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A composite nanofiber composed of three polymers, namely polyvinyl alcohol/polyvinyl pyrrolidone/polyethylene oxide, is produced. The experiments are constructed using three design of experiment techniques, Taguchi L-9, Taguchi L-27, and Screening method. The experiments are verified using the analysis of variance (ANOVA) method and later a mathematical model is developed using the regression method. The impact of electrospun processing parameters, namely applied voltage, flow rate, and working distance, on nanofibers' diameter is measured. The working distance is a significant factor in controlling the size of the fiber diameter, while the applied voltage has the lowest effect on it. As a result of the regression equation, a Genetic algorithm is used to find the optimum variables for the required fiber diameter, which is 156 nm for flow rate = 0.001 mL h(-1), voltage = 30 kV, and distance = 200 mm with a 3% difference from the experimental fiber diameter.

Wound dressings made from natural polymers are an important aspect of biomaterials. Protein-based materials are less likely to instigate an immunogenic response and have the capacity to degrade in vivo, also without triggering an inflammatory response. Therefore, gelatin (GEL) was chosen and combined with bacterial cellulose (BC) to produce nanofibres and the potential of an all-natural polymer construct was determined. GEL and BC were successfully electrospun with metformin (Met) and glybenclamide (Gb) using a portable, point of need electrospinning set up. The virgin fibre group exhibited a significant effect on the proliferation of L929 (mouse fibroblast) cells but all fibre samples can safely be applied on wound site without risk of cytotoxicity. According to the results obtained by animal tests, the GEL-BC-Gb group showed better recovery than the GEL-BC-Met group. Diabetic wounds treated with GEL-BC-Met were characterized by moderate re-epithelialization and partially organized granulation tissue. Moderate to complete re-epithelialization and well-formed granulation tissue were observed in diabetic wounds treated with GEL-BC-Gb. The histologic scores obtained on day 14 confirmed that the GEL-BC-Gb group played a stronger wound-healing role compared to the GEL-BC-Met group. The highest decrease of TNF-alpha level was observed in the GEL-BC-Gb group at the end of the experiment but there is no significant difference between drug-loaded fibre groups. Therefore, topical administration of ma and Gb in a sustained release form has a high potential for diabetic wound healing with high bioavailability and fewer systemic side effects but Gb showed better improvement according to the results of the animal tests.

Progesterone-loaded poly(lactic) acid fibrous polymeric patches were produced using electrospinning and pressurized gyration for infra-vaginal application to prevent preterm birth. The patches were intravaginally inserted into rats in the final week of their pregnancy, equivalent to the third trimester of human pregnancy. Maintenance tocolysis with progesterone-loaded patches was elucidated by recording the contractile response of uterine smooth muscle to noradrenaline in pregnant rats. Both progesterone-loaded patches indicated similar results from release and thermal studies, however, patches obtained by electrospinning had smaller average diameters and more uniform dispersion compared to pressurized gyration. Patches obtained by pressurized gyration had better results in production yield and tensile strength than electrospinning; thereby pressurized gyration is better suited for scaled-up production. The patches did not affect cell attachment, viability, and proliferation on Vero cells negatively. Consequently, progesterone-loaded patches are a novel and successful treatment strategy for preventing preterm birth.

In order to provide more effective treatment strategies for the rapid healing of diabetic wounds, novel therapeutic approaches need to be developed. The therapeutic potential of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone hydrochloride (PHR) in two different release kinetic scenarios, burst release and sustained release, were investigated and compared with in vitro and in vivo tests as potential wound healing dressings. PHR-loaded fibrous mats were successfully fabricated using polyvinyl pyrrolidone and polycaprolactone by scalable pressurized gyration. The results indicated that PHR-loaded fibrous mats expedited diabetic wound healing in type-1 diabetic rats and did not show any cytotoxic effect on NIH/3T3 (mouse embryo fibroblast) cells, albeit with different release kinetics and efficacies. The wound healing effects of fibrous mats are presented with histological and biochemical evaluations. PHR-loaded fibrous mats improved neutrophil infiltration, oedema, and inflammation and increased epidermal regeneration and fibroblast proliferation but the formation of hair follicles and completely improved oedema were observed only in the sustained release form. Thus, topical administration of PPAR-γ agonist in sustained release form has high potential for the treatment of diabetic wounds in inflammatory and proliferative phases of healing with high bioavailability and fewer systemic side effects.

