Progressive Destruction Research Articles

Investigation of the deterioration mechanisms induced by moisture and soluble salts in the necropolis of Porta Nocera, Pompeii (Italy)

This paper focuses on the diagnosis of damage processes of decorative Roman renders of a group of tombs in the Porta Nocera necropolis in the ancient city of Pompeii, Italy. Unprotected from various climatic events, the tombs keep on deteriorating since they were first excavated in 1954. Extensive on-site and laboratory diagnostics using non-destructive and low-destructive techniques have been able to demonstrate that soluble salts are among the major agents of deterioration, causing damage in the form of render delamination. Gypsum is formed on the surface of the materials by the deposition of sulfur dioxide, resulting in reduced porosity and hardening of the surface. Soluble salts of nitrates and chlorides that penetrate the tombs’ masonry from the ground and are transported through the render layers tend to crystallize in subsurface. The crystallization—dilution cycles of the soluble salts cause major mechanical pressures, leading to the progressive destruction of the renders. Past conservation strategies to secure plasters have shown only limited effectiveness. In light of the data collected regarding salt decay, the authors propose new strategies, questioning the systematic use of grouts and restoration mortars for conservation treatments and focusing on preventive conservation and maintenance to ensure the long-term preservation of masonry and decorative surfaces of the tombs.

Does Magnetic Resonance Imaging Distinguish Juvenile Idiopathic Arthritis From Other Causes of Progressive Temporomandibular Joint Destruction?

Similarities in initial presentations of temporomandibular joint (TMJ) involvement from juvenile idiopathic arthritis (JIA), idiopathic condylar resorption, and other forms of progressive TMJ destruction in children create diagnostic confusion. Treatment pathways, however, depend on determination of etiology. The purpose of this study was to compare TMJ magnetic resonance images (MRIs) of patients with joint degeneration localized to the TMJs to those with JIA and TMJ involvement. This is a retrospective cross-sectional study including subjects younger than 18years that presented from February 2008 to October 2019 with clinical TMJ degeneration, a gadolinium-enhanced TMJ MRI and a negative pediatric rheumatologic workup ("non-JIA" group), and a series of age and sex-matched subjects with TMJ degeneration on gadolinium-enhanced MRI and JIA ("JIA group"). MRIs were evaluated in a blinded fashion by 1 pediatric radiologist. The primary outcome variable was the radiologist's accuracy in predicting study grouping, assessed in 1 randomly-selected joint per patient. Secondary outcome variables included MRI characteristics of inflammation, osseous damage and articular disc morphology. Independent samples t-tests, sensitivity/specificity, Fisher's exact and Mann-Whitney tests were computed as applicable, and P<.05 was considered significant. The sample included 34 subjects: 16 non-JIA (75% female, age 13.9±2.8years) and 18 JIA (77% female, age 13.6±2.8years) (P≥.738). The radiologist correctly classified 64.7% of subjects as non-JIA or JIA (P=.078, sensitivity=94.4%, specificity=31.3%). Inflammatory and osseous findings were similar between groups (P≥.073). The disc was anteriorly displaced in 9 non-JIA and 0 JIA joints (P<.001, sensitivity=100%, specificity=100%) and flattened in 3 non-JIA and 14 JIA joints (P=.006, sensitivity=38.9%, specificity=90.6%). Inflammatory and osseous findings on gadolinium-enhanced TMJ MRIs are insufficient to determine the etiology of progressive TMJ destruction. Disc characteristics, however, significantly differ between JIA and non-JIA etiologies and may be important in differentiating these conditions.

Fulminant type 1 diabetes developed after influenza split vaccination.

Fulminant type 1 diabetes (FT1D) is a subtype of diabetes characterized by rapid progression of β-cell destruction, hyperglycemia, and diabetic ketoacidosis (DKA). The pathogenesis of this disease remains unclear. However, viral infections, HLA genes, and immune checkpoint inhibitor use were reportedly involved in this disease. A 51-year-old Japanese man with no chronic medical condition was admitted to our hospital with complaints of nausea and vomiting. Cough, sore throat, nasal discharge, and diarrhea were not noted. He had a medical history of at least two influenza infections. His vaccination history was notable for receiving an inactive split influenza vaccine 12 days prior to developing these symptoms. He was diagnosed with DKA associated with FT1D. His HLA class II genotypes were nonsusceptible to FT1D, and he had a negative history of immune checkpoint inhibitor use. The destruction of the pancreas by cytotoxic T cells is reported to be involved in FT1D. Inactive split influenza vaccines do not directly activate cytotoxic T cells. However, these could activate the redifferentiation of memory CD8-positive T cells into cytotoxic T cells and induce FT1D, as this patient had a history of influenza infections. Influenza split vaccination could cause fulminant type 1 diabetes (FT1D). The mechanism of influenza split vaccine-induced FT1D might be through the redifferentiation of CD8-positive memory T cells into cytotoxic T cells.

