Anti-inflammatory and healing effect of the polysaccharidic extract of Opuntia ficus-indica cladodes in cutaneous excisional wounds in rats.

This study aimed to investigate the anti-inflammatory and wound healing effects of the polysaccharide extract from Opuntia ficus-indica cladodes (TPL-Ofi) using a rat cutaneous wound model. After anaesthesia, four 7-mm-diameter dorsal wounds per animal (n = 6/group for each experimental day of evaluation) were created in female Wistar rats using a surgical punch. The animals were treated topically twice daily with TPL-Ofi (0.01-1%; treated group) or sterile saline (control group) for a period of 21 days. Ulcerated tissue was collected for analysis of histological parameters (inflammation score, number of polymorphonuclear, mononuclear, fibroblast/myofibroblasts and blood vessels), immunohistochemical (fibroblast growth factor 2 [FGF-2]) and oxidative stress markers (myeloperoxidase [MPO] and glutathione [GSH]). After 21 days of treatment, body weight, net organ weight and plasma biochemical levels were measured. TPL-Ofi, containing a total carbohydrate content of 65.5% and uronic acid at 2.8%, reduced oedema on the second day and increased the nociceptive threshold on the second and third days. TPL-Ofi reduced mononuclear infiltrate on the second and MPO activity on the fifth day. TPL-Ofi increased GSH levels on the second day, as well as fibroblast/myofibroblasts counts, neoangiogenesis and FGF-2 levels on the fifth and seventh days. No changes were observed in body weight, net organ weight or toxicology assessment. Topical application of TPL-Ofi exhibited anti-inflammatory and antinociceptive effects, ultimately improving wound healing in cutaneous wounds.

Assessment of the association of myofibroblasts and structural components of the extracellular matrix with histopathological parameters of actinic cheilitis and lower lip squamous cell carcinoma.

BACKGROUND: To evaluate the presence of myofibroblasts (MFs) in the development of lip carcinogenesis, through the correlation of clinical, histomorphometric and immunohistochemical parameters, in actinic cheilitis (ACs) and lower lip squamous cell carcinomas (LLSCCs). METHODS: Samples of ACs, LLSCCs, and control group (CG) were prepared by tissue microarray (TMA) for immunohistochemical TGF-ß, α-SMA, and Ki-67 and histochemical hematoxylin and eosin, picrosirius red, and verhoeff van gieson reactions. Clinical and microscopic data were associated using the Mann-Whitney, Kruskal-Wallis/Dunn, and Spearman correlation tests (SPSS, p < 0.05). RESULTS: ACs showed higher number of α-SMA+ MFs when compared to CG (p = 0.034), and these cells were associated with the vertical expansion of solar elastosis (SE) itself (p = 0.027). Areas of SE had lower deposits of collagen (p < 0.001), immunostaining for TGF-ß (p < 0.001), and higher density of elastic fibers (p < 0.05) when compared to areas without SE. A positive correlation was observed between high-risk epithelial dysplasia (ED) and the proximity of SE to the dysplastic epithelium (p = 0.027). LLSCCs showed a higher number of α-SMA+ MFs about CG (p = 0.034), as well as a reduction in the deposition of total collagen (p = 0.009) in relation to ACs and CG. There was also a negative correlation between the amount of α-SMA+ cells and the accumulation of total collagen (p = 0.041). Collagen and elastic density loss was higher in larger tumors (p = 0.045) with nodal invasion (p = 0.047). CONCLUSIONS: Our findings show the possible role of MFs, collagen fibers, and elastosis areas in the lip carcinogenesis process.

Influence of Fermentation Time and Inoculation of Starter Culture on the Chemical Composition of Fermented Natural Coffee Followed by Depulping.

