Markers Of Degradation Research Articles

Effects of Aging on Collagen in the Skeletal Muscle of Mice.

Aging affects several tissues in the body, including skeletal muscle. Multiple types of collagens are localized in the skeletal muscle and contribute to the maintenance of normal muscle structure and function. Since the effects of aging on muscle fibers vary by muscle fiber type, it is expected that the effects of aging on intramuscular collagen might be influenced by muscle fiber type. In this study, we examined the effect of aging on collagen levels in the soleus (slow-twitch muscle) and gastrocnemius (fast-twitch muscle) muscles of 3-, 10-, 24-, and 28-month-old male C57BL/6J mice using molecular and morphological analysis. It was found that aging increased collagen I, III, and VI gene expression and immunoreactivity in both slow- and fast-twitch muscles and collagen IV expression in slow-twitch muscles. However, collagen IV gene expression and immunoreactivity in fast-twitch muscle were unaffected by aging. In contrast, the expression of the collagen synthesis marker heat shock protein 47 in both slow- and fast-twitch muscles decreased with aging, while the expression of collagen degradation markers increased with aging. Overall, these results suggest that collagen gene expression and immunoreactivity are influenced by muscle fiber type and collagen type and that the balance between collagen synthesis and degradation tends to tilt toward degradation with aging.

Prohibitin2/PHB2, Transcriptionally Regulated by GABPA, Inhibits Cell Growth via PRKN/Parkin-dependent Mitophagy in Endometriosis.

Endometriosis (EMS) is a common benign gynecological disease affecting women of reproductive age. It is characterized by abnormal growth of endometrial tissue outside the uterine cavity, resulting in chronic pelvic pain and infertility. Endometrial physiological and pathological processes are intimately connected to autophagy. Mitophagy is an essential selective mode that protects cells from metabolic stress and hypoxia. Mitochondrial autophagy mediated by prohibitin 2 (PHB2) is dependent on the PRKN/Parkin pathway and is involved in numerous human diseases. Uncertainty remains as to whether mitophagy regulation by PHB2 contributes to the occurrence and progression of EMS. This study aims to investigate the mechanism underlying the role of PHB2 in EMS. This study detected the protein and mRNA expression of PHB2 in ectopic and normal endometrial tissues of ovarian EMS, in addition to ectopic endometrial cell line 12Z and endometrial stromal cell line KC02-44D for gene overexpression or knockdown. Cell function experiments and mitochondrial function experiments were conducted to investigate the role of PHB2 in the endometrium. Bioinformatic analysis and experiments were also used to investigate the upstream transcription factors that influence PHB2 expression. PHB2 was downregulated in ectopic endometrium, and PHB2 overexpression inhibited cell proliferation, migration, and invasion and promoted apoptosis. The upregulation of mitophagy markers, including Parkin and LC3II/I, and the downregulation of autophagy degradation markers P62 and TOMM20 in EMS suggest that PHB2 may contribute to cell proliferation, migration, invasion, and apoptosis via PRKN/Parkin-mediated mitophagy. Analysis and validation of bioinformatics data revealed that the transcription factor GABPA binds directly to the PHB2 promoter region and controls the transcriptional expression of PHB2. This study investigated the role of PHB2 in the onset of EMS. It inhibits EMS growth via PRKN/Parkin-mediated mitophagy, and GABPA controls the transcriptional disorder of PHB2. This study's findings suggest a novel method for investigating the clinical potential of PHB2 in EMS.

Females display relatively preserved muscle quality compared with males during the onset and early stages of C26-induced cancer cachexia.

