Inflammation-Derived and Clinical Indicator-Based Predictive Model for Ischemic Stroke Recovery.

BACKGROUND: Neuroinflammatory responses are closely associated with poststroke prognosis severity. This study aimed to develop a predictive model, combining inflammation-derived markers and clinical indicators, for distinguishing functional outcomes in patients with subacute ischemic stroke. METHODS AND RESULTS: Based on activities of daily living assessments, ischemic stroke participants were categorized into groups with little effective (LE) recovery and obvious effective (OE) recovery. Initial biocandidates were identified by overlapping differentially expressed proteins from proteomics of clinical serum samples (5 LE, 5 OE, and 6 healthy controls) and differentially expressed genes from an RNA sequence of the ischemic cortex in middle cerebral artery occlusion mice (n=3). Multidimensional validations were conducted in ischemia-reperfusion models and a clinical cohort (15 LE, 11 OE, and 18 healthy controls). Models of robust biocandidates combined with clinical indicators were developed with machine learning in the training data set and prediction in another test data set (15 LE and 11 OE). We identified 194 differentially expressed proteins (LE versus healthy controls) and 174 differentially expressed proteins (OE versus healthy controls) in human serum, and 5121 differentially expressed genes (day 3) and 5906 differentially expressed genes (day 7) in middle cerebral artery occlusion mice cortex. Inflammation-derived biomarkers TIMP1 (tissue inhibitor metalloproteinase-1) and galactosidase-binding protein LGLAS3 (galectin-3) exhibited robust increases under ischemic injury in mice and humans. TIMP1 and LGALS3 coupled with clinical indicators (hemoglobin, low-density lipoprotein cholesterol, and uric acid) were developed into a combined model for differentiating functional outcome with high accuracy (area under the curve, 0.8). CONCLUSIONS: The combined model is a valuable tool for evaluating prognostic outcomes, and the predictive factors can facilitate development of better treatment strategies.

Identification and antibiotic susceptibility of microorganisms isolated from diabetic foot ulcers: A pathological aspect.

Diabetic foot ulcers infected with microorganisms increase the risk of amputation. The presence of drug-resistant bacteria in diabetic foot ulcers creates a big challenge during the treatment. The objective of the present study was to determine the bacterial prevalence and antibiotic resistance among bacteria isolated from Chinese patients with diabetic foot ulcers. The present study studied the microbial colonization of diabetic foot ulcers of patients from a single center in China. Wound swabs from 89 patients with diabetic foot ulcers were collected and the presence of microorganisms detected. The isolated microorganisms were subjected to antibiotic susceptibility testing by the disk diffusion method. Of 89 patients, 56 (62.9%) were male and 33 (37.1%) were female, the mean age of patients was 53.2±5.4 years, the mean duration of diabetes was 14.8±2.9 years, the mean random blood sugar was 301±87 mg/dl, mean HbA1c was 7.9±1.4%. Patients with Wanger ulcer grade III (36.0%; P=0.034) and patients within the weight range of 51-75 kg (59.6%; P=0.012) were significantly higher. The prevalence rate of diabetic foot ulcers was 11.3%. Among 153 microorganisms, gram-positive bacteria (52.3%) were more prevalent than gram-negative bacteria (44.4%). Most of the patients with polymicrobial infection were classified to have Wanger III ulcer grade diabetic foot ulcers. Staphylococcus aureus (38.2%) was the most predominant bacteria isolated followed by Staphylococcus epidermidis (29.2%) and Escherichia coli (28.1%). Most of the gram-positive and gram-negative bacteria were resistant to dicloxacillin (73.8%, P=0.021) and cefotaxime (50%), respectively and ~53.4% of the isolates were multi-drug resistance isolates, 61.8% of the Staphylococcus aureus were identified as methicillin-resistant Staphylococcus aureus and 61.8% of the gram-negative bacteria were extended-spectrum ß-lactamase producers. Staphylococcus aureus and Escherichia coli were the predominant gram-positive and gram-negative bacteria isolated, respectively. Penicillin resistance was significantly higher among the gram-negative bacteria (P=0.019). Staphylococcus aureus and Escherichia coli were the predominant gram-positive and gram-negative bacteria isolated and levofloxacin and nitrofurantoin were the most effective antibiotics among the gram-positive and gram-negative bacterial isolates, respectively.

Sustained Release of Magnesium Ions Mediated by a Dynamic Mechanical Hydrogel to Enhance BMSC Proliferation and Differentiation.

Hydrogel scaffolds are promising and widely applicable platforms for various therapeutic agents to facilitate bone tissue regeneration due to their biocompatibility and low immunogenicity. Nevertheless, the improvement of local administration efficiency and on-demand release of drugs from a hydrogel system is still an obstacle. In this work, we reported that a novel injectable hydrogel system was fabricated based on coordination of multiarm thiolated polyethylene glycol (PEG-SH) and magnesium ions for bone marrow-derived mesenchymal stem cell (BMSC) proliferation and differentiation. The dynamic nature coordination bond of Mg-S and the dynamic disulfide bond of S-S provide hydrogels with good mechanical performance and typical rheological behavior and thus endow the hydrogels with a satisfactory swelling rate and degradation property. Mg2+ was incorporated in the system not only to act as an effective cross-linker to enhance the hydrogel network structure but also to mediate the sustained release of Mg2+. Due to the controlled release of Mg2+, the PEG-SH/Mg2+ hydrogel can effectively improve BMSC proliferation and osteoblastic activity via the PI3K/Akt/GSK3ß/ß-catenin signal pathway in vitro. These findings indicated that the novel hydrogel controlled release of a Mg2+ ion is viewed as a promising and flexible platform for bone regeneration clinically.