Enhanced diabetic wound healing with injectable hydrogel containing self-assembling nanozymes.

To build a smart system in response to the variable microenvironment in infected diabetic wounds, a multifunctional wound dressing was constructed by co-incorporating glucose oxidase (GOx) and a pH-responsive self-assembly Cu2-xSe-BSA nanozyme into a dual-dynamic bond cross-linked hydrogel (OBG). This composite hydrogel (OBG@CG) can adhere to the wound site and respond to the acidic inflammatory environment, initiating the GOx-catalyzed generation of H2O2 and the self-assembly activated peroxidase-like property of Cu2-xSe-BSA nanozymes, resulting in significant hydroxyl radical production to attack the biofilm during the acute infection period and alleviate the high-glucose microenvironment for better wound healing. During the wound recovery phase, Cu2-xSe-BSA aggregates disassembled owing to the elevated pH, terminating catalytic reactive oxygen species generation. Simultaneously, Cu2+ released from the Cu2-xSe-BSA not only promotes the production of mature collagen but also enhances the migration and proliferation of endothelial cells. RNA-seq analysis demonstrated that OBG@CG exerted its antibacterial property by damaging the integrity of the biofilm by inducing radicals and interfering with the energy supply, along with destroying the defense system by disturbing thiol metabolism and reducing transporter activities. This work proposes an innovative glucose consumption strategy for infected diabetic wound management, which may inspire new ideas in the exploration of smart wound dressing.

Copper-Loaded Nanoheterojunction Enables Superb Orthotopic Osteosarcoma Therapy via Oxidative Stress and Cell Cuproptosis.

Catalytic tumor therapy based on two-dimensional (2D) nanomaterials is a burgeoning and promising tumor therapeutic modality. However, the inefficient utilization and conversion of exogenous stimulation, single catalytic modality, and unsatisfactory therapeutic efficiency in the tumor microenvironment (TME) have seriously restricted their further application in tumor therapy. Herein, the heterogeneous carbon nitride-based nanoagent named T-HCN@CuMS was successfully developed, which dramatically improved the efficiency of the tumor therapeutic modality. Benefiting from the donor-acceptor (triazine-heptazine) structure within the heterogeneous carbon nitride nanosheets (HCN) and the construction of interplanar heterostructure with copper loaded metallic molybdenum bisulfide nanosheets (CuMS), T-HCN@CuMS presented a favorable photo-induced catalytic property to generate abundant reactive oxygen species (ROS) under near-infrared (NIR) light irradiation. Besides, the choice of CuMS simultaneously enabled this nanoagent to efficiently catalyze the Fenton-like reaction and trigger cell cuproptosis, a recently recognized regulated cell death mode characterized by imbalanced intracellular copper homeostasis and aggregation of lipoylated mitochondrial proteins. Moreover, upon surface modification with cRGDfk-PEG2k-DSPE, T-HCN@CuMS was prepared and endowed with improved dispersibility and αvß3 integrins targeting ability. In general, through the rational design, T-HCN@CuMS was facilely prepared and had achieved satisfactory antitumor and antimetastasis outcomes both in vitro and in a high-metastatic orthotopic osteosarcoma model. This strategy could offer an idea to treat malignant diseases based on 2D nanomaterials.

Clinical trials of stem cell-based therapies for pediatric diseases: a comprehensive analysis of trials registered on ClinicalTrials.gov and the ICTRP portal site.