The fabrication of polymeric micro/nanofibers is gaining attention due to their use in an array of applications including tissue engineering scaffolds, nanosensors, and fiber-reinforced composites. Despite their versatile nature, polymeric fibers are widely underutilized due to the lack of reliable, large-scale production techniques. Upon the discovery of centrifugal spinning and, recently, pressurized gyration techniques, new research directions have emerged. Here, we report a comprehensive study detailing the optimal conditions to significantly improve the morphology, homogeneity, and yield of fibers of varying diameters. A series of polymeric fibers was created using a 21 wt.% solution of polyethylene oxide in distilled water and the fluid behavior was monitored inside a transparent reservoir using a high-speed camera. Fabrication of the fibers took less than 1 s. Using centrifugal spinning, we studied the formation of the fibers at three different rotational speeds, and for pressurized gyration, one rotational speed was studied with three different nitrogen gas pressures. Using the pressurized gyration technique at a gas pressure of 0.3 MPa, there was significant improvement in the production yield of the fibers. We found a strong correlation between the variation of pressure and the rate of the solution leaving the reservoir with the improved morphology of the fibers. The use of reduced power techniques, like centrifugal spinning and pressured gyration, to yield high-quality nonwoven nanofibers and microfibers in large quantities is important due to their use in rapidly expanding markets. (C) 2019 Author(s).

A number of novel coumarin derivatives synthesized by the reaction of 3-carbonyl chloride coumarin with some substituted aryl acid hydrazides to investigate their anti-inflammatory and anticonvulsant activities. Carrageenan (0.1 ml of 1%, w/v) was injected subplantarly in the right paw of rats to induce an acute model of inflammation. Anti-inflammatory efficacy was evaluated for 5 hours at 3 different dosages 5, 10, 25 mg/kg. After that, the changes in the level of paw edema volumes and percentage inhibition of all groups were observed and the most effective coumarin derivative was found as N'-(2-hyroxybenzoyl)-2-oxo-2H-chromene-3-carbohydrazide. In addition, N'-(2-oxo-2H-chromene-3-carbonyl)nicotinohydrazide, (E)-N'-(3-(4-hydroxyphenyl)acryloyl)-2-oxo-2H-chromene-3-carbohydrazide, and N'-(5-amino-2-hydroxybenzoyl)-2-oxo-2H-chromone-3carbohydrazide showed their anti-inflammatory effects in a dose-dependent manner. On the other hand, pentylenetetrazole (PTZ, 80 mg/kg, i.p.)-induced seizure model was used to investigate the anticonvulsant activities of six newly synthesized coumarin derivatives in mice. Hybrid compound of salicylic acid hydrazide and 3-carbonyl chloride coumarin (8d) was found the most promising anticonvulsant agent among all treatment groups according to the onset of seizure and survival rate. Moreover, (E)-N'-cinnamoyl-2-oxo-2H-chromene-3-carbohyrazide (8b) and (E)-N'-(3-(4-hyroxy phenyl)acryloyl)-2-oxo-2H-chromene-3-carbohydrazide (8c) has potential anticonvulsant efficiency in low doses (30 mg/kg). The anticonvulsant effect of these coumarin derivatives may be through enhanced GABA-mediated inhibition in the brain. (C) 2020 Published by Elsevier B.V. on behalf of King Saud University.

Forming polymeric core–sheath nanofibers is gaining prominence owing to their numerous potential applications, most notably in functional scenarios such as antiviral filtration, which is attracting significant attention due to the current COVID pandemic. This study has successfully designed and constructed a novel pressurized gyration vessel to fabricate core–sheath polymer nanofibers. Several water-soluble and water-insoluble polymer combinations are investigated. Both polyethylene oxide and polyvinyl alcohol were used as the core while both poly(lactic acid) (PLA) and poly(caprolactone) (PCL) were used as the sheath; PLA and PCL were used as core and sheath, in different instances; respectively. The fluid behavior of the core–sheath within the vessel was studied with and without applied pressure using computational fluid dynamics to simulate the core–sheath flow within the chamber. A high-speed camera was used to observe the behavior of jetted solutions at core–sheath openings, and the best scenario was achieved using 6000 rpm spinning speed with 0.2 MPa (twice atmospheric) applied pressure. The surface morphology of core–sheath fibers was studied using a scanning electron microscope, and focused ion beam milling assisted scanning electron microscopy was used to investigate the cross-sectional features of the produced fibers. Laser confocal scanning microscopy was also used to verify the core–sheath structure of the fibers, which were further characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. Thus, using a variety of polymer combinations, we show, both theoretically and experimentally, how core–sheath fibers evolve in a vessel that can serve as a scalable manufacturing pressurized gyration production process.

