Exploring the Interplay between Polyphenols and Lysyl Oxidase Enzymes for Maintaining Extracellular Matrix Homeostasis.

Collagen, the most abundant structural protein found in mammals, plays a vital role as a constituent of the extracellular matrix (ECM) that surrounds cells. Collagen fibrils are strengthened through the formation of covalent cross-links, which involve complex enzymatic and non-enzymatic reactions. Lysyl oxidase (LOX) is responsible for catalyzing the oxidative deamination of lysine and hydroxylysine residues, resulting in the production of aldehydes, allysine, and hydroxyallysine. These intermediates undergo spontaneous condensation reactions, leading to the formation of immature cross-links, which are the initial step in the development of mature covalent cross-links. Additionally, non-enzymatic glycation contributes to the formation of abnormal cross-linking in collagen fibrils. During glycation, specific lysine and arginine residues in collagen are modified by reducing sugars, leading to the creation of Advanced Glycation End-products (AGEs). These AGEs have been associated with changes in the mechanical properties of collagen fibers. Interestingly, various studies have reported that plant polyphenols possess amine oxidase-like activity and can act as potent inhibitors of protein glycation. This review article focuses on compiling the literature describing polyphenols with amine oxidase-like activity and antiglycation properties. Specifically, we explore the molecular mechanisms by which specific flavonoids impact or protect the normal collagen cross-linking process. Furthermore, we discuss how these dual activities can be harnessed to generate properly cross-linked collagen molecules, thereby promoting the stabilization of highly organized collagen fibrils.

Dental Adhesives-Surface Modifications of Dentin Structure for Stable Bonding.

The latest advancements in dentin bonding have focused on strategies to impair degradation mechanisms in order to extend the longevity of bonded interfaces. Protease inhibitors can reduce collagen degradation within the hybrid layer (HL). Collagen cross-linkers allow better adhesive infiltration and also inhibit proteases activity. Particles added to adhesive can promote mineral precipitation within the HL, reducing nanoleakage and micropermeability, besides possible antimicrobial and enzymatic inhibition effects. Most of these approaches are still experimental, and aspects of the adhesive under the clinician's control are still determinant for the long-term stability of adhesive restorations.

Collagen Cross-Linking Lignin Improves the Bonding Performance of Etch-and-Rinse Adhesives to Dentin.

To evaluate the biomodification ability of lignin used as pre-treatment in human dentin before the application of an etch-and-rinse adhesive. Experimental hydroethanolic solutions with different cross-linking agents were used: 6.5% proanthocyanidins (PAC, from grape-seed extract); 2% cardanol (CARD, from cashew-nut shell liquid); lignin (LIG, from eucalyptus) at 1, 2 or 4% concentrations. The negative control (NC) was ethanol 50 v%. Extracted molars were prepared, and dentin microtensile bond strength (µTBS) was evaluated after 24 h water storage or 10,000 thermocycling aging. Further specimens were processed for SEM nanoleakage, micropermeability confocal microscopy evaluation and in situ degree of conversion (DC) through micro-Raman spectroscopy. Demineralized dentin sticks were submitted to a three-point bending test to evaluate the elastic modulus (E) before and after 1 min biomodification using the tested solutions. Moreover, it was also evaluated the mass changes and hydroxyproline (HYP) release after 4-weeks of water storage. Vibrational collagen crosslinking identification was evaluated through micro-Raman spectroscopy. The results were analyzed by analysis of variance (ANOVA) and Tukey's test (α = 0.05). A significant reduction in µTBS was observed in groups NC (p < 0.001) and CARD (p = 0.026). LIG-4% showed no significant reduction in µTBS after aging (p = 0.022). Nanoleakage micrographs showed hybrid layer protection with all agents, but reduced micropermeability was attained only with lignin. Polymerization was negatively affected in the presence of all tested cross-linking agents, except LIG-1%. Lignin and cardanol increased the dentin E values, but only lignin reduced the mass loss in dentin specimens. Effective collagen crosslinking (1117 cm−1 and 1235 cm−1) was detected for all agents. HYP release was significantly lower with LIG-1% than NC (p < 0.001). Lignin was able to perform collagen cross-linking and prevent the degradation of unprotected dentin collagen, thereby improving the bonding performance of the composite restorations performed in this study.

Corneal Melting after Collagen Cross-Linking for Keratoconus in a Thin Cornea of a Diabetic Patient Treated with Topical Nepafenac: A Case Report with a Literature Review.

PURPOSE: To report the case of a 50-year-old woman with diabetes that presented with corneal melting and perforation 6 weeks after collagen cross-linking (CxL) for keratoconus (KC) and postoperative use of nepafenac eye drops, a nonsteroidal anti-inflammatory drug (NSAID). METHODS: This is a case report of a patient with diabetes, KC and a thin cornea that had undergone left eye corneal CxL at a different hospital followed by postoperative use of nepafenac eye drops for 6 weeks. RESULTS: The patient presented for the first time to our clinic with left corneal melting, perforation and iris prolapse 6 weeks after corneal CxL and topical nepafenac use. She was treated with a left eye tectonic penetrating keratoplasty, extracapsular cataract extraction, intraocular lens implantation and pupilloplasty. CONCLUSIONS: The corneal melting and perforation in this patient was associated with multiple risk factors: (1) nepafenac eye drop use, (2) CxL in a cornea thinner than 400 µm and (3) diabetes. The recommended corneal thickness limits should be respected. Topical NSAIDs should be used with caution if used as postoperative treatment after corneal CxL and in patients with diabetes, epithelial defect or delayed healing, because of the possible increased risk for corneal melting when multiple risk factors are observed.

Expression analysis of genes involved in collagen cross-linking and its regulation in traumatic anterior shoulder instability.

The molecular alterations involved in the capsule deformation presented in shoulder instability patients are poorly understood. Increased TGFß1 acts as a signal for production of matrix macromolecules by fibrogenic cells at joint injury sites. TGFß1, through its receptor TGFßR1, regulates genes involved in collagen cross-linking, such as LOX, PLOD1, and PLOD2. We evaluated TGFß1, TGFßR1, LOX, PLOD1, and PLOD2 gene expression in the antero-inferior (macroscopically injured region), antero-superior and posterior regions of the glenohumeral capsule of 29 shoulder instability patients and eight controls. We observed that PLOD2 expression was increased in the anterior-inferior capsule region of the patients compared to controls. LOX expression tended to be increased in the posterior portion of patients. Patients with recurrent shoulder dislocation presented upregulation of TGFßR1 in the antero-inferior capsule portion and of PLOD2 in the posterior region. Conversely, LOX was increased in the posterior portion of the capsule of patients with a single shoulder dislocation episode. In the antero-inferior, LOX expression was inversely correlated and TGFßR1 was directly correlated with the duration of symptoms. In the posterior region, PLOD2, TGFß1, and TGFßR1 were directly correlated with the duration of symptoms. In conclusion, PLOD2 expression was increased in the macroscopically injured region of the capsule of patients. Upregulation of TGFß1, TGFßR1, and PLOD2 seems to be related with the maintenance of disease symptoms, especially in the posterior region. LOX upregulation seems to occur only in the initial phase of the affection. Therefore, TGFß1, TGFßR1, LOX, and PLOD2 may play a role in shoulder instability.