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BACKGROUND: A critical factor in the storability of recalcitrant seeds is their moisture content (MC), but its effect on the viability of Cinnamomum cassia (L.) J. Presl (C. cassia) seeds is not fully understood. METHODS AND RESULTS: Measured the germination rate, starch and soluble sugar content, and transcriptome of 8 seed samples with different MC obtained by low-temperature drying method. It was found that the germination rate was significantly negatively correlated with MC. The lethal MC was around 15.6%. During the dehydration process, there was a significant increase in the content of soluble sugars and starch. Transcriptome analysis was performed on CK, W3, W6 showed a total of 62.78 Gb of clean data. Among the 30,228 Unigenes, 28,195 were successfully annotated. In the three comparative groups (CK and W3, CK and W6, W3 and W6), 6,842, 7,640, and 11,628 differentially expressed genes (DEGs) were obtained, respectively. These DEGs were found to be involved in a variety of metabolic pathways, including carbon metabolism, amino acid biosynthesis, starch and sucrose metabolism, glycolysis/gluconeogenesis, and nucleotide and amino sugar metabolism. A total of 1,416 common genes were identified among all three comparison groups. Furthermore, among all the DEGs, a total of 71 transcription factor families were identified, with the C2H2 transcription factor family having the highest number of genes. CONCLUSIONS: This ground-breaking study sheds light on the physiological response and gene expression profiles of C. cassia seeds after undergoing dehydration treatment, which will provide valuable insights for further research and understanding of this process.
Assuntos
Cinnamomum aromaticum , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Germinação , Sementes , Transcriptoma , Sementes/genética , Sementes/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Cinnamomum aromaticum/genética , Cinnamomum aromaticum/metabolismo , Germinação/genética , Perfilação da Expressão Gênica/métodos , Transcriptoma/genética , Desidratação/genética , Amido/metabolismo , Amido/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
The rise of antibiotic-resistant strains demands new alternatives in antibacterial treatment. Bacteriophages, with their precise host specificity and ability to target and eliminate bacteria safely, present a valuable option. Meanwhile, hydrogels, known for their excellent biodegradability and biocompatibility, serve as ideal carriers for bacteriophages. The combination of bacteriophages and hydrogels ensures heightened phage activity, concentration, controlled release, and strong antibacterial properties, making it a promising avenue for antibacterial treatment. This article provides a comprehensive review of different crosslinking methods for phage hydrogels, focusing on their application in treating infections caused by various drug-resistant bacteria and highlighting their effective antibacterial properties and controlled release capabilities.
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Antibacterianos , Bacteriófagos , Hidrogéis , Hidrogéis/química , Bacteriófagos/fisiologia , Antibacterianos/farmacologia , Antibacterianos/química , Humanos , Bactérias/efeitos dos fármacos , Bactérias/virologia , Animais , Infecções Bacterianas/terapia , Terapia por Fagos/métodosRESUMO
Thirty new, highly oxygenated and stereogenic 14-membered macrocyclic diterpenoids, papyrifuranols A-Z (1-26) and AA-AD (27-30), and eight known analogs have been isolated from Boswellia papyrifera resins. All the structures were characterized by detailed spectral analyses, quantum calculations, X-ray diffraction, and modified Mosher's methods. Notably, six previously reported structures were revised. Our study points out misleading factors of macrocyclic cembranoid (CB) representation in the past seven decades by analyzing of 25 X-ray structures, lending a hand for the innately challenging structure identification of such flexible macrocyclic CBs and avoiding following the tracks of an overturned cart during future structure characterization and total synthesis. Biosynthetic conversions of all the isolates are proposed, and wound healing bioassays reveal that papyrifuranols N-P could significantly stimulate the proliferation and differentiation of umbilical cord mesenchymal stem cells.
