Deciphering resistance mechanisms and novel strategies to overcome drug resistance in ovarian cancer: a comprehensive review.

Ovarian cancer is among the most lethal gynecological cancers, primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy. Drug resistance (DR) poses the most significant challenge in treating patients with existing drugs. The Food and Drug Administration (FDA) has recently approved three new therapeutic drugs, including two poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and niraparib) and one vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) for maintenance therapy. However, resistance to these new drugs has emerged. Therefore, understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management. In this review, we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

Healing potential of curcumin nanomicelles in cutaneous burn wounds: an in vitro and in vivo study.

PURPOSE/AIM OF THE STUDY: Curcumin is the active substance of turmeric and has been shown to enhance the healing potential of burn wounds. However, its high hydrophobicity and rapid degradability are great challenges for its clinical applications. The development of new curcumin formulations may provide a potential solution to these issues. METHODS AND RESULTS: In this study, we investigated the use of curcumin nanomicelles for wound dressing and evaluated their effects on fibroblast migration and proliferation in vitro. We found that the application of curcumin nanomicelles to the wounds significantly improved wound contraction and increased the expression of transforming growth factor-1 and basic fibroblast growth factor at day 14 of the healing process. Furthermore, curcumin nanomicelles reduced the expression of interleukin-1 at days 7 and 14 post-wounding. Histopathological analysis revealed that the curcumin nanomicelles-treated burn wounds exhibited more organized granulation tissue, improved angiogenesis, and enhanced re-epithelialization. Additionally, the curcumin treatment led to increased hydroxyproline content and enhanced TGF-ß1 expression level in the wounds. The in vitro studies also demonstrated that the curcumin nanomicelles induced proliferation and migration of fibroblasts. CONCLUSION: Overall, our findings suggest that curcumin nanomicelles can be a promising candidate for the treatment of burn wounds.

Cefazolin-Loaded Double-Shelled Hollow Mesoporous Silica Nanoparticles/Polycaprolactone Nanofiber Composites: A Delivery Vehicle for Regenerative Purposes.

Purpose: As important challenges in burn injuries, infections often lead to delayed and incomplete healing. Wound infections with antimicrobial-resistant bacteria are other challenges in the management of wounds. Hence, it can be critical to synthesize scaffolds that are highly potential for loading and delivering antibiotics over long periods. Methods: Double-shelled hollow mesoporous silica nanoparticles (DSH-MSNs) were synthesized and loaded with cefazolin. Cefazolin-loaded DSH-MSNs (Cef*DSH-MSNs) were incorporated into polycaprolactone (PCL) to prepare a nanofiber-mediated drug release system. Their biological properties were assessed through antibacterial activity, cell viability, and qRT-PCR. The morphology and physicochemical properties of the nanoparticles and nanofibers were also characterized. Results: The double-shelled hollow structure of DSH-MSNs demonstrated a high loading capacity of cefazolin (51%). According to in vitro findings, the Cef*DSH-MSNs embedded in polycaprolactone nanofibers (Cef*DSH-MSNs/PCL) provided a slow release for cefazolin. The release of cefazolin from Cef*DSH-MSNs/PCL nanofibers inhibited the growth of Staphylococcus aureus. The high viability rate of human adipose-derived stem cells (hADSCs) in contact with PCL and DSH-MSNs/PCL was indicative of the biocompatibility of nanofibers. Moreover, gene expression results confirmed changes in keratinocyte-related differentiation genes in hADSCs cultured on the DSH-MSNs/PCL nanofibers with the up-regulation of involucrin. Conclusion: The high drug-loading capacity of DSH-MSNs presents these nanoparticles as suitable vehicles for drug delivery. In addition, the use of Cef*DSH-MSNs/PCL can be an effective strategy for regenerative purposes.

Dentin regeneration based on tooth tissue engineering: A review.

