Tissue Degeneration Research Articles

Cellular Senescence: The Driving Force of Musculoskeletal Diseases.

The aging of the world population is closely associated with an increased prevalence of musculoskeletal disorders, such as osteoporosis, sarcopenia, and osteoarthritis, due to common genetic, endocrine, and mechanical risk factors. These conditions are characterized by degeneration of bone, muscle, and cartilage tissue, resulting in an increased risk of fractures and reduced mobility. Importantly, a crucial role in the pathophysiology of these diseases has been proposed for cellular senescence, a state of irreversible cell cycle arrest induced by factors such as DNA damage, telomere shortening, and mitochondrial dysfunction. In addition, senescent cells secrete pro-inflammatory molecules, called senescence-associated secretory phenotype (SASP), which can alter tissue homeostasis and promote disease progression. Undoubtedly, targeting senescent cells and their secretory profiles could promote the development of integrated strategies, including regular exercise and a balanced diet or the use of senolytics and senomorphs, to improve the quality of life of the aging population. Therefore, our review aimed to highlight the role of cellular senescence in age-related musculoskeletal diseases, summarizing the main underlying mechanisms and potential anti-senescence strategies for the treatment of osteoporosis, sarcopenia, and osteoarthritis.

Fibroblast growth factor 2 enhances BMSC stemness through ITGA2-dependent PI3K/AKT pathway activation.

Bone marrow-derived mesenchymal stem cells (BMSC) are promising cellular reservoirs for treating degenerative diseases, tissue injuries, and immune system disorders. However, the stemness of BMSCs tends to decrease during in vitro cultivation, thereby restricting their efficacy in clinical applications. Consequently, investigating strategies that bolster the preservation of BMSC stemness and maximize therapeutic potential is necessary. Transcriptomic and single-cell sequencing methodologies were used to perform a comprehensive examination of BMSCs with the objective of substantiating the pivotal involvement of fibroblast growth factor 2 (FGF2) and integrin alpha 2 (ITGA2) in stemness regulation. To investigate the impact of these genes on the BMSC stemness in vitro, experimental approaches involving loss and gain of function were implemented. These approaches encompassed the modulation of FGF2 and ITGA2 expression levels via small interfering RNA and overexpression plasmids. Furthermore, we examined their influence on the proliferation and differentiation capacities of BMSCs, along with the expression of stemness markers, including octamer-binding transcription factor 4, Nanog homeobox, and sex determining region Y-box 2. Transcriptomic analyzes successfully identified FGF2 and ITGA2 as pivotal genes responsible for regulating the stemness of BMSCs. Subsequent single-cell sequencing revealed that elevated FGF2 and ITGA2 expression levels within specific stem cell subpopulations are closely associated with stemness maintenance. Moreover, additional in vitro experiments have convincingly demonstrated that FGF2 effectively enhances the BMSC stemness by upregulating ITGA2 expression, a process mediated by the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. This conclusion was supported by the observed upregulation of stemness markers following the induction of FGF2 and ITGA2. Moreover, administration of the BEZ235 pathway inhibitor resulted in the repression of stemness transcription factors, suggesting the substantial involvement of the PI3K/AKT pathway in stemness preservation facilitated by FGF2 and ITGA2. This study elucidates the involvement of FGF2 in augmenting BMSC stemness by modulating ITGA2 and activating the PI3K/AKT pathway. These findings offer valuable contributions to stem cell biology and emphasize the potential of manipulating FGF2 and ITGA2 to optimize BMSCs for therapeutic purposes.

