Extensive Muscle Research Articles

Comparative Transcriptome Analysis of Bovine, Porcine, and Sheep Muscle Using Interpretable Machine Learning Models.

The growth and development of muscle tissue play a pivotal role in the economic value and quality of meat in agricultural animals, garnering close attention from breeders and researchers. The quality and palatability of muscle tissue directly determine the market competitiveness of meat products and the satisfaction of consumers. Therefore, a profound understanding and management of muscle growth is essential for enhancing the overall economic efficiency and product quality of the meat industry. Despite this, systematic research on muscle development-related genes across different species still needs to be improved. This study addresses this gap through extensive cross-species muscle transcriptome analysis, combined with interpretable machine learning models. Utilizing a comprehensive dataset of 275 publicly available transcriptomes derived from porcine, bovine, and ovine muscle tissues, encompassing samples from ten distinct muscle types such as the semimembranosus and longissimus dorsi, this study analyzes 113 porcine (n = 113), 94 bovine (n = 94), and 68 ovine (n = 68) specimens. We employed nine machine learning models, such as Support Vector Classifier (SVC) and Support Vector Machine (SVM). Applying the SHapley Additive exPlanations (SHAP) method, we analyzed the muscle transcriptome data of cattle, pigs, and sheep. The optimal model, adaptive boosting (AdaBoost), identified key genes potentially influencing muscle growth and development across the three species, termed SHAP genes. Among these, 41 genes (including NANOG, ADAMTS8, LHX3, and TLR9) were consistently expressed in all three species, designated as homologous genes. Specific candidate genes for cattle included SLC47A1, IGSF1, IRF4, EIF3F, CGAS, ZSWIM9, RROB1, and ABHD18; for pigs, DRP2 and COL12A1; and for sheep, only COL10A1. Through the analysis of SHAP genes utilizing Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, relevant pathways such as ether lipid metabolism, cortisol synthesis and secretion, and calcium signaling pathways have been identified, revealing their pivotal roles in muscle growth and development.

Assessment of skeletal muscle dynamics and milk production across a 300-day lactation in multiparous dairy cattle

The objective of this study was to evaluate changes in longissimus dorsi muscle depth (LDD) across lactation (0 to 300 DIM) and identify the impact of low versus high muscle reserves immediately after parturition on body weight and body reserve changes as well as production variables across a 300-d lactation. Forty multiparous cows were classified as high muscle (HM; LDD > 5.0 cm; n = 18) or low muscle (LM; LDD ≤ 5.0 cm; n = 22) based on LDD measurements collected within 24 h of parturition. Body weights (BW) and ultrasound scans to assess LDD and back fat depth (BFD) were collected monthly from parturition until 300 DIM. Ultrasound scans captured and measured using available software. Blood samples were taken at 7, 150 and 300 DIM, and plasma was analyzed for markers of metabolic status by measuring insulin, nonesterified fatty acids (NEFA), creatinine, and 3-methylhistidine (3-MH). Milk yield was recorded daily and milk components were analyzed monthly. Data analysis was performed and the statistical models included the fixed effect of muscle group, time, their interaction, and the random effect of cow nested within muscle group with repeated measures using a first-order autoregressive covariance structure. Muscle group was not related with BW or BFD for any of the time points measured. Cows lost BW from 0 to 60 DIM and gained weight from 60 to 300 DIM. Similarly, BFD decreased between 0 to 90 DIM and increased BFD after 90 DIM until 300 DIM. A muscle group by time interaction was observed for LDD. The HM cows had more muscle at 0 DIM, indicative of treatment assignment (1.34 cm more), and 300 DIM (0.78 cm more) and tended to have more muscle at 60 DIM (0.66 cm more) compared with LM. After 240 DIM, both muscle groups began net accretion of muscle reserves until 300 DIM. No differences were observed for blood metabolites measured based on muscle group. However, there were significant time effects for creatinine, 3-MH, and NEFA concentrations, which reflected the observed changes in BFD and LDD measured in ultrasound scans. For statistical analysis of daily milk production, observations were grouped into 3 stages of lactation, early (0-60 DIM), mid (60-240 DIM), and late lactation (240-300 DIM). There was a muscle group by stage of lactation interaction, where in early and mid-lactation, HM cows produced, on average, 1.9 kg more milk/d; however, in late lactation, LM cows produced 1.8 kg more milk/d. Our results indicate that muscle reserves are depleted in early lactation, and accreted in late lactation, whereas BW and BFD started to increase by 90 DIM. Data also supports that cows with more extensive muscle depletion in early lactation had greater milk production, however, substantial muscle accretion in late lactation may result in reduced milk production.

