Interferon-Alpha Induces Psoriatic Inflammation in Mice by Phosphorylating FOXO3.

Psoriasis is a chronic, immune-mediated inflammatory skin disease characterized by epidermal thickening and inflammatory cell infiltration. Excessive proliferation of keratinocytes and resistance to apoptosis lead to thickening of the epidermis. Plasmacytoid dendritic cells are involved in the occurrence of psoriasis mainly by secreting interferon-alpha (IFN-α). IFN-α is a glycoprotein with antiviral, antitumor, and immunomodulatory effects, but its role in psoriasis remains unclear. In this investigation, a mild psoriatic phenotype was observed in mice upon topical application of IFN-α cream, and the inflammation was exacerbated when combined with imiquimod (IMQ). Immunohistochemical analyses demonstrated that IFN-α induces psoriatic inflammation in mice by stimulating phosphorylation of forkhead box O3, consistent with the involvement of this protein in cell proliferation, apoptosis, and inflammation. Our results suggested that topical IFN-α caused psoriatic inflammation and that the psoriatic inflammation was exacerbated by the combination of IFN-α and IMQ, possibly due to the dysfunction of forkhead box O3.

Oxygen-Generating Hydrogels as Oxygenation Therapy for Accelerated Chronic Wound Healing.

Hypoxia in chronic wounds impairs the activities of reparative cells, resulting in tissue necrosis, bacterial infections, decreased angiogenesis, and delayed wound healing. To achieve effective oxygenation therapy and restore oxygen homeostasis, oxygen-generating hydrogels based on different oxygen sources have been developed to release dissolved oxygen in the wound bed, which not only alleviate hypoxia, but also accelerate chronic wound healing. This review first discusses the vital role of oxygen and hypoxia in the wound healing process. The advancements in oxygen-generating hydrogels, which produce oxygen through the decomposition of hydrogen peroxide, metal peroxides, glucose-activated cascade reactions, and photosynthesis of algae microorganisms for chronic wound healing, are discussed and summarized. The therapeutic effects and challenges of using oxygen-generating hydrogels for the clinical treatment of chronic wounds are concluded and prospected.

Guanosine-driven hyaluronic acid-based supramolecular hydrogels with peroxidase-like activity for chronic diabetic wound treatment.

Guanosine is often used to construct supramolecular hydrogels due to its self-assembly properties, however, the high temperature and strong alkaline construction methods greatly limit its application in biomedical fields. In this work, a guanosine-driven hyaluronic acid-based supramolecular hydrogel was developed under mild condition by employing phenylboronic acid-functionalized hyaluronic acid (HA-PBA) backbone and guanosine molecules. Guanosines self-assembled into G-quartet planes under potassium ion conditions, and formed boronic ester bonds with HA-PBA, which induced rapid formation of dynamically cross-linked hydrogels. Hemin was then binding to the G-quartet plane via π-π interactions in the hydrogels, which exhibited peroxidase activity and were highly effective in killing bacteria by generating hydroxyl radicals in the presence of H2O2. Furthermore, glucose oxidase (GOx) was incorporated into the hydrogels and the HP/G@hemin@GOx hydrogels showed good antibacterial properties, modulation of wound glucose and ROS level, and good therapeutic efficacy for diabetic chronic wounds. Overall, the self-assembly of guanosine has been shown for the first time to be a feasible method for constructing natural polymer-based supramolecular hydrogels. This guanosine-driven HA-based supramolecular hydrogel can act as a potential wound dressing for chronic diabetic wound treatment. STATEMENT OF SIGNIFICANCE: Chronic wound repair remains an unsolved clinical challenge. Herein, we propose to utilize phenylboronic acid-modified hyaluronic acid and guanosine to construct supramolecular gels with peroxidase activity for chronic wound treatment. The self-assembly behavior of guanosine drives the natural macromolecular backbone to form the hydrogel, and the proposed method simplifies the gelation conditions and improves its biosafety. The G-quartets formed by the self-assembly of guanosine can act as the loading site for hemin. G-quartet/hemin complex imported peroxidase activity to the hydrogels, endowing them with the ability to kill bacteria and regulate ROS levels of cells in the wound site. This guanosine-driven supramolecular hydrogel significantly increased the rate of wound healing in diabetic mice, promising a new strategy for chronic wound treatment.

