Mechanically Robust Lubricating Hydrogels Beyond the Natural Cartilage as Compliant Artificial Joint Coating.

Natural cartilage exhibits superior lubricity as well as an ultra-long service lifetime, which is related to its surface hydration, load-bearing, and deformation recovery feature. Until now, it is of great challenge to develop reliable cartilage lubricating materials or coatings with persistent robustness. Inspired by the unique biochemical structure and mechanics of natural cartilage, the study reports a novel cartilage-hydrogel composed of top composite lubrication layer and bottom mechanical load-bearing layer, by covalently manufacturing thick polyelectrolyte brush phase through sub-surface of tough hydrogel matrix with multi-level crystallization phase. Due to multiple network dissipation mechanisms of matrix, this hydrogel can achieve a high compression modulus of 11.8 MPa, a reversible creep recovery (creep strain: ≈2%), along with excellent anti-swelling feature in physiological medium (v/v0 < 5%). Using low-viscosity PBS as lubricant, this hydrogel demonstrates persistent lubricity (average COF: ≈0.027) under a high contact pressure of 2.06 MPa with encountering 100k reciprocating sliding cycles, negligible wear and a deformation recovery of collapse pit in testing area. The extraordinary lubrication performance of this hydrogel is comparable to but beyond the natural animal cartilage, and can be used as compliant coating for implantable articular material of UHMWPE to present, offering more robust lubricity than current commercial system.

The role of the mitochondrial ribosomal protein family in detecting hepatocellular carcinoma and predicting prognosis, immune features, and drug sensitivity

Background Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors, with a slow onset, rapid progression, and frequent recurrence. Previous research has implicated mitochondrial ribosomal genes in the development, metastasis, and prognosis of various cancers. However, further research is necessary to establish a link between mitochondrial ribosomal protein (MRP) family expression and HCC diagnosis, prognosis, ferroptosis-related gene (FRG) expression, m6A modification-related gene expression, tumor immunity, and drug sensitivity. Methods Bioinformatics resources were used to analyze data from patients with HCC retrieved from the TCGA, ICGC, and GTEx databases (GEPIA, UALCAN, Xiantao tool, cBioPortal, STRING, Cytoscape, TISIDB, and GSCALite). Results Among the 82 MRP family members, 14 MRP genes (MRPS21, MRPS23, MRPL9, DAP3, MRPL13, MRPL17, MRPL24, MRPL55, MRPL16, MRPL14, MRPS17, MRPL47, MRPL21, and MRPL15) were significantly upregulated differentially expressed genes (DEGs) in HCC tumor samples in comparison to normal samples. Receiver-operating characteristic curve analysis indicated that all 14 DEGs show good diagnostic performance. Furthermore, TCGA analysis revealed that the mRNA expression of 39 MRPs was associated with overall survival (OS) in HCC. HCC was divided into two molecular subtypes (C1 and C2) with distinct prognoses using clustering analysis. The clusters showed different FRG expression and m6A methylation profiles and immune features, and prognostic models showed that the model integrating 5 MRP genes (MRPS15, MRPL3, MRPL9, MRPL36, and MRPL37) and 2 FRGs (SLC1A5 and SLC5A11) attained a greater clinical net benefit than three other prognostic models. Finally, analysis of the CTRP and GDSC databases revealed several potential drugs that could target prognostic MRP genes (AU)

