Connective Tissue Hyperplasia Research Articles

P16 Expression in Multinucleated Stromal Cells of Fibroepithelial Polyps of the Anus (FEPA): A Comprehensive Review and Our Experience

Fibroepithelial polyps of the anus (FEPA) are a common benign polypoid proliferation of the stroma covered by squamous epithelium. They are also an often-overlooked part of pathological practice. Currently, immunohistochemistry (IHC) for p16 is the only recommended test for anal intraepithelial neoplasia, but the expression of p16 in stromal multinucleated atypical cells in FEPA has not been described. We aimed to evaluate the expression of p16 in stromal multinucleated atypical cells in FEPA and its role as a diagnostic biomarker to determine the origin of the atypical multinucleated cells in the stroma of FEPA and to rule out the possibility of a neoplastic process. Therefore, we researched a series of 15 FEPA in middle-aged patients histologically and by IHC. Examination of the subepithelial connective tissue from the FEPA showed bizarre, multinucleated cells, while their causal relationship with human papillomavirus (HPV) infection was rejected. In all cases, these cells showed mild to moderate atypical nuclear features and positive expression for p16, while the overlying squamous epithelium was negative. We concluded that FEPA are benign lesions in the stroma where mononuclear and multinucleated (sometimes atypical) cells showing fibroblastic and myofibroblastic differentiation can be found. Nevertheless, we believe that these cells have a practical diagnostic significance, although sometimes the presence of giant cells is difficult to establish, especially in the inflammatory context. The histological similarity between FEPA and normal anal mucosa supports the hypothesis that FEPA may represent the reactive hyperplasia of subepithelial fibrous connective tissue of the anal mucosa.

Identification, Cause and Surgical Management of Traumatic Fibroma in the Jugal Mucosa: A Case Report

Aims: the objective of the present study is to report a clinical case aimed at the diagnosis and treatment of a traumatic fibroma located in the region of the unilateral buccal mucosa based on clinical and histopathological examination.
 Case Report: A 43-year-old male patient, melanoderma, attended the Nilton Lins University dental clinic reporting the existence of a large nodule in the cheek region. Based on the clinical appearance of the lesion, the diagnostic hypothesis of traumatic fibroma was established; therefore, the surgical excision of the lesion was determined for subsequent referral to confirm the hypothesis. The removed content was transferred to a container containing a 10% formaldehyde solution and sent to the Department of Pathology and Legal Medicine of the Federal University of Amazonas for histopathological analysis, which disclosed benign epithelial thickening with parakeratosis and underlying connective tissue hyperplasia. Given the characteristics presented in the analyzed histological picture, the definitive diagnosis was reactive fibroepithelial hyperplasia.
 Conclusion: Establishing a preliminary diagnosis of the lesion was essential for planning the surgical procedure. The use of the conventional technique for the removal of the reactive fibroepithelial hyperplasia obtained satisfactory results, both for the postoperative recovery and for the infeasibility of recurrence, thus providing satisfactory comfort to the patient.

Effect of LAG3 deficiency on natural killer cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis

To investigate the effect of LAG-3 deficiency (LAG3-/-) on natural killer (NK) cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis. C57BL/6 mice, each weighing (20 ± 2) g, were divided into the LAG3-/- and wild type (WT) groups, and each mouse in both groups was inoculated with 3 000 E. multilocularis protoscoleces via the hepatic portal vein. Mouse liver and spleen specimens were collected 12 weeks post-infection, sectioned and stained with sirius red, and the hepatic lesions and fibrosis were observed. Mouse hepatic and splenic lymphocytes were isolated, and flow cytometry was performed to detect the proportions of hepatic and splenic NK cells, the expression of CD44, CD25 and CD69 molecules on NK cell surface, and the secretion of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin (IL)-4, IL-10 and IL-17A. Sirius red staining showed widening of inflammatory cell bands and hyperplasia of fibrotic connective tissues around mouse hepatic lesions, as well as increased deposition of collagen fibers in the LAG3-/-group relative to the WT group. Flow cytometry revealed lower proportions of mouse hepatic (6.29% ± 1.06% vs. 11.91% ± 1.85%, P < 0.000 1) and splenic NK cells (4.44% ± 1.22% vs. 5.85% ± 1.10%, P > 0.05) in the LAG3-/- group than in the WT group, and the mean fluorescence intensity of CD44 was higher on the surface of mouse hepatic NK cells in the LAG3-/- group than in the WT group (t = -3.234, P < 0.01), while no significant differences were found in the mean fluorescence intensity of CD25 or CD69 on the surface of mouse hepaticNK cells between the LAG3-/- and WT groups (both P values > 0.05). There were significant differences between the LAG3-/- and WT groups in terms of the percentages of IFN-γ (t = -0.723, P > 0.05), TNF-α (t = -0.659, P > 0.05), IL-4 (t = -0.263, P > 0.05), IL-10 (t = -0.455, P > 0.05) or IL-17A secreted by mouse hepatic NK cells (t = 0.091, P > 0.05), and the percentage of IFN-γ secreted by mouse splenic NK cells was higher in the LAG3-/- group than in the WT group (58.40% ± 1.64% vs. 50.40% ± 4.13%; t = -4.042, P < 0.01); however, there were no significant differences between the two groups in terms of the proportions of TNF-α (t = -1.902, P > 0.05), IL-4 (t = -1.333, P > 0.05), IL-10 (t = -1.356, P > 0.05) or IL-17A secreted by mouse splenic NK cells (t = 0.529, P > 0.05). During the course of E. multilocularis infections, LAG3-/- promotes high-level secretion of IFN-γ by splenic NK cells, which may participate in the reversal the immune function of NK cells, resulting in aggravation of hepatic fibrosis.

Pyogenic granuloma of gingiva –A case report

Reactive hyperplasia of connective tissue caused by local irritants is known as pyogenic granuloma. It is a tumor-like development of the oral cavity that is thought to be neoplastic in nature. It is typically found around the skin or anterior teeth. Numerous stressors, such as intense injury, low-grade local discomfort, hormone fluctuations, or certain drugs, are commonly the cause of it. Histologically, the surface epithelium may show foci of ulcerations, hyperkeratosis, or even intact. It sits on top of a thick mass of connective tissue with a high concentration of fully grown collagen. The most often impacted area is the gingiva, which is followed by the lips, tongue, and buccal mucosa. In general, pyogenic granuloma does not develop when the base and its contributing variables are removed.

Establishing a causal link between the human papilloma virus and oral fibromas

Fibroma, a benign tumour of fibrous connective tissue, can be seen as a reactive connective tissue hyperplasia in response to trauma and irritation. They typically have a firm consistency, are nodular and asymptomatic, have a colour that is similar to the mucosa, a sessile base, a smooth surface, and are situated in the buccal mucosa along the line of occlusion, tongue, and lip mucosa. We retrospectively investigated total 79 cases and intriguingly, 41 cases were not associated with any history or clinical evidence of chronic trauma of dental origin suggesting different pathogenesis mechanism. Out of 79 cases of oral fibroma, 18 showed evidence of koilocytes in the overlying epithelium with 14 cases not associated with history of any trauma. This might suggest the cause and effect relationship between HPV and oral fibromas, however, the possibility of secondary infection in already existing fibroma can be considered. This intriguing finding prompt us to propose a novel hypothesis explaining the role of human papilloma virus in the pathogenesis of fibroma.