Correlation of sLOX-1 Levels and MR Characteristics of Culprit Plaques in Intracranial Arteries with Stroke Recurrence.

(1) Background: Symptomatic intracranial artery atherosclerosis (sICAS) is an important cause of acute ischaemic stroke (AIS) and is associated with a high risk of stroke recurrence. High-resolution magnetic resonance vessel wall imaging (HR-MR-VWI) is an effective method for evaluating atherosclerotic plaque characteristics. Soluble lectin-like oxidised low-density lipoprotein receptor-1 (sLOX-1) is closely associated with plaque formation and rupture. We aim to explore the correlation between sLOX-1 levels and culprit plaque characteristics, based on HR-MR-VWI, with stroke recurrence in patients with sICAS. (2) Methods: A total of 199 patients with sICAS underwent HR-MR-VWI between June 2020 and June 2021 in our hospital. The culprit vessel and plaque characteristics were assessed according to HR-MR-VWI, and sLOX-1 levels were measured by ELISA (enzyme linked immunosorbent assay). Outpatient follow-up was performed 3, 6, 9, and 12 months after discharge. (3) Results: sLOX-1 levels were significantly higher in the recurrence group than in the non-recurrence group (p < 0.001). The culprit plaque thickness, degree of stenosis and plaque burden were higher in the recurrence group than in the non-recurrence group (p = 0.003, p = 0.014 and p = 0.010, respectively). The incidence of hyperintensity on T1WI, positive remodelling and significant enhancement (p < 0.001, p = 0.003 and p = 0.027, respectively) was higher in the recurrence group than in the non-recurrence group. Kaplan-Meier curves showed that patients with sLOX-1 levels > 912.19 pg/mL and hyperintensity on T1WI in the culprit plaque had a higher risk of stroke recurrence (both p < 0.001). Multivariate Cox regression analysis showed that sLOX-1 > 912.19 pg/mL (HR = 2.583, 95%CI 1.142, 5.846, p = 0.023) and hyperintensity on T1WI in the culprit plaque (HR = 2.632, 95% CI 1.197, 5.790, p = 0.016) were independent risk factors for stroke recurrence. sLOX-1 levels were significantly associated with the culprit plaque thickness (r = 0.162, p = 0.022), degree of stenosis (r = 0.217, p = 0.002), plaque burden (r = 0.183, p = 0.010), hyperintensity on T1WI (F = 14.501, p < 0.001), positive remodelling (F = 9.602, p < 0.001), and significant enhancement (F = 7.684, p < 0.001) (4) Conclusions: sLOX-1 levels were associated with vulnerability of the culprit plaque and can be used as a supplement to HR-MR-VWI to predict stroke recurrence.

Injectable macro-porous chitosan/polyethylene glycol-silicotungstic acid double-network hydrogels based on "smashed gels recombination" strategy for cartilage tissue engineering.

The lack of interconnected macro-porous structure of most injectable hydrogels lead to poor cell and tissue infiltration. Herein, we present the fabrication of injectable macro-porous hydrogels based on "smashed gels recombination" strategy. Chitosan/polyethylene glycol-silicotungstic acid (CS/PEG-SiW) double-network hydrogels were prepared via dual dynamic interactions. The bulk CS/PEG-SiW hydrogels were then smashed into micro-hydrogels with average sizes ranging from 47.6 to 63.8 µm by mechanical fragmentation. The CS/PEG-SiW micro-hydrogels could be continuously injected and rapidly recombined into a stable porous hydrogel based on the dual dynamic interactions between micro-hydrogels. The average pore size of the recombined porous CS/PEG-SiW hydrogels ranged from 52 to 184 µm. The storage modulus, compress modulus and maximum compressive strain of the recombined porous CS/PEG-SiW1.0 hydrogels reached about 47.2 %, 28.2 % and 127.6 % of the values for their corresponding bulk hydrogels, respectively. The recombined porous hydrogels were cytocompatible and could effectively support proliferation and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In a rat cartilage defect model, recombined porous CS/PEG-SiW hydrogels could promote cartilage regeneration. Hematoxylin and eosin (H&E), Safranin-O/Fast green and immunohistochemical staining confirmed the accumulation of glycosaminoglycans (GAG) and type II collagen (Col II) in regenerated cartilage.