The role of the mitochondrial ribosomal protein family in detecting hepatocellular carcinoma and predicting prognosis, immune features, and drug sensitivity.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors, with a slow onset, rapid progression, and frequent recurrence. Previous research has implicated mitochondrial ribosomal genes in the development, metastasis, and prognosis of various cancers. However, further research is necessary to establish a link between mitochondrial ribosomal protein (MRP) family expression and HCC diagnosis, prognosis, ferroptosis-related gene (FRG) expression, m6A modification-related gene expression, tumor immunity, and drug sensitivity. METHODS: Bioinformatics resources were used to analyze data from patients with HCC retrieved from the TCGA, ICGC, and GTEx databases (GEPIA, UALCAN, Xiantao tool, cBioPortal, STRING, Cytoscape, TISIDB, and GSCALite). RESULTS: Among the 82 MRP family members, 14 MRP genes (MRPS21, MRPS23, MRPL9, DAP3, MRPL13, MRPL17, MRPL24, MRPL55, MRPL16, MRPL14, MRPS17, MRPL47, MRPL21, and MRPL15) were significantly upregulated differentially expressed genes (DEGs) in HCC tumor samples in comparison to normal samples. Receiver-operating characteristic curve analysis indicated that all 14 DEGs show good diagnostic performance. Furthermore, TCGA analysis revealed that the mRNA expression of 39 MRPs was associated with overall survival (OS) in HCC. HCC was divided into two molecular subtypes (C1 and C2) with distinct prognoses using clustering analysis. The clusters showed different FRG expression and m6A methylation profiles and immune features, and prognostic models showed that the model integrating 5 MRP genes (MRPS15, MRPL3, MRPL9, MRPL36, and MRPL37) and 2 FRGs (SLC1A5 and SLC5A11) attained a greater clinical net benefit than three other prognostic models. Finally, analysis of the CTRP and GDSC databases revealed several potential drugs that could target prognostic MRP genes. CONCLUSION: We identified 14 MRP genes as HCC diagnostic markers. We investigated FRG and m6A modification-related gene expression profiles and immune features in patients with HCC, and developed and validated a model incorporating MRP and FRG expression that accurately and reliably predicts HCC prognosis and may predict disease progression and treatment response.

Lipocalin-2 Deficiency Diminishes Canonical NLRP3 Inflammasome Formation and IL-1ß Production in the Subacute Phase of Spinal Cord Injury.

Spinal cord injury (SCI) results in the production of proinflammatory cytokines due to inflammasome activation. Lipocalin 2 (LCN2) is a small secretory glycoprotein upregulated by toll-like receptor (TLR) signaling in various cells and tissues. LCN2 secretion is induced by infection, injury, and metabolic disorders. In contrast, LCN2 has been implicated as an anti-inflammatory regulator. However, the role of LCN2 in inflammasome activation during SCI remains unknown. This study examined the role of Lcn2 deficiency in the NLRP3 inflammasome-dependent neuroinflammation in SCI. Lcn2-/- and wild-type (WT) mice were subjected to SCI, and locomotor function, formation of the inflammasome complex, and neuroinflammation were assessed. Our findings demonstrated that significant activation of the HMGB1/PYCARD/caspase-1 inflammatory axis was accompanied by the overexpression of LCN2 7 days after SCI in WT mice. This signal transduction results in the cleaving of the pyroptosis-inducing protein gasdermin D (GSDMD) and the maturation of the proinflammatory cytokine IL-1ß. Furthermore, Lcn2-/- mice showed considerable downregulation in the HMGB1/NLRP3/PYCARD/caspase-1 axis, IL-1ß production, pore formation, and improved locomotor function compared with WT. Our data suggest that LCN2 may play a role as a putative molecule for the induction of inflammasome-related neuroinflammation in SCI.

Acute mesenteric ischemia secondary to oral contraceptive-induced portomesenteric and splenic vein thrombosis: A case report.

BACKGROUND: Mesenteric ischemia represents an uncommon complication of splanchnic vein thrombosis, and it is less infrequently seen in young women using oral contraceptives. Diagnosis is often delayed in the emergency room; thus, surgical intervention may be inevitable and the absence of thrombus regression or collateral circulation may lead to further postoperative ischemia and a fatal outcome. CASE SUMMARY: We report a 28-year-old female patient on oral contraceptives who presented with acute abdominal pain. Her physical examination findings were not consistent with her symptoms of severe pain and abdominal distention. These findings and her abnormal blood tests raised suspicion of acute mesenteric ischemia (AMI) induced by splanchnic vein thrombosis. Contrast-enhanced abdominal computed tomography revealed ischemia of the small intestine with portomesenteric and splenic vein thrombosis (PMSVT). We treated the case promptly by anticoagulation after diagnosis. We then performed delayed segmental bowel resection after thrombus regression and established collateral circulation guided by collaboration with a multidisciplinary team. The patient had an uneventful postoperative course and was discharged 14 d after surgery and took rivaroxaban orally for 6 mo. In subsequent follow-up to date, the patient has not complained of any other discomfort. CONCLUSION: AMI induced by PMSVT should be considered in young women who are taking oral contraceptives and have acute abdominal pain. Prompt anticoagulation followed by surgery is an effective treatment strategy.

