A Human Model of Small Fiber Neuropathy to Study Wound Healing

The aim of this study was to develop a human model of acute wound healing that isolated the effects of small fiber neuropathy on the healing process. Twenty-five healthy subjects had the transient receptor vanilloid 1 agonist capsaicin and placebo creams topically applied to contralateral areas on the skin of the thigh for 48 hours. Subjects had shallow (1.2 millimeter) and deep (>3 millimeter) punch skin biopsies from each thigh on days 1 and 14. Biopsy wound healing was monitored photographically until closure. Intra-epidermal and sweat-gland nerve fiber densities were measured for each biopsy. Shallow wounds in capsaicin-treated sites healed more slowly than in placebo treated skin with biopsies taken on day 1 (P<0.001) and day 14 (P<0.001). Deep biopsies in the capsaicin and placebo areas healed at similar rates at both time points. Nerve fiber densities were reduced only in capsaicin treated regions (P<0.01). In conclusion, topical application of capsaicin causes a small fiber neuropathy and is associated with a delay in healing of shallow, but not deep wounds. This novel human model may prove valuable in the study of wound healing in patients with neuropathy.     

Comparison of the clinical effect of DHS and PFNA on senile osteoporotic fracture and their significance of changes in BALP expression level

Objective:To investigate the clinical effects of dynamic hip screw (DHS) and proximal femoral nail anti-rotation (PFNA) on senile osteoporosis patients and their effects on the expression level of bone-specific alkaline phosphatase (BALP).Methods:116 elderly patients with osteoporotic fracture were divided into DHS group (n=67) and PFNA group (n=49). BALP values were measured by ELISA before operation and 30 days after operation.Results:The operation time, the bleeding volume, and the weight-bearing time of PFNA group was shorter than DHS group (p<0.05); the dominant blood loss and occult blood loss in PFNA group were less than those in DHS group (p<0.05); the healing time and detumescence time, the complications of PFNA group was fewer than the DHS group (p<0.05). The ten-meter walking speed and the five sitting tests in PFNA group were shorter than that in DHS group (p<0.05); the excellent and good rate and Harris score in PFNA group were higher than those in DHS group (p<0.05). The expression of BALP in PFNA group was lower than that in DHS group (p<0.05).Conclusion:PFNA surgery has less trauma, fewer complications, more optimistic postoperative healing and recovery degree, and is more conducive to the reduction of BALP expression level.     

Evaluation of Electrical Impedance as a Biomarker of Myostatin Inhibition in Wild Type and Muscular Dystrophy Mice

ObjectivesNon-invasive and effort independent biomarkers are needed to better assess the effects of drug therapy on healthy muscle and that affected by muscular dystrophy (mdx). Here we evaluated the use of multi-frequency electrical impedance for this purpose with comparison to force and histological parameters.MethodsEight wild-type (wt) and 10 mdx mice were treated weekly with RAP-031 activin type IIB receptor at a dose of 10 mg kg⁻¹ twice weekly for 16 weeks; the investigators were blinded to treatment and disease status. At the completion of treatment, impedance measurements, in situ force measurements, and histology analyses were performed.ResultsAs compared to untreated animals, RAP-031 wt and mdx treated mice had greater body mass (18% and 17%, p < 0.001 respectively) and muscle mass (25% p < 0.05 and 22% p < 0.001, respectively). The Cole impedance parameters in treated wt mice, showed a 24% lower central frequency (p < 0.05) and 19% higher resistance ratio (p < 0.05); no significant differences were observed in the mdx mice. These differences were consistent with those seen in maximum isometric force, which was greater in the wt animals (p < 0.05 at > 70 Hz), but not in the mdx animals. In contrast, maximum force normalized by muscle mass was unchanged in the wt animals and lower in the mdx animals by 21% (p < 0.01). Similarly, myofiber size was only non-significantly higher in treated versus untreated animals (8% p = 0.44 and 12% p = 0.31 for wt and mdx animals, respectively).ConclusionsOur findings demonstrate electrical impedance of muscle reproduce the functional and histological changes associated with myostatin pathway inhibition and do not reflect differences in muscle size or volume. This technique deserves further study in both animal and human therapeutic trials.     

