCL17, IL10, TNF-α, and CXCL10) changed, accompanied by increased expression of cGAS. However, CSD treatment based on inflammation can inhibit the expression of cGAS protein and mRNA, lower the level of inflammatory factors, promote the expression of anti-inflammatory factors, and regulate macrophage polarization. CONCLUSION: We concluded that CSD alleviated DSS-induced UC by inhibiting cGAS, thus regulating macrophage polarization.

2.
Circ Res ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629274

RESUMO

BACKGROUND: Medial arterial calcification is a chronic systemic vascular disorder distinct from atherosclerosis and is commonly observed in patients with chronic kidney disease, diabetes, and aging individuals. We previously showed that NR4A3 (nuclear receptor subfamily 4 group A member 3), an orphan nuclear receptor, is a key regulator in apo (apolipoprotein) A-IV-induced atherosclerosis progression; however, its role in vascular calcification is poorly understood. METHODS: We generated NR4A3-/- mice and 2 different types of medial arterial calcification models to investigate the biological roles of NR4A3 in vascular calcification. RNA-seq was performed to determine the transcriptional profile of NR4A3-/- vascular smooth muscle cells under ß-glycerophosphate treatment. We integrated CUT&Tag analysis and RNA-seq data to further investigate the gene regulatory mechanisms of NR4A3 in arterial calcification and target genes regulated by histone lactylation. RESULTS: NR4A3 expression was upregulated in calcified aortic tissues from chronic kidney disease mice, 1,25(OH)2VitD3 overload-induced mice, and human calcified aorta. NR4A3 deficiency preserved the vascular smooth muscle cell contractile phenotype, inhibited osteoblast differentiation-related gene expression, and reduced calcium deposition in the vasculature. Further, NR4A3 deficiency lowered the glycolytic rate and lactate production during the calcification process and decreased histone lactylation. Mechanistic studies further showed that NR4A3 enhanced glycolysis activity by directly binding to the promoter regions of the 2 glycolysis genes ALDOA and PFKL and driving their transcriptional initiation. Furthermore, histone lactylation promoted medial calcification both in vivo and in vitro. NR4A3 deficiency inhibited the transcription activation and expression of Phospho1 (phosphatase orphan 1). Consistently, pharmacological inhibition of Phospho1-attenuated calcium deposition in NR4A3-overexpressed vascular smooth muscle cells, whereas overexpression of Phospho1 reversed the anticalcific effect of NR4A3 deficiency in vascular smooth muscle cells. CONCLUSIONS: Taken together, our findings reveal that NR4A3-mediated histone lactylation is a novel metabolome-epigenome signaling cascade mechanism that participates in the pathogenesis of medial arterial calcification.

3.
Sensors (Basel) ; 24(7)2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38610277

RESUMO

The accurate prediction of the future trajectories of traffic participants is crucial for enhancing the safety and decision-making capabilities of autonomous vehicles. Modeling social interactions among agents and revealing the inherent relationships is crucial for accurate trajectory prediction. In this context, we propose a goal-guided and interaction-aware state refinement graph attention network (SRGAT) for multi-agent trajectory prediction. This model effectively integrates high-precision map data and dynamic traffic states and captures long-term temporal dependencies through the Transformer network. Based on these dependencies, it generates multiple potential goals and Points of Interest (POIs). Through its dual-branch, multimodal prediction approach, the model not only proposes various plausible future trajectories associated with these POIs, but also rigorously assesses the confidence levels of each trajectory. This goal-oriented strategy enables SRGAT to accurately predict the future movement trajectories of other vehicles in complex traffic scenarios. Tested on the Argoverse and nuScenes datasets, SRGAT surpasses existing algorithms in key performance metrics by adeptly integrating past trajectories and current context. This goal-guided approach not only enhances long-term prediction accuracy, but also ensures its reliability, demonstrating a significant advancement in trajectory forecasting.