Predictive value of the combination between the intracranial arterial culprit plaque characteristics and the Essen Stroke Risk Score for short-term stroke recurrence.

AIM: In the current study we aim the identification of the culprit plaque characteristics of intracranial arteries using high-resolution magnetic resonance vessel wall imaging (HR-MR-VWI). Moreover, we target the evaluation of the predictive value of culprit plaque characteristics for short-term stroke recurrence combined with ESRS. MATERIALS AND METHODS: We conducted a prospective cohort study on 342 patients diagnosed with symptomatic intracranial atherosclerotic stenosis (sICAS), out of which 243 were men and 99 were women with an average age of 64 ± 12 years. 184 cases of anterior circulation ischemia (ACIS) and 158 cases of posterior circulation ischemia (PCIS) were included in the study. All of them underwent HR-MR-VWI during the period between February 2020 and June 2021 in the Second Affiliated Hospital of Nantong University, Nantong, China. The culprit vessel and culprit plaque characteristics were assessed based on HR-MR-VWI images, and the patients' ESRS were obtained from the electronic medical records of the hospital. Concerning the obtained results from the 6-month follow-up, the patients were divided into the non-recurrence group and the recurrence group, and the differences in the above-mentioned features between the two groups were compared. The univariate Cox regression analysis combined with ESRS was performed to screen out the independent risk factors associated with recurrent stroke with P < 0.1. Receiver operating characteristic curves (ROC curves) were plotted to analyze the predictive performance of the culprit plaque characteristics, ESRS and combined variables for stroke recurrence. We used the area under the curve (AUC) ROC, while the sensitivity and specificity were calculated at the optimal threshold. The Delong test was employed to compare the quality of the AUC of the predictors. RESULTS: A total of 15.5% (53/342) of patients had a stroke recurrence within six months, with statistically significant differences (P < 0.05) between the two groups regarding the ESRS, medical history of diabetes mellitus, myocardial infarction, data for previous acute ischemic stroke (AIS) or transient ischemic attack(TIA), history of peripheral vascular disease, and serum brain natriuretic peptide level. In the patients with ACIS, the incidence of hyperintensity on the T1-weighted imaging (T1WI) was significantly different between the recurrence and the non-recurrence groups (P < 0.05). In the patients with PCIS, statistically significant differences between the recurrence and the non-recurrence group were detected in the culprit plaque burden, degree of enhancement, and incidence of hyperintensity on T1WI (P < 0.05). The ESRS (hazard ratios [HR], 1.598, 95% confidence interval [CI], 1.193-2.141, P = 0.002) ,degree of enhancement (HR = 1.764, 95% CI 0.985-3.087, P = 0.047) and hyperintensity on T1WI (HR = 2.745, 95% CI 1.373-5.488, P = 0.004) proved to be independent risk factors for stroke recurrence. The ESRS predicted stroke recurrence with AUC = 0.618 (95% CI 0.564-0.670), while the best cut-off value was 2 points. Furthermore, the registered sensitivity and specificity were 60.4% and 58.5%, respectively. Regarding the degree of enhancement in the culprit plaque, the prediction of stroke recurrence was with AUC = 0.628 (95% CI 0.574-0.679) as well as with sensitivities and specificities of 58.5% and 64.4%, respectively. Regarding the hyperintensity on T1WI in culprit plaque, the prediction of stroke recurrence was with AUC = 0.678 (95% CI 0.626-0.727) as well as with sensitivities and specificities of 66.0% and 70.0%, respectively. The ESRS combined with the degree of enhancement predicted stroke recurrence with an AUC = 0.685 (95CI% 0.633-0.734), while the recorded sensitivity and specificity were 56.6% and 73.4%, respectively. The ESRS combined with hyperintensity on the T1WI predicted stroke recurrence with an AUC = 0.745 (95CI% 0.696-0.791). The recorded sensitivity and specificity were 64.2% and 76.8%, respectively. The AUC quality of the ESRS combined with hyperintensity on T1WI was higher than that of other indices (P < 0.05). CONCLUSIONS: The hyperintensity on T1WI of the culprit plaque in intracranial arteries combined with ESRS demonstrated better predictive ability for short-term stroke recurrence. We consider this of high importance for clinical application since it provides an easier way of obtaining data for precise diagnosis.

