Connective Tissue Degradation Research Articles

The Impact of Prevotella on Neurobiology in Aging: Deciphering Dendritic Cell Activity and Inflammatory Dynamics.

Prevotella species, notably Prevotella copri, significantly populate the human gut. In particular, P. copri is prevalent among non-Western populations with diets high in fiber. These species show complex relationships with diverse health aspects, associating with beneficial outcomes, including reduced visceral fat and improved glucose tolerance. Studies implicate various Prevotella species in specific diseases. Prevotella nigrescens and Porphyromonas gingivalis were linked to periodontal disease, promoting immune responses and influencing T helper type 17 (Th17) cells. Prevotella bivia was associated with bacterial vaginosis and a specific increase in activated cells in the vaginal mucosa. In contrast, they have shown substantial potential for inducing connective tissue degradation and alveolar bone resorption. Prevotella's role in neuroinflammatory disorders and autoinflammatory conditions such as Alzheimer's disease and Parkinson's disease has also been noted. The complex relationship between Prevotella and age-related conditions further extends to neurobiological changes in aging, with varying associations with Alzheimer's, Parkinson's, and other inflammatory conditions. Studies have also identified Prevotella to be implicated in cognitive decline in middle aged and the elderly. Future directions in this research area are anticipated to explore Prevotella-associated inflammatory mechanisms and therapeutic interventions. Investigating specific drug targets and immunomodulatory measures could lead to novel therapeutic strategies. Understanding how Prevotella-induced inflammation interacts with aging diseases would offer promising insights for treatments and interventions. This review urges ongoing research to discover therapeutic targets and mechanisms for moderating Prevotella-associated inflammation to further enhance our understanding and improve health outcomes.

A comprehensive study of sous-vide cooked Korat chicken breast processed by various conditions: texture, compositional/structural changes, and consumer acceptance

Korat chicken (KC), is a slow-growing crossbreed renowned for its excellent growth and firm texture. This study investigated the effect of various sous-vide (SV) conditions (60 and 70°C, 1-3 h) on their texture, protein structure and degradation, as well as consumer acceptability, with the traditional boiling served as control. Texture showed significant improvement under all SV conditions compared to the control, as demonstrated by increased water holding capacity (WHC), cooking loss, and decreased shear force, hardness, and chewiness (P < 0.05). These changes corresponded to the higher sensory scores (P < 0.05). Among the SV samples, increased temperatures and longer cooking times led to higher degradation of myofibrils and connective tissue, as evidenced by a decrease in water-, salt-soluble proteins, and soluble collagen (P < 0.05). These findings aligned with the scanning electron microscopy (SEM) results, which showed a looser muscle structure in the meat under more intense cooking conditions. Based on synchrotron radiation-based Fourier transform infrared (SR-FTIR) results, a gradual increase in antiparallel forms within the amide I bands (1700-1600 cm−1) of the total spectra with higher temperature and longer cooking times was observed (P < 0.05), while the fluctuations were observed in the changes of α-helix, β-sheet, and β-turn structures. This suggested that the antiparallel structure represented a looser configuration developing during intense SV cooking. Combined with the principal component analysis (PCA) results, the findings indicated that the suitable SV condition for KC breast meat was 70°C for varying durations (1-3 h), as it showed the strongest correlation with sensory scores, particularly in terms of tenderness. In summary, these findings provided a better understanding of molecular changes and discovered SV conditions to enhance the texture quality of the KC meat.

Granzyme B promotes matrix metalloproteinase-1 (MMP-1) release from gingival fibroblasts in a PAR1- and Erk1/2-dependent manner: A novel role in periodontal inflammation.

