In-vitro evaluation of dexpanthenol-loaded nanofiber mats for wound healing

Purpose: To prepare a novel dexpanthenol (DEX)-loaded nanofiber mats for wound healing.Methods: A novel bioactive wound dressing formulation with  dexpanthenol was developed by electrospinning method. Poly (lactic-co-glycolic acid), poly (ethylene oxide) and poly (caprolactone) were used as polymers. Morphological features, swelling properties, in-vitro release behavior, and cell viability properties of the formulations were evaluated.Results: Morphological examination of mats confirmed successful formation of the fibers. Swelling of nanofiber mats results was 34.44 ± 1.05, 18.59 ± 2.11, 86.06 ± 3.25 and 44.62 ± 1.75 % for polycaprolactone (PCL), PCL + DEX, poly lactic-co-glycolic acid (PLGA) and PLGA + DEX, respectively, and occurred in a controlled manner. PLGA + DEX formulation has advantage over PCL + DEX and poly (ethylene oxide) (PEO) + DEX due to controlled in-vitro release of DEX. The highest cell viability was afforded by PLGA+DEX formulation.Conclusion: DEX-loaded PLGA nanofiber formulation may be useful as an alternative wound dressing due its suitable mechanical and biological properties.Keywords: Dexpanthenol, Electrospinning, Wound dressing,  Polycaprolactone, Poly lactic-co-glycolic acid, Poly (ethylene oxide

İskemik akut renal yetmezlikte oksidatif/nitrozatif stres ve endoplazmik retikulum (ER) stresinin etkileşimleri ve ER stres yanıt proteini MANF/ARMET'in fonksiyonunun araştırılması

Bu çalışmanın ilk bölümünde insan proksimal tübüler epitelyal (HK-2) hücre hattında iskemik akut böbrek yetmezliği (ABY) modeli oluşturulduktan sonra, hipoksi-reperfüzyon koşullarında oksidatif stres (OS), nitrozatif stres (NS) ve endoplazmik retikulum (ER) stresleri 'time course' deneyleri yapılarak IB tekniği ile incelenmiştir. HK-2 hücrelerinde hipoksi-reperfüzyonun OS, NS ve ER stresine neden olduğu tespit edilmiştir. Normoksi ve hipoksi-reperfüzyon koşullarında elde edilen sonuçlar; OS ve NS artışının iskemik böbrek doku hasarı gelişiminde başlıca etmenler olduğuna ve UPR aktivasyonun OS ve NS'e karşı adaptif bir yanıt olarak geliştiğine işaret etmektedir. İkinci bölümde ise bir ER stresi yanıt proteini olan MANF/ARMET'in normoksi ve hipoksi-reperfüzyon koşullarındaki protein düzeyleri incelenmiş ve olası parakrin etkisi ve hücresel stresler üzerindeki etkisi araştırılmıştır. HK-2 hücrelerinde OS, NS, ER stresi, hipoksi ve hipoksi-reperfüzyon koşullarının MANF/ARMET protein düzeyinde artışa neden olduğu belirlenmiştir. MANF/ARMET over-ekspresyonu ve MANF/ARMET siRNA uygulaması gerçekleştirilen hücrelerde: a) MANF/ARMET düzeyi ile hücre proliferasyon hızı arasında ters bir ilişki olduğu, b) OS, ER stresi ve hipoksi-reperfüzyon hasarına bağlı gelişen hücre ölümünün ve hücre içi stres düzeylerinin MANF/ARMET over-ekspresyonu ile azaldığı, MANF siRNA uygulaması ile arttığı, c) Besiyerine salgılanan MANF/ARMET proteinin OS, NS, ER stresi ve hipoksi-reperfüzyon hasarına bağlı gelişen hücre ölümünü azalttığı tespit edilmiştir. Elde edilen bulgular ile HK-2 hücrelerinde MANF/ARMET'in hem hipoksi-reperfüzyon, hem de OS, NS ve ER stresi ile gelişen hücre hasarına karşı koruyucu etkisinin olabileceği ilk kez bu çalışma ile gösterilmiştir

Development of novel mucoadhesive gels containing nanoparticle for buccal administration of dexamethasone

