Threshold of hyperglycaemia associated with mortality in critically ill patients: a multicentre, prospective, observational study using continuous glucose monitoring.

AIMS/HYPOTHESIS: Continuous glucose monitoring (CGM) provides comprehensive information on the exposure to dysglycaemia. This study aimed to investigate the threshold of hyperglycaemia related to mortality risk in critically ill patients using CGM technology. METHODS: A total of 293 adult critically ill patients admitted to intensive care units of five medical centres were prospectively included between May 2020 and November 2021. Participants wore intermittently scanned CGM for a median of 12.0 days. The relationships between different predefined time above ranges (TARs), with the thresholds of hyperglycaemia ranging from 7.8 to 13.9 mmol/l (140-250 mg/dl), and in-hospital mortality risk were assessed by multivariate Cox proportional regression analysis. Time in ranges (TIRs) of 3.9 mmol/l (70 mg/dl) to the predefined hyperglycaemic thresholds were also assessed. RESULTS: Overall, 66 (22.5%) in-hospital deaths were identified. Only TARs with a threshold of 10.5 mmol/l (190 mg/dl) or above were significantly associated with the risk of in-hospital mortality, after adjustment for covariates. Furthermore, as the thresholds for TAR increased from 10.5 mmol/l to 13.9 mmol/l (190 mg/dl to 250 mg/dl), the hazards of in-hospital mortality increased incrementally with every 10% increase in TARs. Similar results were observed concerning the associations between TIRs with various upper thresholds and in-hospital mortality risk. For per absolute 10% decrease in TIR 3.9-10.5 mmol/l (70-190 mg/dl), the risk of in-hospital mortality was increased by 12.1% (HR 1.121 [95% CI 1.003, 1.253]). CONCLUSIONS/INTERPRETATION: A glucose level exceeding 10.5 mmol/l (190 mg/dl) was significantly associated with higher risk of in-hospital mortality in critically ill patients.

Extracellular vesicles and cancer stemness in hepatocellular carcinoma - is there a link?

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy, with high recurrence rates and notorious resistance to conventional chemotherapy. Cancer stemness refers to the stem-cell-like phenotype of cancer cells and has been recognized to play important roles in different aspects of hepatocarcinogenesis. Small extracellular vesicles (sEVs) are small membranous particles secreted by cells that can transfer bioactive molecules, such as nucleic acids, proteins, lipids, and metabolites, to neighboring or distant cells. Recent studies have highlighted the role of sEVs in modulating different aspects of the cancer stemness properties of HCC. Furthermore, sEVs derived from diverse cellular sources, such as cancer cells, stromal cells, and immune cells, contribute to the maintenance of the cancer stemness phenotype in HCC. Through cargo transfer, specific signaling pathways are activated within the recipient cells, thus promoting the stemness properties. Additionally, sEVs can govern the secretion of growth factors from non-cancer cells to further maintain their stemness features. Clinically, plasma sEVs may hold promise as potential biomarkers for HCC diagnosis and treatment prediction. Understanding the underlying mechanisms by which sEVs promote cancer stemness in HCC is crucial, as targeting sEV-mediated communication may offer novel strategies in treatment and improve patient outcome.

Sr2[B5O8(OH)]2 ⋠[B(OH)3] ⋠H2O: A Strontium Borate That Shows Deep-Ultraviolet-Transparent Nonlinear Optical Properties.

A new noncentrosymmetric strontium borate, P1-Sr2[B5O8(OH)]2 ⋅ [B(OH)3] ⋅ H2O (1), has been synthesized under the hydrothermal condition. The P1-Sr2[B5O8(OH)]2 ⋅ [B(OH)3] ⋅ H2O shows a layered B-O network with 9-ring windows in the ab plane. Sr2+ cations, H3BO3, and H2O molecules are located in the voids of layers and interlayers, respectively. The P1-Sr2[B5O8(OH)]2 ⋅ [B(OH)3] ⋅ H2O is the first synthetic phase of veatchite, while the other three polymorphs are found in different natural minerals. This strontium borate is a potential deep-ultraviolet-transparent nonlinear-optical (NLO) crystal whose second-harmonic-generation (SHG) intensity is 1.7 times that of KH2PO4 (KDP) and is phase-matchable. The short wavelength cutoff edge of compound 1 is below 190 nm. Density functional theory (DFT) calculations show that the B-O units are responsible for the nonlinear optical property.

An injectable thermosensitive hyaluronic acid/pluronic F-127 hydrogel for deep penetration and combination therapy of frozen shoulder.

