In situ photo-crosslinkable hyaluronic acid-based hydrogel embedded with GHK peptide nanofibers for bioactive wound healing.

A versatile hydrogel was developed for enhancing bioactive wound healing by introducing the amphiphilic GHK peptide (GHK-C16) into a photo-crosslinkable tyramine-modified hyaluronic acid (HA-Ty). GHK-C16 self-assembled into GHK nanofibers (GHK NF) in HA-Ty solution, which underwent in situ gelation after the wound area was filled with precursor solution. Blue light irradiation (460-490 nm), with riboflavin phosphate as a photoinitiator, was used to trigger crosslinking, which enhanced the stability of the highly degradable hyaluronic acid and enabled sustained release of the nanostructured GHK derivatives. The hydrogels provided a microenvironment that promoted the proliferation of dermal fibroblasts and the activation of cytokines, leading to reduced inflammation and increased collagen expression during wound healing. The complexation of Cu2+ into GHK nanofibers resulted in superior wound healing capabilities compared with non-lipidated GHK peptide with a comparable level of growth factor (EGF). Additionally, nanostructured Cu-GHK improved angiogenesis through vascular endothelial growth factor (VEGF) activation, which exerted a synergistic therapeutic effect. Furthermore, in vivo wound healing experiments revealed that the Cu-GHK NF/HA-Ty hydrogel accelerated wound healing through densely packed remodeled collagen in the dermis and promoting the growth of denser fibroblasts. HA-Ty hydrogels incorporating GHK NF also possessed improved mechanical properties and a faster wound healing rate, making them suitable for advanced bioactive wound healing applications. STATEMENT OF SIGNIFICANCE: By combining photo-crosslinkable tyramine-modified hyaluronic acid with self-assembled Cu-GHK-C16 peptide nanofibers (Cu-GHK NF), the Cu-GHK NF/HA-Ty hydrogel offers remarkable advantages over conventional non-structured Cu-GHK for wound healing. It enhances cell proliferation, migration, and collagen remodeling-critical factors in tissue regeneration. The incorporation of GHK nanofibers complexed with copper ions imparts potent anti-inflammatory effects, promoting cytokine activation and angiogenesis during wound healing. The Cu-GHK NF/hydrogel's unique properties, including in situ photo-crosslinking, ensure high customization and potency in tissue regeneration, providing a cost-effective alternative to growth factors. In vivo experiments further validate its efficacy, demonstrating significant wound closure, collagen remodeling, and increased fibroblast density. Overall, the Cu-GHK NF/HA-Ty hydrogel represents an advanced therapeutic option for wound healing applications.

Molecular Weight Distribution of Two Types of Living Chains Formed during Nitroxide-Mediated Polymerization of Styrene.

Different types of polymer chains generated during the nitroxide-mediated polymerization of styrene are separated for the first time, and their molecular weight distribution (MWD) is investigated. Living and dead chains are monitored during the reaction; specifically, two types of living chains derived from the initiation of the alkoxyamine (RT) and the self-initiation of styrene and dead chains present in the as-prepared polystyrene (PS). To distinguish between each polymer species, different numbers of hydroxyl groups are introduced onto the T and R groups of the alkoxyamine (one and two groups, respectively). Each living and dead chains is resolved according to the distinct number of hydroxyl groups on its chain-end using high-performance liquid chromatography. Molecular structures of the fractionated PS are characterized using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 1 H nuclear magnetic resonance spectroscopy, and the results of which show two distinct initiation paths: one originating from RT and the other from the self-initiation of styrene. Molecular weight and MWD are measured using size-exclusion chromatography and reveal a narrow MWD for the living chains derived from RT. Contrastingly, a broad and skewed MWD is observed for the other living chains derived from the self-initiation of styrene and the dead chains.

Hepatitis B Virus Infection Is Independently Associated With Advanced Colorectal Adenoma.

BACKGROUND: Studies on the association of chronic hepatitis B virus (HBV) infection with colonic neoplasm are rare. We aimed to investigate the association between chronic HBV infection and the development of colonic adenoma. MATERIALS AND METHODS: One hundred thirty-three patients with chronic HBV infection who underwent colonoscopic examination, were enrolled. A healthy HBV-uninfected group was matched with the HBV group. Those with a previous history of colorectal cancer, inflammatory bowel diseases or colorectal surgery were excluded from both HBV and HBV-uninfected groups. Clinical information and data on age, sex, body mass index, smoking, alcohol consumption and comorbidities were obtained. Advanced adenoma was defined as tubular adenoma ≥10mm, or adenoma with a villous component or high-grade dysplasia. RESULTS: The HBV group had a higher rate of colorectal adenoma and advanced adenoma than the HBV-uninfected group. Patients in the HBV group had larger colorectal polyps than those in the HBV-uninfected group. In the chi square test, HBV DNA positivity was significantly associated with colorectal adenoma (P < 0.001) and advanced adenoma (P = 0.007). HBV infection (odds ratio [OR] = 23.961, 95% CI: 9.400-61.076), diabetes mellitus (OR = 2.633, 95% CI: 1.071-6.473) and age (OR = 1.057, 95% CI: 1.020-1.095) were significantly associated with advanced adenoma in the multivariable logistic regression analysis. Multivariable logistic regression analysis within the HBV group revealed that HBV DNA (OR = 1.236, 95% CI: 1.029-1.485) was associated with advanced adenoma. CONCLUSIONS: HBV DNA in patients with HBV infection and HBV infection are independently associated with advanced colorectal adenoma development.