Development of silk microfiber-reinforced bioink for muscle tissue engineering and in situ printing by a handheld 3D printer

Volumetric muscle loss (VML) presents a significant challenge in tissue engineering due to the irreparable nature of extensive muscle injuries. In this study, we propose a novel approach for VML treatment using a bioink composed of silk microfiber-reinforced silk fibroin (SF) hydrogel. The engineered scaffolds are predesigned to provide structural support and fiber alignment to promote tissue regeneration in situ. We also validated our custom-made handheld 3D printer performance and showcased its potential applications for in situ printing using robotics. The fiber contents of SF and gelatin ink were varied from 1 to 5 %. Silk fibroin microfibers reinforced ink offered increased viscosity of the gel, which enhanced the shape fidelity and mechanical strength of the bulk scaffold. The fiber-reinforced bioink also demonstrated better cell-biomaterial interaction upon printing. The handheld 3D printer enabled the precise and on-demand fabrication of scaffolds directly at the defect site, for personalized and minimally invasive treatment. This innovative approach holds promise for addressing the challenges associated with VML treatment and advancing the field of regenerative medicine.

Bioreactors: A Regenerative Approach to Skeletal Muscle Engineering for Repair and Replacement

Engineering skeletal muscle tissue is crucial for the repair and replacement of damaged or dysfunctional muscle. Despite numerous studies emphasizing the significance of skeletal muscle engineering, challenges persist in effectively replacing or repairing large muscle sections in vivo. Bioreactors that facilitate the rapid expansion of muscle precursor cells present a promising solution for addressing extensive muscle loss. Specifically, bioreactors that mimic the native microenvironment of muscle tissue can induce biomimetic stimuli, selectively promoting the expansion of muscle precursors with optimal myo‐regenerative potential. In this review, the advancements made in utilizing bioreactors to enhance the myo‐regenerative phenotype of cells for skeletal muscle engineering are highlighted.

Preparation and Performance of a Novel Polyurethane Microporous Film on Polypropylene Medical Mesh Surface

This study aims to develop a medical patch surface material featuring a microporous polyurethane (PU) membrane and to assess the material's properties and biological performance. The goal is to enhance the clinical applicability of pelvic floor repair patch materials. PU films with a microporous surface were prepared using PU prepolymer foaming technology. The films were produced by optimizing the PU prepolymer isocyanate index (R value) and the relative humidity (RH) of the foaming environment. The surface morphology of the PU microporous films was observed by scanning electron microscopy, and the chemical properties of the PU microporous films, including hydrophilicity, were analyzed using infrared spectroscopy, Raman spectroscopy, and water contact angle measurements. In vitro evaluations included testing the effects of PU microporous film extracts on the proliferation of L929 mouse fibroblasts and observing the adhesion and morphology of these fibroblasts. Additionally, the effect of the PU microporous films on RAW264.7 mouse macrophages was studied. Immune response and tissue regeneration were assessed in vivo using Sprague Dawley (SD) rats. The PU films exhibited a well-defined and uniform microporous structure when the R value of PU prepolymer=1.5 and the foaming environment RH=70%. The chemical structure of the PU microporous films was not significantly altered compared to the PU films, with a significantly lower water contact angle ([55.7±1.5]° ) compared to PU films ([69.5±1.7]° ) and polypropylene (PP) ([ 104.3±2.5]°), indicating superior hydrophilicity. The extracts from PU microporous films demonstrated good in vitro biocompatibility, promoting the proliferation of L929 mouse fibroblasts. The surface morphology of the PU microporous films facilitated fibroblast adhesion and spreading. The films also inhibited the secretion of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β by RAW264.7 macrophages while enhancing IL-10 and IL-4 secretion. Compared to 24 hours, after 72 hours of culture, the expression levels of TNF-α and IL-1β were reduced in both the PU film and PU microporous film groups and were significantly lower than those in the PP film group (P<0.05), with the most notable decreases observed in the PU microporous film group. IL-10 and IL-4 levels increased significantly in the PU microporous film group, surpassing those in the PP film group (P<0.01), with the most pronounced increase in IL-4. The PU microporous film induced mild inflammation with no significant fibrous capsule formation in vivo. After 60 days of implantation, the film partially degraded, showing extensive collagen fiber growth and muscle formation in its central region. The PU microporous film exhibits good hydrophilicity and biocompatibility. Its surface morphology enhances cell adhesion, regulates the function of RAW264.7 macrophages, and promotes tissue repair, offering new insights for the design of pelvic floor repair and reconstruction patch materials.

