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1.
Front Plant Sci ; 15: 1407240, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39109056

RESUMEN

We focused on the geminiviral vector systems to develop an efficient vector system for plant biotechnology. Begomoviruses and curtoviruses, which belong to the Geminiviridae family, contain an intergenic region (IR) and four genes involved in replication, including replication-associated protein (Rep, C1), transcriptional activator (TrAP, C2), and replication enhancer (REn, C3). Geminiviruses can amplify thousands of copies of viral DNA using plant DNA polymerase and viral replication-related enzymes and accumulate viral proteins at high concentrations. In this study, we optimized geminiviral DNA replicon vectors based on tomato yellow leaf curl virus (TYLCV), honeysuckle yellow vein virus (HYVV), and mild curly top virus (BMCTV) for the rapid, high-yield plant-based production of recombinant proteins. Confirmation of the optimal combination by co-delivery of each replication-related gene and each IR harboring the Pontellina plumata-derived turbo green fluorescence protein (tGFP) gene via agroinfiltration in Nicotiana benthamiana leaves resulted in efficient replicon amplification and robust protein production within 3 days. Co-expression with the p19 protein of the tomato bush stunt virus, a gene-silencing suppressor, further enhanced tGFP accumulation by stabilizing mRNA. With this system, tGFP protein was produced at 0.7-1.2 mg/g leaf fresh weight, corresponding to 6.9-12.1% in total soluble protein. These results demonstrate the advantages of rapid and high-level production of recombinant proteins using the geminiviral DNA replicon system for transient expression in plants.

2.
PLoS One ; 19(8): e0308010, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39106279

RESUMEN

The lung is recognized as a site for initiating the formation of self-antigen and autoimmune responses in rheumatoid arthritis (RA). We aimed to investigate the association of upper respiratory microbiota with RA, autoantibody production, and disease activity. Forty-six patients with RA and 17 controls were examined. Nasopharyngeal swab samples were sequenced for microbiome profiling using the V3-V4 region of the 16S rRNA gene. The microbial diversity and relative abundance were compared between RA patients and controls. Correlation analyses were conducted to evaluate the relationship between microbial abundance and clinical markers such as autoantibodies and disease activity. Microbial diversity analysis revealed no major differences between RA patients and healthy controls. However, beta diversity analysis indicated a subtle distinction in microbial composition (unweighted UniFrac distance) between the two groups (P = 0.03), hinting at a minor subset of microbiota associated with disease status. Differential abundance analysis uncovered specific taxa at various taxonomic levels, including Saccharibacteria (TM7) [O-1] (PFDR = 2.53 × 10-2), TM7 [F-1] (PFDR = 5.20 × 10-3), Microbacterium (PFDR = 3.37 × 10-4), and Stenotrophomonas (PFDR = 2.57 × 10-3). The relative abundance of ten genera correlated significantly with anti-cyclic citrullinated peptide (anti-CCP) antibody levels (PFDR < 0.05) and 11 genera were significantly associated with disease activity markers, including ESR, CRP, DAS28-ESR, and DAS-CRP (PFDR < 0.05). In particular, Saccharibacteria TM7 [G-3] and Peptostreptococcaceae [XI] [G-1] were correlated with all disease activity biomarkers. Dysbiosis in the upper respiratory mucosa is associated with RA, anti-CCP antibody levels, and disease activity.


Asunto(s)
Artritis Reumatoide , Autoanticuerpos , Microbiota , ARN Ribosómico 16S , Mucosa Respiratoria , Humanos , Artritis Reumatoide/microbiología , Artritis Reumatoide/inmunología , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Persona de Mediana Edad , Femenino , Masculino , ARN Ribosómico 16S/genética , Mucosa Respiratoria/microbiología , Mucosa Respiratoria/inmunología , Adulto , Anciano , Estudios de Casos y Controles
3.
Int J Mol Sci ; 25(13)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-39000052