This study aimed to develop promising and innovative mucoadhesive gel systems containing dexamethasone-loaded nanoparticle to increase the effectiveness of treatment for oral precancerous lesions and to reduce side effects. In this respect, a dexamethasone-loaded nanoparticle formulation was prepared by using emulsification/solvent evaporation method. The nanoparticle has high zeta potential (-10.3±0.5 mV), low particle size (218.42±2.1), low polydispersity index (0.070±0.014) and high encapsulation efficiency (95.018±2.982%). To improve the mucosal retention time, the dexamethasone-loaded nanoparticle was dispersed in mucoadhesive gel using gellan gum. The developed gels offered appropriate pH value, high drug content, suitable mechanical and mucoadhesive performance and appropriate viscosity for mucosal administration. All formulations exhibited plastic flow and typical gel-type mechanical spectra after the determined frequency value. The developed formulations exhibited extended drug release as intended for these systems. Cytotoxicity was tested by MTT assay in human epithelioid carcinoma cell (HeLa) in vitro. The MTT assay showed that the blank formulations were non-toxic to cells. It was observed that the bioactivity of the free dexamethasone was potentiated by mucoadhesive gels containing dexamethasone-loaded nanoparticle in HeLa cells. Results from this study indicate that mucoadhesive gels are effective for the local treatment of precancerous lesions. Our findings showed that the developed formulations were worthy of further studies

Antioxidant and prooxidant properties of selected herbs and Citrus bergamia Risso et Poiteau (bergamot) used for the management of hyperlipidemia

Background and Aims: In recent years, there has been an increased interest in the search for herbs to aid the management of hyperlipidemia. There is currently very little data on the simultaneous evaluation of the antioxidant and prooxidant properties of antihyperlipidemic herbs. This study was designed to evaluate the antioxidant and prooxidant properties of four antihyperlipidemic herbal drugs and also of bergamot. Methods: Antioxidant property was determined by ferric ions (Fe3+) reducing capacity (IRC), DPPH radical scavenging activity (DPPH IC50) and trolox equivalent antioxidant capacity (TEAC); deoxyribose degradation test was used for prooxidant property. Results: The highest total phenolic content (TPC) was in the myrtle leaf (ML)(135.35±3.46 mg GAE/g, p<0.05) whereas the highest total flavonoid content (TFC) was in green tea (GT) (48.76±0.69 mg QE/g, p<0.05) both of which were maintained from a pharmacy. Among the bergamot samples, the highest TPC and TFC values were in filtered fruit juice (BFFJ) as 197.35±6.29 mg GAE/100 mL; and 94.14±1.39 mg QE/100 mL; p<0.05, respectively. GT showed the highest antioxidant capacity in IRC and TEAC assays (2.29±0.12 mM TE/g; and 2.32±0.07 mmol TE/mg, p<0.05). The lowest DPPH IC50 was identified in ML from a pharmacy (6.95±0.08 ?g/mL; p<0.01). BFFJ had the highest IRC (2.94±0.031 mM TE/10?L), TEAC (5.14±0.084 mmol TE/10 ul) and the lowest DPPH IC50 value (10.561±0.17 ?L). GT from a pharmacy and 1mg/mL concentration BFLFJ (filtered and lyophilized) were associated with the lowest hydroxyl radical scavenger activity (0.171±0.013 ?M MDA equivalent, p<0.05 and 0.144±0.015 ?M MDA equivalent, p<0.05). Conclusion: BFLFJ and GT got the highest attention due to high TPC, TFC, antioxidant and low prooxidant properties. Our results highlight the necessity of clarifying the value of bergamot and GT in this field with further studies

Peroxiredoxins and Hypoxia-Inducible Factor-1α in Duodenal Tissue: Emerging Factors in the Pathophysiology of Pediatric Celiac Disease Patients