In vitro evaluation of coenzyme Q10 on primary fibroblast culture

Chronic inflammation in periodontitis results in continuous production of Reactive Oxygen Species (ROS), so the levels are excessive, causing destruction of the gingiva, periodontal ligament, and alveolar bone through a variety of mechanisms including DNA damage and the formation of proinflammatory cytokine. One way to prevent periodontal tissue damage caused by excessive ROS formation is by administering antioxidants. Coenzyme Q10 is a powerful antioxidant that is beneficial for inhibiting free radicals to prevent the progression of periodontal tissue destruction and accelerate healing processes. The purpose of this study was to evaluate the fibroblast proliferation of the combination of Coenzyme Q10 and vegetable glycerin compared to PerioQ. Materials used were made of original Coenzyme Q10 dissolved in glycerin that was prepared in a ratio of 2:8 and 1:9, and Perio Q as the control. Each group consisted of six samples (n = 6). Primary fibroblasts were derived from healthy gingival tissue. Observations on day-1, -3, and -5 using MTT assay at a wavelength of 550nm. Statistical analysis used a Two-Way ANOVA test followed by a Post Hoc test. The experiment showed the absorbance values were high in all the groups, the highest value was on day 3, namely Coenzyme Q10 at a concentration of 2:8, followed by Coenzyme Q10 at a concentration of 1:9, and PerioQ. The statistical tests showed significant differences in the 3 groups (p &lt; 0.05). It is concluded that Coenzyme Q10 in 1:9 and 2:8 concentrations were both as viable as Perio Q towards primary gingival fibroblast culture.

Возможности туннелизации в лечении остеоартрита коленного сустава

Introduction Surgical treatment of knee osteoarthritis is a controversial issue. Knee replacement is the treatment of choice in the orthopedic practice for patients with severe knee osteoarthritis. However, total knee arthroplasty (TKA) has not only beneficial results and implant survivorship is limited in time. In recent years, the number of publications devoted to the limitation of indications for TKA in patients with osteoarthritis has been increased. The use of drilled tunneling in its modern modifications enables to delay or, in some cases, avoid knee joint arthroplasty. Purpose To substantiate the safety, low invasiveness and effectiveness of the tunneling method as a minimally invasive organ-preserving treatment for knee joint osteoarthritis. Materials and methods The electronic Pub-Med/MEDLINE and eLibrary databases were searched for works published for the last 30 years. The search was carried out with keywords and phrases: knee joint osteoarthritis, articular cartilage, bone drilling, arthroscopy of the knee joint. Results The effectiveness of tunneling is based on the concept of simultaneous revascularization, drainage and decompression of the subchondral sections of the knee joint and the medullary cavity of the tubular bones. Up to 96 % of patients report a positive effect of tunneling immediately after surgery. Intraosseous pressure decreases for up to 2 years in 88 % of patients. Discussion The tunneling method in the treatment of knee osteoarthritis helps to reduce pain in the projection of the femur and tibia, including night pain, improves the functional parameters of the joint, inhibits the progress of cartilage destruction, improves the quality of life of patients and reduces the need for replacement of the affected joint. In addition, tunneling does not require serious economic costs. Due to the fact that this method is a minimally invasive surgical intervention, the risk of infection is noticeably lower than with TKA. Conclusion Thus, the tunneling of the articular ends is a simple, safe, low invasive and effective method of treating knee joint osteoarthritis.

Assessment of Salivary Levels of the RANKL and RANK in Patients with Healthy Gingiva on Reduced Periodontium Versus Periodontitis

Introduction: We aimed to compare the changes in the two salivary biomarkers, RANKL and RANK, among patients with healthy gingiva on reduced periodontium versus generalized periodontitis stages II and III. Methods: Study subjects were divided into three groups: (1) healthy periodontium (control group) (n = 15), (2) generalized periodontitis stages II and III (n = 30), and (3) healthy gingiva on reduced periodontium (n = 30). Salivary levels of RANKL and RANK were assessed using an enzyme-linked immunosorbent assay. Data analysis was done by the one-way ANOVA and the Tukey post hoc test using R software. Results: There was a statistically significant difference among the three study groups regarding salivary levels of the RANKL (P &lt; 0.001) and RANK (P &lt; 0.001). A Post hoc test showed that the difference between salivary levels of the RANKL (P = 0.50) and RANK (P = 0.86) among periodontitis groups and healthy gingiva in the reduced periodontium group was not statistically significant. Conclusion: High salivary levels of RANKL and RANK in comparison with healthy gingiva are not necessarily associated with the active phase of periodontal disease and progressive bone destruction.