Effects of social dominance and acute social stress on morphology of microglia and structural integrity of the medial prefrontal cortex

Chronic stress increases activity of the brain’s innate immune system and impairs function of the medial prefrontal cortex (mPFC). However, whether acute stress triggers similar neuroimmune mechanisms is poorly understood. Across four studies, we used a Syrian hamster model to investigate whether acute stress drives changes in mPFC microglia in a time-, subregion-, and social status-dependent manner. We found that acute social defeat increased expression of ionized calcium binding adapter molecule 1 (Iba1) in the infralimbic (IL) and prelimbic (PL) and altered the morphology Iba1+ cells 1, 2, and 7 days after social defeat. We also investigated whether acute defeat induced tissue degeneration and reductions of synaptic plasticity 2 days post-defeat. We found that while social defeat increased deposition of cellular debris and reduced synaptophysin immunoreactivity in the PL and IL, treatment with minocycline protected against these cellular changes. Finally, we tested whether a reduced conditioned defeat response in dominant compared to subordinate hamsters was associated with changes in microglia reactivity in the IL and PL. We found that while subordinate hamsters and those without an established dominance relationships showed defeat-induced changes in morphology of Iba1+ cells and cellular degeneration, dominant hamsters showed resistance to these effects of social defeat. Taken together, these findings indicate that acute social defeat alters microglial morphology, increases markers of tissue degradation, and impairs structural integrity in the IL and PL, and that experience winning competitive interactions can specifically protect the IL and reduce stress vulnerability.

Engineered hybrid carbon nanohorns-lipid platforms for the delivery of cisplatin to the colorectal cancer

Carbon nanostructures are considered distinctive multi-functional drug delivery platforms for cancer therapy. However, their potential biocompatibility is still a significant challenge and rational design of these carriers is a prospect in the context of efficient cancer therapy. Herein, we report on the synthesis of two bio-inspired carbon nanohorns (CNH) platforms with tumor targeting capabilities for the delivery of cisplatin. Oxidized CNH wrapped with either polyethylene glycol (PEG) and fusogenic lipids (PEG/DSPG CNH-CP) or glutamic acid-cisplatin complex (CNH-GA-CP), revealed nanosized dahlia-like structure approved by dynamic light scattering (DLS) and transmission electron microscopy (TEM) analysis. Further structure features analysis by using RAMAN, FTIR spectroscopy and TGA indicated CNH surface modification. Excitingly, the superior nanofeatures of the CNH platforms was due to the reduced hydrophobic interactions, and thus closely linked to the surface modifications. Both platforms preserved cisplatin toxicity in vitro on C26 cells. The PEGylated nanoplatform demonstrated elongated circulation time compared to the free drug, and showed a site-specific delivery to the tumor site, while reducing the accumulation within kidney. Following 3 i.v. doses at 3 mg/kg of cisplatin, PEGylated CNH significantly delayed tumor growth and improved the life span of C26-bearing BALB/c mice. These notable results were further approved by the histopathological data, demonstrating reduced degeneration, necrosis and inflammation in both kidney and liver tissues following PEGylated nanoplatform administration. In conclusion, our findings suggest that the systemic toxicity of cisplatin including nephrotoxicity can be resolved by delivering this chemotherapeutic through a rationally-fabricated surface-modified carbon nanoplatform to improve the cancer therapy outcome.

IL-32 aggravates metabolic disturbance in human nucleus pulposus cells by activating FAT4-mediated Hippo/YAP signaling

