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Ethnopharmacological Relevance: Clove is used in Indian and Chinese traditional medicine for viral diseases. Palmarosa essential oils have been traditionally used in India and Southeast Asia since ancient times and have made considerable use of them. In New Caledonia, niaouli oil is used in aromatherapy and pharmaceutical formulations to treat pain and viral diseases. Since ancient times, the South Pacific region has used tamanu oil as a traditional medicine to treat a wide range of skin conditions., Aim of the Study: This study investigates the antiviral properties of essential oils (EOs) from Eugenia aromaticum (clove oil, CL-R030424005 (CL)), Cymbopogon martinii (palmarosa oil, PA-R040923008 (PA)), Melaleuca viridiflora (niaouli oil, NI-R290124038 (NI)), and Calophyllum inophyllum (tamanu oil, TA-F140224029 (TA)), and their mixture against human papillomavirus (HPV) infection., Materials and Methods: A D-optimal mixture design is used to determine the most effective EO combinations and evaluate their antiviral efficacy through IC 50 values. The EOs were tested for their ability to inhibit HPV-related oncogenes (L1, L2, E1, E2, E6, and E7) in HPV-infected cells with ELISA, qPCR, and Western blot analyses., Results and Discussion: The optimal mixture (31.5% CL, 31.5% PA, and 37% NI) demonstrated significant antiviral activity, reducing viral replication and protein expression in HPV-infected cells. Ex-vivo permeation studies showed higher permeation rates in healthy tissues compared to infected ones, indicating the oils' potential in targeted drug delivery. Additionally, cytotoxicity assessments confirmed the safety of the EOs at effective concentrations in HPVCs, DoTc2, and HEKa cells. Molecular docking studies further elucidated the interactions between EO components and HPV proteins, supporting their antiviral mechanisms., Conclusion: These findings suggest that EOs, particularly in optimized combinations, offer a promising natural supportive treatment for managing HPV infections, warranting further in vivo animal tests and clinical trials., Competing Interests: Declaration of competing interest The authors have no competing interests., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Epilepsy is one of the oldest neurological disorders discovered by mankind. This condition is firmly coupled with unprovoked seizures stimulated by irrepressible neuroelectrical blasts. Orally taken valproate family has been employed for prophylactic management; however, oral administration is not applicable for critical scenarios, thus calling for medication routes fulfilling necessities of immediate innervation. In order to address this shortcoming, sodium valproate entrapped in poly(ethylene oxide)/polyvinylpyrrolidone (PEO/PVP) nanofibrous patches was developed with the aim of sublingual drug delivery. Initially, the production process was designed and optimized via the central composite design (CCD). Nanofiber fabrication was accomplished with a novel device by using the pressurized gyration method. Fabricated biomaterials were chemically, spatially, and thermally inspected. The beanless and homogeneous appearance of both virgin and impregnated nanofibrous patches was morphologically demonstrated via scanning electron microscopy. Additionally, adequately oro-dispersed impregnated patches released more than 90% of their drug content in under a minute. Following in vitro cyto-safety assurance acquired through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay on SH-SY5Y neuroblastoma cells, the protective antiepileptic effect of impregnated patches was affirmed in vivo via pentylenetetrazole kindled-induced Mus musculus animal modeling. The parameter of in vivo behavioral evaluation was the Racine scoring system. Moreover, histopathological distinctions detected between different test groups were highlighted via fluorescence staining. Finally, the oxidative stress was determined according to quantitative variations of malondialdehyde, glutathione, superoxide dismutase, and catalase levels. The overall conclusion herein suggests that sodium valproate-loaded PEO/PVP nanofibrous patches strikingly prevented behavioral, structural, and oxidative deteriorations caused by pentylenetetrazole.