Tomentosin suppressed M1 polarization via increasing MERTK activation mediated by regulation of GAS6

Ethnopharmacological relevanceXanthium sibiricum Patrin ex Widder (X. sibiricum) are widely used traditional herbal medicines for arthritis treatment in China. Rheumatoid arthritis (RA) is characterized by progressive destructions of joints, which is accompanied by chronic, progressive inflammatory disorder. According to our previous research, tomentosin was isolated from X. sibiricum and revealed anti-inflammatory activity. However, the potential therapeutic effect of tomentosin on RA and the anti-inflammatory mechanism of tomentosin remain to be clarified. The present study lays theoretical support for X. sibiricum in RA treatment, also provides reference for further development of X. sibiricum in clinic. Aim of the studyTo investigate the effect of tomentosin in collagen-induced arthritis (CIA) mice and reveal its underlying mechanism. Materials and methodsIn vivo, tomentosin (10, 20 and 40 mg/kg) was given to CIA mice for seven consecutive days, to evaluate its therapeutic effect and anti-inflammatory activity. In vitro, THP-1-derived macrophages were used to verify the effect of tomentosin on inflammation. Then, molecular docking and experiments in vitro was conducted to predict and explore the mechanism of tomentosin inhibiting inflammation. ResultsTomentosin attenuated the severity of arthritis in CIA mice, which was evidenced by the swelling of the hind paws, arthritis scores, and pathological changes. Particularly, tomentosin effectively reduced the ratio of M1 macrophage and TNF-α levels in vitro and vivo. Then, molecular docking and experiments in vitro was carried out, indicating that tomentosin inhibited M1 polarization and TNF-α levels accompanied by the increase of MERTK and up-regulated GAS6 levels. Moreover, it has been proved that GAS6 was necessary for MERTK activation and tomentosin could up-regulate GAS6 levels effectively in transwell system. Further mechanistic studies revealed that tomentosin suppressed M1 polarization via increasing MERTK activation mediated by regulation of GAS6 in transwell system. ConclusionTomentosin relieved the severity of CIA mice by inhibiting M1 polarization. Furthermore, tomentosin suppressed M1 polarization via increasing MERTK activation mediated by regulation of GAS6.

LES ASPECTS EPIDEMIOLOGIQUES ET EVOLUTIFS DE LA SARCOIDOSE MEDIASTINOPULMONAIRE AU SEIN DU SERVICE DE PNEUMOLOGIE CHU HASSAN II FES

Introduction:Sarcoidosis is a non-necrotizing systemic granulomatosis of unknown cause characterized by a predominant pulmonary tropism. It is a disease of very variable manifestation and evolution. Its evolutionary course is difficult to predict: from spontaneous resolution in the absence of treatment to progressive organ destruction despite several lines of therapy. Objectives: The aim of our study is to describe the evolutionary profile of mediastinopulmonary sarcoidosis followed in the pneumology department of CHU Hassan II Fez. Material and methods:This is a retrospective study, covering the cases of mediastinopulmonary sarcoidosis followed in our department between January 2016 and December 2019 we required a follow-up period of at least 3 years to be able to retain the cure. Results:We collected 41 patients, the average age was 45.68 years (28-65), with a clear female predominance, 95 ,1% of women, type I was found in 12.2% of cases, type II in 73.2% of cases, type III in 7.3% of cases, and type IV in 7.3% of cases also. Histological confirmation was obtained by mediastinoscopy in 41.5% of cases, and by staged bronchial biopsies in 46.4% of cases. We opted for a therapeutic abstention in 46.3% of the cases (19 patients), 3 of them required treatment during their follow-ups. 22 patients required treatment with oral corticosteroids from the start, 4 relapses were noted after stopping corticosteroids, 4 patients required a second line of azathioprine, and 15 patients were cured after at least 3 years of no treatment.