Relationship between annular calcification of plaques in the carotid sinus and perioperative hemodynamic disorder in carotid angioplasty and stenting.

OBJECTIVE: To investigate the correlation between annular plaque calcification in the carotid sinus and perioperative hemodynamic disorder (HD) in carotid angioplasty and stenting (CAS). METHODS: The clinical data of 49 patients undergoing CAS due to narrowing of the carotid sinus were retrospectively analyzed. All patients had preoperative carotid computed tomography angiography (CTA) and were divided into HD and non-HD groups based on the occurrence of HD in the perioperative period of CAS. HD was defined as persistent bradycardia (heart rate < 60 beats per min) or persistent hypotension (systolic blood pressure < 90 mmHg) in the perioperative period and lasting for at least 1 h. The baseline data, including the degree of carotid artery stenosis, plaque length, plaque thickness, calcified plaque morphologies (i.e., plaque circumferential angle: < 90° defined as dotted calcification; 90°-180° defined as arcuate calcification; > 180° defined as annular calcification), contralateral carotid artery conditions, balloon diameter, and stent types, were compared between the two groups. Binary logistic regression was used to analyze the risk factors for the occurrence of HD. RESULTS: Among the 49 patients undergoing CAS, 14 (28.57%) developed perioperative HD, and 35 did not. Annular calcification was more common in the patients in the HD group than in the non-HD group. No significant differences in the probabilities of dotted and arcuate calcifications were found between the two groups (p > 0.05). The duration of continuous dopamine consumption in the HD group was 9-71 h. The average hospital stay of the HD group (10.14 ± 4.17 days) was significantly longer than that of the non-HD group (6.57 ± 1.9 days; p < 0.001). Patients in the HD group had significantly more pronounced lumen stenosis (p = 0.033) and longer plaque length (p = 0.034) than those in the non-HD group. After adjusting for age and sex, multivariate regression analysis showed that the presence of annular plaque calcification was an independent predictor of HD (odds ratio: 7.68, 95% confidence interval: 1.46-40.37, p = 0.016). CONCLUSIONS: The occurrence of annular plaque calcification in the carotid sinus was an independent risk factor for perioperative HD in CAS. Preoperative carotid CTA assists with the early identification of high-risk patients who may develop HD.

Correlation of the characteristics of symptomatic intracranial atherosclerotic plaques with stroke types and risk of stroke recurrence: a cohort study.

