Percentage Of Wound Closure Research Articles

New series of 4,6-diaryl pyrimidines: facile synthesis and antiproliferative activity as dual EGFR/VEGFR-2 inhibitors

IntroductionWe developed and produced a new series of 4,6-diaryl-pyrimidines 9–29 as antiproliferative agents targeting EGFR/VEGFR-2.MethodsThe antiproliferative efficacy of the novel targets was assessed against a panel of 60 NCI cancer cell lines and four cancer cell lines in vitro.Results and DiscussionCompounds 14, 17, 19, 22, 25, and 29 demonstrated the greatest potency among the derivatives, with GI50 values between 22 and 33 nM; compounds 22 and 29 exhibited the highest potency, with GI50 values of 22 and 24 nM, respectively. We subsequently examined the most efficient derivatives as dual EGFR/VEGFR-2 inhibitors, finding that compounds 22 and 29 functioned as dual inhibitors. Moreover, 22 and 29 can act as apoptotic inducers by increasing Bax levels and decreasing levels of the anti-apoptotic protein Bcl2. At both 24- and 48-h intervals, the cell migration rates of compounds 22 and 29 were lower than those of untreated cells, according to the migration rate and wound closure percentage assessment. The wound closure rate reached 100% after 72 h of therapy with compound 22 but only 80% with compound 29. The docking study showed that compounds 22 and 29 had docking scores similar to those of Erlotinib and Sorafenib, co-crystallized ligands, for the EGFR and VEGFR-2 proteins. The experiments on lipophilicity showed that the new pyrimidines had a consistent result. This group of compounds has better biological activity in all the biological systems studied with low lipophilicity.

Myristicin Inhibit Invasion and Migration of Melanoma Cells through Suppression of MMP2 and MMP9 Gene Expression

Melanoma is the deadliest type of skin cancer, having a high mortality rate. This cancer has an aggressive nature, is highly invasive, and has the tendency to metastasize. Matrix metalloproteinases (MMPs) are essential in that process, especially MMP2 and MMP9. Their expression is upregulated during metastasis progression. Myristicin is one example of a compound that can be utilized to target MMP 2 and MMP 9 in melanoma. This research concerns the activity of myristicin to inhibit melanoma cell invasion and migration by suppressing MMP2 and MMP9 gene expression. The MTT assay in this study demonstrated that myristicin exhibited strong cytotoxic activity against melanoma cells. This compound works in a dose-dependent manner by inhibiting cell migration and invasion. The invasion test was performed using the transwell assay, whereas the migration test was performed using the wound healing assay. The invasion assay results were consistent with MMP2 and MMP9 gene expression. These two genes were analyzed using the RT-qPCR technique. It has been demonstrated that low gene expression in melanoma cells inhibits cell invasion. In contrast, higher MMP2 and MMP9 gene expression was associated with an increase in the number of invasive cells on average. However, MMP2 and MMP9 in excessive expression and uncontrolled activity impair the ability of melanoma cells to form a monolayer sheet to cover wound gaps. This condition significantly reduced the migration rate and percentage of wound closure.

Biochemical, immunological markers, histology and ultrastructural changes of open wound healing in rats treated with ethyl acetate extract of Zingiber zerumbet rhizomes

Research on plant-based wound healing agents has been one of the current developing areas in modern biomedical science. This study aimed to assess the effects of ethyl acetate extract of Zingiber zerumbet rhizome (ZZRE) on open wound healing activity in Wistar rats. Ninety male Wistar rats (220–320 g) were divided into three groups treated with phosphate buffered saline (PBS) (negative control), Solcoseryl gel (positive control), and 10 % ZZRE (treatment group), respectively. Six circular full-skin thickness wounds of 6.0 mm in diameter were induced bilaterally on the dorsal surface of each rat. Six rats were sacrificed on Day-1, Day-3, Day-6, Day-10 and Day-14 respectively from each group after wound induction. All data obtained are considered statistically significant at p < 0.05. Macroscopic observations showed that the 10 % ZZRE treated wounds healed faster compared to other groups. The wound closure percentage showed that the wound treated with 10 % ZZRE is significantly higher (p < 0.05) than the PBS group on Day-6, Day-10 and Day-14. Protein levels of the 10 % ZZRE group decreased significantly at Day-1 compared to the PBS group and significantly (p < 0.05) higher at Day-14 compared to both control groups. The hexosamine and uronic acid levels of the 10 % ZZRE group showed a significant (p < 0.05) decrease on Day-14. Conversely, hydroxyproline levels showed significant (p < 0.05) increase starting from Day-3 until Day-14. As for the immunological markers, the level of total TGF-β1 of the 10 % ZZRE group was significantly (p < 0.05) higher than the PBS group on Day-14, whereas the level of IL-10 on the wound tissue of the 10 % ZZRE group was significantly (p < 0.05) lower than the PBS group on Day-1 but significantly (p < 0.05) higher on Day-10 and Day-14 compared to both control groups. Histological observation showed that the wounds treated with 10 % ZZRE infiltrated with lesser inflammatory cells while collagen deposition was denser as compared to both control groups. Based on the result obtained, it is clearly proven that treatment of 10 % ZZRE on open wound healing in rats, showed that the extract was effective in healing the wound and accelerated the healing process. Therefore, the 10 % ZZRE tested has the potential to be developed as an alternative wound healing agent in the future.