Assuntos
Boswellia , Diterpenos , Boswellia/química , Raios X , Resinas Vegetais/química , Diterpenos/química , Difração de Raios XRESUMO
To reveal the biomedical effects and mechanisms of hydrogen molecules urgently needs hydrogen molecular imaging probes as an imperative tool, but the development of these probes is extremely challenging. A catalytic hydrogenation strategy is proposed to design and synthesize a ratiometric fluorescent probe by encapsulating Pd nanoparticles and conjugating azido-/coumarin-modified fluorophore into mesoporous silica nanoparticles, realizing inâ vitro and inâ vivo fluorescence imaging of hydrogen molecules. The developed hydrogen probe exhibits high sensitivity, rapid responsivity, high selectivity and low detection limit, enabling rapid and real-time detection of hydrogen molecules both in cells and in the body of animal and plant. By application of the developed fluorescent probe, we have directly observed the super-high transmembrane and ultrafast transport abilities of hydrogen molecules in cells, animals and plants, and discovered inâ vivo high diffusion of hydrogen molecules.
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Corantes Fluorescentes/química , Hidrogênio/análise , Imagem Molecular , Animais , Azidas/química , Cumarínicos/química , Corantes Fluorescentes/síntese química , Humanos , Paládio/química , Dióxido de Silício/química , Fatores de TempoRESUMO
(±)-Petchilactones A-C (1-3), three pairs of enantiomeric meroterpenoids respectively with a 6/6/5/5 or a 5/5/5/7/6 ring system were isolated from Ganoderma petchii. Their structures including absolute configurations were assigned by using spectroscopic, computational, and X-ray diffraction methods. Compounds 1 and 2 represent a new skeletal meroterpenoid. Biological evaluation found that (-)-1 and (-)-3 could induce umbilical cord mesenchymal stem cells into keratinocyte-like cells.
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Ganoderma/química , Queratinócitos/citologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Terpenos/química , Terpenos/farmacologia , Linhagem Celular , Transdiferenciação Celular/efeitos dos fármacos , Técnicas de Reprogramação Celular/métodos , Cristalografia por Raios X , Humanos , Queratinócitos/efeitos dos fármacos , Modelos Moleculares , Estereoisomerismo , Terpenos/isolamento & purificação , Cordão Umbilical/citologiaRESUMO
Andrographis Herba is a commonly used plant medicine, and has been recorded in pharmacopeias of different countries. However, there are some differences in the quality standards. Based on this, this paper compare the quality standards of Andrographis Herba between Chinese Pharmacopoeia, Hong Kong Chinese Materia Medica Standards, United States Pharmacopoeia, European Pharmacopoeia and Indian Pharmacopoeia, including origin, botanical characteristics, identification(microscopic identification and chromatographic identification), content determination, specific test(such as impurities, loss on drying, extractives, pesticides, heavy metals, mycotoxins, and other items) and storage requirements, so as to provide a reference for studying international quality standards of Andrographis.
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Andrographis , Medicamentos de Ervas Chinesas , Materia Medica , Padrões de ReferênciaRESUMO
The new sesquiterpene dimers commiphoroids A-D (1-4) were isolated from Resina Commiphora, and their structures were assigned by spectroscopic methods and X-ray diffraction analysis. Compounds 1 and 2 are stereoisomers of putative [2 + 4]-cycloaddition reactions, and 3 is a trinorsesquiterpene dimer containing a 6/6/5/6/6/6 hexacyclic framework, while 4 possesses a 8-oxabicyclo[3.2.1]oct-6-ene skeletal core. Plausible biosynthetic pathways for 1-4 are proposed. Biochemical studies show that compound 1 promotes ca. 60% expression of keratinocyte-specific markers in adipose-derived stem cells at 10 µM.
