Introduction of a new recombinant vaccine based on GRP78 for breast cancer immunotherapy and evaluation in a mouse model.

Introduction: Breast cancer is one of the most prevalent malignancies in women. Several treatment options are available today, including surgery, chemotherapy, and radiotherapy. Immunotherapy, as a highly specific therapy, involves adaptive immune responses and immunological memory. In our present research, we used the recombinant C-terminal domain of the GRP78 (glucose- regulated protein 78) protein to induce an immune response and investigate its therapeutic impact in the 4T1 breast cancer model. Methods: BALB/c mice were immunized with the cGRP78 protein. The humoral immune response was assessed by ELISA. Then, BALB/c mice were injected subcutaneously with 1×106 4T1 tumor cells. Subsequently, tumor size and survival rate measurements, MTT, and cytokine assays were performed. Results: The animals receiving the cGRP78 vaccine showed significantly more favorable survival and slower tumor growth rates compared with unvaccinated tumor-bearing mice as the negative control mice. Circulating levels of tumoricidal cytokines such as IFNγ were higher, whereas tolerogenic cytokines such as IL-2, 6, and 10 either did not increase or had a decreasing trend in mice receiving cGRP78. Conclusion: cGRP78 vaccines generated potent immunotherapeutic effects in a breast cancer mouse model. This novel strategy of targeting the GRP78 protein can promote the development of cancer vaccines and immunotherapies for breast cancer malignancies.

Optimization of plasmid electrotransformation into Bacillus subtilis using an antibacterial peptide.

Bacillus subtilis can potentially serve as an efficient expression host for biotechnology due to its ability to secrete extracellular proteins and enzymes directly into the culture medium. One of the important challenges in the biotechnology industry is to optimize the transformation conditions of B. subtilis bacteria. This study aims to provide a new method to optimize the transformation conditions and improve the transformation efficiency of B. subtilis WB600. To increase the transformation efficiency in B. subtilis, two methods of adding CM11 antibacterial peptides to the bacterial medium along with electroporation and optimizing the variables including the growth medium composition, time to adding CM11 peptide, electroporation voltage, recovery medium, and cell recovery time are used. The results of this study showed that the addition of antimicrobial peptides (AMPs) with a concentration of 2 µg/ml increases the transformation efficiency by 4 times compared to the absence of AMP in the bacterial medium. Additionally, the findings from our study indicated that the most optimal rate of transformation for B. subtilis was observed at a voltage of 7.5 kV/cm, with a recovery period of 12 h. With the optimized method, the transformation efficiency came up to 1.69 × 104 CFU/µg DNA. This improvement in transformation efficiency will be attributed to the research of expression of exogenous genes in B. subtilis, gene library construction for transformation of wild-type B. subtilis strains.

Applications of SMILE-extracted lenticules in ophthalmology.

AIM: To review recent innovations, challenges, and applications of small incision lenticule extraction (SMILE) extracted lenticule for treating ocular disorders. METHODS: A literature review was performed in the PubMed database, which was last updated on 30 December 2021. There was no limit regarding language. The authors evaluated the reference lists of the collected papers to find any relevant research. RESULTS: Due to the simplicity and accuracy of modern femtosecond lasers and the extensive development of SMILE surgery, many healthy human corneal stromal lenticules were extracted during surgery, motivating some professionals to investigate the SMILE lenticule reusability in different ocular disorders. In addition, new approaches had been developed to preserve, modify, and bioengineer the corneal stroma, leading to the optimal use of discarded byproducts such as lenticules from SMILE surgery. The lenticules can be effectively re-implanted into the autologous or allogenic corneas of human subjects to treat refractive errors, corneal ectasia, and corneal perforation and serve as a patch graft for glaucoma drainage devices with better cosmetic outcomes. CONCLUSION: SMILE-extracted lenticules could be a viable alternative to human donor corneal tissue.

An inspired microenvironment of cell replicas to induce stem cells into keratocyte-like dendritic cells for corneal regeneration.

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.

Combination of natural scaffolds and conditional medium to induce the differentiation of adipose-derived mesenchymal stem cells into keratocyte-like cells and its safety evaluation in the animal cornea.

