RESUMEN
Injectable, self-crosslinking collagen-based hydrogels are beneficial for chondrocytes to secrete matrix, positioning them as promising candidates for cartilage tissue engineering. However, previous studies lacked insight into the ability of cell-free collagen-based hydrogels to regenerate hyaline cartilage defect. Therefore, this study aimed to evaluate the potential of collagen-based hydrogels (Col and ColHA) to induce chondrogenic differentiation of stem cells and in situ hyaline cartilage regeneration. Both Col and ColHA hydrogels self-crosslinked in situ and exhibited similar physical properties. In vitro experiments showed they supported the survival, adhesion, spreading, and proliferation of bone marrow stem cells (BMSCs). Moreover, both hydrogels induced ectopic differentiation of BMSCs into chondrocytes when implanted subcutaneously into the back of nude mice. ColHA hydrogel notably enhanced type II collagen secretion. The results of repairing cartilage defects in situ revealed both hydrogels facilitated hyaline cartilage regeneration and maintained cartilage phenotype without exogenous BMSCs. Hydrogels encapsulating BMSCs expedited cartilage repair, and ColHA/BMSC constructs showed better mechanical properties, suggesting their potential for cartilage repair applications. This study implies that collagen-based hydrogels are good candidates for hyaline cartilage regeneration.
Asunto(s)
Diferenciación Celular , Condrogénesis , Colágeno , Cartílago Hialino , Hidrogeles , Regeneración , Hidrogeles/química , Hidrogeles/farmacología , Condrogénesis/efectos de los fármacos , Animales , Regeneración/efectos de los fármacos , Ratones , Colágeno/química , Colágeno/metabolismo , Diferenciación Celular/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Condrocitos/citología , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Ratones Desnudos , Ingeniería de Tejidos/métodos , Proliferación Celular/efectos de los fármacosRESUMEN
Type I collagen (Col I) and hyaluronic acid (HA), derived from the extracellular matrix (ECM), have found widespread application in cartilage tissue engineering. Nevertheless, the potential of cell-free collagen-based scaffolds to induce in situ hyaline cartilage regeneration and the related mechanisms remain undisclosed. Here, we chose Col I and HA to construct Col I hydrogel and Col I-HA composite hydrogel with similar mechanical properties, denoted as Col and ColHA, respectively. Their potential to induce cartilage regeneration was investigated. The results revealed that collagen-based hydrogels could regenerate hyaline cartilage without any additional cells or growth factors. Notably, ColHA hydrogel stood out in this regard. It elicited a moderate activation, recruitment, and reprogramming of macrophages, thus efficiently mitigating local inflammation. Additionally, ColHA hydrogel enhanced stem cell recruitment, facilitated their chondrogenic differentiation, and inhibited chondrocyte fibrosis, hypertrophy, and catabolism, thereby preserving cartilage homeostasis. This study augments our comprehension of cartilage tissue induction theory by enriching immune-related mechanisms, offering innovative prospects for the design of cartilage defect repair scaffolds. STATEMENT OF SIGNIFICANCE: The limited self-regeneration ability and post-injury inflammation pose significant challenges to articular cartilage repair. Type I collagen (Col I) and hyaluronic acid (HA) are extensively used in cartilage tissue engineering. However, their specific roles in cartilage regeneration remain poorly understood. This study aimed to elucidate the functions of Col I and Col I-HA composite hydrogels (ColHA) in orchestrating inflammatory responses and promoting cartilage regeneration. ColHA effectively activated and recruited macrophages, reprogramming them from an M1 to an M2 phenotype, thus alleviating local inflammation. Additionally, ColHA facilitated stem cell homing, induced chondrogenesis, and concurrently inhibited fibrosis, hypertrophy, and catabolism, collectively contributing to the maintenance of cartilage homeostasis. These findings underscore the clinical potential of ColHA for repairing cartilage defects.