Missing or damaged teeth due to caries, genetic disorders, oral cancer, or infection may contribute to physical and mental impairment that reduces the quality of life. Despite major progress in dental tissue repair and those replacing missing teeth with prostheses, clinical treatments are not yet entirely satisfactory, as they do not regenerate tissues with natural teeth features. Therefore, much of the focus has centered on tissue engineering (TE) based on dental stem/progenitor cells to create bioengineered dental tissues. Many in vitro and in vivo studies have shown the use of cells in regenerating sections of a tooth or a whole tooth. Tooth tissue engineering (TTE), as a promising method for dental tissue regeneration, can form durable biological substitutes for soft and mineralized dental tissues. The cell-based TE approach, which directly seeds cells and bioactive components onto the biodegradable scaffolds, is currently the most potential method. Three essential components of this strategy are cells, scaffolds, and growth factors (GFs). This study investigates dentin regeneration after an injury such as caries using TE and stem/progenitor cell-based strategies. We begin by discussing about the biological structure of a dentin and dentinogenesis. The engineering of teeth requires knowledge of the processes that underlie the growth of an organ or tissue. Then, the three fundamental requirements for dentin regeneration, namely cell sources, GFs, and scaffolds are covered in the current study, which may ultimately lead to new insights in this field.

Effects of hydroxyapatite nanorods prepared through Elaeagnus Angustifolia extract on modulating immunomodulatory/dentin-pulp regeneration genes in DPSCs.

Dental pulp stem cells (DPSCs) are a new type of mesenchymal stem cells (MSCs) found in the oral cavity with immunomodulation and tissue regeneration capacities. This study determined the impacts of nano-hydroxyapatite (nHA) prepared through Elaeagnus Angustifolia extract (EAE) to enhance the relative expression of immunomodulatory/dentin-pulp regeneration genes in DPSCs. To produce nHA and modified nHA via EAE (nHAEA), the sol-gel technique was used. The functional groups of nanoparticles (NPs), morphological, and optical features were determined using Fourier transform infrared (FTIR), X-ray diffraction (XRD), Scanning electron microscopy (SEM) together with energy-dispersive X-ray analysis (EDAX), and Transmission electron microscopy (TEM). The cell viability was then determined using the MTT method in the presence of various EAE, nHA, and nHAEA concentrations. Target gene expression was quantified using a real-time PCR procedure after treating DPSCs with an optimally non-toxic dose of EAE and NPs. The presence of the HA phase was reported with the XRD and FTIR results. According to the results of SEM and TEM, the rod-like NPs could be fabricated. nHAEAs were found to be characterized with low crystallite size, reduced diameter, lengthier, needle-like, and less agglomerated particles compared with nHA. The real-time PCR results demonstrated that nHAEA remarkably increased the expression of human leukocyte antigen-G5 (HLA-G5), vascular endothelial growth factor (VEGF), dentin sialophosphoprotein (DSPP), and interleukin6 (IL6) genes compared to the nHA group. These findings suggest that nHAEAs might have the potential application in the stemness capability of DPSCs for the treatment of inflamed/damaged pulp.

Effect of PCL/nHAEA nanocomposite to osteo/odontogenic differentiation of dental pulp stem cells.

PURPOSE: The green synthesis of nanoparticles has recently opened up a new route in material production. The aim of this study was to evaluate the effect of nanohydroxyapatite (nHA) synthesized from Elaeagnus angustifolia (EA) extract in polycaprolactone (PCL) nanofibers (PCL/nHAEA) to odontogenic differentiation of dental pulp stem cells (DPSCs) and their potential applications for dentin tissue engineering. METHODS: Green synthesis of nHA via EA extract (nHAEA) was done by the sol-gel technique. Then electrospun nanocomposites containing of PCL blended with nHA (P/nHA) and nHAEA (P/nHAEA) were fabricated, and the characterization was evaluated via X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and the contact angle. The morphology of nanofibers and the cell adhesion capacity of DPSCs on nanofibers were evaluated using SEM. Cytocompatibility was assessed by MTT. Osteo/odontogenic differentiation ability of the nanocomposites were assessed using alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and quantitative real-time polymerase chain reaction (qPCR) technique. RESULTS: Viability and adhesion capacity of DPSCs were higher on P/nHAEA nanofibers than PCL and P/nHA nanofibers. ARS assay, ALP activity, and qPCR analysis findings confirmed that the nHAEA blended nanofibrous scaffolds substantially increased osteo/odontogenic differentiation of DPSCs. CONCLUSION: PCL/nHAEA nanocomposites had a noticeable effect on the odontogenic differentiation of DPSCs and may help to improve cell-based dentin regeneration therapies in the future.