Keratocytes are the main cellular components of the corneal stroma. This cell is quiescent and cannot be cultured easily. The aim of this study was to investigate differentiate human adipose mesenchymal stem cells (hADSCs) into corneal keratocyte cells by combining natural scaffolds and conditioned medium (CM) and evaluating their safety in the rabbit's cornea. Keratocytes were cultured in an optimal culture medium and this medium was collected and kept as a CM. hADSCs were cultured on the decellularized human small incision lenticule extraction (SMILE) lenticule (SL), amniotic membrane (AM), and collagen-coated plates, and were exposed to keratocyte-CM (KCM) for 7, 14, and 21 days. Differentiation was evaluated using Real-time PCR and immunocytochemistry (ICC). hADSCs were cultured on the SL scaffolds and implanted in the corneal stroma of 8 New Zealand male rabbits. Rabbits were followed for 3 months and the safety was evaluated by clinical and histological variables. Real-time PCR results showed a significant increase in the expression of keratocyte-specific markers on the 21 day of differentiation compared to the control group. ICC also confirmed the induction of differentiation. Implantation of SLs containing differentiated cells in the cornea of animals showed no serious complications including neovascularization, corneal opacity, inflammation, or signs of tissue rejection. Furthermore, the evaluation of the presence of keratocyte-like cells after three months in the rabbit stroma was confirmed by Real-time PCR and immunohistochemistry (IHC) analysis. Our results showed that combination of combination of corneal extracellular matrix and KCM can induced keratocytes differentiation of hADSC and can be introduced as a alternative method to supply the required keratocytes in corneal tissue engineering.

The Effect of Amniotic Membrane Extracted Eye Drop on Repairing The Corneal Epithelial in Patients after Trans-Epithelial Photorefractive Keratectomy: An Interventional and Historical Study.

OBJECTIVE: Recent studies imply extensive applications for the human amniotic membrane (hAM) and its extract in medicine and ophthalmology. The content of hAM meets many requirements in eye surgeries, such as refractive surgery as the most important and commonly used method for treating the dramatically increasing refractive errors. However, they are associated with complications such as corneal haziness and corneal ulcer. This study was designed to evaluate the impact of amniotic membrane extracted eye drop (AMEED) on Trans-PRK surgery complications. MATERIALS AND METHODS: This randomized controlled trial was performed during two years (July 1, 2019-September 1, 2020). Thirty-two patients (64 eyes), including 17 females and 15 males, aged 20 to 50 years (mean age of 29.59 ± 6.51) with spherical equivalent between -5 to -1.5 underwent Trans Epithelial Photorefractive Keratectomy (Trans-PRK) surgery. One eye was selected per case (case group) and the other eye was considered as control. Randomization was done using the random allocation rule. The case group was treated with AMEED, and the artificial tear drop every 4 hours. The control eyes received artificial tear drops instilled every 4 hours. The evaluation continued for three days after the Trans-PRK surgery. RESULTS: A significant decrease in CED size was found in the AMEED group on the second day after surgery (P=0.046). Also, this group had a substantial reduction in pain, hyperemia, and haziness. CONCLUSION: This study showed that AMEED drop can increase the healing rate of corneal epithelial lesions after Trans- PRK surgery and reduce the early and late complications of Trans-PRK surgery. Researchers and Ophthalmologists should consider AMEED as a selection in patients with persistent corneal epithelial defects and patients who have difficulty in corneal epithelial healing. We understood AMEED has a different effect on the cornea after surgery; therefore, the researcher must know AMEED's exact ingredients and help expand AMEED uses (registration number: TCTR20230306001).

Histopathology Study of Patients with Delayed Mustard Gas Keratopathy 30 Years After Exposure.

Background & Objective: Delayed mustard gas keratopathy (DMGK) is the main chronic outcome in eye-chemical injured patients. The aim of this study was the histopathological evaluation of mustard-exposed cornea after more than 30 years. Methods: Fourteen corneas after Lamellar keratoplasty were evaluated in this study. Corneal tissues were prepared by histologic methods and stained by H&E. Results: The main histopathological findings in these cases were the presence of severe stromal edema and corneal scar. In the sections with visible superficial epithelium, subepithelial bullae formation was observed. Focal or diffuse disruption of Bowman's membrane and replacement with fibrosis were also seen. There was no evidence of stromal vascularization and inflammation in all specimens. Conclusion: After more than 30 years, an extensive corneal scar is seen in sulfur mustard exposed patients. Scar tissue without vascularization and fibroblastic proliferation is the main finding in the sulfur mustard exposed cornea. This pathology result is different from other scars. No evidence of inflammation or immune cell infiltration should be considered in managing DMGK.