The combination of oral antidiabetic drugs, pioglitazone, metformin, and glibenclamide, which also exhibit the strongest anti-inflammatory action among oral antidiabetic drugs, were loaded into chitosan/gelatin/polycaprolactone (PCL) by electrospinning and polyvinyl pyrrolidone (PVP)/PCL composite nanofibrous scaffolds by pressurized gyration to compare the diabetic wound healing effect. The combination therapies significantly accelerated diabetic wound healing in type-1 diabetic rats and organized densely packed collagen fibers in the dermis, it also showed better regeneration of the dermis and epidermis than single drug-loaded scaffolds with less inflammatory cell infiltration and edema. The formation of the hair follicles started in 14 days only in the combination therapy and lower proinflammatory cytokine levels were observed compared to single drug-loaded treatment groups. The combination therapy increased the wettability and hydrophilicity of scaffolds, demonstrated sustained drug release over 14 days, has high tensile strength and suitable cytocompatibility on L929 (mouse fibroblast) cell and created a suitable area for the proliferation of fibroblast cells. Consequently, the application of metformin and pioglitazone-loaded chitosan/gelatin/PCL nanofibrous scaffolds to a diabetic wound area offer high bioavailability, fewer systemic side effects, and reduced frequency of dosage and amount of drug.

This novel face mask is designed to be a reusable respirator with a small and highly efficient disposable fabric filter. Respirator material requirements are reduced by 75% compared to traditional designs and allow repeated cleaning or sterilization. The probability of virus particle inhalation is reduced using novel air filtration pathways, through square-waveform design to increase filter airflow. Air enters the mask from right and left side filters, while the area in front of the mouth is isolated. Clear epoxy is used for a transparent frame, allowing lip-reading, and mask edges contain a silicone seal preventing bypass of the filters. The mask is manufactured using silicone molds, eliminating electricity requirements making it economical and viable in developing countries. Computational fluid dynamics numerical studies and Fluent ANSYS software were used to simulate airflow through the filter to optimize filter air path geometry and validate mask design with realistic human requirements. The breathing cycle was represented as a transient function, and N95 filter specifications were selected as a porous medium. The novel design achieved 1.2 × 10−3 kg s−1, 20% higher than human requirements, with air streamlines velocity indicating local high speed, forcing and trapping virus particles against filter walls through centrifugal forces.

Wound dressings made from natural polymers are an important aspect of biomaterials. Protein-based materials are less likely to instigate an immunogenic response and have the capacity to degrade in vivo, also without triggering an inflammatory response. Therefore, gelatin (GEL) was chosen and combined with bacterial cellulose (BC) to produce nanofibres and the potential of an all-natural polymer construct was determined. GEL and BC were successfully electrospun with metformin (Met) and glybenclamide (Gb) using a portable, point of need electrospinning set up. The virgin fibre group exhibited a significant effect on the proliferation of L929 (mouse fibroblast) cells but all fibre samples can safely be applied on wound site without risk of cytotoxicity. According to the results obtained by animal tests, the GEL-BC-Gb group showed better recovery than the GEL-BC-Met group. Diabetic wounds treated with GEL-BC-Met were characterized by moderate re-epithelialization and partially organized granulation tissue. Moderate to complete re-epithelialization and well-formed granulation tissue were observed in diabetic wounds treated with GEL-BC-Gb. The histologic scores obtained on day 14 confirmed that the GEL-BC-Gb group played a stronger wound-healing role compared to the GEL-BC-Met group. The highest decrease of TNF-α level was observed in the GEL-BC-Gb group at the end of the experiment but there is no significant difference between drug-loaded fibre groups. Therefore, topical administration of Met and Gb in a sustained release form has a high potential for diabetic wound healing with high bioavailability and fewer systemic side effects but Gb showed better improvement according to the results of the animal tests.