MicroRNAs Dysregulation as Potential Biomarkers for Early Diagnosis of Endometriosis.

Endometriosis is a benign chronic disease in women that is characterized by the presence of active foci of the endometrium or endometrial tissue occurring outside of the uterus. The disease causes disabling symptoms such as pelvic pain and infertility, which negatively affect a patient's quality of life. In addition, endometriosis imposes an immense financial burden on the healthcare system. At present, laparoscopy is the gold standard for diagnosing the disease because other non-invasive diagnostic tests have less accuracy. In addition, other diagnostic tests have low accuracy. Therefore, there is an urgent need for the development of a highly sensitive, more specific, and non-invasive test for the early diagnosis of endometriosis. Numerous researchers have suggested miRNAs as potential biomarkers for endometriosis diagnosis due to their specificity and stability. However, the greatest prognostic force is the determination of several miRNAs, the expression of which varies in a given disease. Despite the identification of several miRNAs, the studies are investigatory in nature, and there is no consensus on them. In the present review, we first provide an introduction to the dysregulation of miRNAs in patients with endometriosis and the potential use of miRNAs as biomarkers in the detection of endometriosis. Then we will describe the role of the mir-200 family in endometriosis. Several studies have shown that the expression of the mir-200 family changes in endometriosis patients, suggesting that they could be used as a diagnostic biomarker and therapeutic target for endometriosis.

The effect of polyunsaturated fatty acids on the severity and mortality of COVID patients: A systematic review.

BACKGROUND: Covid-19 mortality is largely associated with a severe increase in inflammatory cytokines and polyunsaturated fatty acids (PUFAs) play an important role in modulating immune pathways and inflammatory responses; so this study was done to evaluate the effect of polyunsaturated fatty acids on the prognosis of Covid-19 disease. METHODS AND MATERIALS: A comprehensive search was conducted in PubMed, Scopus and Web of Science. For systematic identification, the search was performed based on the following keywords COVID-19, SARS-CoV-2, COVID, Coronavirus Disease 19, SARS COV- 2 Infection, SARS-CoV-2, COVID19, Coronavirus Disease, Fatty Acids, Omega-3, Omega-3 Fatty Acid, Omega-6, n 3 Fatty and Omega-9 in the mentioned databases, using OR, and AND. All searched articles were included in the study and retrieved, and End-Note X7 software was used to manage the studies. RESULTS: Findings on the relationship between omega-3 and omega-6 fatty acids and the risk of Covid-19 are various, but omega-3 supplements have been found to be 12 to 21% effective in reducing the risk of Covid-19. Most studies emphasized the increasing severity of the disease and the need for mechanical ventilation and hospitalization due to polyunsaturated fatty acid deficiency. It is also demonstrated that omega-3 fatty acid deficiency increased mortality in patients with Covid-19. However, there is also a warning that in critical cases, elevated levels of fatty acids in patients' lungs and a cytokine storm are the main reasons for mortality in Covid-19 patients. CONCLUSION: Polyunsaturated fatty acids can reduce the risk of covid-19 which could be considered as a preventative, inexpensive and safe method. However, the risk of taking high-dose omega-3 supplements before or during SARS-COV-2 infection needs to be investigated.

Effectiveness of the adipose stem cells in burn wound healing: literature review.

Adipose- stem cells (ASCs) have received much attention in the recent years and several articles have investigated the role of these cells on burn wound healing. To understand the outcomes of the ASCs therapy on burn wound healing, a systematic review was performed. This study was conducted by searching in Pubmed, ISI, and Scopus until May 2021. Thirty-six animal studies were included in this study. The findings revealed that although treatment with ASCs somewhat enhanced the healing rate, cultured ASCs on scaffolds or its combination with hydrogels could significantly increase the viability of ASCs and promote rate of healing. However, clinical studies are necessary to gain a better understanding of the role of ASCs in burn wound healing.

Fabrication and characterization of jujube extract-loaded electrospun polyvinyl alcohol nanofiber for strawberry preservation.