4.
Aging Med (Milton) ; 7(1): 131-135, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38571671

RESUMO

Background: Individuals with pre-existing chronic kidney disease (CKD) are at an increased risk of experiencing severe symptoms if infected with COVID-19. This report presents the case of a patient with CKD who contracted COVID-19 and subsequently experienced rapid deterioration of kidney function, hair loss, and spontaneous remission of facial warts. Case presentation: A 60-year-old Chinese man with a decade-long history of abnormal serum creatinine (Scr) levels and recently heightened fatigue sought treatment. The disease was previously managed and deemed resolved in 2020. However, when he contracted the novel coronavirus on December 20, 2022, he experienced persistent fatigue without other symptoms. In early January 2023, Scr levels was examined as more than 300 µmol/L. This was followed by hair loss, including eyebrows and lashes, and the spontaneous resolution of a longstanding facial wart. During this period, although the patient received kidney-protecting drugs and a lifestyle optimization, Scr increased continuously and the disease eventually progressed to the uremic stage. As the patient still had relatively abundant urine volume, the patient chose peritoneal dialysis treatment. At a two-month follow-up, he had adhered to the CAPD protocol without complications and his hair had begun to regrow. After eight months, his hair had mostly regrown, and his Scr levels kept stable. Conclusion: This case may represent the inaugural instance of CKD patients experiencing rapid deterioration of renal function, hair loss, and spontaneous remission of common warts. The underlying mechanisms of this unique phenomenon warrant further researches and debate.

5.
Nat Immunol ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561495

RESUMO

Cancer remains one of the leading causes of mortality worldwide, leading to increased interest in utilizing immunotherapy strategies for better cancer treatments. In the past decade, CD103+ T cells have been associated with better clinical prognosis in patients with cancer. However, the specific immune mechanisms contributing toward CD103-mediated protective immunity remain unclear. Here, we show an unexpected and transient CD61 expression, which is paired with CD103 at the synaptic microclusters of T cells. CD61 colocalization with the T cell antigen receptor further modulates downstream T cell antigen receptor signaling, improving antitumor cytotoxicity and promoting physiological control of tumor growth. Clinically, the presence of CD61+ tumor-infiltrating T lymphocytes is associated with improved clinical outcomes, mediated through enhanced effector functions and phenotype with limited evidence of cellular exhaustion. In conclusion, this study identified an unconventional and transient CD61 expression and pairing with CD103 on human immune cells, which potentiates a new target for immune-based cellular therapies.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38588566

RESUMO

OBJECTIVE: To describe the clinical features of Chinese patients with hydroxychloroquine (HCQ)-induced pigmentation and analyze the potential risk factors associated with HCQ-induced pigmentation. METHODS: A cross-sectional study was conducted over a duration of 7 months, during which patients who had received HCQ treatment for >6 months were included. Data was collected through a structured questionnaire that encompassed demographic and geographic characteristics, information on HCQ and concomitant medication usage, sun exposure characteristics, and hyperpigmentation-related characteristics. Univariate and multivariate analyses were employed to calculate the statistical association between HCQ-induced pigmentation and multiple variables. RESULTS: Out of 316 patients, 83 (26.3%) patients presented hyperpigmentation during HCQ treatment. Hyperpigmentation presented after a median duration of HCQ treatment of 12 months (interquartile range, 6.0 months-30.0 months) with a median cumulative dose of 108 g of HCQ (interquartile range, 36-288 g). The most frequently affected sites of pigmentation were the face (60.2%), lower limbs (36.1%), and hands (20.5%). There was a linear decrease in the incidence of pigmentation with increasing daily sun exposure time (p= 0.030). In the multivariate analysis, variables (cumulative HCQ dose and daily sun exposure time) were included in the final models. The results revealed an independent correlation between HCQ-induced pigmentation and daily sun exposure exceeding 1 h (OR: 0.431; 95%CI: 0.208-0.892; p= 0.023). CONCLUSIONS: The occurrence of HCQ-induced pigmentation is not uncommon, with an incidence rate of 26.3%. Daily sun exposure time exhibited a protective effect against HCQ-induced pigmentation.

