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Modern Pathology : An Official Journal... Jun 2024PLAG1 gene fusions were recently identified in a subset of uterine myxoid leiomyosarcomas (M-LMS). However, we have encountered cases of PLAG1-rearranged uterine...
PLAG1 gene fusions were recently identified in a subset of uterine myxoid leiomyosarcomas (M-LMS). However, we have encountered cases of PLAG1-rearranged uterine sarcomas (PLAG1-US) lacking M-LMS-like morphology and/or any expression of smooth muscle markers. To better characterize their clinicopathological features, we performed a multi-institutional search which yielded 11 cases. The patients ranged in age from 34-72 years (mean: 57). All tumors arose in the uterine corpus, ranging in size from 6.5-32 cm (mean: 15). The most common stage at presentation was pT1b (n=6), three cases had stage pT1 (unspecified) and one case each presented in stage pT2a and pT3b. Most were treated only by hysterectomy with adnexectomy. The follow-up (range: 7-71 months; median: 39 months) was available for 7 patients. Three cases (7-21 months of follow-up) had no evidence of disease. Three out of 4 remaining patients died of disease within 55-71 months, while the last developed peritoneal spread and was transferred for palliative care at 39 months. Morphologically, the tumors showed a high inter- and intratumoral heterogeneity. M-LMS-like and epithelioid LMS-like morphology was present in 3 and 5 primary tumors, respectively, the rest mostly presented as non-descript ovoid/spindle cell sarcomas. Unusual morphological findings included prominently hyalinized stroma (n=3), adipocytic differentiation with areas mimicking myxoid liposarcoma (n=2), osteosarcomatous differentiation (n=1) and undifferentiated pleomorphic sarcoma-like areas (n=1). The mitotic activity ranged from 3-24 mitoses/10 high-power fields (mean: 9), 3/10 cases showed necrosis. In 3/11 cases, no expression of SMA, h-caldesmon or desmin was noted, whereas 5/5 cases expressed PLAG1. By RNA-sequencing, the following fusion partners were identified: PUM1, CHCHD7 (each n=2), C15orf29, CD44, MYOCD, FRMD6, PTK2 and TRPS1 (each n=1). One case only showed PLAG1 gene break by FISH. Our study documents a much broader morphological spectrum of PLAG1-US than previously reported, encompassing but not limited to M-LMS-like morphology with occasional heterologous (particularly adipocytic) differentiation. Since it is currently difficult to precisely define their line of differentiation, for the time being, we suggest using a descriptive name PLAG1-rearranged uterine sarcoma.
PubMed: 38942115
DOI: 10.1016/j.modpat.2024.100552 -
Nature Communications Jun 2024Neuromuscular control of bionic arms has constantly improved over the past years, however, restoration of sensation remains elusive. Previous approaches to reestablish...
Neuromuscular control of bionic arms has constantly improved over the past years, however, restoration of sensation remains elusive. Previous approaches to reestablish sensory feedback include tactile, electrical, and peripheral nerve stimulation, however, they cannot recreate natural, intuitive sensations. Here, we establish an experimental biological sensorimotor interface and demonstrate its potential use in neuroprosthetics. We transfer a mixed nerve to a skeletal muscle combined with glabrous dermal skin transplantation, thus forming a bi-directional communication unit in a rat model. Morphological analyses indicate reinnervation of the skin, mechanoreceptors, NMJs, and muscle spindles. Furthermore, sequential retrograde labeling reveals specific sensory reinnervation at the level of the dorsal root ganglia. Electrophysiological recordings show reproducible afferent signals upon tactile stimulation and tendon manipulation. The results demonstrate the possibility of surgically creating an interface for both decoding efferent motor control, as well as encoding afferent tactile and proprioceptive feedback, and may indicate the way forward regarding clinical translation of biological communication pathways for neuroprosthetic applications.
Topics: Animals; Bionics; Rats; Muscle, Skeletal; Feedback, Sensory; Proprioception; Ganglia, Spinal; Mechanoreceptors; Muscle Spindles; Male; Female; Touch; Skin
PubMed: 38914540
DOI: 10.1038/s41467-024-49580-8 -
Ecotoxicology and Environmental Safety Jun 2024Deoxynivalenol (DON), commonly known as vomitoxin, is a mycotoxin produced by fungi and is frequently found as a contaminant in various cereal-based food worldwide....