Recently, using of natural ingredients gains much attention in the field of food science and active packaging. In this study, first, jujube extract was investigated for its antimicrobial and antioxidant properties, and then, the effect of electrospun PVA/JE (jujube extract loaded into Poly vinyl alcohol) nanofiber as active packaging was evaluated to increase the shelf-life of strawberry. PVA/ZE nanofiber film was prepared using electrospinning method, and their morphology was confirmed by scanning electron microscopy (SEM). Fruit preservation abilities of the nanofiber film were tested on strawberries. The strawberries were then kept at 4℃ for 15 days and characterized in terms of their properties (weight loss, TSS, firmness, and sensory analysis). Results indicated that flavonoid content of jujube extract ranged from 4.80 ± 0.01 to 13.54 ± 0.08 mg CEQ/100 g, and the DPPH free radical-scavenging activity was from 210 ± 2.66 to 1498 ± 2.65 (GAE/g DW). The jujube extract also presented potent antibacterial activity against the investigated bacteria and fungi. The scanning electron microscopy (SEM) images of nanofibers had a linear morphology and bead-free structure; however, PVA/JE (jujube extract encapsulated into PVA nanofiber) had strip and flat organization. Strawberries in control group showed signs of decay and a decrease in visual appearance on the 6th. However, fruits in PVA/JE group had acceptable overall appearance for marketing, as no obvious sign of decay was observed on 12th day of storage. Active packaging containing herbal extracts and essential oils preserves the organoleptic and physicochemical properties of the fruits.

The effect of low serum calcium level on the severity and mortality of Covid patients: A systematic review and meta-analysis.

INTRODUCTION: Imbalances of various electrolytes, including calcium, are associated with the prognosis of Covid disease. This study investigated the relationship between serum calcium and clinical outcomes in patients with COVID-19. METHOD: This study is a systematic review and meta-analysis by searching PubMed, Scopus, web of sciences until August 2021 using the keywords COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID, coronavirus disease, SARS-COV-infection. 2, SARS-COV-2, COVID19, calcium, calcium isotopes, calcium radioisotopes, hypercalcemia, and hypocalcemia were performed. Heterogeneity of studies was investigated using I2 index, data were analyzed using meta-analysis (random effects model) with Comprehensive Meta-Analysis Software software. RESULTS: Finally, 25 articles were included in the study. Clinical data from 12 articles showed that 59% (95% confidence interval [CI]: 0.49-0.68) of people with COVID-19 have hypocalcemia. The results of meta-analysis showed that hypocalcemia was significantly associated with severity of the disease (p = .002), mortality in patients with COVID-19 (odds ratio [OR] = 6.99, 95% CI: 2.71-17.99), number of hospitalization days (p < .001) and admission to the intensive care unit (OR = 5.09, 95% CI: 2.14-12.10). The results also showed that there is a direct relationship between low serum calcium levels with increasing D-dimer levels (p = .02) and decreasing lymphocyte counts (p = .007). CONCLUSION: Based on the results of meta-analysis in people with lower calcium, mortality and complications are higher, therefore, serum calcium is a prognostic factor in determining the severity of the disease. Consequently, it is suggested that serum calcium levels should be considered in initial assessments.

Comparison of botulinum toxin type A and aprotinin monotherapy with combination therapy in healing of burn wounds in an animal model.

Burns are one of the most common injuries that are complicated by many challenges including infection, severe inflammatory response, excessive expression of proteases, and scar formation. The aim of this study was to investigate the effect of botulinum toxin type A (BO) and aprotinin (AP) separately or in combination (BO-AP) in healing process. Four burn wounds were created in each rat and randomly filled with silver sulfadiazine (SSD), BO, AP and BO-AP. The rats were euthanized after 7, 14, and 28 days, and their harvested wound samples were evaluated by gross pathology, histopathology, gene expression, biochemical testing, and scanning electron microscopy. Both BO and AP significantly reduced expression of interleukin-1ß (IL-1ß) and transforming growth factor-ß1 (TGF-ß1) at the 7th post wounding day. Moreover, they inhibited scar formation by reducing the TGF-ß1 level and increasing basic fibroblast growth factor (bFGF) at the 28th day. AP by decreasing protease production showed more effective role than BO in wound regeneration. AP increased tissue organization and maturation and improved cosmetic appearance of wounds, at 28 days. The best results gained when combination of BO and AP were used in healing of burn wounds. Treatment by BO-AP significantly subsided inflammation compared to the BO, AP, and SSD treated wounds. Treatment with BO-AP also reduced collagen density and led to minimal scar formation. Combination of botulinum toxin type A and aprotinin considerably increased structural and functional properties of the healing wounds by reducing scar formation and decreasing production of proteases.