To gain insights into how proteases signal to connective tissues cells in the periodontium. The connective tissue degradation observed in periodontitis is largely due to matrix metalloproteinase (MMP) release by gingival fibroblasts. Granzyme B (GzmB) is a serine protease whose role in periodontitis is undefined. Human gingival crevicular fluid (GCF) samples were obtained from sites with periodontal disease and healthy control sites. GzmB was quantified in the GCF ([GzmB]GCF ) by ELISA. Gingival fibroblasts (GF) were cultured in the presence or absence of recombinant GzmB. Culture supernatants were analyzed by ELISA to quantify GzmB-induced release of interstitial collagenase (MMP-1). In some experiments, cells were pre-treated with the inhibitor PD98059 to block MEK/ERK signaling. The protease-activated receptor-1 (PAR-1) was blocked with ATAP-2 neutralizing antibody prior to GzmB stimulation. Systemic MMP-1 levels were measured in plasma from wild-type (WT) and granzyme-B-knockout (GzmB-/- ) mice. The [GzmB]GCF in human samples was ~4-5 fold higher at sites of periodontal disease (gingivitis/periodontitis) compared to healthy control sites, suggesting an association between GzmB and localized matrix degradation. GzmB induced a ~4-5-fold increase in MMP-1 secretion by cultured fibroblasts. GzmB induced phosphorylation of Erk1/2, which was abrogated by PD98059. GzmB-induced upregulation of MMP-1 secretion was also reduced by PD98059. Blockade of PAR-1 function by ATAP-2 abrogated the increase in MMP-1 secretion by GF. Circulating MMP-1 was similar in WT and GzmB-/- mice, suggesting that GzmB's effects on MMP-1 release are not reflected systemically. These data point to a novel GzmB-driven signaling pathway in fibroblasts in which MMP-1 secretion is upregulated in a PAR1- and Erk1/2-dependent manner.

Successful treatment of disseminated granuloma annulare with adalimumab

Granuloma annulare (GA) is a chronic inflammatory necrobiotic granulomatous skin disease, which is based on a delayed hypersensitivity reaction caused by the production of interferon- (IFN-) by tissue macrophages and th1-limocytes, tumor necrosis factor- (TNF-) and matrix metalloproteinases (MMP), which leads to the degradation of connective tissue.&#x0D; The most frequent form of GA if localized which is characterized clinically by grouped papules and plaques of red or pink color on the extremities. although disseminated variants of disease occur in 15% of all cases of ag. in contrast to the practically asymptomatic course of the localized form, typical signs of disseminated form are intensive sense of itching, the presence of at least ten foci of skin lesions, recurrent and resistance to treatment course.&#x0D; A 53-year-old female patient with a long-term recurrent course of annular granuloma after a weak clinical response to therapy with pentoxifilin, methotrexate and azathioprine turned to the dermatology department of the university hospital. In light of the lack of satisfactory treatment options anti-cytokine therapy with adalimumab was recommended at a daily dosage of 80 mg, once a week, for 2 weeks, then 1 time every two weeks for 1.5 months. Already on the 5th day after receiving the first injection, the patient reported that the feeling of itching disappeared. By the end of the second week of the induction phase of biotherapy, it became obvious that new rashes did not appear, and the old elements of the skin rash had significantly flattened, turned pale and decreased in volume. After the second week of consolidated therapy, the dermatologist confirmed the convalescence.

The Degradation of Intramuscular Connective Tissue In Vitro with Purified Cathepsin L from Bovine Pancreas.

To investigate the possible degradation of the intramuscular connective tissue (IMCT) with cathepsin L, isolated IMCTs were incubated with purified cathepsin L in vitro. Here, we prepared purified cathepsin L from bovine pancreas by using DEAE Sephacel, Sephacryl S-100 HR, SP Sepharose FF, and con A-Sepharose affinity chromatography in sequence. An SDS-PAGE analysis of CNBr-digested peptides showed that the degradation of collagen in IMCT could take place on terminal non-helical peptides rather than the triple helix region. Decorin (DCN) was clearly degraded at a pH of 5.0. The TP and TO of intramuscular connective tissue decreased to 41.41 °C and 43.79 °C, respectively. In the cathepsin L treatment of pH 5.0, the decreases in the TP and TO of IMCT were more sensitive than they were at pH 5.5~6.5.