Phytochemical Profiles and Antioxidant Activities in Six Species of Ramie Leaves

Increased consumption of vegetables or plant food has been associated with decreased risk of developing major chronic diseases, such as cancers, diabetes, cardiovascular diseases, and age-related functional decline. Ramie leaves are rich in phenolics and flavonoids, which have been suggested for human health benefits. Phenolic contents, flavonoid contents, phenolic compounds, and anti-cancer properties in six species of ramie leaves were analyzed by Folin-reagent method, sodium borohydride/chloranil-based assay (SBC), HPLC method and antiproliferation, cytoxicity, respectively. Antioxidant activities were measured through peroxyl radical scavenging capacity (PSC) method, oxygen radical absorbance capacity (ORAC) method, and cellular antioxidant activity (CAA). Research indicated that Boehmeria penduliflora contained the highest total phenolic content (2313.7±27.28 mg GAE/100 g FW), and flavonoid content (1682.4±27.70 mg CAE/100 g FW). Boehmeria tricuspis showed the highest PSC value (9574.8±117.63 µM vit. C equiv./100 g FW), while Boehmeria penduliflora indicated the highest ORAC value (330.44±16.88 µmol Trolox equiv./g FW). The antioxidant activities were correlated with phenolic contents and flavonoid contents. Boehmeria tricuspis had the highest antiproliferative capacity with the lowest EC₅₀ (4.11±0.19 mg/mL). The results for the analyzed ramie for CAA were significantly different from each other (p<0.05), Boehmeria tricuspis had the highest CAA value (133.63±7.10 µmol QE/100 g). Benzoic acid, 4-coumaric acid, caffeic acid, and ferulic acid were the dominant phenolic ingredients in the ramie leaves according to HPLC analysis. Our research is the first report to study the phytochemical profiles and antioxidant activities in different species of ramie leaves for their health benefit.     

Phytochemical screening and anti-oxidant activity of Sargassum wightii enhances the anti-bacterial activity against Pseudomonas aeruginosa

In this study, the phytochemical, phenolic, flavonoid and bioactive compounds were successfully screened from crude extract of Sargassum wightii by LC-MS analysis after NIST interpretation. Bacterial growth inhibition study result was shown with 24 mm zone inhibition at 200 µg/mL concentration against P. aeruginosa. The increased phenolic content was much closed to gallic acid and the range was observed at 250 μg/mL concentration. In addition, flavonoid contents of the algae extract was indicated more significant with rutin at 200 μg/mL. In result, both the phenolic and flavonoid contents of the extract were more correlated with gallic acid and rutin. Further, the total anti-oxidant and DPPH radical scavenging activities were shown increased activity at 200 μg/mL concentrations. Furthermore, the excellent anti-bacterial alteration result was observed at 200 μg/mL concentration by minimum inhibition concentration. Therefore, the result was revealed that the marine algae Sargassum wightii has excellent phytochemical and anti-oxidant activities, and it has improved anti-bacterial activity against P. aeruginosa.     

Acute Stress Reduces Wound-Induced Activation of Microbicidal Potential of Ex Vivo Isolated Human Monocyte-Derived Macrophages

Background

Psychological stress delays wound healing but the precise underlying mechanisms are unclear. Macrophages play an important role in wound healing, in particular by killing microbes. We hypothesized that (a) acute psychological stress reduces wound-induced activation of microbicidal potential of human monocyte-derived macrophages (HMDM), and (b) that these reductions are modulated by stress hormone release.

Methods

Fourty-one healthy men (mean age 35±13 years) were randomly assigned to either a stress or stress-control group. While the stress group underwent a standardized short-term psychological stress task after catheter-induced wound infliction, stress-controls did not. Catheter insertion was controlled. Assessing the microbicidal potential, we investigated PMA-activated superoxide anion production by HMDM immediately before and 1, 10 and 60 min after stress/rest. Moreover, plasma norepinephrine and epinephrine and salivary cortisol were repeatedly measured. In subsequent in vitro studies, whole blood was incubated with norepinephrine in the presence or absence of phentolamine (norepinephrine blocker) before assessing HMDM microbicidal potential.

