ABSTRACT
The influence of surface topography on stem cell behavior and differentiation has garnered significant attention in regenerative medicine and tissue engineering. The cell-imprinting method has been introduced as a promising approach to mimic the geometry and topography of cells. The cell-imprinted substrates are designed to replicate the topographies and dimensions of target cells, enabling tailored interactions that promote the differentiation of stem cells towards desired specialized cell types. In fact, by replicating the size and shape of cells, biomimetic substrates provide physical cues that profoundly impact stem cell differentiation. These cues play a pivotal role in directing cell morphology, cytoskeletal organization, and gene expression, ultimately influencing lineage commitment. The biomimetic substrates' ability to emulate the native cellular microenvironment supports the creation of platforms capable of steering stem cell fate with high precision. This review discusses the role of mechanical factors that impact stem cell fate. It also provides an overview of the design and fabrication principles of cell-imprinted substrates. Furthermore, the paper delves into the use of cell-imprinted polydimethylsiloxane (PDMS) substrates to direct adipose-derived stem cells (ADSCs) differentiation into a variety of specialized cells for tissue engineering and regenerative medicine applications. Additionally, the review discusses the limitations of cell-imprinted PDMS substrates and highlights the efforts made to overcome these limitations.
ABSTRACT
Corneal stromal disorders due to the loss of keratocytes can affect visual impairment and blindness. Corneal cell therapy is a promising therapeutic strategy for healing corneal tissue or even enhancing corneal function upon advanced disorders, however, the sources of corneal keratocytes are limited for clinical applications. Here, the capacity of cell-imprinted substrates fabricated by molding human keratocyte templates to induce differentiation of human adipose-derived stem cells (hADSCs) into keratocytes, is presented. Keratocytes are isolated from human corneal stroma and grown to transmit their ECM architecture and cell-like topographies to a PDMS substrate. The hADSCs are then seeded on cell-imprinted substrates and their differentiation to keratocytes in DMEM/F12 (with and without chemical factors) are evaluated by real-time PCR and immunocytochemistry. The mesenchymal stem cells grown on patterned substrates present gene and protein expression profiles similar to corneal keratocytes. In contrast, a negligible expression of myofibroblast marker in the hADSCs cultivated on the imprinted substrates, is observed. Microscopic analysis reveals dendritic morphology and ellipsoid nuclei similar to primary keratocytes. Overall, it is demonstrated that biomimetic imprinted substrates would be a sufficient driver to solely direct the stem cell fate toward target cells which is a significant achievement toward corneal regeneration.
Subject(s)
Corneal Diseases , Corneal Keratocytes , Humans , Cornea , Stem Cells , Dendritic Cells , RegenerationABSTRACT
Helicobacter pylori is the cause of most cases of stomach ulcers and also causes some digestive cancers. The emergence and spread of antibiotic-resistant strains of H. pylori is one of the most important challenges in the treatment of its infections. The present study aims to develop a concanavalin A (ConA) coated chitosan (CS) nanocarrier-based drug delivery for the targeted release of peptides to the site of H. pylori infection. Accordingly, chitosan was used as an encapsulating agent for CM11 peptide delivery by applying ionotropic gelation method. Con-A was used for coating CS nanoparticles to target H. pylori. The CS NPs and ConA-CS NPs were characterized by FTIR, dynamic light scattering (DLS), and scanning electron microscopy (SEM). The MIC of CM11-loaded ConA-CS NPs against H. pylori SS1 strain was analyzed in vitro. In order to evaluate the treatment efficiency in vivo, a gastric infection model of H. pylori SS1 strain was established in mice and histopathological studies and IL-1ß cytokine assay were performed. Based on the results, the size frequency for CS NPs and ConA-CS NPs was about 200 and 350 nm, respectively. The prepared CM11-loaded ConA-CS NPs exhibited antibacterial activity against H. pylori SS1 strain with a concentration of 32 µg/ml. The highest healing process was observed in synthesized CM11-loaded ConA-CS NPs treatments and a significant decrease in IL-1ß was observed. Our findings highlight the potential of chitosan nanoparticles as a drug delivery vehicle in the treatment of gastric infection model of H. pylori SS1 strain.