Cancer cachexia is clinically defined by involuntary weight loss >5% in <6 mo, primarily affecting skeletal muscle. Here, we aimed to identify sex differences in the onset of colorectal cancer cachexia with specific consideration to skeletal muscle contractile and metabolic functions. Eight-weeks old BALB/c mice (69 males, 59 females) received subcutaneous C26 allografts or PBS vehicle. Tumors were developed for 10-, 15-, 20-, or 25 days. Muscles and organs were collected, in vivo muscle contractility, protein synthesis rate, mitochondrial function, and protein turnover markers were assessed. One-way ANOVA within sex and trend analysis between sexes were performed, P < 0.05. Gastrocnemius and tibialis anterior (TA) muscles became atrophic in male mice at 25 days, whereas female mice exhibited no significant differences in muscle weights at endpoints despite presenting hallmarks of cancer cachexia (fat loss, hepatosplenomegaly). We observed lowered muscle contractility and protein synthesis concomitantly to muscle mass decay in males, with higher proteolytic markers in muscles of both sexes. mRNA of Opa1 was lower in TA, whereas Bnip3 was higher in gastrocnemius after 25 days in male mice, with no significant effect in female mice. Our data suggest relative protections to skeletal muscle in females compared with males despite other canonical signs of cancer cachexia and increased protein degradation markers; suggesting we should place onus upon nonmuscle tissues during early stages of cancer cachexia in females. We noted potential protective mechanisms relating to skeletal muscle contractile and mitochondrial functions. Our findings underline possible heterogeneity in onset of cancer cachexia between biological sexes, suggesting the need for sex-specific approaches to treat cancer cachexia.NEW & NOTEWORTHY Our study demonstrates biological-sex differences in phenotypic characteristics of cancer cachexia between male and female mice, whereby females display many common characteristics of cachexia (gonadal fat loss and hepatosplenomegaly), protein synthesis markers alterations, and common catabolic markers in skeletal muscle despite relatively preserved muscle mass in early-stage cachexia compared with males. Mechanisms of cancer cachexia appear to differ between sexes. Data suggest need to place onus of early cancer cachexia detection and treatment on nonmuscle tissues in females.

CLINICAL AND PATHOANATOMICAL PARALLELS OF THE HEART DAMAGE DUE TO COVID-19

The aim – to investigate the clinical and pathomorphological features of the heart damagein patients who died due to COVID-19 pneumonia.Materials and methods. A retrospective analysis of the medical records of 556 patients,hospitalized to Lviv Clinical Emergency Care Hospital in January- February 2021, witha diagnosis of COVID-19 pneumonia and 90 reports of pathological examination ofthe causes of death of patients with COVID-19 pneumonia was carried out. Clinicalparameters (demographic data, comorbidities, presence of COVID-19 pneumoniacomplications, complaints, medical history, results of physical examination andadditional laboratory and instrumental investigations, performed during hospitalization,including levels of NT-proBNP and troponin, determined by immunofluorescence method)and results of pathological examination were evaluated.The results. During life, most patients who died due to COVID-19 pneumonia werediagnosed with acute respiratory distress syndrome (ARDS), the development of multipleorgan failure, rarely PE. They showed significantly lower capillary blood oxygensaturation indicators compared to similar indicators of recovered patients, as well asan increase in markers of systemic inflammation (level of leukocytes and interleukin-6),fibrin degradation products (D-dimers) and markers of multiorgan failure (creatinine,NT-proBNP, troponin I). The most frequent pathomorphological signs of heartdamage in patients with COVID-19 were interstitial edema with hyperemia (63.5 %) and fragmentation of cardiomyocytes (34.1 %). Every fourth patient had mononuclear cell infiltration, which was associated with increased level of NTproBNP, oxygen saturationdecrease in capillary blood, and increase in aspartate aminotransferase. Myocardialinfarction, pericarditis, and myocarditis occurred more rarely in patients with COVID-19.Conclusions. The variety of clinical scenarios of heart damage requires a high level ofsuspicion in the early stages of the disease and the use of appropriate investigations toidentify its cause.

Biomarkers in assessing the vulnerability of atherosclerotic plaques: a narrative review

Aim. To study the role of biomarkers in assessing the vulnerability of atherosclerotic plaques.Material and methods. A review of literature sources investigating the biomarker assessment of the vulnerability of atherosclerotic plaques published for the period 01.01.2016 to 31.12.2022 was carried out. Literature search was carried out in English and Russian in PubMed databases, in Google Academy, Elibrary.ru according to the following keywords: “biomarkers of plaque vulnerability”, “NLR and vulnerable plaque”, “CRP and vulnerable plaque”, ”MMP-9 and vulnerable plaque”, “TIMP-1 and vulnerable plaque”, ”galectin-3 and vulnerable plaque”, “NGAL and vulnerable plaque”. A total of 183 articles were found, of which 42 articles in full-text format containing original clinical studies were selected for the preparation of this review.Results. Numerous studies have shown that the vulnerability and rupture of the plaque, rather than its size and severity of stenosis, are the main cause of cardiovascular events in patients with coronary heart disease. Small plaques rich in lipids often become unstable due to an inflammatory reaction supported by the interaction between lipoproteins, monocytes, macrophages, T-lymphocytes and vascular wall cells. NLR, CRP, NGAL, Galectin-3, as well as markers of extracellular matrix degradation (MMP-9, TIMP-1) can play a special role in assessing the vulnerability of plaques.Conclusion. The development of acute coronary syndrome is based on the destabilization of the atherosclerotic plaque, which occurs not only due to changes in its lipid composition, but also infiltration by immuno-inflammatory cells, degradation of the extracellular matrix, as well as an active inflammatory reaction and neovascularization of the plaque. Therefore, traditional imaging methods that characterize the plaque by its appearance and size are not enough to predict the risk of rupture and the development of an acute thrombotic event. Thus, there is a need to identify new biomarkers that would correlate with the instability of plaque atheroma.