Deoxynivalenol (DON), commonly known as vomitoxin, is a mycotoxin produced by fungi and is frequently found as a contaminant in various cereal-based food worldwide. While the harmful effects of DON have been extensively studied in different tissues, its specific impact on the proliferation of skeletal muscle cells remains unclear. In this study, we utilized murine C2C12 myoblasts as a model to explore the influence of DON on their proliferation. Our observations indicated that DON exhibits dose-dependent toxicity, significantly inhibiting the proliferation of C2C12 cells. Through the application of RNA-seq analysis combined with gene set enrichment analysis, we identified a noteworthy downregulation of genes linked to the extracellular matrix (ECM) and condensed chromosome. Concurrently with the reduced expression of ECM genes, immunostaining analysis revealed notable changes in the distribution of fibronectin, a vital ECM component, condensing into clusters and punctate formations. Remarkably, the exposure to DON induced the formation of multipolar spindles, leading to the disruption of the normal cell cycle. This, in turn, activated the p53-p21 signaling pathway and ultimately resulted in apoptosis. These findings contribute significant insights into the mechanisms through which DON induces toxicity within skeletal muscle cells.
PubMed: 38908055
DOI: 10.1016/j.ecoenv.2024.116607 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Jun 2024The core components of the Hippo signaling pathway encompass upstream regulatory molecules, core kinase cascade complexes, and downstream transcriptional regulation...
The core components of the Hippo signaling pathway encompass upstream regulatory molecules, core kinase cascade complexes, and downstream transcriptional regulation complexes. This pathway modulates cellular biological behaviors by influencing the effector molecules of its core components and plays a pivotal role in immune regulation. Effector molecules,such as Yes-associated protein (YAP), transcriptional coactivator with PDZ-binding motif (TAZ), transcriptional enhanced associate domain transcriptional factor (TEAD), monopolar spindle-one binder (MOB1), large tumor suppressor (LATS), can stimulate fibroblast-like synovial cell migration and invasion in rheumatoid arthritis, regulate osteoarthritis disease progression, promote pathological new bone formation in ankylosing spondylitis, sustain submandibular gland development while delaying Sjogren's syndrome progression, mediate alpha-smooth muscle actin in systemic sclerosis, and refine the regulation of target genes associated with pulmonary fibrosis. This article provides an overview of the regulatory mechanisms involving Hippo signaling pathway-related effector molecules in the pathogenesis and progression of rheumatic immune system diseases, to serve as a reference for exploring novel therapeutic targets of rheumatic immune system diseases.
PubMed: 38899353
DOI: 10.3724/zdxbyxb-2023-0567 -
Cureus May 2024Primary orbital melanoma and metastatic cutaneous melanoma of the orbit are extremely rare. Desmoplastic melanoma (DM) is an infrequent variant of melanoma that can...
Primary orbital melanoma and metastatic cutaneous melanoma of the orbit are extremely rare. Desmoplastic melanoma (DM) is an infrequent variant of melanoma that can extend from a superficial location into deep tissues by neurotropic mechanisms. A 78-year-old male was referred to us with a periocular mixed malignant melanoma (spindle cell melanoma with desmoplastic reaction) in his left lower eyelid with uncontrollable disease (orbital and inferior orbital rim invasion) despite treatment. The surgical technique consisted of an extended orbital exenteration, maxillectomy, and ethmoidectomy, with a 2 cm macroscopic surgical margin. We performed a delayed socket reconstruction with a temporalis muscle flap using a transorbital approach. The patient remained disease-free for 1.5 years with a good quality of life since exenteration surgery. At this time, he presented a recurrence in the area of the malar scar with a new orbital invasion, and finally, he died due to mediastinal, pleural, and pulmonary metastasis. The treatment of a cutaneous melanoma arising in the periocular region is a challenging reconstructive problem and it may compromise the globe and visual function.
