RESUMEN

Bone tissue engineering is a promising technology being studied globally to become an effective and sustainable method to treat the problems of damaged or diseased bones. In this work, we developed an in situ cross-linking hydrogel system that combined N-succinyl chitosan (NSC) and oxidized alginate (OA) at varying mixing ratios through Schiff base cross-linking. The hydrogel system also contains biphasic calcium phosphate (BCP) and ascorbic acid (AA), which could enhance biological characteristics and accelerate bone repair. The hydrogels' properties were examined through physicochemical tests such as scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FT-IR), x-ray diffraction (XRD), pore size and porosity measurement, swelling ratio, degradation rate, AA release study, as well as cytocompatibility, including live/dead and cytotoxicity assays. The results revealed that the supplementation of AA and BCP components can affect the physico-mechanical properties of the hydrogel system. However, they exhibited noncytotoxic properties. Overall, the results demonstrated that the hydrogel composed of 3% (w/v) NSC and 3% (w/v) OA (NSC: OA volume ratio is 8:2) loaded with 40% (w/w) BCP and 0.3 mg/mL AA has the potential for bone regeneration.

RESUMEN

Our investigation seeks to uncover the intricate nature of mercury dynamics in the free troposphere through analysis of the isotopic composition of total gaseous elemental mercury (TGM) at the high altitude Mauna Loa Observatory (MLO, 3397 m) in Hawaii, USA. By focusing on this unique site, we aim to provide essential insights into the behavior and cycling of mercury, contributing valuable data to a deeper understanding of its global distribution and environmental impacts. Forty-eight hours of TGM sampling from January to September 2022 revealed significant variations in δ202Hg (-1.86 % to -0.32 %; mean = -1.17 ± 0.65 %, 2 SD, n = 34) and small variations in Δ199Hg (-0.27 % to 0.04 %; mean = -0.13 ± 0.14 %, 2 SD, n = 34) and Δ200Hg (-0.20 % to 0.06 %; mean = -0.05 ± 0.13 %, 2 SD, n = 34). During the sampling period, GEM was negatively correlated with gaseous oxidized mercury (GOM). However, the GOM/GEM ratio was not -1, suggesting that GEM oxidation and subsequent scavenging occurred previously. The δ202Hg isotopic compositions of TGM at MLO were different from those of reported values of high-altitude mountains; the δ202Hg of TGM at MLO was lower than the isotopic ratios that were obtained from other mountain regions. The unique atmospheric conditions at Mauna Loa, with (upslope winds during the day and downslope winds at night, likely result in the) possibly mixing of GEMs from terrestrial (and possibly oceanic GEM emission) sources with and tropospheric sources, influencing and affect the isotopic composition. During the late summer to early fall (September 14-28), negative correlations were found between relative humidity and GOM and between particle number concentrations and Δ199Hg, indicating the gas-to-particle partitioning of the atmospheric mercury during this period. This study will improve our understanding on mercury dynamics of marine origin and high altitudes and shed light on its complex interactions with environmental factors.

RESUMEN

BACKGROUND: Several oxylipins including hydroxy- and epoxy-polyunsaturated fatty acids act as lipid mediators. In biological samples they can be present as non-esterified form, but the major part occurs esterified in phospholipids (PL) or other lipids. Esterified oxylipins are quantified indirectly after alkaline hydrolysis as non-esterified oxylipins. However, in this indirect analysis the information in which lipid class oxylipins are bound is lost. In this work, an untargeted liquid chromatography high-resolution mass spectrometry (LC-HRMS) method for the direct analysis of PL bearing oxylipins was developed. RESULTS: Optimized reversed-phase LC separation achieved a sufficient separation of isobaric and isomeric PL from different lipid classes bearing oxylipin positional isomers. Individual PL species bearing oxylipins were identified based on retention time, precursor ion and characteristic product ions. The bound oxylipin could be characterized based on product ions resulting from the α-cleavage occurring at the hydroxy/epoxy group. PL sn-1/sn-2 isomers were identified based on the neutral loss of the fatty acyl in the sn-2 position. A total of 422 individual oxPL species from 7 different lipid classes i.e., PI, PS, PC, PE, PC-P, PC-O, and PE-P were detected in human serum and cells. This method enabled to determine in which PL class supplemented oxylipins are incorporated in HEK293 cells: 20:4;15OH, 20:4;14Ep, and 20:5;14Ep were mostly bound to PI. 20:4;8Ep and 20:5;8Ep were esterified to PC and PE while other oxylipins were mainly found in PC. SIGNIFICANCE: The developed LC-HRMS method enables the comprehensive detection as well as the semi-quantification of isobaric and isomeric PL species bearing oxylipins. With this method, we show that the position of the oxidation has a great impact and directs the incorporation of oxylipins into the different PL classes in human cells.