NOTCH3 and Pulmonary Arterial Hypertension.

NOTCH3 receptor signaling has been linked to the regulation of smooth muscle cell proliferation and the maintenance of smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension (World Health Organization Group 1 idiopathic disease: PAH) is a fatal disease characterized clinically by elevated pulmonary vascular resistance caused by extensive vascular smooth muscle cell proliferation, perivascular inflammation, and asymmetric neointimal hyperplasia in precapillary pulmonary arteries. In this review, a detailed overview of the specific role of NOTCH3 signaling in PAH, including its mechanisms of activation by a select ligand, downstream signaling effectors, and physiologic effects within the pulmonary vascular tree, is provided. Animal models showing the importance of the NOTCH3 pathway in clinical PAH will be discussed. New drugs and biologics that inhibit NOTCH3 signaling and reverse this deadly disease are highlighted.

The Use of Titanium Pins for the Management and Fixation of Free Gingival Grafts and Apically Repositioned Flaps During Vestibuloplasty. A Technique Report.

The presence of adequate keratinized mucosa (KM) around dental implants and natural dentition is pivotal for the long-term success of dental restorations. Despite various techniques to augment KM, challenges persist in achieving stable, keratinized, and adherent mucosa, especially in the context of significant muscle pull or compromised tissue conditions. This study introduces a novel application of titanium pins for the fixation of free gingival grafts (FGG) and apically repositioned flaps (APF) during vestibuloplasty, aiming to overcome important limitations associated with traditional suturing methods and shorten the treatment time and patient morbidity. Three patients with insufficient KM width, presenting discomfort during oral hygiene and inflammation around implant restorations and natural teeth, underwent soft tissue augmentation using titanium pins traditionally used in guided bone regeneration (GBR) for the stabilization of FGGs and APFs. This method ensures intimate contact between the graft and the periosteum, facilitating proper graft perfusion and revascularization, minimizing shrinkage and the risk for necrosis of the graft. Postoperative follow-up revealed successful integration of the grafts, with minimal shrinkage and increased width and depth of KM. The use of titanium pins allowed for reliable fixation in challenging surgical sites, where traditional suturing methods were impractical due to the presence of extensive muscle pull and an unstable recipient bed. The application of titanium pins for the fixation of FGGs and APFs during vestibuloplasty provides a promising alternative to traditional suturing techniques, particularly in complex cases where the recipient bed is suboptimal for suturing. This method simplifies and shortens the procedure, offering a predictable outcome with increased mechanical stability and minimal shrinkage of the graft. Randomized clinical trials are recommended to further evaluate the efficacy of this technique.

Iatrogenic Full-length Rupture of Posterior Trachea: A Multidsciplinary Management

Iatrogenic trachealis muscle rupture (ITR) following elective intubation is a potentially fatal complication with a low incidence of 0.05-0.37%. Tears involving the whole length has not been reported. We report a case of a 26-year-old lady with seropositive rheumatoid arthritis who underwent total thyroidectomy for Hashimoto Thyroiditis. Intraoperatively, a complete linear trachealis muscle rupture from the carina to the first tracheal ring was diagnosed by the Otorhinolaryngology (ORL) team by tracheoscopy through the endotracheal tube (ETT). Unlike the common presentation of subcutaneous emphysema or pneumomediastinum, the surgeon noticed the ETT cuff in the left operative field. Initial repair of the lateral defect was performed immediately by opposing the sternocleidomastoid muscle to the adjacent infrahyoid muscles. However, serial computed tomography and flexible tracheoscopy showed complete tear of the trachealis muscle with presence of pneumomediastinum and dynamic changes of the injury. We illustrate a concerted effort of multidisciplinary teams of ORL, Cardiothoracic Surgery, Intensivist, Anaesthetist, Radiologist and Speech Therapist in the steps of management which involved series of tracheoscopy and imaging prior to extubation. In view of extensive trachealis muscle tear with hemodynamically stable patient, conservative management was opted for this patient as it outweighs the benefit of the surgery. We include the outpatient management until the patient’s trachea fully healed 6 months after the injury. The management is compared to the management review in the literature. This case has taught multiple new important lessons in the management of challenging tracheal rupture in a patient.International Journal of Human and Health Sciences Supplementary Issue 01: 2024 Page: S54