This study describes the synthesis and characterization of a series of novel hydrazide-hydrazone derivatives containing a 1,2,4-triazole ring. The compounds were characterized using various spectroscopic techniques, such as FT-IR, 1 H-NMR, 13 C-NMR, HRMS, and elemental analysis. The antiproliferative activity of the synthesized compounds was evaluated against a panel of human cancer cell lines (HCT-116, HepG-2, KLN205, LTPA, U138, and SW620) and healthy cell lines (HSkMC and iPSCs). Among the compounds tested, compounds 4, 5p, 5r, and 5s showed the highest effectiveness in inhibiting the growth of cancer cells with Bcl-xL inhibitory concentration (IC 50 ) values. These compounds further demonstrated selective cytotoxicity against the Bcl-xL-dependent lymphoma cell line (DBs). Molecular docking studies were also performed to investigate the potential binding interactions of compounds 4, 5p, 5r, and 5s with the active site of Bcl-xL (PDB ID: 7LH7, 1.4 Å). Mechanistic studies revealed that compounds 4, 5r, and 5s induced apoptosis predominantly through the intrinsic mitochondrial pathway, while compound 5p exhibited a distinct cell cycle arrest profile, impacting both the S and G2/M phases. Western blot analysis suggested that these compounds may downregulate cyclin expression, thereby blocking its association with Bcl-xL. Overall, these results demonstrate the potential of these novel hydrazide-hydrazone derivatives as anticancer agents with activity comparable or superior to doxorubicin and 5-fluorouracil., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Background: Targeted nanoparticles (NPs) are aimed at improving clinical outcomes by enhancing the diagnostic and therapeutic efficacy of drugs in the treatment of Alzheimer's disease (AD)., Methods: Curcumin (CUR)-loaded poly-lactic-co-glycolic acid (PLGA) NPs (CNPs) were produced to demonstrate a prolonged release and successfully embedded into 3D printed sodium alginate (SA)/gelatin (GEL) scaffolds that can dissolve rapidly sublingually. Characterization and in vitro activity of the NPs and scaffolds were evaluated., Results: Based on the in vitro drug release studies, 99.6 % of the encapsulated CUR was released in a controlled manner within 18 days for the CNPs. In vitro cell culture studies showed that all samples exhibited cell viability above 84.2 % and no significant cytotoxic effect on SH-SY5Y cells. The samples were analyzed through 2 different pathways by PCR analysis. Real-time PCR results indicated that CNP and CNP-embedded SA/GEL scaffolds (CNPSGS) may show neuroprotective effects by modulating the Wnt/β-catenin pathway. The gene expression level of β-catenin slightly increased compared to the gene expression levels of other proteins and enzymes with these treatments. However, the PI3K/Akt/GSK-3β signaling pathway was regulated at the same time because of the crosstalk between these 2 pathways., Conclusion: CNPSGS might be an effective therapeutic alternative for AD treatment., Competing Interests: Declaration of competing interest The authors have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, Teucrium polium (TP) methanolic extract, which has antidiabetic activity and protects the β-cells of the pancreas, was loaded in polyethylene oxide/sodium alginate nanofibers by electrospinning and administered sublingually to evaluate their effectiveness in type-2 diabetes mellitus (T2DM) by cell culture and in vivo studies. The gene expressions of insulin, glucokinase, GLUT-1, and GLUT-2 improved in TP-loaded nanofibers (TPF) on human beta cells 1.1B4 and rat beta cells BRIN-BD11. Fast-dissolving (<120 s) sublingual TPF exhibited better sustainable anti-diabetic activity than the suspension form, even in the twenty times lower dosage in streptozotocin/nicotinamide-induced T2DM rats. The levels of GLP-1, GLUT-2, SGLT-2, PPAR-γ, insulin, and tumor necrosis factor-alpha were improved. TP and TPF treatments ameliorated morphological changes in the liver, pancreas, and kidney. The fiber diameter increased, tensile strength decreased, and the working temperature range enlarged by loading TP in fibers. Thus, TPF has proven to be a novel supportive treatment approach for T2DM with the features of being non-toxic, easy to use, and effective., Competing Interests: Declaration of Competing Interest The authors have no competing interests., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Ulcerative colitis (UC) which has a global impact on the health care system with its recurrent and incompletely curable characteristics, affects the patients' quality of life. Gilaburu (GB; Viburnum opulus L.) is a fruit with rich polyphenol ingredient which is used ethnobotanically in Türkiye for medicinal purposes (for example, to pass kidney stones, to treat stomach, heart, and liver diseases, hemorrhages, hypertension, ulcers, common cold, tuberculosis, rheumatic and