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BACKGROUND: There is an increased tissue expression of matrix metalloproteinases (MMPs) on Dupuytren contracture (DC). Genetic polymorphisms (single nucleotide polymorphism [SNPs]) in genes of these enzymes may individually influence these transcriptions. Haplotype analysis, which is the observation of a group of alleles, could be more useful to identify the association between SNPs and DC. The purpose of this study was to evaluate the influence of MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs individually and in haplotype on DC. METHODS: A total of 60 patients with a clinical diagnosis of DC were evaluated and matched, according to age and gender, with the control group of 100 patients without this clinical diagnosis. Genomic DNA was extracted from saliva samples, and genotypes were obtained by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis of the results included Mann-Whitney U test, Chi-squared test, and PHASE and R software, with a significance level of 5%. RESULTS: The 3 SNPs studied showed significant differences in allele and genotype frequencies between the groups: 2G in MMP-1 (P = .018; odds ratio [OR] 1.80 (95% confidence interval [CI], 1.13-2.88)), T in MMP-8 (P = .015; OR 0.53 (95% CI, 0.33-0.88)), and A in MMP-13 (rs2252070) SNPs (P = .040, OR 0.54 (95% CI, 0.33-0.90)) are risk alleles. The global haplotype analysis indicated a significant difference between both groups. CONCLUSIONS: In conclusion, MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs, individually and in haplotype, are a risk factor for DC, indicating that these SNPs may be a potential diagnostic and prognostic factor for DC.

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OBJECTIVES: The aim of this scoping review was to evaluate the available scientific evidence regarding the use of flavonoids in the treatment of caries-affected dentin focusing on bonding to dentin. METHODS: A comprehensive literature search was performed in five databases from March 2022 and updated in April 2023: PubMed, EMBASE, Scopus, Web of Science, and Scielo. Additionally, the references of included studies were manually searched. Gray literature was excluded from the review. STUDY SELECTION: Inclusion criteria included in vitro, in situ, and in vivo studies (animal or human) published in English. Abstracts, reviews, case reports, book chapters, doctoral dissertations, guidelines, and studies using pure plant extracts were excluded. Data collected from the selected studies were summarized and subjected to narrative and descriptive analysis. Out of the 91 studies identified, only 16 studies met the inclusion criteria. RESULTS: The review analyzed eight different flavonoids (hesperidin, galardin, proanthocyanidin, genipin, quercetin, naringin, epigallocatechin-3-gallate, and other catechins subtypes) used as pretreatment or loaded into adhesive systems, primers, and phosphoric acid. The use of flavonoids improved the mechanical properties of the materials and modified the biological properties of the dentin, reducing collagen loss by the inhibition of proteolytic activity of matrix metalloproteinases (MMPs). CONCLUSIONS: Based on the findings of this scoping review, it can be concluded that the use of flavonoids as pretreatment or incorporation into dental materials preserves collagen in the hybrid layer, inhibiting the MMPs activities, modifying the collagen fibrils of the dentin matrix and improving the mechanical properties of the dental adhesive systems. Therefore, it represents a promising approach for promoting dentin biomodification. This can result in more stable bonding of adhesive restorations to caries-affected dentin.

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COVID-19 is a devastating disease and imbalanced matrix metalloproteinase (MMP) activity may contribute to its pathophysiology. This exploratory study examined whether increased circulating concentrations of MMP-2 and MMP-9, and their endogenous inhibitors, the tissue inhibitors of MMP (TIMP)-1, TIMP-2, TIMP-3 and TIMP-4 are persistently found in patients 2 weeks after their recovery from severe or critical COVID-19 as compared with those in healthy controls. Subjects who had severe (n = 26) or critical (n = 25) PCR-confirmed COVID-19 and healthy controls (n = 21) had blood samples drawn 2 weeks after recovery and serum MMP-2, MMP-9, TIMP-1, TIMP-2, TIMP-3 and TIMP-4 were determined using two Human Luminex® Discovery Assays. Circulating MMP activity was also determined by gel zymography. Patients who had severe or critical COVID-19 had increased circulating MMP-9 and MMP-2 concentrations, with increased MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios indicating increased MMP activity, confirmed by gel zymography (all p < 0.05). Higher circulating MMP-9 (but not MMP-2) concentrations were found in critical versus severe COVID-19 (p < 0.05). We found increased circulating MMP-9 and MMP-2 concentrations and activity many days after recovery from the acute disease, with MMP-9 levels associated with disease severity. These biochemical alterations suggest that MMP-2 and MMP-9 may be important pharmacological targets in COVID-19.