Fermentation using starter cultures has been considered an alternative and economically viable technology for the production of specialty coffees. This type of technology promotes several benefits, such as increased sensory quality, control over the fermentation process, predictability of the final product and added value. Coffee (Coffea arabica L.) samples for this study were collected in Presidente Olegário - MG (2018/19 crop year) in the Cerrado region of Minas Gerais. The effects of natural fermentation and inoculation of the yeast Torulaspora delbrueckii and duration of fermentation (0, 24, 48, 72 and 96 hours) on the sensory and chemical quality (analysis of bioactive, volatile, and organic compounds and fatty acids) of coffee were evaluated. The objective of this study was to determine the effect of fermentation time and starter culture inoculation on the chemical composition of fermented coffees. Fermentation time significantly influenced the sensory description of the coffee beverage, with notes of honey, brown sugar and almond predominating up to 48 hours, for coffees fermented for 72 and 96 hours the notes described were and fruity, winey notes. The chemical composition was primarily influenced by fermentation time.

Zoledronate treatment exerts sex-independent effects on bone and dental physicochemical properties in mice jaw necrosis.

INTRODUCTION: Bisphosphonate (BF) therapy is strongly related to the occurrence of medication-related osteonecrosis of the jaw (ONJ). However, no previous study has evaluated if there are sex-related differences on the ONJ establishment together with bone biomechanical alterations, and if they could have a synergy with the ZA treatment. MATERIALS AND METHODS: This study aimed to analyze the physicochemical properties of mineralized tissues in a zoledronate (ZA)-related osteonecrosis mouse model, by a 2 × 2-factorial design, considering sex (female/male) and treatment (ZA/Saline) factors (n = 8/group). After three ZA (1.0 mg/kg) or saline administrations (days 0, 7, 14), the lower left second molar was extracted (day 42). Further ZA administration (day 49) and euthanasia (day 70) were conducted. After confirmation of ZA-induced jaw necrosis (histologic and microtomographic analysis), spectroscopic and mechanical parameters were assessed. RESULTS: ZA-treated groups presented lower bone density due to impaired healing of tooth extraction socket. Sex-related alterations were also observed, with lower bone density in females. Regarding biomechanical parameters, sex and treatment exerted independent influences. ZA, although decreasing flexural modulus and yield stress, increases stiffness mainly due to a higher bone volume. Females show less resistance to higher loads compared to males (considering dimension-independent parameters). Additionally, ZA increases crystallinity in bone and dental structure (p < 0.05). In summary, although strongly related to osteonecrosis occurrence, ZA modifies bone and dental mineral matrix, improving bone mechanical properties. CONCLUSION: Despite sex-dependent differences in bone biomechanics and density, osteonecrosis was established with no sex influence. No synergistic association between sex and treatment factors was observed in this study.

Can SARS-CoV-2 screening in oral biopsies aid epidemiological surveillance?

BACKGROUND: Three years after the first confirmed COVID-19 case in Brazil, the outcomes of Federal government omissions in managing the crisis and anti-science stance heading into the pandemic have become even more evident. With over 36 million confirmed cases and nearly 700 000 deaths up to January 2023, the country is one of the hardest-hit places in the world. The lack of mass-testing programs was a critical broken pillar responsible for the quick and uncontrolled SARS-CoV-2 spread throughout the Brazilian population. Faced with this situation, we aimed to perform the routine SARS-CoV-2 screening through RT-qPCR of oral biopsies samples to aid in the asymptomatic epidemiological surveillance during the principal outbreak periods. METHODS: We analyzed 649 formalin-fixed paraffin-embedded oral tissue samples from five important oral and maxillofacial pathology laboratories from the north, northeast, and southeast geographic regions of Brazil. We also sequenced the whole viral genome of positive cases to investigate SARS-CoV-2 variants. RESULTS: The virus was detected in 9/649 analyzed samples, of which three harbored the Variant of Concern Alpha (B.1.1.7). CONCLUSION: Although our approach did not value aiding asymptomatic epidemiological surveillance, we could successfully identify a using FFPE tissue samples. Therefore, we suggest using FFPE tissue samples from patients who have confirmed diagnosis of SARS-CoV-2 infection for phylogenetic reconstruction and contraindicate the routine laboratory screening of these samples as a tool for asymptomatic epidemiological surveillance.