menstrual pain, and diabetes). On the other hand, the effects of GB in the experimental UC model have not been studied., Aim of the Study: This study aimed to explore the potential antioxidant and anti-inflammatory effects of GB fruit extract in improving acetic acid (AA)-induced UC., Materials and Methods: Starting immediately after (AA + GB group) or 1 week before (GB + AA + GB group) the colitis induced by intrarectal AA (5%; v/v) administration, the rats orally received GB (100 mg/kg) once per day for 3 days. The control and AA groups were administered orally saline (1 ml), while the AA + SS group were administered sulfasalazine (SS; 100 mg/kg; orally) as a positive control once per day for 3 days. Distal colonic tissue specimens were obtained for the histological and biochemical [myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), chemiluminescence (CL), caspase-3, 8-hydroxy-2 ' -deoxyguanosine (8-OHdG), matrix metalloproteinase (MMP)-9, transforming growth factor (TGF)-β 1 , smad-3 and cytokine (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, interferon (IFN)-γ), measurements] evaluations on the 3 rd day., Results: Elevated macroscopic and microscopic damage scores, high tissue wet weight values, increased tissue-associated MPO, MDA, CL, caspase-3, 8-OHdG, cytokines (TNF-α, IL-1β, IL-6, IL-8), MMP-9, TGF-β 1 , smad-3 levels, and decreased GSH values of the AA group were all reversed by GB treatments (AA + GB and GB + AA + GB groups) (p < 0.05-0.001). However, sulfasalazine treatment (AA + SS group) did not change the IL-8, 8-OHdG, MMP-9, and TGF-β 1 measurements significantly., Conclusions: Gilaburu shows both anti-inflammatory and antioxidant effects against AA-induced colonic damage by suppressing neutrophil infiltration, regulating inflammatory mediators, inhibiting reactive species production, lipid peroxidation, and apoptosis, conserving endogenous antioxidant glutathione, and ameliorating oxidative DNA damage. Since the current ulcerative colitis drugs display limited benefits and adverse side effects, potential therapeutic and/or prophylactic role of gilaburu can be evaluated in ulcerative colitis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is a neurodegeneration type that is biologically recognizable via β-amyloid plaques and tau neurofibril tangles. Global estimation for the total count of individuals enduring AD will rise up to 131 million by 2050. Investigations suggested the existence of a direct proportion between the likelihood of AD occurrence and vitamin B 12 (VB 12 ) hypovitaminosis. Approved VB 12 administrations, intramuscular and oral, each has serious defects broaching the demand for alternative routes. This work developed VB 12 -loaded chitosan/tripolyphosphate/polyvinyl alcohol (CS/TPP/PVA) nanoparticles (NPs) embedded in polyvinylpyrrolidone (PVP) and polyvinylpyrrolidone/polycaprolactone (PVP/PCL) nanofibrous (NFs) produced by pressurized gyration (PG) for sublingual and transdermal routes, respectively. Biomaterials were investigated morphologically, chemically, and thermally. Moreover, degradation, disintegration, release behavior, and release kinetics were analyzed. The effectiveness and safety of nanomaterials were assessed and proven with the alamarBlue test on the Aβ 1-42 -induced SH-SY5Y model. The final evaluation suggested the feasibility, safety, and effectiveness of produced systems. Consequently, two alternative VB 12 application routes were developed with high effectivity and low toxicity with the power of nanotechnology., Competing Interests: Declaration of competing interest The authors all declare that there is no existing conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Recent studies claim that Type-2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) overlap in several common pathological pathways which from neuronal damage to impaired memory performance. It is known that the use of Rosa canina L. (R. canina) as medicine in folk medicine dates back to ancient times and is used in the treatment of nervous diseases in Persian medicine. However, the effect of R. canina on diabetes-related cognitive decline and memory impairment has not yet been studied., Aim of the Study: We evaluated the impact of T2DM on AD-like alterations and examined the molecular mechanism of a possible effect of R. canina on cognitive alterations in diabetic rats., Materials&methods: R. canina ethanol extract was obtained by maceration method. This study was performed with male Sprague-Dawley rats fed with a high-fat diet (HFD) for 8 weeks, low-dose streptozotocin (STZ; 35 mg/kg IP) injection for 4 weeks, and R. canina (250 mg/kg; per oral) and metformin (400 mg/kg; per oral) administration for 4 weeks. The weight and blood glucose of rats were measured weekly. To evaluate glucose tolerance area under the curve (AUC) was calculated by performing an oral glucose tolerance