Background: Symptomatic intracranial atherosclerotic stenosis (sICAS) patients had a higher risk of stroke recurrence, and the risk of acute ischemic stroke (AIS) was higher than transient ischemic attack (TIA). Therefore, it is important to explore the risk factors associated with sICAS clinical subtypes and the risk of stroke recurrence. The purpose of this study was to investigate the association between intracranial arterial culprit plaque characteristics with sICAS clinical subtypes and the risk of stroke recurrence. Methods: A total of 206 patients with sICAS were included. Baseline demographic data and relevant serologic indices were collected from all participants. All participants were assessed by high-resolution vessel wall imaging (HR-VWI) for culprit vessel and culprit plaque characteristics. The follow-up method was outpatient or telephone follow-up. Associated factors for sICAS clinical subtypes were analyzed by binary logistic regression. Cox proportional hazard regression analysis were used to analysis the independent risk factors for recurrent stroke. Results: In this group, there were 154 patients with AIS, 52 patients with TIA, 124 patients with anterior circulation ischemic symptom (ACiS), and 82 patients with posterior circulation ischemic symptom (PCiS). Male gender [odds ratio (OR) =5.575, 95% confidence interval (CI): 2.120 to 14.658], history of previous statin use (OR =0.309, 95% CI: 0.113 to 0.843) and serum apolipoprotein A/B values (OR =0.363, 95% CI: 0.139 to 0.948) were associated factors for AIS. A total of 24 patients (11.7%) experienced stroke recurrence during the 1-year follow-up period. Hyperintensity on T1 weighted imaging (T1WI) in the culprit plaque [hazard ratio (HR) =3.798, 95% CI: 1.433 to 10.062] was an independent risk factor for stroke recurrence. The incidence of significant enhancement (62.2% vs. 39.5%, χ2=9.681, P=0.002), positive remodeling (69.5% vs. 52.4%, χ2=5.661, P=0.020), and hyperintensity on T1WI (42.7% vs. 22.6%, χ2=16.472, P=0.003) was higher in the posterior circulation than in the anterior circulation. Conclusions: The characteristics of intracranial arterial culprit plaques were independent risk factors for recurrent stroke, and there were differences in the plaque characteristics of anterior and posterior circulation. Early HR-VWI examination for sICAS patients is of great significance for patient risk stratification and personalized management.

Lipocalin 2 Participates in the Epidermal Differentiation and Inflammatory Processes of Psoriasis.

As a multifunctional cytokine, lipocalin 2 is weakly expressed in skin and serum under normal conditions. However, it is over-expressed by neutrophils and keratinocytes in the skin lesions and sera in several skin diseases. Recent studies demonstrated that lipocalin 2 participates in the pathogenesis of psoriasis by exerting versatile effects on skin resident cells and infiltrating immune cells. Lipocalin 2 inhibits the synthesis of keratin, involucrin, and loricrin in keratinocytes, leading to epidermal parakeratosis via the Tcf7l1-lipocalin 2 signaling axis. It also recruits inflammatory cells such as T cells and neutrophils into skin lesions via the IL-23/IL17, p38-MAPK, and ERK-1/2 signaling pathways. Additionally, lipocalin 2 and other cytokines such as IL-17 have the synergetic effects on skin cells. The neutralization of lipocalin 2 or relevant cytokines can alleviate psoriasis, verifying that lipocalin 2 is an effective interfering target for psoriasis. In this review, we summarize the roles of lipocalin 2 in the processes of psoriatic inflammation and the promising therapeutic strategies based on lipocalin 2-related molecules.

Light-Triggered Unique Shape Transformation of Giant Polymersomes with Tubular Protrusions.

Light-triggered unique shape transformation of calcein-loaded giant polymersomes with tubular protrusions, which serve as a reservoir membrane area during the shape transformation, is reported here. Under irradiation at the excitation wavelength of calcein, the tubular protrusions form strings of budded vesicles and then reintegrate into the mother vesicle. The initial giant polymersomes transform to two connected spherical vesicles via two pathways to alleviate the osmotic pressure imbalance across the vesicle membrane. The two connected spherical vesicles further transform to a mother vesicle with an inner daughter vesicle after switching off the light to relieve the bending energy. The finding provides a promising platform to mimic cell morphology changes.

The prognosis prediction significance of Hounsfield unit value for stroke patients treated by intravenous thrombolysis.