Is photobiomodulation effective during maxillary expansion? A systematic review and meta-analysis.

We performed a systematic review on literature associated with meta-analyses to elucidate whether (I) low-level laser therapy (C) compared to placebo accelerates (O) bone neoformation in the region of the midpalatal suture in (P) patients undergoing transverse maxillary expansion. Two reviewers blindly performed targeted searches using the selection criteria (PICOS) in seven major databases and three grey literature databases, employing specific terms and their entrenchments. The RevMan® software (Review Manager, version 5.3, Cochrane Collaboration) was used to adapt the RoB summary illustration to the Cochrane 2.0 tool questions. Meta-analysis was performed using standardized mean difference (SMD) and Cohen's d calculation on random effects, tests for heterogeneity (I2 ) and publication bias (Egger and Begg), and one-of-out sensitivity analysis. GRADE (Grading of Recommendations Assessment, Development and Evaluation) was used for evidence quality analysis. Among the five studies included in the qualitative synthesis, three were included in the meta-analysis. All analysed studies were prospective randomized clinical trials. The risk of bias was such that the Egger (P = .1991) and Begg (P = .024) tests showed no significant risk of publication bias. The meta-analysis showed high heterogeneity (I2  = 81%, P < .00001), and 3 months after the operation, there was no significant difference between the photobiomodulation (PBMT) group and control group (P = .850) or between the subgroups of the periods evaluated after 3 months (P = 0.490). GRADE showed an SMD of 0.62. Photobiomodulation as an adjuvant therapy in patients undergoing transverse maxillary expansion has few benefits and is limited in shape, as it contributes to bone healing in the midpalatal suture region after a period of 3 months.

N-Methyl-(2S,4R)-trans-4-hydroxy-L-proline isolated Sideroxylon obtusifolium attenuates TPA-induced irritant contact dermatitis in mice.

Dermatitis is defined as a set of inflammatory diseases that affect the skin, with varied causes. Among the different types of dermatitis, contact dermatitis is the most prevalent. Although the current therapy is often effective, it is associated with adverse effects and the possibility of drug tolerance. N-Methyl-(2S, 4R)-trans-4-hydroxy-L-proline is a L-proline amino acid derivative found in the leaves of Sideroxylon obtusifolium, a species traditionally used to treat inflammatory diseases. The aim of this study was to investigate the topical anti-inflammatory effect of N-methyl-(2S, 4R)-trans-4-hydroxy-L-proline (NMP) in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced irritant contact dermatitis in mice. Topically administered NMP, at doses of 0.03 - 0.50 mg/ear, reduced TPA-induced ear edema and neutrophil migration, as evidenced by low tissue myeloperoxidase activity and verified by histological examination. In addition, NMP (0.06 mg/ear) reduced tissue levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß, INF-γ and MCP-1) and of the anti-inflammatory cytokine IL-10, and reduced gene expression of TNF-α, IL-6 and IL-1ß increased by TPA. The data suggest that N-methyl-(2S, 4R)-trans-4-hydroxy-L-proline acts as a topical anti-inflammatory agent that decreases the expression of inflammatory cytokines, making it useful for the treatment of skin inflammation. Further investigations are necessary for its development as a therapeutic agent.

Outcomes of Apert Syndrome Hand Reconstruction With Tilapia Skin: A Prospective Study.

