Human Dermal Fibroblast Cells Research Articles

Synthesis and Biological Evaluation of 12-Aryl-11-hydroxy-5,6-dihydropyrrolo[2″,1″:3',4']pyrazino[1',2':1,5]pyrrolo[2,3-d]pyridazine-8(9H)-one Derivatives as Potential Cytotoxic Agents.

In the present paper, a facile and efficient synthetic procedure has been applied to obtain dihydrodipyrrolo[1,2-a:2',1'-c]pyrazine-2,3-dicarboxylates (5a-s), which have subsequently gone through the cyclization in the presence of hydrazine hydrate to afford 12-aryl-11-hydroxy-5,6-dihydropyrrolo[2″,1″:3',4']pyrazino[1',2':1,5]pyrrolo[2,3-d]pyridazine-8(9H)-ones (7a-q). The molecular structures of these novel compounds were extensively examined through the analysis of spectroscopic data in combination with X-ray crystallography techniques. Following that, the in vitro cytotoxic activities of all derivatives against three human cancer cell lines (Panc-1, PC3, and MDA-MB-231) were comprehensively evaluated alongside the assessment on normal human dermal fibroblast (HDF) cells using the MTT assay. Among the compounds, the 3-nitrophenyl derivative (7m) from the second series showed the best antiproliferative activity against all tested cell lines, particularly against Panc-1 cell line, (IC50 = 12.54 μM), being nearly twice as potent as the standard drug etoposide. The induction of apoptosis and sub-G1 cell cycle arrest in Panc-1 cancer cells by compound 7m was confirmed through further assessment. Moreover, the inhibition of kinases and the induction of cellular apoptosis by compound 7m in Panc-1 cancer cells were validated using the Western blotting assay.

Inhibitory Effects of Latilactobacillus curvatus BYB3 Cell-Free Extract on Human Melanoma B16F10 Cells and Tumorigenic Mice.

Latilactobacillus curvatus BYB3 (BYB3) is a species of lactic acid bacteria, formerly named Lactobacillus curvatus, which is isolated from kimchi. In this study, the effect of BYB3, Lactobacillus rhamnosus GG, and Lactobacillus acidophilus GP1B strain extracts at various concentrations was examined on B16F10, a mouse melanoma cell line. Cell viability was examined via MTT assay, and the results indicated that compared to the other two probiotics, BYB3 significantly decreased the total percentages of viable cells. The effects of BYB3 on cell migration and proliferation in B16F10 cells were evaluated using wound healing mobility and proliferation assays, respectively; the results indicated that BYB3 inhibits cell migration and proliferation in a concentration-dependent manner. Using human dermal fibroblast cells to investigate BYB3 extract in vivo had no effect on skin-related cells. Nonetheless, the BYB3 extract inhibited tumor growth in a mouse model, as demonstrated by liver slices. Therefore, this suggests that using BYB3 extract to inhibit melanoma may be a novel approach.

Fabrication of wound dressings: Herbal extract-loaded nanoliposomes embedded in fungal chitosan/polycaprolactone electrospun nanofibers for tissue regeneration.

Wound healing is a complex process and one of the major therapeutic and economic subjects in the pharmaceutical area. In recent years, the fabrication of nano-sized wound dressing models has attracted great attention for tissue regeneration. Plant extracts loaded nanoparticles are environmentally friendly and non-toxic and the release of the bioactive substance will be controlled to the wound area. This study aims to fabricate wound dressing models that contain bioactive components for tissue regeneration. Fungal chitosan/polycaprolactone nanofiber was fabricated by electrospinning and it has been characterized. Plant extracts loaded nanoliposomes were prepared, characterized, and embedded in nanofiber structures. The effectiveness of wound dressing models for tissue regeneration was evaluated by in vitro and in vivo studies. It was observed that all wound dressing models positively affect the cell viability of human dermal fibroblast cells. It was determined that plant extracts loaded nanoparticles embedded in nanofibers increased in cell viability than nanoparticles that were non-embedded in nanofiber structures. Histological analysis showed that plant extract-loaded nanoliposomes embedded in chitosan/PCL nanofibers were used for tissue regeneration. The most effective nanofibers were determined as Wd-ClNL nanofibers. RESEARCH HIGHLIGHTS: Hypericum perforatum L. and Cistus laurifolius L. were prepared by modified ultrasonic extraction method. Fungal chitosan/polycaprolactone nanofiber was fabricated by electrospinning and it has been characterized. Plant extract-loaded nanoliposomes were prepared, and characterized. They were embedded in chitosan/polycaprolactone nanofiber. Effects of the wound dressing model were analyzed by in vitro and in vivo assays for tissue regeneration.