Astaxanthin as a Potent Antioxidant for Promoting Bone Health: An Up-to-Date Review.

In recent years, bone loss and its associated diseases have become a significant public health concern due to increased disability, morbidity, and mortality. Oxidative stress and bone loss are correlated, where oxidative stress suppresses osteoblast activity, resulting in compromised homeostasis between bone formation and resorption. This event causes upregulation of bone remodeling turnover rate with an increased risk of fractures and bone loss. Therefore, supplementation of antioxidants can be proposed to reduce oxidative stress, facilitate the bone remodeling process, suppress the initiation of bone diseases, and improve bone health. Astaxanthin (3,3'-dihydroxy-4-4'-diketo-β-β carotene), a potent antioxidant belonging to the xanthophylls family, is a potential ROS scavenger and could be a promising therapeutic nutraceutical possessing various pharmacological properties. In bone, astaxanthin enhances osteoblast differentiation, osteocytes numbers, and/or differentiation, inhibits osteoclast differentiation, cartilage degradation markers, and increases bone mineral density, expression of osteogenic markers, while reducing bone loss. In this review, we presented the up-to-date findings of the potential anabolic effects of astaxanthin on bone health in vitro, animal, and human studies by providing comprehensive evidence for its future clinical application, especially in treating bone diseases.

ACE Inhibitors Improve Skeletal Muscle by Preserving Neuromuscular Junctions in Patients with Alzheimer's Disease.

Hypertension and skeletal muscle decline are common findings in patients with Alzheimer's disease (AD). Angiotensin-converting enzyme (ACE) inhibitors preserve skeletal muscle and physical capacity; however, the driving mechanisms are poorly understood. We investigated the effects of ACE inhibitors on the neuromuscular junction (NMJ) with relevance to skeletal muscle and physical capacity in AD patients and age-matched controls. We evaluated controls (n = 59) and three groups of AD patients, including normotensive (n = 51) and patients with hypertension taking ACE inhibitors (n = 53) or other anti-hypertensive medications (n = 49) at baseline and one year later. We measure plasma c-terminal agrin fragment-22 (CAF22) as a marker of NMJ degradation, handgrip strength (HGS), and Short Physical Performance Battery (SPPB) as markers of physical capacity. At baseline AD patients demonstrated lower HGS and SPPB scores and higher CAF22 levels than controls, irrespective of the hypertension status (all p < 0.05). The use of ACE inhibitors was associated with higher HGS and relative maintenance of SPPB scores, gait speed, and plasma CAF22 levels. Conversely, other anti-hypertensive medications were associated with an unaltered HGS, reduced SPPB scores and elevated plasma CAF22 levels (both p < 0.05). We also found dynamic associations of CAF22 with HGS, gait speed, and SPPB in AD patients taking ACE inhibitors (all p < 0.05). These changes were associated with reduced oxidative stress in AD patients taking ACE inhibitors (p < 0.05). Altogether, ACE inhibitors are associated with higher HGS, preserved physical capacity, and the prevention of NMJ degradation in hypertensive AD patients.

Collagen turnover is associated with cardiovascular autonomic and peripheral neuropathy in type 1 diabetes: novel pathophysiological mechanism?

BackgroundDiabetic cardiovascular autonomic neuropathy (CAN) and distal symmetrical polyneuropathy (DSPN) are severe diabetic complications. Collagen type VI (COL6) and III (COL3) have been associated with nerve function. We investigated if markers of COL6 formation (PRO-C6) and COL3 degradation (C3M) were associated with neuropathy in people with type 1 diabetes (T1D).MethodsIn a cross-sectional study including 300 people with T1D, serum and urine PRO-C6 and C3M were obtained. CAN was assessed by cardiovascular reflex tests: heart rate response to deep breathing (E/I ratio), to standing (30/15 ratio) and to the Valsalva maneuver (VM). Two or three pathological CARTs constituted CAN. DSPN was assessed by biothesiometry. Symmetrical vibration sensation threshold above 25 V constituted DSPN.ResultsParticipants were (mean (SD)) 55.7 (9.3) years, 51% were males, diabetes duration was 40.0 (8.9) years, HbA1c was 63 (11 mmol/mol, (median (IQR)) serum PRO-C6 was 7.8 (6.2;11.0) ng/ml and C3M 8.3 (7.1;10.0) ng/ml. CAN and DSPN were diagnosed in 34% and 43% of participants, respectively. In models adjusted for relevant confounders a doubling of serum PRO-C6, was significantly associated with odds ratio > 2 for CAN and > 1 for DSPN, respectively. Significance was retained after additional adjustments for eGFR only for CAN. Higher serum C3M was associated with presence of CAN, but not after adjustment for eGFR. C3M was not associated with DSPN. Urine PRO-C6 analyses indicated similar associations.ConclusionsResults show previously undescribed associations between markers of collagen turnover and risk of CAN and to a lesser degree DSPN in T1D.