Asunto(s)

Espectrometría de Masas , Oxilipinas , Fosfolípidos , Oxilipinas/análisis , Oxilipinas/química , Humanos , Fosfolípidos/análisis , Fosfolípidos/química , Espectrometría de Masas/métodos , Cromatografía Liquida/métodos , Isomerismo

RESUMEN

For group 14 mono-elemental 2D materials, such as silicene, germanene, and stanene, oxidation is a severe problem that alters or degrades their physical properties. This study shows that the oxidized germanene on Ag(111)/Ge(111) can be reformed to germanene by simple heating ≈500 °C in a vacuum. The key reaction in reforming germanene is the desorption of GeO and GeO2 during heating ≈350 °C. After removing surface oxygen, Ge further segregates to the surface, resulting in the reformation of germanene. The reformed germanene has the same crystal structure, a (7√7 × 7√7) R19.1° supercell with respect to Ag(111), and has equivalent high quality to that of as-grown germanene on Ag(111)/Ge(111). Even after air oxidation, germanene can be reformed by annealing in a vacuum. On the other hand, the desorption of GeO and GeO2 at high temperatures is not suppressed in the O2 backfilling atmosphere. This instability of oxidized germanene/Ag(111)/Ge(111) at high temperatures contributes to the ease of germanene reformation without residual oxygen. In other words, the present germanene reformation, as well as the segregation of germanene on Ag(111)/Ge(111), is a highly robust process to synthesize germanene.

RESUMEN

BACKGROUND: Chrysin, a polyphenolic compound, possesses antioxidant and anti-inflammatory properties. In this study, we investigated the effect of chrysin on the expression of A disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), a protease enzyme involved in degrading extracellular matrix associated with atherosclerosis. METHODS AND RESULTS: We have studied the cell viability by MTT assay and foam cell formation by oil red O staining. The mRNA and protein expression of ADAMTS-4 was studied using quantitative polymerase chain reaction (qPCR) and Western blotting, respectively. Our study showed that chrysin significantly downregulates the expression of ADAMTS-4 in foam cells. CONCLUSION: Chrysin's ability to downregulate the expression of ADAMTS-4, a protease involved in degrading the extracellular matrix, bestows upon it a new therapeutic potential for managing atherosclerosis.

Asunto(s)

Proteína ADAMTS4 , Regulación hacia Abajo , Flavonoides , Células Espumosas , Flavonoides/farmacología , Proteína ADAMTS4/metabolismo , Proteína ADAMTS4/genética , Células Espumosas/efectos de los fármacos , Células Espumosas/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Humanos , Supervivencia Celular/efectos de los fármacos , Aterosclerosis/metabolismo , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/genética