Preventive effect of andrographolide against ultraviolet-B radiation-induced oxidative stress and apoptotic signaling in human dermal fibroblasts.

Ultraviolet radiation induces oxidative photoaging in the skin cells. In this study, we investigated the ability of andrographolide (ADP) to protect human dermal fibroblasts (HDFa) from UVB radiation-induced oxidative stress and apoptosis. The HDFa cells were exposed to UVB (19.8 mJ/cm2 ) radiation in the presence or absence of ADP (7 μM) and then oxidative stress and apoptotic protein expression were analyzed. UVB exposure resulted in a significant decline in the activity of antioxidant enzymes and altered mitochondrial membrane potential (MMP). Furthermore, UVB-irradiation causes increased intracellular reactive oxygen species(ROS) production, apoptotic morphological changes, and lipid peroxidation levels in the HDFa. Moreover, the pretreatment with ADP reduced the UVB-induced cytotoxicity, ROS production, and increased antioxidant enzymes activity. Further, the ADP pretreatment prevents the UVB-induced loss of MMP and apoptotic signaling in HDFa cells. Therefore, the present results suggest that ADP protects HDFa cells from UVB-induced oxidative stress and apoptotic damage.

Study of anticancer effects of platinum levetiracetam and levetiracetam via cancer biomarkers genes expression on HepG2 cell line.

High expression of some anticancer biomarkers such as telomerase and B cell lymphoma-2(Bcl-2), microRNA-21(miRNA-21), and low expression FAS ligand (FASLG) are reported in many cancers. Some anticancer drugs such as Levetiracetam(Lev) produce their effects via the change of expression of these biomarkers. The present study aimed to evaluate the anti-cancer effects of a new compound, Platinum Levetiracetam(Pt-Lev), gene expression of mentioned biomarkers on hepatocyte G2 (HepG2) cells compared to Lev. In this study, Human Dermal fibroblast cells (HDF) were used as the negative control group (group A) HepG2 cells were divided into three groups: untreated cancer cells as positive group (group B), groups C and D were treated with, Lev and Pt-Lev, respectively. After evaluating lethal concentration 50% (LC50) for the examined drugs using the MTT test, biomarker gene expression was evaluated by real-time PCR. No Apoptotic cell was found in groups C or D before drug treatment, but it was present using different concentrations of the drugs. Results indicated that telomerase and miRNA-21 genes expression was significantly lower and FASLG was higher in group D compared with group C but there was no significant difference for Bcl-2 expression between these two groups. For the first time, it was indicated that Pt-Lev has anticancer effects by inhibiting telomerase and Bcl-2 and miRNA-21 and increasing FASLG gene expression and its effects were more than Lev. It effectively exerted its anticancer effects by extending apoptosis on HepG2 cells.

Porous Poly(2-hydroxyethyl methacrylate) Hydrogel Scaffolds for Tissue Engineering: Influence of Crosslinking Systems and Silk Sericin Concentration on Scaffold Properties.