Frozen shoulder (FS) is a common and progressive shoulder disorder that causes glenohumeral joint stiffness, characterized by inflammation and fibrosis. The treatment options are quite limited, and the therapeutic response is hindered by the fibrous membrane formed by excessive collagen and the rapid removal by synovial fluid. To address these challenges, we designed a hyaluronic acid/Pluronic F-127 (HP)-based injectable thermosensitive hydrogel as a drug carrier loaded with dexamethasone and collagenase (HPDC). We screened for an optimal HP hydrogel that can sustain drug release for approximately 10 days both in vitro and in vivo. In the meanwhile, we found that HP hydrogel could inhibit the proliferation and diminish the adhesion capacity of rat synovial cells induced by transforming growth factor-ß1. Furthermore, using an established immobilization rat model of FS, intra-articular injection of HPDC significantly improved joint range of motion compared to medication alone. Relying on sustained drug release, the accumulated collagen fibers were degraded by collagenase to promote the deep delivery of dexamethasone. These findings showed a positive combined treatment effect of HPDC, providing a novel idea for the comprehensive treatment of FS.

Clinically relevant stratification of patients with type 2 diabetes by using continuous glucose monitoring data.

AIM: The wealth of data generated by continuous glucose monitoring (CGM) provides new opportunities for revealing heterogeneities in patients with type 2 diabetes mellitus (T2DM). We aimed to develop a method using CGM data to discover T2DM subtypes and investigate their relationship with clinical phenotypes and microvascular complications. METHODS: The data from 3119 patients with T2DM who wore blinded CGM at an academic medical centre was collected, and a glucose symbolic pattern (GSP) metric was created that combined knowledge-based temporal abstraction with numerical vectorization. The k-means clustering was applied to GSP to obtain subgroups of patients with T2DM. Clinical characteristics and the presence of diabetic retinopathy and albuminuria were compared among the subgroups. The findings were validated in an independent population comprising 773 patients with T2DM. RESULTS: By using GSP, four subgroups were identified with distinct features in CGM profiles and parameters. Moreover, the clustered subgroups differed significantly in clinical phenotypes, including indices of pancreatic ß-cell function and insulin resistance (all p < .001). After adjusting for confounders, group C (the most insulin resistant) had a significantly higher risk of albuminuria (odds ratio = 1.24, 95% confidence interval: 1.03-1.39) relative to group D, which had the best glucose control. These findings were confirmed in the validation set. CONCLUSION: Subtyping patients with T2DM using CGM data may help identify high-risk patients for microvascular complications and provide insights into the underlying pathophysiology. This method may help refine clinically meaningful stratification of patients with T2DM and inform personalized diabetes care.

Libman-Sacks endocarditis in a child with systemic lupus erythematosus: a case report and literature review.

Libman-Sacks endocarditis (LSE) is a cardiac condition characterized by the growth of verrucous vegetation. Although relatively rare in children, LSE is nevertheless a known cardiac manifestation of autoimmune diseases, including systemic lupus erythematosus (SLE). The mitral valve is the most commonly affected region, followed by the aortic valve, while the tricuspid and pulmonary valves are rarely affected. The management of established Libman-Sacks vegetation poses significant challenges, often necessitating surgical interventions, although surgery is not the primary treatment modality. Herein, we present the case of a 14-year-old Chinese female patient whose initial lupus manifestation included LSE, among other symptoms and signs that provided insights into the final diagnosis of SLE. After early comprehensive pharmacological treatment, tricuspid regurgitation and vegetation disappeared within 28 days without necessitating cardiac surgery, indicating that the resolution of LSE vegetation in this patient was achieved through a combination of immunosuppressive and anticoagulant therapy. These findings suggest the potential of this treatment approach as a viable model for the management of LSE in young patients.

MicroRNA-146a-loaded magnesium silicate nanospheres promote bone regeneration in an inflammatory microenvironment.

Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge, as chronic local inflammation can largely impair bone healing. Here, we used magnesium silicate nanospheres (MSNs) to load microRNA-146a-5p (miR-146a) to fabricate a nanobiomaterial, MSN+miR-146a, which showed synergistic promoting effects on the osteogenic differentiation of human dental pulp stem cells (hDPSCs). In addition, miR-146a exhibited an anti-inflammatory effect on mouse bone marrow-derived macrophages (BMMs) under lipopolysaccharide (LPS) stimulation by inhibiting the NF-κB pathway via targeting tumor necrosis factor receptor-associated factor 6 (TRAF6), and MSNs could simultaneously promote M2 polarization of BMMs. MiR-146a was also found to inhibit osteoclast formation. Finally, the dual osteogenic-promoting and immunoregulatory effects of MSN+miR-146a were further validated in a stimulated infected mouse mandibular bone defect model via delivery by a photocuring hydrogel. Collectively, the MSN+miR-146a complex revealed good potential in treating inflammatory irregular oral-maxillofacial bone defects.

