Evaluation of Melatonin and its Nanostructures Effects on Skin Disorders Focused on Wound Healing.

Skin is the largest organ of the human body functioning as a great primitive defensive barrier against different harmful environmental factors. However, it is damaged through varying injuries such as different wounds, burns, and skin cancers that cause disruption in internal organs and essential mechanisms of the body through inflammation, oxidation, coagulation problems, infection, etc. Melatonin is the major hormone of the pineal gland that is also effective in skin disorders due to strong antioxidant and anti-inflammatory features with additional desirable antiapoptotic, anti-cancer, and antibiotic properties. However, melatonin characteristics require improvements due to its limited water solubility, halflife and stability. The application of nanocarrier systems can improve its solubility, permeability, and efficiency, as well as inhibit its degradation and promote photostability. Our main purpose in the current review is to explore the possible role of melatonin and melatonin-containing nanocarriers in skin disorders focused on wounds. Additionally, melatonin's effect in regenerative medicine and its structures as a wound dressing in skin damage has been considered.

Biomolecules-Loading of 3D-Printed Alginate-Based Scaffolds for Cartilage Tissue Engineering Applications: A Review on Current Status and Future Prospective.

Osteoarthritis (OA) can arise from various factor including trauma, overuse, as well as degeneration resulting from age or disease. The specific treatment options will vary based on the severity of the condition, and the affected joints. Some common treatments for OA include lifestyle modifications, medications, physical therapy, surgery and tissue engineering (TE). For cartilage tissue engineering (CTE), three-dimension (3D) scaffolds are made of biocompatible natural polymers, which allow for the regeneration of new cartilage tissue. An ideal scaffold should possess biological and mechanical properties that closely resemble those of the cartilage tissue, and lead to improved functional of knee. These scaffolds are specifically engineered to serve as replacements for damaged and provide support to the knee joint. 3D-bioprinted scaffolds are made of biocompatible materials natural polymers, which allow for the regeneration of new cartilage. The utilization of 3D bioprinting method has emerged as a novel approach for fabricating scaffolds with optimal properties for CTE applications. This method enables the creation of scaffolds that closely mimic the native cartilage in terms of mechanical characteristics and biological functionality. Alginate, that has the capability to fabricate a cartilage replacement customized for each individual patient. This polymer exhibits hydrophilicity, biocompatibility, and biodegradability, along with shear-thinning properties. These unique properties enable Alginate to be utilized as a bio-ink for 3D bioprinting method. Furthermore, chondrogenesis is the complex process through which cartilage is formed via a series of cellular and molecular signaling. Signaling pathway is as a fundamental mechanism in cartilage formation, enhanced by the incorporation of biomolecules and growth factors that induce the differentiation of stem cells. Accordingly, ongoing review is focusing to promote of 3D bioprinting scaffolds through the utilization of advanced biomolecules-loading of Alginate-based that has the capability to fabricate a cartilage replacement tailored specifically to each patient's unique needs and anatomical requirements.

Biochemical Aspects of Scaffolds for Cartilage Tissue Engineering; from Basic Science to Regenerative Medicine.

Chondral defects are frequent and important causes of pain and disability. Cartilage has limited self-repair and regeneration capacity. The ideal approach for articular cartilage defects is the regeneration of hyaline cartilage with sustainable symptom-free constructs. Tissue engineering provides new strategies for the regeneration of functional cartilage tissue through optimized scaffolds with architectural, mechanical, and biochemical properties similar to the native cartilage tissue. In this review, the basic science of cartilage structure, interactions between proteins, stem cells, as well as biomaterials, scaffold characteristics and fabrication methods, as well as current and potential therapies in regenerative medicine will be discussed mostly from a biochemical point of view. Furthermore, the recent trends in scaffold-based therapies and supplementary factors in cartilage tissue engineering will be considered.

Association of TIMP-1 and COL4A4 Gene Polymorphisms with Keratoconus in an Iranian Population.

PURPOSE: Keratoconus (KC) is a bilateral and noninflammatory disease, characterized by progressive thinning and anterior protrusion of the cornea and may result in severe visual impairment due to irregular astigmatism. Matrix metalloproteinases (MMP) are the main group of enzymes that degrade extracellular matrix proteins including collagens; Type IV collagen is found in the corneal stroma. MMP enzymatic activity is inhibited by tissue inhibitor of metalloproteinase-1 (TIMP-1). A decrease in TIMP-1 level is associated with the development of KC. In the present study, we investigated the impact of COL4A4 rs2228557 C/T and TIMP-1 rs4898 C/T (X-chromosome) variants on the odds of KC development in a sample of Iranian population. METHODS: This case-control study was conducted on 140 patients with KC and 150 healthy control subjects. We used modified methods of Nested-PCR and ARMS-PCR in combination (Nested-ARMS-PCR) and confirmed their validity with RFLP-PCR. RESULTS: Significant differences were noticed between KC patients and healthy individuals regarding the genotype TY or T allele frequencies of rs4898 in the male subjects (OR = 0.43, 95%CI: 0.20-0.92, P = 0.03), whereas no significant differences were identified in the female subjects (OR = 1.07, 95%CI: 0.52-2.20, P = 0.85). The rs2228557, T allele was associated with KC (OR = 0.69, 95% CI: 0.50-0.97, P = 0.035). CONCLUSION: In the rs2228557 variant, T allele acts as a protective factor from the disease and decreases the risk of KC compared with the C allele. Also, in our investigation about rs4898, we found that TY genotype or T allele decreased the risk of KC compared with the C allele in males and was a protective factor for KC in our population.