Tailored porous structures of poly(2-hydroxyethyl methacrylate) (PHEMA) and silk sericin (SS) were used to create porous hydrogel scaffolds using two distinct crosslinking systems. These structures were designed to closely mimic the porous nature of the native extracellular matrix. Conventional free radical polymerization of 2-hydroxyethyl methacrylate (HEMA) was performed in the presence of different concentrations of SS (1.25, 2.50, 5.00% w/v) with two crosslinking systems. A chemical crosslinking system with N'N-methylene bisacrylamide (MBAAm) and a physical crosslinking system with dimethylurea (DMU) were used: C-PHEMA/SS (crosslinked using MBAAm) and C-PHEMA/pC-SS (crosslinked using MBAAm and DMU). The focus of this study was on investigating the impact of these crosslinking methods on various properties of the scaffolds, including pore size, pore characteristics, polymerization time, morphology, molecular interaction, in vitro degradation, thermal properties, and in vitro cytotoxicity. The various crosslinked networks were found to appreciably influence the properties of the scaffolds, especially the pore sizes, in which smaller sizes and higher numbers of pores with high regularity were seen in C-PHEMA/1.25 pC-SS (17 ± 2 μm) than in C-PHEMA/1.25 SS (34 ± 3 μm). Semi-interpenetrating networks were created by crosslinking PHEMA-MBAAm-PHEMA while incorporating free protein molecules of SS within the networks. The additional crosslinking step involving DMU occurred through hydrogen bonding of the -C=O and -N-H groups with the SS, resulting in the simultaneous incorporation of DMU and SS within the PHEMA networks. As a consequence of this process, the scaffold C-PHEMA/pC-SS exhibited smaller pore sizes compared to scaffolds without DMU crosslinking. Moreover, the incorporation of higher loadings of SS led to even smaller pore sizes. Additionally, the gelation time of C-PHEMA/pC-SS was delayed due to the presence of DMU in the crosslinking system. Both porous hydrogel scaffolds, C-PHEMA/pC-SS and PHEMA, were found to be non-cytotoxic to the normal human skin dermal fibroblast cell line (NHDF cells). This promising result indicates that these hydrogel scaffolds have potential for use in tissue engineering applications.

Co-delivery of simvastatin and microRNA-21 through liposome could accelerates the wound healing process

The gene delivery approach, mainly microRNAs (miRNA) as key wound healing mediators, has recently received extensive attention. MicroRNA-21 (miR-21) has strongly impacted wound healing by affecting the inflammation and proliferation phases. Previous studies have also demonstrated the beneficial effect of simvastatin on wound healing. Therefore, we designed a dual-drug/gene delivery system using PEGylated liposomes that could simultaneously attain the co-encapsulation and co-delivery of miRNA and simvastatin (SIM) to explore the combined effect of this dual-drug delivery system on wound healing.The PEG-liposomes for simvastatin and miR-21 plasmid (miR-21-P/SIM/Liposomes) were prepared using the thin-film hydration method. The liposomes showed 85 % entrapment efficiency for SIM in the lipid bilayer and high physical entrapment of miR-21-P in the inner cavity. In vitro studies demonstrated no cytotoxicity for the carrier on normal human dermal fibroblast cells (NHDF) and 97 % cellular uptake over 2 h incubation. The scratch test revealed excellent cell proliferation and migration after treatment with miR-21-P/SIM/Liposomes. For the in vivo experiments, a full-thickness cutaneous wound model was used. The wound closure on day 8 was higher for Liposomal formulation containing miR-21-P promoting faster re-epithelialization. On day 12, all treated groups showed complete wound closure. However, following histological analysis, the miR-21-P/SIM/Liposomes revealed the best tissue regeneration, similar to normal functional skin, by reduced inflammation and increased re-epithelialization, collagen deposition and angiogenesis.In conclusion, the designed miR-21-P/SIM/Liposomes could significantly accelerate the process of wound healing, which provides a new strategy for the management of chronic wounds.

Effects of Hyperglycemia and Doxorubicin on Aging Induction Optimization: Focus on the Role of p53 and mTOR in Human Dermal Fibroblast Cells

Aging, a kind of physiological process, is influenced by a number of different biological and genetic factors, the driver for all age-related diseases. Aging of the skin can use samples of human fibroblasts (preputium) which are induced with high glucose media and doxorubicin using cell culture methods. Aging is measured using markers at the genetic level, namely p53 and mTOR. The p53 protein is one of the most important markers of apoptosis and the mTOR protein plays an important role in the proliferation, growth, motility, survival, autophagy of cell, including the synthesis of protein. Therefore, the optimization strategy of cell aging is well suited to physiological aging conditions In this review, we explore the optimization of aging in fibroblast cell cultures induced by high-glucose media and doxorubicin and review signs of aging, namely the biomarkers p53 and mTOR. The hope to be able to know aging is close to the original condition so that it becomes an opportunity as well as a challenge for the transition of basic research into developing interventions. Several major electronic databases, including Embase, PubMed, Cochrane, and CINAHL were used to select articles from the period between February 2013 and February 2023. From 5 available literatures, we demonstrated the activity of high-glucose media and doxorubicin as induction of fibroblast senescence. High-glucose media and doxorubicin showed an aging effect by increasing p53 and mTOR markers in fibroblast cell cultures. It is hoped that, with this article on aging optimization, insights into future research directions can be achieved.

Dipeptide-Based Photoreactive Instant Glue for Environmental and Biomedical Applications.