Subject(s)
Helicobacter pylori , Nanoparticles , Chitosan/chemistry , Nanoparticles/chemistry , Concanavalin A/chemistry , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Helicobacter pylori/drug effects , Humans , Male , Animals , Mice , Cell Line, Tumor , Mice, Inbred C57BL , Hydrogen-Ion Concentration , Cell Survival/drug effectsABSTRACT
Microbial diseases are a great threat to global health and cause considerable mortality and extensive economic losses each year. The medications for treating this group of diseases (antibiotics, antiviral, antifungal drugs, etc.) directly attack the pathogenic agents by recognizing the target molecules. However, it is necessary to note that excessive use of any of these drugs can lead to an increase in microbial resistance and infectious diseases. New therapeutic methods have been studied recently using emerging drugs such as mesenchymal stem cell-derived exosomes (MSC-Exos) and antimicrobial peptides (AMPs), which act based on two completely different strategies against pathogens including Host-Directed Therapy (HDT) and Pathogen-Directed Therapy (PDT), respectively. In the PDT approach, AMPs interact directly with pathogens to interrupt their intrusion, survival, and proliferation. These drugs interact directly with the cell membrane or intracellular components of pathogens and cause the death of pathogens or inhibit their replication. The mechanism of action of MSC-Exos in HDT is based on immunomodulation and regulation, promotion of tissue regeneration, and reduced host toxicity. This review studies the potential of mesenchymal stem cell-derived exosomes/ATPs therapeutic properties against microbial infectious diseases especially pulmonary infections and sepsis.
ABSTRACT
Antimicrobial peptides (AMPs) are among the compounds that have significant potential to deal with infectious skin wounds. Using wound dressings or skin scaffolds containing AMPs can be an effective way to overcome infections caused by antibiotic-resistant strains. In this study, we developed an amniotic membrane-based skin scaffold using silk fibroin to improve mechanical properties and CM11 peptide as an antimicrobial peptide. The peptide was coated on the scaffold using the soaking method. The fabricated scaffold was characterised by SEM and FTIR, and their mechanical strength, biodegradation, peptide release, and cell cytotoxicity analyses were performed. Then, their antimicrobial activity was measured against antibiotic-resistant strains of Pseudomonas aeruginosa and Staphylococcus aureus. The in vivo biocompatibility of this scaffold was evaluated by subcutaneously implanting it under the skin of the mouse and counting lymphocytes and macrophages in the implanted area. Finally, the regenerative ability of the scaffold was analyzed in the mouse full-thickness wound model by measuring the wound diameter, H&E staining, and examining the expression rate of genes involved in the wound healing process. The developed scaffolds exerted an inhibiting effect on the bacteria growth, indicating their proper antimicrobial property. In vivo biocompatibility results showed no significant count of macrophages and lymphocytes between the test and control groups. The wound closure rate was significantly higher in the wound covered with fibroin electrospun-amniotic membrane loaded with 32 µg/mL CM11, where the relative expression rates of collagen I, collagen III, TGF-ß1 and TGF-ß3 were higher compared with the other groups.