Assuntos
Tecido Adiposo/citologia , Diferenciação Celular/efeitos dos fármacos , Commiphora/química , Dimerização , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Células-Tronco/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Células-Tronco/citologiaRESUMO
To reveal the effect of plant growth regulator GA3 and DPC on the active components and its possible mechanism of Lonicera japonica. GA and DPC were applied at the stage of flower bud differentiation, and the content of active ingredients was measured by LC-MS-MS, the content of endogenous hormones were measured by ELISA, and the expression of key enzyme enes expression was determined by qRT-PCR. The level of endogenous hormone GA3, IAA, ZR, DHZR and iPA in the GA treatment group was significantly improved, the expression of C4H1, C4H2, 4CL1 and HQT2 were also significantly increased. The content of chlorogenic acid, luteolin, luteoloside, isoquercetin and caffeic acid increased significantly. Spraying DPC did not affect or inhibit the accumulation of active components of L. japonica. Spraying GA can increase the content of endogenous GA3, thus enhance the expression of C4H1, C4H2, 4CL1 and HQT2, and then increase the content of chlorogenic acid and luteolin.
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Lonicera , Ácido Clorogênico , Reguladores de Crescimento de Plantas , Espectrometria de Massas em TandemRESUMO
Spatholobi Caulis, the vine stem of Spatholobus suberectus and widely used in China and Southeast Asian nations, has the effects on nourishing the blood and promoting blood flow, regulating menstruation and relieving pain, and invigorating the nerves. Through consulting the herbal textual and local chronicles, we summarized the original textual research and medicinal evolution on Spatholobi Caulis to analyze the changes of varieties in different historical periods. Further, the major active ingredient in Spatholobi Caulis was discussed. According to the literature to date, 60 flavonoids compounds have been isolated and could be divided into isoflavones, dihydroflavones, flavanols, dihydroflavonols, procyaninides, chalcones, pterocarpans, isoflavanols, isoflavanones and aurone according to their molecular structures. These indicative ingredients in Spatholobi Caulis showed pharmacological activities on regulation of the blood system, anti-tumor, anti-oxidation, anti-virus, anti-bacteria and inhibition of melanin deposition. This review will provide reference and basis for the sustainable use of resources and industry development on Spatholobi Caulis.
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Medicamentos de Ervas Chinesas/farmacologia , Fabaceae/química , Flavonoides/análise , China , Humanos , Caules de Planta/químicaRESUMO
BACKGROUND: The incapacity of articular cartilage (AC) for self-repair after damage ultimately leads to the development of osteoarthritis. Stem cell-based therapy has been proposed for the treatment of osteoarthritis (OA) and induced pluripotent stem cells (iPSCs) are becoming a promising stem cell source. RESULTS: Three steps were developed to differentiate human iPSCs into chondrocytes which were transplanted into rat OA models induced by monosodium iodoacetate (MIA). After 6 days embryonic body (EB) formation and 2 weeks differentiation, the gene and protein expression of Col2A1, GAG and Sox9 has significantly increased compare to undifferentiated hiPSCs. After 15 weeks transplantation, no immune responses were observed, micro-CT showed gradual engraftment and the improvement of subchondrol plate integrity, and histological examinations demonstrated articular cartilage matrix production. CONCLUSIONS: hiPSC could be an efficient and clinically translatable approach for cartilage tissue regeneration in OA cartilages.