Peritendinous adhesion: Therapeutic targets and progress of drug therapy

Peritendinous adhesion (PA) is one of the most common complications following hand surgery and characterized with abnormal hyperplasia of connective tissue and excessive deposition of extracellular matrix. Subsequently, various clinical symptoms such as chronic pain, limb dyskinesia and even joint stiffness occur and patients are always involved in the vicious cycle of “adhesion – release – re-adhesion”, which seriously compromise the quality of life. Until present, the underlying mechanism remains controversial and lack of specific treatment, with symptomatic treatment being the only option to relieve symptoms, but not contributing no more to the fundamentally rehabilitation of basic structure and function. Recently, novel strategies have been proposed to inhibit the formation of adhesion tissues including implantation of anti-adhesion barriers, anti-inflammation, restraint of myofibroblast transformation and regulation of collagen overproduction. Furthermore, gene therapy has also been considered as a promising anti-adhesion treatment. In this review, we provide an overview of anti-adhesion targets and relevant drugs to summarize the potential pharmacological roles and present subsequent challenges and prospects of anti-adhesion drugs.

Synthesis and antitumor activity of a 2-hydroxy substituted chalcone (C6)

Cancers account for approximately 13% of all deaths each year with breast cancer being one of the most common. Chemotherapeutic agents used in cancer usually have nonspecific toxicity which kills both tumor and normal cells and cause serious side effects that often limit their efficacy. This study aimed to synthesize chalcone and evaluate its antitumor activity. Chalcone was synthesized using Claisen-Schmidt condensation and characterized using spectroscopic techniques. The LD50 of the synthesized compound was estimated using OECD-425 guidelines in rats. A mammary tumor was induced with a single subcutaneous administration of 65 mg/kg of 1-methyl nitrosourea (MNU). The rats were palpated weekly to determine the size of the tumor. Eight weeks post MNU administration, the rats were divided into five groups of six rats each and treated with graded doses (12.5, 25, and 50 mg/kg) of the compound and paclitaxel (10 mg/kg) for six weeks. Before treatment, three rats were randomly selected and sacrificed, and mammary gland samples were subjected to histological assessment to confirm the induction of the tumor. At the end of the treatment, the rats were euthanized, and mammary glands were collected and subjected to histological evaluation. The possible mechanism of action of the synthesized compound was elucidated in silico using molecular docking. The compound was synthesized and named C6. C6 was found to be relatively safe with LD50 above 2000 mg/kg and exhibited remarkable antitumor activity. MNU-induced mammary tumor rats treated with C6 produced a significant decrease in tumor diameter when compared with the untreated group, histology slides displayed fewer signs of hyperplasia and small numbers of connective tissue with larger lobules when compared with the untreated group. In silico tubulin-binding interactions revealed that C6 binding to tubulin was like that of colchicine, and also has higher affinity to tubulin than colchicine. The synthesized chalcone demonstrated significant antitumor activities in MNU-induced mammary tumors in rats postulated via inhibition of tubulin polymerization.

Synthesis and anti-tumor activity of piperonal substituted chalcone

Objectives: Chalcones have been identified as potential antitumor agents with a novel target, the tubulin. The aim of the study was to synthesize a piperonal substituted chalcone and evaluate its in vivo antitumor activity. Materials and Methods: Piperonal substituted chalcone was synthesized using Claisen-Schmidt condensation and characterized using various spectroscopic techniques. The lethal dose (LD50) of the synthesized compound was estimated using OECD-425 guidelines in rats. Antitumor activity of the synthesized compound was evaluated on 1-methyl nitrosourea (MNU)-induced mammary tumor in female Wistar rats. Histological evaluation was used to confirm tumor induction and assess treatment with the synthesized compound. The possible mechanism of action of the synthesized compound was elucidated in silico using molecular docking. Results: The compound was synthesized and named C2. C2 was found to be relatively safe with LD50 &gt;2000 mg/kg orally. Moreover, C2 exhibited remarkable antitumor activity, at all the tested doses in a dose dependent manner. Histological evaluation of the MNU-induced mammary tumor rats treated with C2 displayed fewer signs of hyperplasia and small numbers of connective tissue with larger lobules when compared with the untreated group. In silico tubulin-binding interactions revealed that the kinetics of C2 binding to tubulin was like that of colchicine. Comparison of crystal structures of tubulin-C2 and tubulin-colchicine complexes showed that the binding mode of C2 to tubulin was like that of colchicine to tubulin and produced the same conformational changes on the tubulin structure as colchicine. Conclusion: The synthesized chalcone demonstrated remarkable antitumor activities in MNU-induced mammary tumors in rats possibly through inhibition of tubulin polymerization.