BACKGROUND: Tilapia skin has already been used in various medical scenarios, but there are no studies showing the use of tilapia skin for hand reconstruction in Apert syndrome. The objective of this study is to determine whether the use of tilapia skin during graft bed preparation for children with Apert syndrome can shorten wound reepithelialization intervals, reduce the number of dressing changes, and decrease patient discomfort. METHODS: This is a prospective study on consecutive patients with Apert syndrome who underwent hand reconstruction at our Hospital. Patients were divided into 2 groups: (1) a control group consisting of patients who underwent conventional digit separation hand reconstruction surgery (2) an experimental group consisting of patients who underwent similar digit separation hand reconstruction surgery that commenced with the placement of a thin layer of tilapia skin at the raw commissures during a first operation, which was subsequently replaced by an autologous skin graft during a second operation staged 10 days postoperatively. Pain assessment was performed using the Visual Analog Scale. The number of dressing changes was also assessed. A T test compared the total number of dressings changes and pain data. RESULTS: Experimental group patients (n = 8) required an average of 9.4 days of daily dressing changes, and control group patients (n = 5) required an average of 20.8 days of daily dressing changes ( P < 0.05) and tended to experience significantly less pain when compared with patients in the control group ( P = 0.079). CONCLUSION: Tilapia skin can shorten wound reepithelialization intervals by reducing the total number of dressing changes.

Outcomes of Oral and Oropharyngeal Squamous Cell Carcinoma Related to Healthcare Coverage: A Retrospective Cohort Study in Brazil.

We investigated the differences in prognosis according to the type of healthcare coverage of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). This study included 875 medical records. Patients covered by the publicly funded Unified Health System (SUS) had a low educational level, with advanced T stage and delayed treatment initiation. Multivariate analyses revealed an association between T stage (p = .035) and poor prognosis in oral squamous cell carcinoma, and age (p = .029) in oropharyngeal squamous cell carcinoma. Surgical treatment (p = .036) and marital status (p = .015) were considered predictors of better prognosis in OOSCC. Exclusive SUS-dependency can be considered an indirect prognostic factor for OOSCC.

Risk factors for renal impairment in patients with hematological cancer receiving antineoplastic treatment.

PURPOSE: Antineoplastic treatments, mainly chemotherapy, affect the kidneys, causing toxicity, and can trigger acute and chronic kidney injuries. This study aimed to analyze the prevalence of renal disorders in patients with oncohematological neoplasms receiving antineoplastic treatment. METHODS: This retrospective cohort study included 75 patients with hematological cancer who underwent chemotherapy between 2012 and 2018 in the Hematology Sector of the Walter Cantídeo University Hospital of the Federal University of Ceará. Sociodemographic and clinical data, blood biochemical assessment findings, and glomerular filtration rate (GFR) were analyzed using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The data were tabulated; transferred to the Statistical Package for the Social Sciences software, version 20.0; and analyzed using Pearson's chi-square test or Fisher's exact test for categorical variables followed by a multinomial logistic regression model (p < 0.05). RESULTS: The prevalence of renal disorders was 52.4% according to the CKD-EPI equation for GFR events. There was a significant association between the decrease in GFRs and the following variables: female sex (p = 0.002), diagnosis of multiple myeloma (p = 0.008), start of treatment within 40 days (p = 0.005), and the following antineoplastic treatments: cyclophosphamide, vincristine, and prednisone (p = 0.026); irarubicin (p = 0.032); azacytidine, dexamethasone, and cyclophosphamide (p < 0.001); zoledronic acid (p < 0.001); and pamidronate (p = 0.012). CALGB 8811 (p < 0.001) was inversely associated with a reduction in the GFR. CONCLUSIONS: The prevalence of renal disorders was high in patients with oncohematological neoplasms receiving antineoplastic treatment. This requires periodic monitoring of the evaluation of renal function since reductions in GFRs were significantly associated with different treatment protocols used.

Photobiomodulation therapy prevents dysgeusia chemotherapy induced in breast cancer women treated with doxorubicin plus cyclophosphamide: a triple-blinded, randomized, placebo-controlled clinical trial.