In Turkey, Helichrysum genus is represented by 26 taxa belonging to 20 species in Turkish flora of which 14 ones are endemic to Turkey. The aerial parts of Helichrysum plicatum subsp. plicatum are used kidney stones, kidney and stomach ailments. The extraction procedures and solvents are important step in processing of bioactive constituents from the plant materials. Therefore, the aim of this study was to evaluate in vitro antioxidant, antimicrobial, anti-urease, anticholinesterase and in vivo anti-inflammatory activities of Helichrysum plicatum subsp. plicatum different extracts. In addition, the phenolic characterization of the Soxhlet and maceration methanol extracts which showed significant antioxidant, anti-urease, antimicrobial, anti-inflammatory and anticholinesterase activities were performed by HPLC-DAD and LC-MS/MS. In the present study, the Soxhlet methanol extract exhibited strong antioxidant, antimicrobial and anticholinesterase activities than other extracts. The maceration methanol extract showed the strongest anti-urease activity. The Soxhlet methanol and maceration methanol extracts showed in vivo anti-inflammatory activities very close to each other. As a result of this study, chlorogenic acid, dicaffeoylquinic acid, luteolin, luteolin-7-O-glucoside, naringenin-O-hexoside and isoquercitrin compounds were analysed in plant. Therefore, it is thought that methanol extracts can be used as a natural source in the future for food and pharmaceutical industries.

Objective: Novel investigations have confirmed that hyperglycemia is strictly associated with the development of cognitive impairment and dementia. Sodium-dependent glucose transporter (SGLT) inhibitors, which are oral antidiabetic drugs, are currently being investigated as the medication in Alzheimer's disease (AD). In our study, Camellia sinensis (green tea), which inhibits sodium-dependent glucose transporter-1 (SGLT-1), was used in the treatment of type 2 diabetes mellitus (T2DM)-induced AD-like alterations via its antidiabetic effects.Methods: High-fat diet/streptozotocin-treated rat model was chosen to provide T2DM-induced AD-like alterations. Antidiabetic effects were evaluated with the measurement of blood glucose level (BGL), oral glucose tolerance test (OGTT), and insulin tolerance test (ITT). On the other hand, novel object recognition test (NORT), open field test (OFT), passive avoidance test (PAT), and Morris’s water maze (MWM) test were performed to investigate the anti-Alzheimer's effects of C. Sinensis.Results: C. sinensis tolerated BGL for a short time but metformin, the first medication prescribed for T2DM, tolerated BGL during the test for 120 min. C. sinensis increased the number of square crosses and the frequency of grooming activity in a similar manner to metformin in OFT. C. sinensis treatment improved exploratory behavior and memory retention components in NORT. The step-through latency decreased in HFD/STZ-treated rat model but it improved with metformin and C. sinensis treatment in PAT. According to the results obtained by the MWM test, C. sinensis treatment slightly improved learning.Conclusion: C. sinensis improved short-term memory and increased the locomotor activity in rats according to the results obtained by NORT, OFT, and PA.

The purpose of this study was to comparatively reveal for the first time the antioxidant, anti-inflammatory effects of Phlomis pungens and Coridothymus capitatus methanol extracts obtained by using maceration extraction method. According to the results of anti-inflammatory activity, P. pungens methanolic extract demonstrated a more prominent and intensive antiinflammatory effect with 24.7% of inhibitive capacity in the altered edema size after the first hour of carrageenan injection compared to C. capitatus methanolic extract. P. pungens methanolic extract inhibitory effect increased during three hours and reached maximum by 41.9%. According to the results obtained from antioxidant activity experiments, methanol extract of C. capitatus exhibited stronger free radical scavenging (DPPH), cupric reducing (CUPRAC), ferric reducing/antioxidant power (FRAP) and ABTS radical cation scavenging activity than P. pungens extract. In additon, C. capitatus extract had higher ABTS radical cation scavenging and ferric reducing/antioxidant power activity than ascorbic acid, BHT and BHA, respectively. Therefore, this extract can be used in both medicine and food industry as a natural antioxidant source.

In order to provide more effective treatment strategies for the rapid healing of diabetic wounds, novel therapeutic approaches need to be developed. The therapeutic potential of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone hydrochloride (PHR) in two different release kinetic scenarios, burst release and sustained release, was investigated and compared with in vitro and in vivo tests as potential wound healing dressings. PHR-loaded fibrous mats were successfully fabricated using polyvinyl-pyrrolidone and polycaprolactone by scalable pressurized gyration. The results indicated that PHR-loaded fibrous mats expedited diabetic wound healing in type-1 diabetic rats and did not show any cytotoxic effect on NIH/3T3 (mouse embryo fibroblast) cells, albeit with different release kinetics and efficacies. The wound healing effects of fibrous mats are presented with histological and biochemical evaluations. PHR-loaded fibrous mats improved neutrophil infiltration, oedema, and inflammation and increased epidermal regeneration and fibroblast proliferation, but the formation of hair follicles and completely improved oedema were observed only in the sustained release form. Thus, topical administration of PPAR-γ agonist in sustained release form has high potential for the treatment of diabetic wounds in inflammatory and proliferative phases of healing with high bioavailability and fewer systemic side effects.