Subject(s)
Anti-Infective Agents , Fibroins , Nanofibers , Mice , Animals , Fibroins/therapeutic use , Fibroins/chemistry , Fibroins/pharmacology , Nanofibers/therapeutic use , Amnion , Wound Healing , Collagen , Peptides , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacologyABSTRACT
Repairing of large bone injuries is an important problem in bone regeneration field. Thus, developing new therapeutic approaches such as tissue engineering using 3D scaffolds is necessary. Incorporation of some bioactive materials and trace elements can improve scaffold properties. We made chitosan/alginate/strontium-doped bioglass composite scaffolds with optimized properties for bone tissue engineering. Bioglass (BG) and Sr-doped bioglasses (Sr-BG) were synthesized using Sol-Gel method. Alginate-Chitosan (Alg/Cs) scaffold and scaffolds containing different ratio (10%, 20% and 30%) of BG (Alg/Cs/BG10, 20, 30) or Sr-BG (Alg/Cs/Sr-BG10, 20, 30) were fabricated using freeze drying method. Characterization of bioglasses/scaffolds was done using zeta sizer, FTIR, XRD, (FE) SEM and EDS. Also, mechanical strength, antibacterial effect degradation and swelling profile of scaffolds were evaluated. Bone differentiation efficiency and viability of MSCs on scaffolds were determined by Alizarin Red, ALP and MTT methods. Cell toxicity and antibacterial effect of bioglasses were determined using MTT, MIC and MBC methods. Incorporation of BG into Alg/Cs scaffolds amplified biomineralization and mechanical properties along with improved swelling ratio, degradation profile and cell differentiation. Mechanical strength and cell differentiation efficiency of Alg/Cs/BG20 scaffold was considerably higher than scaffolds with lower or higher BG concentrations. Alg/Cs/Sr-BG scaffolds had higher mechanical stability and more differentiation efficiency in comparison with Alg/Cs and Alg/Cs/BG scaffolds. Also, Mechanical strength and cell differentiation efficiency of Alg/Cs/Sr-BG20 scaffold was considerably higher than scaffolds with various Sr-BG concentrations. Biomineralization of Alg/Cs/BG scaffolds slightly was higher than Alg/Cs/Sr-BG scaffolds. Overall, we concluded that Alg/Cs/Sr-BG20 scaffolds are more suitable for repairing bone major injuries.
Subject(s)
Chitosan , Hydrogels , Alginates/pharmacology , Anti-Bacterial Agents/pharmacology , Bone Regeneration , Cell Proliferation , Ceramics , Chitosan/pharmacology , Hydrogels/pharmacology , Strontium/pharmacology , Tissue Engineering/methods , Tissue ScaffoldsABSTRACT
Bisphosphonates (BPs) such as Zoledronic acid (ZA) are a subset of synthetic small molecules, which are now marketed as the main drugs to stimulate the growth and differentiation of osteoblast cells, thereby increasing bone formation as well as preventing bone loss. Also, Halloysite Nanotubes (HNTs)-polymer composites have attracted a lot of attention due to their high surface-to-volume ratio, low density, and high hydrophilicity, and are easily dispersed in hydrophilic biopolymers. In addition, their ability to carry enough amounts of drugs and the ability to control release has been demonstrated. Based on studies, the Gelatin-based scaffold with Halloysite nanotube (HNT) has the capacity as a drug carrier and Zoledronic acid (ZA) sustains release. Previous studies show that using ZA intravenously has some severe side effects and limitations. But by attention to the advantages of its osteogenesis, the current study has been done in order to reduce the side effects of local delivery of it. The 3-dimensional scaffolds were prepared by the Freeze-drying method. Characterization methods such as FE-SEM, FTIR, XRD, and release behavior of the scaffold has been performed to evaluate the features of the scaffolds. In fact, as-prepared Gel-HNT/ZA release 49% ZA in Phosphate Buffered Saline (PBS) within 21 days. The mechanical properties have been increased after adding HNTs and ZA from 10.27 to 26.18 MPa. Also, the water absorption has been increased after adding HNTs and ZA from 1.67 to 5.02 (g/g). Seeded human Adipose stem cells (hASCs) on the prepared scaffolds showed that the ZA effectively elevated the proliferation of the hASCs and also the MTT results proved the non-toxicity of all prepared scaffolds by high cell viability (Ë80%). The osteogenic differentiation has been accelerated as displayed by ALP and Ca assay. The results propose that the HNTs-loaded Gelatin scaffold could control the releasing of ZA and its localized delivery at the defect site, simultaneously promoting the mechanical and osteogenesis ability of gelatin-based scaffolds.