Evaluation of preclinical efficacy of human umbilical cord mesenchymal stem cells in ankylosing spondylitis.

Umbilical cord mesenchymal stem cells (UCMSCs) have significant regenerative, tissue repair, and immunomodulatory properties that can help reduce inflammatory responses in patients with ankylosing spondylitis (AS). In this study, we used a combination of bovine proteoglycan and dimethyldioctadecylammonium (DDA) to establish a mouse model of proteoglycan-induced spondylitis (PGISp). To evaluate the therapeutic effects of UCMSCs, we treated PGISp mice with different doses of hUCMSCs via tail vein injection. At week 13, the PGISp mice exhibited thickened, erythematous paws, erythema in the extremities, and lameness. CT scans revealed necrotic lysis of chondrocytes, formation of fissures, visible hemorrhage, connective tissue hyperplasia, and focal infiltration of lymphocytes in the intervertebral discs. At week 14, the PGISp mice were randomly divided into three groups and administered different doses of hUCMSCs (0.25, 0.5, and 1.0×107 cells/kg, iv, QOW×2, n=10). To assess the therapeutic effects of hUCMSCs, we evaluated Th cell subsets in the spleen, spleen and thymus coefficients, peripheral blood inflammatory factors, and pathological and imaging observations of the spines and lumbar spines in the PGISp mice. The results demonstrated that injection of hUCMSCs shifted the balance axis between Th1 and Th2 cells in the spleen towards Th2 cells. Moreover, the spleen coefficient and levels of inflammatory cytokines (TNF-α and CCL-2) in the serum decreased after hUCMSC injection. CT imaging and pathological analysis indicated that hUCMSC treatment inhibited ectopic osteogenesis and maintained clear small joint gaps, which slowed down the progression of structural lesions in the disc, nucleus pulposus, fibrous ring, and cartilage in PGISp mice. Administering hUCMSCs at the 14th week after modeling proved to be an effective treatment for PGISp mice. This experiment offers a valuable reference for the pre-clinical use of hUCMSCs in the treatment of AS.

Pyogenic granuloma in a 6-year-old boy - a rare case report

The gingiva, also known as the gums, is the pink-coloured keratinized mucosa that surrounds and protects the teeth. Gingival enlargement or gingival overgrowth, a common trait of gingival disease, is characterized by an increase in the size of gingiva. Irritation fibroma is an exophytic soft tissue mass in the oral mucosa. Indeed, it is not a real neoplasm, but a focal hyperplasia of fibrous connective tissue induced by local trauma or chronic irritation. Pyogenic granuloma is one of the inflammatory hyperplasia seen in the oral cavity, majority are found on the marginal gingiva with only 15% of the tumours on the alveolar part. It predominantly occurs in the second decade of life in young females, male to female ratio is 1:99, and size of lesion varies in diameter from few millimetres to several centimetres. This article presents a case of pyogenic granuloma in an 6year old boy who presented with a gingival overgrowth in his mandibular left buccal surface region i.r.t 31 including marginal and attached gingiva. He had discomfort during mastication, interferes with occlusion there was episode of bleeding during brushing. The lesion was excised and histopathological report confirmed the diagnosis. Case was followed up for six months and no recurrence of the lesion. Etiological factors, clinical features, differential diagnosis and different treatment options are discussed based on the review of current literature available.

Characterization and pathogenicity of a novel variant infectious bursal disease virus in China.

