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•Novel bioactive composite scaffold with capability to release loaded platelet-derived growth factor in sustained manner was prepared.•Prepared composite scaffolds exhibited in vitro ...antibacterial and osteoconductive activities.•In vivo accelerated formation of cranial bone with prepared composite scaffold established their possible application in clinical settings.
The repair of bone defects has long been a challenging and significant health question. Here, collagen hydrogel incorporating platelet-derived growth factor (PDGF)-loaded photopolymerizable ZIF-8-PDA nanoparticles (PDGF@ZIF-8-PDA@COL hydrogel) was prepared and perfused into 3D printed poly (lactide-co-glycolide)-tricalcium phosphate (PLGA-TCP) scaffolds. The resulting PDGF@ZIF-8-PDA@COL/PLGA-TCP composite scaffolds were applied as a bone substitute for cranial bone defect repair. The photopolymerizable ZIF-8-PDA nanoparticles had a mean size of 226.2 ± 5.3 nm with photothermal conversion capacity. PDGF@ZIF-8-PDA@COL/PLGA-TCP composite scaffolds showed a slower release of PDGF compared to PDGF release from collagen hydrogels. The composite scaffolds exhibited excellent antibacterial properties and good in vitro osteoconductive capacity. The osteoconductive activities of PDGF@ZIF-8-PDA@COL/PLGA-TCP composite scaffolds were also investigated in a rat cranial bone defect model in vivo by micro-CT imaging, hematoxylin and eosin staining, Masson’s trichrome staining, and immunohistochemical staining of osteogenesis-related markers. The PDGF@ZIF-8-PDA@COL/PLGA-TCP composite scaffolds accelerated cranial bone formation and gradually degraded over time. All these results provided strong evidence that PDGF@ZIF-8-PDA@COL/PLGA-TCP composite scaffolds might be a promising system for bone defect repair.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Recent studies have shown that autophagy was associated with the development of osteoarthritis (OA), the purpose of this research was to determine the exact role of autophagy in OA and investigate ...effective therapeutic drugs to inhibit the pathological progression of OA.
In this study, a cellular OA model was generated by stimulating SW1353 cells with IL-1β and a rabbit OA model was established by intra-articular injection of collagenase, followed by treatment with Torin 1 or 3-Methyladenine (3-MA). The mRNA expression levels of VEGF, MMP-13 and TIMP-1 were determined by quantitative real-time PCR. The caitilage degeneration was examined by histological evaluation, chondrocytes degeneration and autophagosomes were observed by transmission electron microscopy. Expression levels of Beclin-1 and LC3 were evaluated by western blotting and immunofluorescence.
The degeneration of SW 1353 cells, cartilage and chondrocytes was related to the loss of autophagy in experimental OA. 3-MA increased the severity of degeneration of cells and cartilage by autophagy inhibition, while Torin 1 reduced that by autophagy activation.
The loss of autophagy is linked with the experimental OA and autophagy may play a protective role in the pathogenesis of OA. Treatment of Torin 1 can inhibit the degenerative changes of experimental OA by activating autophagy and it may be a useful therapeutic drug for OA.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Oxidative stress and inflammation are implicated in the development of sepsis-related acute lung injury (ALI). MicroRNA-1224-5p (miR-1224-5p) plays critical roles in regulating inflammatory response ...and reactive oxygen species (ROS) production. The present study is aimed at investigating the role and underlying mechanisms of miR-1224-5p in sepsis-related ALI. Mice were intratracheally injected with lipopolysaccharide (LPS, 5 mg/kg) for 12 h to induce sepsis-related ALI. To manipulate miR-1224-5p level, mice were intravenously injected with the agomir, antagomir, or matched controls for 3 consecutive days. Murine peritoneal macrophages were stimulated with LPS (100 ng/mL) for 6 h to further validate the role of miR-1224-5p in vitro. To inhibit adenosine 5′-monophosphate-activated protein kinase alpha (AMPKα) or peroxisome proliferator activated receptor-gamma (PPAR-γ), compound C or GW9662 was used in vivo and in vitro. We found that miR-1224-5p levels in lungs were elevated by LPS injection, and that the miR-1224-5p antagomir significantly alleviated LPS-induced inflammation, oxidative stress, and ALI in mice. Conversely, the miR-1224-5p agomir aggravated inflammatory response, ROS generation, and pulmonary dysfunction in LPS-treated mice. In addition, the miR-1224-5p antagomir reduced, while the miR-1224-5p agomir aggravated LPS-induced inflammation and oxidative stress in murine peritoneal macrophages. Further findings revealed that miR-1224-5p is directly bound to the 3′-untranslated regions of PPAR-γ and subsequently suppressed PPAR-γ/AMPKα axis, thereby aggravating LPS-induced ALI in vivo and in vitro. We demonstrate for the first time that endogenous miR-1224-5p is a critical pathogenic factor for inflammation and oxidative damage during LPS-induced ALI through inactivating PPAR-γ/AMPKα axis. Targeting miR-1224-5p may help to develop novel approaches to treat sepsis-related ALI.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A new class of metal-free, easy to synthesize redox catalysts based on a triarylimidazole framework is described. With those synthesized thus far, one can access a potential range of ca. 410 mV. They ...proved to be useful mediators for the activation of benzylic C–H bonds under mild conditions.