Genetically engineered CXCR4-modified exosomes for delivery of miR-126 mimics to macrophages alleviate periodontitis

Biofilm-related diseases are a group of diseases that tolerate antimicrobial chemotherapies and therefore are refractory to treatment. Periodontitis, a non-device chronic biofilm disease induced by dental plaque, can serve as an excellent in vivo model to study the important effects of host factors on the biofilm microenvironment. Macrophage activity is one of the key factors that modulate the progression of inflammation-driven destruction in periodontitis; therefore it is an important host immunomodulatory factor. In this study, the reduction of microRNA-126 (miR-126) with the recruitment of macrophages in periodontitis was confirmed in clinical samples, and a strategy for targeted delivery of miR-126 to macrophages was explored. Exosomes overexpressing the C-X-C motif chemokine receptor 4 (CXCR4) loaded with miR-126 (CXCR4-miR126-Exo) was successfully constructed, which reduced off-target delivery to macrophages and regulated macrophages toward the anti-inflammatory phenotype. In vivo local injection of CXCR4-miR126-Exo into sites of periodontitis in rats effectively reduced bone resorption and osteoclastogenesis and inhibited the progression of periodontitis. These results provide new insights for designing novel immunomodulatory factor targeted delivery systems to treat periodontitis and other biofilm-related diseases.

Periodontal pathogens and antibiotic resistance genes in individuals with chronic generalized periodontitis

Relevance. Considering the role of personalized medicine in dental practice, the accumulation of knowledge about the genetic determinants of bacterial resistance and the use of antibacterial drugs, the learning of periodontal microbiota, sensitivity to antimicrobial drugs, the identification of key periodontal pathogens will allow predicting the development mechanisms of inflammatory periodontal diseases and monitoring and prescribing effective antibacterial therapy.Aim. The study aimed to determine the prevalence of pathogens and the occurrence of antibiotic resistance genes in individuals with chronic generalized periodontitis (CGP).Materials and methods. Clinical and laboratory examinations studied 163 subjects aged 18 to 45 years, of which there were 100 patients with inflammatory periodontal diseases and 63 subjects with intact periodontium. The study obtained periodontal pocket and gingival crevice swabs. The real-time PCR isolated marker bacteria and resistance genes to glycopeptide and β-lactam antibiotics.Results. The patients with chronic periodontitis demonstrated a periodontal pathogen detection rate of 96.4 %. Among the isolated periodontal pathogens, bacteria of the red complex were the most common: T. forsythia (81%; p &lt; 0.001), T. denticola (63%; p = 0.054) and P. gingivalis (69%; p &lt; 0.001). In healthy individuals with intact periodontium, P. gingivalis (12.7%), T. denticola (47.62%), and T. forsythia (36.51%) prevailed in the studied material, i.e., gingival fluid. The mean ratio of bone loss in relation to the root length (the Fuchs Index) was 0.83 ± 0.03 in patients with mild CGP and 0.71 ± 0.05 with moderate CGP. The β-lactam antibiotic resistance genes appeared to occur frequently (%). So, TEM and SHV genes were in 72% and 26%. The control group demonstrated the TEM gene in 41.27% (p &lt; 0.001) and the SHV gene in 4.76% (p &lt; 0.001).The group with CGP appeared to have resistance genetic markers: MecA to cephalosporins (15%) and OXA-51 to carbapenems (9%). The control group detected MecA (6.35%; p = 0.0948), while OXA-51 markers were absent (p = 0.014). Both groups did not show resistance genes to other antibiotic groups (AB).Conclusion. The "red complex" microorganisms T. forsythia, T. denticola and P. gingivalis, which were the most frequent during the progression of bone destruction, appeared to play the leading role in the onset and progression of inflammatory periodontal diseases.The oral microbiome can serve as a reservoir for the transfer of resistance genes: the study results indicate a high incidence rate (%) of β-lactam antibiotic resistance genes in the group of patients with chronic periodontitis. The group with chronic periodontitis revealed TEM and SHV genes in 72% and 26%, respectively. The group with intact periodontium also demonstrated a high occurrence rate of the TEM gene in 58.3 % of cases.