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BACKGROUND: Bullous pilomatricoma is a rare variant of pilomatricoma. As it has been published in sporadic case reports, a limited understanding of its clinicopathological characteristics restricts its effective diagnosis and treatment. OBJECTIVES: This study aimed to analyze the clinicopathological and immunohistochemical characteristics of bullous pilomatricoma to better understand the bullous transformation of pilomatricoma. METHODS: The authors conducted a retrospective study of 12 patients with bullous pilomatricoma and compared their clinical, histopathological, and immunohistochemical data with those of patients with ordinary pilomatricoma. RESULTS: Bullous pilomatricoma showed no sex preference, with a mean onset age of 31.2 years. The common sites were the upper extremities and trunk. Bullous pilomatricoma had a shorter disease duration, a larger diameter, and a greater tendency to increase in size than those of ordinary pilomatricoma. Histopathologically, bullous pilomatricoma had a shorter duration, lesser calcification, more mitotic figures, and distinct dermal features from those of ordinary pilomatricoma. Immunohistochemically, the expression of Matrix Metalloprotease (MMP)-2, MMP-9, vascular endothelial growth factor receptor-3 (VEGFR-3), and VEGF-C was elevated. STUDY LIMITATIONS: The study was retrospective, and the sample size was small. CONCLUSION: The distinctive features of bullous pilomatricoma potentially result from dermal changes associated with the release of angiogenic factors and proteolytic enzymes. This comprehensive analysis provides novel insights into the clinical features and pathogenesis of bullous pilomatricoma.

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Periodontitis is an oral-cavity inflammatory disease and is the principal cause associated with tooth loss. Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are important proteases involved in periodontal tissue destruction. The omega-3 polyunsaturated fatty acids (ω-3 PUFA) have been demonstrated to possess immunoregulatory properties in periodontitis. The aim of the study was to investigate the effects of ω-3 PUFA on inflammation and on the expression of MMP-2 and -9 in a murine periodontitis model. Twenty-four male C57BL/6 mice were divided into control mice (Control), control mice treated with ω-3 PUFA (O3), mice with periodontitis (P), and mice with periodontitis treated with ω-3 PUFA (P + O3). ω-3 PUFA were administered orally once a day for 70 days. Periodontitis in mice was induced by Porphyromonas gingivalis-infected ligature placement around the second maxillary molar. The mice were sacrificed, and blood and maxillary samples were collected. Flow cytometry was used to quantify tumor necrosis factor-alpha (TNFα), interleukin (IL)-2, IL-4, IL-5, and interferon-gamma. Histologic analysis and immunohistochemistry for MMP-2 and -9 were performed. The data were statistically evaluated using analysis of variance (ANOVA) and the Tukey post hoc test. Histological analysis showed that ω-3 PUFA supplementation prevented inflammation and tissue destruction and revealed that bone destruction was more extensive in the P group than in the P + O3 group (p < 0.05). Also, it decreased the serum expressions of TNFα and IL-2 and the tissue expression of MMP-2 and -9 in the periodontitis-induced model (p < 0.05). ω-3 PUFA supplementation prevented alveolar bone loss and periodontal destruction, probably by decreasing the expression of MMP-2 and MMP-9 and its immunoregulatory properties.

