Single-Walled (Magnetic) Carbon Nanotubes in a Pectin Matrix in the Design of an Allantoin Delivery System.

Single-walled carbon nanotubes (SWCNTs) outperform other materials due to their high conductivity, large specific surface area, and chemical resistance. They have numerous biomedical applications, including the magnetization of the SWCNT (mSWCNT). The drug loading and release properties of see-through pectin hydrogels doped with SWCNTs and mSWCNTs were evaluated in this study. The active molecule in the hydrogel structure is allantoin, and calcium chloride serves as a cross-linker. In addition to mixing, absorption, and swelling techniques, drug loading into carbon nanotubes was also been studied. To characterize the films, differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), Fourier transform infrared (FTIR) spectroscopy, surface contact angle measurements, and opacity analysis were carried out. Apart from these, a rheological analysis was also carried out to examine the flow properties of the hydrogels. The study was also expanded to include N-(9-fluorenyl methoxycarbonyl)glycine-coated SWCNTs and mSWCNTs as additives to evaluate the efficiency of the drug-loading approach. Although the CNT additive was used at a 1:1000 weight ratio, it had a significant impact on the hydrogel properties. This effect, which was first observed in the thermal properties, was confirmed in rheological analyses by increasing solution viscosity. Additionally, rheological analysis and drug release profiles show that the type of additive causes a change in the matrix structure. According to TGA findings, even though SWCNTs and mSWCNTs were not coated more than 5%, the coating had a significant effect on drug release control. In addition to all findings, cell viability tests revealed that hydrogels with various additives could be used for visual wound monitoring, hyperthermia treatment, and allantoin release in wound treatment applications.

Association of Serum Irisin Levels with Body Composition, Metabolic Profile, Leptin, and Adiponectin Levels in Lean and Obese Children.

Background and Objectives: Irisin is an adipo-myokine with potential metabolic effects in the body, and its association with childhood obesity is still controversial. This study aimed to investigate the relationship between serum irisin levels and anthropometric parameters, body composition, metabolic profiles, leptin, and adiponectin in obese and normal-weight children. Methods: The study sample consisted of a total of 80 children aged 6-10, including 44 obese children (BMI ≥ 97th percentile) and 36 normal-weight children. Anthropometric parameters were measured. Body composition was determined with the use of the Bioelectrical Impedance Analysis (BIA) method. Metabolic profiles, as well as irisin, leptin, and adiponectin levels, were analyzed. Results: Anthropometric parameters and body composition were found to be significantly different between the obese and normal-weight groups (p < 0.05). Fasting blood glucose, insulin, HOMA-IR, and leptin levels were found to be significantly higher in the obese group, while the normal-weight group had significantly higher HDL cholesterol and adiponectin levels (p < 0.05). Serum irisin levels did not differ between the obese and normal-weight groups, or based on sex, vitamin D levels, and insulin resistance status. There was also no statistically significant correlation between serum irisin levels and anthropometric parameters, metabolic profile, leptin, and adiponectin. Conclusions: The study concluded that the obese children who participated in this study had high leptin levels and low adiponectin levels, with no significant difference in the irisin levels between the groups. More comprehensive clinical studies are needed to investigate the relationship between irisin and adipokines in children.

The angiogenic gene profile of pulmonary endarterectomy specimens: Initial study.