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Cartilagem Articular/crescimento & desenvolvimento , Condrócitos/citologia , Condrócitos/transplante , Células-Tronco Pluripotentes Induzidas/citologia , Osteoartrite/patologia , Osteoartrite/terapia , Animais , Cartilagem Articular/imunologia , Cartilagem Articular/patologia , Diferenciação Celular/imunologia , Células Cultivadas , Condrócitos/imunologia , Condrogênese/imunologia , Osteoartrite/imunologia , Ratos , Ratos Sprague-Dawley , Resultado do TratamentoRESUMO
Stroke has a greater effect on women. However, sex differences in outcome and factors associated with outcome among elderly patients are unknown. From January 2009 to December 2011, 810 patients with acute ischemic stroke aged 75 years or older were recruited in China. Clinical profile and risk factors were recorded. Outcomes and associated risk factors at 12 and 36 months after stroke were assessed by sex. Hypertension, diabetes mellitus, dyslipidemias, and obesity prevalence rates were higher in women than in men; opposite trends were found for smoking and alcohol consumption. The mortality rate at 12 months after stroke was significantly greater in men than in women (23.3% versus 16.6%, P = .015). Large-artery atherothrombotic and cardioembolic stroke subtypes were risk factors for mortality, recurrence, and dependency in both sexes. In men, atrial fibrillation was a risk factor of mortality at 12 months after stroke (relative ratio [RR], 2.12; 95% confidence interval [CI], 1.38-3.27), but obesity was a protective factor of mortality at 36 months after stroke (RR, .30; 95% CI, .10-.94). However, in women, atrial fibrillation was a risk factor of recurrence at 12 months (RR, 2.32; 95% CI, 1.31-4.12) and dependency at 36 months after stroke (RR, 7.68; 95% CI, 1.60-36.82). We assessed sex differences in stroke outcomes and associated risk factors at 12 and 36 months after stroke in a large hospital-based stroke registry of elderly patients from Northern China. Thus, it is crucial to emphasize risk management to elderly patients to reduce mortality, recurrence, and dependency after stroke.
Assuntos
Envelhecimento , Isquemia Encefálica/complicações , Caracteres Sexuais , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/mortalidade , Taxa de Sobrevida , Fatores de TempoRESUMO
Metal coordination hydrogels (MC-HGs) that introduce dynamically coordinate bonds together with metal ionic conduction have attracted considerable attention in flexible electronics. However, the traditional soaking method alleged to have technical scalability faces the challenge of forming MC-HGs with a "core-shell" structure, which undoubtedly reduces the whole mechanical properties and ionic stimulation responsiveness required for flexible electronics materials. Herein, a novel strategy referred to as "masking" has been proposed based on the theory of the valence bond and coordination chemistry. By regulating the masking agents and their concentrations as well as pairing mode with the metal ions, the whole mechanical properties of the resulting composites (MC-HGsMasking) show nearly double the values of their traditional soaking samples (MC-HGsSoaking). For example, the fracture stress and toughness of Fe-HGsMasking(SA, 5.0 g/L) are 1.55 MPa and 2.14 MJ/m3, almost twice those of Fe-HGsSoaking (0.83 MPa and 0.93 MJ/m3, respectively). Microstructure characterization combined with finite element analysis, molecular dynamics, and first-principles simulations demonstrates that the masking strategy first facilitating interfacial permeation of metal complexes and then effective coordination with functional ligands (carboxylates) of the hydrogels is the mechanism to strengthen the mechanical properties of composites MC-HGsMasking, which has the potential to break through the limitations of current MC-HGs in flexible electronic sensor applications.
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Determination of Fe, Zn, Cu, K, P, Ca, Mg, Na, B and Al in cistanche and its extractives was carried out by the inductively coupled plasma atomic emission spectrometry (ICP-AES). The results showed that (1) the contents of Mn, K, Ca, Mg and Na in cistanche deserticola Y. C. Ma were 17.70, 16,278. 03, 1,947.25, 1,662.76, and 106.79 respectively (microg.g-1), much higher than in Cistanche tubulosa (Schrenk) Wight; (2) the contents of Fe, Cu and P in 50% methanol extract of Cistanche deserticola were 1.5, 2.4, and 1.1 times that of aqueous extract respectively, the contents of Mn, Zn, K, P, Mg and Na were 3.8, 1.2, 1.6, 2.3, 2.2, and 1.1 times that of methanol extract respectively; (3) the contents of Cu and P in 50% methanol extract of Cistanche tubulosa were 1.6 and 1.2 times that of aqueous extract, the contents of Mn, Zn, K, P, Mg, Na and Al were 2.0, 1.6, 1.6, 1.4, 1.8, 1.2, and 1.2 times that of methanol extract respectively; (4) the leaching rate of 11 mineral elements in Cistanche deserticola and Cistanche tubulosa were 60.79%-83. 10% and 44. 58%-83.84% in 50% methanol respectively, and the leaching rate of Mn, Zn, K, P, Ca, Na and Al were much higher than in water and 100% methanol extracted. The research provided the basic data of mineral element in comparative study on Cistanche deserticola and Cistanche tubulosa, and provide scientific basis for efficient utilization of mineral element in cistanche.
