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Multilayer PVA/gelatin nanofibrous scaffolds incorporated with Tanacetum polycephalum essential oil and amoxicillin for skin tissue engineering application
No full textWound infection is still an important challenge in healing of different types of skin injuries. This highlights the need for new and improved antibacterial agents with novel and different mechanisms of action. In this study, by electrospinning process Tanacetum polycephalum essential oil (EO), as a natural antibacterial and anti-inflammatory agent, along with Amoxicillin (AMX) as an antibiotic are incorporated into PVA/gelatin-based nanofiber mats individually and in combination to fabricate a novel wound dressing. Briefly, we fabricated PVA/gelatin loaded by Amoxicillin as first layer for direct contact with wound surface to protects the wound from exogenous bacteria, and then built a PVA/gelatin/Tanacetum polycephalum essential oil layer on the first layer to help cleanses the wound from infection and accelerates wound closure. Finally, PVA/gelatin layer as third layer fabricated on middle layer to guarantee desirable mechanical properties. For each layer, the electrospinning parameters were adjusted to form bead-free fibers. The morphology of fabricated nanofiber scaffolds was characterized by Fourier-transform infrared (FTIR) and scanning electron microscopy (SEM). Microscopic images demonstrated the smooth bead-free microstructures fabrication of every layer of nanofiber with a uniform fiber size of 126.888 to 136.833 nm. While, EO and AMX increased the diameter of nanofibers but there was no change in physical structure of nanofiber. The water contact angle test demonstrated hydrophilicity of nanofibers with 47.35°. Although EO and AMX had little effect on reducing hydrophilicity but nanofibers with contact angle between 51.4° until 65.4° are still hydrophilic. Multilayer nanofibers loaded by EO and AMX killed 99.99 % of both gram-negative and gram-positive bacteria in comparison with control and PVA/gelatin nanofiber. Also, in addition to confirming the non-toxicity of nanofibers, MTT results also showed the acceleration of cell proliferation. In vivo wound evaluation in mouse models showed that designed nanofibrous scaffolds could be an appropriate option for wound treatment due to their positive effect on angiogenesis, collagen deposition, granulation tissue formation, epithelialization, and wound closure
MIR96 Has Good Potential to Differentiate Human Bone Marrow-Derived Mesenchymal Stem Cells into Photoreceptor-Like Cells
No full textObjectives: MicroRNAs play an important role in the development and function of neuron cells. Among these, the miRNA known as MIR96 is abundantly expressed in mammalian retina and significantly affects differentiation, maturation, and survival of human photoreceptor cells. In this study, a mimic to miRNA-96 was transfected into human bone marrow-derived mesenchymal stem cells to explore the biological functions of MIR96 at differentiation processing. Materials and Methods: A mimic to miRNA-96 and a competitive control were transfected into human bone marrow-derived mesenchymal stem cells using Lipofectamine. After 24 and 48 hours, we evaluated changes in expression levels of genes associated with neural progenitor and photoreceptor differentiation (OTX2, NRL, protein kinase C, SLC1A1, and recoverin) by real-time polymerase chain reaction. In addition, we measured expression of mRNA and protein of the CRX gene (neuroretinal progenitor cell marker) and the RHO gene (terminal differentiation marker) using real-time polymerase chain reaction and immunocytochemistry, respectively. Results: Real-time polymerase chain reaction results showed increased levels of RHO and recoverin mRNA after 24 hours in transfected cells. In addition, mRNA levels of OTX2, CRX, NRL, RHO, recoverin, and protein kinase C increased after 48 hours in transfected cells. Immunocytochemistry results confirmed these findings by demonstrating RHO and CRX at both 24 and 48 hours in transfected cells. Conclusions: Control of the expression of MIR96 can be a good strategy to promote cell differentiation and can be used in cell therapy for retinal degeneration. Our results showed that human bone marrow-derived mesenchymal stem cells can differentiate into photoreceptor cells after transfection with MIR96. These results support therapeutic use of MIR96 in retinal degeneration and suggest human bone marrow-derived mesenchymal stem cells as a promising tool for interventions
Insights into the interplay between Epstein‐Barr virus (EBV) and multiple sclerosis (MS): A state‐of‐the‐art review and implications for vaccine development
No full textBackground and Aims: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS). MS results from an inflammatory process leading to the loss of neural tissue and increased disability over time. The role of Epstein Barr Virus (EBV), as one of the most common global viruses, in MS development has been the subject of several studies. However, many related questions are still unanswered. This study aimed to review the connection between MS and EBV and provide a quick outline of MS prevention using EBV vaccination. Methods: For this narrative review, an extensive literature search using specific terms was conducted across online databases, including PubMed/Medline, Scopus, Web of Science, and Google Scholar, to identify pertinent studies. Results: Several studies proved that almost 100% of people with MS showed a history of EBV infection, and there was an association between high titers of EBV antibodies and an increased risk of MS development. Various hypotheses are proposed for how EBV may contribute to MS directly and indirectly: (1) Molecular Mimicry, (2) Mistaken Self, (3) Bystander Damage, and (4) Autoreactive B cells infected with EBV. Conclusion: Given the infectious nature of EBV and its ability to elude the immune system, EBV emerges as a strong candidate for being the underlying cause of MS. The development of an EBV vaccine holds promise for preventing MS; however, overcoming the challenge of creating a safe and efficacious vaccine presents a significant obstacl