A new hydrogel with fluorapatite nanoparticles for osteogenic differentiation of human adipose-derived stem cells in tissue engineering field.

Since scaffolds are engineered to support functional tissue formation, their design and materials play an essential role in medical fields by providing different mechanical function. The aim of this study was to investigate the synthesis and structural characterization of collagen-gelatin (COL-GEL) composite scaffolds containing fluorapatite (FA) nanoparticles as well as evaluation of the osteogenic differentiation of human adipose-derived stem cells (hADSCs). First, the composite scaffolds were evaluated using Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction. The cytotoxicity of scaffolds and various concentrations of FA nanoparticles was studied through MTT assay and acridine orange/ethidium bromide staining. Next, the differentiated hADSCs were analyzed using Alizarin red and von Kossa staining, calcium content assay, alkaline phosphatase (ALP) activity, real-time RT-PCR, and immunocytochemical analyses. According to the characterization analyses, the composite scaffolds were properly integrated. The results also illustrated that COL-GEL composite scaffolds in the presence of FA nanoparticles not only showed no cytotoxicity but also increased ALP activity and calcium deposition as well as the expression of osteogenic genes, including Runx2, Col-I, ALP, and osteocalcin and the synthesis of proteins such as osteocalcin and osteopontin in vitro. The obtained data were confirmed by Alizarin red and von Kossa staining. These results are very promising for further tissue engineering experiments, in which FA nanoparticle incorporation into COL-GEL composite scaffolds is a novel approach that improves the surface COL-GEL composite scaffolds for tissue engineering application in vitro.

Tear proteomics analysis of patient suffered from delayed mustard gas keratopathy.

Understanding the molecular and cellular mechanisms involved in the pathogenesis of ocular injured induced by mustard gas can help better identify complications and discover appropriate therapies. This study aimed to analyze the proteomics of tears of chemical warfare victims with mustard gas ocular injuries and compare it with healthy individuals. In this case-control research, 10 mustard gas victims with long-term ocular difficulties (Chronic) were included in the patient group, while 10 healthy persons who were age and sex matched to the patients were included in the control group. Schirmer strips were used to collect the tears of the participants. Proteomics experiments were performed using the high-efficiency TMT10X method to evaluate the tear protein profile, and statistical bioinformatics methods were used to identify the differently expressed proteins. 24 proteins had different expressions between the two groups. Among these 24 proteins, 8 proteins had increased expression in veterans' tears, while the remaining 16 proteins had decreased expression. Reactome pathways were used to look at proteins with various expressions, and 13 proteins were found to be engaged in the immune system, 9 of which were effective in the innate immune system, and 5 proteins were effective in the complement cascade. Ocular mustard gas exposure may cause a compromised immune system on the eye's surface, exposing the cornea to external and endogenous infections, and eventually causing corneal opacity and reduced vision.

The role of saffron in improvement of ocular surface disease in a mouse model of Lacrimal Gland Excision-induced dry eye disease.

One of the most prevalent eye disorders is dry eye disease (DED), described by ocular dryness due to the tear insufficiency. Prolonged dry eye causes damage and ulcer to the surface of the cornea. The core of the DED mechanism is inflammation which is a biological response of the body to pathogens. Several studies have indicated that saffron has many beneficial biological effects, such as anti-inflammatory and free radical scavenging. This research aims to examine possible positive impact of saffron in the mice model of DED. The animals were divided into 4 groups. Induction of DED was done by right Lacrimal Gland Excision (LGE). Treatment was done by intraperitoneal (i.p.) injection of saffron (1 mg/kg/day, for 28 days after induction of DED) in the SAF group, betamethasone (the BET group) (i.p., 1 mg/kg/day, for 28 days after induction of DED), the LGE group (received normal saline i.p. for 28 days after induction of DED) and the sham group (no induction of DED). Ophthalmological assay with fluorescein staining on the 0, 14 and, 28 days, histopathological analysis (H & E assay) on the last day and, pro-inflammatory cytokine assays of eyes were done. Saffron and betamethasone reduced the fluorescein score of the eyes (P < 0.0001) and improved the ocular surface disease in H & E assay as well as reduced the eye levels of TNF-α (P < 0.01), IL-1ß (P < 0.0001) and, IL-6 (P < 0.001) compared to those of the LGE group. The current study indicated that treatment with saffron has a beneficial effect on LGE (Lacrimal gland excision)-induced DED in mice via its anti-inflammatory properties.