Asunto(s)
Homeostasis , Cartílago Hialino , Ácido Hialurónico , Hidrogeles , Regeneración , Hidrogeles/química , Hidrogeles/farmacología , Animales , Regeneración/efectos de los fármacos , Cartílago Hialino/efectos de los fármacos , Homeostasis/efectos de los fármacos , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Condrogénesis/efectos de los fármacos , Ratones , Inmunomodulación/efectos de los fármacos , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Colágeno Tipo I/metabolismo , Diferenciación Celular/efectos de los fármacos , Andamios del Tejido/química , Macrófagos/efectos de los fármacos , Macrófagos/metabolismoRESUMEN
Collagen and hyaluronic acid are commonly applied in cartilage tissue engineering, yet there has been limited investigation into their inflammatory response, a crucial factor in articular cartilage repair. This study aimed to evaluate the impact of components and physical properties of hydrogels on inflammatory response and cartilage repair. Three kinds of hydrogels with comparable storage moduli at low frequencies were designed and fabricated, namely, methacrylic anhydride-modified hyaluronic acid hydrogel (HAMA), methacrylic anhydride-modified type I collagen hydrogel (CMA) and unmodified type I collagen hydrogel (Col). HAMA hydrogel was unfavorable for adhesion and spreading of BMSCs. Furthermore, HAMA hydrogel stimulated rapid migration and pro-inflammatory M1 polarization of macrophages, leading to persistent and intense inflammation, which was unfavorable for cartilage repair. CMA and Col hydrogels possessed the same component and facilitated the adhesion, spreading and proliferation of BMSCs. Compared with CMA hydrogel, Col hydrogel induced rapid migration and moderate M1 polarization of macrophages at the early stage of injury, which was mainly influenced by its fast dissolution rate, small pore size fiber network structure and rapid stress relaxation. In addition, the phenotype of macrophages timely transformed into anti-inflammatory M2 due to the properties of the collagen component, which shortened the duration of inflammation and enhanced cartilage repair. The results indicated that moderate macrophage activation adjusted by hydrogel components and physical properties was critical in modulating inflammation and cartilage regeneration.
Asunto(s)
Cartílago Articular , Hidrogeles , Humanos , Hidrogeles/farmacología , Hidrogeles/química , Condrocitos , Ácido Hialurónico/farmacología , Ácido Hialurónico/química , Colágeno Tipo I , Colágeno/química , Inflamación/tratamiento farmacológico , AnhídridosRESUMEN
Apple growth and yield are largely dependent on plant height and flowering characteristics. The BELL1-like homeobox (BLH) transcription factors regulate extensive plant biological processes. However, the BLH-mediated regulation of plant height and flowering in apple remains elusive. In the current study, 19 members of the MdBLH family were identified in the apple genome. Segmental duplication and purifying selection are the main reasons for the evolution of the MdBLH genes. A BLH1-like gene, MdBLH14, was isolated and functionally characterized. The MdBLH14 was preferentially expressed in flower buds, and downregulated during the floral induction period. The subcellular localization in tobacco leaves indicated that MdBLH14 is a nuclear protein. Overexpression of MdBLH14 in Arabidopsis led to a significant dwarfing and late-flowering phenotype by hindering active GA accumulation. Additionally, MdKNOX19, another member of the TALE superfamily, physically interacts with MdBLH14 and synergistically inhibits the expression of MdGA20ox3. This is the first report on the function of the MdBLH14 from apple, and its mechanism involving plant flower induction and growth. The data presented here provide a theoretical basis for genetically breeding new apple varieties.