The Role of Local Angiotensin II/Angiotensin Type 1 Receptor in Endometriosis: A Potential Target for New Treatment Approaches
No full textEndometriosis is a chronic inflammatory disorder described by the presence of functional endometrial-like tissues at extra-uterine locations that are related to chronic pelvic pain and infertility. Multiple molecular mechanisms, including inflammation, reactive oxygen species (ROS) generation, fibrotic reactions, and angiogenesis, are involved in the pathogenesis of endometriosis; however, the exact cause of this disorder still remains a matter of discussion. Recently, it has been shown that the local renin-angiotensin system (RAS) has been expressed in different tissues, like the gynecological tract, and alterations in its expression are associated with multiple pathological conditions like endometriosis. Angiotensin II (Ang II), as a main peptide of the RAS through angiotensin type 1 receptor (AT1R), upregulates signal transduction pathways such as nuclear factor kappa B (NF-κB), mitogen activation protein kinase (MAPK), and transforming growth factor beta (TGF-β) to promote inflammation, oxidative stress, and fibrogenesis. Angiotensin receptor blockers (ARBs) control high blood pressure, which is increased by excessive AT1R activity. Recently, it has been recognized that ARBs have tissue protective effects because of their anti-inflammatory and antifibrotic effects. In this review, we focused on the role of local Ang II/AT1R axis activity in endometriosis pathogenesis and justified the use of ARB agents as a potential therapeutic strategy to improve endometriosi
Role of Small Non-Coding RNA in Gram-Negative Bacteria: New Insights and Comprehensive Review of Mechanisms, Functions, and Potential Applications
No full textSmall non-coding RNAs (sRNAs) are a key part of gene expression regulation in bacteria. Many physiologic activities like adaptation to environmental stresses, antibiotic resistance, quorum sensing, and modulation of the host immune response are regulated directly or indirectly by sRNAs in Gram-negative bacteria. Therefore, sRNAs can be considered as potentially useful therapeutic options. They have opened promising perspectives in the field of diagnosis of pathogens and treatment of infections caused by antibiotic-resistant organisms. Identification of sRNAs can be executed by sequence and expression-based methods. Despite the valuable progress in the last two decades, and discovery of new sRNAs, their exact role in biological pathways especially in co-operation with other biomolecules involved in gene expression regulation such as RNA-binding proteins (RBPs), riboswitches, and other sRNAs needs further investigation. Although the numerous RNA databases are available, including 59 databases used by RNAcentral, there remains a significant gap in the absence of a comprehensive and professional database that categorizes experimentally validated sRNAs in Gram-negative pathogens. Here, we review the present knowledge about most recent and important sRNAs and their regulatory mechanism, strengths and weaknesses of current methods of sRNAs identification. Also, we try to demonstrate the potential applications and new insights of sRNAs for future studies
The effect of celastrol in combination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cell lines
No full textBackground: Despite the availability of chemotherapy drugs such as 5-fluorouracil (5-FU), the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side effects. This study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines (AGS and EPG85-257). Materials and Methods: In this in vitro study, AGS and EPG85-257 cells were treated with different concentrations of celastrol, 5-FU, and their combination. Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The synergistic effect of 5-FU and celastrol was studied using Compusyn software. The DNA content at different phases of the cell cycle and apoptosis rate was measured using flow cytometry. Results: Co-treatment with low concentrations (10% inhibitory concentration (IC10)) of celastrol and 5-FU significantly reduced IC50 (p < 0.05) so that 48 h after treatment, IC50 was calculated at 3.77 and 6.9 μM for celastrol, 20.7 and 11.6 μM for 5-FU, and 5.03 and 4.57 μM for their combination for AGS and EPG85-257 cells, respectively. The mean percentage of apoptosis for AGS cells treated with celastrol, 5-FU, and their combination was obtained 23.9, 41.2, and 61.9, and for EPG85-257 cells 5.65, 46.9, and 55.7, respectively. In addition, the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis phase. Conclusions: Although celastrol could decrease the concentration of 5-fluorouracil that sufficed to suppress gastric cancer cells, additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol
Turmeric as a Gut-Microbiota Modulator for Cardio-Metabolic Risk Factors: An Updated Comprehensive Review