BACKGROUND: The aim of this study was to evaluate the possible protective effects of dapagliflozin in an experimental sepsis model in rats. METHODS: Saline (1 mL/kg, p.o.) or dapagliflozin (10 mg/kg, p.o.) was administered to Sprague-Dawley rats for 5 days prior to the surgical procedures. Under anesthesia, sepsis was induced by cecal ligation puncture, while sham control groups underwent laparotomy only. Blood urea nitrogen, creatinine, and glucose levels were measured in serum samples and the levels of malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), tumor necrosis factor alpha, interleukin 1 beta, caspase 8, and caspase 9 were determined in tissue samples (kidney, liver, and lung). Histological evaluation was also performed. RESULTS: The administration of dapagliflozin in a sepsis model reduced oxidative stress (MDA), increased antioxidant levels (GSH), and reduced inflammation (MPO) in the kidney (p

Progesterone-loaded poly(lactic) acid fibrous polymeric patches were produced using electrospinning and pressurized gyration for intra-vaginal application to prevent preterm birth. The patches were intravaginally inserted into rats in the final week of their pregnancy, equivalent to the third trimester of human pregnancy. Maintenance tocolysis with progesterone-loaded patches was elucidated by recording the contractile response of uterine smooth muscle to noradrenaline in pregnant rats. Both progesterone-loaded patches indicated similar results from release and thermal studies, however, patches obtained by electrospinning had smaller average diameters and more uniform dispersion compared to pressurized gyration. Patches obtained by pressurized gyration had better results in production yield and tensile strength than electrospinning; thereby pressurized gyration is better suited for scaled-up production. The patches did not affect cell attachment, viability, and proliferation on Vero cells negatively. Consequently, progesterone-loaded patches are a novel and successful treatment strategy for preventing preterm birth.

Some Salvia and Thymus species of Lamiaceae family come into prominence with strong antidiabetic effects. Compared to the other species, there are limited studies on antidiabetic activity of Salvia triloba (ST) and Thymus praecox subsp. skorpilii var. skorpilii (TPS). The aim of this study was to adjust the dosage and to determine the antidiabetic effects of methanol extracts of ST and TPS in streptozotocin/nicotinamide-induced diabetic rats. Type II diabetes mellitus (T2DM) was induced by a single intraperitoneal (i. p.) injection of streptozotocin (STZ) dissolved in 0.1 M cold citrate buffer (pH 4.5) at a dose of 55 mg/kg/body weight (b.w.) and nicotinamide (100 mg/kg/b.w.) was given prior to STZ injection. For adjusting dosage, oral glucose tolerance test (OGTT) was used while insulin tolerance test (ITT), OGTT, blood glucose levels and animal weights were used to evaluate the antidiabetic effects of ST and TPS. According to the OGTT, the most effective doses for ST and TPS were 200 mg/kg and 100 mg/kg, respectively. At the end of three weeks, blood glucose levels of control goup reached to 462.50 mg/dl, whereas ST and TPS-treated groups blood glucose levels decreased less than 200.00 mg/dl. In conclusion, the present study suggests that both of ST and TPS methanolic extracts may be of therapeutic benefit in diabetes and thus need to further studies.

The fabrication of polymeric micro/nanofibers is gaining attention due to their use in an array of applications including tissue engineering scaffolds, nanosensors, and fiber-reinforced composites. Despite their versatile nature, polymeric fibers are widely underutilized due to the lack of reliable, large-scale production techniques. Upon the discovery of centrifugal spinning and, recently, pressurized gyration techniques, new research directions have emerged. Here, we report a comprehensive study detailing the optimal conditions to significantly improve the morphology, homogeneity, and yield of fibers of varying diameters. A series of polymeric fibers was created using a 21 wt.% solution of polyethylene oxide in distilled water and the fluid behavior was monitored inside a transparent reservoir using a high-speed camera. Fabrication of the fibers took less than 1 s. Using centrifugal spinning, we studied the formation of the fibers at three different rotational speeds, and for pressurized gyration, one rotational speed was studied with three different nitrogen gas pressures. Using the pressurized gyration technique at a gas pressure of 0.3 MPa, there was significant improvement in the production yield of the fibers. We found a strong correlation between the variation of pressure and the rate of the solution leaving the reservoir with the improved morphology of the fibers. The use of reduced power techniques, like centrifugal spinning and pressured gyration, to yield high-quality nonwoven nanofibers and microfibers in large quantities is important due to their use in rapidly expanding markets. (C) 2019 Author(s).