RESUMEN

Introduction: Cerebral cavernous malformations (CCMs) are pathologic lesions comprised of clusters of thin-walled capillaries characterized by abnormal proliferation, angiogenesis, and bleeding secondary to somatic or germline mutations in endothelial cells. CCMs can cause headaches, seizures and/or neurological defects. There is a clinical need to develop better tools to detect CCMs and follow their progression in conjunction with the current use of neuroimaging techniques. Here we present data supporting the utility of LOX-1 (lectin-type oxidized LDL receptor 1), a 50 kDa transmembrane protein implicated in endothelial cell dysfunction and ischemia, as a putative biomarker for CCM. Methods: CCM urine samples (n = 23) were collected from pediatric CCM patients. Matched healthy controls (n = 24) were collected from pediatric patients with either Chiari I malformation or fatty filum terminale, and otherwise normal findings. All samples were collected with patient/family consent and institutional review board approval.Samples were analyzed with Olink Proteomic Proximity Extension Assay (PEA). Differences in expression for 2,925 unique proteins were quantified between healthy control urine samples and CCM urine samples. The results were normalized, validated, and analyzed for demographic bias. In addition to urine samples, CCM tissue from patients was harvested and used to create primary cell lines for in vitro analysis of LOX-1 expression, in addition to immunofluorescence of lesional tissue excised at surgery. Results: ANOVA analysis of the CCM urine samples showed a statistically significant increase in LOX-1 compared to the control samples, with CCM patients exhibiting a > 5-fold increase in urinary expression. Corroborating these elevated levels of circulating marker, analysis of source tissue from surgically resected CCMs revealed that LOX-1 is increased in both CCM patient cavernoma primary cell lines and operative specimens. Conclusion: LOX-1 is involved with pathways implicated in CCM pathogenesis and our data here reveals that LOX-1 expression is significantly elevated in CCM patients as compared to matched healthy control individuals, including both source tissue from surgically excised CCMs and in analysis of samples collected from outside of the central nervous system, particularly urine. This proof-of-principle data suggests that LOX-1 may have potential utility as a target for CCM treatment and supports further investigation related to its potential mechanistic impact on CCM pathogenesis.

RESUMEN

Biliary atresia (BA) is a severe pediatric liver disease characterized by progressive bile duct destruction and fibrosis, leading to significant liver damage and frequently necessitating liver transplantation. This study elucidates the role of LOX-1+ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in BA pathogenesis and assesses their potential as non-invasive early diagnostic biomarkers. Using flow cytometry, immunofluorescence, and molecular profiling, we analyzed the expression and activity of these cells in peripheral blood and liver tissues from BA patients and controls. Our findings reveal a significant increase in the frequencies and function of LOX-1+PMN-MDSCs in BA patients, along with MAPK signaling pathway upregulation, indicating their involvement in disease mechanisms. Additionally, the frequencies of LOX-1+PMN-MDSC in peripheral blood significantly positively correlate with liver function parameters in BA patients, demonstrating diagnostic performance comparable to traditional serum markers. These findings suggest that LOX-1+PMN-MDSCs contribute to the immunosuppressive environment in BA and could serve as potential diagnostic targets.

RESUMEN

Polyunsaturated fatty acids (PUFAs) play numerous roles in living organisms but are also prone to rapid aerobic oxidation, resulting in the production of a wide range of isomeric metabolites called oxylipins. Among these, isoprostanes, discovered in the 1990s, are formed non-enzymatically from ω-3 and ω-6 PUFAs with 16 to 22 carbon atoms. Over nearly 35 years of research, two nomenclature systems for isoprostanes have been proposed and have evolved. However, as research progresses, certain aspects of the current nomenclature remain unclear and require further clarification to ensure precise identification of each metabolite and its corresponding parent PUFA. Therefore, we propose an update to the current nomenclature system, along with practical guidelines for assessing isoprostanoid diversity and identifying their PUFA origins.

RESUMEN

In obesity, the process of adipogenesis largely determines the number of adipocytes in body fat depots. Adipogenesis is regulated by several adipocyte-selective micro-ribonucleic acids (miRNAs) and transcription factors that modulate adipocyte proliferation and differentiation. However, some miRNAs block the expression of master regulators of adipogenesis. Since the specific miRNAs display different expressions during adipogenesis, in mature adipocytes and permanent obesity, their use as biomarkers or therapeutic targets is feasible. Upregulated miRNAs in persistent obesity are downregulated during adipogenesis. Moreover, some of the downregulated miRNAs in obese individuals are upregulated in mature adipocytes. Induction of adipocyte stress and hypertrophy leads to the release of adipocyte-derived exosomes (AdEXs) that contain the cargo molecules, miRNAs. miRNAs are important messengers for intercellular communication involved in metabolic responses and have very specific signatures that direct the metabolic activity of target cells. While each miRNA targets multiple messenger RNAs (mRNAs), which may coordinate or antagonize each other's functions, several miRNAs are dysregulated in other tissues during obesity-related comorbidities. Deletion of the miRNA-processing enzyme DICER in pro-opiomelanocortin-expressing cells results in obesity, which is characterized by hyperphagia, increased adiposity, hyperleptinemia, defective glucose metabolism, and alterations in the pituitary-adrenal axis. In recent years, RNA-based therapeutical approaches have entered clinical trials as novel therapies against overweight and its complications. Development of lipid droplets, macrophage accumulation, macrophage polarization, tumor necrosis factor receptor-associated factor 6 activity, lipolysis, lipotoxicity, and insulin resistance are effectively controlled by miRNAs. Thereby, miRNAs as epigenetic regulators are used to determine the new gene transcripts and therapeutic targets.