Results

Compared with stress-controls, HMDM of the stressed subjects displayed decreased superoxide anion-responses after stress (p’s <.05). Higher plasma norepinephrine levels statistically mediated lower amounts of superoxide anion-responses (indirect effect 95% CI: 4.14–44.72). Norepinephrine-treated HMDM showed reduced superoxide anion-production (p<.001). This effect was blocked by prior incubation with phentolamine.

Conclusions

Our results suggest that acute psychological stress reduces wound-induced activation of microbicidal potential of HMDM and that this reduction is mediated by norepinephrine. This might have implications for stress-induced impairment in wound healing.     

Overexpression of heat shock protein 70 inhibits epithelial-mesenchymal transition and cell migration induced by transforming growth factor-β in A549 cells

Heat shock protein 70 (HSP70) is a key member of the HSP family that contributes to a pre-cancerous environment; however, its role in lung cancer remains poorly understood. The present study used geranylgeranylacetone (GGA) to induce HSP70 expression, and transforming growth factor-β (TGF-β) was used to construct an epithelial-mesenchymal transition (EMT) model by stimulating A549 cells in vitro. Western Blot was performed to detect protein levels of NADPH oxidase 4 (NOX4) and the EMT-associated proteins E-cadherin and vimentin both before and after HSP70 expression. Cell morphological changes were observed, and the effect of HSP70 on cell migration ability was detected via the wound healing. The results demonstrated that GGA at 50 and 200 μmol/L could significantly induce HSP70 expression in A549 cells (P < 0.05). Furthermore, HSP70 induced by 200 μmol/L GGA significantly inhibited the changes of E-cadherin, vimentin, and cell morphology induced by TGF-β (P < 0.05), while HSP70 induced by 50 μmol/L GGA did not. The results of the wound healing assay indicated that 200 μmol/L GGA significantly inhibited A549 cell migration induced by TGF-β. Taken together, the results of the present study demonstrated that overexpression of HSP70 inhibited the TGF-β induced EMT process and changed the cell morphology and migratory ability induced by TGF-β in A549 cells.     

Differential effects of Oroxylum indicum bark extracts: antioxidant, antimicrobial, cytotoxic and apoptotic study

Stem bark of Oroxylum indicum (L) (SBOI) is used by ethnic communities of North East India as health tonic and in treating diseases of humans and animals. The objective of this research was to carry out a detailed investigation including total phenolic and flavonoid content, antioxidant, antimicrobial, cytotoxic and apoptotic activities of different solvent extracts of SBOI and to establish correlation between some parameters. Among petroleum ether (PE), dichloromethane and methanol (MeOH) extract of SBOI, MeOH extract contained the highest amount of total phenolic (320.7 ± 34.6 mg Gallic acid equivalent/g extract) and flavonoid (346.6 ± 15.2 mg Quercetin equivalent/g extract) content. In vitro antioxidant activity (IC₅₀ 22.7 μg/ml) was highest in MeOH extract (p > 0.05) and also a significant inverse correlation was observed between phenolic (r = 0.886)/flavonoid (r = 0.764) content and corresponding DPPH IC₅₀. Only MeOH extract inhibited both bacteria and fungi. Although, individual extract showed cytotoxicity on HeLa cells with characteristic features of apoptosis, PE extract caused maximum cytotoxicity (IC₅₀ of 112.3 μg/ml, p < 0.05) and apoptotic activity (33.2 % sub-G0/G1 population) on HeLa cells. But, there was a significant non-inverse correlation of the MTT IC₅₀ with total phenolic (r = 0.812, p < 0.05)/flavonoid (r = 0.998, p < 0.05) content in the three solvent extracts. TLC analysis showed three unique compounds in PE extract which may have a role in apoptosis mediated cytotoxicity. These results called for futher chemical characterisation of MeOH and PE extract of SBOI for specific bioactivity.     