PURPOSE: To evaluate the effectiveness of photobiomodulation (PBMT) in preventing dysgeusia in breast cancer patients treated with doxorubicin-cyclophosphamide (AC). METHODS: This is a phase II, randomized, triple-blind, placebo-controlled clinical trial involving 112 breast cancer patients treated with AC. The patients were divided equally into two groups: a test group treated with 2 J red laser and 3 J infrared laser on 21 points that were symmetrically distributed on the tongue on day 0 of four cycles of AC, and an equal placebo group treated with simulated PBMT to blind the patient, evaluator, and statistician. The clinicopathological and sociodemographic data, results of taste test, and subjective taste analysis, and the QoL, ECOG performance status, body mass index, and other side effects were recorded. The data were analyzed using ANOVA-RM/Bonferroni, Friedman/Dunn, and chi-square/Fisher's exact tests. RESULTS: PBMT patients showed less objective and subjective taste loss (p<0.05). On the other hand, the placebo group showed a higher ECOG status (p=0.037) and more significant weight loss (p<0.001) after four cycles of AC. The QoL was significantly higher in the PBMT group (p<0.05) at all assessment periods, and PBMT treatment also reduced the incidence of cachexia (p=0.020), anorexia (p<0.001), diarrhea (p=0.040), oral mucositis (p=0.020), and vomiting (p=0.008). CONCLUSION: PBMT reduced the taste loss and improved the overall health status and QoL of patients with breast cancer treated with AC. TRIAL REGISTRATION: Brazilian Clinical Trials Registry ( www.ensaiosclinicos.gov.br ) approval number RBR-9qnm34y, registered on 01/05/2021.

Streptococcus mutans in atherosclerotic plaque: Molecular and immunohistochemical evaluations.

OBJECTIVES: To verify the presence of Streptococcus mutans (S. mutans) in atherosclerotic plaque (AP) using techniques with different sensitivities, correlating with histological changes in plaque and immunoexpression of inflammatory markers. MATERIALS AND METHODS: Thirteen AP samples were subjected to real-time polymerase chain reaction (qRT-PCR), histopathological analyses, histochemical analysis by Giemsa staining (GS), and immunohistochemical analysis for S. mutans, IL-1ß, and TNF-α (streptavidin-biotin-peroxidase method). Ten necropsy samples of healthy vessels were used as controls. RESULTS: All AP samples showed histopathological characteristics of severe atherosclerosis and were positive for S. mutans (100.0%) in qRT-PCR and immunohistochemical analyses. GS showed that Streptococcus sp. colonized the lipid-rich core regions and fibrous tissue, while the control group was negative for Streptococcus sp. IL-1ß and TNF-α were expressed in 100% and 92.3% of the AP tested, respectively. The control samples were positive for S. mutans in qRT-PCR analysis, but negative for S. mutans, IL-1ß, and TNF-α in immunohistochemical analyses. CONCLUSION: The detection of S. mutans in AP and the visualization of Streptococcus sp. suggested a possible association between S. mutans and atherosclerosis. The results obtained from the control samples suggested the presence of DNA fragments or innocuous bacteria that were not associated with tissue alteration. However, future studies are necessary to provide more information.

Intense orthodontic force induces the three dental pulp nitric oxide synthase isoforms and leads to orofacial discomfort in rats.

OBJECTIVE: The objective of this study was to evaluate the role of nitric oxide synthase (NOS) isoforms influence during tooth movement with different forces. SETTINGS AND SAMPLE POPULATION: 100 male Wistar rats (n = 10/group) were divided into a Sham group (animals not submitted to device installation nor Induced Toot Movement [ITM]), Negative Control Group (NCG) (animals submitted to device installation but not to ITM) and three experimental groups (F1, F2 and F3) (submitted to ITM with forces of 25, 50 and 100 gF respectively). MATERIALS AND METHODS: A daily count of biting and scratching on the vibrissae and the Grimace scale were applied. After 4 (D4) and 11 (D11) days, the molar diastema was measured, and the animals were euthanized for histological (vascular parameters) and immunohistochemistry (iNOS, eNOS and nNOS) in the dental pulp. RESULTS: On D4, there was significant movement in the F3 group (P = .001) and on D11 in F1, F2 and F3 (P < .001). The number of bites (P < .001) and scratching (P = .006) was higher in F2-F3, and F3 had higher Grimace scores (P < .001) and weight loss (P < .001). At D4, there was an increase in pulp ectasia in F2-F3 (P = .021) and a reduction in the number of vessels in F3 (P = .005). In D4 and D11, there was a significant increase in immunostaining for iNOS and eNOS in F1 (P = .025 and P < .001 respectively) and F2 (P = .007 and P < .001 respectively). At D4, F2 and F3 showed higher immunostaining for nNOS (P = .027). CONCLUSION: Thus, IDM induced inflammatory changes in the dental pulp reflecting in force-dependent pain/suffering signs.