RESUMEN

Triacylglycerols (TAGs) are the storage oils of plant seeds, and these lipids provide energy for seed germination and valuable oils for human consumption. Three diacylglycerol acyltransferases (DGAT1, DGAT2, and DGAT3) and phospholipid:diacylglycerol acyltransferases participate in the biosynthesis of TAGs. DGAT1 and DGAT2 participate in the biosynthesis of TAGs through the endoplasmic reticulum (ER) pathway. In this study, we functionally characterized CsDGAT1 and CsDGAT2 from camelina (Camelina sativa). Green fluorescent protein-fused CsDGAT1 and CsDGAT2 localized to the ER when transiently expressed in Nicotiana benthamiana leaves. To generate Csdgat1 and Csdgat2 mutants using the CRISPR/Cas9 system, camelina was transformed with a binary vector carrying Cas9 and the respective guide RNAs targeting CsDGAT1s and CsDGAT2s via the Agrobacterium-mediated floral dip method. The EDD1 lines had missense and nonsense mutations in the CsDGAT1 homoeologs, suggesting that they retained some CsDGAT1 function, and their seeds showed decreased eicosaenoic acid (C20:1) contents and increased C18:3 contents compared to the wild type (WT). The EDD2 lines had a complete knockout of all CsDGAT2 homoeologs and a slightly decreased C18:3 content compared to the WT. In conclusion, CsDGAT1 and CsDGAT2 have a small influence on the seed oil content and have an acyl preference for C20:1 and C18:3, respectively. This finding can be applied to develop oilseed plants containing high omega-3 fatty acids or high oleic acid.


Asunto(s)
Brassicaceae , Diacilglicerol O-Acetiltransferasa , Ácidos Grasos , Proteínas de Plantas , Semillas , Ácidos Grasos/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Diacilglicerol O-Acetiltransferasa/metabolismo , Diacilglicerol O-Acetiltransferasa/genética , Semillas/metabolismo , Semillas/genética , Brassicaceae/genética , Brassicaceae/metabolismo , Sistemas CRISPR-Cas , Triglicéridos/metabolismo , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente/genética , Mutación , Edición Génica
4.
Nat Commun ; 15(1): 5860, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38997268

RESUMEN

Lithium batteries with solid-state electrolytes are an appealing alternative to state-of-the-art non-aqueous lithium-ion batteries with liquid electrolytes because of safety and energy aspects. However, engineering development at the cell level for lithium batteries with solid-state electrolytes is limited. Here, to advance this aspect and produce high-energy lithium cells, we introduce a cell design based on advanced parametrization of microstructural and architectural parameters of electrode and electrolyte components. To validate the cell design proposed, we assemble and test (applying a stack pressure of 3.74 MPa at 45 °C) 10-layer and 4-layer solid-state lithium pouch cells with a solid polymer electrolyte, resulting in an initial specific energy of 280 Wh kg-1 (corresponding to an energy density of 600 Wh L-1) and 310 Wh kg-1 (corresponding to an energy density of 650 Wh L-1) respectively.