Successive Redox-Reaction-Triggered Interface Radical Polymerization for Growing Hydrogel Coatings on Diverse Substrates.

Growing lubricating hydrogel coatings in controllable manners on diverse material surfaces demonstrates promising applications. Here, a surface modification method is reported for in situ growing hydrogel coatings onto surfaces of diverse substrates in the absence of UV assistance. It is performed by decorating substrates with a universal mussel-inspired synthetic adhesive with catechol groups. Upon being immersed in reaction solution, these groups can assist substrate bonding and in situ capture and reduce Fe3+ into Fe2+ for decomposing S2 O8 2- into SO4 - ⋅ catalytically at the interface to initiate interface polymerization of monomers. As a result, hydrogel coatings with controllable thickness could be grown on surfaces of arbitrary substrates to change their surface characteristics regardless of materials size, category, geometry and transparency, implying considerable potential in surface engineering.

Substrates, Plants, and Their Combinations for Water Purification of Urban Household Aquaponics Systems.

To make full use of urban household balcony space, an urban aquaponics system for balconies was constructed to investigate the purification effects of four different substrates (volcanic stone, ceramic pellets, ceramic rings, and nanorods) and six plants (mung bean sprouts, hollow cabbage, water celery, lettuce, leek, and water chestnut) on fish culture wastewater. Through the determination of contaminants such as nitrogen and phosphorus and through the use of 16SrDNA sequencing technology, the substrate material and plant combinations with the best purification effects were screened. The results show that volcanic stone and nanorods have strong purification capacities. Compared to the other substrate types, there were more unique bacterial species on the surface of volcanic stone, among which amoeba species were the most dominant (92.42%). Among the six tested plant species, mung bean sprouts had the highest contribution to nitrogen uptake (94.96%), and water chestnut had the highest contribution to phosphorus uptake at 12.07%. Finally, the combination of nanorods and water celery was the best at purifying the wastewater. This study provides a theoretical basis and new ideas for the construction of urban aquaponics systems on balconies, which will help to achieve green farming and the efficient utilization of water resources.

CRIP1 suppresses BBOX1-mediated carnitine metabolism to promote stemness in hepatocellular carcinoma.

Carnitine metabolism is thought to be negatively correlated with the progression of hepatocellular carcinoma (HCC) and the specific molecular mechanism is yet to be fully elucidated. Here, we report that little characterized cysteine-rich protein 1 (CRIP1) is upregulated in HCC and associated with poor prognosis. Moreover, CRIP1 promoted HCC cancer stem-like properties by downregulating carnitine energy metabolism. Mechanistically, CRIP1 interacted with BBOX1 and the E3 ligase STUB1, promoting BBOX1 ubiquitination and proteasomal degradation, and leading to the downregulation of carnitine. BBOX1 ubiquitination at lysine 240 is required for CRIP1-mediated control of carnitine metabolism and cancer stem-like properties. Further, our data showed that acetylcarnitine downregulation in CRIP1-overexpressing cells decreased beta-catenin acetylation and promoted nuclear accumulation of beta-catenin, thus facilitating cancer stem-like properties. Clinically, patients with higher CRIP1 protein levels had lower BBOX1 levels but higher nuclear beta-catenin levels in HCC tissues. Together, our findings identify CRIP1 as novel upstream control factor for carnitine metabolism and cancer stem-like properties, suggesting targeting of the CRIP1/BBOX1/ß-catenin axis as a promising strategy for HCC treatment.