Genetic Polymorphisms of Catalase and Glutathione Peroxidase-1 in Keratoconus.

BACKGROUND: Keratoconus (KC) is a degenerative eye disease which results from thinning of the cornea and causes vision distortion. Oxidative stress damage to KC corneas may be because of the failure of corneas to process reactive oxygen species which leads to corneal thinning and loss of vision. Genetic variants in antioxidant defense genes such as catalase (CAT) and glutathione peroxidase (GPX) can decrease antioxidant capacity or increase oxidative stress and alter the risk of KC in patients. We investigated and evaluated the effects of single nucleotide polymorphisms in CAT, GPX-1 on the risk of KC in an Iranian population sample. METHODS: This case-control study was performed on 140 patients with KC and 150 healthy control subjects in a sample of Iranian population from Zahedan, southern Iran in 2015. Genotyping of CAT rs7943316 and GPX-1 rs1050450 polymorphisms was done using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: CAT rs7943316 A/T, AA genotype and A allele have a protective role against disease (OR =0.28, 95% CI =0.13-0.61, P=0.001 and OR = 0.50, 95% CI =0.35-0.72, P=0.0001, respectively) and decreased the risk of KC. Moreover, GPX-1 rs1050450 T allele increased the risk of KC in comparison with C allele (OR = 1.42, 95% CI = 1.01-2.03, P=0.03). CONCLUSION: CAT rs7943316 A/T, AA genotype, and A allele decreased the risk of KC. Moreover, in GPX-1 rs1050450 C/T polymorphism, T allele was associated with an increased risk of KC in our population.

Association of COL4A3 (rs55703767), MMP-9 (rs17576)and TIMP-1 (rs6609533) gene polymorphisms with susceptibility to type 2 diabetes.

Type 2 diabetes (T2D) is defined by high levels of glucose in the blood. The collagen IV level is associated with conditions of hyperglycemia and insulin resistance. Collagen type IV α3 chain (COL4A3) is a structural protein of the extracellular matrix (ECM). Matrix metallopeptidase 9 (MMP-9) is an enzyme that degrades the extracellular matrix and its activity is moderated by TIMP metallopeptidase inhibitor 1 (TIMP-1). The aim of the current study was to examine the association between genetic polymorphisms of COL4A3 (rs55703767), MMP-9 (rs17576) and TIMP-1 (rs6609533) in patients with T2D. This case-control study was performed on 120 Iranian patients with T2D and 120 healthy individuals. Genotypes were analyzed using the amplification refractory mutation system-polymerase chain reaction technique. The findings demonstrated significant differences between genotypic and allelic distributions of COL4A3 (G/T) and MMP-9 (A/G) polymorphisms as follows: COL4A3 (G/T); TT vs. GG, odds ratio (OR)=0.235, 95% confidence interval (CI)=0.063-0.0802 (P=0.013) and T vs. G, OR=0.592, 95% CI=0.371-0.943 (P=0.026); MMP-9 (A/G); AG vs. GG, OR=2.429, 95% CI=1.232-4.820 (P=0.008) and A vs. G, OR=2.176, 95% CI=1.155-4.130 (P=0.013). No significant association was identified between TIMP-1 (A/G) polymorphism and T2D in females and males. Thus, the genotypic and allelic distributions of COL4A3 (G/T) and MMP-9 (A/G) polymorphisms were associated with T2D. In addition, no significant association was identified in the genotypic distribution of the TIMP-1 (A/G) gene in females and in males. Further studies in other ethnic groups are required to confirm these findings.

Correlation between the COL4A3, MMP-9, and TIMP-1 polymorphisms and risk of keratoconus.