Nature-inspired smart materials offer numerous advantages over environmental friendliness and efficiency. Emulating the excellent adhesive properties of mussels foot proteins, where the lysine is in close proximity with the 3,4-dihydroxy-l-phenylalanine (DOPA), we report the synthesis of a novel photocurable peptide-based adhesive consisting exclusively of these two amino acids. Our adhesive is a highly concentrated aqueous solution of a monomer, a cross-linker, and a photoinitiator. Lap-shear adhesion measurements on plastic and glass surfaces and comparison with different types of commercial adhesives showed that the adhesive strength of our glue is comparable when applied in air and superior when used underwater. No toxicity of our adhesive was observed when the cytocompatibility on human dermal fibroblast cells was assessed. Preliminary experiments with various tissues and coral fragments showed that our adhesive could be applied to wound healing and coral reef restoration. Given the convenience of the facile synthesis, biocompatibility, ease of application underwater, and high adhesive strength, we expect that our adhesive may find application, but not limited, to the biomedical and environmental field.

Design, Synthesis, and Potent Anticancer Activity of Novel Indole-Based Bcl-2 Inhibitors.

The Bcl-2 family plays a crucial role in regulating cell apoptosis, making it an attractive target for cancer therapy. In this study, a series of indole-based compounds, U1-6, were designed, synthesized, and evaluated for their anticancer activity against Bcl-2-expressing cancer cell lines. The binding affinity, safety profile, cell cycle arrest, and apoptosis effects of the compounds were tested. The designed compounds exhibited potent inhibitory activity at sub-micromolar IC50 concentrations against MCF-7, MDA-MB-231, and A549 cell lines. Notably, U2 and U3 demonstrated the highest activity, particularly against MCF-7 cells. Respectively, both U2 and U3 showed potential BCL-2 inhibition activity with IC50 values of 1.2 ± 0.02 and 11.10 ± 0.07 µM using an ELISA binding assay compared with 0.62 ± 0.01 µM for gossypol, employed as a positive control. Molecular docking analysis suggested stable interactions of compound U2 at the Bcl-2 binding site through hydrogen bonding, pi-pi stacking, and hydrophobic interactions. Furthermore, U2 demonstrated significant induction of apoptosis and cell cycle arrest at the G1/S phase. Importantly, U2 displayed a favourable safety profile on HDF human dermal normal fibroblast cells at 10-fold greater IC50 values compared with MDA-MB-231 cells. These findings underscore the therapeutic potential of compound U2 as a Bcl-2 inhibitor and provide insights into its molecular mechanisms of action.

Bio-based surfactants derived from pectin

Surfactants derived from renewable resources and synthesized using renewable feedstock and sustainable methods have become a major research focus over the past decade in the surfactant industry. This research presents an approach for rapidly converting readily available polysaccharides, like pectin derived from fruit waste, into safely biodegradable surface-active polymers. Commercially available pectin was modified with n-alkyl amines having different alkyl chain lengths using potassium carbonate as a catalyst. The effect of pectin molecular weight, alkyl chain length and degree of substitution (DS) on surface-active properties of the modified pectin derivatives was studied. Surface tension decreased slightly with lowering molecular weight, whereas interfacial tension decreased dramatically. Cytotoxicity evaluations using human dermal fibroblast, HepG2 and Jurkat cells demonstrated that these polysaccharide-based surfactants exhibit lower cytotoxicity compared to the conventional surfactants such as octyl phenol ethoxylates (i.e., Triton™ X-100), and therefore are more environmentally friendly. Biodegradation studies show that all modified pectins are “ultimately biodegradable” except for Pectin-amide C8 (1:10).

Green synthesis of LAE@ZnO/Ag nanoparticles: Unlocking the multifaceted potential for biomedical and environmental applications