Astrocytic Nrf2 expression protects spinal cord from oxidative stress following spinal cord injury in a male mouse model.

BACKGROUND: Spinal cord injury (SCI) induces a multitude of deleterious processes, including neuroinflammation and oxidative stress (OS) which contributed to neuronal damage and demyelination. Recent studies have suggested that increased formation of reactive oxygen species (ROS) and the consequent OS are critical events associated with SCI. However, there is still little information regarding the impact of these events on SCI. Astrocytes are key regulators of oxidative homeostasis in the CNS and astrocytic antioxidant responses promote the clearance of oxidants produced by neurons. Therefore, dysregulation of astrocyte physiology might largely contribute to oxidative damage. Nuclear factor erythroid 2-related factor 2 (Nrf2) is the main transcriptional regulator of cellular anti-oxidative stress responses. METHODS: In the current study, we hypothesized that astrocytic activation of Nrf2 protects the spinal cord post injury via suppression of neuroinflammation. Thus, using mice line with a GFAP-specific kelch-like ECH-associated protein 1 (Keap1)-deletion, we induced a hyperactivation of Nrf2 in astrocytes and further its effects on SCI outcomes. SCI-induction was performed in mice using the Infinite Horizon Spinal Cord Impactor with a force of 60 kdyn. To assess the quantitative pattern of Nrf2/ARE-activation, we included transgenic ARE-Luc mice. Data were analyzed with GraphPad Prism 8 (GraphPad Software Inc., San Diego, CA, USA). Brown-Forsythe test was performed to test for equal variances and normal distribution was tested with Shapiro-Wilk. RESULTS: In ARE-Luc mice, a significant induction of luciferase-activity was observed as early as 1 day post-injury, indicating a functional role of Nrf2-activity at the epicenter of SCI. Furthermore, SCI induced loss of neurons and oligodendrocytes, demyelination and inflammation in wild type mice. The loss of myelin and oligodendrocytes was clearly reduced in Keap1 KO mice. In addition, Keap-1 KO mice showed a significantly better locomotor function and lower neuroinflammation responses compared to wild type mice. CONCLUSIONS: In summary, our in vivo bioluminescence data showed Nrf2-ARE activation during primary phase of SCI. Furthermore, we found that cell specific hyperactivation of Nrf2 was sufficient to protect the spinal cord against injury which indicate a promising therapeutic approach for SCI-treatment.

BODIPY-conjugated bis-terpyridine Ru(II) complexes showing ultra-long luminescence lifetimes and applications to triplet-triplet annihilation upconversion.

The poor excited-state properties of bis-terpyridine Ru(II) complexes have significantly limited the applications of these complexes as sensitizers in photocatalysis and triplet-triplet annihilation upconversion. In the present work, two novel ruthenium bis-terpyridine complexes (Ru-1 and Ru-2) conjugated with visible-light-harvesting bodipy chromophores were synthesized. These complexes showed strong absorption of visible light, the bodipy-localized intraligand triplet state (3IL) was efficiently populated, and the phosphorescence of bodipy at room temperature in both complexes was observed. The luminescence lifetimes of these complexes were significantly prolonged, with that of the heteroleptic complex Ru-2 prolonged to 37.9 µs and that of the homoleptic bis-terpyridine complex Ru-1 unprecedentedly prolonged to 356 µs, which was hundreds of times longer than the current longest emissive state achieved in ruthenium terpyridine complexes. The ultra-long triplet lifetimes and strong visible-light absorbing ability made them new candidates of triplet sensitizers, and were first applied to TTA-UC for terpyridine Ru(II) complexes with a Ru-1/Py system showing a ΦUC of 2.93% in dilute solutions at concentrations as low as 1.0 µM.

Neuroprotective effect of the Nrf2/ARE/miRNA145-5p signaling pathway in the early phase of spinal cord injury.