Evaluating the Effects of BSA-Coated Gold Nanorods on Cell Migration Potential and Inflammatory Mediators in Human Dermal Fibroblasts.

Albumin-coated gold nanoparticles display potential biomedical applications, including cancer research, infection treatment, and wound healing; however, elucidating their interaction with normal cells remains an area with limited exploration. In this study, gold nanorods (GNR) were prepared and coated with bovine serum albumin (BSA) to produce GNR-BSA. The functionalized nanoparticles were characterized based on their optical absorption spectra, morphology, surface charge, and quantity of attached protein. The interaction between GNR-BSA and BSA with normal cells was investigated using human dermal fibroblasts. The cytotoxicity test indicated cell viability between ~63-95% for GNR-BSA over concentrations from 30.0 to 0.47 μg/mL and ~85-98% for BSA over concentrations from 4.0 to 0.0625 mg/mL. The impact of the GNR-BSA and BSA on cell migration potential and wound healing was assessed using scratch assay, and the modulation of cytokine release was explored by quantifying a panel of cytokines using Multiplex technology. The results indicated that GNR-BSA, at 10 μg/mL, delayed the cell migration and wound healing 24 h post-treatment compared to the BSA or the control group with an average wound closure percentage of 6% and 16% at 6 and 24 h post-treatment, respectively. Multiplex analysis revealed that while GNR-BSA reduced the release of the pro-inflammatory marker IL-12 from the activated fibroblasts 24 h post-treatment, they significantly reduced the release of IL-8 (p < 0.001), and CCL2 (p < 0.01), which are crucial for the inflammation response, cell adhesion, proliferation, migration, and angiogenesis. Although GNR-BSA exhibited relatively high cell viability towards human dermal fibroblasts and promising therapeutic applications, toxicity aspects related to cell motility and migration must be considered.

Effects of ascorbic acid augmented albumin platelet-rich fibrin on the wound healing activity of human gingival fibroblasts: an in vitro trial.

The current in vitro study aimed to assess the effects of ascorbic acid augmented albumin platelet-rich fibrin (AA Alb-PRF) on the wound healing activity of human gingival fibroblasts (HGFs) purported to be a regenerative biomaterial in surgical procedures. All assays were performed on three HGF groups, group I: complete media; group II: Alb-PRF, and group III: AA Alb- PRF. Alb-PRF was prepared following the protocol by Fujioka-Kobayashi et al. (2021). For preparation of AA Alb-PRF, 2,500 μg AA was added to the blood pre-centrifugation. All groups were subjected to 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to estimate cell viability and proliferation, scratch assay for migration (0, 4, 12, and 24 hours) and transwell migration assay for chemotactic migration assessment (24 hours). Outcome variables were optical density (OD) for MTT assay, percentage of wound closure in scratch assay, and number of migrated cells in transwell migration assay. One-way ANOVA for MTT and transwell migration assays and two-way ANOVA for scratch assay with Bonferroni correction were performed with significance set at P<0.05. Cell viability and proliferation (OD: 0.684±0.003 and proliferation: 28%) and wound closure (49.92%±1.62% at 4 hours and 61.39%±0.88% at 12 hours) were significantly higher in group III, while group II demonstrated the maximum number of HGFs migrating across the transwell membrane (9.25±2.49) with P<0.05. HGFs demonstrated a significant increase in viability and proliferation along with rapid wound closure in the presence AA Alb-PRF compared to Alb-PRF alone, indicating additional beneficial effects of AA. Thus, AA Alb-PRF potentiates the wound healing activity of HGFs and could be employed in oral, maxillofacial, and periodontal surgeries as a regenerative biomaterial.