test. Then the rats were subjected to behavioural tests, and their hippocampus and cortex tissues were obtained for biochemical and morphological analyses., Results: R. canina could manage glucose responsiveness by reducing post-prandial blood glucose levels, preventing weight loss, and raising serum insulin levels in T2DM-induced rats. Behavioural tests showed that R. canina significantly improves diabetes-related cognitive decline in recall and long-term memory. Treatment with R. canina significantly reversed HFD/STZ-induced increases in insulin, amyloid-β, amyloid precursor protein levels, and acetylcholinesterase activity in the prefrontal cortex and hippocampus. Furthermore, histological analyzes revealed the protection of R. canina against neuronal disruption in the cortical and hippocampal CA3 region caused by chronic hyperglycemia., Conclusion: Analyzed collectively, these results suggest that R. canina can correct T2DM-related cognitive decline may be attributed to insulin pathway modulation, prevention of amyloid deposition, and increased cholinergic transmission., Competing Interests: Declaration of competing interest The authors all declare that there is no existing conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Drug delivery systems that not only show efficacy through multiple therapeutic pathways but also facilitate patient drug use and exhibit a high bioavailability profile represent a promising strategy in the treatment of Alzheimer's disease (AD). Here, donepezil (DO)/memantine (MM)/curcumin (CUR)-loaded electrospun nanofibers (NFs) were produced for the treatment of AD. DSC, XRD, and FT-IR studies demonstrated the complete incorporation of the drug into PVA/PVP NFs. The disintegration profile was improved by loading the drugs in PVA/PVP with fast wetting (less than 1 s), the start of disintegration (21 s), and dispersion in 110 s. The desired properties for sublingual application were achieved with the dissolution of NFs in 240 s. The cell viability in DO/MM/CUR-loaded NFs was similar to the control group after 48 h in the cell culture. DO/MM/CUR-loaded NFs enhanced the expressions of BDNF (13.5-fold), TUBB3 (8.9-fold), Neurog2 (5.6-fold), NeuroD1 (5.8-fold), Nestin (166-fold), and GFAP (115-fold). DO/MM/CUR-loaded NFs and powder of these drugs contained in these fibers were daily administered sublingually to intracerebroventricular-streptozotocin (icv-STZ) treated rats. DO/MM/CUR-loaded NFs treatment improved the short-term memory damage and enhanced memory, learning ability, and spatial exploration talent. Results indicated that the levels of Aβ, Tau protein, APP, GSK-3β, AChE, and TNF-α were significantly decreased, and BDNF was increased by DO/MM/CUR-loaded NFs treatment compared to the AD group. In the histopathological analysis of the hippocampus and cortex, neuritic plaques and neurofibrillary nodes were not observed in the rats treated with DO/MM/CUR-loaded NFs. Taken together, the sublingual route delivery of DO/MM/CUR-loaded NFs supports potential clinical applications for AD., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that is increasingly common all over the world with a high risk of progressive hyperglycemia and high microvascular and macrovascular complications. The currently used drugs in the treatment of T2DM have insufficient glucose control and can carry detrimental side effects. Several drug delivery systems have been investigated to decrease the side effects and frequency of dosage, and also to increase the effect of oral antidiabetic drugs. In recent years, the use of microbubbles in biomedical applications has greatly increased, and research into microactive carrier bubbles continues to generate more and more clinical interest. In this study, various monodisperse polymer nanoparticles at different concentrations were produced by bursting microbubbles generated using a T-junction microfluidic device. Morphological analysis by scanning electron microscopy, molecular interactions between the components by FTIR, drug release by UV spectroscopy, and physical analysis such as surface tension and viscosity measurement were carried out for the particles generated and solutions used. The microbubbles and nanoparticles had a smooth outer surface. When the microbubbles/nanoparticles were compared, it was observed that they were optimized with 0.3 wt % poly(vinyl alcohol) (PVA) solution, 40 kPa pressure, and a 110 μL/min flow rate, thus the diameters of the bubbles and particles were 100 ± 10 μm and 70 ± 5 nm, respectively. Metformin was successfully loaded into the nanoparticles in these optimized concentrations and characteristics, and no drug crystals and clusters were seen on the surface. Metformin was released in a controlled manner at pH 1.2 for 60 min and at pH 7.4 for 240 min. The process and structures generated offer great potential for the treatment of T2DM.