Chronic systemic corticosteroid therapy influences the development of pulp necrosis and experimental apical periodontitis, exacerbating the inflammatory process and bone resorption in rats.

AIM: The main aim of the study was to evaluate the inflammatory response and development of apical periodontitis in rats chronically treated with glucocorticoids. METHODOLOGY: Male Wistar rats (Rattus novergicus) were randomly divided into two groups: the experimental group, which was treated with prednisone (5 mg/kg/day) and a control group, which was administered saline solution for 30 days before induction of apical periodontitis, continuing until the day of euthanasia days 0, 7, 14 and 28 after injury induction. The mandibles were subjected to histological evaluation to determine the size of the lesion, was also performed for the presence and absence of pulp necrosis, bone resorption and micro abscesses, and histomorphometric analyses were performed based on the number of polymorphonuclear cells and mononuclear cells. Histochemical analysis was also performed to assess the percentage of collagen fibres and their typification, in addition to immunohistochemistry for the inflammatory markers interleukin IL-1ß, IL-6, TNF-α and TRAP. RESULTS: Despite after 7 days, there was no differences between groups, a significant increase in the root pulp necrosis (p = .001), micro-abscesses (p = .026) and the size of the apical lesion on the 14th day of treatment with prednisone (p = .008). On the same day, there was also an increase in the number of polymorphonuclear cells (p = .042) and cells immunostained for IL-1ß (p = .006), IL-6 (p < .001) and TRAP (p = .002) in animals treated with prednisone. The numbers of mononuclear cells also increase in 28 days (p = .025) and TNF-α ± increases in the prednisone group on the 7th day (p = .041). The prednisone group also showed a decrease in collagen after 14 (both type I [p = .041] and type III [p = .046]) and 28 type III (p = .002) days after the coronary opening. CONCLUSIONS: The glucocorticoids modified the development of experimental apical periodontitis induced in rats, causing an early increase in periapical bone resorption and pulp necrosis. These effects are associated with alterations in cytokine levels, in the inflammatory response and in collagen deposition, in the 14th day after injury induction.

Tumor necrosis factor alpha (TNF-α) blockage reduces acute inflammation and delayed wound healing in oral ulcer of rats.

Oral traumatic ulcers (OTU) are common in dental routine, and the control of proinflammatory cytokines, such as the tumor necrosis factor-alpha (TNF-α), may interfere with OTU repair. Our aim was to evaluate the role of TNF-α in the healing process of OTU in rats. Wistar male rats were divided into six groups: a control-group (treated with 0.1 mL/kg of saline) and five groups treated with anti-TNF-α infliximab (INF) at 1, 3, 5, 7, and 10 mg/kg immediately before OTU production. The animals were weighed (day 0) and euthanized on days 1, 3, 7, 14 and 21 after ulceration. The ulcers were clinically measured, and the mucosa samples were histologically (scores 0-4), histochemically (collagen assay (pircrosirius)), histomorphometrically (cell counting), and immunohistochemically (TNF-α, α-smooth-muscle-actin (α-SMA), monocyte-chemoattractive-protein-1 (MCP-1), interleukin-8 (IL-8), and fibroblast-growth-factor (FGF)) analyzed. The Evans blue assay was used to measure the vascular permeability. ANOVA-1-2-way/Bonferroni, Kruskal-Wallis/Dunn, and correlation analyses were performed (GraphPad Prism 5.0, p < 0.05). High doses of INF reduced the OTU area (p = 0.043), body mass loss (p = 0.023), vascular permeability (p < 0.001), and reduced delayed histologic scores (p < 0.05), polymorphonuclear (p < 0.001) and mononuclear (p < 0.001) cells, blood vessel counting (p = 0.006), and total (p < 0.001), type-I (p = 0.018), and type-III (p < 0.001) collagen. INF treatment reduced TNF-α immunostaining and delayed MPC-1, FGF, and α-SMA expression, with little/none influence in IL-8 immunostaining. TNF-α blockage by INF reduced acute inflammation in OTU but delayed cell migration and wound healing.