Therapeutic Effect of Stem Cells from Different Sources on Diabetic Foot Ulcers: Systematic Review and Network Meta-Analysis.

To evaluate the efficacy of stem cell therapy from different sources on the ankle-brachial index, wound closure percentage, and wound closure time in the treatment of diabetic foot ulcers (DFUs). A literature search was conducted in PubMed, Embase, Cochrane Library's Central Register of Controlled Trials, and Web of Science, extending through June 29, 2023. Quality evaluation was done using the Cochrane's bias risk assessment tool (RoB 2.0). Employing a Bayesian approach, the statistical computations was executed with the JAGS software, leveraging the gemtc 0.8-2 and rjags 4-10 libraries, within the R environment 4.1.2. The included interventions came from peripheral blood, bone marrow, placenta, umbilical cord blood, adipose tissue, or others. A preliminary search identified 2286 articles, of which 23 randomized controlled trials met the inclusion criteria and were ultimately included. The analysis findings indicated that mesenchymal stem cells derived from the umbilical cord (HUCMSCs) led to a notable enhanced the ankle-brachial index in patients with DFUs compared to standard treatment (MD: 0.2; 95% CI [0.01, 0.36]). HUCMSCs were found to be the optimal therapeutic approach for enhancing the ankle-brachial index (SUCRA = 82.7%). Research on the wound closure percentage revealed that compared to platelet-rich plasma (PRP), processed microvascular tissue (PMVT), peripheral blood stem cells (PBSCs), microfragmented adipose tissue (MFAT), autologous bone marrow-derived stem cell therapy (ABMSCT), adipose-derived stem cells (ASCs), and dehydrated human umbilical cord allograft (EpiCord), Huoxue Shengji Decoction (HXSJD) + ABMSCT (H_Group_hematopoietic) significantly increased the wound closure percentage in DFU patients (P < 0.05). According to the SUCRA ranking, HXSJD + ABMSCT was the best therapeutic method to increase the percentage of wound closure (SUCRA = 93.8%). This study employed a network meta-analysis method, combining direct and indirect comparisons, to analyze the latest clinical data and concluded that umbilical cord mesenchymal stem cells and the combination of HXSJD + autologous bone marrow hematopoietic stem cell treatment as adjunctive therapies for DFUs may have beneficial effects. Future research needs to focus on this.

Development of alginate/chitosan hydrogel loaded with obestatin and evaluation of collagen type I, III, VEGF and TGF-β1 gene expression for skin repair in a rat model (in vitro and in vitro study).

Skin injuries have long been recognized as a prevalent type of physical injury. As a result, numerous research studies have been performed to discover an effective mechanism for wound healing. Therefore, tissue engineering of skin has developed as a potential solution for traditional methods of treating skin injuries. Alginate/Chitosan hydrogel was mixed with 1, 10, 100, and 150µM Obestatin, and evaluated the morphology, cumulative release, hemocompatibility and cytocompatibility, water absorption, cell viability, weight loss, and antibacterial characteristics of three-dimensional (3D) alginate (Alg) and chitosan (Cs) hydrogels during the process of wound curing. Various concentrations of Obestatin (Obes) were utilized for this purpose. Finally, the hydrogels that were made were tested on a full-thickness dermal wound in a Wistar rat model. The curative effects were determined by analyzing RNA expression and examining tissue stained with Masson's trichrome (MT) and hematoxylin-eosin (H&E). The biodegradability of this hydrogel was verified using weight loss testing, which demonstrated a reduction of around 90% after a period of 3 days. Furthermore, the MTT assay demonstrated that hydrogels have a beneficial effect on cell proliferation without inducing any harmful effects. Furthermore, the hydrogels produced demonstrated higher wound closure in vivo compared to the wounds treated with gauze (negative control group). Among the hydrogel groups, the chitosan/alginate/obestatin 100µM group exhibited the apical percentage of wound closure, gene expression, and secondary epithelialization, but in 150µM concentrations, we saw a lower rate of cell growth and proliferation and increase in hemolysis. In addition, RT-PCR analysis demonstrated that a concentration of 100µM obestatin resulted in an upregulation in the expression of mRNA for vascular endothelial growth factor (VEGF), collagen type I & type III, and transforming growth factor-beta (TGF-β). The present study suggests that 3D Alg/Cs hydrogels with a concentration of 100µM obestatin have the potential for clinical application in the treatment of skin injuries.