Asunto(s)

Adipogénesis , Epigénesis Genética , MicroARNs , Obesidad , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Obesidad/genética , Obesidad/metabolismo , Adipogénesis/genética , Animales , Adipocitos/metabolismo , Exosomas/metabolismo , Exosomas/genética , Regulación de la Expresión Génica

RESUMEN

Parallel to the increasing prevalence of obesity in the world, the mortality from cardiovascular disease has also increased. Low-grade chronic inflammation in obesity disrupts vascular homeostasis, and the dysregulation of adipocyte-derived endocrine and paracrine effects contributes to endothelial dysfunction. Besides the adipose tissue inflammation, decreased nitric oxide (NO)-bioavailability, insulin resistance (IR), and oxidized low-density lipoproteins (oxLDLs) are the main factors contributing to endothelial dysfunction in obesity and the development of cardiorenal metabolic syndrome. While normal healthy perivascular adipose tissue (PVAT) ensures the dilation of blood vessels, obesity-associated PVAT leads to a change in the profile of the released adipo-cytokines, resulting in a decreased vasorelaxing effect. Higher stiffness parameter ß, increased oxidative stress, upregulation of pro-inflammatory cytokines, and nicotinamide adenine dinucleotide phosphate (NADP) oxidase in PVAT turn the macrophages into pro-atherogenic phenotypes by oxLDL-induced adipocyte-derived exosome-macrophage crosstalk and contribute to the endothelial dysfunction. In clinical practice, carotid ultrasound, higher leptin levels correlate with irisin over-secretion by human visceral and subcutaneous adipose tissues, and remnant cholesterol (RC) levels predict atherosclerotic disease in obesity. As a novel therapeutic strategy for cardiovascular protection, liraglutide improves vascular dysfunction by modulating a cyclic adenosine monophosphate (cAMP)-independent protein kinase A (PKA)-AMP-activated protein kinase (AMPK) pathway in PVAT in obese individuals. Because the renin-angiotensin-aldosterone system (RAAS) activity, hyperinsulinemia, and the resultant IR play key roles in the progression of cardiovascular disease in obesity, RAAS-targeted therapies contribute to improving endothelial dysfunction. By contrast, arginase reciprocally inhibits NO formation and promotes oxidative stress. Thus, targeting arginase activity as a key mediator in endothelial dysfunction has therapeutic potential in obesity-related vascular comorbidities. Obesity-related endothelial dysfunction plays a pivotal role in the progression of type 2 diabetes (T2D). The peroxisome proliferator-activated receptor gamma (PPARγ) agonist, rosiglitazone (thiazolidinedione), is a popular drug for treating diabetes; however, it leads to increased cardiovascular risk. Selective sodium-glucose co-transporter-2 (SGLT-2) inhibitor empagliflozin (EMPA) significantly improves endothelial dysfunction and mortality occurring through redox-dependent mechanisms. Although endothelial dysfunction and oxidative stress are alleviated by either metformin or EMPA, currently used drugs to treat obesity-related diabetes neither possess the same anti-inflammatory potential nor simultaneously target endothelial cell dysfunction and obesity equally. While therapeutic interventions with glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide or bariatric surgery reverse regenerative cell exhaustion, support vascular repair mechanisms, and improve cardiometabolic risk in individuals with T2D and obesity, the GLP-1 analog exendin-4 attenuates endothelial endoplasmic reticulum stress.