ABSTRACT
In the current study, we investigated the antibacterial activity of main quorum sensing autoinducers of Pseudomonas aeruginosa, C12-HSL and C4-HSL, against MDR Staphylococcus aureus isolates and their synergistic effects with some common antibiotics. Forty clinical isolates of S. aureus were collected and their antibiotic susceptibility pattern was evaluated. Then, 10 resistant isolates were selected for further studies. In the following, the antibacterial activity of quorum sensing C12-HSL and C4-HSL inducers of P. aeruginosa was evaluated against selected isolates based on the microdilution method and Time Killing assay as well as their synergistic activity with selected antibiotics. The ability of inductors to hemolysis and their cytotoxicity on CHO and HeLa cell lines was also assessed. For the assessment of antibacterial activity, Acinetobacter baumannii was used as negative control. The results demonstrated that C12 and C4 have antibacterial activity against MDR S. aureus isolates but had no effect on A. baumannii. Time Killing test showed that at 2X MIC concentration, the maximum inhibition (100%) is observed after 120 min for C12 and 240 min for C4. The IC50 of inducers was about 512 µg/ml. In addition, no synergistic effects were observed.
Subject(s)
Pseudomonas aeruginosa , Quorum Sensing , 4-Butyrolactone/analogs & derivatives , Animals , Anti-Bacterial Agents/pharmacology , HeLa Cells , Humans , Staphylococcus aureusABSTRACT
In the last century, the emergence of in silico tools has improved the quality of healthcare studies by providing high quality predictions. In the case of COVID-19, these tools have been advantageous for bioinformatics analysis of SARS-CoV-2 structures, studying potential drugs and introducing drug targets, investigating the efficacy of potential natural product components at suppressing COVID-19 infection, designing peptide-mimetic and optimizing their structure to provide a better clinical outcome, and repurposing of the previously known therapeutics. These methods have also helped medical biotechnologists to design various vaccines; such as multi-epitope vaccines using reverse vaccinology and immunoinformatics methods, among which some of them have showed promising results through in vitro, in vivo and clinical trial studies. Moreover, emergence of artificial intelligence and machine learning algorithms have helped to classify the previously known data and use them to provide precise predictions and make plan for future of the pandemic condition. At this contemporary review, by collecting related information from the collected literature on valuable data sources; such as PubMed, Scopus, and Web of Science, we tried to provide a brief outlook regarding the importance of in silico tools in managing different aspects of COVID-19 pandemic infection and how these methods have been helpful to biomedical researchers.
ABSTRACT
SARS-CoV-2 is a corona virus that has been the cause for one of the deadliest pandemics of history, started since 2019. Suppressing the activity of the critical enzymes in the SARS-CoV-2 could potentially inhibit a vital step in viral life cycle. Papain-like protease (PLpro) could be regarded as a critical enzyme in viral replication of SARS-CoV-2. In this research, it was aimed to suppress the activity of PLpro enzyme by using potential plant-derived protease inhibitor peptides. For this purpose, 11 plant derived peptides that could potentially inhibit protease activity were selected from literature. The structures of the PLpro and the peptide ligands were acquired from PDB (protein data bank) and after structural optimization, were docked by using HADDOCK 2.4 program. Analyzing the results indicated that VcTI from Veronica hederifolia provides effective molecular interactions at both liable Zn site and classic active site of PLpro, making it a potential inhibitory ligand for this enzyme that could be used for halting the replication of SARS-CoV-2. Molecular dynamic assay confirmed that the selected receptor and ligand complex was stable. Future in vitro and in vivo investigations are required to verify the efficiency of this compound as a potential therapeutic against SARS-CoV-2 infection. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10989-021-10331-8.