Mucoadhesive Chitosan Composite Sponge as a Carrier for β-Sitosterol Cubosomes for Thermal Burn Treatment

Our study aimed to explore the potential of using nanostructured lipid carriers (NLCs) to enhance the topical administration of β-sitosterol, a bioactive that is poorly soluble in water. Here, we have taken advantage of the unique characteristics that cubosomes have to provide as a drug delivery system. These characteristics include a large surface area, thermal stability, and the capacity to encapsulate molecules that are hydrophobic, amphiphilic, and hydrophilic. The cubosomal formulation was optimized by building a central composite design. The optimum dispersion exhibited a particle size of 88.3 nm, a zeta potential of -43, a polydispersity index of 0.358, and drug entrapment of 95.6%. It was composed of 15% w/w oleic acid and 5% w/w pluronic F127. The optimized cubosome dispersion was incorporated into a sponge formulation. The optimized cubosome sponge achieved a higher drug release compared with the cubosome dispersion. The SEM micrograph of the selected sponge showed that it has an interwoven irregular fibrous lamellar structure with low density and high porosity. The in-vivo data revealed that topical application of the β-sitosterol cubosomal sponge showed significant higher wound closure percentage relative to the β-sitosterol product (Mebo)®.Graphical

Effects of Fitoscar™ (dry extract of Stryphnodendron adstringens 50%) on the healing of acute wounds in Wistar rats

Several studies show the potential of Stryphnodendron adstringens (Mart.) Coville bark preparations in wound healing. A medicine called Fitoscar™ is based on this herbal medicine, which is commercially available and facilitates its acquisition by the patient. However, studies with Fitoscar™ are necessary to determine its effects during the healing processes. The aim of this study was to evaluate the effects of Fitoscar™ on different wound healing events induced in Wistar rats. Excisional wounds were experimentally induced in Wistar rats, divided into two groups: control: wound cleaning with warm 0.9% saline solution (39° to 40°C) and treated with Fitoscar™, subdivided into 04 subgroups, corresponding to 3, 7, 14 and 21 days of experimental period. Morphometric, macroscopic and microscopic analyzes were performed. Fitoscar™ influenced fibroblast migration and stimulated angiogenesis at days 3 and 7 respectively. While there was greater intensity of miofibroblasts at day 14. At 21 days, Fitoscar™ induced more crust and hypergranulation. While Fitoscar™ group presented lower percentage of wound closure on days 7 and 14, however all wounds healed completely in a similar time, 21 days. Fitoscar™ may favor wound healing, leading to fibroblast migration and angiogenesis during the inflammatory and proliferative phases in acute experimental wounds.

Development and Characterization of a Photocrosslinkable, Chitosan-Based, Nerve Growth Factor-Eluting Hydrogel for the Ocular Surface.

Recombinant human nerve growth factor (rhNGF; cenegermin-bkbj, OXERVATE) is the first and only U.S. Food and Drug Administration-approved treatment for moderate to severe neurotrophic keratopathy. The aim of this study was to determine the feasibility of incorporating a version of rhNGF in a mucoadhesive hydrogel capable of sustained drug release to the ocular surface. Hydrogels loaded with rhNGF were synthesized by conjugating chitosan with azidobenzoic acid (Az-Ch), adding rhNGF, and exposing the solution to ultraviolet (UV) radiation to induce photocrosslinking. Az-Ch hydrogels were evaluated for physical properties and rhNGF release profiles. Cytocompatbility of Az-Ch was assessed using immortalized human corneal limbal epithelial (HCLE) cells. TF1 erythroleukemic cell proliferation and HCLE cell proliferation and migration were used to assess the bioactivity of rhNGF released from Az-Ch hydrogels. Az-Ch formed hydrogels in <10 seconds of UV exposure and demonstrated high optical transparency (75-85 T%). Az-Ch hydrogels exhibited good cytocompatibility with no demonstratable effect on HCLE cell morphology or viability. rhNGF was released gradually over 24hours from Az-Ch hydrogels and retained its ability to induce TF1 cell proliferation. No significant difference was observed between rhNGF released from Az-Ch and freshly prepared rhNGF solutions on HCLE cell proliferation or percent wound closure after 12hours; however, both were significantly better than control (P < 0.01). rhNGF-loaded Az-Ch hydrogels exhibited favorable physical, optical, and drug-release properties, as well as retained drug bioactivity. This drug delivery system has the potential to be further developed for in vivo and translational clinical applications. Az-Ch hydrogels may be used to enhance rhNGF therapy in patients with NK.

The Effect of Breast Milk from Different Lactation Stages on in Vitro Wound Healing.