Clinicopathological Characteristics of Gynecological Cancer Associated with Hypoxia-Inducible Factor 1α Expression: A Meta-Analysis Including 6,612 Subjects

BackgroundGynecological cancer is characterized by tumor hypoxia. However, the role of hypoxia-inducible factor 1α (HIF-1α) in gynecological cancer remains unclear.MethodElectronic databases including Cochrane Library, PUBMED, Web of Knowledge and clinical trial registries were searched from inception through October 2014 for published, case-control studies assessing the association between HIF-1α and the clinicopathological characteristics of gynecological cancer. We pooled results from 59 studies using fixed or random-effects models and present results as odds ratios (ORs) following the PRISMA guidelines.ResultsOur meta-analysis, which included 6,612 women, demonstrated that the expression of HIF-1α was associated with the clinicopathological characteristics of gynecological cancer. The expression of HIF-1α in cancer or borderline tissue was significantly higher than that in normal tissue (cancer vs. normal: odds ratio (OR) =9.59, 95% confidence interval (CI): 5.97, 15.39, p<0.00001; borderline vs. normal: OR=4.13, 95% (CI): 2.43, 7.02, p<0.00001; cancer vs. borderline: OR=2.70, 95% (CI): 1.69, 4.31, p<0.0001). The expression of HIF-1α in III‒IV stage or lymph node metastasis was significantly higher than that in I‒II stage or that without lymph node metastasis, respectively (OR=2.66, 95% (CI): 1.87,3.79, p<0.00001; OR= 3.98, 95% (CI): 2.10,12.89, p<0.0001). HIF-1α was associated with histological grade of cancer (Grade 3 vs. Grade 1: OR=3.77, 95% (CI): 2.76,5.16, p<0.00001; Grade 3 vs. Grade 2: OR=1.62, 95% (CI): 1.20,2.19, p=0.002; Grade 2 vs. Grade 1: OR=2.34, 95% (CI): 1.82,3.00, p<0.00001),5-years disease free survival (DFS) rates (OR=2.93, 95% (CI):1.43,6.01, p=0.001) and 5-years overall survival (OS) rates (OR=5.53, 95% (CI): 2.48,12.31, p<0.0001).ConclusionHIF-1α is associated with the malignant degree, FIGO stage, histological grade, lymph node metastasis, 5-years survival rate and recurrence rate of gynecological cancer. It may play an important role in clinical treatment and prognostic evaluation.     

Clinical and Prognostic Significance of Preoperative Plasma Fibrinogen Levels in Patients with Operable Breast Cancer

Purpose

Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in different cancer patients. The objective of this study was to investigate the clinical and prognostic value of preoperative plasma fibrinogen levels in patients with operable breast cancer.

Methods

Two hundred and twenty-three patients diagnosed with breast cancer were retrospectively evaluated in this study. Plasma fibrinogen levels were examined before treatment and analyzed along with patient clinicopathological parameters, disease-free survival (DFS) and overall survival(OS). Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with DFS and OS.

Results

Elevated preoperative plasma fibrinogen levels were directly associated with age of diagnose (≤47 vs. >47, p<0.001), menopause (yes vs. no, p<0.001), tumor size (T1&T2 vs.T3&T4, p = 0.033), tumor stage (Ⅰvs.Ⅱvs.Ⅲ, p = 0.034) and lymph node involvement (N = 0 vs. 1≤N≤3 vs. N≥4, p<0.001), but not with histological grade, molecular type and other Immunohistochemical parameters(ER, PR, HER2 and Ki-67). In a univariate survival analysis, tumor stage, tumor size, lymph node involvement (p<0.001/ p<0.001)and plasma fibrinogen (p<0.001/ p<0.001) levels were associated with disease-free and overall survival, but just lymph nodes involvement (p<0.001, hazard ratio [HR] = 2.9, 95% confidence interval [CI] = 1.6–5.3/ p = 0.006, HR = 3.2, 95% CI = 1.4–7.3) and plasma fibrinogen levels (p = 0.006, HR = 3.4, 95% CI = 1.4–8.3/ p = 0.002, HR = 10.1, 95% CI = 2.3–44.6) were associated with disease-free and overall survival in a multivariate survival analysis, respectively.

Conclusions

This study demonstrates that elevated preoperative plasma fibrinogen levels are associated with breast cancer progression and are independently associated with a poor prognosis in patients with operable breast cancer.     