Gellan gum-gelatin based cardiac models support formation of cellular networks and functional cardiomyocytes

Cardiovascular diseases remain as the most common cause of death worldwide. To reveal the underlying mechanisms in varying cardiovascular diseases, in vitro models with cells and supportive biomaterial can be designed to recapitulate the essential components of human heart. In this study, we analyzed whether 3D co-culture of cardiomyocytes (CM) with vascular network and with adipose tissue-derived mesenchymal stem/stromal cells (ASC) can support CM functionality. CM were cultured with either endothelial cells (EC) and ASC or with only ASC in hydrazide-modified gelatin and oxidized gellan gum hybrid hydrogel to form cardiovascular multiculture and myocardial co-culture, respectively. We studied functional characteristics of CM in two different cellular set-ups and analyzed vascular network formation, cellular morphology and orientation. The results showed that gellan gum-gelatin hydrogel supports formation of two different cellular networks and functional CM. We detected formation of a modest vascular network in cardiovascular multiculture and extensive ASC-derived alpha smooth muscle actin -positive cellular network in multi- and co-culture. iPSC-CM showed elongated morphology, partly aligned orientation with the formed networks and presented normal calcium transients, beating rates, and contraction and relaxation behavior in both setups. These 3D cardiac models provide promising platforms to study (patho) physiological mechanisms of cardiovascular diseases.

Tongue exercise-induced plasticity in upper airway EMG activity in a model of hypoglossal motor neuron loss

Motor neuron diseases (MNDs) are a group of neuromuscular disorders in which motor neurons (MNs) required for activities of daily living are lost. Patients with MNDs often develop swallowing and breathing dysfunction due to pathology of the hypoglossal (XII) axis ( e.g., XII lower motor neurons, LMNs). These co-dependent, vital functions require reciprocal roles of the tongue during swallowing, and impaired control and coordination of these opposing behaviors can lead to aspiration pneumonia and respiratory failure. Due to a lack of research, available treatments for patients with MNDs are largely palliative, and there is a critical need for therapies targeting the preservation of upper airway function and coordination. The extensive tongue muscle weakness in patients with MNDs suggests a potential role for therapeutic exercise, but suffcient evidence is lacking to conclude if tongue exercise is beneficial or harmful. A barrier in studying the impact of XII LMN degeneration and developing therapies to improve swallowing and breathing function/coordination has been the lack of an appropriate model. We therefore developed a novel rodent model of XII LMN loss using intralingual injections of cholera toxin B conjugated to saporin (CTB-SAP), which has tongue motility and swallowing deficits that are mitigated by a high-repetition/low resistance tongue exercise paradigm for muscle growth. Here, we simultaneously studied upper airway (geniohyoid) and diaphragm EMG activity with swallowing ( via videofluoroscopy swallow studies; VFSS) and breathing ( via plethysmography) to discern whether CTB-SAP induced XII LMN loss results in upper airway deficits and discoordination of swallowing and breathing functions. We hypothesized that geniohyoid (not diaphragm) EMG activity would be decreased and swallow-breathing coordination would be altered in unanesthetized and spontaneously breathing CTB-SAP rats vs. controls, and that tongue exercise would mitigate these deficits. Using custom-made headcap implants, we embedded EMG electrodes into the geniohyoid and diaphragm muscles in adult male rats prior to intralingual injection of CTB-SAP or control (CTB unconjugated to SAP) and studied chronic EMG activity during VFSS or during plethysmography studies +/- tongue exercise (N=4-6/group). Our preliminary findings show decreased geniohyoid (but not diaphragm) EMG activity as well as swallow/breathing discoordination that appears to be reversed with tongue exercise in CTB-SAP rats vs. controls. In conclusion, tongue exercise appears to enhance XII axis plasticity to improve upper airway function and coordination in the face of XII LMN degeneration. Studies are now underway to understand the underlying mechanism of tongue exercise-induced neuroplasticity, which may help guide future translational studies in patients with MNDs. R01 HL153612 and Phi Zeta. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Influence of puberty on high intensity exercise induced skeletal muscle damage and inflammatory response in sedentary boys