Celiac disease (CD) is an autoimmune enteropathy. Peroxiredoxins (PRDXs) are powerful antioxidant enzymes having an important role in significant cellular pathways including cell survival, apoptosis, and inflammation. This study aimed at investigating the expression levels of all PRDX isoforms (1–6) and their possible relationships with a transcription factor, HIF-1α, in the small intestinal tissue samples of pediatric CD patients. The study groups consisted of first-diagnosed CD patients (n = 7) and non-CD patients with functional gastrointestinal tract disorders as the controls (n = 7). The PRDXs and HIF-1α expression levels were determined by using real-time PCR and Western blotting in duodenal biopsy samples. It was observed that the mRNA and protein expression levels of PRDX 5 were significantly higher in the CD patients, whereas the PRDX 1, -2, and -4 expressions were decreased in each case compared to the control group. No significant differences were detected in the PRDX 3 and PRDX 6 expressions. The expression of HIF-1α was also significantly elevated in CD patients. These findings indicate, for the first time, that PRDXs, particularly PRDX 5, may play a significant role in the pathogenesis of CD. Furthermore, our results suggest that HIF-1α may upregulate PRDX-5 transcription in the duodenal tissue of CD

Chemical Profile and Cytotoxicity Evaluation of Aerial Parts of Marrubium vulgare L. From Different Locations in Turkey

Marrubium vulgare L. (Lamiaceae) is used for respiratory and gastrointestinal system disorders in folk medicine. According to European Pharmacopoeia criteria, standardization of the plant is defined by its marrubiin content. In present study, phenolics, marrubiin and essential oil compositions of M. vulgare from different locations in Turkey were analyzed quantitatively by UPLC, GC and GC/MS. Besides, their cytotoxic potentials were evaluated.In the samples, forsythoside B (77-400 mg/100 g dw), arenarioside (forsythoside F) (0-241 mg/100 g dw), verbascoside (acteoside) (171-416 mg/100 g dw) and apigenin-7-O-glucoside (0-17 mg/100 g dw) were determined in different ranges. Marrubiin contents (0.58-1.46 %) of some samples were two times higher than European Pharmacopoeia standards (0.7 %). beta-Caryophyllene (7.24-20.34 %), (Z)-beta-farnesene (1.58-34.85 %), germacrene D (9.8-13.37 %), bicyclogermacrene (1.71-8.63 %) and beta-bisabolene (0-16.68 %) were detected as major compounds in essential oils. The sample from the west of Aegean Region showed cytotoxicity against human neuroblastoma (SH-SY5Y) cell lines (IC50: 59.80 mu g/mL) although it has no effect on non-cancerous NIH-3T3cell lines.This is the first report on phenolic profiles of M. vulgare populations from Turkey. Their potential as marrubiin source for pharmaceutical industry should be considered.Acknowledgments The authors thank to Dr. Fulya Aydin-Kandemir who generated the spatial distribution map of the collected M. vulgare samples via GIS software (ArcGIS pro) (Figure 6). This work was supported by TUBITAK (The Scientific and Technological Research Council of Turkey), Turkey (Grant number: 120-S-117).TUBITAK (The Scientific and Technological Research Council of Turkey), Turkey [120-S-117

In vitro cytotoxic properties of six artemisia L. species

Methanolic extracts of Artemisia L. taxons (Artemisia absinthium L., Artemisia arborescens L., Artemisia campestris L., Artemisia scoparia Waldst;amp;Kit, Artemisia santonicum L., Artemisia vulgaris L. and Artemisia arborescens L.) were investigated for their cytotoxic activities against three human cancer cell lines, MCF7, A549, HeLa, and two human normal cell lines, A7R5 and 293T. The cytotoxic activities were analyzed by real-time cell analysis system measuring electrical impedance. Artemisia scoparia Waldst;amp;Kit. showed significant effect on MCF7 ($IC_{50}$: 34 jug/mL) and HeLa (LC50: 90 jug/mL). A. absinthium exhibited selective cytotoxic activity on MCF7 ($IC_{50}$: 270 fig/mL).Bu gahsmada Artemisia L. (Artemisia absinthium L., Artemisia arborescens L., Artemisia campestris L., Artemisia scoparia Waldst;Kit, Artemisia santonicum L., Artemisia vulgaris L. ve Artemisia arborescens L) Mrlerine ait metanollü ekstrelerin üg insan kanserli Mere hattında (MCF7, A549, HeLa) ve iki normal insan Mere hattında (A7R5 and 293T ) sitotoksik aktiviteleri araştinldı. Sitotoksik aktiviteler elektriksel empedans ölgen gergek zamanh Mere analiz sistemi He ölguldü. Sonugta Artemisia scoparia Waldst;Kit ekstresinin MCF7(LC50: 34 jug/mL) ve HeLa ($IC_{50}$: 90 jug/mL) üzerinde oldukga yüksek aktivite gösterdiği saptandı. Ayrıca A.absinthium’un da MCF7($IC_{50}$: 270 fig/mL) üzerinde segici etkisi olduğu gözlendi