Objectives: The underlying mechanisms for the development of chronic thromboembolic pulmonary hypertension and prognostic biomarkers are not clear yet. Thus, our aim is to assess and identify new biomarkers for the expression of 84 key genes linked to angiogenesis. Methods: Patients who had levels more than 1000 dynes·sec·cm-5 were included in the test group, and the other patients were included in the control group. Twelve specimens were taken from the patients. RT2 Profiler PCR Array (Qiagen) was used to quantify the expression of the 84 key genes. Results: Eight patients (6 male, 2 female, median age 54.4 ± 13.1 years) who underwent pulmonary endarterectomy were included. Pulmonary vascular resistance improved significantly from 811 ± 390 dyn/s/cm-5 to 413.3 ± 144.9 dyn/s/cm-5 (P < .005). A difference was also detected in median mean pulmonary arterial pressure, which decreased from 49.8 ± 9 mm Hg to 32.62 ± 2.50 mm Hg (P > .005) after surgery. Median length of hospital stay was 11.62 ± 2.97 days. The test group had a distinct pattern of impaired angiogenic and antiangiogenic genes. The expression levels of TGFA, TGFB1, THBS2, THBS1, TGFBR1, SERPINE1, SERPINF1, TGFB2, TIMP2, VEGFC, IFNA1, TNF, CXCL10, NOS3, IGF1, and MMP14 were downregulated in the specimens from the patients who had higher pulmonary vascular resistance values, whereas some genes, including PDGFA, showed upregulation that was statistically nonsignificant in the same group. Conclusions: These results can lead to the development of new markers that could predict adverse outcomes of patients with CTEPH. Identification of new markers that are related to worse outcomes would enable screening patients for early diagnosis and treatment.

Pectin-Zeolite-Based Wound Dressings with Controlled Albumin Release.

Hypoalbuminemia can lead to poor and delayed wound healing, while it is also associated with acute myocardial infarction, heart failure, malignancies, and COVID-19. In elective surgery, patients with low albumin have high risks of postoperative wound complications. Here, we propose a novel cost-effective wound dressing material based on low-methoxy pectin and NaA-zeolite particles with controlled albumin release properties. We focused on both albumin adsorption and release phenomena for wounds with excess exudate. Firstly, we investigated albumin dynamics and calculated electrostatic surfaces at experimental pH values in water by using molecular dynamics methods. Then, we studied in detail pectin-zeolite hydrogels with both adsorption and diffusion into membrane methods using different pH values and albumin concentrations. To understand if uploaded albumin molecules preserved their secondary conformation in different formulations, we monitored the effect of pH and albumin concentration on the conformational changes in albumin after it was released from the hydrogels by using CD-UV spectroscopy analyses. Our results indicate that at pH 6.4, BSA-containing films preserved the protein's folded structure while the protein was being released to the external buffer solutions. In vitro wound healing assay indicated that albumin-loaded hydrogels showed no toxic effects on the fibroblast cells.

Fmoc-PEG Coated Single-Wall Carbon Nanotube Carriers by Non-covalent Functionalization: An Experimental and Molecular Dynamics Study.

Due to their structural characteristics at the nanoscale level, single-walled carbon nanotubes (SWNTs), hold great promise for applications in biomedicine such as drug delivery systems. Herein, a novel single-walled carbon nanotube (SWNT)-based drug delivery system was developed by conjugation of various Fmoc-amino acid bearing polyethylene glycol (PEG) chains (Mw = 2,000, 5,000, and 12,000). In the first step, full-atom molecular dynamics simulations (MD) were performed to identify the most suitable Fmoc-amino acid for an effective surface coating of SWNT. Fmoc-glycine, Fmoc-tryptophan, and Fmoc-cysteine were selected to attach to the PEG polymer. Here, Fmoc-cysteine and -tryptophan had better average interaction energies with SWNT with a high number of aromatic groups, while Fmoc-glycine provided a non-aromatic control. In the experimental studies, non-covalent modification of SWNTs was achieved by Fmoc-amino acid-bearing PEG chains. The remarkably high amount of Fmoc-glycine-PEG, Fmoc-tryptophan-PEG, and Fmoc-cysteine-PEG complexes adsorbed onto the SWNT surface, as was assessed via thermogravimetric and UV-vis spectroscopy analyses. Furthermore, Fmoc-cysteine-PEG5000 and Fmoc-cysteine-PEG12000 complexes displayed longer suspension time in deionized water, up to 1 and 5 week, respectively, underlying the ability of these surfactants to effectively disperse SWNTs in an aqueous environment. In vitro cell viability assays on human dermal fibroblast cells also showed the low cytotoxicity of these two samples, even at high concentrations. In conclusion, synthesized nanocarriers have a great potential for drug delivery systems, with high loading capacity, and excellent complex stability in water critical for biocompatibility.