The present investigation examined the influence of age and pubertal transition on magnitude of muscle damage and inflammatory response following high intensity incremental treadmill running till volitional exhaustion in sixty-four sedentary prepubertal (n ​= ​32) and postpubertal (n ​= ​32) boys who were randomly recruited in the study. Muscle damage and inflammatory markers like creatine kinase (CK), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotranferase (AST), C–Reactive Protein (CRP) and Interleukin-6 (IL–6) were estimated before and after exercise. Serum CK, LDH, AST, ALT, CRP and IL–6 levels significantly increased after exercise in both the groups in comparison to respective pre–exercise values. Although CK, LDH, CRP and IL–6 responses were significantly higher in postpubertal boys, no intergroup variation was noted in post-exercise ALT activity. Age and body mass index (BMI) had significant positive correlation with post-exercise CK, LDH, AST, CRP, and IL–6 levels. Muscle injury and inflammation were significantly higher in postpubertal boys, suggesting a rise in these responses as a function of age and muscle mass during onset of puberty. Post–exercise release pattern of ALT was not influenced by age and puberty. Data also revealed that concentric endurance exercise did not induce extensive muscle damage and inflammation in both the groups. Drastic elevation in IL–6 level despite lower muscle damage implied that this marker was released from contracting muscle fibers independent of muscle damage and acute inflammation. The magnitude of this post–exercise IL–6 release increased as a function of age and BMI.

Wiltse Approach for Lumbar Microdiscectomy and Foraminotomy: 2-Dimensional Operative Video.

Far lateral disc herniations account for between 7% and 12% of all disk herniations and occur predominantly at L3/4 and L4/5.1,2 They can cause severe radicular pain due to dorsal root ganglion involvement and are exacerbated by lateral bending to the side of the lesion. Back pain is less of a feature with this pathology.3 The Wiltse approach was first described in the 1960s as an approach to L5/S1 noninstrumented fusion for isthmic spondylolisthesis4; its use in pedicle screws and far lateral discs was described in 1988.5 It has been shown to reduce muscle atrophy, wound infection, and blood loss.6,7 The Wiltse approach for a far lateral disc herniation provides a direct route to the disc pathology and as such is useful in cases with this isolated pathology. It confers less extensive muscle dissection and therefore less postoperative pain, minimal bone resection with preservation of the integrity of the facet joint, and it does not rely on endoscopy (rather the traditional operating microscope). It can also be used where endoscopy is contraindicated such as in revision cases. Here we present the case of a 53-year-old woman who presented with several weeks of back pain and right L3 radiculopathy, as well as right hip flexion and knee extension weakness. A Wiltse approach microdiscectomy was proposed for her far lateral disk herniation, and the patient consented to the procedure. At 6 weeks of follow-up, her radicular pain had resolved and there was improvement in hip flexion and knee extension. Image at 5:50 of Surgical Video is used with permissions from the Wiltse, L, Bateman, JD, Hutchinson, RH, and Nelson, WE. The Paraspinal Sacrospinalis-Splitting Approach to the Lumbar Spine. J Bone Joint Surg Am. 1968;50(5):919-926. Copyright © 1968 by The Journal of Bone and Joint Surgery, Inc.

Juvenile-onset anti-nuclear matrix protein 2 (NXP-2) antibody-positive dermatomyositis with joint contractures before manifestation of myositis: a case report

A 23-year-old man was admitted to our hospital with a one-year history of muscle weakness and atrophy. He had noticed contractures of the fingers of both hands from the age of 18. Examination revealed a skin rash including heliotrope rash and Gottron's sign, joint contractures in the extremities, dysphagia, extensive muscle weakness and marked muscle atrophy. The serum creatine kinase level was 272 ‍IU/l and muscle biopsy showed typical perifascicular atrophy but little lymphocyte invasion. There was no interstitial pneumonia or malignancy, but muscle tendons showed elevated CT values suggesting calcification or fibrosis. Anti-nuclear matrix protein 2 (NXP-2) antibody-positive dermatomyositis was diagnosed on the basis of the serum antibody level. Methylprednisolone pulse therapy ameliorated the skin rash and bulbar palsy, but muscle weakness, atrophy and joint contractures were resistant to the treatment. There have been no previous reports of young adults with anti-NXP-2 antibody-positive dermatomyositis in whom joint contracture became evident as early as 4 years beforehand, which is a important feature for differential diagnosis of dermatomyositis.

Fabrication of 3D Biomimetic Smooth Muscle Using Magnetic Induction and Bioprinting for Tissue Regeneration.