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Abstract Background Bullous pilomatricoma is a rare variant of pilomatricoma. As it has been published in sporadic case reports, a limited understanding of its clinicopathological characteristics restricts its effective diagnosis and treatment. Objectives This study aimed to analyze the clinicopathological and immunohistochemical characteristics of bullous pilomatricoma to better understand the bullous transformation of pilomatricoma. Methods The authors conducted a retrospective study of 12 patients with bullous pilomatricoma and compared their clinical, histopathological, and immunohistochemical data with those of patients with ordinary pilomatricoma. Results Bullous pilomatricoma showed no sex preference, with a mean onset age of 31.2 years. The common sites were the upper extremities and trunk. Bullous pilomatricoma had a shorter disease duration, a larger diameter, and a greater tendency to increase in size than those of ordinary pilomatricoma. Histopathologically, bullous pilomatricoma had a shorter duration, lesser calcification, more mitotic figures, and distinct dermal features from those of ordinary pilomatricoma. Immunohistochemically, the expression of Matrix Metalloprotease (MMP)-2, MMP-9, vascular endothelial growth factor receptor-3 (VEGFR-3), and VEGF-C was elevated. Study limitations The study was retrospective, and the sample size was small. Conclusion The distinctive features of bullous pilomatricoma potentially result from dermal changes associated with the release of angiogenic factors and proteolytic enzymes. This comprehensive analysis provides novel insights into the clinical features and pathogenesis of bullous pilomatricoma.

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Abstract The aim of this study was to investigate the effect of acid challenge on the activation of matrix metalloproteinases (MMPs) in the Dentinoenamel junction of primary and permanent teeth submitted to radiotherapy. For this purpose, a total of 178 dental fragments obtained from molars were used, and randomly divided into 2 groups (primary and permanent teeth) / 4 experimental subgroups (irradiated and non-irradiated, demineralized and non-demineralized). The fragments were exposed to radiation, with a dose fraction of 2 Gy, for 5 consecutive days, until a total dose of 60 Gy was reached, with a total of 30 cycles, for 6 weeks. To determine the activity of MMPs on the dentinoenamel junction (DEJ), in situ zymography assays on 0.6mm dental fragments were performed. To assess whether MMP activity would be impacted by an acidic environment, the fragments were placed in a demineralizing solution (pH of 4.8). The finding was that irradiation activated MMPs in DEJ and these effects were more evident in permanent when compared with primary teeth. When the effect of an acid challenge on MMPs activity was investigated, demineralization was observed not to increase MMPs activity in non-irradiated teeth, but it did increase MMPs activity in irradiated teeth. In conclusion, an acid challenge was found to exacerbate activation of MMPs in DEJ of permanent teeth submitted to irradiation, but not in primary teeth.

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Abstract Conventional views associate microbial biofilm with demineralization in root caries (RC) onset, while research on their collagenases role in the breakdown of collagen matrix has been sporadically developed, primarily in vitro. Recent discoveries, however, reveal proteolytic bacteria enrichment, specially Porphyromonas and other periodontitis-associated bacteria in subgingivally extended lesions, suggesting a potential role in RC by the catabolism of dentin organic matrix. Moreover, genes encoding proteases and bacterial collagenases, including the U32 family collagenases, were found to be overexpressed in both coronal and root dentinal caries. Despite these advancements, to prove microbial collagenolytic proteases' definitive role in RC remains a significant challenge. A more thorough investigation is warranted to explore the potential of anti-collagenolytic agents in modulating biofilm metabolic processes or inhibiting/reducing the size of RC lesions. Prospective treatments targeting collagenases and promoting biomodification through collagen fibril cross-linking show promise for RC prevention and management. However, these studies are currently in the in vitro phase, necessitating additional research to translate findings into clinical applications. This is a comprehensive state-of-the-art review aimed to explore contributing factors to the formation of RC lesions, particularly focusing on collagen degradation in root tissues by microbial collagenases.

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Purpose: Osteoarthritis (OA) is a degenerative joint disease which is categorized via destruction of joint cartilage and it also affects the various joints, especially knees and hips. Sinomenine active phytoconstituents isolated from the stem of Sinomenium acutum and already proof anti-inflammatory effect against the arthritis model of rodent. In this experimental protocol, we scrutinized the anti-osteoarthritis effect of sinomenine against monosodium iodoacetate (MIA) induced OA in rats. Methods: MIA (3 mg/50 µL) was used for inducing the OA in the rats, and rats received the oral administration of sinomenine (2.5, 5 and 7.5 mg/kg body weight) up to the end of the experimental study (four weeks). The body and organs weight were estimated. Aggrecan, C-terminal cross-linked telopeptide of type II collagen (CTX-II), glycosaminoglycans (GCGs), monocyte chemoattractant protein-1 (MCP-1), Interferon gamma (IFN-γ), antioxidant, inflammatory cytokines, inflammatory mediators and matrix metalloproteinases (MMP) were analyzed. Results: Sinomenine significantly (P < 0.001) boosted the body weight and reduced the heart weight, but the weight of spleen and kidney remain unchanged. Sinomenine significantly (P < 0.001) reduced the level of nitric oxide, MCP-1 and improved the level of aggrecan, IFN-γ and GCGs. Sinomenine remarkably upregulated the level of glutathione, superoxide dismutase and suppressed the level of malonaldehyde. It effectually modulated the level of inflammatory cytokines and inflammatory mediators and significantly (P < 0.001) reduced the level of MMPs, like MMP-1, 2, 3, 9 and 13. Conclusions: Sinomenine is a beneficial active agent for the treatment of OA disease.