Hyaluronic acid hydrogel loaded by adipose stem cells enhances wound healing by modulating IL-1ß, TGF-ß1, and bFGF in burn wound model in rat.

Application of hydrogels can be an effective technique in transferring the adipose-derived stem cells (ASCs) to injured tissue and their protection from further complications. Besides, acellular dermal matrix (ADM) has successfully been used in treatment of wounds. In this study, a combination of hylauronic acid (HA) and ASCs (HA/ASCs) was applied on burn wounds and the injured area was then covered by an ADM dressing in a rat model (ADM-HA/ASCs). Wound healing was evaluated by histopathological, histomorphometrical, molecular, biochemical, and scanning electron microscopy assessments on days 7, 14, and 28 post-wounding. ADM-HA/ASCs stimulated healing significantly more than the ADM-HA and ADM treated wounds, as it led to reduced inflammation, and improved angiogenesis and enhanced granulation tissue formation. Expression of interleukin-1ß (IL-1ß) and transforming growth factor-ß1 (TGF-ß1) was lower in the ADM-HA/ASCs treated wounds than the ADM-HA and ADM groups, at the seventh post-wounding day. ADM-HA/ASCs also enhanced the expression level of TGF-ß1 mRNA at 14 day post-wounding that was parallel to the experimental data from histological and biochemical assessments and confirmed the positive role of ASCs in repair of burn wounds. Additionally, increase in basic fibroblast growth factor (bFGF) expression and decreased TGF-ß1 level on the 28th post-wounding day indicated the anti-scarring activity of ASCs. HA loaded by adipose stem cells can represent a promising strategy in accelerating burn wound healing.

Application of honey as a protective material in maintaining the viability of adipose stem cells in burn wound healing: A histological, molecular and biochemical study.

Enhanced resistance to oxidative stress makes the adipose stem cells (ASCs) able to promote wound repair and regeneration. Such cells can be achieved by addition of an anti-oxidant to cell culture medium. In this study, a combination of honey (H) and ASCs was applied on burn wounds and the injured area was then covered by a tegaderm (T) dressing in a rat model. Wound healing was evaluated by histopathological, histomorphometrical, molecular, scanning electron microscopy, and biochemical assessments on days 7, 14, and 28 post-wounding. Treatment with ASCs-containing honey (T-H/ASC) resulted in substantial reduction in the level of pro-inflammatory cytokines including interleukin-1ß (IL-1ß) and transforming growth factor-ß1 (TGF-ß1) in wound bed, at 7 day post-surgery. T-H/ASCs also elevated the level of bFGF expression, indicating that ASCs enhanced angiogenesis, at 7 day post-wounding. T-H/ASCs significantly improved angiogenesis, re-epithelialization, and granulation tissue formation compared to other treatment regimes, at 14 day post-surgery. These outcomes were in exceptionally good agreement with the histological and biochemical findings. Increased bFGF level in the T-H/ASCs treated wounds at the 28th day post-surgery showed the anti-scarring activity of ASCs. Honey can be considered as a protective material in maintaining the viability of ASCs and improving the cellular resistance to oxidative stress. Furthermore, combination of ASCs and honey can provide a nutrient media for the ASCs and enhance the ability of regeneration of the ASC-based therapies.

Basic concepts, current evidence, and future potential for gene therapy in managing cutaneous wounds.