Cartilaginous glycoprotein‑39 as laboratory marker of dynamics of course and effectiveness of treatment in patients with osteoarthritis

Backgrounds. Osteoarthritis (OA) occupies the first rank among diseases of the musculoskeletal system and accounts for 18.4% of the structure of this pathology. Currently, OA is considered as a disease in which there is a violation of the processes of remodeling (degradation and synthesis) of cartilage tissues, subchondral bone, joint capsule, tendon-ligamentous and muscular apparatus. An increased concentration of cartilage glycoprotein-39 (CGP-39) in the circulation is associated with inflammatory diseases and the processes of active tissue restructuring. To date, CGP-39 is a marker of chondrocyte activation and a sign of progressive OA, which determines its clinical significance. Along with this, the role of this biomarker in evaluating the effectiveness of anti-inflammatory therapy is relevant.The purpose. Comparative assessment of the quantitative content of CGP-39 in patients with knee joint OA, depending on the severity of inflammatory changes in the joints, the dynamics of the disease and the effectiveness of therapy.Methods. The study included 36 patients with OA and 30 practically healthy volunteers, identical in gender and age to the examined patients. The mean age of patients was 64 years, the average duration of the disease was 6 years. The diagnosis was determined according to the diagnostic criteria of the American College of Rheumatology (ACR, 1991). Along with the generally accepted clinical, laboratory and instrumental diagnosis of OA, in all patients and in control persons the levels of circulating CGP-39 were measured by enzyme immunoassay (ELISA). All examined patients received Ambene® Bio for 20 days, followed by repeated determination of the level of CGP-39. For statistical processing of the obtained data, we have used the programs Microsoft Excel 2007 and Statistica 10.0. Using the application program KRelRisk 1.1, the relative risk indicator for the studied factor was determined.Results. In the blood of patients with OA, a significant increase in the levels of CGP-39 has been found in comparison with the group of healthy individuals, which indicates increased degradation of articular cartilage in OA. As the severity of knee OA increased, the concentration of CGP-39 in the blood serum significantly raised, including in comparison with the control group. Reliable direct correlations were found between CGP-39 and clinical indices of knee OA severity. The content of CGP-39 in serum in patients with stage III radiological OA was significantly higher than in patients with stage I–II. The highest level of CGP-39 in patients with OA is associated with the presence of synovitis. TThe level of CGP-39 significantly decreased in patients with knee OA after a course of Ambene® Bio therapy, which confirms the participation of CGP-39 in inflammation on the one hand and the possibility of its use as an indicator of the effectiveness of anti-inflammatory therapy on the other hand.Conclusions. CGP-39 as a marker of inflammation and degradation of articular cartilage reflects the severity of the course of OA. The investigation of this biomarker is useful not only for diagnostic purposes, but also to assess the response to anti-inflammatory treatment in patients with knee OA.

Assessment of Biomarker Profile in Patients Post Carotid Angioplasty and Stenting