Extracellular matrix (ECM) metabolism disorders in the inflammatory microenvironment play a key role in the pathogenesis of intervertebral disc degeneration (IDD). Interleukin-32 (IL-32) has been reported to be involved in the progression of various inflammatory diseases; however, it remains unclear whether it participates in the matrix metabolism of nucleus pulposus (NP) cells. Therefore, this study aimed to investigate the mechanism of IL-32 on regulating the ECM metabolism in the inflammatory microenvironment. RNA-seq was used to identify aberrantly expressed genes in NP cells in the inflammatory microenvironment. Western blotting, real-time quantitative PCR, immunohistochemistry and immunofluorescence analysis were performed to measure the expression of IL-32 and metabolic markers in human NP tissues or NP cells treated with or without tumor necrosis factor-α (TNF-α). In vivo, an adeno-associated virus overexpressing IL-32 was injected into the caudal intervertebral discs of rats to assess its effect on IDD. Proteins interacting with IL-32 were identified via immunoprecipitation and mass spectrometry. Lentivirus overexpressing IL-32 or knocking down Fat atypical cadherin 4 (FAT4), yes-associated protein (YAP) inhibitor-Verteporfin (VP) were used to treat human NP cells, to explore the pathogenesis of IL-32. Hippo/YAP signaling activity was verified in human NP tissues. IL-32 expression was significantly upregulated in degenerative NP tissues, as indicated in the clinical samples. Furthermore, IL-32 was remarkably overexpressed in TNF-α-induced degenerative NP cells. IL-32 overexpression induced IDD progression in the rat model. Mechanistically, the elevation of IL-32 in the inflammatory microenvironment enhanced its interactions with FAT4 and mammalian sterile 20-like kinase1/2 (MST1/2) proteins, prompting MST1/2 phosphorylation, and activating the Hippo/YAP signaling pathway, causing matrix metabolism disorder in NP cells. Our results suggest that IL-32 mediates matrix metabolism disorders in NP cells in the inflammatory micro-environment via the FAT4/MST/YAP axis, providing a theoretical basis for the precise treatment of IDD.

Stem cells tightly regulate dead cell clearance to maintain tissue fitness

Billions of cells are eliminated daily from our bodies1–4. Although macrophages and dendritic cells are dedicated to migrating and engulfing dying cells and debris, many epithelial and mesenchymal tissue cells can digest nearby apoptotic corpses1–4. How these non-motile, non-professional phagocytes sense and eliminate dying cells while maintaining their normal tissue functions is unclear. Here we explore the mechanisms that underlie their multifunctionality by exploiting the cyclical bouts of tissue regeneration and degeneration during hair cycling. We show that hair follicle stem cells transiently unleash phagocytosis at the correct time and place through local molecular triggers that depend on both lipids released by neighbouring apoptotic corpses and retinoids released by healthy counterparts. We trace the heart of this dual ligand requirement to RARγ–RXRα, whose activation enables tight regulation of apoptotic cell clearance genes and provides an effective, tunable mechanism to offset phagocytic duties against the primary stem cell function of preserving tissue integrity during homeostasis. Finally, we provide functional evidence that hair follicle stem cell-mediated phagocytosis is not simply redundant with professional phagocytes but rather has clear benefits to tissue fitness. Our findings have broad implications for other non-motile tissue stem or progenitor cells that encounter cell death in an immune-privileged niche.

Bisphenol AF Caused Reproductive Toxicity in Rats and Cineole Co-Treatment Exhibited Protective Effect.

Bisphenol AF (BPAF) is increasingly used and now found in products intended for human consumption. The protective effect of 1,8-cineole (CIN) against BPAF-induced reproductive toxicity was investigated. Four groups were created, with each group consisting of eight rats: control, BPAF (200mg/kg), CIN (200mg/kg), and BPAF + CIN groups. The results demonstrated that the BPAF group exhibited a decline in testosterone levels and a decrease in sperm parameters compared with the control. Additionally, higher levels of MDA were observed, along with lower levels of GSH and GPx activity. CAT activity also decreased slightly. Tnf-α, Nf-κB levels were significantly higher, and caspase-3 expression was elevated, while PCNA expression decreased. BPAF significantly increased tissue degeneration compared with the control. However, the BPAF + CIN group showed statistically significant improvements in sperm parameters, except for concentration. They also exhibited an increase in testosterone levels and an improvement in MDA and GSH levels compared with the BPAF group. However, GPx activity partially enhanced. Tnf-α and Nf-κB levels were significantly reduced, and caspase-3 levels declined while PCNA and Bcl-2 levels increased. The Johnsen Testicular Biopsy score showed a substantial increase. Overall, these results suggest that CIN co-treatment in rats enhanced reproductive health and exhibited antioxidant, antiapoptotic, and anti-inflammatory properties against BPAF-induced testicular damage.