Delivery of therapeutic peptides via sublingual administration is extremely desired and 3D printed scaffolds are potential candidates as carriers to enhance insulin delivery. 3D printed sublingual sodium alginate (SA)/polyethylene glycol (PEG) composite scaffolds were produced for enhancing insulin delivery by examining the chemical, morphological, mechanical, thermal, cytotoxic, and pharmacokinetic features. The tensile strength and flexibility of scaffolds increased after loading insulin due to the crystalline structure of insulin. Furthermore, insulin-loaded 9SA/3PEG scaffolds showed ultrafast wetting (<1 s), disintegration (<6 s), and also dissolution (<30 s) according to Hixson-Crowell kinetic model. The cell viability of L929 cells on 3D printed scaffolds was examined and these scaffolds could be safely applied on animals. Pharmacokinetic parameters and blood glucose level were evaluated following sublingual administration of scaffolds to type-1 diabetic rats. A single dose of scaffold presented a longer hypoglycemic effect, reducing ~60% of glycemia after 30 min and it lasted for 12 h by increasing the bioavailability of insulin. Scaffolds indicated a sustained profile for serum insulin levels, which continued to increase slightly after 3 h during the study. The polymeric scaffold with a high safety and efficacy holds a new promising delivery strategy for administering injectable insulin through the sublingual route., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Vitamin D 3 , vitamin K 2 , and Mg (10%, 1.25%, and 5%, w/w, respectively)-loaded PLA (12%, w/v) (TCP (5%, w/v))/PCL (12%, w/v) 1:1 (v/v) composite nanofibers (DKMF) were produced by electrospinning method (ES) and their osteoinductive effects were investigated in cell culture test. Neither pure nanofibers nor DKMF caused a significant cytotoxic effect in fibroblasts. The induction of the stem cell differentiation into osteogenic cells was observed in the cell culture with both DKMF and pure nanofibers, separately. Vitamin D 3, vitamin K 2 , and magnesium demonstrated to support the osteogenic differentiation of mesenchymal stem cells by expressing Runx2, BMP2, and osteopontin and suppressing PPAR-γ and Sox9. Therefore, the Wnt/β-catenin signaling pathway was activated by DKMF. DKMF promoted large axonal sprouting and needle-like elongation of osteoblast cells and enhanced cellular functions such as migration, infiltration, proliferation, and differentiation after seven days of incubation using confocal laser scanning microscopy. The results showed that DKMF demonstrated sustained drug release for 144 h, tougher and stronger structure, higher tensile strength, increased water up-take capacity, decreased degradation ratio, and slightly lower Tm and Tg values compared to pure nanofibers. Consequently, DKMF is a promising treatment approach in bone tissue engineering due to its osteoinductive effects., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Dual-drug delivery systems were constructed through coaxial techniques, which were convenient for the model drugs used the present work. This study aimed to fabricate core-shell electrospun nanofibrous membranes displaying simultaneous cell proliferation and antibacterial activity. For that purpose, phenytoin (Ph), a well-known proliferative agent, was loaded into a polycaprolactone (PCL) shell membrane, and as-prepared silver-chitosan nanoparticles (Ag-CS NPs), as biocidal agents, were embedded in a polyvinyl alcohol (PVA) core layer. The morphology, chemical composition, mechanical and thermal properties of the nanofibrous membranes were characterized by FESEM/STEM, FTIR and DSC. The coaxial PVA-Ag CS NPs/PCL-Ph nanofibers (NFs) showed more controlled Ph release than PVA/PCL-Ph NFs. There was notable improvement in the morphology, thermal, mechanical, antibacterial properties and cytobiocompatibility of the fibers upon incorporation of Ph and Ag-CS NPs. The proposed core-shell PVA/PCL NFs represent promising scaffolds for tissue regeneration and wound healing by the effective dual delivery of phenytoin and Ag-CS NPs., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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., Competing Interests: Conflict of interestThe authors declare that there is no conflict of interest., (© The Author(s) 2020.)