Introduction. Cardiovascular diseases are predominantly caused by atherosclerosis as a multifactorial chronic condition. Alterations in the hematological system and the blood vessel wall are considered as highly significant for onset and development of cerebrovascular disorders associated with atherosclerosis. Biomarkers as measurable indicators are to verify abnormal activity.&#x0D; Objective: to assess atherogenesis biomarkers in patients after carotid angioplasty and stenting (CAS) as associated with development of cerebrovascular disease.&#x0D; Materials and methods. We evaluated 50 individuals (50% men, 50% women; average age 65.4 6.4 years) with established cerebrovascular disease associated with brain atherosclerosis. All of them had hemodynamically significant abnormalities in the internal carotid artery (ICA) with both symptomatic (stenosis 60% and more) and asymptomatic (stenosis 70% and more) stenoses confirmed by duplex scanning of the brachiocephalic arteries. All patients underwent CAS as indicated. Before and 1 year after the intervention, we performed clinical and neurological examinations, brain magnetic resonance imaging, and laboratory tests of atherogenesis biomarkers.&#x0D; Results. At baseline, all the individuals demonstrated a pro-atherogenic shift in the assessed indicators, predominantly markers of extracellular matrix degradation, inflammation and atherogenesis (including osteoprotegerin and chromogranin А). Additionally, we established a direct correlation between osteoprotegerin levels and the characteristics of mostly hyperechoic atherosclerotic plaques (r = 0.29; p 0.05). A year later, no signs of restenosis were shown in follow-up ultrasound assessment of stented arteries in any patient.&#x0D; In 1 year post CAS, we found significant changes in the levels of osteoprotegerin (decrease to 1.765 pg/mL [1.592; 1.937]; p 0.05) and chromogranin А (elevation to 31.3 g/L [13.9; 90.7]; p 0.05). Re-assessment demonstrated association between changes in the pattern of the nitrogen oxide system, which tends to improve (NO elevation to 38.23 mol/L [32.95; 43.51]; p 0.001), and atheroprotective shift in the morphology of atherosclerotic plaques and biomarker profile.&#x0D; Conclusion. Prospective, 1-year long observation for patients who underwent CAS for symptomatic/asymptomatic hemodynamically significant ICA stenoses revealed favourable atheroprotective shift in both ultrasound and hematological atherogenesis biomarker ratio. This shift contributed to the absence of cerebral atherosclerosis progression during the follow-up. The process may be mediated by chromogranin А and osteoprotegerin, and their further research is needed from perspective of atherogenesis.

433-P: Syndecan-1, a Marker of Endothelial Glycocalyx Degradation, Is Associated with Albuminuria in Type 2 Diabetes

The endothelial glycocalyx (EG) covers the luminal surface of vascular endothelium and is involved in various functions of endothelium including the microvascular permeability. Syndecan (SDC)-1 is a transmembrane heparan sulfate proteoglycan and is a major component of EG. Since the extracellular domain of SDC-1 is shed by inflammatory mediators, increased circulating levels of SDC-1 is considered as a marker of EG degradation. No study has thus far investigated the relationship between EG degradation and albuminuria in type 2 diabetes. This study aimed to investigate the association between EG degradation assessed by serum SDC-1 levels and urinary albumin to creatinine ratio (ACR) in type 2 diabetes. This study enrolled 370 Japanese patients with type 2 diabetes (T2D) and 219 nondiabetic controls (ND). Patients with severe kidney dysfunction whose estimate glomerular filtration rate (eGFR) was less than 30 mL/min/1.73m2 were excluded. T2D patients were divided into normoalbuminuria (A1), microalbuminuria (A2) and macroalbuminuria (A3) by ACR. Median value of serum SDC-1 levels in T2D with A1 stage was 24.5 ng/mL which was higher than that in ND (16.0 ng/mL) (p &amp;lt;0.001). Median values of SDC-1 in T2D with A2 and A3 stages were 29.0 and 38.7 ng/mL, respectively, which were significantly different among albuminuria stages (p &amp;lt;0.001). First, multivariate analysis including T2D patients with A1 stage and ND revealed that the presence of T2D was independently associated with serum SDC-1 level (β = 0.356, p &amp;lt;0.001). Next, multivariate analysis in T2D patients with all albuminuria stages revealed that serum SDC-1 level was independently associated with ACR (β = 0.121, p = 0.012) after adjustment for known other risk factors for albuminuria. In conclusion, serum SDC-1 level is increased in T2D compared to ND and is an independent determinant of ACR in T2D patients. This study suggests a potential involvement of the EG degradation in albuminuria in T2D. Disclosure Y. Kakutani: None. T. Morioka: None. Y. Yamazaki: None. A. Ochi: None. S. Fukumoto: None. T. Shoji: Research Support; Ono Pharmaceutical Co., Ltd., Bayer Inc. Other Relationship; Kowa Company, Ltd. M. Emoto: None.

Efficacy of a proprietary combination of Tamarindus indica seeds and Curcuma longa rhizome extracts in osteoarthritis: a clinical investigation.