Polysaccharide extract of Caesalpinia ferrea (Mart) pods attenuates inflammation and enhances the proliferative phase of rat cutaneous wounds.

Pods of Caesalpinia ferrea, popularly used to treat inflammatory processes, were collected to obtain the polysaccharide-rich extract, presenting anti-inflammatory and antinociceptive effects in acute inflammation models. This study aimed to evaluate the anti-inflammatory, antinociceptive and healing activities of the polysaccharide-rich extract from Caesalpinia ferrea pods (PEp-Cf) in the rat model of cutaneous excisional wound. PEp-Cf (0.025-0.1%) or 0.9% NaCl was topically applied in the wounds at dorsal thoracic region (2×/day) during 21 days for measurement of clinical signs (hyperemia, inflammatory exudate, edema, nociception), wound size, histopathological/histomorphometric, oxidative/inflammatory markers and systemic toxicity. PEp-Cf at 0.1% reduced wound area and increased ulcer contraction [days 2 and 10 (21-78%)]. PEp-Cf reduced clinical signs [days 2 and 5 (2.2-2.8×)] and modulated the healing inflammatory phase via stimulation of epithelialization (days 10 and 14), and inhibition of polymorphonuclears [days 2 and 5 (71-74%)], protein leakage [days 2 and 5 (28-41%)], nitrate [days 2 and 5 (2.2-6×)] and malondialdehyde [days 2 and 5 (46-49%)]. PEp-Cf increased the number of blood vessels [days 5 and 7 (3.1-9.6×)], fibroblasts [days 5 and 7 (2.1-6.4×)] and collagen [days 5 to 14 (1.5-1.8×)]. In conclusion, the topical application of PEp-Cf at 0.1% accelerates the healing process of rat cutaneous wounds via modulation of the inflammatory and proliferative phases, being devoid of systemic alterations.

COL1A1, COL4A3, TIMP2 and TGFB1 polymorphisms in cervical insufficiency.

OBJECTIVES: To investigate the association between selected single nucleotide polymorphisms (SNPs) with cervical insufficiency and its relationship with obstetric history. METHODS: Twenty-eight women with cervical insufficiency (case group) and 29 non-pregnant women (control group) were included. The SNPs sequenced included rs2586490 in collagen type I alpha 1 chain (COL1A1), rs1882435 in collagen type IV alpha 3 chain (COL4A3), rs2277698 in metallopeptidase inhibitor 2 (TIMP2), and rs1800468 in transforming growth factor beta 1 (TGFB1). RESULTS: We found a higher frequency of the normal allele in the control group (65.5%) and the homozygous mutated genotype in the case group (64.3%) for rs2586490 in COL1A1 (p=0.023). An unplanned finding in the cervical insufficiency group was a higher gestational age of delivery (median≥38 weeks) in the mutated allele than in the wild-type genotype (median of 28.2 weeks) for rs2857396, which is also in the COL1A1 gene (p=0.011). CONCLUSIONS: The findings of the present study corroborate the hypothesis that cervical insufficiency has a genetic component and probably involves genes encoding proteins in the extracellular matrix, in addition to inflammatory processes.

Prevalence of malignant neoplastic oral lesions among children and adolescents: A systematic review and meta-analysis.