Antitumor and antimetastatic effects of walnut oil in esophageal adenocarcinoma cells.

BACKGROUND: Walnuts contain many components including specific fatty acids, which could be active against cancer. Even though the anticarcinogenic effect of some of the individual fatty acids in walnut oil has been described, the effect of walnut oil itself on esophageal cancer cells hasn't yet been investigated. OBJECTIVE: We aimed to investigate whether walnut oil affects tumor growth and metastatic potential in esophageal cancer cells. METHODS: The human esophageal adenocarcinoma cell line, OE19, was treated with different doses of walnut oil and cell viability, apoptosis/necrosis and cell cycle analyses were performed using WST-1 assay and flow cytometry respectively. Adhesion, colony formation and wound healing assays were performed to assess the antimetastatic effects of walnut oil. NFkB expression was evaluated with western blot analysis. RESULTS: Walnut oil decreased the cell viability of esophageal cancer cells in a dose-dependent manner. 20 mg/mL walnut oil reduced cell viability by ∼50% when compared with control. The analysis revealed that necrosis and accumulation of cells in G0/G1 phase was induced in the cells treated with high doses of walnut oil. It also down-regulated the protein levels of NFkB. Walnut oil suppressed the adhesion, migration and colony formation of the cells. CONCLUSIONS: High-dose short-term administration of walnut oil reduces the cell viability and metastatic ability of esophageal cancer cells, while exhibiting anticarcinogenic effect by inducing necrosis and cell cycle arrest at the G0/G1 phase, probably through suppression of the NFkB pathway. These data indicate that walnut oil, and by extension walnut consumption, may have beneficial effects in esophageal cancer in humans. This should be tested by clinical trials in the future.

Supplementation of docosahexaenoic acid (DHA) / Eicosapentaenoic acid (EPA) in a ratio of 1/1.3 during the last trimester of pregnancy results in EPA accumulation in cord blood.

Omega-3 fatty acids (n-3 FA), specifically DHA, are associated with fetal growth and development. We aimed to determine the levels of DHA and EPA in cord serum after n-3 FA supplementation during the last trimester of pregnancy. Among 55 women, 23 were administered daily one capsule of n-3 FA supplement, involving DHA/EPA in a ratio of 1/1.3. Twenty nine women were enrolled as control group. Blood samples were collected at 22-24 weeks of gestation and at delivery. Fatty acids were analyzed with the method of GC-MS. Cord DHA level increased and EPA level decreased in both groups between the days of 22-24 and delivery. However, decrease in cord EPA level was significant in control group (p < 0.001) but not in supplement group (p > 0.05). Supplementation of DHA/EPA in a ratio of 1/1.3 during the last trimester of pregnancy caused higher cord EPA level compared to control group indicating an accumulation in umbilical cord.

Alpha linolenic acid and oleic acid additively down-regulate malignant potential and positively cross-regulate AMPK/S6 axis in OE19 and OE33 esophageal cancer cells.

OBJECTIVE: Both oleic acid (OA) and alpha-linolenic acid (ALA) have been proposed to down-regulate cell proliferation of prostate, breast, and bladder cancer cells. However, direct evidence that OA and/or ALA suppresses to the development of esophageal cancer has not been studied. Also, no previous studies have evaluated how OA and/or ALA regulates malignant potential (cell proliferation, migration, colony formation and adhesion) and intracellular signaling pathways, and whether their effects might be synergistic and/or additive in esophageal cancer cells has not yet been elucidated. MATERIALS/METHODS: We conducted in vitro studies and evaluated whether OA and ALA alone or in combination may regulate malignant potential in OE19 and OE33 esophageal cancer cell lines. RESULTS: Both OA and ALA significantly down-regulated cell proliferation, adhesion and/or migration. OA and/or ALA did not change the number of colonies but decrease colony sizes when compared to control. Also, we observed that OA and/or ALA positively cross-regulates the expression levels of AMPK/S6 axis. Moreover, OA and ALA up-regulated tumor suppressor genes (p53, p21, and p27) and these effects are abolished by AMPK siRNA administration. Importantly, we observed that these effects are additively regulated by OA and ALA in combination when compared to control in OE19 and OE33 esophageal cancer cell lines. CONCLUSIONS: Our novel mechanistic studies provide evidence for an important role for OA and ALA in esophageal cancer, and suggest that OA and/or ALA might be useful agents in the management or chemoprevention of esophageal cancer.