7.
Lipids Health Dis ; 23(1): 98, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570797

RESUMO

Pulmonary fibrosis (PF) is a severe pulmonary disease with limited available therapeutic choices. Recent evidence increasingly points to abnormal lipid metabolism as a critical factor in PF pathogenesis. Our latest research identifies the dysregulation of low-density lipoprotein (LDL) is a new risk factor for PF, contributing to alveolar epithelial and endothelial cell damage, and fibroblast activation. In this study, we first integrative summarize the published literature about lipid metabolite changes found in PF, including phospholipids, glycolipids, steroids, fatty acids, triglycerides, and lipoproteins. We then reanalyze two single-cell RNA-sequencing (scRNA-seq) datasets of PF, and the corresponding lipid metabolomic genes responsible for these lipids' biosynthesis, catabolism, transport, and modification processes are uncovered. Intriguingly, we found that macrophage is the most active cell type in lipid metabolism, with almost all lipid metabolic genes being altered in macrophages of PF. In type 2 alveolar epithelial cells, lipid metabolic differentially expressed genes (DEGs) are primarily associated with the cytidine diphosphate diacylglycerol pathway, cholesterol metabolism, and triglyceride synthesis. Endothelial cells are partly responsible for sphingomyelin, phosphatidylcholine, and phosphatidylethanolamines reprogramming as their metabolic genes are dysregulated in PF. Fibroblasts may contribute to abnormal cholesterol, phosphatidylcholine, and phosphatidylethanolamine metabolism in PF. Therefore, the reprogrammed lipid profiles in PF may be attributed to the aberrant expression of lipid metabolic genes in different cell types. Taken together, these insights underscore the potential of targeting lipid metabolism in developing innovative therapeutic strategies, potentially leading to extended overall survival in individuals affected by PF.


Assuntos
Fibrose Pulmonar , Humanos , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Análise da Expressão Gênica de Célula Única , Metabolismo dos Lipídeos/genética , Células Endoteliais/metabolismo , Fosfolipídeos/metabolismo , Colesterol/metabolismo , Fosfatidilcolinas
8.
J Chem Theory Comput ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640423

RESUMO

Addressing both dynamic and static correlations accurately is a primary goal in electronic structure theory. Nonorthogonal configuration interaction (NOCI) is a versatile tool for treating static correlation, offering chemical insights by combining diverse reference states. Nevertheless, achieving quantitative accuracy requires the inclusion of the missing dynamic correlation. This work introduces a framework for compressing orthogonal single and double excitations into a NOCI of a much smaller dimension. This compression is repeated with each Slater determinant in a reference NOCI, resulting in another NOCI that includes all of its single and double excitations (NOCISD), effectively recovering the missing dynamic correlations from the reference. This compressed NOCISD is further refined through a selection process using metric and energy tests (SNOCISD). We validate the effectiveness of SNOCISD through its application to the dissociation of the nitrogen molecule and the hole-doped two-dimensional Hubbard model at various interaction strengths.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38637157

RESUMO

The development of nanopesticides provides new avenues for pesticide reduction and efficiency improvement. However, the size effect of nanopesticides remains unclear, and its underlying mechanisms of influence have become a major obstacle in the design and application of pesticide nanoformulations. In this research, the noncarrier-coated emamectin benzoate (EB) solid dispersions (Micro-EB and Nano-EB) were produced under a constant surfactant-to-active ingredient ratio by a self-emulsifying-carrier solidification technique. The particle size of Micro-EB was 162 times that of spherical Nano-EB. The small size and large specific surface area of Nano-EB facilitated the adsorption of surfactants on the surface of the particles, thereby improving its dispersibility, suspensibility, and stability. The pinning effect of nanoparticles significantly suppressed droplet retraction and rebounding. Moreover, Nano-EB exhibited a 25% higher retention of the active ingredient on cabbage leaves and a 70% higher washing resistance than Micro-EB, and both were significantly different. The improvement of abilities in wetting, spreading, and retention of Nano-EB on crop leaves contributed to the increase in foliar utilization, which further resulted in a 1.6-fold enhancement of bioactivity against target Spodoptera exigua compared to Micro-EB. Especially, Nano-EB did not exacerbate the safety risk to the nontarget organism zebrafish with no significant difference. This study elaborates the size effect on the effectiveness and safety of pesticide formulations and lays a theoretical foundation for the development and rational utilization of efficient and environmentally friendly nanopesticides.

11.
Front Pharmacol ; 15: 1354806, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601461

RESUMO

Lung injury leads to respiratory dysfunction, low quality of life, and even life-threatening conditions. Circular RNAs (circRNAs) are endogenous RNAs produced by selective RNA splicing. Studies have reported their involvement in the progression of lung injury. Understanding the roles of circRNAs in lung injury may aid in elucidating the underlying mechanisms and provide new therapeutic targets. Thus, in this review, we aimed to summarize and discuss the characteristics and biological functions of circRNAs, and their roles in lung injury from existing research, to provide a theoretical basis for the use of circRNAs as a diagnostic and therapeutic target for lung injury.