Assuntos
Cistanche/química , Extratos Vegetais/química , Espectrofotometria Atômica/métodos , Oligoelementos/análise , Minerais/análiseRESUMO
Accumulating experimental data have shown that endogenous hormones play important roles in regulating seed dormancy and germination. Zanthoxylum nitidum is a medicinal plant that propagates via seeds, which require a long dormancy period for normal germination, and complex changes in metabolites occur during the germination process. However, the regulatory network of endogenous hormones and metabolites during the germination of Z. nitidum seeds remains unclear. This study investigated the dynamic changes in the levels of metabolites and endogenous hormones during the germination of Z. nitidum seeds. The results revealed an increase in the levels of gibberellin 3 (GA3), 12-oxophytodienoic acid (OPDA), 1-aminocyclopropane-1-carboxylic acid (ACC) and trans-zeatin (TZ) and decrease in the levels of abscisic acid (ABA), jasmonic acid (JA), N-[(-)-jasmonoyl]-(S)-isoleucine (JA-Ile) and trans-zeatin riboside (TZR). Overall, 112 differential metabolites (DAMs) were screened from 3 seed samples (Sa, Sb and Sc), most of which are related to primary metabolism. A total of 16 DAMs (including 3 monosaccharides, 3 phosphate lipids, 3 carboxylic acids, 1 amino acid, 2 pyrimidines, and 4 nucleotides) were identified in the three sample comparison pairs (Sa vs Sb, Sa vs Sc, and Sb vs Sc); these DAMs were significantly enriched in purine metabolism; glycerophospholipid metabolism, citrate cycle (TCA cycle), alanine, aspartate and glutamate metabolism and pyruvate metabolism. OPDA, ACC and GAs were significantly positively correlated with upregulated metabolites, whereas ABA and JA were significantly positively correlated with downregulated metabolites. Finally, a hypothetical metabolic network of endogenous hormones that regulate seed germination was constructed. This study deepens our understanding of the importance of endogenous hormonal profiles that mediate seed germination.
Assuntos
Germinação , Zanthoxylum , Ácido Abscísico , Aminoácidos , SementesRESUMO
Zanthoxylum nitidum (Roxb.) is a commonly used traditional Chinese medicine. However, the collection and protection of wild germplasm resources of Z. nitidum are still insufficient, and there is limited research on its genetic diversity and fingerprint. In the present study, 15 simple sequence repeat (SSR) markers were developed by genotyping based on multiplexed shotgun sequencing. The genetic diversity of 51 populations (142 individuals) of Z. nitidum was evaluated using these 15 SSRs. A total of 245 alleles (Na) were detected, with an average value of 16.333, and the average polymorphism information content was 0.756. The genetic distance among 51 populations was 0.164~1.000, with an average of 0.659. Analysis of molecular variance showed low genetic differentiation (40%) and high genetic differentiation (60%) between populations and individuals, respectively. The genetic differentiation coefficient (Fst) of the population was 0.338, indicating that 66.2% of the genetic variation occurred within the population, and the gene flow (Nm) was 0.636, demonstrating that the gene exchange between populations was low. Clustering analysis revealed that the genetic similarity coefficient was 0.30, dividing the 51 populations into 4 groups of 2, 17, 3, and 29 populations. There was no specific relationship between geographical location differences and genetic distance. The genetic diversity level of Z. nitidum is relatively high, and our results provide a theoretical basis for the rapid identification of Z. nitidum germplasm resources and variety selection.