5.
Porcine Health Manag ; 10(1): 9, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38365750

RESUMEN

BACKGROUND: Our previous study confirmed that large litter size adversely affects prepartum maternal hormones and behaviour, concurrently with heightened oxidative stress in primiparous sows. The purpose of this study was to examine the effect of large litter size on litter performance, postpartum maternal behaviour, salivary cortisol levels, and colostral immunoglobulin levels in sows, as well as investigate their correlations with the levels of oxidative stress parameters. RESULTS: A total of 24 primiparous sows (Landrace[Formula: see text]Large white) and their offspring were categorised into two groups based on litter size: NORMAL (n = 8) with litter size ranging from 7 to 14 (mean 11.5[Formula: see text]2.7), and LARGE (n=16) with litter size ranging from 15 to 20 (mean 15.9[Formula: see text]1.4). All sows were housed in a group housing system during gestation and transitioned to an adaptable loose housing system (2.4[Formula: see text]2.3 m) during the farrowing and lactation periods. The nursing and carefulness behaviour of the sows was monitored over a 24-h period between 72 and 96 h after parturition. Saliva samples were collected for cortisol assay on 35, 21, and 7 days before parturition (D-35, D-21, and D-7, respectively), as well as on days 1, 7, and 28 after parturition (D1, D7, and D28, respectively). On D1, higher piglet mortality rates were observed among the LARGE group compared to the NORMAL group (p<0.01). The total and successful nursing behaviours of the sows were less frequent in the LARGE group than in the NORMAL group (p<0.05, for both), and the carefulness score of the LARGE group was also lower than that of the NORMAL group (p< 0.01). On D1, cortisol levels in LARGE sows were higher than those in NORMAL sows (p< 0.05), and for other time points (D-21, D-7, D7, and D28), cortisol levels in LARGE sows tended to be higher than those in NORMAL sows (p < 0.10, for all). Successful nursing behaviour displayed negative correlations with levels of salivary cortisol and certain oxidative stress parameters measured on D1. CONCLUSIONS: These findings suggest that the strategy for alleviating physiological and oxidative stress during the peripartum periods could benefit potential postpartum maternal behaviour and litter performance in the sows with large litters.

7.
Antioxidants (Basel) ; 13(2)2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38397808

RESUMEN

Hyperprolific sows often experience increased oxidative stress during late gestation and lactation periods, which can adversely affect the farrowing process and overall lactation performance. This study examines the influence of providing a coconut coir mat (CCM; 1 × 1 m) as nesting material, supplementing high-dose vit-C (HVC; 20% vit-C, 10 g/kg feed) as an antioxidant, or both on maternal behavior, the farrowing process, oxidative status, cortisol levels, and preovulatory follicle developments in sows with large litters. In total, 35 sows (Landrace × Yorkshire; litter size 15.43 ± 0.27) were allocated to the following four treatment groups: control (n = 9, basal diet), vit-C (n = 8, basal diet + HVC), mat (n = 10, basal diet + CCM), and mat + vit-C (n = 8, basal diet + HVC + CCM). A post-hoc analysis showed that compared with sows that were not provided CCM, mat and mat + vit-C groups demonstrated increased durations of nest-building behavior during the period from 24 h to 12 h before parturition (p < 0.05 for both), reduced farrowing durations, and decreased intervals from birth to first udder contact (p < 0.01 for both). The mat group exhibited lower advanced oxidation protein product (AOPP) levels during late gestation and lactation periods than the control group (p < 0.05). Sows with HVC supplementation showed longer farrowing durations than those without HVC supplementation (p < 0.0001). The vit-C group had higher salivary cortisol levels on day 1 after farrowing than the other treatment groups (p < 0.05). Furthermore, the follicle diameters on day 3 after weaning in the vit-C group tended to be smaller than those in the control group (p = 0.077). HVC supplementation prolonged farrowing and increased the physiological stress on postpartum, and no advantageous effects on maternal behavior and developmental progression of preovulatory follicles were observed. Hence, alternative solutions beyond nutritional approaches are required to address increased oxidative stress in hyperprolific sows and secure their welfare and reproductive performance. The present results substantiated the positive impact of providing CCM as nesting material for sows with large litters on nest-building behavior and the farrowing process, which could mitigate the deleterious consequences induced by peripartum physiological and oxidative stress.