ABSTRACT
Short-chain bioactive peptides are new and promising antimicrobial, immune moderating, and antioxidant agents. Therefore, the present study was conducted to evaluate in vitro antibacterial activity of CM11, a short antimicrobial peptide (AMP), against Streptococcus iniae and Yersinia ruckeri as fish pathogenic bacteria using standard disk diffusion and microdilution assays. In addition, in vivo effects of CM11 on fish growth, immunity, antioxidant activity, and disease resistance were evaluated using zebrafish (Danio rerio) as an animal model. For in vivo study, based on in vitro susceptibility results, four diets were designed to include zero (as control), 10, 20, and 50 µg of CM11 per g diet referred to as control, P1, P2, and P3 treatments, respectively. After eight weeks of dietary trial, fish were challenged with Streptococcus iniae, and the survival rate was calculated for a period of two weeks. Results showed that CM11 effectively inhibited the growth of S. iniae and Y. ruckeri on agar plates at a concentration of eight µg/ml. Minimum inhibitory and minimum bactericidal concentrations of CM11 were measured at 8 and 32 µg/ml for S. iniae and 16 and 64 µg/ml Y. ruckeri, respectively. In vivo results showed no noticeable effects on fish growth parameters, however, feed conversion ratio (FCR) was found lower in P3 and P2 compared to control (P < 0.05). Immunological and antioxidant responses were found strongly affected by CM11 in all treatment groups in which the highest values were found in the P3 treated group. Key immune and antioxidant genes were up-regulated particularly in fish receiving the highest level of CM11 (P3). Fish receiving the CM11 peptide showed better survival when challenged with S. iniae. These findings suggest the potential of CM11 for use in aquaculture as an antibacterial and immunostimulant agent.
Subject(s)
Fish Diseases , Streptococcal Infections , Yersinia Infections , Animal Feed/analysis , Animals , Anti-Bacterial Agents/pharmacology , Antimicrobial Cationic Peptides , Antimicrobial Peptides , Antioxidants , Diet/veterinary , Dietary Supplements , Disease Resistance , Streptococcal Infections/veterinary , Streptococcus iniae , Yersinia Infections/veterinary , ZebrafishABSTRACT
Wound infections are still problematic in many cases and demand new alternatives for current treatment strategies. In recent years, biomaterials-based wound dressings have received much attention due to their potentials and many studies have been performed based on them. Accordingly, in this study, we fabricated and optimized an antibacterial chitosan/silk fibroin (CS/SF) electrospun nanofiber bilayer containing different concentrations of a cationic antimicrobial peptide (AMP) for wound dressing applications. The fabricated CS/SF nanofiber was fully characterized and compared to the electrospun silk fibroin and electrospun chitosan alone in vitro. Then, the release rate of different concentrations of peptide (16, 32, and 64 µg/ml) from peptide-loaded CS/SF nanofiber was investigated. Finally, based on cytotoxic activity, the antibacterial activity of scaffolds containing 16 and 32 µg/ml of the peptide was evaluated against standard and multi-drug resistant strains of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa isolated from burn patients. The peptide-loaded CS/SF nanofiber displayed appropriate mechanical properties, high water uptake, suitable biodegradation rate, a controlled release without cytotoxicity on Hu02 human foreskin fibroblast cells at the 16 and 32 µg/ml concentrations of peptide. The optimized CS/SF containing 32 µg/ml peptide showed strong antibacterial activity against all experimental strains from standard to resistance. The results showed that the fabricated antimicrobial nanofiber has the potential to be applied as a wound dressing for infected wound healing, although further studies are needed in vivo.