Association of sudomotor dysfunction with risk of diabetic retinopathy in patients with type 2 diabetes.

PURPOSE: Sudomotor dysfunction is considered as one of the earliest manifestations of diabetic peripheral neuropathy. We aimed to investigate the association between sudomotor dysfunction non-invasively detected by the SUDOSCAN device and diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: A total of 2010 patients admitted to a tertiary hospital located in Shanghai were included from March 2020 to September 2023. Sudomotor function was assessed by the SUDOSCAN device, and sudomotor dysfunction was defined as feet electrochemical skin conductance (FESC) <60 µs. Fundus radiography was used for DR assessment, which was graded according to the severity, specifically: (1) non-DR; (2) mild nonproliferative DR (NPDR); (3) moderate NPDR/vision-threatening DR (VTDR). RESULTS: Among the enrolled 2010 patients, 525 patients had sudomotor dysfunction; 648 were diagnosed with DR, which was equivalent to 32.2% of all patients. Patients with sudomotor dysfunction had a significantly higher prevalence of DR, compared to those with normal sudomotor function (40.8% vs. 29.2%, P < 0.05). After controlling for confounding factors including HbA1c, sudomotor dysfunction was significantly associated with any DR (odd ratio [OR] = 1.57, 95% CI 1.26-1.96). When FESC was considered as a continuous variable, the multivariable-adjusted OR of DR was 1.29 (95% CI 1.17-1.42) for per 1-SD decrease in FESC. Furthermore, multinomial logistic regression revealed significant associations between sudomotor dysfunction and all stages of DR (mild NPDR: OR = 1.40, 95% CI 1.11-1.78; moderate NPDR/VTDR: OR = 2.35, 95% CI 1.60-3.46). CONCLUSIONS: Sudomotor dysfunction was significantly associated with DR in patients with type 2 diabetes.

Glycemic variability: Measurement, target, impact on complications of diabetes and does it really matter?

Over the past two decades, there has been continuous advancement in the accuracy and complexity of continuous glucose monitoring devices. Continuous glucose monitoring provides valuable insights into blood glucose dynamics, and can record glucose fluctuations accurately and completely. Glycemic variability (GV) is a straightforward measure of the extent to which a patient's blood glucose levels fluctuate between high peaks and low nadirs. Many studies have investigated the relationship between GV and complications, primarily in the context of type 2 diabetes. Nevertheless, the exact contribution of GV to the development of diabetes complications remains unclear. In this literature review, we aimed to summarize the existing evidence regarding the measurement, target level, pathophysiological mechanisms relating GV and tissue damage, and population-based studies of GV and diabetes complications. Additionally, we introduce novel methods for measuring GV, and discuss several unresolved issues of GV. In the future, more longitudinal studies and trials are required to confirm the exact role of GV in the development of diabetes complications.

Dilemmas and support strategies in dementia care: Experiences of case managers in Taiwan.

Objective: This study aimed to examine the dilemmas encountered and the countermeasures adopted by case managers, who care for individuals with dementia. The study also aimed to identify the types of support and assistance case managers require.Methods: In this qualitative study, the researchers conducted semi-structured interviews with 10 case managers, six from integrated dementia care centers and four from community-based dementia care centers in Taiwan.Results: The results are as follows: (1) Case managers providing services for individuals with dementia primarily encountered two major dilemmas, including cognitive differences (such as a lack of understanding of dementia, differences in ideas about dementia care, and distrust of the professionalism of case managers) with family members and their own insufficient professional capabilities, which made it difficult to reach a consensus on caregiving with family members and address the diverse conditions of individuals with dementia. (2) In response to these dilemmas, case managers adopted various approaches to enhance families' understanding of dementia and facilitate reaching a consensus on care. They also improved their professional capabilities through team discussions and resource networking. (3) The support and assistance required by case managers are continuous learning, the enhancement of their professional competencies, organizational support, and workload management.Conclusion: The findings of this study contribute to an understanding of the dilemmas faced by case managers in Taiwan's centers for integrated dementia care and community-based dementia care centers during policies implementation, as well as the strategies they adopted and the assistance they required. These results can also offer recommendations for policies, professional training, dementia services, and resources to reduce the disparity between policy and practice.