8.
Front Vet Sci ; 10: 1219572, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37675077

RESUMEN

The study examined 24 primiparous sows (Landrace × Large white) and their offspring, which were grouped based on litter size: NORMAL (n = 8, average litter size 11.5 ± 1.2), with litter size between 7 and 14, and LARGE (n = 16, average litter size 15.9 ± 1.0), with litter size between 15 and 20. Sows were group-housed during gestation, and housed in an adjustable loose housing system (2.4 × 2.3 m) during farrowing and lactation. All the sows were confined in the farrowing crates (0.6 × 2.3 m) for 7 days after the onset of parturition. Saliva samples of sows were collected on days 35, 21, and 7 before farrowing (D-35, D-21 and D7, respectively), and on days 1, 7, and 28 after farrowing (D1, D7, and D28, respectively) to measure the levels of Trolox equivalent antioxidant capacity (TEAC), hydrogen peroxide (H2O2), advanced oxidation protein products (AOPP), and tumor necrosis factor-alpha (TNF-α). Colostrum samples were collected for oxytocin and prolactin assays. Nest-building behavior (NB) for 24 h before parturition and farrowing was observed through video analysis. The results showed that LARGE sows had higher levels of H2O2 on D1 and D7 and AOPP during late gestation (p < 0.05, for all) and lower TEAC levels during late gestation and on D7 and D28 after farrowing (p < 0.05, for all) than NORMAL sows. Additionally, LARGE sows tended to have higher levels of TNF-α on D1 and D7 (p < 0.10, for both). LARGE sows showed shorter duration and lower frequency of NB during 24-12 h before parturition (p < 0.05, for both), and tended to have lower prolactin levels (p = 0.10). Furthermore, large sows tended to show longer farrowing duration and higher stillbirth rate (p = 0.06, p = 0.07, respectively). In conclusion, this study confirmed that large litter size may increase oxidative stress in sows during late gestation and lactation. The data also suggested that this could adversely impact prolactin release, leading to reduced NB.

9.
Genes Genomics ; 45(12): 1475-1487, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37768516

RESUMEN

BACKGROUND: The biological clock allows an organism to anticipate periodic environmental changes and adjust its physiology and behavior accordingly. OBJECTIVE: This retrospective cross-sectional study examined circadian gene polymorphisms and clinical characteristics associated with insulin resistance (IR). METHODS: We analyzed data from 1,404 Korean adults aged 30 to 55 with no history of cancer and cardio-cerebrovascular disease. The population was classified according to sex and homeostasis model assessment of insulin resistance (HOMA-IR) values. Demographics, anthropometric and clinical characteristics, and single nucleotide polymorphisms (SNPs) were analyzed with respect to sex, age, and HOMA-IR values. We used association rule mining to identify sets of SNPs from circadian and metabolic sensing genes that may be associated with IR. RESULTS: Among the subjects, 15.0% of 960 women and 24.3% of 444 men had HOMA-IR values above 2. Most of the parameters differed significantly between men and women, as well as between the groups with high and low insulin sensitivity. Body fat mass of the trunk, which was significantly higher in insulin-resistant groups, had a higher correlation with high sensitivity C-reactive protein and hemoglobin levels in women, and alanine aminotransferase and aspartate aminotransferase levels in men. Homozygous minor allele genotype sets of SNPs rs17031578 and rs228669 in the PER3 gene could be more frequently found among women with HOMA-IR values above 2 (p = .014). CONCLUSION: Oxidative stress enhanced by adiposity and iron overload, which may also be linked to NRF2 and PER3-related pathways, is related to IR in adulthood. However, due to the small population size in this study, more research is needed.


Asunto(s)
Resistencia a la Insulina , Masculino , Adulto , Humanos , Femenino , Resistencia a la Insulina/genética , Índice de Masa Corporal , Estudios Retrospectivos , Estudios Transversales , Polimorfismo de Nucleótido Simple , República de Corea
10.
Arch Pharm Res ; 46(7): 646-658, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37537405

RESUMEN

Colon-targeted oral drug delivery systems comprising nanoparticles and microparticles have emerged as promising tools for the treatment of ulcerative colitis (UC) because they minimize side effects and maximize the local drug concentration. Dexamethasone sodium phosphate (DSP) is a potent anti-inflammatory glucocorticoid used for the treatment of UC. However, it remains a rather short-term treatment option owing to its side effects. In the present study, we developed the alginate gel encapsulating ionically bridged DSP-zinc-poly(lactic-co-glycolic acid) (PLGA) nanocomplex (DZP-NCs-in-microgel) for the oral local treatment of UC. The successful encapsulation of DSP-zinc-PLGA nanocomplex (DZP-NCs) in alginate microgel was confirmed by SEM imaging. The prepared gel released DZP-NCs in the stimulated intestinal fluid and dampened the release of DSP in the upper gastrointestinal tract. Furthermore, DZP-NCs-in-microgel alleviated colonic inflammation in a mouse model of dextran sodium sulfate-induced colitis by relieving clinical symptoms and histological marks. Our results suggest a novel approach for the oral colon-targeted delivery of dexamethasone sodium phosphate for the treatment of UC.