Arthroscopic synovectomy versus intra-articular injection of corticosteroids for the management of refractory psoriatic or rheumatoid arthritis of the wrist: study protocol for a randomized controlled trial (ARCTIC trial)

BackgroundRheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory diseases that often affect the wrist and, when affected, can lead to impaired wrist function and progressive joint destruction if inadequately treated. Standard care consists primarily of disease-modifying anti-rheumatic drugs (DMARDs), often supported by systemic corticosteroids or intra-articular corticosteroid injections (IACSI). IACSI, despite their use worldwide, show poor response in a substantial group of patients. Arthroscopic synovectomy of the wrist is the surgical removal of synovitis with the goal to relieve pain and improve wrist function. The primary objective of this study is to evaluate wrist function following arthroscopic synovectomy compared to IACSI in therapy-resistant patients with rheumatoid or psoriatic arthritis. Secondary objectives include radiologic progress, disease activity, health-related quality of life, work participation and cost-effectiveness during a 1-year follow-up.MethodsThis protocol describes a prospective, randomized controlled trial. RA and PsA patients are eligible with prominent wrist synovitis objectified by a rheumatologist, not responding to at least 3 months of conventional DMARDs and naïve to biological DMARDs. For 90% power, an expected loss to follow-up of 5%, an expected difference in mean Patient-Rated Wrist Evaluation score (PRWE, range 0–100) of 11 and α = 0.05, a total sample size of 80 patients will be sufficient to detect an effect size. Patients are randomized in a 1:1 ratio for arthroscopic synovectomy with deposition of corticosteroids or for IACSI. Removed synovial tissue will be stored for an ancillary study on disease profiling. The primary outcome is wrist function, measured with the PRWE score after 3 months. Secondary outcomes include wrist mobility and grip strength, pain scores, DAS28, EQ-5D-5L, disease progression on ultrasound and radiographs, complications and secondary treatment. Additionally, a cost-effectiveness analysis will be performed, based on healthcare costs (iMCQ questionnaire) and productivity loss (iPCQ questionnaire). Follow-up will be scheduled at 3, 6 and 12 months. Patient burden is minimized by combining study visits with regular follow-ups.DiscussionPersistent wrist arthritis continues to be a problem for patients with rheumatic joint disease leading to disability. This is the first randomized controlled trial to evaluate the effect, safety and feasibility of arthroscopic synovectomy of the wrist in these patients compared to IACSI.Trial registrationDutch trial registry (CCMO), NL74744.100.20. Registered on 30 November 2020.ClinicalTrials.gov NCT04755127. Registered after the start of inclusion on 15 February 2021.

Complexity of Inflammation in the Trajectory of Vascular Disease: Interleukin 6 and Beyond

Takayasu's arteritis, first described by Dr. Mikito Takayasu in 1908, is a systemic vasculitis that mostly affects the aorta and its major branches. Although the etiology of the disease is yet unknown, genetic and environmental factors may both play a role. One hundred years after the discovery of Takayasu's arteritis, inflammation is finally widely recognized as a fundamental condition common to all vascular diseases, and clinical trials have proven the efficacy of molecularly targeted drugs that block each step of the NLRP3 inflammasome/interleukin (IL)-1β/IL-6 cascade in patients with atherosclerotic vascular disease and elevated C-reactive protein (CRP). Recent advances have also been made in the treatment of Takayasu's arteritis. The randomized controlled trials and subsequent open-label and post-marketing surveillance studies in Japan have demonstrated that tocilizumab, an anti-IL-6 receptor antibody, is effective in the treatment of Takayasu's arteritis and prevents relapse during tapering of prednisolone doses. IL-6 is also heavily engaged in the remodeling of large vessels after acute aortic dissection as demonstrated in animal studies. In patients with acute aortic dissection, those with markedly elevated CRP levels in the acute phase are known to have an increased risk of aorta-related events, such as rupture due to aortic diameter enlargement, in the subacute and chronic phases. We discovered that elevated CRP levels following aortic dissection are caused by IL-6, which is produced by neutrophils that infiltrate the adventitia of the dissected aorta. In a mouse model of acute aortic dissection, we showed that IL-6 produced by these neutrophils causes progressive destruction of the arterial wall structure and that blockade of IL-6 signaling can prevent post-dissection vascular remodeling and improve life outcome. Therefore, inhibiting IL-6 signaling is anticipated to be effective in the secondary prevention of myocardial infarction and suppression of vascular modeling after dissection and even as an anti-inflammatory therapy for Takayasu's arteritis; however, this approach does not solve everything. Undoubtedly, the mechanisms of inflammation in vascular disease are diverse and complex, and the cytokines and cell populations involved at each site (coronary artery vs. aorta) and in each phenotype (atherosclerosis vs. aortic aneurysm vs. aortic dissection) need to be understood for each type of inflammation. Osteopontin (OPN) is a recruiter of monocytes and macrophages, induces cellular immune responses as a Th1 cytokine, acts as a fibrosis-promoting factor, and has been shown to be deeply involved in the pathogenesis of vascular diseases. We have shown that senescent T cells, which emerge with obesity and aging, secrete significant amounts of OPN, leading to metabolic abnormalities and chronic inflammation. Neutrophil extracellular traps (NETs) released from activated neutrophils have been shown to contribute to the pathogenesis of acute coronary syndromes (ACS) by interacting with macrophages, platelets, and vascular endothelial cells and thus promoting plaque erosion and immunothrombosis. In addition to standard anticoagulant and antiplatelet therapies, the effectiveness of anti-immunothrombotic therapies targeting NETs as a new preventive and therapeutic approach for ACS will be examined in the future.