AIMS: Spinal cord injury (SCI) is a debilitating neurological condition often associated with chronic neuroinflammation and redox imbalance. Oxidative stress is one of the main hallmark of secondary injury of SCI which is tightly regulated by nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling. In this study, we aimed at investigating the interplay between inflammation-related miRNAs and the Nrf2 pathway in animal model of SCI. MATERIALS AND METHODS: The expression of selected four validated miRNA-target pairs (miRNA223-3p, miRNA155-5p, miRNA145-5p, and miRNA124-3p) was examined at different time points (6 h, 12 h, 1 day, 3 day and 7 day) after SCI. Further, using GFAP-specific kelch-like ECH-associated protein 1 deletion (Keap1-/-) and whole-body Nrf2-/- knockout mice, we investigated the potential interplay between each miRNA and the Keap1/Nrf2 signaling system. KEY FINDINGS: The expression of all miRNAs except miRNA155-5p significantly increased 24 h after SCI and decreased after 7 days. Interestingly, Keap1-/- mice only showed significant increase in the miRNA145-5p after 24 h SCI compared to the WT group. In addition, Keap1-/- mice showed significant decrease in CXCL10/12 (CXCL12 increased in Nrf2-/- mice), and TNF-α, and an increase in Mn-SOD and NQO-1 (Mn-SOD and NQO-1 decreased in Nrf2-/- mice) compared to WT mice. SIGNIFICANCE: Our results suggest that astrocytic hyperactivation of Nrf2 exert neuroprotective effects at least in part through the upregulation of miRNA145-5p, a negative regulator of astrocyte proliferation, and induction of ARE in early phase of SCI. Further studies are needed to investigate the potential interplay between Nrf2 and miRNA145-5p in neuroinflammatory condition.

N-acetylneuraminic acid and chondroitin sulfate modified nanomicelles with ROS-sensitive H2S donor via targeting E-selectin receptor and CD44 receptor for the efficient therapy of atherosclerosis.

Currently, very limited therapeutic approaches are available for the drug treatment of atherosclerosis(AS). H2S-donor is becoming a common trend in much life-threatening research. Several studies have documented that H2S-lyase is predominantly present in endothelial cells. N-Acetylneuraminic acid (SA), natural carbohydrate, binds specifically to the E-selectin receptor of endothelial cells. Meanwhile, recent studies related to Chondroitin sulfate have excellent target binding ability with CD44 receptor. We conjecture that the N-Acetylneuraminic acid and Chondroitin sulfate modified nanomicelles not only enhances the accumulation of the drug but also cleaves the H2S donor in the lesion, thus one stone two birds. Given these findings, we synthesized two kinds of nanoparticles, Carrier I (SCCF) and Carrier II (SCTM), for atherosclerosis to validate our guesses. Initially, S-allyl-L-cysteine and 4-methoxyphenylthiourea were used as H2S donors for SCCF and SCTM, respectively. After the introduction of ROS-sensitive groups. Then, micelles with N-Acetylneuraminic acid and Chondroitin sulfate were prepared to load rapamycin(RAP). Further, in atherosclerosis Oil Red O staining (ORO) results confirmed remarkable treatment effect with SCCF@RAP and SCTM@RAP. Thus, we conclude that the effect of dual-targeting nanomicelles with ROS-sensitive H2S donor based on N-Acetylneuraminic acid and Chondroitin sulfate will have a better role in atherosclerosis.

Corosolic acid inhibits tumour growth without compromising associating liver partition and portal vein ligation-induced liver regeneration in rats.