Immunomodulatory Behavior of Tendon Magnetic Cell Sheets can be Modulated in Hypoxic Environments under Magnetic Stimulus.

Tissue environments play a crucial role in orchestrating cell behavior, guided by a complex interplay of various factors. Long lasting inflammatory signals compromise tendon homeostasis and promote tissue degeneration, while tissue oxygen levels affect local cells' responses with hypoxic environments influencing apoptosis, inflammatory mediators, and matrix production. Recent works have unveiled the therapeutic potential of pulsed electromagnetic field (PEMF) in modulating inflammatory signals expressed by human tendon cells (hTDCs), and in mitigating the hypoxia-induced effects on the regulation of inflammatory cytokines. Thus, we sought to investigate the role of hypoxic environments, namely, 1 and 2% oxygen tension, in the inflammatory profiles of magnetic cell sheets (magCSs) formed by magnetic nanoparticles internalized in contiguous hTDCs with intact cell-cell junctions and deposited matrix. We also aimed to explore the impact of PEMF over hypoxia-treated magCSs, including IL-1β-primed-magCSs, with the objective of harnessing magnetic stimulation to guide abnormal inflammatory cell responses toward efficient treatments supporting tendon regenerative potential. Our findings revealed that low oxygen tensions amplified the expression of hypoxia-associated genes and of inflammatory markers in IL-1β-primed-magCSs with an involvement of the NF-κB signaling pathway. Encouragingly, when PEMF was applied to IL-1β-primed-magCSs under hypoxic conditions, it successfully modulated inflammatory cues by favoring IL-10 and IL-4, via the NF-κB pathway. These results signify the remarkable potential of PEMF in driving proregenerative strategies and opens up new approaches in tendon therapies, highlighting the transformative impact of immunomodulatory magnetic cell sheets.

Sonography of muscles : Rheumatology-Neurology-Geriatrics-Sports medicine-Orthopedics

Muscle sonography is used in rheumatology, neurology, geriatrics, sports medicine and orthopedics. Muscular atrophy with fatty and connective tissue degeneration can be visualized and must be interpreted in conjunction with the sonographic findings of the supplying nerves. Sonography is becoming increasingly more important for the early diagnosis of sarcopenia in rheumatology, geriatrics and osteology. Even if its significance has not yet been conclusively clarified, many publications confirm the high reliability of the method. Sonography can ideally be used in addition to magnetic resonance imaging (MRI) in the diagnostics of myositis as it can speed up the diagnosis, muscle groups that were not imaged by MRI can also be assessed sonographically and all muscle groups can be examined during the course of the procedure. Sonography also helps to make aquick and uncomplicated diagnosis of many sports injuries in addition to MRI and is therefore the basis for atargeted therapeutic approach.

Biomimetic Proteoglycans Strengthen the Pericellular Matrix of Normal and Osteoarthritic Human Cartilage.

In osteoarthritis (OA), degradation of cartilage pericellular matrix (PCM), the proteoglycan-rich immediate cell microniche, is a leading event of disease initiation. This study demonstrated that biomimetic proteoglycans (BPGs) can diffuse into human cartilage from both normal and osteoarthritic donors and are preferentially localized within the PCM. Applying immunofluorescence (IF)-guided AFM nanomechanical mapping, we show that this localization of BPGs increases the PCM micromodulus of both normal and OA specimens. These results illustrate the capability of BPGs to integrate with degenerative tissues and support the translational potential of BPGs for treating human OA and other diseases associated with proteoglycan degradation.

