Enhanced wound regeneration by PGS/PLA fiber dressing containing platelet-rich plasma: an in vitro study.

Novel wound dressings with therapeutic effects are being continually designed to improve the wound healing process. In this study, the structural, chemical, physical, and biological properties of an electrospun poly glycerol sebacate/poly lactide acid/platelet-rich plasma (PGS/PLA-PRP) nanofibers were evaluated to determine its impacts on in vitro wound healing. Results revealed desirable cell viability in the Fibroblast (L929) and macrophage (RAW-264.7) cell lines as well as human umbilical vein endothelial cells (HUVEC). Cell migration was evident in the scratch assay (L929 cell line) so that it promoted scratch contraction to accelerate in vitro wound healing. Moreover, addition of PRP to the fiber structure led to enhanced collagen deposition (~ 2 times) in comparison with PGS/PLA scaffolds. While by addition PRP to PGS/PLA fibers not only decreased the expression levels of pro-inflammatory cytokines (IL-6 and TNF-α) in RAW-264.7 cells but also led to significantly increased levels of cytokine (IL-10) and the growth factor (TGF-ß), which are related to the anti-inflammatory phase (M2 phenotype). Finally, PGS/PLA-PRP was found to induce a significant level of angiogenesis by forming branching points, loops, and tubes. Based on the results obtained, the PGS/PLA-PRP dressing developed might be a promising evolution in skin tissue engineering ensuring improved wound healing and tissue regeneration.

Carboxymethyl cellulose/sodium alginate hydrogel with anti-inflammatory capabilities for accelerated wound healing; In vitro and in vivo study.

Recently, managing the chronic skin wounds has become increasingly challenging for healthcare professionals due to the intricate orchestration of cellular and molecular processes involved that lead to the uncontrollable inflammatory reactions which hinder the healing process. Therefore, different types of wound dressings with immunomodulatory properties have been developed in recent years to effectively regulate the immune responses, enhance angiogenesis, promote re-epithelialization, and accelerate the wound healing process. This study aims to develop a new type of immunomodulatory wound dressing utilizing carboxymethyl cellulose (CMC)/sodium alginate (Alg)-simvastatin (SIM) to simultaneously enhance the inflammatory responses and the wound healing ratio. The CMC/Alg-SIM hydrogels exhibited appropriate swelling ratio, water vapor transmission rate, and desirable degradation rate, depending on the SIM content. The fabricated dressing showed sustained release of SIM (during 5 days) that improved the proliferation of skin cells. According to the in vitro findings, the CMC/Alg-SIM hydrogel exhibited controlled pro-inflammatory responses (decreased 2.5- and 1.6-times IL-6 and TNF-α, respectively) and improved secretion of anti-inflammatory cytokines (increased 1.5- and 1.3-times IL-10 and TGF-ß, respectively) in comparison with CMC/Alg. Furthermore, the CMC/Alg-SIM hydrogel facilitated rapid wound healing in the rat model with a full-thickness skin defect. After 14 days post-surgery, the wound healing ratio in the CMC/Alg hydrogel group (∼93%) was significantly greater than the control group (∼58%). Therefore, the engineered CMC/Alg-SIM hydrogel with desired immunomodulatory properties possesses the potential to enhance and accelerate skin regeneration for the management of chronic wound healing.

Co-release of nitric oxide and L-arginine from poly (ß-amino ester)-based adhesive reprogram macrophages for accelerated wound healing and angiogenesis in vitro and in vivo.

Recently, insufficient angiogenesis and prolonged inflammation are crucial challenges of chronic skin wound healing. The sustained release of L-Arginine (L-Arg) and nitric oxide (NO) production can control immune responses, improve angiogenesis, enhance re-epithelialization, and accelerate wound healing. Here, we aim to improve wound healing via the controlled release of NO and L-Arg from poly (ß-amino ester) (PßAE). In this regard, PßAE is functionalized with methacrylate poly-L-Arg (PAMA), and the role of PAMA content (50, 66, and 75 wt%) on the adhesive properties, L-Arg, and NO release, as well as collagen deposition, inflammatory responses, and angiogenesis, is investigated in vitro and in vivo. Results show that the PAMA/ PßAE could provide suitable adhesive strength (~25 kPa) for wound healing application. In addition, increasing the PAMA content from 50 to 75 wt% results in an increased release of L-Arg (approximately 1.4-1.7 times) and enhanced NO production (approximately 2 times), promoting skin cell proliferation and migration. The in vitro studies also show that compared to PßAE hydrogel, incorporation of 66 wt% PAMA (PAMA 66 sample) reveals superior collagen I synthesis (~ 3-4 times) of fibroblasts, controlled pro-inflammatory and improved anti-inflammatory cytokines secretion of macrophages, and accelerated angiogenesis (~1.5-2 times). In vivo studies in a rat model with a full-thickness skin defect also demonstrate the PAMA66 sample could accelerate wound healing (~98 %) and angiogenesis, compared to control (untreated wound) and Tegaderm™ commercial wound dressing. In summary, the engineered multifunctional PAMA functionalized PßAE hydrogel with desired NO and L-Arg release, and adhesive properties can potentially reprogram macrophages and accelerate skin healing for chronic wound healing.