The effect of Irisin on antioxidant system in liver.

Nonalcoholic fatty liver disease (NAFLD) is a global health problem and lead to subacute liver failure, cirrhosis and/or hepatocellular carcinoma. An increased generation of reactive oxygen species (ROS) and antioxidant depletion is found in the liver of obese patients with NAFLD. Irisin is a recently identified exercise-induced myokine. It increases total energy consumption, reduces body weight, and insulin resistance. It was shown that irisin levels were significantly lower in patients with NAFLD. The aim of the present study was to investigate the effect of irisin on prooxidant-antioxidant balance in liver. In the first phase; AML12 liver cells were divided into 4 groups: control, hydrogen peroxide (H2O2)-treated, 10nM irisin-treated and 50nM irisin-treated groups. ROS accumulation in these groups was analyzed by FACS. In the second phase; to see if there is any protective role of irisin on ROS production in the liver, AML12 liver cells were divided into 4 groups: control, H2O2 -treated, H2O2+10nM irisin-treated and H2O2+50nM-irisin treated groups. After measuring ROS accumulation again in these groups, the levels of enzymes related with prooxidant-antioxidant balance via oxidative stress in liver were measured by western blotting. In H2O2 treatment groups, ROS production was increased in AML12 liver cells, on the other hand in irisin treatment groups ROS production was slightly changed. Irisin might be a potential target for metabolic diseases like NAFLD.

Resveratrol: French paradox revisited.

Resveratrol is a polyphenol that plays a potentially important role in many disorders and has been studied in different diseases. The research on this chemical started through the "French paradox," which describes improved cardiovascular outcomes despite a high-fat diet in French people. Since then, resveratrol has been broadly studied and shown to have antioxidant, anti-inflammatory, anti-proliferative, and anti-angiogenic effects, with those on oxidative stress possibly being most important and underlying some of the others, but many signaling pathways are among the molecular targets of resveratrol. In concert they may be beneficial in many disorders, particularly in diseases where oxidative stress plays an important role. The main focus of this review will be the pathways affected by resveratrol. Based on these mechanistic considerations, the involvement of resveratrol especially in cardiovascular diseases, cancer, neurodegenerative diseases, and possibly in longevity will be is addressed.

Cellular protection and therapeutic potential of tocotrienols.

Tocotrienols, components belonging to vitamin E members, are used as potent therapeutics in the treatment of several diseases. Recent studies suggested tocotrienol to have better activity in many situations compared to tocopherols. Tocotrienols have been shown to lower the atherogenic apolipoprotein B and lipoprotein plasma levels. Additionally, tocotrienols with their anti-tumor effect together with anti-angiogenic and anti-thrombotic effects may serve as effective agents in cancer therapy. Besides these effects, some properties such as water insolubility and low stability limit the usage of tocotrienols in the clinic. However recent studies tried to increase the bioavailability with esterification and combination use. These efforts for the clinical usage of tocotrienols which may help them to take a wide place in the clinic and additional studies are needed to identify their therapeutical mechanisms.

Effects of short-term streptozotocin-induced diabetes and vitamin C on platelet non-enzymatic glycation.