Protein and peptide-based renal targeted drug delivery systems.

Renal diseases have become an increasingly concerned public health problem in the world. Kidney-targeted drug delivery has profound transformative potential on increasing renal efficacy and reducing extra-renal toxicity. Protein and peptide-based kidney targeted drug delivery systems have garnered more and more attention due to its controllable synthesis, high biocompatibility and low immunogenicity. At the same time, the targeting methods based on protein/peptide are also abundant, including passive renal targeting based on macromolecular protein and active targeting mediated by renal targeting peptide. Here, we review the application and the drug loading strategy of different proteins or peptides in targeted drug delivery, including the ferritin family, albumin, low molecular weight protein (LMWP), different peptide sequence and antibodies. In addition, we summarized the factors influencing passive and active targeting in drug delivery system, the main receptors related to active targeting in different kidney diseases, and a variety of nano forms of proteins based on the controllable synthesis of proteins.

Case report: Ultrasound-guided median nerve electrical stimulation on functional recovery of hemiplegic upper limb after stroke.

Background: Functional restoration of hemiplegic upper limbs is a difficult area in the field of neurological rehabilitation. Electrical stimulation is one of the treatments that has shown promising advancements and functional improvements. Most of the electrical stimulations used in clinical practice are surface stimulations. In this case, we aimed to investigate the feasibility of a minimally invasive, ultrasound-guided median nerve electrical stimulation (UG-MNES) in improving the upper limb motor function and activity of a patient with right-sided hemiparesis. Case presentation: A 65-year-old male recovering from a left massive intracerebral hemorrhage after open debridement hematoma removal had impaired right limb movement, right hemianesthesia, motor aphasia, dysphagia, and complete dependence on his daily living ability. After receiving 3 months of conventional rehabilitation therapy, his cognitive, speech, and swallowing significantly improved but the Brunnstrom Motor Staging (BMS) of his right upper limb and hand was at stage I-I. UG-MNES was applied on the right upper limb for four sessions, once per week, together with conventional rehabilitation. Immediate improvement in the upper limb function was observed after the first treatment. To determine the effect of UG-MNES on long-term functional recovery, assessments were conducted a week after the second and fourth intervention sessions, and motor function recovery was observed after 4-week of rehabilitation. After completing the full rehabilitation course, his BMS was at stage V-IV, the completion time of Jebsen Hand Function Test (JHFT) was shortened, and the scores of Fugl-Meyer Assessment for upper extremity (FMA-UE) and Modified Barthel Index (MBI) were increased. Overall, the motor function of the hemiplegic upper limb had significantly improved, and the right hand was the utility hand. Electromyography (EMG) and nerve conduction velocity (NCV) tests were normal before and after treatment. Conclusion: The minimally invasive, UG-MNES could be a new alternative treatment in stroke rehabilitation for functional recovery of the upper limbs.

Incidence rate and risk factors for hypoglycemia among individuals with type 1 diabetes or type 2 diabetes in China receiving insulin treatment.

AIMS: We investigated the real-world incidence of hypoglycemic events among patients with type 1 or type 2 diabetes (T1DM or T2DM) receiving insulin in routine clinical practice in China. METHODS: In this observational study, data were collected electronically via the Lilly Connected Care Program (LCCP) electronic system from adults with T1DM or T2DM who had registered on LCCP between 1 February 2019 and 31 January 2022, had used insulin for a full 12-week period following registration. The following outcomes were assessed during the 12 weeks following registration: incidence of level 1 and level 2 hypoglycemia. RESULTS: In total, 22,752 patients were enrolled. Among patients with monitoring data, over the 12-week study period, level 1 and 2 hypoglycemia were experienced by 48.8% and 25.9% of patients with T1DM and 26.5% and 13.9% of patients with T2DM. The proportion of patients treated with oral anti-diabetes drugs (OADs) capable of producing hypoglycemia (sulfonylurea or glinide) was 1.3% in T1DM and 1.6% in T2DM, respectively. Questionnaire data revealed that up to 92.5% of hypoglycemic events occurred outside of hospital and 18.6% were serious. CONCLUSIONS: These real-world data collected from Chinese patients with diabetes receiving insulin treatment reveal a relatively high percentage of patients experiencing hypoglycemia, with around one quarter of these events classified as severe and as many as 92.5% occurring outside of a hospital or clinic.