Asunto(s)
Arabidopsis , Malus , Malus/genética , Malus/metabolismo , Genes Homeobox , Fitomejoramiento , Flores/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
Articular cartilage is refractory to self-healing due to the absence of vascular, nervous, and lymphatic systems, and its repair remains a clinical challenge. Tissue regeneration through in situ recruitment of stem cells via cell-free scaffolds is a promising alternative strategy. Herein, a kind of functional injectable hydrogel system (Col-Apt@KGN MPs), which is a collagen-based and microsphere-embedded cell-free scaffold, was designed to achieve spatiotemporal regulation of endogenous mesenchymal stem cells (MSCs) recruitment and their chondrogenic differentiation by respective release of aptamer 19S (Apt19S) and kartogenin (KGN). In vitro results confirmed that the Col-Apt@KGN MPs hydrogel had sequential release characteristics. Apt19S was rapidly released from the hydrogel within 6 days, while KGN was slowly released for 33 days via the degradation of poly(lactic-co-glycolic acid) (PLGA) microspheres. When cultured with MSCs, the Col-Apt@KGN MPs hydrogel supported the adhesion, proliferation, and chondrogenic differentiation of MSCs. In vivo results indicated that the Col-Apt@KGN MPs hydrogel effectively promoted the recruitment of endogenous MSCs in a rabbit full-thickness cartilage defect model; furthermore, the Col-Apt@KGN MPs hydrogel enhanced the secretion of cartilage specific extracellular matrix and achieved the reconstruction of subchondral bone. This study demonstrates that the Col-Apt@KGN MPs hydrogel possesses great potential in recruitment of endogenous stem cells and cartilage tissue regeneration.
Asunto(s)
Enfermedades de los Cartílagos , Cartílago Articular , Células Madre Mesenquimatosas , Animales , Conejos , Hidrogeles/metabolismo , Diferenciación CelularRESUMEN
The suitable seeding cells and scaffolds are very important for tissue engineering to create functional cartilage. Although the physicochemical properties of scaffold and co-culture system of mesenchymal stem cells (MSCs) and chondrocytes could affect functional properties of engineered cartilage tissues respectively, the combined effects of them on chondrogenesis is currently unknown. Herein, methacrylated collagen (CMA30 and CMA80) hydrogels with different degradation rate and stiffness were prepared. The MSCs and chondrocytes were co-cultured or monocultured in collagen, CMA30 and CMA80 hydrogels in vitro or in vivo. The results demonstrated that cell spreading and proliferation was regulated by degradation rate and stiffness of hydrogels. Compared to single MSCs culture, co-culture cells in all collagen-based hydrogels significantly improved chondrogenesis. CMA30 hydrogel with moderate degradation rate and low storage modulus was the most effective for co-culture system to promote chondrogenesis compared to Col and CMA80 hydrogel in vitro culture, while there was no obvious difference between CMA30 and CMA80 hydrogel in vivo. Furthermore, the intercellular substance exchange was very important for co-culture system to maintain the positive effect on chondrogenesis. Overall, the current study highlights the synergistic effects of the physicochemical properties of collagen-based hydrogel and co-culture system on cartilage formation. STATEMENT OF SIGNIFICANCE: Scaffolds and cells play a key role in cartilage tissue engineering. The combined effects of physicochemical properties of collagen hydrogels and co-culture system (MSCs and chondrocytes) on chondrogenesis is unknown. In contrast to the studies that investigated the effect of single factor (scaffolds or cells) on cartilage formation, this manuscript explored the synergistic regulation of both scaffold properties and biological factors on chondrogenesis, and provided a promising strategy for cartilage tissue engineering.