Coaxial electrospun PGS/PCL and PGS/PGS-PCL nanofibrous membrane containing platelet-rich plasma for skin tissue engineering.

Wound healing will be enhanced using structures with therapeutic effects. This study fabricated a novel nanofibrous scaffold for skin tissue regeneration using a coaxial structure polyglycerol sebacate (PGS)/platelet-rich plasma (PRP) was embedded in the core and two different compositions were selected for the shell; in one group, polycaprolactone (PCL), and in the other group, PGS/PCL blend was used. The physical, mechanical behavior, drug delivery patterns, and cell response of scaffolds were evaluated. Results revealed that by adding PRP to the core and PGS to the shell, fiber diameters decreased to 260.8 ± 31.3 nm. It also decreased the water contact angle from 66° to 32°, that is ideal candidate for cell attachment. The drug release showed a burst release pattern in the first 30 min, followed by a continuous and slow release during the first day. Adding PGS to the shell decreased the elastic modulus, and its value reached about 500 kPa, which is near the skin elastic modulus and will lead to greater mechanical compatibility for cell proliferation. Particularly, the addition of PRP to the fiber structure enhanced the cell viability and cell adhesion with a suitable morphology. Based on the results, nanofibrous PGS-PRP/PGS-PCL dressing can enhance skin tissue regeneration.

Antibacterial and pH-sensitive methacrylate poly-L-Arginine/poly (ß-amino ester) polymer for soft tissue engineering.

During the last decade, pH-sensitive biomaterials containing antibacterial agents have grown exponentially in soft tissue engineering. The aim of this study is to synthesize a biodegradable pH sensitive and antibacterial hydrogel with adjustable mechanical and physical properties for soft tissue engineering. This biodegradable copolymer hydrogel was made of Poly-L-Arginine methacrylate (Poly-L-ArgMA) and different poly (ß- amino ester) (PßAE) polymers. PßAE was prepared with four different diacrylate/diamine monomers including; 1.1:1 (PßAE1), 1.5:1 (PßAE1.5), 2:1 (PßAE2), and 3:1 (PßAE3), which was UV cross-linked using dimethoxy phenyl-acetophenone agent. These PßAE were then used for preparation of Poly-L-ArgMA/PßAE polymers and revealed a tunable swelling ratio, depending on the pH conditions. Noticeably, the swelling ratio increased by 1.5 times when the pH decreased from 7.4 to 5.6 in the Poly-L-ArgMA/PßAE1.5 sample. Also, the controllable degradation rate and different mechanical properties were obtained, depending on the PßAE monomer ratio. Noticeably, the tensile strength of the PßAE hydrogel increased from 0.10 ± 0.04 MPa to 2.42 ± 0.3 MPa, when the acrylate/diamine monomer molar ratio increased from 1.1:1 to 3:1. In addition, Poly-L-ArgMA/PßAE samples significantly improved L929 cell viability, attachment and proliferation. Poly-L-ArgMA also enhanced the antibacterial activities of PßAE against both Escherichia coli (~5.1 times) and Staphylococcus aureus (~2.7 times). In summary, the antibacterial and pH-sensitive Poly-L-ArgMA/PßAE1.5 with suitable mechanical, degradation and biological properties could be an appropriate candidate for soft tissue engineering, specifically wound healing applications.

A double-blind randomized clinical trial of Dracocephalum kotschyi Boiss. in the patients with diarrhea-predominant irritable bowel syndrome.