BACKGROUND: Intravenous thrombolysis (IVT) is a rapid and effective treatment in the early stage of ischemic stroke patients and the purpose of this work is to explore the significance of Hounsfield unit (HU) value in Alberta Stroke Program Early CT Score (ASPECTS) for predicting the clinical prognosis of stroke patients with middle cerebral artery occlusion (MCAO) treated by IVT. METHODS: The 84 stroke patients with MCAO treated by IVT were divided into good prognosis group (48 cases) and poor prognosis group (36 cases). HU ratio and HU difference calculated from non-contrast computed tomography between groups were analyzed. RESULTS: The HU ratio of good prognosis group was higher than that in poor prognosis group and the HU difference of good prognosis group was lower than that in poor prognosis group (P < 0.05). The HU ratio and ASPECTS were negatively correlated with the infarct volume, and the HU difference was positively correlated with the infarct volume (P < 0.05). HU difference was an independent risk factor for prognosis of patients with MCAO treated by IVT. The area under the receiver operating characteristic curve of HU ratio and HU difference for prognosis was 0.743 and 0.833 respectively. CONCLUSION: The HU value changes are related to the clinical prognosis of stroke patients with MCAO treated by IVT, HU value may be a prognostic indicator for stroke patients with MCAO treated by IVT.

Fibroblast growth factor inducible 14 signaling facilitates anti-dsDNA IgG penetration into mesangial cells.

Anti-double-stranded DNA (dsDNA) antibodies induce renal damage in patients with systemic lupus erythematosus by triggering fibrotic processes in kidney cells. However, the precise mechanism underlying penetration of anti-dsDNA immunoglubolin G (IgG) into cells remains unclear. This study was designed to investigate the effect of tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor inducible 14 (Fn14) signaling on anti-dsDNA IgG penetration into cells. Mesangial cells were cultured in vitro, and stimulated with TWEAK and anti-dsDNA IgG. The results revealed that TWEAK dose-dependently enhanced cellular internalization of anti-dsDNA IgG and the expression of high-mobility group box 1 (HMGB1). In addition, TWEAK and anti-dsDNA IgG synthetically downregulate suppressor of cytokine signaling 1, and induce the expression of various fibrotic factors. Furthermore, inhibition of HMGB1 attenuates the enhancement effect of TWEAK on anti-dsDNA IgG internalization. The TWEAK upregulation of HMGB1 involves the nuclear factor-κB and phosphatidylinositide 3-kinase/protein kinase B pathways. Therefore, TWEAK/Fn14 signaling contributes to the penetration of anti-dsDNA IgG and relevant fibrotic processes in mesangial cells.

FLAIR vascular hyperintensity: an unfavorable marker of early neurological deterioration and short-term prognosis in acute ischemic stroke patients.

BACKGROUND: To investigate the value of fluid-attenuated inversion recovery (FLAIR) Vascular Hyperintensity (FVH) in predicting early neurological deterioration (END) and short-term prognosis in acute ischemic stroke (AIS) patients who beyond the time window for recanalization therapy. METHODS: We retrospectively analyzed the AIS patients from 24 to 72 hours after symptom onset, who received dual antiplatelet therapy (DAPT). The patients were divided into the END and no early neurological deterioration (NEND) group according to the change of the National Institutes of Health Stroke Scale (NIHSS) score. The patients were also divided into the favorable and unfavorable prognosis group according to the 90 day modified Rankin Scale (mRS). The Alberta Stroke Program Early CT Score (ASPECTS) was used to assess the scope of infarction on DWI; the modified ASPECTS was used to assess the presence of FVH on FLAIR and multiple hypointense vessels (MHV) on SWI. We performed binary stepwise regression analysis with END and short-term prognosis as dependent variables to evaluate the odds ratio (OR) and its 95% confidence interval (CI) of primary outcomes. Next, we sequentially excluded nonsignificant variables from the last model to determine the risk factors of END. RESULTS: Two-hundred sixty-seven patients were included in this study. The median NIHSS score at admission was 6 [interquartile range (IQR) 5, 9], the median DWI-ASPECTS at admission was 8 (IQR 6, 9), the median FVH score was 7 (IQR 3, 7), and the median MHV-ASPECTS was 8 (IQR 6, 8). The NIHSS score at admission was higher in the END group. The MHV-ASPECTS, DWI-ASPECTS, and FVH-ASPECTS were lower in the END group. Binary stepwise regression analysis showed that the FVHASPECTS (OR =0.39, 95% CI: 0.174-0.872) and vascular stenosis/occlusion (OR =0.015, 95% CI: 0.000- 0.943) were independent risk factors of END. CONCLUSIONS: For AIS patients beyond the time window for recanalization therapy who are receiving DAPT, a low FVH-ASPECTS is associated with a higher risk of END. In patients with vascular occlusion/ stenosis, FVH may be used as a predictor of END and an unfavorable 90-day prognosis in patients beyond the time window for recanalization therapy who are receiving DAPT.