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IJS, KILJ, NUK, PNG, UL, UM
The indirect anodic oxidation of chalcone epoxides in the presence of electron-rich heteroarenes mediated by a triarylimidazole (Med) was investigated by cyclic voltammetry (CV) and controlled ...potential electrolysis. The CV results indicate that a homogeneous electron transfer between Med•+ and chalcone epoxides is facilitated by an electron-rich heteroarene that serves as an arylation reagent. The preparative scale electrolysis generated epoxide-ring-opened/Friedel–Crafts arylation products in moderate to good yields. The fact that only a catalytic amount of charge was required suggests that Med•+ initiates a chain reaction. In addition, overoxidation of the products is avoided even though their oxidation potential is less than that of the starting chalcone epoxides.
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IJS, KILJ, NUK, PNG, UL, UM
Accumulating evidence suggests that autophagy is closely related to the pathogenesis of osteoarthritis (OA). The aim of this study was to determine the changes in autophagy during the progression of ...OA and to elucidate the specific role of autophagy in OA. For this purpose, a cellular model of OA was generated by stimulating SW1353 cells with interleukin (IL)-1β and a rabbit model of OA was also established by an intra-articular injection of collagenase, followed by treatment with the autophagy specific inhibitor, 3-methyladenine (3-MA). Cell viability was analyzed by MTS assay, and the mRNA expression levels of matrix metalloproteinases (MMP)-13 and tissue inhibitor of metalloproteinase (TIMP)-1 were determined by RT-qPCR. Cartilage degeneration was examined under a light microscope, and autophagosome and chondrocyte degeneration was observed by transmission electron microscopy. The protein expression of Beclin-1 and light chain 3 (LC3)B was evaluated by western blot analysis and immunofluorescence staining. We found that the autophagy was enhanced during the early stages and was weakened during the late stages of experimental OA. The inhibition of autophagy by 3-MA significantly aggravated the degeneration of chondrocytes and cartilage in experimental OA. Our results thus determine the changes in autophagy during different stages of OA, as well as the role of impaired autophagy in the development of OA. Our data suggest that the regulation of autophagy may be a potential therapeutic strategy with which to attenuate OA.
A series of triarylimidazoles was synthesized and characterized electrochemically. The synthetic route is general, providing a pathway to 30 redox mediators that exhibit a > 700 mV range of ...accessible potentials. Most of the triarylimidazoles display three oxidation peaks where the first redox couple is quasi-reversible. The electronic character of the substituents affects the oxidation potential. This is exemplified by a linear correlation between the first oxidation potential and the sum of the Hammett σ+ substituent constants, as well as with a series of calculated ionization potentials. We close by putting forward a rule of thumb stating that for a given mediator, the upper limit of accessible potentials can be extended by at least 500 mV beyond the largest recorded value. A rationale, the conditions under which the rule is likely to apply, and an example are provided.
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IJS, KILJ, NUK, PNG, UL, UM
Inflammation and oxidative stress contribute to the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury (ALI). MicroRNA-762 (miR-762) has been implicated in the progression of ...inflammation and oxidative stress; however, its role in ALI remains unclear. In this study, we aim to investigate the role and underlying mechanisms of miR-762 in LPS-induced ALI.