Infectious bursal disease (IBD) is a highly epidemic and immunosuppressive disease of 3- to 6-week-old chicks caused by infectious bursal disease virus (IBDV). Since 2017, there has been a notable increase in the isolation rates of novel variant IBDV strains in China, of which characteristic amino acid residues were different from those of early antigen variants. In this study, one IBDV strain was isolated from a farm with suspected IBD outbreak in Shandong Province, China, which was designated LY21/2. The strain LY21/2 could replicate in MC38 cells with previous culture adaption in SPF chick embryos. Phylogenetic analysis revealed that LY21/2 formed one branch with novel variant IBDVs and shared 96.8-98.6% nucleotide sequence identity with them. Moreover, LY21/2 serving as the major parent underwent the recombination event of a variant strain (19D69), while the minor parent was a very virulent strain (Harbin-1). SPF chicks inoculated with LY21/2 showed no gross clinic symptom, whereas bursal atrophy was exhibited and apoptosis was occurred in 55.21% of bursal cells. The results of histopathology and immunohistochemical staining showed that lymphocyte depletion and connective tissue hyperplasia and IBDV antigen-positive cells were observed in the bursa of LY21/2-infected chicks. Besides, DNA fragmentation was detected in the LY21/2-infected bursal tissue section by TUNEL assay. Collectivtely, these data presented analysis and evaluation of the genetic characteristics and pathogenicity of a novel variant IBDV strain. This study may help in the development of biosafety strategies for the prevention and control of IBDV in poultry.

Bioinformatics analysis and verification of m6A related genes based on the construction of keloid diagnostic model.

Keloids are formed due to abnormal hyperplasia of the skin connective tissue. We explored the relationship between N6-methyladenosine (m6A)-related genes and keloids. The transcriptomic datasets (GSE44270 and GSE185309) of keloid and normal skin tissues samples were obtained from the Gene Expression Omnibus database. We constructed the m6A landscape and verified the corresponding genes using immunohistochemistry. We extracted hub genes for unsupervised clustering analysis using protein-protein interaction (PPI) network; gene ontology enrichment analysis was performed to determine the biological processes or functions affected by the differentially expressed genes (DEGs). We performed immune infiltration analysis to determine the relationship between keloids and the immune microenvironment using single-sample gene set enrichment analysis and CIBERSORT. Differential expression of several m6A genes was observed between the two groups; insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was significantly upregulated in keloid patients. PPI analysis elucidated six genes with significant differences between the two keloid sample groups. Enrichment analysis revealed that the DEGs were mainly enriched in cell division, proliferation, and metabolism. Moreover, significant differences in immunity-related pathways were observed. Therefore, the results of this study will provide a reference for the elucidation of the pathogenesis and therapeutic targets of keloids.

Traumatic neuroma of the right posterior hepatic duct with an anatomic variation masquerading as malignancy: a case report

Traumatic neuroma (TN), also known as amputation neuroma, is a reactive hyperplasia of nerve fibers and connective tissue arising from Schwann cells after trauma or surgery. TN of the bile duct is usually asymptomatic, but rarely can lead to right upper quadrant pain, biliary obstruction, and acute cholangitis. It is very difficult to discriminate TN from malignancy before surgery, although doing so could avoid an unnecessary radical resection of the lesion. In the course of surgery, TN can be caused by unintentional injury of a nerve fiber near the common bile duct (CBD) and heat damage to an artery, complete ligation of an artery, and excessive manipulation of the CBD. Therefore, to prevent TN after cholecystectomy, surgery should be performed carefully with appropriate consideration of anatomic variations, and a cystic duct should not be resected too close to the CBD. The possibility of TN should be considered if a patient who has undergone CBD resection with hepaticojejunostomy or cholecystectomy long ago experiences symptoms of jaundice, cholangitis, or obliteration of the CBD. In this report, we present a case of TN mimicking cholangiocarcinoma that emerged from a cystic duct stump after cholecystectomy.