Subject(s)
Antimicrobial Cationic Peptides/administration & dosage , Bandages , Chitosan/chemistry , Drug Carriers/chemical synthesis , Fibroins/chemistry , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacokinetics , Antimicrobial Cationic Peptides/chemistry , Antimicrobial Cationic Peptides/pharmacokinetics , Body Fluids/chemistry , Bombyx , Cells, Cultured , Chitosan/pharmacology , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Electroplating , Fibroins/pharmacology , Humans , Materials Testing , Microbial Sensitivity Tests , Microtechnology , Nanofibers/chemistry , Nanofibers/therapeutic use , Wound Healing/drug effects , Wound Infection/prevention & controlABSTRACT
The Coronaviridae family comprises large enveloped single-stranded RNA viruses. The known human-infecting coronaviruses; severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), novel SARS-CoV-2, human coronavirus (HCoV)-NL63, HCoV-229E, HCoV-OC43 and HKU1 cause mild to severe respiratory infections. The viral diseases induced by mammalian and avian viruses from Coronaviridae family pose significant economic and public health burdens. Due to increasing reports of viral resistance, co-infections and the emergence of viral epidemics such as COVID-19, available antiviral drugs show low or no efficacy, and the production of new treatments or vaccines are also challenging. Therefore, demand for the development of novel antivirals has considerably increased. In recent years, antiviral peptides have generated increasing interest as they are from natural and computational sources, are highly specific and effective, and possess the broad-spectrum activity with minimum side effects. Here, we have made an effort to compile and review the antiviral peptides with activity against Coronaviridae family viruses. They were divided into different categories according to their action mechanisms, including binding/attachment inhibitors, fusion and entry inhibitors, viral enzyme inhibitors, replication inhibitors and the peptides with direct and indirect effects on the viruses. Reported studies suggest optimism with regard to the design and production of therapeutically promising antiviral drugs. This review aims to summarize data relating to antiviral peptides particularly with respect to their applicability for development as novel treatments.
Subject(s)
Antiviral Agents/pharmacology , Coronavirus/drug effects , Peptides/pharmacology , Antiviral Agents/pharmacokinetics , Peptides/pharmacokinetics , Virus Internalization/drug effectsABSTRACT
Lead (Pb) is a known toxic heavy metal which accumulates in different tissues and causes oxidative stress (OS) and inflammation. The brain tissue is considered as one of the most vulnerable organs to the Pb-induced toxicity. The aim of this study was to investigate the therapeutic effects of vitamin D3 (VD) supplementation against the damages caused by chronic Pb toxicity in the cerebral cortex. Forty Wistar rats were divided into four equal groups and were treated as follows: control group received no treatment, VD group received 1000 IU/kg of VD by intramuscular injection every other day, Pb group received 1000 mg/L of Pb in drinking water, and Pb + VD group received VD and Pb simultaneously. The experiment lasted for 4 weeks and the analyses were conducted 24 h after the last administrations. The obtained results demonstrated that Pb significantly increased cortical lipid peroxidation and reactive oxygen species (ROS) levels. At the same time, there was a significant reduction in glutathione (GSH) content, catalase (CAT), and superoxide dismutase (SOD) activities, as well as a significant increase in the tissue level of inflammatory cytokines. Furthermore, Pb increased the messenger RNA (mRNA) expression level of nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB). Anyhow, VD administration during the period of Pb exposure suppressed the OS and inflammation by increasing the antioxidant molecules and decreasing the inflammatory cytokines and consequently repaired Pb-induced cortical tissue damages. Remarkably, these responses were concomitant with the alterations in Nrf2 and NF-κB gene expressions. In conclusion, the present study discloses the potential protective effects for VD against Pb-induced neurotoxicity via anti-inflammatory and antioxidative mechanisms.