Role for Heat Shock Protein 90α in the Proliferation and Migration of HaCaT Cells and in the Deep Second-Degree Burn Wound Healing in Mice

Inflammation, proliferation, and tissue remodeling are essential steps for wound healing. The hypoxic wound microenvironment promotes cell migration through a hypoxia—heat shock protein 90 alpha (Hsp90α)—low density lipoprotein receptor-related protein-1 (LRP-1) autocrine loop. To elucidate the role of this autocrine loop on burn wound healing, we investigated the expression profile of Hsp90α at the edge of burn wounds and found a transient increase in both mRNA and protein levels. Experiments performed with a human keratinocyte cell line—HaCaT also confirmed above results. 17-dimethylaminoethylamino-17demethoxygeldanamycin hydrochloride (17-DMAG), an Hsp90α inhibitor, was used to further evaluate the function of Hsp90α in wound healing. Consistently, topical application of Hsp90α in the early stage of deep second-degree burn wounds led to reduced inflammation and increased tissue granulation, with a concomitant reduction in the size of the wound at each time point tested (p<0.05). Consequently, epidermal cells at the wound margin progressed more rapidly causing an expedited healing process. In conclusion, these results provided a rationale for the therapeutic effect of Hsp90α on the burn wound management.     

Attenuation of methylglyoxal-induced glycation and cellular dysfunction in wound healing by Centella cordifolia

Current pre-clinical evidences of Centella focus on its pharmacological effects on normal wound healing but there are limited studies on the bioactivity of Centella in cellular dysfunction associated with diabetic wounds. Hence we planned to examine the potential of Centella cordifolia in inhibiting methylglyoxal (MGO)-induced extracellular matrix (ECM) glycation and promoting the related cellular functions. A Cell-ECM adhesion assay examined the ECM glycation induced by MGO. Different cell types that contribute to the healing process (fibroblasts, keratinocytes and endothelial cells) were evaluated for their ability to adhere to the glycated ECM. Methanolic extract of Centella species was prepared and partitioned to yield different solvent fractions which were further analysed by high performance liquid chromatography equipped with photodiode array detector (HPLC-PDA) method. Based on the antioxidant [2,2-diphenyl-1-picrylhydrazyl (DPPH) assay] screening, anti-glycation activity and total phenolic content (TPC) of the different Centella species and fractions, the ethyl acetate fraction of C. cordifolia was selected for further investigating its ability to inhibit MGO-induced ECM glycation and promote cellular distribution and adhesion. Out of the three Centella species (C. asiatica, C. cordifolia and C. erecta), the methanolic extract of C. cordifolia showed maximum inhibition of Advanced glycation end products (AGE) fluorescence (20.20 ± 4.69 %, 25.00 ± 3.58 % and 16.18 ± 1.40 %, respectively). Its ethyl acetate fraction was enriched with phenolic compounds (3.91 ± 0.12 mg CAE/μg fraction) and showed strong antioxidant (59.95 ± 7.18 μM TE/μg fraction) and antiglycation activities. Improvement of cells spreading and adhesion of endothelial cells, fibroblasts and keratinocytes was observed for ethyl acetate treated MGO-glycated extracellular matrix. Significant reduction in attachment capacity of EA.hy926 cells seeded on MGO-glycated fibronectin (41.2%) and attachment reduction of NIH3t3 and HaCaT cells seeded on MGO-glycated collagen (33.7% and 24.1%, respectively) were observed. Our findings demonstrate that ethyl acetate fraction of C. cordifolia was effective in attenuating MGO-induced glycation and cellular dysfunction in the in-vitro wound healing models suggesting that C. cordifolia could be a potential candidate for diabetic wound healing. It could be subjected for further isolation of new phytoconstituents having potential diabetic wound healing properties.     

Grape Seed Extract Dose-Responsively Decreases Disease Severity in a Rat Model of Mucositis; Concomitantly Enhancing Chemotherapeutic Effectiveness in Colon Cancer Cells

Objective

Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the effects of increasing grape seed extract doses on the severity of chemotherapy in a rat model and its coincident impact on chemotherapeutic effectiveness in colon cancer cells.