Effects of Bifidobacteria bifidum strains on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced acute colitis and its potential mechanism

Microbiota-based therapies for improving symptoms of Crohn's disease (CD) are receiving increasing attention. Probiotics and second-generation probiotics can potentially prevent this disease. However, the therapeutic action and underlying molecular mechanisms of probiotics remain largely unknown. Efficient screening of probiotics is also challenging. In this study, we screened eight B. bifidum strains with CD-relieving potential using a 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis mouse model. We also observed that B. bifidum CJ238 could prevent but not cure the colitis-symptoms (weight loss, colon shortening and connective tissue hyperplasia) in mice model. The 16S rRNA sequencing data showed that supplementation with B. bifidum did not alter the composition of the intestinal microbiota. B. bifidum CJ238 administration also provided full protection against acute colitis in pseudo germ-free mice. Therefore, we infered that the protective effect of B. bifidum strains does not depend on their interaction with the gut microbiota. Furthermore, heat-killed (95 °C for 20min) B. bifidum cells (109 CFU/mouse) also protected mice against acute colitis. In-vitro adhesion and immunomodulatory activities of the B. bifidum strains were measured. Combined with the in-vivo results, the anti-colitis effect of B. bifidum was positively associated with its strong anti-inflammatory and adhesion capacity in-vitro. This study provides insights into the in-vitro screening and clinical application of probiotics in CD prevention.

Efekat metaboličkog sindroma na incidencu i stepen hipertrofije miokarda leve komore kod hipertenzivnih pacijenata

Metabolic syndrome (MetS) is characterized by the simultaneous presence of obesity, hypertension, dyslipidemia and hyperglycemia in an individual, which leads to an increased risk of cardiovascular disease (CVD). Left ventricular hypertrophy (LVH) is thickening of the heart muscle wall -hypertrophy of cardiomyocytes in concentric and/or elongation of cardiomyocytes and hyperplasia of connective tissue in eccentric hypertrophy with the participation of hemodynamic and non-hemodynamic factors (genetics, stress, other external factors). MetS, which essentially includesinsulin resistance, hyperinsulinemia, and hyperglycemia, alters myocardial metabolism and promotes myocardial inflammation, fibrosis, hypertrophy, and left ventricular remodeling. OBJECTIVE: To determine the impact of MetS, that is, obesity to the incidence and degree of severity of LVH in hypertensive patients with metabolic syndrome in comparison with the control group -hypertensive patients without metabolic syndrome. PATIENTS AND METHODS: Consecutive patients of the Office of Internal Medicine "Dr. Bastać" were examined, a total of 55 patients with hypertension, who were divided into two groups: the first group with MetS, 22 people, average age 56±8.5 years with BMI&gt;30kg /m 2 and waist circumference more than 80 cm for women and &gt;94 cm for men, the second control group without MetS-33 people, average age 52±14 years, with BMI&lt;30kg/m 2 . Echocardiography was done for all subjects on a Power Vision 6000 Toshiba echo camera with standard echocardiographic measurements in the M, B and Doppler technique, and the mass of the left ventricular myocardium was determined for them using the Devereux formula. RESULTS: The prevalence of LVH in group 1 with metabolic syndrome (MetS) was 64%, while in the control group without (MetS) it was 36%. There was a statistically significantly higher number of patients with LVH in hypertension with MetS compared to hypertensive patients of the control group without MetS (X2, p=0.027). In the group of hypertensive patients with MetS, the degree of severity of myocardial hypertrophy, that is, the myocardial mass , was statistically significantly higher compared to the control group (respectively 302±84g versus 224±89g, p=0.0002). Arterial pressure values were higher for both systolic and diastolic blood pressure 168/106 mmHg in hypertensive patients with MetS, but did not reach statistical significance in relation to blood pressure values in hypertensive patients without MetS (156/95 mmHg, p=0.16). CONCLUSION. Patients with metabolic syndrome and hypertension have a statistically significantly higher prevalence of left ventricular myocardial hypertrophy and a highly statistically significant degree of left ventricular hypertrophy compared to the control group of hypertensive individuals without MetS. Given that mean values of arterial pressure do not differ between groups, it can be concluded that non-hemodynamic factors for the development of LVH have an important role in the induction of a more severe degree of LVH in hypertensive patients with metabolic syndrome.

The Potential Roles of CHI3L1 in Failed Autologous Arteriovenous Fistula in End-Stage Renal Disease.