Asunto(s)

Endotelio Vascular , Obesidad , Humanos , Obesidad/metabolismo , Obesidad/fisiopatología , Obesidad/tratamiento farmacológico , Obesidad/complicaciones , Endotelio Vascular/fisiopatología , Endotelio Vascular/metabolismo , Endotelio Vascular/efectos de los fármacos , Animales , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/etiología , Tejido Adiposo/metabolismo , Tejido Adiposo/fisiopatología , Estrés Oxidativo

RESUMEN

Chloropropanols have been identified as processing-induced food contaminants which occur as by-products of the manufacturing of refined food oils and hydrolyzed vegetable protein. There has been a paucity of research on the 2-monochloropropane-1,3-diol (2-MCPD) isomer, thus forming a data gap for regulatory risk assessment. Previous studies suggest 2-MCPD causes adverse cardiotoxic, nephrotoxic, and myotoxic effects. Our study profiled the effects of 2-MCPD on oxylipins and oxidized phosphatidylcholines, using HPLC-MS/MS, in heart, kidney, serum, and skeletal muscle of male and female F344 rats orally exposed to 2-MCPD (40 mg/kg BW/d) for 90 days. Cardiac n-3 polyunsaturated fatty acid-derived oxylipins, particularly DHA-derived oxylipins, were lower with 2-MCPD exposure, coincident with cardiac lesions. Lipoxygenase-derived oxylipins were decreased in the serum with a greater effect in the male 2-MCPD treatment group. Few oxylipin alterations were seen in the kidney and there was an absence of alterations in the tibialis anterior. Oxidized phosphatidylcholines and isoprostanes were not altered in this study, indicating that oxidative stress was not elevated by 2-MCPD. These findings add to the weight of the evidence for 2-MCPD toxicity and support the use of serum oxylipins as potential biomarkers of 2-MCPD exposure.

RESUMEN

Endothelial dysfunction is a risk factor for atherosclerosis and includes impaired endothelium-dependent vasodilatation. We have shown previously that low density lipoprotein (LDL) can be oxidized by iron in the lysosomes of macrophages. Macrophage lysis in atherosclerotic lesions might expose endothelial cells to this oxidized LDL and adversely affect their function. LDL was oxidized by ferrous sulfate (5 µM) for 24 h at pH 4.5 at 37 °C. Aortas from male Wistar rats were cut into rings and subjected to wire myography for isometric tension recording. The rings were incubated with or without oxidized LDL (50 µg protein/ml) for one hour, constricted with 100 nM phenylephrine and relaxation to acetylcholine (1 nM - 3 µM) was measured. There was about 50% less relaxation in the presence of this oxidized LDL. Endothelial-independent vasodilatation induced by sodium nitroprusside was less affected by oxidized LDL. Oxidized LDL increased the formation of reactive oxygen species by the aortic rings and by cultured human aortic and dermal microvascular endothelial cells, which might have inactivated nitric oxide. Acetylcholine increased the activatory phosphorylation of eNOS (ser-1177), but oxidized LDL had little effect on this activation in cultured human aortic endothelial cells. These findings raise the possibility that LDL oxidized in lysosomes and released from lysed macrophages might decrease vasodilatation in atherosclerotic arteries.

RESUMEN

Rapid hemostasis, potent antimicrobial activity, and efficient wound management are critical factors in enhancing the survival of trauma patients. Chitosan, as a green and sustainable biomaterial with low cost, degradability and biocompatibility, is widely used in the biomedical field. However, chitosan dissolves in an acidic environment, which is not conducive to wound healing. In this study, chitosan was chemically modified to address this limitation. A mussel-inspired hydrogel composed of caffeic acid-grafted chitosan, gallic acid-grafted chitosan, and oxidized microcrystalline cellulose (CHI-C/CSG/OMCC) was designed. This hydrogel exhibits blood-responsive gelation behavior and offers a synergistic combination of tissue adhesion, antimicrobial properties, and tissue repair capabilities. The carboxyl, hydroxyl, phenolic hydroxyl and aldehyde groups within the hydrogel system endowed the hydrogel with excellent adhesion properties (53.1 kPa adhesion strength to porcine skin-adherent tissues), biocompatibility, and excellent antimicrobial properties. Surprisingly, this hydrogel not only achieved rapid and effective hemostasis, but also effectively promoted wound healing in a mouse skin injury model. In addition, its remarkable efficacy in stopping bleeding within approximately 2 min without rebleeding was demonstrated in a porcine model of acute gastrointestinal hemorrhage in the esophagus, stomach, and intestines. This blood-responsive ternary hydrogel offers a promising alternative to wound management materials due to its excellent overall performance and superior efficacy in all phases of wound healing.