Objective: Wound healing is a complex and dynamic process essential for restoring tissue integrity and homeostasis. It is thought that breast milk contributes positively to the wound healing process, thanks to the components it contains. The aim of this study is to compare the effects of breast milk on the wound healing process at different lactation stages and to evaluate the underlying mechanism(s). Materials and Methods: The effects of breast milk from different lactation stages (colostrum, transitional, and mature milk) on wound healing were determined by in vitro scratch assay in L929 fibroblast cells. 2,2-Diphenyl-1-picrylhydrazyl (DPPH), total oxidant, and antioxidant capacity were used to confirm antioxidant effects. The effect of breast milk on netrin-1 levels in L929 cells was elucidated by ELISA. Results: Breast milk at different lactation stages promoted wound healing. While the wound closure percentage was determined as 48.7% in the control group, this rate was determined to be the highest at 81.6% in the mature milk group (p:0.0002). The free radical scavenging capacity of colostrum, transitional, and mature milk with DPPH was determined as 49.69%, 60.64%, and 80.85%, respectively, depending on the lactation stages. Netrin-1 levels detected by ELISA were determined as 490.1 ± 6.5 pg/mL in the control group, while the lowest level was determined as 376.6 ± 4.5 pg/mL in mature milk (p:0.0003). Conclusions: Breast milk, especially mature milk, promoted wound healing on L929 cells by suppressing netrin-1 levels and scavenging free radicals.

Impact of donor pool size on the variability of platelet lysate-derived extracellular vesicles for regenerative medicine

Aim: The objective of the present study was to determine the variability of platelet lysate-derived extracellular vesicles (pEV), in terms of characteristics and functionality through wound healing assays, when isolated either from platelet concentrates (PC, obtained from 5 donors) or from multiple PC (MPC, that is 50 donors). Methods: pEV were isolated under GMP-like conditions in a clean room using Size Exclusion Chromatography (SEC). The differential characteristics between pEV obtained from PC (PC-EV) or MPC (MPC-EV) were evaluated by means of protein concentration, Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM), and flow cytometry using the MACSPlex™ arrays for surface analysis profiling of EV. The functionality of the isolated pEV was determined in cell culture by metabolic activity and LDH activity determination and through a wound healing assay after 24 h treatment. Results: No significant differences were observed in the pEV characteristics evaluated, whether isolated from PC or MPC. As regards functionality, a higher wound closure percentage was obtained in those pEV pools isolated from PC (5 donors). No differences in the coefficient of variation (CV) were found when comparing all the evaluated variables of pEV derived either from PC (5 donors) or from MPC (50 donors). Conclusion: Our findings challenge the necessity of a larger donor pool for pEV isolation, revealing no significant variations in the analyzed variables of MPC-EV and PC-EV. Notably, our results suggest that, unlike platelet concentrates, a high number of donors is not required to reduce the variability of pEV, showing that the pool of only 5 donors can provide a consistent and reliable therapeutic product.

Anti-oxidant and Wound Healing Potentials of Gnetum africanum Welw and Ficus vogelii Miq Extracts

Background: Gnetum africanum and Ficus vogelii are vegetables consumed in some parts of Africa. They are used in ethno medicine for treatment of different diseases, and are particularly known to hasten wound healing. The study aimed at investigating the wound healing properties of the plants in a rat model. Materials and Methods: The powdered leaves of the two plants were successively extracted with hexane, ethyl acetate and methanol using a Soxhlet apparatus. The crude methanol extract was screened for secondary metabolites and anti-oxidant properties. The wound healing activity was evaluated using excision wound model. Thirty healthy female Wistar albino rats (150-200 kg) were used for the experiment and randomized into 5% extract + ointment, 3.5% extract + ointment, simple ointment, and gentamicin treatment groups. The ointments were administered topically daily, and wound contraction was measured every alternate day. The percentage wound closure rate and histopathology of healed wound area were determined. The antioxidant activity of the plants was determined using the DPPH scavenging activity and ferric ion reducing antioxidant power assay (FRAP). Results: The methanol extracts of both plants showed the presence tannins, alkaloids, flavonoids, saponins, and steroids in varying amounts. The antioxidant assays revealed that the extracts of both plants had good anti-oxidant properties. Extracts of Gnetum africanum at 3.5% w/w and Ficus vogelii 5% w/w exhibited potent healing activity, eliciting 100% wound closure by day 7. Conclusion: The study revealed that Gnetum africanum and Ficus vogelii have wound healing properties which scientifically justifies its use for treatment of wounds traditionally and could be developed into useful drugs for wound treatment and management.