OBJECTIVE: Several studies have investigated the role of gene therapy in the healing process. The aim of this review is to explain the gene delivery systems in wound area. RESULTS: Ninety-two studies were included and comprehensively overviewed. We described the importance of viral vectors such as adenoviruses, adeno-associated viruses, and retroviruses, and conventional non-viral vectors such as naked DNA injections, liposomes, gene gun, electroporation, and nanoparticles in achieving high-level expression of genes. Application of viral transfection, liposomal vectors, and electroporation were the main gene delivery systems. Genes encoding for growth factors or cytokines have been shown to result in a better wound closure in comparison to application of the synthetic growth factors. In addition, a combination of stem cell and gene therapy has been found an effective approach in regeneration of cutaneous wounds. CONCLUSIONS: This article gives an overview of the methods and investigations applied on gene therapy in wound healing. However, clinical investigations need to be undertaken to gain a better understanding of gene delivery technologies and their roles in stimulating wound repair.

Role of sugar-based compounds on cutaneous wound healing: what is the evidence?

Cutaneous wound healing is a complex orchestrated process influenced by many endogenous and exogenous imbalances. The main goal of tissue regeneration in wound healing is to increase wound contraction and reduce scar formation, effectively to regenerate a new healthy epidermis and prevent scar contracture. Additionally, prevention, control and treatment of wound infections, particularly in burn wounds, is a vital strategy in the healing process. It was previously supposed that local application of sugar-based materials increases the chance of wound infection and delays wound healing. This review shows that topical application of sugar-based compounds has no negative effects on different wound types. Whereas, hyperglycaemia created by diabetes, stress or certain medications can act to impair wound healing. Therefore, this work was designed to review the recent studies that evaluated the role of sugar-based compounds on wound healing and to demonstrate in various cutaneous wound models how these compounds may be involved in healing. It also deals with different physio-pharmacologic conditions resulting in hyperglycaemia in different models of cutaneous wound healing in order to illustrate the role of endogenous glucose in wound healing and remodelling.

Healing potential of injectable Aloe vera hydrogel loaded by adipose-derived stem cell in skin tissue-engineering in a rat burn wound model.

Adipose stem cells (ASCs) are a great promise in wound healing due to their potential in differentiating into various cell lineages and secreting growth factors. The purpose of this study is to evaluate the in vivo effects of Aloe vera hydrogel loaded by allogeneic ASCs on a rat burn wound model. The ASCs were isolated, cultured and mixed with 50% Aloe vera hydrogel and injected intradermally around the wound. Demineralized bone matrix (DBM) was used as dressing in the experiment. The burn wound-healing properties of different experimental groups were investigated by histopathological, molecular, scanning electron microscopic and biochemical analysis at the 7th, 14th and 28th days post-wounding. The Aloe vera and DBM-Aloe vera groups showed almost similar healing properties, while treatment by DBM-Aloe vera/ASCs significantly enhanced wound healing. The levels of transforming growth factor-ß1 (TGF-ß1) and interleukin-1ß markedly decreased at the 7th day post-injury, in the DBM-Aloe vera/ASC-treated group, suggesting that this treatment regime subsided the inflammatory responses. Angiogenesis, re-epithelialization and the level of TGF-ß1 in the wounds treated with DBM-Aloe vera/ASCs were also remarkably higher than those of other groups, at the 14th day post-injury. Besides, scar formation significantly decreased in the DBM-Aloe vera/ASC-treated wounds when compared with other groups. Our biochemical results were in agreement with the molecular and histopathological findings and strongly demonstrated that a DBM-Aloe vera/ASC composite can stimulate burn wound healing. These results suggest that the DBM-Aloe vera/ASC composite can be considered as a promising therapeutic strategy in the treatment of burn wounds.

Kefir Accelerates Burn Wound Healing Through Inducing Fibroblast Cell Migration In Vitro and Modulating the Expression of IL-1ß, TGF-ß1, and bFGF Genes In Vivo.