A home-based low-intensity resistance exercise programme with supervision for secondary sarcopenia in a patient with established rheumatoid arthritis: A case report.

Patients with established rheumatoid arthritis (RA) are at risk of developing secondary sarcopenia. Both pharmacological and exercise interventions are essential for treatment. However, for such patients, exercise loads may lead to the progression of joint destruction and worsening of pain. The purpose of this report was to assess the feasibility of a home-based, low-intensity resistance exercise programme. The case was a 70-year-old female patient with sarcopenia secondary to RA. She was diagnosed with RA at 57 years of age and began medication, maintaining remission of disease activity. However, she did not exercise habitually and was relatively inactive in her daily life. Furthermore, she had kinesiophobia associated with her RA-related symptoms. We suggested implementing a home-based low-intensity resistance exercise programme >3 months, with the goal of exercising the lower extremities daily. The patient was asked to self-monitor using an exercise diary and attend monthly outpatient visits for repeat counselling and feedback. As a result, she was able to perform the exercise programme safely with high compliance, improving her kinesiophobia as well as physical inactivity, although her skeletal muscle mass did not change. Regular exercise and increased physical activity may help prevent the onset of sarcopenia. These results demonstrate the feasibility of implementing our exercise programme and support its potential for preventing the progression of sarcopenia. While questions remain in terms of treating sarcopenia, we believe that our findings will lead to the establishment of an exercise programme for patients with sarcopenia secondary to established rheumatoid arthritis.

Periodontal Disease Pathogens, Pathogenesis, and Therapeutics: The CRISPR-Cas Effect.

Periodontal disease (PD) is an immune-inflammatory disease affecting the supporting structures of the teeth, which results in progressive destruction of the hard and soft tissues surrounding teeth, ultimately resulting in tooth loss. The primary etiological factor for this disease is the presence of pathogenic microorganisms. Pathogenic bacteria face antagonistic conditions and foreign DNA components during the infection stage and depend on defense mechanisms such as clustered regularly interspaced short palindromic repeats (CRISPR)-Cas to counter them. Virulence genes regulated by the CRISPR-Cas system are often expressed by bacteria as part of the stress response to the presence of stress conditions and foreign elements. There is ever-growing evidence regarding the role of CRISPR-Cas in virulence of periodontal pathogens. The same CRISPR-Cas system may also be targeted to reduce bacterial virulence and it may also be utilized to develop diagnostic and therapeutic strategies for prevention and control of PD progression. This review article describes the CRISPR-Cas systems in the periodontal dysbiotic microbial communities, their role in the virulence of periodontal pathogens, and their potential role in understanding the pathogenesis of periodontitis and treatment of PD.

Circular RNA SLTM as a miR-421-competing endogenous RNA to mediate HMGB2 expression stimulates apoptosis and inflammation in arthritic chondrocytes.

Osteoarthritis (OA) is the most common age-related joint disease characterized by chronic inflammation, progressive articular cartilage destruction, and subchondral sclerosis. Accumulating evidence suggests that circular RNAs (circRNAs) play key roles in OA, but the function of circSLTM in OA remains greatly unknown. Therefore, this study focused on interleukin-1β (IL-1β)-treated primary human chondrocytes as well as a rat model to investigate the expression pattern and functional role of circSLTM in OA in vitro and in vivo. CircSLTMand high mobility group protein B2(HMGB2) were upregulated in IL-1β-induced chondrocytes, whereas miR-421 was downregulated. Knockdown of circSLTM or overexpression of miR-421 ameliorated IL-1β-induced chondrocyte apoptosis and inflammation. The regulatory relationship between circSLTM and miR-421, as well as that between miR-421 and HMGB2, was predicted by bioinformatics and then verified by theRNA immunoprecipitationexperiment and dual-luciferase reporter gene assay. Furthermore, silencing of circSLTM increased cartilage destruction and decreased cartilage tissue apoptosis rate and inflammation in a rat model of OA. Taken together, our findings demonstrate the fundamental role of circSLTM in OA progression and provide a potential molecular target for OA therapy.