Nanoemulsion containing Jatropha gossypiifolia leaf extract reduces dermonecrosis induced by Bothrops erythromelas venom and accelerates wound closure

Ethnopharmacological relevanceThe species Jatropha gossypiifolia, popularly known as “pinhão-roxo”, is distributed throughout Brazil, is commonly employed for topical or oral administration in treating wounds, inflammations, and snake bites. Given the significant impact of snakebites on public health and the limitations of antivenom, coupled with the diverse molecular composition of this plant species, investigating its healing and antidermonecrotic capacities is relevant. Aim of the studyThis study aimed to develop a topical nanoemulsion incorporating the hydroethanolic extract of J. gossypiifolia leaves, to evaluate its therapeutic potential, particularly in terms of its efficacy in wound healing and inhibition of dermonecrosis induced by B. erythromelas venom (BeV). Material and methodsThe extract of J. gossypiifolia (JgE) leaves was obtained by maceration and remaceration. The phytochemical analysis was conducted and J. gossypiifolia nanoemulsion (JgNe) was obtained, characterized and assessed for stability. The cytotoxicity was determined in normal cells (erythrocytes and 3T3) using hemolytic assay and cell viability assay using crystal violet staining. The antioxidant activity was evaluated by the reduction of ABTS and DPPH radicals. The evaluation of wound healing was conducted in vivo following treatment with JgNe, wherein the percentage of wound closure and inflammatory mediators. The skin irritation test was assessed in vivo by applying JgNe directly to the animal's skin. In vitro, the antivenom capacity was evaluated through enzymatic inhibition assays (phospholipase A2 and hyaluronidase) of BeV. Additionally, the in vivo antidermonecrotic activity of JgNe was evaluated by measuring the reduction of the dermonecrotic halo. ResultsThe HPLC-DAD analysis identified flavonoids, specifically vitexin, luteolin derivatives and apigenin derivatives. In addition, 95.08 ± 5.46 mg of gallic acid/g of extract and 137.92 ± 0.99 mg quercetin/g extract, was quantified. JgNe maintained stability over a 4-week period. Moreover, JgE and JgNe demonstrated no cytotoxicity in human erythrocytes and murine fibroblasts at tested concentrations (32.25–250 μg/mL). Additionally, exhibited significant antioxidant activity by reducing ABTS and DPPH radicals. The treatment with JgNe did not induce skin irritation and accelerated wound healing, with significant wound closure observed from 5th day and reduction in nitrite levels, myeloperoxidase activity, and cytokine. Both JgE and JgNe demonstrated in vitro inhibition of the phospholipase and hyaluronidase enzymes of BeV. Moreover, JgNe exhibited antidermonecrotic activity by reducing the dermonecrotic halo caused by BeV after 24 h. ConclusionsJgNe and JgE exhibited no cytotoxicity at the tested concentrations. Additionally, our findings demonstrate that JgNe has the ability to accelerate wound closure and reduce dermonecrosis caused by BeV, indicating to be promising formulation for complementary therapy to antivenom treatment.

Enhancing cutaneous wound healing: A study on the beneficial effects of nano-gelatin scaffold in rat models.

The challenges in achieving optimal outcomes for wound healing have persisted for decades, prompting ongoing exploration of interventions and management strategies. This study focuses on assessing the potential benefits of implementing a nano-gelatin scaffold for wound healing. Using a rat skin defect model, full-thickness incisional wounds were created on each side of the thoracic-lumbar regions after anesthesia. The wounds were left un-sutured, with one side covered by a gelatin nano-fibrous membrane and the other left uncovered. Wound size changes were measured on days 1, 4, 7, and 14, and on day 14, rats were sacrificed for tissue sample excision, examined with hematoxylin and eosin, and Masson's trichrome stain. Statistical comparisons were performed. The gelatin nanofibers exhibited a smooth surface with a fiber diameter of 260 ± 40 nm and porous structures with proper interconnectivity. Throughout the 14-day experimental period, significant differences in the percentage of wound closure were observed between the groups. Histological scores were higher in the experiment group, indicating less inflammation but dense and well-aligned collagen fiber formation. A preliminary clinical trial on diabetic ulcers also demonstrated promising results. This study highlights the potential of the nano-collagen fibrous membrane to reduce inflammatory infiltration and enhance fibroblast differentiation into myofibroblasts during the early stages of cutaneous wound healing. The nano-fibrous collagen membrane emerges as a promising candidate for promoting wound healing, with considerable potential for future therapeutic applications.