İn ovo T3 HormonuEnjeksiyonunun Soğuk Stresine Maruz Kalan Etlik Piliçlerde Performans, Bazı Kan Parametreleri ve Oksidatif Stabilite Üzerine Etkileri

This study was conducted to determine the effects of in ovo injection of T3 hormone on performance, blood lipid profile, ascites and oxidative stability in broilers exposed to cold stress. For this purpose, fertile eggs except control group were injected with 25 ng T3 on the 17th day of incubation. In both groups, half of the chicks were reared under at standart temperatures while the other half was applied low temperature early (20?10 C from 4 to 6 d old) and late (15?10 C from 35 to 37 d old) ages. In ovo T3 injection did not significantly affect broiler performance. At 21 d of age, cold stress treatment decreased body weight and feed intake but did not affect feed conversion ratio. Growth depression due to cold stress might not be compensated until slaughter age. There was no a significant difference in terms of mortality and no deaths from ascites have been observed. At an early age, in ovo T3 injection increased hemotocrit value while cold stress reduced rectal temperature (P0.05). In broilers exposed to cold stress, heart ratio significantly raised. The levels of glucose, triglyceride, cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL) and T3 were not significantly affected by in ovo T3 injection. Cold stress at an early age decreased triglyceride level and increased cholesterol, HDL and LDL concentrations (P0.05). Cold stress at late age only significantly reduced LDL level. In ovo T3 injection and cold stress did not affect malondialdehyde (MDA) and trolox equivalent antioxidant capacity (TEAC) values. In ovo T3 and cold stress treatments did not cause oxidative damage in broilersBu çalışma in ovo T3 hormonu enjeksiyonunun soğuk stresine maruz kalan etlik piliçlerde performans, kan lipid profili, asites oluşumu ve oksidatif stabilite üzerine etkilerini saptamak amacı ile yürütülmüştür. Bu amaçla, kontrol grubu dışındaki döllü yumurtalara kuluçkanın 17. gününde 25 ng T3 enjekte edilmiştir. Her iki grupta, civcivlerin yarısı standart sıcaklıklarda yetiştirilirken diğer yarısına erken (4-6. günler arasında 20?1 0 C) ve geç (35-37. günler arasında 15?1 0 C) yaşlarda düşük sıcaklık uygulanmıştır. İn ovo T3 enjeksiyonu etlik piliçlerin performansını önemli düzeyde etkilememiştir. Soğuk stresi uygulaması 21. günde canlı ağırlığı ve yem tüketimini azaltmış ancak yemden yararlanmayı etkilememiştir. Soğuk stresinden kaynaklanan büyüme performanstaki gerileme kesim yaşına kadar telafi edilememiştir. Ölüm oranı bakımından gruplar arasında önemli bir farklılık oluşmamıştır ve asites kaynaklı ölüm görülmemiştir. Erken yaşlarda, soğuk stresi rektal sıcaklığı azaltırken in ovo T3 enjeksiyonu hematokrit değerini artırmıştır (P0.05). Soğuk stresine maruz kalan piliçlerde kalp oranı önemli düzeyde yükselmiştir. Glukoz, trigliserit, kolesterol, yüksek yoğunluklu lipoprotein (HDL), düşük yoğunluklu lipoprotein (LDL) ve T3 düzeyleri in ovo T3 enjeksiyonundan önemli düzeyde etkilenmemiştir. Erken yaşta soğuk stresi trigliserit düzeyini azaltmış ve kolesterol, HDL ve LDL konsantrasyonlarını arttırmıştır (P0.05). Geç yaşta soğuk stresi sadece LDL düzeyini önemli düzeyde azaltmıştır. İn ovo T3 enjeksiyonu ve soğuk stresi malondialdehit (MDA) ve trolox eşdeğer antioksidan kapasite (TEAK) değerlerini etkilememiştir. İn ovo T3 ve soğuk stresi uygulamaları etlik piliçlerde oksidatif hasara neden olmamıştır