Smooth muscles play a vital role in peristalsis, tissue constriction, and relaxation but lack adequate self-repair capability for addressing extensive muscle defects. Engineering scaffolds have been broadly proposed to repair the muscle tissue. However, efforts to date have shown that those engineered scaffolds focus on cell alignment in 2-dimension (2D) and fail to direct muscle cells to align in 3D area, which is irresolvable to remodel the muscle architecture and restore the muscle functions like contraction and relaxation. Herein, we introduced an iron oxide (Fe3O4) filament-embedded gelatin (Gel)-silk fibroin composite hydrogel in which the oriented Fe3O4 self-assembled and functioned as micro/nanoscale geometric cues to induce cell alignment growth. The hydrogel scaffold can be designed to fabricate aligned or anisotropic muscle by combining embedded 3D bioprinting with magnetic induction to accommodate special architectures of muscular tissues in the body. Particularly, the bioprinted muscle-like matrices effectively promote the self-organization of smooth muscle cells (SMCs) and the directional differentiation of bone marrow mesenchymal stem cells (BMSCs) into SMCs. This biomimetic muscle accelerated tissue regeneration, enhancing intercellular connectivity within the muscular tissue, and the deposition of fibronectin and collagen I. This work provides a novel approach for constructing engineered biomimetic muscles, holding significant promise for clinical treatment of muscle-related diseases in the future.

IMPROVING SURGICAL STRATEGIES FOR TREATING EXTENSIVE SOFT TISSUE WOUNDS RESULTING FROM MINE AND EXPLOSIVE TRAUMA

Introduction.Since February 24, 2022, a primary focus of surgical care in Ukraine has been to provide assistance to citizens affected by Russian aggression. A significant proportion of wounds and injuries sustained in this context involves mine-explosive wounds, manifesting as soft tissue damage in the form of lacerations, shrapnel injuries, and wounds of varying degrees of contamination and size.&#x0D; The widespread adoption of Vacuum-Assisted Closure (VAC) therapy for wounds characterized by extensive muscle and skin defects involves the localized application of negative pressure to damaged tissues. Typically, this precedes planned autodermoplasty, which, despite being a scheduled intervention, follows urgent surgical corrections. These interventions offer a distinct opportunity for individuals with substantial soft tissue injuries— and, as evidenced by experience, not limited to them— to restore their pre-injury quality of life.&#x0D; The aim of this study is to enhance the quality of life for individuals affected by mine-explosive injuries and extensive soft tissue wounds.&#x0D; Materials and methods. The outcomes of surgical treatment of 57 civilian victims afflicted by landmine-explosive wounds and extensive soft tissue injuries were examined. These individuals underwent treatment at the Surgical Department of the Regional Clinical Hospital" during the period 2022 – 2023. Among the cohort, 34 were women, constituting 59%, while 23 were men, representing 41%, the ages of the patients ranged from 34 to 74 years.&#x0D; Results and discussion. All 57 patients initially underwent surgical treatment of wounds, involving the removal of foreign bodies if present, necrectomy, and subsequent application of the second-stage Vacuum-Assisted Closure (VAC) therapy. The VAC therapy was used to cleanse the wounds and reduce their surface area. Continuous VAC therapy was administered at a negative pressure ranging from 50 mmHg (on the anterior abdominal wall and the back surface of the chest) to 110 mmHg (on tissues of the lower extremities). The replacement of the VAC dressing occurred every 3-5 days, contingent upon the quantity and quality of the exudate, with typically 2-3 changes required. The third stage involved the application of free autodermoplasty utilizing a perforated skin flap. Mechanical wound treatment was performed iteratively until the level of "bloody dew" was reached.&#x0D; We suggest that all these stages are essential for achieving favorable treatment outcomes, irrespective of any severe accompanying pathology that may arise. Indeed, comorbidity stands out as a defining factor that distinguishes the civilian population qualitatively from the military category.&#x0D; Conclusions. The application of Vacuum-Assisted Closure (VAC) therapy followed by autodermoplasty in the management of extensive soft tissue injuries caused by mine-explosive incidents significantly enhances the efficacy of surgical treatment and reduces the period of patient incapacitation, presenting clear economic benefits. Autodermoplasty, in particular, holds a commendable position within the realm of reconstructive surgery for mine and explosive wounds. Within this context, autodermoplasty emerges as a surgical intervention that not only yields positive aesthetic outcomes but also facilitates an accelerated adaptation of the affected body part. This, in turn, contributes to an improved quality of life for victims of mine-explosive trauma grappling with substantial soft tissue damage.