12.
Physiol Plant ; 176(2): e14272, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38566275

RESUMO

The Dehydration-Responsive Element Binding (DREB) subfamily of transcription factors plays crucial roles in plant abiotic stress response. Ammopiptanthus nanus (A. nanus) is an eremophyte exhibiting remarkable tolerance to environmental stress and DREB proteins may contribute to its tolerance to water deficit and low-temperature stress. In the present study, an A. nanus DREB A5 group transcription factor gene, AnDREB5.1, was isolated and characterized in terms of structure and function in abiotic stress tolerance. AnDREB5.1 protein is distributed in the nucleus, possesses transactivation capacity, and is capable of binding to DRE core cis-acting element. The transcription of AnDREB5.1 was induced under osmotic and cold stress. Tobacco seedlings overexpressing AnDREB5.1 displayed higher tolerance to cold stress, osmotic stress, and oxidative stress compared to wild-type tobacco (WT). Under osmotic and cold stress, overexpression of AnDREB5.1 increased antioxidant enzyme activity in tobacco leaves, inhibiting excessive elevation of ROS levels. Transcriptome sequencing analysis showed that overexpression of AnDREB5.1 raised the tolerance of transgenic tobacco seedlings to abiotic stress by regulating multiple genes, including antioxidant enzymes, transcription factors, and stress-tolerant related functional genes like NtCOR413 and NtLEA14. This study provides new evidence for understanding the potential roles of the DREB A5 subgroup members in plants.


Assuntos
Resposta ao Choque Frio , Fabaceae , Resposta ao Choque Frio/genética , Antioxidantes , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fabaceae/genética , Estresse Fisiológico/genética , Plântula/genética , Plântula/metabolismo , Tabaco/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Temperatura Baixa
13.
Artigo em Inglês | MEDLINE | ID: mdl-38635211

RESUMO

Improving the efficiency of platinum group metals (Pt, Pd, Rh, etc.) in catalytic oxidation reactions remains an urgent topic. The conflict between the low-temperature activity and high-temperature stability of noble metals can hardly reach a consensus. For instance, Pt cluster catalysts supported on CeO2 with high low-temperature activity will suffer from deactivation due to the redispersion under high-temperature lean-burn reaction conditions. Herein, two Pt1/CeO2 prepared by the incipient wetness impregnation method using different Pt precursors possessed varied Pt-O and Pt-O-Ce coordination numbers (CNs). They showed various priorities in CO oxidation versus NH3 selective catalytic oxidation, materials with higher CNPt-O-Ce selectively catalyzing NH3 oxidation to N2 more superior, conversely materials with lower CNPt-O-Ce performing better in CO oxidation. After activation by H2 reduction, both formed massive Pt clusters on the CeO2 surface but showed drastically distinct stability in lean-burn CO oxidation reactions. By summarizing the experimental results of high-angle annular dark-field scanning transmission electron microscopy, X-ray absorption spectroscopy, Raman spectroscopy, in situ diffuse reflectance infrared Fourier transform spectroscopy, etc., it is beyond doubt that the difference in the initial states of Pt1 due to distinct precursors indeed determine the redispersion behavior of the reduced Pt clusters on CeO2. Materials with lower CNPt-O-Ce and higher CNPt-O are more likely to form robust Pt clusters, as they are not conducive to Pt anchoring, thus restricting the reversible structural evolution occurring under lean-burn CO oxidation and reductive conditions. This approach serves as a guide for the convenient and efficient construction and exploration of robust Pt cluster catalysts.

14.
Sci Total Environ ; : 172558, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38643884

RESUMO

Compost-based organic fertilizers often contain high levels of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs). Previous studies focused on quantification of total ARGs and MGEs. For a more accurate risk assessment of the dissemination risk of antibiotic resistance, it is necessary to quantify the intracellular and extracellular distribution of ARGs and MGEs. In the present study, extracellular ARGs and MGEs (eARGs and eMGEs) and intracellular ARGs and MGEs (iARGs and iMGEs) were separately analyzed in 51 commercial composts derived from different raw materials by quantitative polymerase chain reaction (qPCR) and metagenomic sequencing. Results showed that eARGs and eMGEs accounted for 11-56 % and 4-45 % of the total absolute abundance of ARGs and MGEs, respectively. Comparable diversity, host composition and association with MGEs were observed between eARGs and iARGs. Contents of high-risk ARGs were similar between eARGs and iARGs, with high-risk ARGs in the two forms accounting for 6.7 % and 8.2 % of the total abundances, respectively. Twenty-four percent of the overall ARGs were present in plasmids, while 56.7 % of potentially mobile ARGs were found to be associated with plasmids. Variation partitioning analysis, null model and neutral community model indicated that the compositions of both eARGs and iARGs were largely driven by deterministic mechanisms. These results provide important insights into the cellular distribution of ARGs in manure composts that should be paid with specific attention in risk assessment and management.