No full textTurmeric is a medicinal herb with antioxidant and anti-inflammatory components that can affect metabolic parameters via various pathways, including the gut-brain axis. Although positive effects of turmeric on health have been reported, findings are conflicting. Accordingly, the current review aimed to provide an overview of the biochemical and biological characteristics of turmeric and examine the impacts of turmeric on cardio-metabolic risk factors with a special focus on its abilities to modulate gut microbiota. In the present comprehensive review, findings of systematic reviews/narrative reviews, clinical trials, animal, and in vitro studies on turmeric in the English language published between 2010 and March 2023 were summarized. Findings revealed that turmeric is a safe medicinal herb with mild gastrointestinal side effects in some cases. It can help improve the glycemic status, lipid profile, and blood pressure. However, food processing and fermentation can affect the bioavailability of its effective components, including curcumin. Several mechanisms, including those affecting intestinal microbiota diversity, intestinal permeability, inflammatory and oxidative pathways, are proposed for their positive effects on metabolic factors. However, due to high between-study heterogeneity, limited high-quality clinical trials, differences in the duration of the intervention, and the form of turmeric supplement, more studies on each metabolic parameter are needed to determine effective dosages and confirm its efficacy as a complementary therapy to modulate microbiota and cardio-metabolic parameters
Evaluating the effects of permanent subcutaneous insulin infusion versus multiple daily insulin injections on glycated hemoglobin (HbA1c) levels in patients with type 2 diabetes: a systematic review and meta-analysis based on clinical trials
No full textBackground. Diabetes is one of the most common chronic and metabolic diseases. This systematic review and meta-analysis study aimed to compare the effects of multiple daily insulin injections against permanent subcutaneous insulin injections on glycated hemoglobin (HbA1C) levels in type 2 diabetic patients. Methods. Studies that compared the impacts of multiple daily insulin injections against permanent subcutaneous insulin injections on HbA1C levels and were published until the end of 2022 in international databases were searched and retrieved (nine randomized clinical trial studies). The Chi-squared test and I2 were used to determine the presence and size of heterogeneity. Results. The results of the analysis demonstrated that compared to the group of multiple daily insulin injections, HbA1C was significantly reduced in the group of permanent subcutaneous insulin injections, so that the standardized mean difference was equal to-0.26 (95% confidence interval:-0.46–-0.06 P=0.025). According to the results of Egger’s (P=0.333) and Begg’s (P=0.667) tests, publication bias was not observed in this study. Conclusion. Based on the available evidence, permanent subcutaneous injection of insulin could be significantly successful in reducing and controlling the level of HbA1C because the patients in the permanent subcutaneous injection group had lower levels of HbA1C. Practical Implications. In patients with type 2 diabetes, insulin treatment with the permanent subcutaneous injection method can better control the level of HbA1C than the multiple daily injection method
Studying Probability of Domino Effect in Chemical Storage Tanks Using Hazard Index
No full textThe accidents caused by the domino effect in industries are highly harmful. This study aims to analyze the occurrence probability of the domino effect with respect to possible explosion and fire scenarios in chemical tanks. Using the results obtained by previous studies, reviewing past accidents, and according to the equipment damage models, threshold values were used for extraction process equipment and inherent safety distances as a criterion to prevent domino accidents. According to primary scenarios and experimental equations, the escalation vector was determined for different tanks. According to the assumption that fire radius is equivalent to inherent safety distance, the fireball radius for tank 1 was calculated 535.7 m. According to the results, the DCP index of tank 3 can be considered the most critical unit. This research studies the probability of the domino effect and means to prevent them according to criteria and hazard index parameters
A State of Art Review: Volatile Organic Compounds and Periodontitis
No full textPeriodontitis is a notable public health issue impacting more than 1 billion individuals globally, and its connection with volatile organic compounds (VOCs) has attracted growing interest. This review seeks to explore the existing knowledge on the link between VOCs and periodontitis. Materials and Methods: An extensive literature review was performed to pinpoint key VOCs associated with periodontitis. Results: The review revealed that several VOCs, such as hydrogen sulfide, methanethiol, indole, limonene, formaldehyde, 1,4-dichlorobenzene, 2-Aminothiazoline-4-carboxylic acid, ethyl acetate, methyl mercaptan, dimethyl sulfide, acetone, pyridine, picolines, o-xylene, mandelic acid, and N-acetyl-S-(4-hydroxy-2-butenyl)-L-cysteine, are linked to periodontitis, with some contributing to heightened oral infection, direct tissue harm, oral malodor, and inflammatory responses, while the causality of this phenomenon remains unclear as it is uncertain which event occurs first. Conclusion: This review enumerates the VOCs that may either contribute to or arise from periodontitis; hydrogen sulfide appears to be the most extensively studied VOC in the context of periodontitis. This review highlights the intricate relationship between VOCs and periodontitis and underscores the necessity for additional research to clarify the mechanisms underlying this association and to guide the creation of effective prevention and treatment strategies