Diabetes mellitus is one of the most prevalent metabolic syndromes worldwide. Glycation, a chemical modification of proteins with reducing sugars, indicates a possible explanation for the association between hyperglycemia and the wide variety of tissue pathologies. Non-enzymatic glycation (NEG) of platelet proteins is one of the key mechanisms in the pathogenesis of diabetic complications and may be significant in diabetic atherothrombosis. The aim of this study was to investigate the effects of streptozotocin (STZ)-induced short-term experimental diabetes on the glycation of platelets and to find out if vitamin C affected this glycation. A total of 40 male Wistar albino rats, 200-250 g, were randomly divided into 4 groups (2 diabetic and 2 control groups). The diabetic groups were made diabetic by intraperitoneal injection of STZ (65 mg/kg, citrate buffer pH 4.5). By daily intraperitoneal injection, 80 mg/kg vitamin C (Roche, Turkey) was administered until the end of the experiment. Blood glucose levels of the diabetic groups were significantly higher than those at day 0 and also higher than those of the non-diabetic control groups. The changes in total protein, NEG and vitamin C levels were not statistically significant. Although the differences among the groups were not statistically significant, vitamin C administration increased NEG levels in the diabetic group. The results of this study demonstrate that 8 days of STZ-induced short-term diabetes did not cause a significant increase in NEG of platelets. However, the effect of vitamin C on platelet NEG needs to be further investigated.

Interferon-gamma knockout fails to confer protection against obliteration in heterotopic murine tracheal allografts.

BACKGROUND: Interferon-gamma, produced by T-helper cells, activates macrophages and increases expression of major histocompatibility complex (MHC) products in acute and chronic rejection. We investigated the role of interferon-gamma in murine heterotopic tracheal allografts. METHODS: Tracheas from BALB/c mice were heterotopically transplanted to BALB/c (12 isografts: 2 weeks [n = 6] and 4 weeks [n = 6], C57BL/6 (12 allografts: 2 weeks [n = 6] and 4 weeks [n = 6]) and C57BL/6 interferon-gamma knockout mice (12 interferon-gamma knockout allografts: 2 weeks [n = 4] and 4 weeks [n = 8]). BALB/c interferon-gamma knockout tracheas were transplanted to C57BL/6 mice (reverse knockout: 4 weeks [n = 6]) and BALB/c interferon-gamma knockout mice (4 weeks [n = 2]). C57BL/6 tracheas were transplanted to Bm12 mice (MHC Class II mismatch allografts: 4 weeks [n = 6]). Conventional histology and immunohistochemistry for CD4, CD8 and CD11b were performed. RESULTS: Minimal (<20%) obliteration was seen at 2 weeks in the allograft groups. No obliteration was seen in the isograft groups. However, all allografts were completely obliterated at 4 weeks. Interferon-gamma knockout allograft combinations displayed severe rejection characterized by intense intra- and extraluminal infiltration by CD4-, CD8- and CD11b-labeled cells. The MHC Class II mismatch allograft group showed normal epithelium and mild sub-epithelial infiltration by CD4+ cells at 4 weeks (CD8-, CD11b-). CONCLUSIONS: Absence of interferon-gamma does not protect the allograft from obliteration. Epithelial destruction by cytotoxic T cells appears to be an important mechanism in the development of obliteration in murine heterotopic tracheal allografts.

Tumor necrosis factor receptor -1 and -2 double deficiency reduces graft arterial disease in murine cardiac allografts.

Graft arterial disease (GAD) remains the leading cause of long-term solid organ allograft failure. Tumor necrosis factor (TNF) promotes multiple aspects of allograft rejection via binding to type 1 (p55) and type 2 (p75) receptors. We used TNF type 1 receptor deficient (TNFR1KO), type 2 receptor deficient (TNFR2KO) and receptor double-deficient (TNFRDKO) mice to assess the relative roles of TNFR in acute rejection and GAD. Heterotopic cardiac transplantation was performed between C57BL/6 (B/6) and Balb/c (B/c) mice (total allomismatches) to assess the effects on graft survival; B/6 and Bm12 mice (class II mismatches) were used to assess the effects on GAD 8 weeks after transplantation. We found that graft survival in the total allomismatch combinations was the same regardless of TNFR status. In class II mismatches, wild-type (WT) combinations showed severe GAD, and GAD was not diminished when WT hearts were transplanted into TNFRDKO hosts. TNFR1KO donors or TNFR2KO donors had GAD comparable to WT donors, however, GAD was significantly diminished in B/6 TNFRDKO donor hearts. We conclude that both p55 and p75 signals on donor vascular wall cells are involved in the development of GAD, and either TNFR is capable of mediating a response that will culminate in GAD.