BACKGROUND: Associating liver partition and portal vein ligation (ALPPS) technique is a promising strategy for unresectable primary liver tumours without sufficient future liver remnants (FLRs). OBJECTIVE: Our study explored the effect of corosolic acid (CA) on inhibiting tumour growth without compromising ALPPS-induced liver regeneration. METHODS: The ALPPS procedure was performed in Sprague-Dawley rats with orthotopic liver cancer. Blood, tumour, and FLR samples were collected, and the effect of CA on the inhibition of tumour progression and ALPPS-induced liver regeneration, and its possible mechanism, were investigated. RESULTS: The tumour weight in the implantation/ALPPS group was higher than in the implantation without ALPPS group (p < .05), and the tumour weight in the implantation/ALPPS/CA group was lower than in the implantation/ALPPS group (p < .05). On postoperative day 15, the hepatic regeneration rate, and the expression of Ki67+ hepatocytes in the FLRs had increased significantly in the group that underwent ALPPS. The number of cluster of differentiation (CD) 86+ macrophages markedly increased in the FLRs and in the tumours of groups that underwent the ALPPS procedure. Additionally, the number of CD206+ macrophages was higher than the number of CD86+ macrophages in the tumours of the implantation and the implantation/ALPPS groups (p < .01, respectively); however, the opposite results were observed in the CA groups. The administration of CA downregulated the expression of transforming growth factor-beta (TGF-ß), CD31, and programmed cell death protein 1 (PD-1) but increased the number of CD8+ lymphocytes in tumours. CONCLUSION: Corosolic acid inhibits tumour growth without compromising ALPPS-induced liver regeneration. This result may be attributed to the CA-induced downregulation of PD-1 and TGF-ß expression and the increased CD8+ lymphocyte infiltration in tumour tissue associated with the suppression of M2 macrophage polarisation. Key MessagesThis study aimed to investigate the effect of CA on ALPPS-induced liver regeneration and hepatic tumour progression after ALPPS-induced liver regeneration.Corosolic acid inhibits tumour growth without compromising ALPPS-induced liver regeneration. This result may be attributed to the CA-induced downregulation of PD-1 and TGF-ß expression and the increased CD8+ lymphocyte infiltration in tumour tissue associated with the suppression of M2 macrophage polarisation.

Bioinspired Design of a Cartilage-like Lubricated Composite with Mechanical Robustness.

Natural articular cartilages show extraordinary tribological performance based on their penetrated surface lubricated biomacromolecules and good mechanical tolerance. Hydrogels are considered to be potential alternatives to cartilages due to their low surface friction and good biocompatibility, although the poor mechanical properties limited their applications. Inspired by the excellent mechanical properties and the remarkable surface lubrication mechanism of natural articular cartilages, one kind of cartilage-like composite material with a lubrication phase (Composite-LP) was developed by chemically grafting a thick hydrophilic polyelectrolyte brush layer onto the subsurface of a three-dimensional manufactured elastomer scaffold-hydrogel composite architecture. The Composite-LP exhibited good load-bearing capacities because of the nondissipation strategy and the stress dispersion mechanism resulting from the elastomer scaffold enhancement. In the presence of the top lubrication layer, the Composite-LP showed superior friction reduction functionality and wear resistance under a dynamic shearing process. This design concept of coupling the non-dissipative mechanism and interface lubrication provides a new avenue for developing cartilage-like hydrogels and soft robots.

Modulus adaptive lubricating prototype inspired by instant muscle hardening mechanism of catfish skin.

In nature, living organisms evolve unique functional components with mechanically adaptive compatibility to cater dynamic change of interface friction/lubrication. This mechanism can be used for developing intelligent artificial lubrication-regulation systems. Inspired by the muscle hardening-triggered lubrication of longsnout catfish, here we report a modulus adaptive lubricating hydrogel prototype consisting of top mucus-like hydrophilic lubricating layer and muscle-like bottom hydrogel that can stiffen via thermal-triggered phase separation. It exhibits instant switch from soft/high frictional state (~0.3 MPa, µ~0.37) to stiff/lubricating state (~120 MPa, µ~0.027) in water upon heating up. Such switchable lubrication is effective for wide range of normal loads and attributed to the modulus-dominated adaptive contact mechanism. As a proof-of-concept, switchable lubricating hydrogel bullets and patches are engineered for realizing controllable interface movements. These important results demonstrate potential applications in the fields of intelligent motion devices and soft robots.

Lipocalin 2 as a Putative Modulator of Local Inflammatory Processes in the Spinal Cord and Component of Organ Cross talk After Spinal Cord Injury.