Design

Female Dark Agouti rats were gavaged with grape seed extract (400–1000 mg/kg) or water (day 3–11) and were injected intraperitoneally with 5-Fluorouracil (150 mg/kg) or saline (control) on day 9 to induce mucositis. Daily metabolic data were collected and rats were sacrificed on day 12. Intestinal tissues were collected for histological and myeloperoxidase analyses. Caco-2 cell viability was examined in response to grape seed extract in combination with 5-Fluorouracil by 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide) assay.

Results

Compared with 5-Fluorouracil controls, grape seed extract (400–1000 mg/kg) significantly decreased the histological damage score (P<0.05) in the jejunum. Grape seed extract (1000 mg/kg) increased jejunal crypt depth by 25% (P<0.05) in 5-Fluorouracil treated rats compared to 5-Fluorouracil controls, and attenuated the 5-Fluorouracil -induced reduction of mucosal thickness (25%, P<0.05). Grape seed extract (600 mg/kg) decreased myeloperoxidase activity by 55% (P<0.01) compared to 5-Fluorouracil controls. Grape seed extract was more effective at ameliorating 5-Fluorouracil induced intestinal injury, with effects most pronounced in the proximal jejunum. Grape seed extract (10–25 ug/mL) significantly enhanced the growth-inhibitory effects of 5-Fluorouracil by 26% (P<0.05) in Caco-2 cells and was more potent than 5-Fluorouracil at 50–100 µg/mL.

Conclusion

Grape seed extract may represent a new therapeutic option to decrease the symptoms of intestinal mucositis while concurrently impacting on the viability of colon cancer cells.     

Effects of Prunella vulgaris on the Mice Immune Function

The present study was designed to evaluate the effects of Prunella Vulgaris (P. vulgaris) on the immune function in mice. The mice were randomly divided into one control group and three treatment groups of 10 mice each. The control group received pure water and the treatment groups received P. vulgaris extract at concentrations of 0.15, 0.30 and 0.90 g/kg BW orally for 30 days, respectively. Changes in cell immune function, non-specific immunity and humoral immunity function were evaluated. Active lymphocytes and T lymphocyte subsets were determined by fluorescence-activated cell sorting (FACS). Certain Serum concentrations of cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that, for cell immune function, compared with the control group, foot pad thickness in high dose group increased significantly (p<0.01), whereas no significant difference in the proliferative ability of splenic lymphocytes was observed among all groups (p>0.05). For non-specific immunity, NK cell activity increased significantly in a dose-dependent manner in P. vulgaris treated mice (p<0.01), mononuclear-macrophage function in medium and high dose P. vulgaris treated mice were significantly higher than that of the control group (p<0.05). For humoral immunity, no significant differences were observed in terms of the half value of hemolysis (HC50), number of hemolytic plaques and serum IgG level (p>0.05). The percentage of active T and Th lymphocytes of mice peripheral blood in high dose group were significantly higher than that of the control group (p<0.01). There was no significant difference in serum levels of IL-1β, IL-4, IL-10 and IFN-γ among all of the four groups (p>0.05). The data indicated that 0.90 g/kg BW P. vulgaris extract (equivalent to 7.5 g/kg BW crude drug) had some effect on cellular immune function and non-specific immune function in mice.     

Regulation of Wound Healing by Granulocyte-Macrophage Colony-Stimulating Factor after Vocal Fold Injury

Objectives

Vocal fold (VF) scarring remains a therapeutic challenge. Granulocyte-macrophage colony-stimulating factor (GM-CSF) facilitates epithelial wound healing, and recently, growth factor therapy has been applied to promote tissue repair. This study was undertaken to investigate the effect of GM-CSF on VF wound healing in vivo and in vitro.

Methods

VF scarring was induced in New Zealand white rabbits by direct injury. Immediately thereafter, either GM-CSF or PBS was injected into the VFs of rabbits. Endoscopic, histopathological, immunohistochemical, and biomechanical evaluations of VFs were performed at 3 months post-injury. Human vocal fold fibroblasts (hVFFs) were cultured with GM-CSF. Production of type I and III collagen was examined immunocytochemically, and the synthesis of elastin and hyaluronic acids was evaluated by ELISA. The mRNA levels of genes related to ECM components and ECM production-related growth factors, such as HGF and TGF-ß1, were examined by real time RT-PCR.