PURPOSE: Keratoconus (KC) is thinning of the central cornea. Its etiology is unknown, but it may result from degrading of collagen type IV. The major protein in the cornea is collagen. Matrix metalloproteinase-9 (MMP-9) is able to degrade collagen type IV from the basement membrane and extracellular matrix (ECM). MMP-9 enzymatic activity is inhibited by the tissue inhibitor of metalloproteinase-1 (TIMP-1). In the present study, we sought to investigate and evaluate the effects of single nucleotide polymorphisms in COL4A3, MMP-9, and TIMP-1 on the risk of KC in an Iranian population sample. METHODS: This case-control study was performed on 140 KC patients and 150 healthy controls. Genotyping of the COL4A3 rs55703767, MMP-9 rs17576, and TIMP-1 rs6609533 polymorphisms was done using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). RESULTS: Our findings showed that the rs55703767G/T polymorphism decreased the risk of KC (OR = 0.26, 95% CI = 0.08-0.82, P = 0.022). rs17576A/G, associated with KC and the A allele, was significantly overrepresented in healthy individuals. rs6609533A/G (X-chromosome) increased the risk of KC in females (OR = 2.27, 95% CI = 1.06-4.76, P = 0.036). In males, the allele frequency was not associated with KC risk/protection. CONCLUSIONS: This study indicates that in our population, the COL4A3 rs55703767 polymorphism decreased the risk of KC. However, the TIMP-1 rs6609533 polymorphism was associated with an increased risk of KC.

Evaluation of possible relationship between COL4A4 gene polymorphisms and risk of keratoconus.

PURPOSE: Keratoconus (KC) is a genetically heterogeneous corneal dystrophy with unknown etiology that causes loss of visual acuity. Evidence has shown that corneas from patients with KC contain reduced amounts of total collagen proteins, and collagen type IV has been suggested as a candidate gene in KC pathogenesis. This study aimed to evaluate the possible associations between collagen type IV alpha-4 chain (COL4A4) polymorphisms (rs2229813 G/A, M1327V and rs2228555 A/G, V1516V) and susceptibility to KC. METHODS: A total of 262 Iranian subjects including 112 patients with KC and 150 healthy individuals as controls were recruited in this case-control study. Diagnosis was based on clinical examination, electronic refractometry, and keratometry. Genotyping for the COL4A4 rs2229813 and rs2228555 variants was executed using allele-specific polymerase chain reaction and Tetra-ARMS polymerase chain reaction, respectively. RESULTS: A significant difference was found between the 2 groups regarding allelic and genotyping distribution of COL4A4 polymorphism at position rs2229813 G>A. The COL4A4 rs2229813 AA and GA+AA genotypes were risk factors for developing KC (odds ratio [OR] = 2.1, P = 0.036 and OR = 1.7, P = 0.042, for the AA and GA+AA genotypes, respectively). The COL4A4 rs2229813 A allele was also associated with an increased risk for KC (OR = 1.5, 95% confidence intervals: 1.1-2.2, P = 0.018). However, in our study, we found no association between COL4A4 rs2228555 polymorphism and the risk of KC. CONCLUSIONS: We suggest that the COL4A4 rs2229813 AA and GA+AA genotypes as well as the A allele play roles as risk factors for developing KC in our population.

Association of Lysyl oxidase (LOX) Polymorphisms with the Risk of Keratoconus in an Iranian Population.

BACKGROUND: Keratoconus is a connective tissue-related eye disease with unknown etiology that causes the loss of visual acuity. Lysyl oxidase (LOX) is an amine oxidase that catalyzes the covalent cross-link of collagens and elastin in the extracellular environment, thus determining the mechanical properties of connective tissue. The current study aimed to investigate the possible associations between two LOX polymorphisms, rs1800449 and rs2288393, and susceptibility to keratoconus. METHODS: A total of 262 Iranian subjects including 112 patients with keratoconus and 150 healthy individuals as controls were recruited. Genotyping for the LOX variants was performed using allele-specific PCR. RESULTS: A significant difference was found between two groups regarding allelic and genotyping distribution of LOX polymorphism at position rs1800449 G>A. The frequency of AA and GA + AA genotypes were increased in patients compared to controls (17% versus 8% and 62.5% versus 50%, respectively), showing a statistically significant difference (OR = 2.827, 95% CI: 1.251-6.391, p = 0.012). The A allele was associated with an increased risk for keratoconus, with the frequency of 39.9% and 29% in patients and controls, respectively (OR = 1.614, 95% CI: 1.119-2.326, p = 0.011). Furthermore, the haplotype analysis revealed that the rs1800449G/rs2288393C is a protective factor against keratoconus (OR = 0.425, 95% CI = 0.296-0.609, p = 0.001). Conversely, the +473A/rs2288393C (OR = 3.703, 95% CI = 2.230-6.149, p = 0.001) and +473G/rs2288393G (OR = 15.48, 95% CI = 3.805-63.03, p = 0.001) haplotypes were identified as risk factors for keratoconus. CONCLUSION: Our study demonstrated that the LOX rs1800449 genotypes (AA and GA + AA) and allele (A) appears to confer risk for susceptibility to keratoconus.