NXT15906F6 (TamaFlex™) is a proprietary blend containing standardized Tamarindus indica seeds and Curcuma longa rhizome extracts. Earlier, NXT15906F6 supplementation demonstrated reduced knee joint pain and improved musculoskeletal functions in healthy and knee osteoarthritis (KOA) subjects. The present randomized, double-blind, placebo-controlled study was focused on validating the clinical efficacy of NXT15906F6 in a larger number of subjects with KOA. Male and female subjects (age: 40-70 years; body mass index [BMI]: 20-29 kg/m2] were randomized into three groups receiving placebo (n = 50), NXT15906F6 (n = 50) or a blend of C. longa and Boswellia serrata extracts (CLBS) (n = 50). Subjects consumed 250 mg NXT15906F6, 1,000 mg CLBS or a matched placebo daily after breakfast over a period of 30 consecutive days. The primary efficacy outcome was the improvement in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, and the secondary efficacy measures included various tests on joint pain and musculoskeletal functions and evaluations ofserum high-sensitivity C-reactive protein (hs-CRP) and a cartilage degradation marker, C-terminal telopeptide of type II collagen in urine (uCTX-II). NXT15906F6 significantly (P < 0.001) reduced the WOMAC scores and improved musculoskeletal function scores in the participants as compared with baseline and placebo. NXT15906F6 participants reduced knee pain and improved musculoskeletal functions as early as day 5 of supplementation. In contrast, CLBS supplementation failed to show early efficacies in pain and functional scores, except for 30s-CST and primary knee flexion. The NXT1506F6-supplemented participants significantly reduced serum hs-CRP and uCTX-II levels from baseline and as compared with the placebo. Both supplementations did not alter the subjects' clinical chemistry, hematology, and vital parameters. The anti-inflammatory botanical composition NXT15906F6 supplementation mitigated joint pain and improved musculoskeletal functions and joint motility in KOA subjects. This botanical composition was also well-tolerated by the volunteers.

Are lower levels of apoptosis and autophagy behind adenomyotic lesion survival?

Research questionHow are markers of cell death, invasiveness and progesterone signalling expressed in endometrium and ectopic lesions from adenomyosis patients? DesignFormalin-fixed paraffin-embedded tissue was collected from 15 control and 15 adenomyosis participants . To assess cell survival capacity, caspase 3 and microtubule-associated proteins 1A/1B light chain 3B (LC3B) were immunolabelled as markers of apoptosis and autophagy respectively. Matrix metalloproteinase 9 (MMP9) expression served as a marker of extracellular matrix degradation and invasion activity. Progesterone receptors were immunostained to detect evidence of progesterone resistance. ResultsCaspase 3 expression was significantly lower in the stromal (P = 0.0013) and epithelial (P = 0.0157) compartments of adenomyotic lesions than in healthy endometrial tissue. In the stroma, caspase 3 expression was significantly weaker in lesions than in corresponding eutopic endometrium (P = 0.0006). LC3B immunostaining was significantly decreased in adenomyotic stroma compared with corresponding eutopic endometrium (P = 0.0349). A significantly higher expression of MMP9 was detected in eutopic stroma from adenomyosis patients than in healthy tissue (P = 0.0295). Progesterone receptor immunostaining was found to be significantly weaker in the stroma of endometrium and ectopic lesions from adenomyosis patients than disease-free women (P = 0.0001; P = 0.0021). ConclusionsAdenomyotic lesions show lower levels of apoptosis and autophagy, suggesting that aberrant cell survival may be involved in disease pathogenesis. MMP9 appears to contribute to endometrial invasiveness in adenomyosis, as its expression is more pronounced in endometrium from these women than women without the disease. Evidence of progesterone resistance can be found in endometrium and ectopic lesions from adenomyosis patients, and may drive disease development and account for the failure of certain patients to respond to progestogens.

Development of New Accelerated Aging Test for Comparison of the Quality of Different Insulating Papers Based on Cellulose.

The aim of this study is to propose a test method for the determination of the quality of transformer paper insulation. For this purpose, the oil/cellulose insulation systems were exposed to various accelerated aging tests. The results of the aging experiments of normal Kraft and thermally upgraded papers, two different types of transformer oil (mineral and natural ester), and copper are shown. Aging was carried out in various experiments at 150 °C, 160 °C, 170 °C, and 180 °C with dry (initial values ≤ 0.5%) and moistened cellulose insulation (initial values 3-3.5%). Following insulating oil and paper, degradation markers were measured: the degree of polymerization, tensile strength, furan derivates, methanol/ethanol, acidity, interfacial tension, and dissipation factor. It was found that the aging of cellulose insulation in cycles was 1.5-1.6 times faster in comparison to continuous aging, due to the more pronounced effect of hydrolytic mechanism in cyclic aging owing to the produced and absorbed water. Furthermore, it was observed that the high initial water content in cellulose increases the aging rate two to three times more than in the dry experimental setup. The proposed aging test in cycles can be used to achieve faster aging and to compare the quality of different insulating papers.