Asunto(s)

Antibacterianos , Bivalvos , Hemostasis , Hidrogeles , Cicatrización de Heridas , Hidrogeles/química , Hidrogeles/farmacología , Animales , Cicatrización de Heridas/efectos de los fármacos , Hemostasis/efectos de los fármacos , Ratones , Bivalvos/química , Antibacterianos/farmacología , Antibacterianos/química , Quitosano/química , Quitosano/farmacología , Porcinos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Celulosa/química , Celulosa/farmacología , Ácidos Cafeicos/farmacología , Ácidos Cafeicos/química

RESUMEN

This review summarises the data from long-term experimental studies and literature data on the role of oxidatively modified low-density lipoproteins (LDL) in atherogenesis and diabetogenesis. It was shown that not "oxidized" (lipoperoxide-containing) LDL, but dicarbonyl-modified LDL are atherogenic (actively captured by cultured macrophages with the help of scavenger receptors), and also cause expression of lectin like oxidized low density lipoprotein receptor 1 (LOX-1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (NOX-1) genes in endotheliocytes, which stimulate apoptosis and endothelial dysfunction. The obtained data allowed us to justify new approaches to pharmacotherapy of atherosclerosis and diabetes mellitus.

RESUMEN

Wound healing is influenced by various factors, including oxidative damage, bacterial infection, and inadequate angiogenesis, which collectively contribute to a protracted healing process. In this work, we designed innovative multifunctional hydrogels based on fibrin integrated with Bletilla striata polysaccharides (BSP) or oxidated Bletilla striata polysaccharides (OBSP) for use as wound dressings. The preliminary structure and bioactivity of BSP and OBSP were investigated. The effect of polysaccharides on the self-assembly process of fibrin hydrogels were also evaluated. BSP and OBSP significantly altered the initial fibrin fibrillogenesis and the ultimate structure of the fibrin network. Relative to pure fibrin hydrogel, the incorporation of BSP and OBSP enhanced water swelling and retention, and decelerated the degradation of hydrogels in PBS. Furthermore, BSP and OBSP augmented the antioxidant, antibacterial, and anti-inflammatory properties of fibrin hydrogels, with OBSP demonstrating superior performance in these aspects. Through the development of a murine wound model, it was observed that the wound healing efficacy of hydrogels incorporating BSP and OBSP surpassed that of the pure fibrin group. Notably, the hydrogel formulated with 25 mg/mL OBSP exhibited the most pronounced therapeutic effect, achieving a healing rate approaching 100 %. Consequently, fibrin-OBSP composite hydrogels demonstrate significant potential as wound dressings.

RESUMEN

Bone defects caused by trauma, infection and congenital diseases still face great challenges. Dihydromyricetin (DHM) is a kind of flavone extracted from Ampelopsis grossedentata, a traditional Chinese medicine. DHM can enhance the osteogenic differentiation of human bone marrow mesenchymal stem cells with the potential to promote bone regeneration. Hydrogel can be used as a carrier of DHM to promote bone regeneration due to its unique biochemical characteristics and three-dimensional structure. In this study, oxidized phellinus igniarius polysaccharides (OP) and L-arginine chitosan (CA) are used to develop hydrogel. The pore size and gel strength of the hydrogel can be changed by adjusting the oxidation degree of oxidized phellinus igniarius polysaccharides. The addition of DHM further reduce the pore size of the hydrogel (213 µm), increase the mechanical properties of the hydrogel, and increase the antioxidant and antibacterial activities of the hydrogel. The scavenging rate of DPPH are 72.30 ± 0.33 %, and the inhibition rate of E.coli and S.aureus are 93.12 ± 0.38 % and 94.49 ± 1.57 %, respectively. In addition, PCAD has good adhesion and biocompatibility, and its extract can effectively promote the osteogenic differentiation of MC3T3-E1 cells. Network pharmacology and molecular docking show that the promoting effect of DHM on osteogenesis may be achieved by activating the PI3K/AKT and MAPK signaling pathways. This is confirmed through in vitro cell experiments and in vivo animal experiments.