Gut microbiota and rheumatic diseases: new insights into pathogenesis

Background: Rheumatic diseases are a group of disorders characterised by a loss of immune tolerance, which leads to chronic inflammation, degeneration or metabolic abnormalities in various organs or tissues. Despite the lack of clarity surrounding the causes of these diseases, both environmental and genetic factors play an important role. Recent research indicates that alterations in the composition of the gut microbiota, known as gut dysbiosis, may contribute to the development of a number of rheumatic diseases, including rheumatoid arthritis, systemic lupus, ankylosing spondylitis, systemic scleroderma and Sjögren's syndrome. The gut microbiota influences the balance between pro- and anti-inflammatory immune responses, which may have important implications for the pathogenesis of these diseases. Furthermore, studies have indicated that the composition of the gut microbiota may be associated with the response to therapies used to treat rheumatic diseases, thus opening up new avenues for the development of microbiota-targeted treatments for these conditions. Aim of the study: The objective of this review is to investigate the impact of the gut microbiota on the pathogenesis of rheumatic diseases and to evaluate potential therapies targeting the manipulation of the gut microbiota. Material and methods: The present study is based on literature available in scientific databases from 2019-2024, such as PubMed, Corchane Library and Google Scholar.Results and conclusions: A growing body of evidence suggests a potential link between the gut microbiota and rheumatic diseases. Patients often exhibit a reduced ratio of Firmicutes to Bacteroidetes and abnormal numbers of Bacteroides. Molecular mimicry and a potential association with short-chain fatty acids have also been observed. Further human studies are needed to more fully understand the role of the gut microbiota and potential therapeutic interventions.

Dysregulated lipid metabolism and intervertebral disc degeneration: the important role of ox-LDL/LOX-1 in endplate chondrocyte senescence and calcification

BackgroundLipid metabolism disorders are associated with degeneration of multiple tissues and organs, but the mechanism of crosstalk between lipid metabolism disorder and intervertebral disc degeneration (IDD) has not been fully elucidated. In this study we aim to investigate the regulatory mechanism of abnormal signal of lipid metabolism disorder on intervertebral disc endplate chondrocyte (EPC) senescence and calcification. MethodsHuman intervertebral disc cartilage endplate tissue, cell model and rat hyperlipemia model were performed in this study. Histology and immunohistochemistry were used to human EPC tissue detection. TMT-labelled quantitative proteomics was used to detect differential proteins, and MRI, micro-CT, safranin green staining and immunofluorescence were performed to observe the morphology and degeneration of rat tail intervertebral discs. Flow cytometry, senescence-associated β-galactosidase staining, alizarin red staining, alkaline phosphatase staining, DCFH-DA fluorescent probe, and western blot were performed to detect the expression of EPC cell senescence, senescence-associated secretory phenotype, calcification-related proteins and the activation of cell senescence-related signaling pathways. ResultsOur study found that the highly expressed oxidized low-density lipoprotein (ox-LDL) and Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) in human degenerative EPC was associated with hyperlipidemia (HLP). TMT-labelled quantitative proteomics revealed enriched pathways such as cell cycle regulation, endochondral bone morphogenesis and inflammation. The rat model revealed that HLP could induce ox-LDL, LOX-1, senescence and calcification markers high expression in EPC. Moreover, we demonstrated that ox-LDL-induced EPCs senescence and calcification were dependent on the LOX-1 receptor, and the ROS/P38-MAPK/NF-κB signaling pathway was implicated in the regulation of senescence induced by ox-LDL/LOX-1 in cell model.ConclusionsSo our study revealed that ox-LDL/LOX-1-induced EPCs senescence and calcification through ROS/P38-MAPK/NF-κB signaling pathway, providing information on understanding the link between lipid metabolism disorders and IDD.