A Single Bout of High Heels Dancing Causes an Increase in Circulating Markers of Muscle Tissue Degradation and MMP-3 in Young Healthy Women.

Prolonged wearing of high heels can cause chronic injury and inflammation. Herein, we investigated the presence of muscle injury, inflammation, and neutrophil function in young women after a single bout of stiletto dance class. Sixteen volunteers (23.4 ± 3.8 years; 61.7 ± 8.1 kg; 23.4 ± 2.3 kg/m2; and 27.2 ± 3.8% body fat) participated in the study. The plasma biomarkers matrix metalloproteinase 3 (MMP-3), muscle damage (myoglobin (Mb), total creatine kinase (CK), and lactate dehydrogenase (LDH)), and inflammation (interleukin 8 (IL-8), tumour necrosis factor-alpha (TNF-α), interleukin (IL]-1β, and IL-6) were quantified before and immediately after a single stiletto class (60 min) of moderate intensity. After class, our data showed that the plasma concentration of MMP-3, Mb, and CK increased by 56% (p = 0.04; d = 0.8), 113% (p = 0.007; d = 1.1), and 21% (p < 0.001; d = 0.4), respectively. Reactive oxygen species produced by neutrophils and the plasma concentration of IL-8, TNF-α, IL-1β, and IL-6 were not affected under the study conditions. We concluded that a single bout of stiletto dance class caused muscle damage but did not alter the plasma concentration of proinflammatory cytokines. These findings are crucial in preventing the progress of chronic injuries that are often noted in dancers with synovitis and arthritis.

Targeting of biomolecular condensates to the autophagy pathway.

Biomolecular condensates are membraneless compartments formed by liquid-liquid phase separation. They can phase transit into gel-like and solid states. The amount and state of biomolecular condensates must be tightly regulated to maintain normal cellular function. Autophagy targets biomolecular condensates to the lysosome for degradation or other purposes, which we term biocondensophagy. In biocondensophagy, autophagy receptors recognize biomolecular condensates and target them to the autophagosome, the vesicle carrier of autophagy. Multiple types of autophagy receptors have been identified and they are specifically involved in targeting biomolecular condensates with different phase transition states. The receptors also organize the phase transition of biomolecular condensate to facilitate biocondensophagy. Here, we briefly discuss the latest discoveries regarding how biomolecular condensates are recognized by autophagy receptors.

Assessment of volatile emissions by aging books.

Indoor air quality (IAQ) has attracted a lot of attention due to its complexity and direct effect on human health. Indoor settings in libraries entail various volatile organic compounds (VOCs) linked to the aging and degradation of print material. The effect of the storage environment on paper life expectancy was investigatedby targeting the VOC emissions of old and new books using headspace solid phase micro extraction-gas chromatography/mass spectrometry (HS-SPME-GC/MS) analysis. "Sniffing" of book degradation markers showed both ubiquitously and infrequently occurring VOCs. Old book "degradomics" revealed mostly alcohols (57%) and ethers (12%), whereas new books resulted mainly to ketones (40%) and aldehydes (21%). Chemometric processing of the results with principal component analysis (PCA) corroborated our initial observations and was able to discriminate the books by age into three groups: very old books (from the 1600s to mid-1700), old books (from the 1800s to the early 1900s), and modern books (from the mid-twentieth century onwards) based on their gaseous markers. The measured mean concentrations of selected VOCs (acetic acid, furfural, benzene, and toluene) were below the respective guidelines set for similar places (i.e. museums). The applied non-invasive, green analytical methodology (HS-SPME-GC/MS) can assist librarians, stakeholders, and researchers to evaluate the IAQ, as well as the degree of degradation, and take the appropriate measures for book restoration and monitoring protocols.

Effects of projected end-of-century temperature on the muscle development of neonate epaulette sharks, Hemiscyllium ocellatum