Subject(s)
Cholecalciferol/pharmacology , Lead/toxicity , NF-E2-Related Factor 2/antagonists & inhibitors , NF-kappa B/antagonists & inhibitors , Signal Transduction/drug effects , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Lipid Peroxidation/drug effects , Lipid Peroxidation/physiology , Male , NF-E2-Related Factor 2/biosynthesis , NF-kappa B/biosynthesis , Oxidative Stress/drug effects , Oxidative Stress/physiology , Rats , Rats, Wistar , Reactive Oxygen Species/antagonists & inhibitors , Reactive Oxygen Species/metabolism , Signal Transduction/physiologyABSTRACT
INTRODUCTION: With the development of various branches of sciences, we will be able to resolve different clinical aspects of various diseases better. The convergence of these sciences can potentially tackle the new corona crisis. AREAS COVERED: In this review, we attempted to explore and describe various scientific branches studying COVID-19. We have reviewed the literature focusing on the prevention, diagnosis, and treatment of COVID-19. The primary databases targeted were Science Direct, Scopus and PubMed. The most relevant reports from the recent two decades were collected utilizing keywords including SARS-CoV, MERS-CoV, COVID-19, epidemiology, therapeutics and diagnosis. EXPERT OPINION: Based on this literature review, both traditional and emerging approaches are vital for the prevention, diagnosis and treatment of COVID-19. The traditional sciences play an essential role in the preventive and supportive care of corona infection, and modern technologies appear to be useful in the development of precise diagnosis and powerful treatment approaches for this disease. Indeed, the integration of these sciences will help us to fight COVID-19 disease more efficiently.
Subject(s)
COVID-19/prevention & control , Delivery of Health Care, Integrated , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/therapy , Computational Biology , Humans , Life Style , Medicine, Traditional , Nutritional SupportABSTRACT
BACKGROUND & OBJECTIVE: Enterococcus Species are the common cause of nosocomial infections, which are highly resistant to different antibiotics. Therefore, determination of their antibiotic susceptibility patterns and simultaneous resistance to antibiotics is important for better treatment strategies. METHODS: 400 clinical Enterococcus isolates were collected from different hospitals in Tehran, Iran. Standard phenotypic-biochemical tests and PCR were used to identify the Enterococcus species. The antimicrobial susceptibility patterns and simultaneous resistance to selected antibiotics were determined by disk diffusion method according to the CLSI guidelines. All data analysis was performed using Python packages Scipy and Stats models. RESULTS: According to the biochemical and PCR analyses, among 400 Enterococcus species, 72% of samples were Enterococcus faecalis, 10.75% Enterococcus faecium, and 17.25% other Enterococcus species. The results determined antimicrobial resistances of these strains against gentamicin, vancomycin, fosfomycin trometamol, teicoplanin, and quinupristin/dalfopristin. Results confirmed a significant correlation between resistance to vancomycin and resistance to teicoplanin. This correlation remains significant when including only E. faecium or E. faecalis species. We also found a negative correlation between resistance to teicoplanin and quinupristin/dalfopristin. Additionally, Quinupristin/dalfopristin was the least effective antibiotic while vancomycin and teicoplanin were the most effective ones. CONCLUSION: Based on the results and association between simultaneous resistance to some antibiotics such as vancomycin and teicoplanin, in the case of antibiotic resistance, the choice of a second antibiotic can be very important which can lead to good or bad effects.
ABSTRACT
Schwann cells, in addition to forming myelin sheaths, have pivotal roles in regeneration of injured axons in the peripheral nervous system such as producing a natural permissive conduit between distal and proximal stumps and secreting nerve growth factors. Due to the atrophy and senescence of Schwann cells in long nerve gap, and the need to ensure the presence of nerve growth factors and basal lamina tubes for axon regeneration in a critical time, injection of Schwann cells with the aid of an engineered conduit seems to be an effective approach to induce axon regrowth. Stem cells with high differentiation and proliferation capability can provide an adequate number of Schwann cells in healthy state for regeneration purposes. Guidance of stem cells differentiation into desired lineages, control of implanted Schwann cells fate, maintenance of nerve growth factors expression, and guidance of axon regrowth are possible with the aid of biomaterials with appropriate chemical, physical, and mechanical properties. Biomaterials' surface chemistry and biomolecules interacting with cells' receptors initiate specific intracellular signaling cascades and direct cells fate. In addition, biomaterials' surface topography in association with cells contact area, focal adhesion, and cytoskeletal remodeling by mechanotransduction process influences cells behavior and induces specific differentiation. The main objective of this review is to investigate the chemical, topographical, and mechanical properties of biomaterials which influence the fate of Schwann cells and the nerve regeneration process.