Numerical modelling of multiple sclerosis: A tissue-scale model of brain lesions

Multiple Sclerosis (MS) is an autoimmune condition leading to the degeneration of brain tissue, occurring when the immune system attacks the myelin sheath surrounding axons of white brain matter thereby disrupting brain signals. This study aimed to evaluate how MS lesions alter stress distribution through grey and white brain matter with lesions (active, chronic, and inactive). A linear viscoelastic model represents the tissue-scale dynamic deformation and time dependency of brain tissue. A Prony series expansion was used to model viscous effects including stress relaxation. An elastic modulus, within the viscoelastic model, was either reduced by 11 % for active lesions, or increased by 35 % increase for inactive lesions. These material properties were then implemented to model healthy tissue, active, chronically inflamed, and inactive lesions. Finite element analysis enabled stress evaluation in response to a peak cyclic displacement of 0.5 mm (1 % strain) with the healthy model acting as a control model. Chronic lesions had the largest effect on stress induced, in terms of high (171 Pa) and low stress (108 Pa). Inactive lesions induced an increase in stress of 11 Pa with areas of low stress (105 Pa). Active lesions caused the least deviation in peak induced stress (7 Pa). In conclusion, a hierarchy in stress induced across the lesion types has been found, from highest to lowest: chronic, inactive and active, with potential implications for lesion progression. In conclusion, MS lesions within brain tissue should model lesions, avoid assuming homogeneity during degeneration, and should distinguish between active and passive lesions.

Arsenic-induced transition of thymic inflammation-to-fibrosis involves Stat3-Twist1 interaction: Melatonin to the rescue.

Groundwater arsenic is a notorious toxicant and exposure to environmentally relevant concentrations persists as a healthcare burden across the world. Arsenic has been reported to jeopardize the normal functioning of the immune system, but there are still gaps in the understanding of thymic T cell biology. Immunotoxic influence of arsenic in thymic integrity demands a potent restorative molecule. The objectives of this study were to examine key signaling cross-talks associated with arsenic-induced immune alterations in the thymus and propose melatonin as a potential candidate against immunological complications arising from arsenic exposure. Swiss albino mice were exposed to sodium arsenite (0.05 mg/L; in drinking water) and melatonin (IP:10 mg/kg BW) for 28 days. Melatonin successfully protected thymus from arsenic-mediated tissue degeneration and maintained immune homeostasis including T cell maturation and proliferation by mitigating oxidative stress through Nrf2 upregulation. Additionally, melatonin exerted ameliorative effect against arsenic-induced apoptosis and inflammation by inhibiting p53-mediated mitochondrial cell death pathway and NF-κB-p65/STAT3-mediated proinflammatory pathway, respectively. For the first time, we showed that arsenic-induced profibrotic changes were inhibited by melatonin through targeting of inflammation-associated EMT. Our findings clearly demonstrate that melatonin can be a viable and promising candidate in combating arsenic-induced immune toxicity with no collateral damage, making it an important research target.

Correlation between the Long Head of the Biceps Microscopic Degeneration and Extent of Apoptotic Process.

Objectives: The purpose of this study was to determine the correlation between microscopic degeneration in the long head of the biceps tendon (LHBT) and the apoptotic process. Methods: This study included 26 consecutive patients who had undergone arthroscopic biceps tenodesis or tenotomy for symptomatic LHBT with or without concomitant rotator cuff tears (RCTs). Histological examination of the specimens under a light microscope was conducted after staining with hematoxylin, eosin, and the Alcian blue. Histopathological changes were assessed using the original Bonar score and the modified Bonar score and then correlated with the expression of the subsequent apoptosis markers: activated caspase-3 (casp3), tumor protein p53 (p53), and B-cell lymphoma 2 (BCL-2). Results: The mean original Bonar score was 8.65 (range 5-11), while the modified Bonar score was 7.61. There was no correlation between the original Bonar score and the age of the patients, but a positive correlation was found between the modified Bonar score and the age of the patients (p = 0.0022). There was no correlation between the age of patients and the expression indexes of BCL-2 and casp3. However, the expression of the p53 index showed a positive correlation with patient aging (p = 0.0441). Furthermore, there was no correlation observed between the expression of apoptotic indexes and both the original and modified Bonar scale. Conclusions: In LHB tendinopathy, the expression of apoptosis does not seem to directly correlate with the extent of degeneration, particularly in the late stages of tendinopathy. However, the transformations observed in collagen and ground substance were significantly associated with age, as well as tendinous tissue degeneration quantified according to modified Bonar score. The age of patients was also linked with the expression of the p53 index, as an increased apoptosis in the studied population.