Experimental study of Pruthvisara taila in excised wound model in Wistar albino rats

Pruthvisara taila is a formulation indicated in the chikitsa of vrana as topical medicine in classical text Chakradatta. It contains Shuddha chitrakamoola, Shuddha vatsanabha, Shuddha karaveera, Nirgundi moola, Nadibeeja, Kanji and Karanja taila as the base. Aims and Objectives: Evaluation of wound healing property of Pruthvisara taila through experimental study. Methodology: Wound healing property in albino rats by excision wound healing model and its histopathology study. Results: Results of the study on the parameters assessed like percentage of wound contraction and histopathology study; percentage of wound closure was observed in Control group was 94.92%, in standard it was 93.73% and in test drug the percentage of wound contraction was 95.73%.The test drug, Pruthvisara taila showed more angiogenesis and formation of new blood vessels than standard group and in control group there was absence of formation of new blood vessels and proliferation of fibroblast cells. The control group did not show any collagen formation and scab formation the test drug Pruthvisara taila showed moderate formation and deposition compared to standard drug. Compared to control and standard group, the test drug, Pruthvisara taila selected in this study showed remarkable wound healing property in excised wound.

In vitro and in vivo assessment of gallic acid-chitosan/polycaprolactone conjugate electrospun nanofibers for wound healing

The development of innovative multifunctional wound healing materials based on natural bioactives has attracted a great deal of attention in recent years due to their ability to potentiate the healing process and minimize the challenges linked with conventional wound dressings. The current study demonstrates the development and evaluation of a novel nanofibrous wound healing mat made of Gallic acid-chitosan conjugate (GAC) incorporated within a polycaprolactone (PCL) matrix using an electrospinning technique. The GAC conjugate was synthesized by green synthesis using a free radical polymerization reaction to improve the chitosan's free radical scavenging properties. FTIR, DSC, XRD, and UV spectral analysis characterized the formation of GAC conjugate. The red shift observed in the UV spectrum suggested alterations in electronic transitions resulting from the creation of covalent bonds between Chitosan (CA) and Gallic acid (GA). The appearance of broader and weaker peaks in DSC and the reduced crystallinity in XRD spectrum, signify structural modifications, thereby providing valuable insights into the interaction and structural changes occurring in the GAC conjugates.The SEM image revealed a porous flake-like structural network of GAC conjugate due to the reduced intermolecular hydrogen bonding between them. The functional layer of the nanofibrous mat was produced by electrospinning GAC conjugate with polycaprolactone (PCL) to provide mechanical integrity to the nanofibrous mat. The electrospun nanofibers were characterized using FTIR, DSC, and SEM and evaluated for cell cytotoxicity, angiogenesis, and in vivo wound healing potential in female Wistar rats. The FTIR spectra confirmed the presence of GAC conjugate in the nanofibers, validating the conjugation process. The results demonstrated the successful incorporation of GAC conjugate within the PCL nanofibrous mat, thereby confirming the improvement in the biological properties of the mats. The nanofibrous mat showed angiogenesis activity in the yolk sac membrane assay confirming the property of nanofibers to facilitate cellular adhesion, migration and promotion of angiogenesis with no cytotoxic effect on the viability of mouse stromal cells. On the sixteenth day of therapy, wounds dressed with GAC/PCL nanofibrous mat exhibited a significant improvement in the percent wound closure (94.43%) as compared to the control group (p < 0.05). These results supported the application of GAC/PCL as a novel biomaterial for wound dressing to accelerate the process of wound healing.

Investigating the Wound Healing Activity of Silymarin Nanoemulsion Loaded in Chitosan Gel

Wound healing is a complex biological process involving a series of coordinated cellular and molecular events to restore tissue integrity and functionality. Challenges in achieving optimal wound healing have prompted the search for innovative therapeutic strategies. In recent years, nanotechnology-based approaches have gained attention for their potential in promoting wound healing outcomes. Silymarin, a natural polyphenolic compound, possesses diverse therapeutic properties including anti-inflammatory, antioxidant, and wound healing effects. Loading these compounds in a chitosan-based nanoemulgel formulation enhances their stability, bioavailability, and targeted delivery to the wound site. In this study, we evaluated the efficacy of silymarin nanoemulsion-loaded chitosan gel (SLY-CS-NEG) through in vitro and in vivo experiments. The evaluation encompassed wound closure percentage, inflammation reduction, and tissue regeneration assessments. The selected formulation No (F6) of SLY-CS-NEG, boasted remarkable characteristics, with a mean droplet size of 49.94±0.21 nm, a negative surface charge of −29.9±0.61, and sustained drug release over the 24 h. Animal experiments unveiled that SLY-CS-NEG significantly promoted wound healing compared to the control group. The results of this study demonstrated that the nanomedicine-based approach utilizing chitosan and nanoemulsion technology presents an innovative solution to overcome the limitations of silymarin and advance wound healing therapies.