Lipocalin 2 (LCN2), an immunomodulator, regulates various cellular processes such as iron transport and defense against bacterial infection. Under pathological conditions, LCN2 promotes neuroinflammation via the recruitment and activation of immune cells and glia, particularly microglia and astrocytes. Although it seems to have a negative influence on the functional outcome in spinal cord injury (SCI), the extent of its involvement in SCI and the underlying mechanisms are not yet fully known. In this study, using a SCI contusion mouse model, we first investigated the expression pattern of Lcn2 in different parts of the CNS (spinal cord and brain) and in the liver and its concentration in blood serum. Interestingly, we could note a significant increase in LCN2 throughout the whole spinal cord, in the brain, liver, and blood serum. This demonstrates the diversity of its possible sites of action in SCI. Furthermore, genetic deficiency of Lcn2 (Lcn2-/-) significantly reduced certain aspects of gliosis in the SCI-mice. Taken together, our studies provide first valuable hints, suggesting that LCN2 is involved in the local and systemic effects post SCI, and might modulate the impairment of different peripheral organs after injury.

Transient Focal Cerebral Ischemia Leads to miRNA Alterations in Different Brain Regions, Blood Serum, Liver, and Spleen.

Ischemic stroke is characterized by an occlusion of a cerebral blood vessel resulting in neuronal cell death due to nutritional and oxygen deficiency. Additionally, post-ischemic cell death is augmented after reperfusion. These events are paralleled by dysregulated miRNA expression profiles in the peri-infarct area. Understanding the underlying molecular mechanism in the peri-infarct region is crucial for developing promising therapeutics. Utilizing a tMCAo (transient Middle Cerebral Artery occlusion) model in rats, we studied the expression levels of the miRNAs (miR) 223-3p, 155-5p, 3473, and 448-5p in the cortex, amygdala, thalamus, and hippocampus of both the ipsi- and contralateral hemispheres. Additionally, the levels in the blood serum, spleen, and liver and the expression of their target genes, namely, Nlrp3, Socs1, Socs3, and Vegfa, were assessed. We observed an increase in all miRNAs on the ipsilateral side of the cerebral cortex in a time-dependent manner and increased miRNAs levels (miR-223-3p, miR-3473, and miR-448-5p) in the contralateral hemisphere after 72 h. Besides the cerebral cortex, the amygdala presented increased expression levels, whereas the thalamus and hippocampus showed no alterations. Different levels of the investigated miRNAs were detected in blood serum, liver, and spleen. The gene targets were altered not only in the peri-infarct area of the cortex but selectively increased in the investigated non-affected brain regions along with the spleen and liver during the reperfusion time up to 72 h. Our results suggest a supra-regional influence of miRNAs following ischemic stroke, which should be studied to further identify whether miRNAs are transported or locally upregulated.

Self-Assembled Herbal Medicine Encapsulated by an Oxidation-Sensitive Supramolecular Hydrogel for Chronic Wound Treatment.

Inflammation has been assumed to affect the pathology of wound healing and is associated with many nonhealing chronic wounds. Naturally derived herbal medicines with anti-inflammatory properties are of interest because of their effectiveness and affordability in clinical treatment. Herein, we report a supramolecular hydrogel comprising self-assembled natural herb rhein and an oxidative responsive cross-linked network based on ferrocene and ß-cyclodextrin host-guest recognitions. Rhein can directly self-assemble into fibrils, exerting better anti-inflammation efficiency than its free drug form. The adaption of the supramolecular network can greatly improve the stability and retain the structural integrity of encapsulated self-assembled rhein. In addition, host-guest recognition confers dissolution of the hydrogel under oxidative stress, thereby delivering self-assembled rhein to the wound site and exerting better therapeutic efficiency. Evaluations in diabetic mice indicate that the resultant hydrogel promoted chronic wound healing by suppressing excess reactive oxygen species, facilitating the transition of the wound healing process, and restoring the normal wound-repair process. Therefore, the proposed hydrogel has a potential value as an herbal-based dressing for future clinical chronic wound management.