Mice were intravenously injected with miR-762 antagomir, agomir or the negative controls for 3 consecutive days and then received a single intratracheal instillation of LPS (5 mg/kg) for 12 h to establish ALI model. Adenoviral vectors were used to knock down the endogenous SIRT7 expression.
An increased miR-762 expression was detected in LPS-treated lungs. miR-762 antagomir significantly reduced inflammation, oxidative stress and ALI in mice, while the mice with miR-762 agomir treatment exhibited a deleterious phenotype. Besides, we found that SIRT7 upregulation was essential for the pulmonoprotective effects of miR-762 antagomir, and that SIRT7 silence completely abolished the anti-inflammatory and anti-oxidant capacities of miR-762 antagomir.
miR-762 is implicated in the pathogenesis of LPS-induced ALI via modulating inflammation and oxidative stress, which depends on its regulation of SIRT7 expression. It might be a valuable therapeutic target for the treatment of ALI.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the ...risk factors for severe COVID-19 to improve treatment guidelines.
A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19.
A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval CI: 1.317-5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002-3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126-9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752-6.706, P < 0.001), and/or diarrhea (OR: 2.629, 95% CI: 1.109-6.231, P = 0.028) on admission had a higher risk of severe disease. Moreover, stratification analysis indicated that male patients with diabetes were more likely to have severe COVID-19 (71.4% vs. 28.6%, χ2 = 8.183, P = 0.004).
The clinical characteristics of those with severe and nonsevere COVID-19 were significantly different. The elderly, male patients with COVID-19, diabetes, and presenting with cough and/or diarrhea on admission may require close monitoring to prevent deterioration.
This study provides an integrated interpretation for the Mesozoic ‐ Cenozoic tectonothermal evolutionary history of the Permian strata in the Qishan area of the southwestern Weibei Uplift, Ordos ...Basin. Apatite fission‐track and apatite/zircon (U‐Th)/He thermochronometry, bitumen reflectance, thermal conductivity of rocks, paleotemperature recovery, and basin modeling were used to restore the Meso‐Cenozoic tectonothermal history of the Permian Strata. The Triassic AFT data have a pooled age of ∼180±7 Ma with one age peak and P(χ2)=86%. The average value of corrected apatite (U‐Th)/He age of two Permian sandstones is ∼168±4 Ma and a zircon (U‐Th)/He age from the Cambrian strata is ∼231±14 Ma. Bitumen reflectance and maximum paleotemperature of two Ordovician mudstones are 1.81%, 1.57% and ∼210°C, ∼196°C respectively. After undergoing a rapid subsidence and increasing temperature in Triassic influenced by intrusive rocks in some areas, the Permian strata experienced four cooling‐uplift stages after the time when the maximum paleotemperature reached in late Jurassic: (1) A cooling stage (∼163 Ma to ∼140 Ma) with temperatures ranging from ∼132°C to ∼53°C and a cooling rate of ∼3°C/Ma, an erosion thickness of ∼1900 m and an uplift rate of ∼82 m/Ma; (2) A cooling stage (∼140 Ma to ∼52 Ma) with temperatures ranging from ∼53°C to ∼47°C and a cooling rate less than ∼0.1°C Ma, an erosion thickness of ∼300 m and an uplift rate of ∼3 m/Ma; (3) (∼52 Ma to ∼8 Ma) with ∼47°C to ∼43°C and ∼0.1°C /Ma, an erosion thickness of ∼500 m and an uplift rate of ∼11 m/Ma; (3) (∼8 Ma to present) with ∼43°C to ∼20°C and ∼3°C/Ma, an erosion thickness of ∼650 m and an uplift rate of ∼81 m/Ma. The tectonothermal evolutionary history of the Qishan area in Triassic was influenced by the interaction of the Qinling Orogeny and the Weibei Uplift, and the south Qishan area had the earliest uplift‐cooling time compared to other parts within the Weibei Uplift. The early Eocene at ∼52 Ma and the late Miocene at ∼8 Ma, as two significant turning points after which both the rate of uplift and the rate of temperature changed rapidly, were two key time for the uplift‐cooling history of the Permian strata in the Qishan area of the southwestern Weibei Uplift, Ordos Basin.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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