Asunto(s)

Regeneración Ósea , Quitosano , Flavonoles , Hidrogeles , Sistema de Señalización de MAP Quinasas , Osteogénesis , Fosfatidilinositol 3-Quinasas , Polisacáridos , Proteínas Proto-Oncogénicas c-akt , Quitosano/química , Quitosano/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Flavonoles/farmacología , Flavonoles/química , Ratones , Hidrogeles/química , Hidrogeles/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Polisacáridos/química , Polisacáridos/farmacología , Osteogénesis/efectos de los fármacos , Regeneración Ósea/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Arginina/química , Arginina/farmacología , Oxidación-Reducción/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Escherichia coli/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Humanos , Antioxidantes/farmacología , Antioxidantes/química , Adhesivos/química , Adhesivos/farmacología

RESUMEN

Background: Local wisdom food ingredients in North Sumatra, Indonesia, are a source of phenolics which have antioxidant, antihyperlipidemia, neuronal survival, and growth. Administering products with antioxidant properties can provide a supporting effect in preventing inflammation and neurodegenerative process. Objective: The main objective of this study was to analyze the formulation of red palm oil (Elaeis guineensis Jacq), koja bay leaves (Murraya koenigii L Spreng), and passion fruit seeds (Passiflora edulis Sims) to improve lipid profile, antioxidant activity, Brain-Derived Neurotrophic Factor (BDNF), and lipase enzyme activity of Sprague-Dawley rats. Methods: This study was an in vivo and pre-post experimental study, starting with analyzing flavonoid of the three extract ingredients, then tested by giving it to rats for 14 days and ending with induction administration of lipopolysaccharide (LPS) for two days. This pre-post study on animals involved 36 rats divided into 6 groups. At the end of the study, termination and examination of malondialdehyde, lipid profile, glucose, BDNF, lipase enzyme activity and histopathological examination were carried out. Results: The study results showed that there were significant values in several parameters, which were body weight, LDL, LDL/HDL ratio, BDNF, and lipase enzyme activity especially in the group of rats given LPS and the group with high calories-fat-protein. This study showed that there were significant differences in body weight, LDL levels, and LDL/HDL ratio in each group of rats, especially in the group given the formulation of the three extract ingredients, the significant dose showed in 300mg/kg body weight (p < 0.001). Conclusion: The formulation of red palm oil, koja bay leaves, and passion fruit seeds showed significant reduction in LDL levels, LDL/HDL ratio, BDNF, and lipase enzyme activity.

RESUMEN

Impaired wound healing in diabetic wounds is common due to infection, inflammation, less collagen synthesis, and vascularization. Diabetic wound healing in patients is still a challenge and needs an ideal wound dressing to treat and manage diabetic wounds. Herein, an efficacious wound dressing biomaterial was fabricated by cross-linking oxidized isabgol (Oisab) and chitosan (Cs) via trisodium trimetaphosphate and Schiff base bonds. l-Arginine (l-Arg) was incorporated as a bioactive substance in the Oisab + Cs scaffold to promote cell adhesion, cell proliferation, collagen synthesis, and vascularization. The fabricated scaffolds showed microporous networks in the scanning electron microscopy analysis. The scaffold also possessed excellent hemocompatibility. In vitro studies using fibroblasts (L929 and human dermal fibroblast cells) confirmed the cytocompatibility of these scaffolds. The results of the in vivo chicken chorioallantoic membrane assay confirmed the proangiogenic activity of the Oisab + Cs + l-Arg scaffolds. The wound-healing potential of these scaffolds was studied in streptozotocin-induced diabetic rats. This in vivo study showed that the period of epithelialization in the Oisab + Cs + l-Arg scaffold-treated wounds was 21.67 ± 1.6 days, which was significantly faster than the control (30.33 ± 2.5 days). Histological and immunohistochemical studies showed that the Oisab + Cs + l-Arg scaffolds significantly accelerated the rate of wound contraction by reducing inflammation, improving collagen synthesis, and promoting neovascularization. These findings suggest that the Oisab + Cs + l-Arg scaffolds could be beneficial in treating diabetic wounds in clinical applications.