BACKGROUND: Research on clinical trials that employ stem cells to treat children's diseases is limited. The clinical trial registry database provides a unique window to us to get known about clinical trial researches with different statuses. However, few studies aimed to perform a comprehensive and thorough analysis of those registered trials in the aforementioned field based on ClinicalTrials.gov and the ICTRP portal site. METHODS: Our study covered the clinical researches about stem cell therapy enrolling subjects aged under 18 years old registered on ClinicalTrials.gov and WHO ICTRP before May 18, 2021. A cross-sectional study was implemented to comprehensively describe and analyze the included trials that met the criteria. Results were available on ClinicalTrials.gov, and publications related to the included trials were identified. All analyses were performed utilizing the SPSS 25.0 software. RESULTS: Eventually, 202 clinical trials were included and evaluated. The participant number of trials tended to be small; 71.3% were enrolled < 50. And 93.5% of the subjects were without gender restrictions. Till May 2020, 112 trials had been preliminary completed, of which only 39 trials had published papers or uploaded results. Most (73.6%) of 186 interventional trials were in phase 1 and phase 2, where 131 (70.4%) trials were conducted without masking, and 26.3% trials were randomized; 55.4% trials were performed single group assignment. Of 16 observational trials, case-only/series took up 37.5%. Hematopoietic stem cells (37.1%) and mesenchymal stem cells (36.1%) were mostly employed, while umbilical cord blood (UCB)-derived cells (24.3%) and bone marrow (BM)-derived cells (20.8%) were the major sources. CONCLUSIONS: This study provided an overall picture of utilizing stem cells for treatment and management of childhood diseases. Since clinical trials in this area are insufficient in quantity and quality, there is an urgent need of larger, better-designed trials. Increased investment in clinical research of stem cell treatment products should be carried out to achieve the transformation of results as soon as possible. Moreover, it is important to optimize the management of the registration platform and shorten the time it takes for research results to be published.

A multi-method evaluation of the effects of Inflammatory cytokines (IL-1ß, IFN-γ, TNF-α) on pancreatic ß-cells.

We aimed to explore the effects of Inflammatory cytokines (IL-1ß, IFN-γ, TNF-α) on pancreatic ß-cells. CCK-8 assay showed that the cell viability decreased after 24 hr treatment of TNF-α, 48 hr of IFN-γ, and 84 hr of IL-1ß. EdU assay illustrated that after 24 hr treatment, there were significantly reduced EdU-labeled red fluorescence cells in TNF-α group while not in IFN-γ and IL-1ß groups. Flow Cytometry results displayed that TNF-α and IFN-γ groups increased apoptosis while IL-1ß group did not. Cell apoptosis results found that there was an increase in the S-phase population of IL-1ß and TNF-α groups, however, there was no significant difference in cell cycle between IFN-γ group and the control. TEM images showed that there were reduction in the number of granules and mitochondria in IL-1ß and IFN-γ groups, in particular paucity of insulin granules and mitochondria in TNF-α group. Radioimmunoassay results presented that TNF-α inhibited glucose-induced insulin secretion, while there were no significant changes in IL-1ß and IFN-γ groups when compared with the control. Metabolomic analysis found amino acid metabolism and Krebs cycle were the most robust altered metabolism pathways after inflammatory cytokines treatments. Overall, the altered amino acid metabolism and Krebs cycle metabolism might be important mechanisms of TNF-α induced mouse pancreatic ß-cells dysfuction.

Associations between maternal exposure to air pollution and birth outcomes: a retrospective cohort study in Taizhou, China.

Previous studies from Western country settings had shown correlation between maternal exposure to air pollution and pregnancy outcomes; however, the evidence is difficult to clearly interpret. We aimed to investigate the association of maternal exposure to air pollution expressed as particulate matter (PM2.5, PM10) and nitrogen dioxide (NO2). The exposure was assessed for the 1st, 2nd, and 3rd trimester and related to the birth outcomes. During each trimester of gestation, the effect of PM2.5, PM10, and NO2 exposure as well as the entire pregnancy on the preterm birth, low birth weight, and term babies' birth weight was explored. The dataset of 26,998 delivered live births between January 1, 2013 and May 31, 2016, were collected from the Taizhou Maternal and Child Care Service Center. Air monitoring data were collected from the Taizhou Municipal Environmental Monitoring Center for the same period. We used multi-variable logistic and linear regression analyses to investigate the correlation of air pollution to maternal and outcomes of birth. In models of adjusted single pollutant for second trimester, NO2 concentration was positively correlated with term low birth weight and preterm birth [aRR for an interquartile range increase: 1.59 (1.44, 1.75); 1.27 (1.12, 1.44)]; likewise, a 1 µg/m3 increase in NO2 was correlated with a reduction in birth weight 2.94 g (P < 0.001) in linear models. Each of PM2.5 and PM10 concentration was also associated with preterm birth [aRR for an interquartile range increase 1.30 (1.21, 1.38); 1.39 (1.27, 1.52)]. In co-pollutant models, the results were similar. Maternal exposure to air pollutant in Taizhou was associated with an increased risk of preterm birth and reduction in birth weight. We reported a potential link between maternal exposure to air pollution and negative outcomes of birth in Taizhou, China.