Epaulette sharks (Hemiscyllium ocellatum) inhabit shallow tropical habitats with elevated and fluctuating temperatures. Yet, according to global climate change projections, water temperatures in these habitats will rise beyond current cyclical variability, warranting further studies incorporating chronically elevated temperature exposure in this species. This study examined the differences in skeletal muscle morphological and metabolic properties in neonate epaulette sharks exposed to their current-day ambient (27 °C) or projected end-of-century (31 °C) habitat temperatures throughout embryonic and neonatal development. Metrics of skeletal muscle, such as muscle fiber size and density, nuclear density, and satellite cell density, were used to assess the relative contribution of hypertrophic and hyperplastic growth processes. Capillary density was measured as a proxy for peripheral oxygen supply to muscle tissue. At 31 °C, sharks hatched earlier, but were similar in body size 60 days post-hatch. Muscle fiber size, nuclear density, and capillary density were similar between temperature regimes. However, fiber density was lower, satellite cell density was higher, and fibers associated with satellite cells were smaller in sharks reared at 31 °C. These results suggest that elevated temperature may impair or slow satellite cell fusion to existing fibers and new fiber formation. To assess potential metabolic and developmental consequences of elevated temperatures, oxidative damage (2,4-DNPH, 8-OHdG, 4-HNE), protein degradation (Ubiquitin, LC3B, Hsp70), and muscle differentiation (Myf5, Myogenin) markers were measured. Protein carbonylation was higher at elevated temperatures, suggesting that warmer incubation temperatures at early life stages may result in oxidative damage accrual. However, protein degradation and muscle differentiation markers did not differ. These results suggest that projected end-of-century temperatures may alter muscle growth and metabolism in tropical shark species with potential consequences to shark growth and fitness.

An alternative mechanism for skeletal muscle dysfunction in long-term post-viral lung disease.

Chronic lung disease is often accompanied by disabling extrapulmonary symptoms, notably skeletal muscle dysfunction and atrophy. Moreover, the severity of respiratory symptoms correlates with decreased muscle mass and in turn lowered physical activity and survival rates. Previous models of muscle atrophy in chronic lung disease often modeled chronic obstructive pulmonary disease (COPD) and relied on cigarette smoke exposure and LPS stimulation, but these conditions independently affect skeletal muscle even without accompanying lung disease. Moreover, there is an emerging and pressing need to understand the extrapulmonary manifestations of long-term post-viral lung disease (PVLD) as found in COVID-19. Here, we examine the development of skeletal muscle dysfunction in the setting of chronic pulmonary disease caused by infection due to the natural pathogen Sendai virus using a mouse model of PVLD. We identify a significant decrease in myofiber size when PVLD is maximal at 49 days after infection. We find no change in the relative types of myofibers, but the greatest decrease in fiber size is localized to fast-twitch-type IIB myofibers based on myosin heavy chain immunostaining. Remarkably, all biomarkers of myocyte protein synthesis and degradation (total RNA, ribosomal abundance, and ubiquitin-proteasome expression) were stable throughout the acute infectious illness and chronic post-viral disease process. Together, the results demonstrate a distinct pattern of skeletal muscle dysfunction in a mouse model of long-term PVLD. The findings thereby provide new insights into prolonged limitations in exercise capacity in patients with chronic lung disease after viral infections and perhaps other types of lung injury.NEW & NOTEWORTHY Our study used a mouse model of post-viral lung disease to study the impact of chronic lung disease on skeletal muscle. The model reveals a decrease in myofiber size that is selective for specific types of myofibers and an alternative mechanism for muscle atrophy that might be independent of the usual markers of protein synthesis and degradation. The findings provide a basis for new therapeutic strategies to correct skeletal muscle dysfunction in chronic respiratory disease.

Multi-omic spatial profiling in COVID-19 lung revels temporal evolution of the disease and novel collagen VI biomarker for outcome

Abstract Whilst the peripheral immune response to COVID-19 infection is well characterised, less is known about the tissue response in the lungs of affected patients. We conducted a multi-omic investigation in post-mortem lung tissue from fatal COVID-19 infection comprising bulk Quantseq RNA sequencing, spatial transcriptomic profiling on the Nanostring GeoMX, multiplex immunohistochemistry on the Lunaphore COMET and in-situ transcriptomcics with RNAscope. We found the SARS-CoV-2 virus was progressively cleared in more temporally advanced disease. Furthermore, collagen VI was found to be transcriptionally up-regulated by bulk sequencing and within the interstitium on spatial transcriptomics. These findings were supported by multiplex immunohistochemistry at a proteomic level which showed fibrillar deposition of collagen VI in the interstitum. To validate these findings clinically, we looked at blood markers for collagen VI synthesis and degradation by ELISA in a cohort of severe and mildly infected COVID-19 patients. Blood markers of collagen VI synthesis (PRO-C6) was significantly predictive for mortality in hospitalised (p = 0.0065) and intensive care (p = 0.028) COVID-19 patients. Overall, blood PRO-C6 levels, based on increase interstitial lung deposition, could help identify high-risk of patients enabling better treatment stratification. The study also demonstrates the power of post-mortem investigation and spatial profiling in elucidating clinically relevant insights into complex disease phenomena.