Exoskeleton Partial-Coated Stem Cells for Infarcted Myocardium Restoring.

The integration of abiotic materials with live cells has emerged as an exciting strategy for the control of cellular functions. Exoskeletons consisting ofmetal-organic frameworks are generated to produce partial-coated bone marrow stem cells (BMSCs) to overcome low cell survival leading to disappointing effects for cell-based cardiac therapy. Partially coated exoskeletons can promote the survival of suspended BMSCs by integrating the support of exoskeletons and unimpaired cellular properties. In addition, partial exoskeletons exhibit protective effects against detrimental environmental conditions, including reactive oxygen species, pH changes, and osmotic pressure. The partial-coated cells exhibit increased intercellular adhesion forces to aggregate and adhere, promoting cell survival and preventing cell escape during cell therapy. The exoskeletons interact with cell surface receptors integrin α5ß1, leading to augmented biological functions with profitable gene expression alteration, such as Vegfa, Cxcl12, and Adm. The partial-coated BMSCs display enhanced cell retention in infarcted myocardium through non-invasive intravenous injections. The repair of myocardial infarction has been achieved with improved cardiac function, myocardial angiogenesis, proliferation, and inhibition of cell apoptosis. This discovery advances the elucidation of potential molecular and cellular mechanisms for cell-exoskeleton interactions and benefits the rational design and manufacture of next-generation nanobiohybrids.

Seneca Valley virus 3Cpro antagonizes host innate immune responses and programmed cell death.

Seneca Valley virus (SVV), a member of the Picornaviridae family, may cause serious water blister diseases in pregnant sows and acute death in newborn piglets, which have resulted in economic losses in pig production. The 3C protease is a vital enzyme for SVV maturation and is capable of regulating protein cleavage and RNA replication of the virus. Additionally, this protease can impede the host's innate immune response by targeting the interferon pathway's principal factor and enhance virus replication by modulating the host's RNA metabolism while simultaneously triggering programmed cell death. This article reviews recent studies on SVV 3C functions, which include viral replication promotion, cell apoptosis modulation and host immune response evasion, and provides a theoretical basis for research on preventing and controlling SVV infection.

Tyrosine catabolism enhances genotoxic chemotherapy by suppressing translesion DNA synthesis in epithelial ovarian cancer.

Amino acid metabolism has been actively investigated as a potential target for antitumor therapy, but how it may alter the response to genotoxic chemotherapy remains largely unknown. Here, we report that the depletion of fumarylacetoacetate hydrolase (FAH), an enzyme that catalyzes the final step of tyrosine catabolism, reduced chemosensitivity in epithelial ovarian cancer (EOC). The expression level of FAH correlated significantly with chemotherapy efficacy in patients with EOC. Mechanistically, under genotoxic chemotherapy, FAH is oxidized at Met308 and translocates to the nucleus, where FAH-mediated tyrosine catabolism predominantly supplies fumarate. FAH-produced fumarate binds directly to REV1, resulting in the suppression of translesion DNA synthesis (TLS) and improved chemosensitivity. Furthermore, in vivo tyrosine supplementation improves sensitivity to genotoxic chemotherapeutics and reduces the occurrence of therapy resistance. Our findings reveal a unique role for tyrosine-derived fumarate in the regulation of TLS and may be exploited to improve genotoxic chemotherapy through dietary tyrosine supplementation.

Sialic Acid-Functionalized Pyroptosis Nanotuner for Epigenetic Regulation and Enhanced Cancer Immunotherapy.

The efficacy of immune checkpoint blockade (ICB) in promoting an immune response against tumors still encounters challenges such as low response rates and off-target effects. Pyroptosis, an immunogenic cell death (ICD) mechanism, holds the potential to overcome the limitations of ICB by activating and recruiting immune cells. However, the expression of the pyroptosis-related protein Gasdermin-E(GSDME) in some tumors is limited due to mRNA methylation. To overcome this obstacle, sialic acid-functionalized liposomes coloaded with decitabine, a demethylation drug, and triclabendazole, a pyroptosis-inducing drug are developed. This nanosystem primarily accumulates at tumor sites via sialic acid and the Siglec receptor, elevating liposome accumulation in tumors up to 3.84-fold at 24 h and leading to the upregulation of pyroptosis-related proteins and caspase-3/GSDME-dependent pyroptosis. Consequently, it facilitates the infiltration of CD8+ T cells into the tumor microenvironment and enhances the efficacy of ICB therapy. The tumor inhibition rate of the treatment group is 89.1% at 21 days. This study highlights the potential of sialic acid-functionalized pyroptosis nanotuners as a promising approach for improving the efficacy of ICB therapy in tumors with low GSDME expression through epigenetic alteration and ICD.