Emerging Therapeutic Approaches to Target the Dark Side of Senescent Cells: New Hopes to Treat Aging as a Disease and to Delay Age-Related Pathologies.

Life expectancy has drastically increased over the last few decades worldwide, with important social and medical burdens and costs. To stay healthy longer and to avoid chronic disease have become essential issues. Organismal aging is a complex process that involves progressive destruction of tissue functionality and loss of regenerative capacity. One of the most important aging hallmarks is cellular senescence, which is a stable state of cell cycle arrest that occurs in response to cumulated cell stresses and damages. Cellular senescence is a physiological mechanism that has both beneficial and detrimental consequences. Senescence limits tumorigenesis, lifelong tissue damage, and is involved in different biological processes, such as morphogenesis, regeneration, and wound healing. However, in the elderly, senescent cells increasingly accumulate in several organs and secrete a combination of senescence associated factors, contributing to the development of various age-related diseases, including cancer. Several studies have revealed major molecular pathways controlling the senescent phenotype, as well as the ones regulating its interactions with the immune system. Attenuating the senescence-associated secretory phenotype (SASP) or eliminating senescent cells have emerged as attractive strategies aiming to reverse or delay the onset of aging diseases. Here, we review current senotherapies designed to suppress the deleterious effect of SASP by senomorphics or to selectively kill senescent cells by "senolytics" or by immune system-based approaches. These recent investigations are promising as radical new controls of aging pathologies and associated multimorbidities.

Kartogenin potentially protects temporomandibular joints from collagenase-induced osteoarthritis via core binding factor β and runt-related transcription factor 1 binding - A rat model study

Background/purposeTemporomandibular joint (TMJ) osteoarthritis (TMJOA) is a chronic disease with progressive destruction of articular cartilage. This study aimed to explore the therapeutic effects of kartogenin on TMJOA via promoting the binding of core binding factor β (CBFβ) and runt-related transcription factor 1 (RUNX1). Materials and methodsType II collagenase was injected into 35 8-week-old male Sprague Dawley rat TMJs to establish the TMJOA model. Kartogenin, or the CBFβ-RUNX1 complex inhibitor (Ro5-3335), was also delivered via intra-articular injection. Subchondral bone was analyzed by MicroCT. The hematoxylin-eosin, Safranin O, and toluidine blue O staining were used to observe histopathology. Immunohistochemical staining of proliferating cell nuclear antigen (PCNA), caspase-3 (CASP3), interleukin-1β (IL-1β), and collagen II (COL2) was performed. ResultsTMJOA was established in rats by intra-articular injection of type II collagenase. The condylar cartilage and subchondral bone were damaged, with decreased PCNA and COL2 and increased CASP3 and IL-1 (P < .001). Compared with the OA group, kartogenin alleviated the destruction of cartilage and subchondral bone, rescued the expression of PCNA and COL2, and decreased the expression of CASP3 and IL-1β (P < .01). Ro5-3335 did not aggravate the pathology of TMJOA but neutralized the therapeutic effects of kartogenin on TMJOA. ConclusionKartogenin has a potential therapeutic effect on TMJOA via promoting the CBFβ-RUNX1 binding.

ZnO nanoparticles-modified polycaprolactone-gelatin membranes for guided/bone tissue regeneration, antibacterial and osteogenic differentiation properties

Periodontitis is a highly prevalent infectious disease that causes the progressive destruction of the periodontal supporting tissues. If left untreated, it can lead to tooth loss impairing oral function, aesthetics, and the patient’s overall quality of life. Guided and Bone Tissue Regeneration (GTR/BTR) are surgical therapies based on the placement of a membrane that prevents epithelial growth into the defect, allowing the periodontal/bone cells (including stem cells) to regenerate or restore the affected tissues. The success of these therapies is commonly affected by the local bacterial colonization of the membrane area and its fast biodegradation, causing postoperative infections and a premature rupture of the membrane limiting the regeneration process. This study presents the antibacterial and osteogenic differentiation properties of polycaprolactone-gelatin (PCL-G) electrospun membranes modified with ZnO nanoparticles (ZnO-NPs). The membranes´ chemical composition, surface roughness, biodegradation, water wettability, and mechanical properties under simulated physiological conditions, were analyzed by the close relationship with their biological properties. The PCL-G membranes modified with 1, 3, and 6% w/w of ZnO-NPs showed a significant reduction in the planktonic and biofilm formation of four clinically relevant bacteria; A. actinomycetemcomitans serotype b, P. gingivalis, E. coli, and S. epidermidis. Additionally, the membranes presented appropriate mechanical properties and biodegradation rates to be potentially used in clinical treatments. Notably, the membranes modified with the lowest concentration of ZnO-NPs (1% w/w) stimulated the production of osteoblast markers and calcium deposits in human bone marrow-derived mesenchymal stem cells (BM-MSC) and were biocompatible to human osteoblasts cells (hFOB). These results suggest that the PCL-G membranes with 1% w/w of ZnO-NPs are high-potential candidates for GTR/BTR treatments, as they were the most effective in terms of better antibacterial effectiveness at a lower NPs-concentration while creating a favorable cellular microenvironment for bone growth.