Subject(s)
Axons/metabolism , Biocompatible Materials , Nerve Regeneration , Nerve Tissue/metabolism , Schwann Cells/metabolism , Tissue Engineering , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/therapeutic use , Humans , Nerve Tissue/cytology , Neurogenesis , Schwann Cells/cytologyABSTRACT
Differentiation of stem cells to Schwann is considered efficient way for nerve regeneration since the sources of human Schwann cells are limited for clinical application. It is demonstrated that mimicking micromechanical forces or micro/nanotopographical environments that stem cells are experienced in vivo could control their fate. Here, the potency of substrates with imprinted cell-like topographies for direct differentiation of adipose-derived mesenchymal stem cells (ADSCs) into Schwann cells (SCs) is reported. For the preparation of substrates with imprinted SC-Like topographies, SCs are isolated from the sciatic nerve, grown, fixed, and then SC morphologies are transferred to polydimethylsiloxane (PDMS) substrates by mold casting. Subsequently, mesenchymal stem cells (MSCs) are seeded on the SC-imprinted substrates and their differentiation to SCs is evaluated by immunocytochemistry, real-time PCR, and western blotting. Analysis of morphology and expression of SC-specific markers show that MSCs cultured on the imprinted substrates have the typical SC-like morphology and express SC-specific markers including S100b, p75NTR, and Sox10. It is believed that specific cell-like topographies and related micromechanical cues can be sufficient for direct differentiation of ADSCs into Schwann cells by cell-imprinting method as a physical technique.
Subject(s)
Adipose Tissue/cytology , Cell Differentiation , Engineering , Mesenchymal Stem Cells/cytology , Schwann Cells/cytology , Animals , Nerve Regeneration , RatsABSTRACT
The field of tissue engineering (TE) experiences its most exciting time in the current decade. Recent progresses in TE have made it able to translate into clinical applications. To regenerate damaged tissues, TE uses biomaterial scaffolds to prepare a suitable backbone for tissue regeneration. It is well proven that the cell-biomaterial crosstalk impacts tremendously on cell biological activities such as differentiation, proliferation, migration, and others. Clarification of exact biological effects and mechanisms of a certain material on various cell types promises to have a profound impact on clinical applications of TE. Chitosan (CS) is one of the most commonly used biomaterials with many promising characteristics such as biocompatibility, antibacterial activity, biodegradability, and others. In this review, we discuss crosstalk between CS and various cell types to provide a roadmap for more effective applications of this polymer for future uses in tissue engineering and regenerative medicine.
Subject(s)
Biocompatible Materials/metabolism , Chitosan/metabolism , Regenerative Medicine , Tissue Engineering/methods , Tissue Scaffolds , Animals , Humans , Signal TransductionABSTRACT
Cutaneous leishmaniasis is one of the most endemic global health problems in many countries all around the world. Pentavalent antimonial drugs constitute the first line of leishmaniasis treatment; however, resistance to these drugs is a serious problem. Therefore, new therapies with new modes of action are urgently needed. In the current study, we examined antimicrobial activity of CM11 hybrid peptide (WKLFKKILKVL-NH2) against promastigote and amastigote forms of L. major (MHRO/IR/75/ER). In vitro anti-leishmanial activity was identified against L. major by parasite viability and metabolic activity after exposure to different peptide concentration. In the presentt study, we demostrated that different concentrations of CM11 result in dose dependent growth inhibition of Leishmania promastigotes. Furthermore, we demostrated that CM11 peptide has significant anti-leishmanial activities on amastigotes. Our results demonstrated that CM11 antimicrobial peptide may provide an alternative therapeutic approach for L. major treatment.