Matrix metalloproteinase- 9 may contribute to collagen structure modification during postmortem aging of beef

Matrix metalloproteinases (MMPs) are responsible for the turnover of intramuscular connective tissue in live animals. We hypothesize that MMPs may play a role in postmortem aging of beef muscles for the degradation of connective tissues. Four different experiments were performed to: 1) characterize MMP activity during postmortem aging of beef; 2) determine if the native beef MMP can contribute to connective tissue degradation in a simulated standard industry postmortem aging condition; 3) explore approaches to improve the native beef MMP activity and 4) characterize MMP activity in beef from cattle supplemented with supranutritional level of Zn. In experiment 1, MMP was active throughout the entire aging periods (3, 21, 42 and 63 d) for beef muscles Longissimus lumborum, Gluteus medius and Gastrocnemius, and the unknown MMP responsible for the collagen degradation was identified as MMP-9 by Western Blot. In experiment 2 and 3, MMP-9 activity was noticeable in the gels after 42 d of storage in the cooler. Moreover, the addition of ZnCl2 in the model system significantly increased MMP-9 activity when compared to the control (P < 0.01). In experiment 4, Longissimus thoracis from animals supplemented with a supranutritional Zn level had increased Zn availability and MMP-9 activity than those from animals fed with a control diet (P < 0.05). Further research is needed better understand MMP-9 mechanism during postmortem aging of meat. With a better understanding of MMP-9 in the aging process, the beef industry can provide better connective tissue management strategies for lower-quality beef cuts.

Molecular profiling of gingival crevicular fluid fails to distinguish between infrabony and suprabony periodontal defects.

To assess the differential molecular profiling of gingival crevicular fluid (GCF) from infrabony and suprabony periodontal defects compared with healthy sites. Seventy-five samples from 25 patients with untreated periodontitis stage III-IV were included. Clinical and radiological parameters as well as GCF samples were collected from an infrabony defect, a suprabony defect and a periodontally healthy site per patient. A multiplex bead immunoassay was performed to assess the level of 18 biomarkers associated with inflammation, connective tissue degradation and regeneration/repair. GCF volume was higher in periodontal sites compared with healthy sites, with no significant difference between infrabony and suprabony defects. Fourteen biomarkers were elevated in infrabony and suprabony sites compared with healthy sites (p < .05). Only interleukin-1α levels were increased in infrabony compared with suprabony sites, whereas there was no difference in probing pocket depth. Although the GCF molecular profile clearly differentiates periodontally affected sites from healthy sites, the different architecture between infrabony and suprabony defects is not reflected in GCF biomarker changes.

Ендотоксикоз і запалення як предиктори поглиблення функціональної недостатності підшлункової залози при хронічному панкреатиті у поєднанні із цукровим діабетом 2 типу

According to scientists, a significant role in the progression of chronic pancreatitis (CP) and diabetes mellitus (DM), as well as in the occurrence of complications of these diseases, is played by inflammation and endogenous intoxication by the products of protein breakdown as a result of the inflammatory process, fibrosis, and degradation of connective tissue in the patient’s body, in particular, and in the pancreas. The aim is to analyze the state of parameters of inflammation, endotoxicosis, and their influence on the functional capacity of the pancreas in the comorbid course of chronic pancreatitis and type 2 diabetes mellitus (DM2). Materials and methods. 112 patients with CP in the phase of mild therapeutic exacerbation in combination with DM2 in the stage of subcompensation were examined. The results. Moderate and moderate inverse correlations were established between CRP and fecal α-elastase in patients with CP and comorbidity of CP and DM2 (respectively r=-0.423 and r=-0.565, p&lt;0,05). An increase in the strength of reliable direct moderate correlations between the levels of HbA1c and CRP in patients with CP in combination with DM2 compared to those with isolated CP (respectively r=0.313 and r=0.410, p&lt;0,05) was proved. Conclusions: We proved a reliable influence of the index of endogenous intoxication on the level of pancreatic functional insufficiency according to the content of fecal α-elastase, which was more significant in the combined course of CP and DM2 compared to that in isolated CP. An increase in the strength of reliable direct, moderate, and moderate correlations between HbA1c levels and the index of endogenous intoxication in patients with isolated CP and CP in combination with DM2 has been proven.