Surgical Management of Chronic Pancreatitis: A Systemic Review.

Chronic pancreatitis is a debilitating disease. It is caused by the progressive destruction of normal pancreatic parenchyma, which is replaced by fibrous tissue causing pain in addition to pancreatic insufficiency. There is no single mechanism of pain in chronic pancreatitis. Several medical, endoscopic, and surgical treatment strategies are available to control this disease. Surgical techniques are divided into resection, drainage, and hybrid procedures. The review aimed to compare various surgical procedures used in the management of chronic pancreatitis. The ideal operation is the one that effectively and persistently relieves the pain and has the least morbidity with favorable pancreatic reserve. All the randomized control trials from inception to January 2023, which fulfilled the inclusion criteria, were extensively searched on PubMed and a systemic review was conducted comparing the surgical outcomes of the variety of operations used in chronic pancreatitis. Duodenum-preserving pancreatic head resection is the common procedure done with favorable outcomes.

Efficacy and safety of selective JAK 1 inhibitor filgotinib in active rheumatoid arthritis patients with inadequate response to methotrexate: comparative study with filgotinib and tocilizumab examined by clinical index as well as musculoskeletal ultrasound assessment (TRANSFORM study): study protocol for a randomized, open-label, parallel-group, multicenter, and non-inferiority clinical trial

BackgroundAdministration of Janus kinase (JAK) inhibitors and biological disease-modifying antirheumatic drugs has dramatically improved even the clinical outcomes in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). Dysregulation of JAK-STAT pathways via overproduction of cytokines, such as interleukin-6, is involved in the pathogenesis of RA. Filgotinib is a selective JAK1 inhibitor pending approval for use in RA. By inhibition of the JAK-STAT pathway, filgotinib is effective in suppressing disease activity and preventing the progression of joint destruction. Similarly, interleukin-6 inhibitors such as tocilizumab also inhibit the JAK-STAT pathways by inhibition of interleukin-6 signaling. We present the protocol for a study that will evaluate whether the effectiveness of filgotinib monotherapy is non-inferior to that of tocilizumab monotherapy in RA patients with an inadequate response to MTX.MethodsThis study is an interventional, multicenter, randomized, open-label, parallel-group, and non-inferiority clinical trial with a 52-week follow-up. Study participants will be 400 RA patients with at least moderate disease activity during treatment with MTX. Participants will be randomized in a 1:1 ratio to administer filgotinib monotherapy or subcutaneous tocilizumab monotherapy switched from MTX. We will evaluate disease activity by measuring clinical disease activity indices and by using musculoskeletal ultrasound (MSUS). The primary endpoint is the proportion of patients who achieve an American College of Rheumatology 50 response at week 12. Secondary endpoints are changes from baseline in the MSUS scores. We will also comprehensively analyze serum levels of multiple biomarkers, such as cytokines and chemokines.DiscussionThe study results are expected to show the non-inferiority of the effectiveness of filgotinib monotherapy to that of tocilizumab monotherapy in RA patients with inadequate response to MTX. The strength of this study is its prospective evaluation of therapeutic efficacy using not only clinical disease activity indices, but also MSUS, which accurately and objectively evaluates disease activity at the joint level among patients drawn from multiple centers with a standardized evaluation by MSUS. We will evaluate the effectiveness of both drugs by integrating multilateral assessments—clinical disease activity indices, MSUS findings, and serum biomarkers.Trial registrationJapan Registry of Clinical Trials (https://jrct.niph.go.jp) jRCTs071200107. Registered on March 3, 2021. ClinicalTrials.gov NCT05090410. Registered on October 22, 2021.