This study presents a green synthesis method for producing ZnO/Ag nanoparticles using Launaea acanthodes extract (LAE@ZnO/Ag NPs). The as-synthesized nanoparticles were characterized using DLS, EDS, TEM, FESEM, FT-IR, and UV-Vis spectroscopy. FESEM and TEM analysis revealed oval-spherical LAE@ZnO/Ag NPs with an average size of approximately 40–55 nm. The photocatalytic efficiency of LAE@ZnO/Ag NPs was evaluated by studying the degradation of Gentamicine (GT) as a model pollutant under UV and visible light irradiations. Key parameters, such as nanocatalyst dose, the initial concentration of GT, and the light source, were investigated to determine the optimal conditions for achieving maximum degradation. The most effective degradation of GT was achieved using LAE@ZnO/Ag NPs, which exhibited degradation efficiencies of 94.2 % under UV irradiation and 83.7 % under visible light irradiation at a nanocatalyst dosage of 0.6 g/l and an initial antibiotic concentration of 5 ppm. The DPPH assay demonstrated the efficient scavenging of DPPH free radicals, with LAE@ZnO/Ag NPs achieving a remarkable scavenging rate of up to 93 %. Furthermore, the nanoparticles exhibited anticancer activity and cytotoxicity against NALM-6 and human dermal fibroblast (HDF) cell lines. Additionally, the nanoparticles were evaluated for their antibacterial and antifungal activities against Gram-positive and Gram-negative strains, showing remarkable efficacy particularly against E. coli and K. pneumoniae strains. The findings of this study indicate that LAE@ZnO/Ag NPs hold substantial promise for diverse applications in society, encompassing pollutant degradation, antibacterial attributes, and the advancement of anti-cancer drug development.

Eflornithine Hydrochloride-Loaded Electrospun Nanofibers as a Potential Face Mask for Hirsutism Application.

Hirsutism is a distressing condition that can affect women's self-esteem due to the excessive amount of hair growth in different body parts, including the face. A temporary managing option is to develop a self-care routine to remove unwanted hair through shaving or waxing. Laser or electrolysis are alternative methods, but in some cases, the use of medications, such as the topical cream Vaniqa®, can help in reducing the growth of unwanted hair. Electrospun fibers have been used in several drug delivery applications, including skin care products, owing to their biocompatibility, biodegradability, high surface area-to-volume ratio, and dry nature that can release the encapsulated drugs with maximum skin penetration. Therefore, polyvinyl pyrrolidone (PVP) fibers were fabricated in combination with hyaluronic acid to deliver the active compound of Vaniqa®, i.e., Eflornithine hydrochloride (EFH), as a face mask to inhibit excess facial hair growth. The prepared drug-loaded fibers showed a diameter of 490 ± 140 nm, with an encapsulation efficiency of 88 ± 7% and a drug loading capacity of 92 ± 7 μg/mg. The in vitro drug release of EFH-loaded fibers exhibited an initial burst release of 80% in the first 5 min, followed by a complete release after 360 min, owing to the rapid disintegration of the fibrous mat (2 s). The in vitro cytotoxicity indicated a high safety profile of EFH at all tested concentrations (500-15.625 μg/mL) after 24-h exposure to human dermal fibroblast (HFF-1) cells. Therefore, this drug-loaded nanofibrous system can be considered a potentially medicated face mask for the management of hirsutism, along with the moisturizing effect that it possesses. Topical applications of the developed system showed reduced hair growth in mice to a certain extent.

Single-cell analysis of human dermal fibroblasts isolated from a single male donor over 35 years.

The aim of this study is to examine the effects of ageing on dermal fibroblast heterogeneity based on samples obtained from the same donor. We used a dermal fibroblast lineage (named ASF-4 cell lines) isolated from the inner side of the upper arm of a healthy male donor over a 35-year period, beginning at 36 years of age. Because clonal analysis of ASF-4 cell lines demonstrated a donor age-dependent loss of proliferative capacity and acquisition of senescent traits at the single-cell level, cultured cells frozen at passage 10 at ages 36 and 72 years were subjected to single-cell RNA sequencing. Transcriptome analysis revealed an increase in senescent fibroblasts and downregulation of genes associated with extracellular matrix remodelling with ageing. In addition, two putative differentiation pathways, with one endpoint consisting of senescent fibroblasts and the other without, were speculated using a pseudo-time analysis. Knockdown of the characteristic gene of the non-senescent fibroblast cluster endpoint, EFEMP2, accelerated cellular senescence. This was also confirmed in two other normal human dermal fibroblast cell lines. The detection of a common cellular senescence-related gene from single-donor analysis is notable. This study provides new insights into the behaviour of dermal fibroblasts during skin ageing.

Bioassay-Guided Fractionation and Biological Activity of Cardenolides from Streptocaulon juventas.