15.
Int J Gen Med ; 17: 1025-1038, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525068

RESUMO

Background and Aims: Elevated eosinophils typically indicate hypersensitive inflammation; however, their involvement in cardiovascular events remains incompletely understood. We investigated the association between the absolute eosinophil count (AEC) and major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Additionally, we determine whether the integration of AEC with the SYNTAX II score could improve predictive ability. Methods and Results: The AECs of 1711 patients with ACS undergoing PCI from June 2016 to November 2017 were analyzed on admission. All recruitments were splitted into three groups based on AEC tertiles and 101 participants underwent one or more noteworthy outcomings. The association between AEC and MACCEs (defined as a composite of cardiovascular death, myocardial infarction [MI], and stroke) was tested by Cox proportional-hazards regression analysis. After adjusting for confounders, AEC was independently associated with MACCEs (HR 11.555, 95% CI: 3.318-40.239). Patients in the lowest AEC tertile (T1) as a reference, those in the higher tertiles had an incrementally higher risk of MACCEs (T3: HR 1.848 95% CI: 1.157-2.952; P for trend=0.008). Inclusion of AEC enhanced the predictive accuracy of the SYNTAX II score for MACCEs (AUC: from 0.701 [95% CI: 0.646-0.756] to 0.728 [95% CI: 0.677-0.780]; DeLong's test, P = 0.020). Conclusion: AEC is independently linked to MACCEs in ACS patients who underwent PCI, and adds incremental predictive information to the SYNTAX II score.

16.
JCI Insight ; 9(5)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38456511

RESUMO

Understanding the immune responses to SARS-CoV-2 vaccination is critical to optimizing vaccination strategies for individuals with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here, we comprehensively analyzed innate and adaptive immune responses in 19 patients with SLE receiving a complete 2-dose Pfizer-BioNTech mRNA vaccine (BNT162b2) regimen compared with a control cohort of 56 healthy control (HC) volunteers. Patients with SLE exhibited impaired neutralizing antibody production and antigen-specific CD4+ and CD8+ T cell responses relative to HC. Interestingly, antibody responses were only altered in patients with SLE treated with immunosuppressive therapies, whereas impairment of antigen-specific CD4+ and CD8+ T cell numbers was independent of medication. Patients with SLE also displayed reduced levels of circulating CXC motif chemokine ligands, CXCL9, CXCL10, CXCL11, and IFN-γ after secondary vaccination as well as downregulation of gene expression pathways indicative of compromised innate immune responses. Single-cell RNA-Seq analysis reveals that patients with SLE showed reduced levels of a vaccine-inducible monocyte population characterized by overexpression of IFN-response transcription factors. Thus, although 2 doses of BNT162b2 induced relatively robust immune responses in patients with SLE, our data demonstrate impairment of both innate and adaptive immune responses relative to HC, highlighting a need for population-specific vaccination studies.


Assuntos
COVID-19 , Lúpus Eritematoso Sistêmico , Humanos , Vacina BNT162 , Vacinas contra COVID-19 , SARS-CoV-2 , COVID-19/prevenção & controle , Vacinação
17.
Antioxidants (Basel) ; 13(3)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38539911

RESUMO

Saffron (Crocus sativus L.) is one of the most expensive spices in the world, boasting rich medicinal and edible value. However, the effective development of active natural substances in saffron is still limited. Currently, there is a lack of comprehensive studies on the saffron stigma protein, and the main effect peptides have not been identified. In this study, the total protein composition of saffron stigmas was analyzed, and two main antioxidant peptides (DGGSDYLGK and VDPYFNK) were identified, which showed high antioxidant activity. Then, the stability of two peptides was further evaluated. Furthermore, our results suggested that these two peptides may protect HepG2 cells from H2O2-induced oxidative damage by significantly improving the activity of endogenous antioxidant enzymes and reducing the malondialdehyde (MDA) content. Collectively, we identified two peptides screened from the saffron protein possessing good antioxidant activity and stability, making them promising candidates for use as functional foods, etc., for health promotion. Our findings indicated that proteomic analysis together with peptide identification is a good method for exploitation and utilization of spice plants.