Assuntos
Zanthoxylum , Humanos , Zanthoxylum/genética , Polimorfismo Genético , Biomarcadores , Repetições de Microssatélites/genética , Alelos , Variação GenéticaRESUMO
Zanthoxylum nitidum (Roxb.) DC. (Z. nitidum) is a type of Chinese Dao-di herb, also called Liangmianzhen, which is widely used to treat arthralgia, rheumatic arthralgia, and stomach pain. However, genomic resources for Z. nitidum are still scarce. This study provides transcriptomic resources for Z. nitidum by applying single-molecule real-time (SMRT) sequencing technology. In total, 456,109 circular consensus sequencing (CCS) reads were generated with a mean length of 2,216 bp from Z. nitidum roots, old stems, young branches, leaves, flowers, and fruits. Of these total reads, 353,932 were full-length nonchimeric (FLNC) reads with an average length of 1,996 bp. A total of 16,163 transcripts with a mean length of 1,171 bp were acquired. Of these transcripts, 14,231 (88%) were successfully annotated using public databases. Across all the 16,163 transcripts, we identified 6,255 long non-coding RNAs (lncRNAs) and 22,780 simple sequence repeats (SSRs). Furthermore, 3,482 transcription factors were identified. Among the SSR loci, 1-3 nucleotide repeats were dominant, occupying 99.36% of the total SSR loci, with mono-, di-, and tri-nucleotide repeats accounting for 61.80%, 19.89%, and 5.02% of the total SSR loci, respectively. A total of 36 out of 100 randomly selected primer pairs were verified to be positive, 20 of which showed polymorphism. These findings enrich the genetic resources available for facilitating future studies and research on relevant topics such as population genetics in Z. nitidum.
Assuntos
Zanthoxylum , Zanthoxylum/genética , Perfilação da Expressão Gênica , Transcriptoma/genética , Polimorfismo Genético , NucleotídeosRESUMO
Recently, spiropyran-based composites have gained more attention on account of their stimuli-responsive essence, especially of the fascinating and green photo stimulus. However, the great dipole moment change between the ring-opened merocyanine and ring-closed spiropyran requires a large free volume available for isomerization, which significantly restrains the photoisomerization of spiropyran-based nanocomposites. Herein, a fascinating pathway by regulating the states both of spiropyran and the immobilized nanoparticle supports was put forward to facilitate the photoisomerization. The results demonstrated that the spiropyran grafting percentage of 5.18% and immobilized supports with less aggregation, high specific surface area, large pore size, and noncrystalline structure were suitable to fabricate spiropyran-based nanocomposites, which showed a significant improvement for Pb2+ and Cr3+ removal from aqueous solution on account of free photoisomerization of spiropyran on the support's surface. This work will pave the pathway to extend the exploitation of spiropyran-based nanocomposites in various fields such as biotechnology, physiology, and electronics to photonics and environmental-friendly fields.
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Overcoming the bacterial infection and promoting angiogenesis are challenge and imperious demands in wound healing and skin regeneration. Hereby, we developed a multifunctional AMP/S1P@PLA/gelatin wound dressing fabricated by electrospinning poly (L-lactic acid) (PLA)/gelatin with antimicrobial polypeptides (AMPs) and sphingosine-1-phosphate (S1P) in order to inhibit the bacteria growth and induce angiogenesis. In our work, AMP/S1P@PLA/gelatin wound dressing was obtained by two-step method of electrospinning and dopamine adsorption. Our results showed that incorporating AMP into PLA/gelatin nanofibrous membranes significantly improved antibacterial properties against both Escherichia coli and Staphylococcus aureus. S1P releasing from AMP/S1P@PLA/gelatin nanofibrous membranes could significantly enhance tube formation. Simultaneously, we found that the AMP/S1P@PLA/gelatin nanofibrous membranes facilitated the adhesion, proliferation, and migration of human umbilical vein endothelial cells (HUVECs) and murine fibroblast (L929). AMP/S1P@PLA/gelatin membranes could also accelerate infected wound healing and skin regeneration by antibacterial and pro-angiogenesis effects. In summary, our developed AMP/S1P@PLA/gelatin nanofibrous membranes could be multifunctional dressing for infected wound healing and skin regeneration. Schematic figure to describe the characterizations and preparation of AMP/S1P@PLA/gelatin nanofibrous membranes.