Comparison of matrix metalloproteinase-13 and tissue inhibitor of metalloproteinase-1 levels and alveolar bone density in chronic periodontitis before and after scaling and root planning

Periodontitis is typically associated with disorders characterized by compromised tooth-supporting tissue. Damage to periodontal tissue is caused by an imbalance between matrix metalloproteinases and their inhibitors. Decreased tissue inhibitor and elevated matrix metalloproteinase levels result in collagen connective tissue and bone degradation. Several studies have shown that high levels of matrix metalloproteinase-13 (MMP-13) and low levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) are also found in gingival crevicular fluid and saliva of patients with periodontitis. The purpose of this study was to determine the comparison of MMP-13 levels, TIMP-1 levels of saliva and bone density in patients with chronic periodontitis before and after scaling and root planning (SRP). The study samples were selected from patients who came for treatment at the Periodontics Installation of Universitas Sumatera Utara. A total of 16 patients were selected (n = 16) with a diagnosis of chronic periodontitis. The result showed that salivary MMP-13 levels in chronic periodontitis patients before SRP were higher than salivary MMP-13 levels after SRP and the difference was statistically significant (p &lt; 0.05). It was also revealed that salivary TIMP-1 levels and alveolar bone density in chronic periodontitis patients before SRP were lower than that after SRP and the difference was statisticallysignificant (p &lt; 0.05). There was a positive correlation between clinical parameters and salivary MMP-13 levels in patients with chronic periodontitis before and after SRP, but it was not statistically significant (p &gt; 0.05). There was a negative correlation between clinical parameters and salivary TIMP-1 levels in patients with chronic periodontitis before and after SRP, but it was not statistically significant (p &gt; 0.05).

Fucosterol Isolated from Dietary Brown Alga Sargassum horneri Protects TNF-α/IFN-γ-Stimulated Human Dermal Fibroblasts via Regulating Nrf2/HO-1 and NF-κB/MAPK Pathways.

Sargassum horneri is a well-known edible brown alga that is widely abundant in the sea near China, Korea, and Japan and has a wide range of bioactive compounds. Fucosterol (FST), which is a renowned secondary metabolite in brown algae, was extracted from S. horneri to 70% ethanol, isolated via high-performance liquid chromatography (HPLC), followed by the immiscible liquid-liquid separation, and its structure was confirmed by NMR spectroscopy. The present study was undertaken to investigate the effects of FST against oxidative stress, inflammation, and its mechanism of action in tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated human dermal fibroblast (HDF). FST was biocompatible with HDF cells up to the 120 μM dosage. TNF-α/IFN-γ stimulation significantly decreased HDF viability by notably increasing reactive oxygen species (ROS) production. FST dose-dependently decreased the intracellular ROS production in HDFs. Western blot analysis confirmed a significant increment of nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) involvement in FST-treated HDF cells. In addition, the downregulation of inflammatory mediators, molecules related to connective tissue degradation, and tissue inhibitors of metalloproteinases were identified. TNF-α/IFN-γ stimulation in HDF cells increased the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) mediators, and its phosphorylation was reduced with the treatment of FST in a dose-dependent manner. Results obtained from western blot analysis of the NF-κB nuclear translocation were supported by immunocytochemistry results. Collectively, the outcomes suggested that FST significantly upregulates the Nrf2/HO-1 signaling and regulates NF-κB/MAPK signaling pathways to minimize the inflammatory responses in TNF-α/IFN-γ-stimulated HDF cells.

A Review of Asteroid Biology in the Context of Sea Star Wasting: Possible Causes and Consequences.

AbstractSea star wasting-marked in a variety of sea star species as varying degrees of skin lesions followed by disintegration-recently caused one of the largest marine die-offs ever recorded on the west coast of North America, killing billions of sea stars. Despite the important ramifications this mortality had for coastal benthic ecosystems, such as increased abundance of prey, little is known about the causes of the disease or the mechanisms of its progression. Although there have been studies indicating a range of causal mechanisms, including viruses and environmental effects, the broad spatial and depth range of affected populations leaves many questions remaining about either infectious or non-infectious mechanisms. Wasting appears to start with degradation of mutable connective tissue in the body wall, leading to disintegration of the epidermis. Here, we briefly review basic sea star biology in the context of sea star wasting and present our current knowledge and hypotheses related to the symptoms, the microbiome, the viruses, and the associated environmental stressors. We also highlight throughout the article knowledge gaps and the data needed to better understand sea star wasting mechanistically, its causes, and potential management.