Results

The GM-CSF-treated VFs showed reduced collagen deposition in comparison to the PBS-injected controls (P<0.05). Immunohistochemical staining revealed lower amounts of type I collagen and fibronectin in the GM-CSF-treated VFs (P<0.05 and P<0.01, respectively). Viscous and elastic shear moduli of VF samples were significantly lower in the GM-CSF group than in the PBS-injected group (P<0.001 and P<0.01, respectively). Mucosal waves in the GM-CSF group showed significant improvement when compared to the PBS group (P = 0.0446). GM-CSF inhibited TGF-β1-induced collagen synthesis by hVFFs (P<0.05) and the production of hyaluronic acids increased at 72 hours post-treatment (P<0.05). The expressions of HAS-2, tropoelastin, MMP-1, HGF, and c-Met mRNA were significantly increased by GM-CSF, although at different time points (P<0.05).

Conclusion

The present study shows that GM-CSF offers therapeutic potential for the remodeling of VF wounds and the promotion of VF regeneration.     

Inhibition of Pediatric Glioblastoma Tumor Growth by the Anti-Cancer Agent OKN-007 in Orthotopic Mouse Xenografts

Pediatric glioblastomas (pGBM), although rare, are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. Here, we describe the use of conventional and advanced in vivo magnetic resonance imaging (MRI) techniques to assess a novel orthotopic xenograft pGBM mouse (IC-3752GBM patient-derived culture) model, and to monitor the effects of the anti-cancer agent OKN-007 as an inhibitor of pGBM tumor growth. Immunohistochemistry support data is also presented for cell proliferation and tumor growth signaling. OKN-007 was found to significantly decrease tumor volumes (p<0.05) and increase animal survival (p<0.05) in all OKN-007-treated mice compared to untreated animals. In a responsive cohort of treated animals, OKN-007 was able to significantly decrease tumor volumes (p<0.0001), increase survival (p<0.001), and increase diffusion (p<0.01) and perfusion rates (p<0.05). OKN-007 also significantly reduced lipid tumor metabolism in responsive animals [(Lip1.3 and Lip0.9)-to-creatine ratio (p<0.05)], as well as significantly decrease tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Furthermore, in relationship to the PDGFRα pathway, OKN-007 was able to significantly decrease SULF2 (p<0.05) and PDGFR-α (platelet-derived growth factor receptor-α) (p<0.05) immunoexpression, and significantly increase decorin expression (p<0.05) in responsive mice. This study indicates that OKN-007 may be an effective anti-cancer agent for some patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRα pathway, and could be considered as an additional therapy for pediatric brain tumor patients.     

Stress response of biomolecules (carbohydrate,protein and lipid profiles) in fish Channa punctatus inhabiting river polluted by Thermal Power Plant effluent

Qualitative and quantitative assessment of heavy metals in the Thermal Power Plant effluent was performed to study the impact of their toxic effects on various biomarkers (carbohydrate, protein and lipid profiles). Heavy metals present in the water were in the order Fe > Cu > Zn > Mn > Ni > Co > Cr. Fe and Ni exceeded and Cr was equal to the USA standards set by UNEPGEMS. Glycogen in liver (p < 0.001) and muscle (p < 0.01) depleted significantly. Insignificant (p < 0.05) decline in blood glucose (−21.0%) and significant (p < 0.05) elevation in both total protein and globulin in serum, liver and muscle was noted. Albumin decreased significantly (p < 0.01) in serum but showed significant (p < 0.05) increase in liver and muscle. Thus A:G ratio fell in serum and rose in liver and muscle. Similarly lipid profile also gets altered where significant elevation in serum total lipid (p < 0.01), total cholesterol (p < 0.01), phospholipid (p < 0.05), triglycerides (p < 0.001), LDL (p < 0.01) was observed but significant (p < 0.05) decline in VLDL was recorded. These biomarkers suggested that fish become hypoglycemic, hyperlipidemic and hypercholesterolemic. Heavy metals also provoked immune response as evident from the rise in globulin. In conclusion the Thermal Power Plant wastewater containing heavy metals induced stress, making fish weak and vulnerable to diseases.