Adenomatoid tumor with extensive reactive smooth muscle: a diagnostic dilemma

Abstract Introduction/Objective Adenomatoid tumors are slow-growing benign tumors of mesothelial origin. They comprise 30% of all tumors of the paratesticular area. In this location, they commonly involve the epididymis, spermatic cord, ejaculatory duct and rarely testicular parenchyma. Histologically, a spectrum of growth patterns can be seen, such as adenoid, tubular, glandular, solid, or cystic. In some cases, a smooth muscle component can also be present. The purpose of this report is to describe a case of adenomatoid tumor with exuberant smooth muscle component, mimicking leiomyoma. Methods/Case Report A 28-year-old male presented with painless left inguinal bulge. He noticed it five years prior, and it had been slowly growing since then. Examination revealed a paratesticular mass which was subsequently excised. Grossly, the tumor was firm with smooth, white-tan cut surfaces. Microscopically, the tumor was well- circumscribed, showing predominance of smooth muscle bundles and rare cuboidal to ovoid cells in tubular growth pattern. In the background there was little intervening stroma. Immunohistochemical stains showed the cuboidal cells to be positive for WT1 and calretinin, confirming the mesothelial origin. Diagnosis of adenomatoid tumor was rendered. In contrast to adenomatoid tumors, leiomyomas are whiter and firmer on gross examination and lack the characteristic tubules or cystic spaces lined by mesothelial cells. Results (if a Case Study enter NA) N/A Conclusion Exuberant smooth muscle differentiation in adenomatoid tumor can mislead to diagnosis of leiomyoma. Careful inspection for tubules of mesothelial origin and appropriate immunohistochemical stains are key to accurate diagnosis. Pathologists need to be aware of this potential pitfall.

Tripartite motif containing 33 demonstrated anticancer effect by degrading c‑Myc: Limitation of glutamine metabolism and proliferation in endometrial carcinoma cells.

Tripartite motif containing 33 (TRIM33) has been reported to be involved in various tumor progression. However, its role in endometrial carcinoma (EC) remains to be elucidated. By mining the publicly available databases UALCAN and TIMER, low expression of TRIM33 was found in tumor tissues of EC patients. Clinically, downregulation of TRIM33 in EC tissues was positively correlated with the extensive muscle invasion and poor differentiation grade. Invitro, experiments performed on human HEC‑1‑A and AN3CA cells showed that overexpression of TRIM33 inhibited the proliferation, migration and invasion of EC cells, whereas TRIM33 knockdown resulted in the opposite results. Furthermore, upregulation of TRIM33 significantly inhibited the glutamine uptake and decreased the intracellular glutamate in EC cells, which is evidenced by the reduction of solute carrier family 1 member 5 and glutaminase. Invivo, TRIM33 also dramatically inhibited tumor growth and glutamine metabolism. Additionally, co‑immunoprecipitation assay confirmed the interaction between TRIM33 and c‑Myc. Overexpression of TRIM33 could reduce the protein stability of c‑Myc by promoting its degradation. In addition, upregulation of c‑Myc could reverse the effects of TRIM33 on EC cells. Together, the present study demonstrated that TRIM33 acted as a tumor suppressor in EC, which is manifested in its inhibition of glutamine metabolism and cell growth via promoting c‑Myc protein degradation.

THU575 The Canonical Wnt/β-catenin Pathway Is Not Involved In Estrogen-induced Skeletal Muscle Fibrosis In A Mouse Model Of Inguinal Hernia