Multiphoton microscopy assessment of the structure and variability changes of dermal connective tissue in vulvar lichen sclerosus: A pilot study.

In this article, we offer a novel classification of progressive changes in the connective tissue of dermis in vulvar lichen sclerosus (VLS) relying on quantitative assessment of the second harmonic generation (SHG) signal received from formalin fixed and deparaffinized tissue sections. We formulate criteria for distinguishing four degrees of VLS development: Initial-Mild-Moderate-Severe. Five quantitative characteristics (length and thickness type I Collagen fibers, Mean SHG signal intensity, Skewness and Coherence SHG signal) are used to describe the sequential degradation of connective tissue (changes in the structure, orientation, shape and density of collagen fibers) up to the formation of specific homogeneous masses. Each of the degrees has a characteristic set of quantitatively expressed features. We focus on the identification and description of early, initial changes of the dermis as the least specific. The results obtained by us and the proposed classification of the degrees of the disease can be used to objectify the dynamics of tissue changes during treatment.

Incidence of multiple bacterial infections in Pacific whiteleg shrimp, Litopenaeus vannamei

A rare incidence of multiple bacterial infections was reported in Litopenaeus vannamei grow-out ponds in India. The pathogenic organisms identified are Aeromonas veronii, Bacillus flexus, Kurthia gibsonii, Shewanella decolorationis, Bacillus cereus and Shewanella amazonensis. The infected shrimp showed various clinical and morphological changes such as mucus secretion in the hepatopancreas, bacterial spots in the carapace, red or pink discoloration of abdomen with black stripes and highly melanized body. The Histological studies of the hepatopancreas revealed bacterial plaque in the lumen, inflammatory response, necrosis of connective tissue and lipid droplets. The histology of stomach detected degradation of spongy connective tissue, hypertrophied nucleus and the abdomen showed bacterial plaques in the gaps of the muscle fibre. Histochemically, both gram-positive and gram-negative bacteria's were identified in the hepatopancreas and the presence of mucus in the lumen of hepatopancreatic microtubules was confirmed by Alcian blue staining. The electron microscopic studies of the infected shrimp showed multiple bacterial infections and cellular responses like phagocytosis in the hepatopancreas, using transmission electron microscope and scanning electron microscopic confirmed the presence of bacillus and coccobacillus-shaped bacteria in carapace.

Native Beef Collagenase MMP-9 May Contribute to Tenderness Improvement by Degrading Connective Tissues in Extended Aged Beef

Objective: Collagen is one of the main components in the connective tissue (CT) and contributes to background toughness in beef. It is known that in living animals, collagen can be degraded and remodeled by collagenase matrix metalloproteinases (MMP); however, it is unclear if collagenase MMP can impact CT texture during postmortem aging of beef. Therefore, this study aimed to understand how collagenase MMP activity may impact postmortem connective tissue degradation in beef in three different cuts and four different aging periods.

Effect of FLU-ACIL RHINO nasal spray on the inflammatory process and recovery of patients after FESS