Autologous arteriovenous fistula (AVF) is commonly placed for hemodialysis treatment. Recent studies show that increased baseline serum level of Chitinase-3-like protein 1 (CHI3L1) is independently associated with a higher risk of the early failure of forearm AVFs. However, the changes and mechanisms of CHI3LI in local vascular tissues of failed AVF have not be revealed. This study aims to conduct the expression and mechanism of CHI3L1 in vascular tissues from patients. Immunoreactivity of CHI3L1, matrix metalloproteinase 2 (MMP-2) and vascular endothelial growth factor-A (VEGF-A) were detected in vascular tissues collected from nine patients with AVF surgery. Due to the significant stenosis clinically, six of the nine patients received arteriovenous fistula reconstruction. The expression differences of CHI3L1 between the initial vascular tissues and failed AVF are significant (P < 0.05). Failed AVF due to stenosis shows intraluminal thrombus, collagen fiber rupture, fibrous connective tissue hyperplasia, tube wall thickening, neovascularization, scattered inflammatory cell infiltration in the tunica media as well as high CHI3L1 expression level, and the expression of MMP-2 (r = 0.9022, P = 0.0139) and VEGF-A (r = 0.8355, P = 0.0393) was positively correlated with CHI3L1. CHI3L1 expression in vascular tissues possibly plays an important role in AVF failure. MMP-2 and VEGF-A may participate in venous stenosis with CHI3L1.

Positive space acquiring asymmetric membranes for guiding alveolar bone regeneration under infectious conditions

To obtain multifunctional materials suitable for guiding alveolar bone regeneration under infectious conditions, we prepared asymmetric membranes comprising space acquiring layer that involves fibroblast inhibitor poly(p-dioxanone-co-L-phenylalanine) (PDPA), an isolating dense layer that forms barrier between two layers and an osteogenesis inducing electrospinning layer which involves hydroxyapatite or hydroxyapatite & minocycline. Then the composition, crystallization, morphology, and hydrophilicity of asymmetric membranes were analyzed. Minocycline incorporated membranes controlled the expansion of Porphyromonas gingivalis (P. gingivalis) in vitro. Hydroxyapatite-incorporated asymmetric membranes promoted the expression of osteogenesis related genes RUNX2, OPN, ALP of MC3T3-E1 cells in vitro. The mineralization of MC3T3-E1 cells cultured with hydroxyapatite-incorporated asymmetric membranes were also promoted in vitro. Asymmetric membranes especially hydroxyapatite-incorporated ones guided the regeneration of the mandibular bone defect in vivo. Bone regeneration guided under infectious conditions was evaluated in a P. gingivalis infected alveolar bone defect model. Specifically, space acquiring layer containing asymmetric membranes effectively controlled connective tissue hyperplasia at defect sites. The excellent guided bone regeneration achieved by applying a single space acquiring layer membrane further indicates the importance of acquiring space actively to induce bone regeneration. Hydroxyapatite-minocycline incorporated symmetric membranes could simultaneously suppress alveolar bone reabsorption caused by infection and guide regeneration of defects. Therefore, the hydroxyapatite-minocycline incorporated asymmetric membrane may be more suitable to be applied in guiding regeneration of bone defects under complex infectious conditions.

Identification of nanoparticle-mediated siRNA-ASPN as a key gene target in the treatment of keloids.

Background: Keloid, also known as connective tissue hyperplasia, is a benign proliferative disorder with a global distribution. The available therapeutic interventions are steroid injections, surgical removal of keloids, radiotherapy, compression therapy, the application of cryosurgery, and many other methods. Objectives: Existing treatments or approaches for keloids may lead to similar or even larger lesions at the site of keloid excision, leading to a high recurrence rate. Therefore, this study aims at identifying a new gene-based therapy for the treatment of keloids. Methods: An ASPN-siRNA/nanoparticle combination (si-ASPN) and a negative siRNA/nanoparticle complex (NC) was developed on the basis of bioinformatics studies and used in vitro and in vivo experiments. Results: The results showed a strong correlation between the development of keloids and high expression of ASPN protein. With the expression of ASPN protein greatly reduced in keloid fibroblasts and nude mice allografts after treatment with si-ASPN, the collagen and fibroblasts were also uniform, thinner, parallel and regular. Conclusion: All the above experimental results suggest that keloid and ASPN are closely related and both fibroblast growth and metabolism of keloid are inhibited after silencing ASPN. Therefore, ASPN-siRNA delivered via nanoparticles can serve as a novel intervention therapy for the treatment of keloids.