Kefir is a natural probiotic compound with a long history of health benefits which can improve wound healing. This study investigated the regeneration potential of kefir in vitro scratch assay and in vivo burn wound in rat model. Cytotoxicity of different concentrations of kefir was evaluated by colorimetric methylthiazoltetrazolium assay. A scratch wound experiment was performed to investigate the ability of kefir in reducing the gap of wounds in a dose-dependent manner, in vitro. The standardized kefir was incorporated into silver sulfadiazine (SSD) and applied on burn wounds in vivo, and was compared with the SSD and negative control groups after 7, 14, and 28 days of treatment. The wound sites were then removed for histopathological and morphometric analyses, assessment of interleukin-1ß (IL-1ß), transforming growth factor-ß1 (TGF-ß1), basic fibroblast growth factor (bFGF), dry weight, and hydroxyproline contents. Kefir enhanced proliferation and migration of human dermal fibroblast (HDF) cells and 12.50, 6.25, and 3.12 µL/mL concentrations showed better effects on the scratch assay. Kefir resulted in reduction of IL-1ß and TGF-ß1 expression at day 7 compared to the negative control. Kefir also reduced the expression of IL-1ß at days 14 and 28 and stimulated bFGF at day 28. It significantly improved the dry matter and hydroxyproline contents in the burn wounds. Kefir also resulted in enhanced angiogenesis and elevated migration and proliferation of fibroblasts and improved fibrous connective tissue formation in the wound area. The morphometric results indicated significant global contraction values in the kefir-treated wounds compared to other groups. Taken together, the findings suggest that kefir has considerable ability to accelerate healing of the burn wounds. Therefore, kefir may be a possible option to improve the outcomes of severe burns.

Topical delivery of chitosan-capped silver nanoparticles speeds up healing in burn wounds: A preclinical study.

This study investigated the effects of topical application of chitosan-capped silver nanoparticles (Ch/AgNPs) on burn wound healing. The chitosan-capped silver nanoparticles were synthesized in one step from the silver nitrate, sodium borohydride, and chitosan and were characterized using transmission electron microscopy, fourier transform infrared spectroscopy, and X-ray diffraction methods. The antioxidant assay was performed to evaluate the scavenging rate. The effects of Ch/AgNPs on burn wound healing was also evaluated by histopathological, molecular, and biochemical evaluations after 7, 14 and 28 days of treatment in a rat model. In comparison to the negative control and silver sulfadiazine groups, the Ch/AgNPs treated wounds exhibited significantly lower inflammatory reaction as determined by the reduced level of interleukin-1ß (IL-1ß) and neutrophil counts. Treatment by Ch/AgNPs also significantly enhanced re-epithelialization, so that complete epithelialization was achieved in the lesions of the animals of this group, at the 7th day post-wounding. Rapid re-epithelialization, improved granulation tissue formation, reduced IL-1ß expression, mild inflammation, and increased transforming growth factor-ß1 and basic fibroblast growth factor, at 7 days post-wounding, are convincing reasons to confirm this idea that Ch/AgNPs are effective in speeding up the wound healing stages. Our histopathological findings are in agreement with the molecular and biochemical results and strongly demonstrate that Ch/AgNPs stimulate burn wound healing by decreasing the length of repair phases. Therefore, on the basis of our findings, Ch/AgNPs can be a promising candidate in stimulating wound repair and regeneration.

Effectiveness of a Crocus sativus Extract on Burn Wounds in Rats.

Crocus sativus is a spice with various pharmacological properties. Crocin, picrocrocin, and safranal are the main compositions of saffron that have recently been considered in the therapy of many diseases. High-performance liquid chromatography analysis revealed presence of these compounds in our saffron extract. This study was carried out to evaluate the effect of saffron on burn wound healing at an in vivo model. Saffron was topically applied on burn wounds in rats; the percentage of wound closure, wound contraction, and the levels of main cytokines and growth factors were measured. The saffron extract was also applied to evaluate the proliferation and migration of human dermal fibroblast (HDF) cells using in vitro scratch assay and resulted in active proliferation and migration of the HDF cells in a dose-dependent manner. A clear enhanced healing was observed in the saffron-treated wounds compared to the silver sulfadiazine and negative control groups. Decreased expression of interleukin-1ß and transforming growth factor-ß1 (TGF-ß1) during the inflammatory phase demonstrated the role of saffron in promoting wound healing. In addition, enhanced TGF-ß1 expression during the proliferative phase and basic fibroblast growth factor during the remodeling phase represented regenerative and anti-scarring role of saffron, respectively. Our histological and biochemical findings also confirmed that saffron significantly stimulated burn wound healing by modulating healing phases. Therefore, saffron can be an optimal option in promoting skin repair and regeneration. Application of this herbal medicinal drug should be encouraged because of its availability and negligible side effects.