Inhibition of suppressor of cytokine signaling 1 mediates the profibrotic effect of TWEAK/Fn14 signaling on kidney cells.

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) engagement with the receptor Fn14 contributes to the fibrotic process of kidney cells in systemic lupus erythematosus. Downregulation of the protein suppressor of cytokine signaling 1 (SOCS1) correlates with amplified production of proinflammatory factors and cell apoptosis, which participate in the pathogenesis of lupus nephritis. To elucidate the potential role of SOCS1 in TWEAK/Fn14 signaling, we determined the SOCS1 levels in primary kidney cells from MRL/MpJ (control strain) or MRL/lpr (lupus-prone) mice. These cells (mesangial cells, glomerular endothelial cells, and tubular epithelial cells) were also evaluated after stimulation with TWEAK (0 to 250 ng/mL). The results showed that the lupus-prone cells exhibited reduced SOCS1 expression. TWEAK induced the production of profibrotic factors (laminin, fibronectin, (CC motif) ligand 20, etc.) in kidney cells from both mouse strains. TWEAK stimulation also decreased both the mRNA and protein levels of SOCS1 in all cells. Moreover, the effect of TWEAK on mesangial cells was amplified by pre-transfection of SOCS1 siRNA but was partly reduced with SOCS1 overexpression by adenoviral delivery. Therefore, TWEAK/Fn14 activation contributes to renal fibrosis in lupus nephritis involving the depression of SOCS1 function.

Thermosensitive Hydrogels as Scaffolds for Cartilage Tissue Engineering.

Articular cartilage defects, caused by trauma, osteoarthritis, or other diseases, always lead to severe joint pain and joint dysfunction. Without access to progenitor cells and the supply of blood and nutrients, the impaired articular cartilage would be short of the capability to self-repair. Although the present clinical treatments, including autogenous and allograft osteochondral transplantation, microfracture technique, and so forth, have shown some efficacies, their drawbacks, such as donor insufficiency and poor-integration with adjacent tissue, limit the satisfactory repair of articular cartilage defects and cause unsatisfied prognosis. Cartilage tissue engineering, involving the combination of progenitor cells with scaffolds, which serve as artificial extracellular matrices (ECMs), provides a promising strategy for cartilage regeneration. Recently, thermosensitive hydrogels have attracted much attention as scaffolds for cartilage tissue engineering owing to their unique physical properties analogous to the native ECM. In this review, we summarize the fabrication, characterization of newly reported thermosensitive hydrogels as cartilage tissue engineering scaffolds. The potential challenges and future perspectives are proposed.

Injectable Enzymatically Cross-linked Hydrogels with Light-Controlled Degradation Profile.

An advanced hydrogel that features facile formation and injectability as well as light-controlled degradation profile is reported here. By modifying 4-arm poly(ethylene glycol) (4-arm PEG) with 2-nitrobenzyl (NB) and phenol, the 4-arm PEG precursor solutions could form enzymatically cross-linked hydrogels in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H2 O2 ). The gelation time, mechanical strength, and porous structure could be simply tuned by the concentration of HRP and H2 O2 . Moreover, the hydrogels underwent controlled degradation under UV light irradiation via photo-cleavage reaction of the NB ester bond. The hydrogels exhibited negligible cytotoxicity toward mouse fibroblast L929 cells in vitro and can be manipulated through injection in vivo.