Acute wounds are a common health problem, with millions of people affected and decreased granulation tissue formation and vascularization, it is also a big challenge for wound care researchers to promote acute wound healing around the globe. This study aims to produce and characterize Satureja cuneifolia plant extract (SC)-blended with sodium alginate (SA) /polyethylene glycol (PEG) scaffolds for the potential treatment of diabetic ulcer. SA/PEG scaffolds were prepared by adding different concentrations (1, 3, and 5 wt%) of PEG to 9 wt% SA. The morphological and chemical composition of the resulting 3D printed composite scaffolds was determined using scanning electron microscopy (SEM) and Fourier transforms infrared spectroscopy (FTIR), respectively. Mechanical and thermal properties, swelling, and degradation behaviours were also investigated. The release kinetics of SC were performed. The antimicrobial analysis was evaluated against Escherichia coli and Staphylococcus aureus strains. 3D printed scaffolds have shown an excellent antibacterial effect, especially against gram-positive bacteria due to the antibacterial SC extract they contain. Furthermore, the cell viability of fibroblast (L929) cells on/within scaffolds were determined by the colourimetric MTT assay. The SA/PEG/SC scaffolds show a great promising potential candidate for diabetic wound healing and against bacterial infections., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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<0.05). Dapagliflozin also decreased oxidative stress (MDA) in lung tissue and decreased inflammation (MPO) in lung and liver tissue (p<0.05). Caspase 8 and 9 levels in kidney, lung, and liver tissue were increased (p<0.05) in the dapagliflozin group compared with the sepsis group. According to the histopathological results, sepsis was moderately improved in renal tissue and slightly attenuated in lung and liver tissue with the administration of dapagliflozin., Conclusion: Dapagliflozin had a preventive effect on sepsis-induced kidney damage, but the protective effect was mild in lung and liver tissue in the present study.

Ethnopharmacological Relevance: Thymus praecox subsp. skorpilii var. skorpilii (syn. Thymus praecox subsp. jankae (Celak.) Jalas) is consumed as a Turkish folk medicine for the treatment of spasm, sore throat and shortness of breath, also having strong antioxidant activity and the leaves of the plant have been utilized for the treatment of diabetes as the decoction in Turkey., Aim of the Study: In the present study, we aimed to investigate the potential mechanism of antidiabetic action of Thymus praecox subsp. skorpilii var. skorpilii methanolic extract (TPSE) on streptozotocin (STZ)/nicotinamide (NA)-induced type 2 diabetic rats., Materials and Methods: Sprague Dawley rats were randomly divided into four groups; control, diabetes, TPSE (100 mg/kg b.w, p.o.) and metformin group (400 mg/kg b.w, p.o.). Diabetes was established in all groups except control group by 55 mg/kg STZ (i.p.) for once 15 min after 100 mg/kg NA injection. 3 days after STZ/NA injection, treatments were administered for three weeks and then rats were decapitated; tissue and blood samples were obtained for measuring the level of glucose transporters (both GLUTs and sodium glucose co-transporters (SGLTs)), enzymes related to glucose (Hexokinase (HK), phosphoenolpyruvate carboxykinase (PEPCK), α-glucosidase) and lipid metabolism (Acetyl-coenzyme carboxylase (ACC)), AST, ALT, creatinine, insulin, anti-inflammatory (IL-10) and inflammatory (TNF-α, IL-1β, IL-6) cytokines, AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma (PPAR-γ) and glucagon like peptide-1 (GLP-1). Histopathological alterations of the pancreas were examined., Results: After three weeks of treatment, TPSE has exhibited a significant reduction of plasma levels of the proinflammatory cytokines. Besides, TPSE treatment elevated plasma insulin levels and normalized blood glucose levels. Moreover, it improved the values of AMPK in liver and GLP-1 in pancreas. Increased α-glucosidase, PEPCK, GLUT-2 and SGLTs levels with the induction of diabetes considerably lowered with TPSE treatment. Especially on SGLT-2, TPSE achieved a more prominent decrease. After the atrophy in Langerhans islets due to diabetes induction, treatment was found to prevent the damage of islets., Conclusions: Based on the findings presented here, it has been concluded that TPSE has marked antidiabetic effects through various pathways on STZ/NA-induced diabetic rats and it may potentially be used as an effective treatment for type 2 diabetes mellitus (T2DM). Further research on isolation of the bioactive components is underway., (Copyright © 2018. Published by Elsevier B.V.)