Emerging tissue engineering strategies for the corneal regeneration.

Cornea as the outermost layer of the eye is at risk of various genetic and environmental diseases that can damage the cornea and impair vision. Corneal transplantation is among the most applicable surgical procedures for repairing the defected tissue. However, the scarcity of healthy tissue donations as well as transplantation failure has remained as the biggest challenges in confront of corneal grafting. Therefore, alternative approaches based on stem-cell transplantation and classic regenerative medicine have been developed for corneal regeneration. In this review, the application and limitation of the recently-used advanced approaches for regeneration of cornea are discussed. Additionally, other emerging powerful techniques such as 5D printing as a new branch of scaffold-based technologies for construction of tissues other than the cornea are highlighted and suggested as alternatives for corneal reconstruction. The introduced novel techniques may have great potential for clinical applications in corneal repair including disease modeling, 3D pattern scheming, and personalized medicine.

Topical Effects of N-Acetyl Cysteine and Doxycycline on Inflammatory and Angiogenic Factors in the Rat Model of Alkali-Burned Cornea.

The aim of this study was to analyze the single and combined effects of N-acetyl cysteine (NAC) and doxycycline (Dox) on the inflammatory and angiogenic factors in the rat model of alkali-burned cornea. Rats were treated with a single and combined 0.5% NAC and 12.5 µg/mL Dox eye drops and evaluated on days 3, 7, and 28. In the corneas of various groups, the activity of Catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) enzymes was assessed. The expression of inflammatory factors (TNF-α, Rel-a, and CXCL-1) and angiogenic factors (VEGF-a, MMP2, and MMP9) was measured using real-time polymerase chain reaction. The antioxidant enzyme activities decreased substantially 3 days after injury with sodium hydroxide (NaOH). NAC and combined NAC+ Dox topical treatments increased the SOD enzyme activity on day 28 (P < 0.05). The expression of TNF-α and Rel-a genes following single and combined treatment of NAC and Dox decreased significantly on days 7 and 28 (P < 0.05). The mRNA level of angiogenic factors and corneal neovascularization (CNV) level declined in NaOH-injured rats treated with Dox (P < 0.05). The topical treatment of Dox could attenuate inflammation and CNV complications. However, NAC treatment may not reduce the expression of angiogenic genes.

NLRP3 inflammasome activation and oxidative stress status in the mild and moderate SARS-CoV-2 infected patients: impact of melatonin as a medicinal supplement.

The inflammasome as a multiprotein complex has a role in activating ASC and caspase-1 resulting in activating IL-1ß in various infections and diseases like corona virus infection in various tissues. It was shown that these tissues are affected by COVID-19 patients. According to the current evidence, melatonin is not veridical while possessing a high safety profile, however, it possesses indirect anti-viral actions owing to its anti-oxidation, anti-inflammation, and immune improving properties. This study aims to assess the impacts of melatonin as the complementary treatments on oxidative stress agents and inflammasome activation in patients with COVID-19. Melatonin supplement (9 mg daily, orally) was provided for the patients hospitalized with a COVID-19 analysis for 14 days. For measuring IL-10, IL-1ß, and TNF-α cytokines and malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) level and the expression of CASP1 and ASC genes, blood samples were gathered from the individuals at the start and termination of the therapy. Our findings indicated that melatonin is used as a complementary treatment to reduce the levels of TNF-α and IL-1ß cytokines, MDA, and NO levels in COVID-19 patients and significantly increase SOD level, however, the levels of IL-10 cytokine possesses no considerable changes. The findings revealed that genes of CASP1 and ASC were dysregulated by melatonin regulating the inflammasome complex. Based on the findings of the current study, it is found that melatonin can be effective as a medicinal supplement in decreasing the inflammasome multiprotein complex and oxidative stress along with beneficial impacts on lung cytokine storm of COVID-19 patients.