Asunto(s)
Colitis Ulcerosa , Colitis , Microgeles , Ratones , Animales , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/patología , Microgeles/uso terapéutico , Zinc/efectos adversos , Alginatos/efectos adversos , Colitis/inducido químicamente , Colon/patología , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad
11.
Bioeng Transl Med ; 8(3): e10527, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37206214

RESUMEN

The gut microbiome is closely linked to gastrointestinal health and disease status. Oral administration of known probiotic strains is now considered a promising therapeutic strategy, especially for refractory diseases such as inflammatory bowel disease. In this study, we developed a nanostructured hydroxyapatite/alginate (HAp/Alg) composite hydrogel that protects its encapsulated probiotic Lactobacillus rhamnosus GG (LGG) by neutralizing hydrogen ions that penetrate the hydrogel in a stomach without inhibiting LGG release in an intestine. Surface and transection analyses of the hydrogel revealed characteristic patterns of crystallization and composite-layer formation. TEM revealed the dispersal of the nanosized HAp crystals and encapsulated LGG in the Alg hydrogel networks. The HAp/Alg composite hydrogel maintained its internal microenvironmental pH, thereby enabling the LGG to survive for substantially longer. At intestinal pH, the encapsulated LGG was completely released upon disintegration of the composite hydrogel. In a dextran sulfate sodium-induced colitis mouse model, we then assessed the therapeutic effect of the LGG-encapsulating hydrogel. This achieved intestinal delivery of LGG with minimal loss of enzymatic function and viability, ameliorating colitis by reducing epithelial damage, submucosal edema, inflammatory cell infiltration, and the number of goblet cells. These findings reveal the HAp/Alg composite hydrogel as a promising intestinal-delivery platform for live microorganisms including probiotics and live biotherapeutic products.

12.
Plant Biotechnol Rep ; 17(1): 53-65, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36820221

RESUMEN

The production of pharmaceutical compounds in plants is attracting increasing attention, as plant-based systems can be less expensive, safer, and more scalable than mammalian, yeast, bacterial, and insect cell expression systems. Here, we review the history and current status of plant-made pharmaceuticals. Producing pharmaceuticals in plants requires pairing the appropriate plant species with suitable transformation technology. Pharmaceuticals have been produced in tobacco, cereals, legumes, fruits, and vegetables via nuclear transformation, chloroplast transformation, transient expression, and transformation of suspension cell cultures. Despite this wide range of species and methods used, most such efforts have involved the nuclear transformation of tobacco. Tobacco readily generates large amounts of biomass, easily accepts foreign genes, and is amenable to stable gene expression via nuclear transformation. Although vaccines, antibodies, and therapeutic proteins have been produced in plants, such pharmaceuticals are not readily utilized by humans due to differences in glycosylation, and few such compounds have been approved due to a lack of clinical data. In addition, achieving an adequate immune response using plant-made pharmaceuticals can be difficult due to low rates of production compared to other expression systems. Various technologies have recently been developed to help overcome these limitations; however, plant systems are expected to increasingly become widely used expression systems for recombinant protein production.