Relationship Between Oxidative Stress in the Rotator Cuff and Transcutaneous Advanced Glycation End-Products Measurement in Diabetic Rats.

Diabetes mellitus increases oxidative stress due to hyperglycemia, resulting in the degeneration of rotator cuff tissue. Currently, there is no established method to non-invasively assess the extent of this oxidative stress. To address this, we aimed to investigate the relationship between the accumulation of advanced glycation end-products (AGEs), a marker of oxidative stress, and transcutaneous autofluorescence intensity in rotator cuff tissue harvested from diabetic rats. Ten control Sprague-Dawley (SD) rats and streptozotocin-induced diabetic rats (n = 10 per group) were used. The rats were euthanized eight and 16 weeks after the induction of diabetes, and rotator cuff attachment sites were collected and histologically analyzed. Prior to euthanasia, autofluorescence intensity was measured transcutaneously in the rotator cuff area. The expressions of AGEs and type I collagen were evaluated immunohistochemically with specific antibodies and the stained areas were quantified. All data were statistically analyzed using the Mann-Whitney U test. Correlation analysis was performed for skin autofluorescence intensity and the percentage of AGEs staining area using Spearman's rank correlation coefficient. The immunohistochemical expression of AGEs at the rotator cuff attachment sites and transcutaneous AGEs measurements were significantly higher in diabetic rats than in the control group at 16 weeks. There was no significant difference in the level of type 1 collagen between the two groups. This study reveals that the accumulation of AGEs in rotator cuff tissue increases due to prolonged hyperglycemia in diabetes. In addition, transcutaneous skin fluorescence intensity may be related to histological oxidative stress at the rotator cuff.

Meniscus Ripstop Stitches: A Useful Technique for Arthroscopic Repair of Challenging Radial Tears of the Meniscus

Radial meniscal tears can be challenging to address and require advanced arthroscopic techniques for satisfactory repair. When radial tears occur in older patients, the surgeon often encounters suboptimal tissue integrity that presents its own challenges. Incorporating ripstop sutures in tie-grip repair constructs for radial tears has been documented in the literature with favorable biomechanical properties. This Technical Note and accompanying video present a reproducible method for incorporating tie-grip and mobile ripstop stitches to fortify traditional meniscal repair configurations for radial tears. This technique augments the biomechanical strength of repair and may prove useful in poor tissue quality and areas of small focal deficiency, especially in scenarios with repairable but degenerative meniscal tissue. This is particularly relevant considering many repairs fail due to pull-through of sutures within the meniscal tissue.

Preoperative Increases in T2-Weighted Fat-Suppressed Magnetic Resonance Imaging Signal Intensities Associated With Advanced Tissue Degeneration and Mitochondrial Dysfunction in Rotator Cuff Tears