Assuntos
Gelatina , Nanofibras , Camundongos , Humanos , Animais , Gelatina/química , Células Endoteliais , Antibacterianos/farmacologia , Antibacterianos/química , Nanofibras/química , Bandagens , Poliésteres/químicaRESUMO
Molecular hydrogen holds a high potential for wound healing owing to its anti-inflammatory effect and high biosafety, but commonly used hydrogen administration routes hardly achieve the sustained supply of high-dosage hydrogen, limiting hydrogen therapy efficacy. Here, two-dimensional Mg2 Si nanosheet (MSN) is exploited as a super-persistent hydrogen-releasing nanomaterial with high biocompatibility, and the incorporation of MSN into the chitosan/hyaluronic acid hydrogel (MSN@CS/HA) is developed as a dressing to repair deeply burned skin. The MSN@CS/HA hydrogel dressing can continuously generate hydrogen molecules for about 1 week in the physiological conditions in support of local, long-term, and plentiful hydrogen supply and remarkably promotes the healing and regeneration of deep second-degree and third-degree burn wounds without visible scar and toxic side effect. Mechanistically, a sustained supply of hydrogen molecules induces anti-inflammatory M2 macrophage polarization in time by enhancing CCL2 (chemokine C-C motif ligand 2) expression to promote angiogenesis and reduce fibrosis and also enhances the proliferation and migration capability of skin cells directly and indirectly by locally scavenging overexpressed reactive oxygen species, synergistically favoring wound repair. The proposed synthesis method, therapeutic strategy, and mechanisms will open a window for synthesizing a variety of MSene nanomaterials and developing their various proangiogenesis applications besides wound healing.
Assuntos
Queimaduras , Cicatrização , Humanos , Pele/metabolismo , Hidrogéis/farmacologia , Queimaduras/tratamento farmacológico , Macrófagos/metabolismoRESUMO
AIMS: Aging impairs cardiac function and increases susceptibility to myocardial ischaemic injury. Cardiac myosin light chain kinase (MLCK3) phosphorylates cardiac myosin regulatory light chain (MLC2), controlling sarcomere organization and cardiomyocyte contraction. Dysregulation of MLCK3 and phosphorylated MLC2 (p-MLC2) contributes to heart failure after myocardial infarction (MI). We aimed at exploring how the MLCK3-p-MLC2 axis changes in aging hearts post MI and at investigating the underlying regulatory mechanisms. METHODS AND RESULTS: We generated adult (3 months) and aged (30 months) MI mouse models to compare their cardiac performance, and then detected MLCK3 expression and MLC2 activity. Aging increased the size of MI-induced infarctions and promoted cardiac contractile dysfunction. Furthermore, MLCK3 expression and MLC2 activity increased in adult hearts after MI, but not in aged hearts. miR-146a was found consistently increased in adult and aged hearts post MI. Mechanistic analyses performed in vitro demonstrated that miR-146a-5p down-regulated matrix metalloprotease (MMP)2/16 expression in cardiomyocytes. This down-regulation in turn increased MLCK3 expression and MLC2 activity. However, miR-146a-5p failed to regulate the MMP2/16-MLCK3-p-MLC2 axis in senescent cardiomyocytes or in cardiac miR-146a conditional knockout mice, with the latter experiencing an exacerbated deterioration of cardiac function post MI. CONCLUSION: These results suggest that an increase of MLCK3 and p-MLC2 contents through decreasing MMP2/16 by miR-146a-5p represents a compensatory mechanism that can protect cardiac contractile function after MI. Aging impairs this miR-146a-5p-regulated MMP2/16-MLCK3-p-MLC2 contractile axis, leading to compromised contractile function and increased susceptibility to heart failure.