Identification of new 5-(2,6-dichlorophenyl)-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-7-carboxylic acids as p38α MAPK inhibitors: Design, synthesis, antitumor evaluation, molecular docking and in silico studies

In pursuit of discovering novel scaffolds that demonstrate potential inhibitory activity against p38α MAPK and possess strong antitumor effects, we herein report the design and synthesis of new series of 17 final target 5-(2,6-dichlorophenyl)-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-7-carboxylic acids (4–20). Chemical characterization of the compounds was performed using FT-IR, NMR, elemental analyses and mass spectra of some representative examples. With many compounds showing potential inhibitory activity against p38α MAPK, two derivatives, 8 and 9, demonstrated the highest activity (>70 % inhibition) among the series. Derivative 9 displayed IC50 value nearly 2.5 folds more potent than 8. As anticipated, they both showed explicit interactions inside the kinase active site with the key binding amino acid residues. Screening both compounds for cytotoxic effects, they exhibited strong antitumor activities against lung (A549), breast (MCF-7 and MDA MB-231), colon (HCT-116) and liver (Hep-G2) cancers more potent than reference 5-FU. Their noticeable strong antitumor activity pointed out to the possibility of an augmented DNA binding mechanism of antitumor action besides their kinase inhibition. Both 8 and 9 exhibited strong ctDNA damaging effects in nanomolar range. Further mechanistic antitumor studies revealed ability of compounds 8 and 9 to arrest cell cycle in MCF-7 cells at S phase, while in HCT-116 treated cells at G0-G1 and G2/M phases. They also displayed apoptotic induction effects in both MCF-7 and HCT-116 with total cell deaths more than control untreated cells in reference to 5-FU. Finally, the compounds were tested for their anti-migratory potential utilizing wound healing assay. They induced a significant decrease in wound closure percentage after 24 h treatment in the examined cancer cells when compared to untreated control MCF-7 and HCT-116 cells better than 5-FU. In silico computation of physicochemical parameters revealed the drug-like properties of 8 and 9 with no violation to Lipinski’s rule of five as well as their tolerable ADMET parameters, thus suggesting their utilization as potential future drug leads amenable for further optimization and development.

Burn wound healing using adipose-derived mesenchymal stem cells and manganese nanoparticles in polycaprolactone/gelatin electrospun nanofibers in rats.

Wound healing is a major therapeutic concern in regenerative medicine. The current study aimed to investigate the second-degree burn wound treatment in rats using rat adipose- derived stem cells (ADSCs) and manganese nanoparticles (MnO2-NPs) in a polycaprolactone/gelatin electrospun nanofiber scaffold. After the synthesis of nanoparticles and electrospinning of nanofibers, the SEM analysis, contact angle, mechanical strength, blood compatibility, porosity, swelling, biodegradability, cell viability, and adhesion assays were performed. According to the results, the PCL/Gel/5%MnO2-NPs nanofiber (Mn-5%) was determined to be the most suitable scaffold. The ADSCs-seeded Mn-5% scaffolds were applied as a burn wound dressing. The wound closure rate, IL-1β, and IL-6 level, hydroxyproline, and glycosaminoglycans content were measured, and the hematoxylin and eosin, Masson's trichrome, and immunohistochemistry stainings were carried out. Based on the results, in Mn+S (ADSCs+PCL/Gel/5%MnO2-NPs nanofiber) and N+S (ADSCs+PCL/Gel nanofiber) groups, the IL-6 and IL-1β levels were reduced, and the percentage of wound closure, glycosaminoglycans, and hydroxyproline content were increased compared to the control group (P<0.05). Also, the lowest amount of α-SMA was observed in these two groups, demonstrating stem cells' role in reducing α-SMA levels and thus preventing fibrosis. Moreover, the amount of α-SMA in the Mn+S group is lower than in the N+S group and, is closer to healthy skin. According to histology results, the best type of treatment was observed in the Mn+S group. In conclusion, the ADSCs-seeded PCL/Gel/5%MnO2-NPs scaffold demonstrated considerable therapeutic effects in burn wound healing.