Topicality: The main method of treatment of chronic rhinosinusitis is functional endoscopic rhinosurgery (FESS). However, the regeneration of tissues damaged during surgery remains important. It has three stages – alteration (primary and secondary), exudation and proliferation – and takes place with the formation of reactive oxygen species. Therefore, determination of total NO synthase activity (NOS), inducible synthase activity (iNOS) and constitutive (cNOS) isoforms are biochemical markers of the inflammatory response. The activity of the alteration process and the degree of postoperative damage is characterized by the concentration of glycosaminoglycans and L-oxyproline. Materials and methods: This study determined the multimodal (multi-vector) effect of Flu-Acyl rhino spray (6% N-acetylcysteine in 3% hypertonic pH-controlled saline) on the inflammatory response of the nasal mucosa in the postoperative period. The study was conducted at the Department of Otolaryngology of NMU named after O.O. Bogomolets on the basis of "Alexander Clinical Hospital of Kyiv". Clinical and laboratory examinations of 52 patients aged 18 to 60 years who underwent FESS were performed. Patients were randomized into two groups. 24 patients received standard treatment (control group), 26 patients – with the addition of nasal spray Flu-Acyl rhino (main group). Results: It was found that the indicators of total activity of NO synthase (NOS) and its isoforms, as well as the concentration of glycosaminoglycans and L-oxyproline were lower in patients of the main group on days 7 and 14 of the postoperative period compared with patients in the control group (р&lt;0,05). These results can be explained by the anti-inflammatory effect of Flu-Acyl rhino spray due to the presence of N-acetylcysteine, which is able to inhibit the activation of the transcription factor NF-kB, which leads to decreased iNOS activity on the 7th and 14th day of treatment. N-acetylicysteine also reduces the degradation of amorphous connective tissue, shifts the balance in the proteolysis / antiproteolysis system towards the predominance of the antiproteolytic component, participates in the normalization of physiological production and utilization of sulfide anion. Conclusions: The use of Flu-Acyl rhino nasal spray in the postoperative period due to multimodal action promotes physiological changes from alteration and exudation to proliferation processes, normalizes mucociliary clearance in the postoperative period, improves healing and reduces recovery and disability.

Angiopoietin-like protein 2 deficiency promotes periodontal inflammation and alveolar bone loss.

Human periodontitis is a highly prevalent inflammatory disease that leads to connective tissue degradation, alveolar bone resorption, and tooth loss. Angiopoietin-like 2 (ANGPTL2) regulates chronic inflammation in various diseases and is functionally involved in maintaining tissue homeostasis and promoting tissue regeneration, but there is limited information about its function in periodontitis. Here we investigated the expression and explicit role of ANGPTL2 in periodontitis. Immunohistochemistry and quantitative real-time PCR (qRT-PCR) were used to detect the ANGPTL2 expression in periodontal tissues and periodontal ligament cells (PDLCs). A ligature-induced periodontitis model was generated in wild-type and ANGPTL2 knockout mice. qRT-PCR and enzyme-linked immunosorbent assay were used to assess the production of inflammatory cytokines and matrix metalloproteinases (MMPs) in cultured PDLCs. Western blot was performed to detect proteins in relevant signaling pathways. Increased ANGPTL2 expression was observed in inflamed periodontal tissues and PDLCs. ANGPTL2 deficiency promoted alveolar bone loss with enhanced osteoclastogenesis and inflammatory reactions in ligature-induced periodontitis. Downregulation of ANGPTL2 remarkably enhanced expression levels of interleukin (IL)-6, IL-8, MMP1, and MMP13 in Porphyromonas gingivalis lipopolysaccharide-induced PDLCs, whereas ANGPTL2-overexpressing PDLCs showed opposite trends. ANGPTL2 downregulation activated STAT3 and nuclear factor-κB pathways and blocked Akt signaling under inflammatory environment. Treatment with a STAT3 inhibitor partially suppressed the inflammatory reaction of PDLCs mediated by ANGPTL2 knockdown. Our study provides the first evidence of an anti-inflammatory effect of ANGPTL2 in murine periodontitis. The findings demonstrate the critical and protective role of ANGPTL2 in alveolar bone loss and periodontal inflammation.

Correction to: Periodontitis and Rheumatoid Arthritis: The Common Thread

The two immunoinflammatory disorders, rheumatoid arthritis (RA) and Periodontitis (PD) are characterized by synovitis, joint damage, and alveolar bone degradation, are triggered by certain inflammatory mediators and leukocyte invasion, respectively. Rheumatoid arthritis is an infectious disorder which attacks changed self-epitopes and thus affects 1% of the human population, whereas 11% of the worldwide population aged is afflicted by extreme periodontal diseases in which commensal microbes upon the tooth surface is substituted by dysbiosis of the bacterial community that facilitate chronic inflammatory periodontal tissue damage. Periodontitis and RA display similarities in terms of pathogenesis amid variations in aetiology; all diseases entail systemic inflammation fuelled by, degradation of connective tissue, pro-inflammatory cytokines, and bone deterioration. Both the disorders have significant serological, epidemiological, and therapeutic connections and also have some common risk factors like aging and smoking. Laboratory and clinical data supporting this correlation is addressed in this aetiology analysis and the possible pathways involved in connecting both the diseases i.e., periodontitis to RA are described.