Asunto(s)
Condrogénesis , Hidrogeles , Hidrogeles/química , Técnicas de Cocultivo , Condrocitos , Colágeno/farmacología , Colágeno/metabolismo , Ingeniería de Tejidos/métodos , Diferenciación Celular , Andamios del Tejido , Células CultivadasRESUMEN
AIM: As a primary cause of death not only in Western countries but also in the People's Republic of China, sepsis is diagnosed as abnormal organ functions as a result of a disordered response to a severe infection. This study was designed to assess the effect of small-dose levosimendan without a loading dose on mortality rates and organ functions in Chinese elderly patients with sepsis. METHODS: Following a prospective, randomized, and double-blinded design, 240 Chinese elderly patients with sepsis shock were admitted to the intensive care unit (ICU). All patients were randomly and evenly assigned into a levosimendan group (number of patients =120) and a control group (number of patients =120). The control group underwent standard care, and the levosimendan group was administered levosimendan in addition to standard care. RESULTS: All participants, comprising 134 males (55.8%) and 106 females (44.2%), were 70 (67-73) years old. Baseline characteristics, preexisting illnesses, initial infections, organ failures, and additional agents and therapies showed no significant difference between the two groups (P>0.05 for all). There were no significant differences in mortality rates at 28 days, at ICU discharge, and at hospital discharge between the two groups (P>0.05 for all). The number of days of ICU and hospital stay in the levosimendan group was significantly less than for those in the control group (P<0.05 for all). Mean daily total sequential organ failure assessment score and all organ scores except the cardiovascular scores showed no significant difference between the two groups (P>0.05 for all). Cardiovascular scores in the levosimendan group were significantly higher than those in the control group (P<0.05 for all). CONCLUSION: Small-dose levosimendan could not reduce the mortality rates or enhance the respiratory, liver, renal, and coagulation functions, but could shorten the days of ICU and hospital stay, and improve the cardiovascular function, which suggests that small-dose levosimendan is valuable for Chinese elderly patients with sepsis.
Asunto(s)
Hidrazonas/uso terapéutico , Puntuaciones en la Disfunción de Órganos , Piridazinas/uso terapéutico , Choque Séptico/tratamiento farmacológico , Choque Séptico/mortalidad , Anciano , China , Método Doble Ciego , Femenino , Mortalidad Hospitalaria , Humanos , Hidrazonas/administración & dosificación , Unidades de Cuidados Intensivos/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Masculino , Estudios Prospectivos , Piridazinas/administración & dosificación , SimendánRESUMEN
By using the observation data from 620 meteorological stations in China, the annual accumulated temperature above 10 degrees C, its starting date, ending date, and duration days from 1951 to 1978 and from 1979 to 2005 were calculated and compared. The results showed that in most areas of China, especially in Northeastern, North, and South China, the accumulated temperature above 10 C from 1979 to 2005 was higher than that from 1951 to 1978. The starting date of accumulated temperature above 10 degrees C in northern areas of Yangtze River was 0-5 days earlier from 1979 to 2005 than from 1951 to 1979, while that in southern areas of Yangtze River was 0-5 days later from 1979 to 2005 than from 1951 to 1979. The ending date of accumulated temperature above 10 degrees C in most areas of China was delayed 0-5 days, except that in near coastal areas of South China and some regions of Southwest China, which was delayed more than 5 days. The duration days of accumulated temperature above 10 C were generally increased by 0-5 days or 5-10 days in most areas of China, but the increase amplitude was different and could not be linked together in different areas. To accurately know the changing trend of accumulated temperature above 10 degrees C could provide an important basis for the adjustment of agricultural production structure and the assessment of agricultural potential productivity.
Asunto(s)
Productos Agrícolas/crecimiento & desarrollo , Ecosistema , Monitoreo del Ambiente/métodos , Temperatura , China , Recolección de DatosRESUMEN
Based on the theory of risk analysis and the nearest 50 years practical unit yield and meteorological data of North China winter wheat region, this paper discussed the assessment of winter wheat yield loss risk and its classification. The mean yield reduction rate of past years, variation coefficient of yield reduction rate in disaster years, different yield reduction rate and its occurrence probability, and disasters-resistance index were selected as the risk assessment indices, and the assessment showed that the distribution of these indices in the region had evident regional differentiation and certain continuity. The model of integrated risk index of North China winter wheat yield loss was established on the basis of the assessment, and the classification index of the risk was put forward. According to the classification result, North China winter wheat region was divided into three risk types, i.e., high risk type mainly including the Loess Plateau areas of Shanxi and Shaanxi Provinces and the parts of North China Plain, medium risk type including the northeastern part of North China Plain, south Henan Province and Taihang Moutain region, and low risk type including most parts of North China Plain and the central Shanxi plain.