13.
Molecules ; 28(4)2023 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-36838877

RESUMEN

Lactobacillus plantarum (L. plantarum) is a probiotic that has emerged as novel therapeutic agents for managing various diseases, such as cancer, atopic dermatitis, inflammatory bowel disease, and infections. In this study, we investigated the potential mechanisms underlying the anticancer effect of the metabolites of L. plantarum. We cultured L. plantarum cells to obtain their metabolites, created several dilutions, and used these solutions to treat human colonic Caco-2 cells. Our results showed a 10% dilution of L. plantarum metabolites decreased cell viability and reduced the expression of autophagy-related proteins. Moreover, we found co-treatment with L. plantarum metabolites and chloroquine, a known autophagy inhibitor, had a synergistic effect on cytotoxicity and downregulation of autophagy-related protein expression. In conclusion, we showed the metabolites from the probiotic, L. plantarum, work synergistically with chloroquine in killing Caco-2 cells and downregulating the expression of autophagy-related proteins, suggesting the involvement of autophagy, rather than apoptosis, in their cytotoxic effect. Hence, this study provides new insights into new therapeutic methods via inhibiting autophagy.


Asunto(s)
Antineoplásicos , Lactobacillus plantarum , Probióticos , Humanos , Lactobacillus plantarum/metabolismo , Células CACO-2 , Antineoplásicos/farmacología , Probióticos/farmacología , Autofagia
14.
J Pineal Res ; 74(1): e12835, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36214640

RESUMEN

N-Acetylserotonin (NAS) is an intermediate in the melatonin biosynthetic pathway. We investigated the anti-inflammatory activity of NAS by focusing on its chemical feature oxidizable to an electrophile. NAS was readily oxidized by reaction with HOCl, an oxidant produced in the inflammatory state. HOCl-reacted NAS (Oxi-NAS), but not NAS, activated the anti-inflammatory nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase (HO)-1 pathway in cells. Chromatographic and mass analyses demonstrated that Oxi-NAS was the iminoquinone form of NAS and could react with N-acetylcysteine possessing a nucleophilic thiol to form a covalent adduct. Oxi-NAS bound to Kelch-like ECH-associated protein 1, resulting in Nrf2 dissociation. Moreover, rectally administered NAS increased the levels of nuclear Nrf2 and HO-1 proteins in the inflamed colon of rats. Simultaneously, NAS was converted to Oxi-NAS in the inflamed colon. Rectal NAS mitigated colonic damage and inflammation. The anticolitic effects were significantly compromised by the coadministration of an HO-1 inhibitor.


Asunto(s)
Colitis , Melatonina , Ratas , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Melatonina/farmacología , Melatonina/uso terapéutico , Hemo-Oxigenasa 1/metabolismo , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Antiinflamatorios/uso terapéutico
15.
Int J Pharm ; 630: 122443, 2023 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-36503847

RESUMEN

5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent for colorectal cancer (CRC) owing to its potent anticancer effects. However, severe systemic side effects and poor drug accumulation in the CRC tissues limit its efficacy. This study aimed to develop 5-FU crystal-incorporated, pH-responsive, and release-modulating poly(d,l-lactide-co-glycolide)/Eudragit FS hybrid microparticles (5FU-EPMPs) for the local CRC-targeted chemotherapy. Approximately 150 µm 5FU-EPMPs were fabricated via the S/O/W emulsion solvent evaporation method, with 7.93 ± 0.24% and 87.23 ± 2.64% 5-FU loading and encapsulation efficiencies, respectively. Drug release profiles in a simulated pH environment of the gastrointestinal tract revealed that premature 5-FU release in the stomach and small intestine was prevented, thereby minimizing systemic 5-FU absorption. After reaching the colon, 5-FU was continuously released for >15 h, allowing long-term exposure of CRC tissues to sufficient 5-FU concentrations. Furthermore, in a CRC mouse model, the 5FU-EPMPs showed potent inhibition of tumor growth without signs of systemic toxicity. Thus, the 5FU-EPMPs represent a promising drug delivery system for local CRC-targeted chemotherapy.