Biomarkers in axial spondyloarthritis and low back pain: a comprehensive review.

The spectrum of axial spondyloarthritis (AxSpA) (including both non-radiographic and radiographic AxSpA), also known as ankylosing spondylitis AS, has achieved growing recognition. With the development of treatments not only effective in controlling disease activity but also in slowing radiographic progression, and given the cost and risk profiles of these novel treatments and the limitations of current clinical criteria, imaging and peripheral blood biomarkers (C-reactive protein, HLA-B27 testing), the need for better biomarkers has never been greater. The purpose of this review is to present up-to-date information on the biomarkers for the diagnosis for assessing disease diagnosis, activity, treatment response, and radiographic progression of AxSpA, and entails multiple search strings used to identify articles of interest published in PubMed and the Cochrane database up to May 1, 2021. We present the current status of research in serologic biomarkers such as cytokines, adipokines, matrix metalloproteinases, calprotectin, CD74, antibodies, bone turnover markers, and circulating protein fragments of cartilage and connective tissue degradation and other biomarkers. Despite a great deal of work, most serologicresults have been disappointing and to date none perform better than CRP. Recent promising preliminary data for some has been published, but require further confirmation. Transcriptomic biomarkers such as micro-RNAs and genetic biomarkers also show promise to assist in diagnosis and possibly for radiographic severity, including a recently developed panel of genetic risk markers used in a polygenic risk score instrument in AS diagnosis. These need further confirmation and application in AS as well as in nr-AxSpA.

28079 Serum proteases upregulate significantly between 20 and 40 years of age: Impact for dermal matrix regulation

Degradation of the dermal extracellular matrix (ECM) is a key hallmark of skin aging. This ECM damage is externally visible as wrinkles and sagging skin later in life, but these phenotypic changes are known to be the result of cumulative damage over time. In the current work proteomics analysis was performed on plasma from Caucasian women in the age groups of 20s, 40s, and 60s from a study we call the Multi-Decade & Ethnicity (MDE). Analysis of this data indicated ∼1/3 more proteins were regulated between 20 and 40 than between 40 and 60. Proteolytic themes are dominant in the 5 most significant process networks identified in our age comparisons with connective tissue degradation and extracellular matrix remodeling strongly regulated in this data. Six major proteases are upregulated between the 20s and 40s which do not show further regulation between 40 and 60. Although other proteases are upregulated between 40 and 60 those regulated between 20 and 40 contain major collagen degrading proteases. This work demonstrates proteolytic enzymes increase in plasma with age and that a significant amount of this regulation happens between 20 and 40 years of age. Concurrent with downregulation of collagen expression as previously demonstrated in the MDE study the 20 to 40-time span is of critical interest for dermal remodeling and structural vulnerability leading to future appearance issues.

Advances in molecular mechanisms of pelvic organ prolapse (Review).

Pelvic organ prolapse (POP) is a common gynecological benign disease occurring in middle-aged and elderly females. Its incidence increases every year. To date, the majority of studies investigating its etiology have not evaluated the underlying molecular mechanisms, which has caused substantial difficulties in the prevention, treatment and prognosis of POP. In the present narrative review, recent research studies concerning the molecular mechanisms of POP were systematically reviewed and the advances were summarized. The association between the incidence of POP and the reduction of the extracellular matrix, activation of oxidative stress, genetic susceptibility, denervation of the pelvic floor and reduction of estrogen infiltration were explored. POP is mainly associated with damage of pelvic floor muscles and connective tissue, which are directly caused by pregnancy and vaginal delivery. The majority of the molecular and genetic mutations associated with POP involve specific components of connective tissue synthesis and degradation. It is likely that macroscopic parameters, such as anatomy, lifestyle and reproductive factors, interact with microscopic parameters, such as physiology and genetics in the female pelvic floor, leading to POP. Additional research studies investigating the molecular mechanisms of POP should be performed, since they may aid public health strategies. In the present narrative review, a summary of these molecular mechanisms underlying the development of POP is provided. This included the relevant proteins and genes involved. On this basis, countermeasures were proposed.