Effects of particulate matter exposure during pregnancy on birth weight: A retrospective cohort study in Suzhou, China.

BACKGROUND: Recent studies have identified that exposure to particulate matter during pregnancy could result in adverse birth outcomes, but the effects of exposure at trimester-specific intervals are inconsistent. OBJECTIVE: Our primary goal was to investigate whether particulate matter exposure during pregnancy could affect birth weight and gestational age of neonates. METHODS: A retrospective cohort study was conducted to examine the relationship between maternal particulate matter exposure and neonatal birth weight. We collected 14,455 births records linked to hospital admission records (delivery and antenatal) from January 2013 to December 2015 in Suzhou Municipal Hospital. Air monitoring data in the same timeframe were also collected from Suzhou Environmental Protection Agency. The risk of low birth weight due to the exposure to PM2.5 (with median aerodynamic diameter≤2.5µm) and PM10 (with median aerodynamic diameter≤10µm) at each trimester and throughout the entire pregnancy were assessed. Linear regression models were applied and potential confounding factors were adjusted for data analysis. Gestational age, which was another important birth outcome, and its association with maternal particulate matter exposure were also studied. RESULTS: The final analysis included 10,915 singleton live births. Using multiple linear regression models, we found that gestational exposure to PM2.5 and PM10 at 10µg/m3 increments in the second trimester led to decreases in birth weight of 4.94g (95% confidence interval: -9.828, -0.046) and 5.65g (95% confidence interval: -10.110, -1.188), respectively. However, gestational age was not significantly associated with maternal particulate matter exposure in term neonates. CONCLUSION: These findings indicate that pregnant women might be more susceptible to particulate matter during the second trimester which may lead to decreased neonatal birth weight.

Association between exposure to particulate matter during pregnancy and birthweight: a systematic review and a meta-analysis of birth cohort studies.

Studies of the associations between maternal exposure to particulate matter (PM) and risk of adverse effects on fetal growth are inconsistent and inconclusive. This question can be well answered by carefully designed birth cohort studies; however, so far the evidence from such studies has not come to the same conclusion. We sought to evaluate the association between maternal exposures to PM and low birthweight (LBW) enrolling 14 studies from 11 centers, and to explore the influence of trimester and exposure assessment methods on between-center heterogeneity in this association. Data were derived from PubMed, Embase, Google Scholar, CNKI, and WanFang database, references from relevant articles, and results from published studies until March 2017. Using a random-effects meta-analysis, we combined the coefficient and odds ratios (OR) of individual studies conducted among 14 birth cohort studies. Random-effect meta-analysis results suggested that a 17% and 6% increase in risk of LBW was relevant to a 10 mg/m3 rise in PM2.5 and PM10 exposure concentrations at the 3rd trimester (pooled odds ratios (OR), 1.17 and 1.06; 95% confidence interval (CI), 0.94-1.46 and 0.97-1.15, respectively), but the null value was included in our 95% CI. Our results showed that exposure to PM2.5 and PM10 during pregnancy has a positive relevance to LBW based on birth cohort studies. However, neither reached formal statistical significance. Negative impacts on outcomes of birth is implied by maternal exposure to PM. Further mechanistic researches are needed to explain the connection between PM pollution and LBW.