The discovery that Na/K-ATPase acts as a signal transducer led us to investigate the structural diversity of cardiotonic steroids and study their ligand effects. By applying Na/K-ATPase activity assay-guided fractionation, we isolated a total of 20 cardiotonic steroids from Streptocaulon juventas, including an undescribed juventasoside B (10: ) and 19 known cardiotonic steroids. Their structures have been elucidated. Using our platform of purified Na/K-ATPase and an LLC-PK1 cell model, we found that 10: , at a concentration that induces less than 10% Na/K-ATPase inhibition, can stimulate the Na/K-ATPase/Src receptor complex and selectively activate downstream pathways, ultimately altering prostate cancer cell growth. By assessing the ligand effect of the isolated cardiotonic steroids, we found that the regulation of cell viability by the isolated cardiotonic steroids was not associated with their inhibitory potencies against Na/K-ATPase activity but reflected their ligand-binding affinity to the Na/K-ATPase receptor. Based on this discovery, we identified a unique active cardiotonic steroid, digitoxigenin (1: ), and verified that it can protect LLC-PK1 cells from hypoxic injury, implicating its potential use in ischemia/reperfusion injury and inducing collagen synthesis in primary human dermal fibroblast cells, and implicating that compound 2: is the molecular basis of the wound healing activity of S. juventas.

Effect of ellagic acid and retinoic acid on collagen and elastin production by human dermal fibroblasts.

Elastin is a fibrous protein key to the structure and support of skin as well as other organ tissues. Elastic fibers are located in the skin's dermal layer and make up approximately 2%-4% of the fat-free dry weight of the dermis in the skin of adults. Aging causes the progressive degradation of elastin fibers. Loss of these fibers can cause skin sagging and wrinkling, loss of healthy blood vessels and lung capacity, aneurysms, and Chronic Obstructive Pulmonary Disease (COPD). We hypothesized that ellagic acid, a polyphenol, will increase elastin in human dermal fibroblasts (HDF) due to polyphenols' elastin binding properties. We treated HDF's with 2μg/ml ellagic acid for 28 days to see the elastin deposition in HDF cell cultures. To test this, we treated HDFs with polyphenols ellagic acid for 3, 7, 14 and 21 days. For comparison purposes, we included a group of ellagic acid and retinoic acid since retinoic acid is already in the market for elastin regeneration purposes. When ellagic acid and retinoic acid were introduced together, insoluble elastin and collagen deposition were significantly higher in HDFs compared to other groups. Polyphenols and retinoic acid can improve skin extracellular matrix production of elastin and collagen and may improve skin fine wrinkles.

Incorporation of Chitosan in Polyurethanes Based on Modified Castor Oil for Cardiovascular Applications.

The increased demand for vascular grafts for the treatment of cardiovascular diseases has led to the search for novel biomaterials that can achieve the properties of the tissue. According to this, the investigation of polyurethanes has been a promising approach to overcome the present limitations. However, some biological properties remain to be overcome, such as thrombogenicity and hemocompatibility, among others. This paper aims to synthesize polyurethanes based on castor oil and castor oil transesterified with triethanolamine (TEA) and pentaerythritol (PE) and with the incorporation of 1% chitosan. Analysis of the wettability, enzymatic degradation, mechanical properties (tensile strength and elongation at break), and thermal stability was performed. Along with the evaluation of the cytotoxicity against mouse fibroblast (L929) and human dermal fibroblast (HDFa) cells, the hemolysis rate and platelet adhesion were determined. The castor-oil-based polyurethanes with and without 1% chitosan posed hydrophobic surfaces and water absorptions of less than 2% and enzymatic degradation below 0.5%. Also, they were thermally stable until 300 °C, with tensile strength like cardiovascular tissues. The synthesized castor oil/chitosan polyurethanes are non-cytotoxic (cell viabilities above 80%) to L929 and HDFa cells and non-thrombogenic and non-hemolytic (less than 2%); therefore, they are suitable for cardiovascular applications.