18.
J Nanobiotechnology ; 22(1): 136, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553716

RESUMO

Pulmonary fibrosis (PF) threatens millions of people worldwide with its irreversible progression. Although the underlying pathogenesis of PF is not fully understood, there is evidence to suggest that the disease can be blocked at various stages. Inhalation therapy has been applied for lung diseases such as asthma and chronic obstructive pulmonary disease, and its application for treating PF is currently under consideration. New techniques in inhalation therapy, such as the application of microparticles and nanoparticles, traditional Chinese medicine monomers, gene therapy, inhibitors, or agonists of signaling pathways, extracellular vesicle interventions, and other specific drugs, are effective in treating PF. However, the safety and effectiveness of these therapeutic techniques are influenced by the properties of inhaled particles, biological and pathological barriers, and the type of inhalation device used. This review provides a comprehensive overview of the pharmacological, pharmaceutical, technical, preclinical, and clinical experimental aspects of novel inhalation therapy for treating PF and focus on therapeutic methods that significantly improve existing technologies or expand the range of drugs that can be administered via inhalation. Although inhalation therapy for PF has some limitations, the advantages are significant, and further research and innovation about new inhalation techniques and drugs are encouraged.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Fibrose Pulmonar , Humanos , Fibrose Pulmonar/tratamento farmacológico , Administração por Inalação , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Asma/tratamento farmacológico , Terapia Respiratória
19.
Int J Biol Macromol ; 266(Pt 1): 131020, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38521330

RESUMO

Ammopiptanthus mongolicus, a rare temperate evergreen broadleaf shrub, exhibits remarkable tolerance to low temperature and drought stress in winter. Late embryogenesis abundant (LEA) proteins, a kind of hydrophilic protein with a protective function, play significant roles in enhancing plant tolerance to abiotic stress. In this present study, we analyzed the evolution and expression of LEA genes in A. mongolicus, and investigated the function and regulatory mechanism of dehydrin under abiotic stresses. Evolutionary analysis revealed that 14 AmLEA genes underwent tandem duplication events, and 36 AmLEA genes underwent segmental duplication events Notably, an expansion in SKn-type dehydrins was observed. Expression analysis showed that AmDHN4, a SKn-type dehydrin, was up-regulated in winter and under low temperature and osmotic stresses. Functional analysis showcased that the heterologous expression of the AmDHN4 enhanced the tolerance of yeast and tobacco to low temperature stress. Additionally, the overexpression of AmDHN4 significantly improved the tolerance of transgenic Arabidopsis to low temperature, drought, and osmotic stress. Further investigations identified AmWRKY45, a downstream transcription factor in the jasmonic acid signaling pathway, binding to the AmDHN4 promoter and positively regulating its expression. In summary, these findings contribute to a deeper understanding of the functional and regulatory mechanisms of dehydrin.

20.
Theor Appl Genet ; 137(4): 89, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536528

RESUMO

KEY MESSAGE: The genetic architecture of symbiotic N fixation and related traits was investigated in the field. QTLs were identified for percent N derived from the atmosphere, shoot [N] and C to N ratio. Soybean [Glycine max (L.) Merr.] is cultivated worldwide and is the most abundant source of plant-based protein. Symbiotic N2 fixation (SNF) in legumes such as soybean is of great importance; however, yields may still be limited by N in both high yielding and stressful environments. To better understand the genetic architecture of SNF and facilitate the development of high yielding cultivars and sustainable soybean production in stressful environments, a recombinant inbred line population consisting of 190 lines, developed from a cross between PI 442012A and PI 404199, was evaluated for N derived from the atmosphere (Ndfa), N concentration ([N]), and C to N ratio (C/N) in three environments. Significant genotype, environment and genotype × environment effects were observed for all three traits. A linkage map was constructed containing 3309 single nucleotide polymorphism (SNP) markers. QTL analysis was performed for additive effects of QTLs, QTL × environment interactions, and QTL × QTL interactions. Ten unique additive QTLs were identified across all traits and environments. Of these, two QTLs were detected for Ndfa and eight for C/N. Of the eight QTLs for C/N, four were also detected for [N]. Using QTL × environment analysis, six QTLs were detected, of which five were also identified in the additive QTL analysis. The QTL × QTL analysis identified four unique epistatic interactions. The results of this study may be used for genomic selection and introgression of favorable alleles for increased SNF, [N], and C/N via marker-assisted selection.


Assuntos
Soja , Fixação de Nitrogênio , Soja/genética , Fixação de Nitrogênio/genética , Locos de Características Quantitativas , Mapeamento Cromossômico/métodos , Fenótipo
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