Background and purpose: Irritable bowel syndrome (IBS) is a disease that shows its impacts on many populations worldwide. It is known as a functional disorder of the gastrointestinal tract followed by diarrhea and fecal inconsistency. Due to the lack of treatment in the allopathic medicine system for IBS, people in the western world use different herbs as alternative medicine. In the present study, we evaluated the dried extract of Dracocephalum kotschyi against IBS. Experimental approach: In a randomized, double-blinded, placebo-controlled clinical trial, 76 diarrhea-predominant IBS patients were randomly assigned to two equal groups: the control group (given the placebo capsule containing 250 mg of dibasic calcium phosphate) and the treatment groups (given the capsule containing 75 mg of the dry extract of D. kotschyi and 175 mg of dibasic calcium phosphate as filler). The study was conducted based on Rome III criteria. We studied symptoms included in Rome III criteria and divided the study into the duration of drug administration and four weeks after drug administration. These groups were compared with those of the control group. Findings/Results: Significant improvements were found in the quality of life, temperament, and IBS symptoms throughout the treatment duration. Quality of life, temperature, and IBS symptoms were slightly decreased in the treatment group 4 weeks after stopping the treatment. While concluding the study, we found D. kotschyi effective against IBS. Conclusion and implications: Whole extract of D. kotschyi modulated symptoms of IBS patients and improved their quality of life.

Current knowledge of immunomodulation strategies for chronic skin wound repair.

In orchestrating the wound healing process, the immune system plays a critical role. Hence, controlling the immune system to repair skin defects is an attractive approach. The highly complex immune system includes the coordinated actions of several immune cells, which can produce various inflammatory and antiinflammatory cytokines and affect the healing of skin wounds. This process can be optimized using biomaterials, bioactive molecules, and cell delivery. The present review discusses various immunomodulation strategies for supporting the healing of chronic wounds. In this regard, following the evolution of the immune system and its role in the wound healing mechanism, the interaction between the extracellular mechanism and immune cells for acceleration wound healing will be firstly investigated. Consequently, the immune-based chronic wounds will be briefly examined and the mechanism of progression, and conventional methods of their treatment are evaluated. In the following, various biomaterials-based immunomodulation strategies are introduced to stimulate and control the immune system to treat and regenerate skin defects. Other effective methods of controlling the immune system in wound healing which is the release of bioactive agents (such as antiinflammatory, antigens, and immunomodulators) and stem cell therapy at the site of injury are reviewed.

Comparing the wound healing effect of a controlled release wound dressing containing curcumin/ciprofloxacin and simvastatin/ciprofloxacin in a rat model: A preclinical study.

Inflammation and infection are two main factors predisposing a wound to become a chronic one. Degradable wound dressings involving the controlled release of suitable drugs at the ulcer site are one of the solutions to make wounds healing progress smoothly and rapidly. In this research, biodegradable dressings made of polyglycerol sebacate/polycaprolactone (PGS/PCL) containing curcumin/ciprofloxacin (CUR/CIP) and simvastatin/ciprofloxacin (SIM/CIP) were prepared by using the coaxial electrospinning method. Transmission electron microscopy for uniform core/shell structure, swelling ratio, and drug release pattern of the wound dressings were evaluated. At the in vivo study, histometric, histopathologic, and collagen expression study was performed. The PGS/PCL samples containing SIM/CIP showed a burst release pattern of CIP with a delay in the release of SIM; meanwhile, in the samples containing CUR/CIP, both drugs showed a burst release behavior. No cytotoxicity response was observed in the study groups. The in vivo study showed that wound closure was almost completed only in the SIM/CIP group after 14 days. After 14 days, in the wound treated with SIM/CIP dressing, the amount of collagen deposition and angiogenesis was higher than that of the others. These results clearly showed the effect of SIM/CIP on the improvement of the wound healing efficiency in the long term (14 days) and the effect of CUR/CIP on wound contraction in the short term (4 day). It seems, therefore, that the use of SIM and CUR simultaneously in a wound dressing could cause a synergistic effect in the wound repair.

Hematological Parameters Changes in Patients with Breast Cancer.

BACKGROUND: Breast cancer is the most common cancer diagnosis among women worldwide. It accounts for 25% of all women's cancers. This cancer is invasive with a high mortality rate. Evaluation of hematological factors is one of the reliable paraclinical methods to diagnose diseases. Hematological parameters can predict severity, mortality, and follow-up treatment in patients with breast cancer. The aim of this study was to evaluate hematological parameters as useful markers to distinguish between patients with breast cancer and healthy individuals. METHODS: This study was conducted on 160 women with breast cancer as case groups and 160 healthy women as controls. Hematological parameters were analyzed using the Sysmex KX-21N™ automated hematology analyzer system. RESULTS: The difference between the breast cancer patients and the control group was significant in Hb, HCT, MCV, RDW parameters, and MPV/PLT ratio (p < 0.05) (effect size > 0.8). Also, there was a moderate difference between the two groups in MPV and MCH parameters (p < 0.05) (0.5 < effect size < 0.8). Meanwhile, two groups had a minimal difference in NLR, PLR, and MCHC parameters and WBC and RBC count (p < 0.05) (0.2 < effect size < 0.5). CONCLUSIONS: The routine blood test is the most accessible and essential examination tool for disease diagnosis. Our results showed that hematological parameters, like MCV, RDW, MPV, MPV/PLT count, NLR, and PLR, can differentiate breast cancer patients from healthy individuals.