An Investigation into the Efficacy of Low Temperature and UV Irradiated Citric Acid Crosslinked Zein/PEO Electrospun Membranes for Wound Healing Using Human Dermal Fibroblast Cells

AbstractA key material capable of effective wound closure is a pertinent demand of the day. Citric acid (CA)‐based crosslinking involves pre‐crosslinking followed by post‐crosslinking at higher temperature. Unlike conventional higher temperature treatment, this piece of work discusses post‐crosslinking at low temperature or under UV irradiation of CAZein/Polyethylene oxide (PEO) blend membranes. A comparative analysis of the wound healing efficiency of both membranes was done. Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC) results showed that UV crosslinked CA Zein/PEO has a fast thermal degradation and the folded structure of the protein perturbed during UV crosslinking. More than 60 % of porosity and water vapor transmission rate (WVTR) of 1500–2000 g m−2 day−1 for both membranes could facilitate faster exudate absorption and gas exchange through the wound site. Thermally crosslinked CA Zein/PEO stimulated 67 % more collagen production within 2 days compared to control cells. Percentage of wound closure is also high for thermally crosslinked CA Zein/PEO compared to UV crosslinked CA Zein/PEO. Though cytotoxicity evaluation confirmed the non‐cytotoxicity of both membranes, thermally crosslinked membrane proved as a better candidate for wound care management.

Co-administration of amoxicillin-loaded chitosan nanoparticles and inulin: A novel strategy for mitigating antibiotic resistance and preserving microbiota balance in Helicobacter pylori treatment

Helicobacter pylori (H. pylori) is a causative agent of various gastrointestinal diseases and eradication mainly relies on antibiotic treatment, with (AMX) being a key component. However, rising antibiotic resistance in H. pylori necessitates the use of antibiotics combination therapy, often disrupting gut microbiota equilibrium leading to further health complications. This study investigates a novel strategy utilizing AMX-loaded chitosan nanoparticles (AMX-CS NPs), co-administered with prebiotic inulin to counteract H. pylori infection while preserving microbiota health. Following microbroth dilution method, AMX displayed efficacy against H. pylori, with a MIC50 of 48.34 ± 3.3 ng/mL, albeit with a detrimental impact on Lactobacillus casei (L. casei). The co-administration of inulin (500 μg/mL) with AMX restored L. casei viability while retaining the lethal effect on H. pylori. Encapsulation of AMX in CS-NPs via ionic gelation method, resulted in particles of 157.8 ± 3.85 nm in size and an entrapment efficiency (EE) of 86.44 ± 2.19 %. Moreover, AMX-CS NPs showed a sustained drug release pattern over 72 h with no detectable toxicity on human dermal fibroblasts cell lines. Encapsulation of AMX into CS NPs also reduced its MIC50 against H. pylori, while its co-administration with inulin maintained L. casei viability. Interestingly, treatment with AMX-CS NPs also reduced the expression of the efflux pump gene hefA in H. pylori. This dual treatment strategy offers a promising approach for more selective antimicrobial treatment, minimizing disruption to healthy microbial communities while effectively addressing pathogenic threats.

Investigating the Protective Role of Rhodanese Enzyme against Cyanide, the Cytotoxic by-product of Amygdalin, in HDF and L929 Cell Lines

Introduction: Amygdalin (AMG) is a plant-based agent that has many therapeutic applications. Metabolism of this herbal remedy may cause cytotoxicity in cells. Objective: In this study, the role of rhodanese (RH) enzyme against the cyanide of amygdalin has been investigated in human and mouse cell lines in vitro. MethodS: We analyzed the cytotoxicity, morphologic changes, apoptotic effects, and gene expression alterations resulting from treatment with AMG and AMG combined with RH (AMG-RH) in mouse fibroblasts (L929) and human dermal fibroblasts (HDF) cell lines. ResultS: The lowest half-maximal inhibitory concentration (IC50) values were 87.95±3.63 mg/ml and 80.82±2.13 mg/ml at 72 h in both cell lines. Cell viability of both cell lines was significantly decreased after AMG treatment; however, it increased following treatment with AMG-RH for 24, 48, and 72 h. Morphological changes were observed in both cell lines after AMG treatment for 72 h. AMG-RH combination did not cause any significant morphological alterations in either cell line. Conclusion: The apoptosis rates were increased in both cell lines treated with AMG and decreased in AMG-RH treatment for 72 h. BAX, CASP-3, BCL-2, and TST genes were upregulated after treatment with AMG for 72 h in both cell lines. BCL-2 and TST genes were upregulated, while BAX and CASP3 were downregulated after treatment with AMG-RH for 72 h. The findings of this study indicate the IC50 dose of AMG could cause cytotoxicity in HDF and L929 cell lines. Furthermore, it was found that the RH enzyme could decrease AMG cytotoxicity and might have a protective role against AMG.