PurposeThe purpose of this study was to investigate the relationship between magnetic resonance imaging (MRI) signal intensities and mitochondrial function in patients undergoing arthroscopic rotator cuff repair, assessed through histological and genetic profiling of tendon tissue. MethodsThis study, conducted between April 2022 and January 2023, included 20 patients undergoing rotator cuff repair for atraumatic/degenerative tears. Rotator cuff tendon edge samples were obtained during arthroscopic rotator cuff repair. Patients were classified based on signal intensity from preoperative T2-weighted fat suppressed MRI. Specifically, they were categorized as having either high or low signal intensity at the rotator cuff tendon edge, with the deltoid muscle serving as a reference. Comparative analyses specifically compared the histological features and genetic profiles of the tendon tissue at the rotator cuff tendon edge. Histological evaluation of harvested tendon specimens during arthroscopic rotator cuff repair employed the modified Bonar score. Real-time polymerase chain reaction was used to assess expression of various mitochondrial and apoptosis-related genes. The mitochondrial morphology of the rotator cuff torn site was examined using electron microscopy. ResultsThe higher signal intensity group showed significantly higher modified Bonar scores (p=0.0068), decreased mitochondrial gene expression, increased TUNEL-positive cells (p=0.032), lower SOD activity (p=0.011), reduced ATP5A (p=0.031), and increased cleaved caspase-9 activity (p=0.026) when compared to the lower signal intensity group. Electron microscopy revealed fewer mitochondrial cristae in the higher signal intensity group. ConclusionOur results suggest correlations between high MRI signal intensities and the presence of degeneration, mitochondrial dysfunction, and increased apoptosis in rotator cuff tissues. This underscores the utility of MRI signal intensity as an indicator of tissue condition. Clinical RelevanceBuilding on the established premise that elevated preoperative MRI signal intensities may indicate higher rates of postoperative rotator cuff re-tears, the current study substantiates these findings from a mitochondrial function perspective.

Degenerative and regenerative peripheral processes are associated with persistent painful chemotherapy-induced neuropathies in males and females

This study investigated the time course of gene expression changes during the progression of persistent painful neuropathy caused by paclitaxel (PTX) in male and female mouse hindpaws and dorsal root ganglia (DRG). Bulk RNA-seq was used to examine these gene expression changes at 1, 16, and 31 days post-last PTX. At these time points, differentially expressed genes (DEGs) were predominantly related to the reduction or increase in epithelial, skin, bone, and muscle development and to angiogenesis, myelination, axonogenesis, and neurogenesis. These processes are accompanied by the regulation of DEGs related to the cytoskeleton, extracellular matrix organization, and cellular energy production. This gene plasticity during the progression of persistent painful neuropathy could be interpreted as a biological process linked to tissue regeneration/degeneration. In contrast, gene plasticity related to immune processes was minimal at 1–31 days after PTX. It was also noted that despite similarities in biological processes and pain chronicity between males and females, specific DEGs differed dramatically according to sex. The main conclusions of this study are that gene expression plasticity in hindpaw and DRG during PTX neuropathy progression similar to tissue regeneration and degeneration, minimally affects immune system processes and is heavily sex-dependent at the individual gene level.

Periprosthetic joint infection after total knee arthroplasty. Lessons learned: a case report and literature review

Introduction. The increasing proportion of the aging population and overweight people with various joint problems leads to an increased demand for joint replacements. As the number of joint arthroplasty surgeries continues to rise, the persistent incidence of periprosthetic joint infections highlights the need for a comprehensive and evolving approach. In addition to the preoperative period, it is also necessary to consider the course of the intraoperative, and to a greater extent the postoperative period, when the development of periprosthetic infection occurs. This case is indicative of the fact that underestimation of the importance of the postoperative period and control of risk factors can lead to the recurrence of infection. This negatively affects the economy due to an increase in the number of disabilities.Case presentation. A 60-year-old female patient was diagnosed with a periprosthetic joint infection following total knee arthroplasty. The patient's premorbid background was aggravated by the presence of type 2 diabetes mellitus, arterial hypertension, secondary cardiomyopathy, and chronic iron-deficiency anemia. Single stage revision of knee arthroplasty, removal of prosthetic components, excision of degenerative tissue, prolonged antibiotic therapy as well as rehabilitation were ineffective, and the pain increased. Therefore, the patient is admitted for the two-stage revision surgery, removal of the endoprosthesis, and installation of a nonarticulating cement spacer of the left knee joint.Conclusion. Through a relevant literature search, we believe that uncorrected chronic iron-deficiency anemia in combination with uncontrolled diabetes mellitus, both in the preoperative and postoperative period for joint replacement, may increase the risk of the development of periprosthetic infection. Moreover, focusing patients' attention on the importance of the postoperative period and strict monitoring of health indicators will help reduce the likelihood of re-prosthetics.