Asunto(s)
Neoplasias Colorrectales , Fluorouracilo , Ratones , Animales , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ácido Láctico , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Concentración de Iones de Hidrógeno , Neoplasias Colorrectales/tratamiento farmacológico
16.
JBI Evid Synth ; 21(1): 214-222, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-35946908

RESUMEN

OBJECTIVE: The objective of this review is to provide a modern definition and identify potential biomarkers of blood stasis in cardio- and cerebrovascular diseases by mapping, comparing, and combining Eastern and Western concepts. INTRODUCTION: Blood stasis is a pathological concept found in both Eastern and Western medical literature. In traditional East Asian medicine, blood stasis is a differential syndrome characterized by stagnant blood flow in various parts of the body. Similarly, in Western medicine, various diseases, especially cardio- and cerebrovascular diseases, are known to be accompanied by blood stasis. Numerous scientific studies on blood stasis have been conducted over the last decade, and there is a need to synthesize those results. INCLUSION CRITERIA: We will use the keywords "blood stasis," "blood stagnation," "blood stagnant," and "blood congestion" in 3 electronic databases: PubMed, Cochrane CENTRAL, and Google Scholar. In addition, we will use the keywords "어혈" and "혈어" in 4 Korean electronic databases (ie, NDSL, OASIS, KISS, and DBpia). Peer-reviewed articles published from 2010 to the present that focus on blood stasis in cardio- and cerebrovascular diseases in human subjects according to the International Classification of Diseases 11 th revision categories BA00-BE2Z, 8B00-8B2Z, 8E64, and 8E65 will be included. Reviews, opinion articles, in vivo, in vitro, and in silico preclinical studies will be excluded. METHODS: We will follow the frameworks by Arksey and O'Malley and Levac et al. as well as JBI guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews. Two reviewers will independently search and screen titles and abstracts followed by full-text screening of eligible studies. If there are discrepancies between the 2 reviewers, a third reviewer will be consulted to make the final decision. We will use descriptive narrative, tabular, and graphical displays, and content analysis to present the results. SCOPING REVIEW REGISTRATION: Open Science Framework https://osf.io/gv4ym.


Asunto(s)
Trastornos Cerebrovasculares , Proyectos de Investigación , Humanos , Trastornos Cerebrovasculares/diagnóstico , Literatura de Revisión como Asunto
17.
Pharmaceutics ; 14(12)2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36559305

RESUMEN

Polyhydroxybutyrate (PHB) has emerged as a novel material for replacing various plastics used in the medical field. However, its application as a drug-delivery carrier for colitis-targeted delivery has not been explored. In this study, we used biosynthesized PHB combined with Eudragit FS (EFS) and cyclosporine A (CSA) to develop pH-responsive controlled CSA-releasing nanoparticles (CSA-PENPs) for colitis-targeted drug delivery and demonstrated its enhanced therapeutic efficacy in a dextran sulfate sodium (DSS)-induced murine colitis model. PHB was successfully biosynthesized in the bacterium Cupriavidus necator, as demonstrated by 1H-NMR and FT-IR analyses. CSA-PENPs were fabricated via the oil-in-water emulsion solvent evaporation method. Owing to the potent pH-responsive and sustained drug release properties provided by PHB and EFS, CSA-PENPs could deliver a sufficient amount of CSA to inflamed tissues in the distal colon; in contrast, CSA-loaded EFS nanoparticles displayed premature burst release before reaching the target site. Due to enhanced CSA delivery to colitis tissues, CSA-PENPs exhibited potent anti-inflammatory effects in the DSS-induced murine colitis model. Overall, CSA-PENPs could be a promising drug-delivery system for treating ulcerative colitis.