Upregulation of IL-37 in epithelial cells: A potential new mechanism of T cell inhibition induced by tacrolimus.

Oral lichen planus (OLP) is a chronic T cell-mediated mucocutaneous disease characterized by T cell infiltration at the connective tissue-epithelium interface. Traditionally, topical corticosteroids are used as the first-line drugs to treat OLP. However, long-term use of corticosteroids may lead to drug tolerance, secondary candidiasis, and autoimmune adrenal insufficiency. Although topical tacrolimus has often been recommended for short-term use in corticosteroid-refractory OLP, the precise role of tacrolimus in epithelial cells remains elusive. This study showed that tacrolimus could directly upregulate the expression of IL-37 in human gingival epithelial cells by promoting the TGF-ßRI/Smad3 pathway independently of calcineurin inhibition and MAPKs. In contrast, dexamethasone, one of the corticosteroids, did not have the same effect. Moreover, IL-37 could inhibit the proliferation of activated T cells and the secretion of effector cytokines and alleviate epithelial cell apoptosis and death caused by activated T cells ina co-culturesystem. Furthermore, compared with healthy controls, IL-37 and p-Smad3 levels significantly increased in the oral mucosa affected by OLP, especially in the epithelium. IL-37 might have mediated a negative feedback mechanism to curb excessive inflammation in OLP. However, the expression of IL-37 was not associated with the infiltration of CD8+ T cells and Tregs in OLP, implying that IL-37 might mostly affect T cell activation rather than T cell differentiation and migration. Overall, this study discovered a potential novel mechanism by which tacrolimus might indirectly inhibit T cell-mediated immune damage by upregulating IL-37 in human gingival epithelial cells.

Animal Models for Studying Protein-Bound Uremic Toxin Removal-A Systematic Review.

Protein-bound uremic toxins (PBUTs) are associated with the progression of chronic kidney disease (CKD) and its associated morbidity and mortality. The conventional dialysis techniques are unable to efficiently remove PBUTs due to their plasma protein binding. Therefore, novel approaches are being developed, but these require validation in animals before clinical trials can begin. We conducted a systematic review to document PBUT concentrations in various models and species. The search strategy returned 1163 results for which abstracts were screened, resulting in 65 full-text papers for data extraction (rats (n = 41), mice (n = 17), dogs (n = 3), cats (n = 4), goats (n = 1), and pigs (n = 1)). We performed descriptive and comparative analyses on indoxyl sulfate (IS) concentrations in rats and mice. The data on large animals and on other PBUTs were too heterogeneous for pooled analysis. Most rodent studies reported mean uremic concentrations of plasma IS close to or within the range of those during kidney failure in humans, with the highest in tubular injury models in rats. Compared to nephron loss models in rats, a greater rise in plasma IS compared to creatinine was found in tubular injury models, suggesting tubular secretion was more affected than glomerular filtration. In summary, tubular injury rat models may be most relevant for the in vivo validation of novel PBUT-lowering strategies for kidney failure in humans.

Adipose-Derived Mesenchymal Stem Cell-Derived Exosomes Biopotentiated Extracellular Matrix Hydrogels Accelerate Diabetic Wound Healing and Skin Regeneration.

Wound healing is an urgent clinical challenge, particularly in the case of chronic wounds. Traditional approaches to wound healing have limited therapeutic efficacy due to lengthy healing times, risk of immune rejection, and susceptibility to infection. Recently, adipose-derived mesenchymal stem cell-derived exosomes (ADSC-exos) have emerged as a promising modality for tissue regeneration and wound repair. In this study, the development of a novel extracellular matrix hydrogel@exosomes (ECM@exo) is reported, which entails incorporation of ADSC-exos into an extracellular matrix hydrogel (ECM hydrogel). This solution forms a hydrogel at physiological temperature (≈37 °C) upon local injection into the wound site. ECM@exo enables sustained release of ADSC-exos from the ECM hydrogel, which maintains high local concentrations at the wound site. The ECM hydrogel displays good biocompatibility and biodegradability. The in vivo and in vitro results demonstrate that ECM@exo treatment effectively reduces inflammation and promotes angiogenesis, collagen deposition, cell proliferation, and migration, thereby accelerating the wound healing process. Overall, this innovative therapeutic approach offers a new avenue for wound healing via a biological hydrogel with controlled exosome release.