Light Deprivation-Induced Inhibition of Chloroplast Biogenesis Does Not Arrest Embryo Morphogenesis But Strongly Reduces the Accumulation of Storage Reserves during Embryo Maturation in Arabidopsis.

The chloroplast is one of the most important organelles found exclusively in plant and algal cells. Previous reports indicated that the chloroplast is involved in plant embryogenesis, but the role of the organelle during embryo morphogenesis and maturation is still a controversial question demanding further research. In the present study, siliques of Arabidopsis at the early globular stage were enwrapped using tinfoil, and light deprivation-induced inhibition of the chloroplast biogenesis were validated by stereomicroscope, laser scanning confocal microscope and transmission electron microscope. Besides, the effects of inhibited chloroplast differentiation on embryogenesis, especially on the reserve deposition were analyzed using periodic acid-Schiff reaction, Nile red labeling, and Coomassie brilliant blue staining. Our results indicated that tinfoil enwrapping strongly inhibited the formation of chloroplasts, which did not arrest embryo morphogenesis, but markedly influenced embryo maturation, mainly through reducing the accumulation of storage reserves, especially starch grains and oil. Our data provide a new insight into the roles of the chloroplast during embryogenesis.

Protein-Cross-Linked Hydrogels with Tailored Swelling and Bioactivity Performance: A Comparative Study.

The design of protein-based hydrogels that include biological activity independent of structural functionality is desirable for many bioengineering applications. Here a general route for construction of protein-based hydrogel is proposed by pretreatment of protein with thiolation agent and succeeding conjugation with 4-arm PEG-acrylate via Michael addition reaction. Different swelling behaviors responding to temperature and ions are comparatively studied for hydrogel cross-linked with hemoglobin (multimeric protein), albumin (monomeric protein), and dithiothreitol (DTT, small molecule). Meanwhile, the microscopic structure change is studied to correlate with the macroscopic hydrogel swelling behavior. Results show that proteins, which function as multisite cross-linkers, affect the gel swelling behaviors, and the effect is more profound for multimeric proteins when exposed to stimulus for protein dissociation. Moreover, the catalytic activity derived from hemoglobin is also preserved in the hydrogel, as demonstrated by the successfully synthesis of the colored product. By taking advantage of each particular protein, a broad range of functional materials can be expected for potential biomedical applications, such as stimuli-responsive hydrogel and immobilized enzyme.

Injectable, Biomolecule-Responsive Polypeptide Hydrogels for Cell Encapsulation and Facile Cell Recovery through Triggered Degradation.

Injectable hydrogels have been widely investigated in biomedical applications, and increasing demand has been proposed to achieve dynamic regulation of physiological properties of hydrogels. Herein, a new type of injectable and biomolecule-responsive hydrogel based on poly(l-glutamic acid) (PLG) grafted with disulfide bond-modified phloretic acid (denoted as PLG-g-CPA) was developed. The hydrogels formed in situ via enzymatic cross-linking under physiological conditions in the presence of horseradish peroxidase and hydrogen peroxide. The physiochemical properties of the hydrogels, including gelation time and the rheological property, were measured. Particularly, the triggered degradation of the hydrogel in response to a reductive biomolecule, glutathione (GSH), was investigated in detail. The mechanical strength and inner porous structure of the hydrogel were influenced by the addition of GSH. The polypeptide hydrogel was used as a three-dimensional (3D) platform for cell encapsulation, which could release the cells through triggered disruption of the hydrogel in response to the addition of GSH. The cells released from the hydrogel were found to maintain high viability. Moreover, after subcutaneous injection into rats, the PLG-g-CPA hydrogels with disulfide-containing cross-links exhibited a markedly faster degradation behavior in vivo compared to that of the PLG hydrogels without disulfide cross-links, implying an interesting accelerated degradation process of the disulfide-containing polypeptide hydrogels in the physiological environment in vivo. Overall, the injectable and biomolecule-responsive polypeptide hydrogels may serve as a potential platform for 3D cell culture and easy cell collection.