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Abstract High expression of MMP-2 and MMP-9 in periapical lesions plays an important role in the degradation of the extracellular matrix. This study aimed to investigate the effect of epigallocatechin-3-gallate (EGCG)-based endodontic paste as an intracanal dressing on the expression of MMP-2 and MMP-9 in periapical lesions. Periapical lesions were experimentally induced in 35 mature beagle dog premolars randomly divided into healthy teeth, untreated periapical lesions, periapical lesions treated in a single session (control groups), and periapical lesions treated in two sessions with EGCG or calcium hydroxide-based pastes (experimental groups). After 120 days, specimens were obtained for histopathologic and immunofluorescence analyses to assess the expression of MMP-2 and MMP-9. The statistical analysis was performed using a p-value of 0.05. Endodontic treatment in two sessions using medication with EGCG and calcium hydroxide-based pastes provided similar repair of the apical and periapical tissues and neoformation of periodontal ligament fibers, cementum, and alveolar bone (p>0.05). The experimental groups treated in two sessions with both medications presented expression of MMP-2 and MMP-9 similar to that in healthy teeth (p>0.05), and significantly lower than teeth treated in a single session or untreated periapical lesions (p <0.001). Expression of MMP-2 and MMP-9 was observed in the cytoplasm of fibroblasts, osteoblasts, cementoblasts, cementocytes, and vascular endothelium. The use of EGCG-based endodontic paste reduced the expression of MMP-2 and MMP-9 and allowed repair of periapical lesions, similar to calcium hydroxide-based paste, and superior to treatment performed in a single session.

Resumo A alta expressão de MMP-2 e MMP-9 em lesões periapicais desempenha um papel importante na degradação da matriz extracelular. Este estudo teve como objetivo investigar o efeito de uma pasta à base de epigalocatequina-3-galato (EGCG) como curativo intracanal na expressão de MMP-2 e MMP-9 em lesões periapicais. Lesões periapicais foram induzidas experimentalmente em 35 pré-molares de cães da raça beagle, maduros, divididos aleatoriamente em dentes saudáveis, lesões periapicais não tratadas, lesões periapicais tratadas em uma única sessão e lesões periapicais tratadas em duas sessões com a pasta de EGCG ou pasta à base de hidróxido de cálcio. O operador monitorou os animais e realizou a eutanásia após 120 dias para análises histopatológicas e de imunofluorescência para avaliar a expressão de MMP-2 e MMP-9. A análise estatística foi realizada utilizando p=0,05. O tratamento endodôntico em duas sessões com pasta à base de EGCG e pasta à base de hidróxido de cálcio proporcionou níveis semelhantes de reparação dos tecidos apicais e periapicais e neoformação de fibras do ligamento periodontal, cemento e osso alveolar. Em ambos os grupos, a expressão de MMP-2 e MMP-9 foi mínima, sendo observada no citoplasma de fibroblastos, osteoblastos, cementoblastos, cementócitos e endotélio vascular. Em ambos os grupos tratados em duas sessões, a expressão de MMP-2 e MMP-9 foi semelhante à dos dentes hígidos e significativamente menor do que nas lesões periapicais tratadas em sessão única ou não tratadas (p < 0,001). O uso da pasta à base de EGCG reduziu a expressão de MMP-2 e MMP-9 e permitiu o reparo de lesões periapicais, semelhante à pasta à base de hidróxido de cálcio, e foi superior ao tratamento realizado em sessão única.