BACKGROUND: Malignant neoplasms that affect children and adolescents are predominantly embryonic and generally affect blood system cells and supporting tissues. AIM: This study aimed to summarize the scientific evidence about the prevalence of malignant lesions in the oral cavity of children and adolescents. DESIGN: In this systematic review and meta-analysis (PROSPERO CRD42020158338), data were obtained from seven databases and the gray literature. Cross-sectional observational studies on the prevalence of biopsied oral pediatric malignancies were included. The Newcastle-Ottawa Scale assessed the quality of the included studies, and the GRADE approach evaluated the evidence certainty. The meta-analysis prevalence was calculated using MedCalc® software, adopting a 95% confidence level (CI; random-effect model). RESULTS: Forty-two studies were included in the meta-analysis. Of the 64,522 biopsies, the prevalence of malignant lesions was 1.93% (n = 1,100; 95% CI = 1.21%-2.80%). Countries with a low socioeconomic profile showed the highest prevalence. The sample size did not influence the prevalence of oral malignancies, and unspecified lymphomas (12.08%; 95% CI = 5.73%-20.37%) and rhabdomyosarcoma (10.53%; 95% CI = 7.28%-14.30%) were the most common lesions. CONCLUSIONS: Oral malignant lesions biopsied in children and adolescents had a prevalence of <3%, and lymphomas and sarcomas were the most prevalent lesions.

Loss of heterozygosity and immunoexpression of PTEN in oral epithelial dysplasia and squamous cell carcinoma.

INTRODUCTION: Oral epithelial dysplasia (OED) is a risk factor for developing subsequent oral squamous cell carcinoma (OSCC). Loss of heterozygosity (LOH) profiles have been validated as risk predictors of malignant transformation of OED. It is still unclear if Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) allelic loss also occurs in initial stage malignant lesions and if the allelic loss is involved as one of the mechanisms of oral carcinogenesis. Thus, this study objective investigate LOH of PTEN gene and the immunohistochemical expression of the protein in OED and OSCC samples. MATERIAL AND METHODS: Formalin-fixed paraffin-embedded samples of 19 OEDs and 16 OSCCs were included to immunohistochemistry and LOH analysis. Two polymorphic microsatellite markers (AFMA086WG9 and D10S1765) located in chromosome 10 were used in this study for LOH analysis. For immunohistochemical analysis, 5 random fields with 400× magnification were evaluated quantitatively and qualitatively in epithelial and neoplastic cells. RESULTS: AFMA086WG9 marker only demonstrated LOH in OEDs cases (10.5%). D10S1765 marker demonstrated LOH in 57.2% of OEDs and 50% of OSCCs. Higher nuclear immunostaining was detected in cases of OSCCs when compared to OEDs (p < .001) and there was strong cytoplasmic immunoexpression in OSCCs (p < .045). CONCLUSIONS: We provide evidence that the allelic loss of PTEN is present in premalignant oral lesions and OSCCs, however the LOH of PTEN does not seems to influence its protein expression.

Antioxidant, anti-inflammatory and healing potential of ethyl acetate fraction of Bauhinia ungulata L. (Fabaceae) on in vitro and in vivo wound model.

The present work aimed to investigate the antioxidant, anti-inflammatory and wound healing potential of ethyl acetate fraction from Bauhinia ungulata L. (FABU) on in vitro and in vivo models. Wound healing assay using human lung adenocarcinoma A549 cell line was employed to evaluate the ability of FABU in modulating cell migration. In addition, a surgical wound model in C57BL/6 mice was used to study the healing potential of FABU incorporated into gel carbomer 940 (Carbopol®). Evaluation of lipid peroxidation, inflammatory and anti-inflammatory mediator gene expression, rate of wound closure, and histological analysis were done. FABU significantly reduced the gap area in in vitro wound healing assay, 24 h after treatment. In the animal model, FABU at 0.5% topically applied once-daily for 5 days to the surgical wounds significantly reduced the lesion area. Moreover, it significantly decreased the levels of lipid peroxidation in the lesions and decreased the relative gene expression levels of IL-1ß and TNF-α in the injured region. In conclusion, our study suggests that Bauhinia ungulata can effectively promote the wound healing, probably by regulating the inflammatory environment during the early stages of the process.