Management of Epulis Fissuratum of Mandibular Anterior Region By Maintaining The Vestibular Depth. A Case Report

OBJECTIVES Epulis Fissuratum or Denture-induced hyperplasia is benign tumor-like hyperplasia of fibrous connective tissue, which develops usually in association with an ill-fitting complete or partial denture. The aim of this report is to present a case showing the treatment of Epulis fissuratum in relation to an ill-fitting denture with a Simple but innovative technique. The epulis was removed with the conventional surgical approach in which the excision of the epulis was carried out by a split-thickness flap approach in which the wound healing is achieved by secondary closure. The existing denture was relined with a soft tissue conditioner to maintain the depth of the vestibule by preventing the post-surgical wound contracture during healing and to prevent further surgery for vestibulopathy. In addition, the patient continued using the existing denture for functional and aesthetic purposes. After two weeks of wound healing, the vestibular depth was maintained by the relined existing denture. Then the new dentures were fabricated accordingly. After one month of follow-up, no signs of recurrence of epulis fissuratum were noticed.

Effect and mechanism of Huangqi Shengmai Decoction in treatment of joint rat model of fatigue and myocardial injury

This study aims to investigate the effects and the underlying mechanism of Huangqi Shengmai Decoction(HQSMD) in the treatment of fatigue and myocardial injury in a joint rat model. Wistar rats were assigned into 4 groups: sham, model, diltiazem hydrochloride(positive control), and HQSMD. The joint model of fatigue and myocardial injury was established by 14-day exhausted swimming followed by high ligation of the left anterior descending coronary artery. The rats in the sham group underwent a sham operation without coronary artery ligation or swimming. Since the fourth day after the ligation, swimming was continued in the model group and the drug-treated groups for the following 4 weeks. Meanwhile, the rats in the positive control group and the HQSMD group were respectively administrated intragastrically with diltiazem hydrochloride(20 mg·kg~(-1)·d~(-1)) and HQSMD(0.95 g·kg~(-1)·d~(-1)) for 4 weeks, while the shams and the models were given the same volume of normal saline. The left ventricular ejection fraction(LVEF), left ventricular fractional shortening(LVFS), grip strength, and myocardial pathophysiological changes were measured to evaluate the anti-fatigue and cardioprotective effects of HQSMD. The protein levels of PTEN-induced putative kinase 1(PINK1) and parkin in the myocardium were measured by Western blot to preliminarily elucidate the mechanism of HQSMD in ameliorating myocardial injury by suppressing mitochondrial autophagy. Compared with the shams, the models showed weakened heart function(LVEF and LVFS, P&lt;0.01), decreased grasping ability(P&lt;0.05), elevated blood urea nitrogen(BUN) and aldosterone(ALD) levels(P&lt;0.01), aggravated myocardial fibrosis and connective tissue hyperplasia(P&lt;0.01), and up-regulated protein levels of PINK1(P&lt;0.01) and parkin(P&lt;0.05). Four-week treatment with HQSMD increased the LVEF and LVFS levels(P&lt;0.01), enhanced the grip strength(P&lt;0.01), reduced the serum levels of BUN(P&lt;0.01) and ALD(P&lt;0.05), alleviated the pathological injury and fibrosis in the myocardium(P&lt;0.01), and down-regulated the protein levels of PINK1(P&lt;0.01) and parkin(P&lt;0.05) in heart tissue. The results demonstrate that HQSMD may alleviate myocardial fibrosis and protect myocardium by suppressing the excessive mitochondrial auto-phagic activity and reducing the excessively elevated ALD level, thereby ameliorating fatigue and myocardial injury.