Abstract Disclosure: T. You: None. H. Zhao: None. T. Potluri: None. P. Yin: None. S.E. Bulun: None. Inguinal hernias affect up to 27% of elderly men, with approximately 800,000 inguinal hernia repair surgeries performed annually. While these procedures are often effective, a significant subset of hernias are refractory to treatment, resulting in high mortality, high recurrence, and chronic pain. Until recently, little research has been done examining the molecular mechanisms that drive hernia-associated lower abdominal wall weakening. Our lab previously created a transgenic mouse model expressing the human aromatase gene (Aromhum) and showed that male Aromhum mice produced high levels of estrogen in the lower abdominal muscle (LAM) tissue, leading to extensive LAM fibrosis, muscle atrophy, and hernia formation. Single-cell analysis of fibrotic LAM tissue in these mice showed high expression of estrogen receptor alpha (ERα) in LAM fibroblasts as well as upregulation of Wnt signaling pathways in these ERα-positive fibroblasts. The canonical Wnt/β-catenin signaling pathway has been implicated in fibroblast activation and fibrosis in multiple organs, including the lung, heart, and skin. Thus, we hypothesized that canonical Wnt/β-catenin signaling acts as a downstream mediator of ERα to cause LAM fibroblast activation, tissue fibrosis, and hernia. To test our hypothesis, we cultured primary ERα-positive LAM fibroblasts from Aromhum mice in the presence of estrogen with or without siRNA knockdown (KD) of β-catenin. However, KD of β-catenin under these conditions did not alter fibroblast proliferation as measured by EdU assay, nor did it alter expression of genes involved in fibroblast activation or extracellular matrix formation. Furthermore, administration of LGK974, a Wnt signaling inhibitor, in male Aromhum mice did not prevent hernia development, decrease hernia size, or decrease the extent of LAM fibrosis and muscle atrophy. Thus, we concluded that the canonical Wnt/β-catenin signaling pathway does not serve as a downstream mediator of estrogen-induced skeletal muscle fibrosis in our Aromhum mouse model of inguinal hernia. Further studies are needed to evaluate the role of Wnt/β-catenin signaling in other inguinal hernia models or in humans. Presentation Date: Thursday, June 15, 2023

Steroids May Be Associated With Extensive Skeletal Muscle Uptake of 18F-FDG.

The possibility of steroid administration inducing the extensive skeletal muscle uptake (ESMU) of FDG in PET scans was investigated. From 8923 consecutive 18F-FDG PET/CT scans taken at our hospital, 23 scans (15 patients) met adult age and ESMU-positive inclusion criteria. Among the 15 patients, 13 with both ESMU-positive and -negative scans were examined for association with steroid administration. Extensive skeletal muscle uptake was associated with a history of steroid administration (χ2 test: P = 0.001). Notably, 20 ESMU-positive scans and 11 ESMU-negative scans were significantly different, with 0 to 95 days (median, 18.5 days) and 0 to 708 days (median, 319.0 days) since the last steroid administration, respectively (Mann-Whitney U test, P = 0.003). A significant correlation was observed between mean skeletal muscle SUVmax and the number of days since the last steroid administration (Spearman rank correlation coefficient, ρ = -0.501, P = 0.004). Specifically, the degree of ESMU tended to decrease over time, after steroid administration. From multiple regression analysis, the number of days since the last steroid administration was significantly associated with mean SUVmax (P = 0.007), but the blood glucose level was not significant (P = 0.204), revealing that the number of days since the last steroid administration was an independent risk factor. Multicollinearity was low (the variance inflation factor was 1.007 for both the number of days since the last steroid administration and blood glucose levels). Steroid administration within months before PET may be one cause of ESMU.

Intramuscular Bleeding and Formation of Microthrombi during Skeletal Muscle Damage Caused by a Snake Venom Metalloprotease and a Cardiotoxin.

The interactions between specific snake venom toxins and muscle constituents are the major cause of severe muscle damage that often result in amputations and subsequent socioeconomic ramifications for snakebite victims and/or their families. Therefore, improving our understanding of venom-induced muscle damage and determining the underlying mechanisms of muscle degeneration/regeneration following snakebites is critical to developing better strategies to tackle this issue. Here, we analysed intramuscular bleeding and thrombosis in muscle injuries induced by two different snake venom toxins (CAMP-Crotalus atrox metalloprotease (a PIII metalloprotease from the venom of this snake) and a three-finger toxin (CTX, a cardiotoxin from the venom of Naja pallida)). Classically, these toxins represent diverse scenarios characterised by persistent muscle damage (CAMP) and successful regeneration (CTX) following acute damage, as normally observed in envenomation by most vipers and some elapid snakes of Asian, Australasian, and African origin, respectively. Our immunohistochemical analysis confirmed that both CAMP and CTX induced extensive muscle destruction on day 5, although the effects of CTX were reversed over time. We identified the presence of fibrinogen and P-selectin exposure inside the damaged muscle sections, suggesting signs of bleeding and the formation of platelet aggregates/microthrombi in tissues, respectively. Intriguingly, CAMP causes integrin shedding but does not affect any blood clotting parameters, whereas CTX significantly extends the clotting time and has no impact on integrin shedding. The rates of fibrinogen clearance and reduction in microthrombi were greater in CTX-treated muscle compared to CAMP-treated muscle. Together, these findings reveal novel aspects of venom-induced muscle damage and highlight the relevance of haemostatic events such as bleeding and thrombosis for muscle regeneration and provide useful mechanistic insights for developing better therapeutic interventions.