A comparative study of laboratory findings in PCR-positive and PCR-negative COVID-19 hospitalized patients.

INTRODUCTION: Given the many misconceptions in terms of both diagnosis and treatment, SARS-CoV-2 continues to infect and victimize. Notwithstanding molecular testing is the gold standard method of in vitro diagnostic, the often long-waiting time, as well as false-negative results are daunting challenges facing us. In this study, we aimed to report the diagnostic value of laboratory findings in COVID-19 patients, with an extensive focus on the differences between PCR-positive and PCR-negative cases. PATIENTS AND METHODS: We did a retrospective single-centre study on a large cohort of 1546 COVID-19 patients in Tehran, Iran. Based on clinical symptoms, chest CTs were performed for all the patients. Also, molecular testing of swab specimens was also performed for 1450 cases. RESULTS: All the data on laboratory results were retrospectively extracted from medical records. Of the 1546 patients, 1040 (67.5%) were male and 506 (32.5%) were female with the mean age of 55.67. On admission, 31.4% of the whole study population displayed lymphopenia and 38.9% showed neutrophilia. Decreased hemoglobin and mild thrombocytopenia were also found in 40% and 18.6% of cases, respectively. Elevated lactate dehydrogenase in nearly 75% of COVID-19 cases was the most common alteration amongst biochemical parameters which together with increased ESR and CRP could serve as diagnostic markers in SARS-CoV-2 infection. Of the 1450 patients with a PCR result, 439 (28.3%) were PCR-negative and 1011 (65.3%) were PCR-positive. Notably, lymphopenia and increased AST were higher in the PCR-positive group than their negative counterparts. Albeit being in the normal range, a significant decrease in the number of monocytes was also evident in the PCR-positive cases. CONCLUSIONS: As far we are aware, this is the first time that we reported a comprehensive exploration of laboratory characteristics of a large cohort of hospitalized COVID-19 patients from Iran, hoping that these data will cast more light on the diagnostic significance of these parameters.

The Role of Inflammatory Cytokines in Neovascularization of Chemical Ocular Injury.

AIM: Chemical injuries can potentially lead to the necrosis anterior segment of the eye, and cornea in particular. Inflammatory cytokines are the first factors produced after chemical ocular injuries. Inflammation via promoting the angiogenesis factor tries to implement the wound healing mechanism in the epithelial and stromal layer of the cornea. METHODS: Narrative review. RESULTS: In our review, we described the patterns of chemical injuries in the cornea and their molecular mechanisms associated with the expression of inflammatory cytokines. Moreover, the effects of inflammation signals on angiogenesis factors and CNV were explained. CONCLUSION: The contribution of inflammation and angiogenesis causes de novo formation of blood vessels that is known as the corneal neovascularization (CNV). The new vascularity interrupts cornea clarity and visual acuity. Inflammation also depleted the Limbal stem cells (LSCs) in the limbus causing the failure of normal corneal epithelial healing and conjunctivalization of the cornea.

Efficacy of a Low Dose of Melatonin as an Adjunctive Therapy in Hospitalized Patients with COVID-19: A Randomized, Double-blind Clinical Trial.

BACKGROUND: Melatonin has been known as an anti-inflammatory agent and immune modulator that may address progressive pathophysiology of coronavirus disease 2019 (COVID-19). AIM OF THE STUDY: To evaluate the clinical efficacy of adjuvant, use of melatonin in patients with COVID-19. METHODS: This single-center, double-blind, randomized clinical trial included 74 hospitalized patients with confirmed mild to moderate COVID-19 at Baqiyatallah Hospital in Tehran, Iran, from April 25, 2020-June 5, 2020. Patients were randomly assigned in a 1:1 ratio to receive standard of care and standard of care plus melatonin at a dose of 3 mg three times daily for 14 d. Clinical characteristics, laboratory, and radiological findings were assessed and compared between two study groups at baseline and post-intervention. Safety and clinical outcomes were followed up for four weeks. RESULTS: A total of 24 patients in the intervention group and 20 patients in the control group completed the treatment. Compared with the control group, the clinical symptoms such as cough, dyspnea, and fatigue, as well as the level of CRP and the pulmonary involvement in the intervention group had significantly improved (p <0.05). The mean time of hospital discharge of patients and return to baseline health was significantly shorter in the intervention group compared to the control group (p <0.05). No deaths and adverse events were observed in both groups. CONCLUSIONS: Adjuvant use of melatonin has a potential to improve clinical symptoms of COVID-19 patients and contribute to a faster return of patients to baseline health.