Asunto(s)

Arginina , Quitosano , Colágeno , Diabetes Mellitus Experimental , Ensayo de Materiales , Cicatrización de Heridas , Animales , Cicatrización de Heridas/efectos de los fármacos , Quitosano/química , Quitosano/farmacología , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Ratas , Colágeno/química , Arginina/química , Arginina/farmacología , Andamios del Tejido/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/síntesis química , Humanos , Masculino , Tamaño de la Partícula , Neovascularización Fisiológica/efectos de los fármacos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Materiales Biomiméticos/síntesis química , Ratones , Ratas Sprague-Dawley , Oxidación-Reducción

RESUMEN

The pulmonary system represents a unique lipidomic environment as it contains cellular membrane-bound lipid species and a specialized reservoir of lipids in the airway epithelial lining fluid. As a major initial point of defense, airway lipids react to inhaled contaminants such as volatile organic compounds, oxides of nitrogen, or ozone (O3), creating lipokine signaling that is crucial for both the initiation and resolution of inflammation within the lung. Dietary modulation of eicosanoids has gained increased attention in recent years for improvements to cardiovascular health. The current study sought to examine how dietary supplementation with eicosanoid precursors (i.e, oils rich in saturated or polyunsaturated fatty acids) might alter the lung lipid composition and subsequently modify the inflammatory response to ozone inhalation. Our study demonstrated that mice fed a diet high in saturated fatty acids resulted in diet-specific changes to lung lipid profiles and increased cellular recruitment to the lung following ozone inhalation. Bioinformatic analysis revealed an ozone-dependent upregulation of several lipid species, including phosphoserine 37:5. Pathway analysis of lipid species revealed the process of lateral diffusion of lipids within membranes to be significantly altered due to ozone exposure. These results show promising data for influencing pulmonary lipidomic profiles via diet, which may provide a pragmatic therapeutic approach to protect against lung inflammation and damage following pulmonary insult.

RESUMEN

Oxidized low-density lipoprotein (oxLDL) induces the formation of atherosclerotic plaques. Apolipoprotein B100 (apoB100) is a crucial protein component in low-density lipoprotein (LDL), which includes oxLDL. The oxidation of amino acids and subsequent alterations in their structure generate oxLDL, which is a significant biomarker for the initial phases of coronary artery disease. This study employed molecular docking and molecular dynamics utilizing the MM/GBSA method to identify aptamers with a strong affinity for oxidized apoB100. Molecular docking and molecular dynamics were performed on two sequences of the aptamer candidates (aptamer no.11 (AP11: 5'-CTTCGATGTAGTTTTTGTATGGGGTGCCCTGGTTCCTGCA-3') and aptamer no.26 (AP26: 5'-GCGAACTCGCGAATCCAGAACGGGCTCGGTCCCGGGTCGA-3')), yielding respective binding free energies of -149.08 kcal/mol and -139.86 kcal/mol. Interaction modeling of the simulation revealed a strong hydrogen bond between the AP11-oxidized apoB100 complexes. In an aptamer-based gold nanoparticle (AuNP) aggregation assay, AP11 exhibits a color shift from red to purple with the highest absorbance ratio, and shows strong binding affinity to oxLDL, correlating with the simulation model results. AP11 demonstrated the potential for application as a novel recognition element in diagnostic methodologies and may also contribute to future advancements in preventive therapies for coronary artery disease.

Asunto(s)

Apolipoproteína B-100 , Aptámeros de Nucleótidos , Lipoproteínas LDL , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Lipoproteínas LDL/química , Lipoproteínas LDL/metabolismo , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/metabolismo , Apolipoproteína B-100/química , Apolipoproteína B-100/metabolismo , Humanos , Oro/química , Nanopartículas del Metal/química