Clinical significance of computed tomography-detected ascites in gastric cancer patients with peritoneal metastases.

Patients with peritoneal metastases (PM) are generally considered incurable; therefore, the presence of PM is a critical factor in deciding between palliative surgery and curative resection as a therapeutic strategy. Previous studies have not determined the predictive value of ascites detected on computed tomography (CT) for the presence of PM. We aimed to analyze the factors that are associated with PM in patients with CT-detected ascites.A total of 2207 consecutive patients who were diagnosed with gastric cancer between 2004 and 2013 were identified. Eleven patients with liver cirrhosis or chronic renal insufficiency with ascites and 57 patients who received previous treatment were excluded. Ninety-eight patients who had definite evidence of distant metastasis or PM on CT and 64 patients who did not undergo surgery were excluded. A total of 91 patients were enrolled in the study to analyze the association between CT-detected ascites and surgically confirmed PM.Seventy-six patients underwent curative resection and 15 patients underwent palliative surgery. Twelve patients exhibited peritoneal seeding and 37 patients showed regional lymph node metastasis. Regional lymph node metastasis, advanced gastric cancer, undifferentiated pathology, and the amount of ascites were significantly associated with PM. Multivariable logistic regression analysis identified the amount of ascites to be an independent risk factor for the presence of PM.Regional lymph node metastasis, advanced gastric cancer, undifferentiated pathology, and the amount of ascites were associated with PM. The amount of ascites was found to be an independent risk factor for PM.

Obstructive sleep apnea is associated with an increased risk of colorectal neoplasia.

BACKGROUND AND AIMS: A recent meta-analysis showed that obstructive sleep apnea (OSA) is associated with a higher prevalence of cancer and cancer-related mortality; however, little information is available on the association between OSA and colorectal neoplasia. METHODS: We identified consecutive patients who underwent overnight polysomnography (PSG) and subsequent colonoscopy. We compared the prevalence of colorectal neoplasia between patients with or without OSA according to the results of PSG. For each patient with OSA, 1 or 2 controls matched for age (±5 years), sex, body mass index (BMI), and smoking who had undergone first-time screening colonoscopy were selected. RESULTS: Of the 163 patients, 111 patients were diagnosed with OSA and 52 patients were within the normal range of the Apnea-Hypopnea Index. Of the 111 patients with OSA, 18 patients (16.2%) had advanced colorectal neoplasia, including 4 (3.6%) colorectal cancers. In the multivariate analyses, OSA was associated with an increased risk of advanced colorectal neoplasia after adjusting for factors including age and sex (mild: odds ratio [OR], 14.09; 95% confidence interval [CI], 1.55-127.83; P = .019; moderate or severe: OR, 14.12; 95% CI, 1.52-131.25; P = .020). Our case-control study revealed that the odds of detecting advanced colorectal neoplasia among patients with OSA were approximately 3.03 times greater than in the controls matched for age, sex, BMI, and smoking (OR, 3.03; 95% CI, 1.44-6.34; P = .002). CONCLUSION: Physicians should be aware of the association between OSA and the development of colorectal neoplasia and explain the need for colonoscopy to patients with OSA.

Hemorheological Approach for Early Detection of Chronic Kidney Disease and Diabetic Nephropathy in Type 2 Diabetes.

BACKGROUND: Hemorheologic alterations or changes in blood viscosity have been suggested to play a role in the pathogenesis of microvascular complications in diabetes. We measured various hemorheologic parameters in type 2 diabetes patients at different stages of chronic kidney disease (CKD) and assessed their possible role as early markers of diabetic nephropathy and renal insufficiency. SUBJECTS AND METHODS: One hundred-five patients with type 2 diabetes were divided into four groups according to glomerular filtration rate (GFR), which represents the kidney function. Hemorheologic parameters, including erythrocyte deformability, fibrinogen/elongation index (EI), and aggregation index (AI) were measured using a microfluidic hemorheometer, and critical shear stress (CSS) was measured using a microfluidic technique. Various metabolic parameters were assessed from fasting blood samples, and the urine albumin-to-creatinine ratio (ACR) was calculated from first morning voided urine. RESULTS: There were significant differences in red blood cell (RBC) deformability, AI, CSS, fibrinogen/EI, and ACR among patients in different stages of CKD (all P<0.05). RBC deformability and fibrinogen/EI significantly differed between normal (GFR >90 mL/min/1.73 m(2)) and CKD stage 2 (GFR 60-90 mL/min/1.73 m(2)) patients, whereas there was no such difference in ACR. In multiple regression analysis, fibrinogen/EI under a moderate shear stress of 3 Pa was an independent predictor of GFR (ß=-0.328, P<0.05). Also, AI, CSS, and fibrinogen/EI were significantly different among patients at different stages of diabetic nephropathy, with a significant difference in fibrinogen/EI between normal and microalbuminuric patients (all P<0.05). CONCLUSIONS: RBC deformability and fibrinogen/EI are sensitive parameters measured via point-of-care testing for detecting erythrocyte alterations in early CKD and nephropathy in patients with type 2 diabetes. Further studies are warranted to verify their use as screening tools for diabetic nephropathy and renal impairment.