Detection of COVID-19 in tears of ICU-admitted patients with SARS-CoV-2 infection.

PURPOSE: Upon the outbreak of 2019, novel coronavirus (COVID-19) pandemic confirmed the cases surpassed 20 million. Despite a few reports identified the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with ocular manifestations, it may assess the ocular symptoms of patients with the COVID-19 by ophthalmologists facilitate the diagnosis and prevent transmission. METHODS: A total of 60 patients with the COVID-19 admitted to Baghiatallah hospital from March 2020 to May 2020 were retrospectively reviewed and analyzed for the ocular manifestations, blood tests, and reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV-2 using nasopharyngeal and conjunctival swabs. RESULTS: Among 60 included patients with clinically confirmed COVID-19, the median age 58.36 years (IQR: 30-88 years), 27 (45%) were male. Furthermore, 29 (48%) and 5 (8%) patients yielded positive for SARS-CoV-2 on RT-PCR from nasopharyngeal swabs and conjunctival specimens, respectively. Among 60 patients, 10 (16%) and 3 (5%), respectively, had the ocular manifestations and positive results for SARS-CoV-2 on RT-PCR from conjunctival and nasopharyngeal swabs. CONCLUSION: Although the positive rate of tear RT-PCR rate is not noticeable as nasopharyngeal swabs yet, COVID-19 transmission through the eyes is biologically plausible.

Safety evaluation of the atmospheric low-temperature plasma (ALTP) on the conjunctiva: an animal study and histopathological findings; 6-month follow-up.

BACKGROUND: Plasma medicine is an innovative research field focused on the application of atmospheric-pressure low-temperature plasmas (ALTP) for therapeutic purposes. Considering the potentials of plasma in ophthalmology, in this study, we evaluated the safety of plasma on the conjunctival tissue in animal models for 6 months. METHODS: Twelve adult male New Zealand albino rabbits were divided into four groups. The right eye of each rabbit was chosen for the test and the left eye was considered as the control. Experiments were performed using the Plexr device (GMV, Rocca Priora, RM, Italy). Four plasma spots were applied on the superior part of the conjunctiva (from 10 to 2 o'clock positions) using the continuous mode and a low power level (white handpiece) of the Plexr. For evaluation of the plasma safety, the histopathological changes were assessed 1 week (A), 1 month (B), 3 months (C), and 6 months (D) after the intervention. RESULTS: According to the histopathological findings, a mild decrease in blood vessels and severe stromal edema, as well as a superficial epithelium loss, were observed in group A. No chronic inflammation, scar tissue, deposition, and hemorrhage were found in group B. Epithelialization was confirmed by the histological examinations after 1 month. There was no evidence of atypia or dysplasia after 3 and 6 months. CONCLUSION: In conclusion, there were no persistent histopathological changes on conjunctival tissue after plasma exposure. Then, plasma can be considered as a minimally invasive alternative method for treating some ocular surface disorders.

Application of mesenchymal stem cells in corneal regeneration.

Due to delicate its structure, the cornea is susceptible to physical, chemical, and genetic damages. Corneal transplantation is the main treatment for serious corneal damage, but it faces significant challenges, including donor shortages and severe complications. In recent years, cell therapy is suggested as a novel alternative method for corneal regeneration. Regarding the unique characteristics of Mesenchymal stem cells including the potential to differentiate into discrete cell types, secretion of growth factors, mobilization potency, and availability from different sources; special attention has been paid to these cells in corneal engineering. Differentiation of MSCs into specialized corneal cells such as keratocytes, epithelial and endothelial cells is reported. Potential for Treatment of keratitis, reducing inflammation, and inhibition of neovascularization by MSCs, introducing them as novel agents for corneal repairing. In this review, various types of MSCs used to treat corneal injuries as well as their potential for restoring different corneal layers was investigated.