18.
ACS Appl Mater Interfaces ; 14(45): 50507-50519, 2022 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-36331408

RESUMEN

A bacteria-infected wound can lead to being life-threatening and raises a great economic burden on the patient. Here, we developed polyethylenimine 1.8k (PEI1.8k) surface modified NO-releasing polyethylenimine 25k (PEI25k)-functionalized graphene oxide (GO) nanoparticles (GO-PEI25k/NO-PEI1.8k NPs) for enhanced antibacterial activity and infected wound healing via binding to the bacterial surface. In vitro antibacterial activity and in vivo wound healing efficacy in an infected wound model were evaluated compared with NO-releasing NPs (GO-PEI25k/NO NPs). Surface modification with PEI1.8k can enhance the ability of nanoparticles to adhere to bacteria. GO-PEI25k/NO-PEI1.8k NPs released NO in a sustained manner for 48 h and exhibited the highest bactericidal activity (99.99% killing) against methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MRPA) without cytotoxicity to L929 mouse fibroblast cells at 0.1 mg/mL. In the MRPA-infected wound model, GO-PEI25k/NO-PEI1.8k NPs showed 87% wound size reduction while GO-PEI25k/NO NPs showed 23% wound size reduction at 9 days postinjury. Masson trichrome and hematoxylin and eosin staining revealed that GO-PEI25k/NO-PEI1.8k NPs enhanced re-epithelialization and collagen deposition, which are comparable to healthy mouse skin tissue. GO-PEI25k/NO-PEI1.8k NPs hold promise as effective antibacterial and wound healing agents.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Nanopartículas , Infección de Heridas , Ratones , Animales , Óxido Nítrico/farmacología , Pseudomonas aeruginosa , Polietileneimina/farmacología , Adhesivos/farmacología , Infección de Heridas/tratamiento farmacológico , Cicatrización de Heridas , Bacterias , Antibacterianos/farmacología
19.
Int J Mol Sci ; 23(22)2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36430574

RESUMEN

Starch is the primary storage carbohydrate in mature pollen grains in many crop plants, including rice. Impaired starch accumulation causes male sterility because of the shortage of energy and building blocks for pollen germination and pollen tube growth. Thus, starch-defective pollen is applicable for inducing male sterility and hybrid rice production. Despite the importance of pollen starch, the details of the starch biosynthesis and breakdown pathway in pollen are still largely unknown. As pollen is isolated from the maternal tissue, photoassimilate transported from leaves must pass through the apoplastic space from the anther to the filial pollen, where it is stored as starch. Several sugar transporters and enzymes are involved in this process, but many are still unknown. Thus, the current review provides possible scenarios for sucrose transport and metabolic pathways that lead to starch biosynthesis and breakdown in rice pollen.


Asunto(s)
Infertilidad Masculina , Oryza , Masculino , Humanos , Oryza/metabolismo , Almidón/metabolismo , Azúcares/metabolismo , Polen/metabolismo , Fertilidad , Redes y Vías Metabólicas , Infertilidad Masculina/metabolismo
20.
Pharmaceutics ; 14(10)2022 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-36297553

RESUMEN

Although various local anti-inflammatory therapies for ulcerative colitis have been developed, rapid drug elimination from inflamed colitis tissue and off-target side effects reduce their therapeutic efficacy. In this study, we synthesized curcumin (Cur)-loaded hyaluronic acid (HA)-conjugated nanoparticles (Cur-HA-PLGA-NPs) that target inflamed colitis tissue via HA-CD44 interaction with resident colonic epithelial cells and subsequently target activated macrophages for ulcerative colitis therapy. The synthesized spherical Cur-HA-PLGA-NPs showed physicochemical properties similar to those of non-HA-conjugated Cur-PLGA-NPs. HA-PLGA-NPs exhibited selective accumulation in inflamed colitis tissue with minimal accumulation in healthy colon tissue. HA functionalization enhanced targeted drug delivery to intestinal macrophages, significantly increasing HA-PLGA-NP cellular uptake. Importantly, the rectal administration of Cur-HA-PLGA-NPs exhibited better therapeutic efficacy than Cur-PLGA-NPs in animal studies. Histological examination revealed that Cur-HA-PLGA-NPs reduced inflammation with less inflammatory cell infiltration and accelerated recovery with re-epithelialization signs. Our results suggest that Cur-HA-PLGA-NPs are a promising delivery platform for treating ulcerative colitis.

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