Corrigendum to "Medicinal Properties and Active Constituents of Dracocephalum kotschyi and Its Significance in Iran: A Systematic Review".

[This corrects the article DOI: 10.1155/2019/9465309.].

Medicinal Properties and Active Constituents of Dracocephalum kotschyi and Its Significance in Iran: A Systematic Review.

OBJECTIVES: Dracocephalum has over 60 species and is found mainly in the temperate regions of Asia and Europe. One of these species, i.e., Dracocephalum kotschyi Boiss, is known to have a number of medicinal properties and active ingredients in many parts of the world. Despite being an endemic wild-flowering plant of great importance, the plant is currently considered endangered in Iran. Besides, there is paucity of information on the significance of the medicinal properties and active constituents of D. kotschyi among the Iranian people. On that account a systematic review of studies reporting on the medicinal properties and active ingredients and its significance to human and animal health was conducted and the existing knowledge gaps were identified. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used in the search for published articles on medicinal properties and active ingredients of D. kotschyi and its significance on humans and animals in Iran. The search was confined to scientific articles from repositories of popular data bases and search engines among them PubMed, Web of Science, Google Scholar, Science Direct, SpringerLink, and Scopus. The search narrowed down on scientific journals, books, and book chapters focusing on the medicinal properties of D. kotschyi in Iran for the period between 1970 and 2018. RESULTS: A total of 1158 scientific articles were sourced from the various databases, out of which 38 met the search criteria and qualified for this review. The studies were conducted in only 9 of the 31 provinces of Iran, with a large proportion in Isfahan province, central Iran. The studies showed that all plant parts (roots, aerial parts, flowers, and leaves) had active constituents. Essential oils and aerial plant parts were the main components studied. Nevertheless, the most frequently reported constituents were xanthomicrol, limonene, luteolin, geranial, apigenin, and calycopterin. A number of medicinal properties were reported among them antioxidant, antibacterial, anticancerous, antinociceptive, antihyperlipidemic, antispasmodic, cytotoxic, and immunomodulatory effects. The plant was also reported to be a remedy for inflammatory pain, headaches, congestion, liver disorders, ulcer, fever, renal pain, dyspepsia, stomach ache, abdominal pain, joints pains, muscle spasm, congestion, bloating, and wound healing effects, among others. CONCLUSION: This review has shown that D. kotschyi is an important medicinal plant with a large number of active constituents and great potential to safeguard human and animal health in Iran. However, over utilization of the D. kotschyi plant is already endangering its existence. Nevertheless, more studies need be conducted across the country.

A New Indole Derivative Decreased SALL4 Gene Expression in Acute Promyelocytic Leukemia Cell Line (NB4)

Background: Acute myeloblastic leukemia (AML) is a clonal disorder due to bone marrow failure and uncontrolled proliferation of myeloid lineage. Acute promyelocytic leukemia (APL) is a subtype of AML. Heterocyclic compounds, such as indole, are considered as attractive candidates for cancer therapy, due to their abundance in nature and known biological activity. Sal-like protein (SALL4) is a zinc finger transcription factor involving in the multi-potency of stem cells, in the NB4 cell line. This study was aimed to evaluate the effects of basal indole and its new derivative, 2-(1-((2, 4-Aril)imino)-2,2,2-trifluoroethyl) phenyl-1H Indole-3- carbaldehyde (TFPHC), on the expression of SALL4. Methods: Cells were cultured and treated with different concentrations (75, 150, and 300 µg/mL) of the new indole derivative and DMSO, as a vehicle control, for 24 and 48 hours. Cell proliferation was evaluated by using Trypan blue exclusion and MTT assays. The percentage of apoptotic cells was determined by flowcytometry analysis using the Annexin V/PI apoptosis detection kit; mRNA expression of SALL4 was studied using absolute quantitative RT-PCR. Data were analyzed by student's t-test. P<0.05 were considered statistically significant. Results: Our findings demonstrated the effects of new indole derivatives on SALL4 mRNA expression. Expression of SALL4 mRNA was significantly decreased at 75, 150, and 300 µg/mL concentrations. Conclusion: SALL4 plays a role in the survival of APL cells. SALL4 expression could be suppressed by the novel indole derivative. Additionally, SALL4 gene suppression can serve as a target in APL therapy.