PubMed: 38887344
DOI: 10.7759/cureus.60541 -
Advances in Experimental Medicine and... 2024This chapter will describe basic structural and functional features of the contractile apparatus of muscle cells of the heart, namely, cardiomyocytes and smooth muscle... (Review)
Review
This chapter will describe basic structural and functional features of the contractile apparatus of muscle cells of the heart, namely, cardiomyocytes and smooth muscle cells. Cardiomyocytes form the contractile myocardium of the heart, while smooth muscle cells form the contractile coronary vessels. Both muscle types have distinct properties and will be considered with respect to their cellular appearance (brick-like cross-striated versus spindle-like smooth), arrangement of contractile proteins (sarcomeric versus non-sarcomeric organization), calcium activation mechanisms (thin-filament versus thick-filament regulation), contractile features (fast and phasic versus slow and tonic), energy metabolism (high oxygen versus low oxygen demand), molecular motors (type II myosin isoenzymes with high adenosine diphosphate [ADP]-release rate versus myosin isoenzymes with low ADP-release rates), chemomechanical energy conversion (high adenosine triphosphate [ATP] consumption and short duty ratio versus low ATP consumption and high duty ratio of myosin II cross-bridges [XBs]), and excitation-contraction coupling (calcium-induced calcium release versus pharmacomechanical coupling). Part of the work has been published (Neuroscience - From Molecules to Behavior", Chap. 22, Galizia and Lledo eds 2013, Springer-Verlag; with kind permission from Springer Science + Business Media).
Topics: Humans; Myocardial Contraction; Animals; Myocytes, Cardiac; Calcium; Energy Metabolism; Myocytes, Smooth Muscle; Excitation Contraction Coupling
PubMed: 38884723
DOI: 10.1007/978-3-031-44087-8_21 -
Journal of Bodywork and Movement... Jul 2024This study aimed to determine whether massage pressure on the target muscles (biceps brachii muscle [BB] and the medial head of the gastrocnemius muscle [MG]) is related...
INTRODUCTION
This study aimed to determine whether massage pressure on the target muscles (biceps brachii muscle [BB] and the medial head of the gastrocnemius muscle [MG]) is related to the massage effect (reducing muscle stiffness).
METHOD
Nine healthy participants participated in this study. A physiotherapist massaged the upper arms and lower legs of participants on a rigid desk in a laboratory. Massage was delivered for 10 min with a 3-min rest. The shear modulus (i.e., the muscle stiffness), assessed by shear wave elastography, was measured at various time points (before [PRE], immediately after [POST], and 5 [POST-5], 10, 15, and 20 min after the massage). The massage pressure data (N) were obtained only during massage by force plate sensors.
RESULTS
The BB shear modulus was significantly reduced POST massage. The MG shear modulus significantly reduced POST massage and remained clearly reduced until POST-5. There was a negative correlation between the total massage pressure and the % change in the shear modulus in both muscles.
DISCUSSION
Since the spindle (BB) and pennate (MG) muscles have structural differences, our results suggest that these differences may affect the pattern of changes in the shear modulus in response to massage.
CONCLUSION
Massage pressure is related to the massage effect (reducing muscle stiffness), and its relationships to POST are not related to the differences in the morphologies of the spindle (BB) and pennate muscles (MG). However, differences in the morphologies of the spindle and pennate muscles may cause differences in the duration of the massage effects.
Topics: Humans; Massage; Muscle, Skeletal; Male; Adult; Female; Young Adult; Pressure; Elasticity Imaging Techniques
PubMed: 38876651
DOI: 10.1016/j.jbmt.2024.03.025 -
Scientific Reports Jun 2024
PubMed: 38862583
DOI: 10.1038/s41598-024-63491-0 -
The Journal of Physiology Jun 2024
PubMed: 38857461
DOI: 10.1113/JP286961 -
International Journal of Surgery Case... Jul 2024Cutaneous leiomyomas, benign tumors from smooth muscle fibers, constitute about 5 % of all leiomyomas. They exhibit diverse inheritance patterns and can be linked to...
INTRODUCTION AND IMPORTANCE
Cutaneous leiomyomas, benign tumors from smooth muscle fibers, constitute about 5 % of all leiomyomas. They exhibit diverse inheritance patterns and can be linked to systemic malignancies. Gastrointestinal stromal tumors (GISTs), arising from the interstitial cells of Cajal, are the most common mesenchymal tumors in the gastrointestinal tract. Despite their prevalence, simultaneous occurrences of cutaneous leiomyomas and GISTs are rare, necessitating exploration of their potential relationship.
CASE PRESENTATION
A 25-year-old male with no significant medical history presented with multiple painful erythematous nodules on his chest, upper back, and arms. Histopathological analysis diagnosed these as multiple cutaneous piloleiomyomatosis. Despite recommendations for surgical intervention, the patient chose medical management and experienced significant pain relief with nifedipine. Later, the development of abdominal symptoms led to the discovery of multiple gastric lesions, diagnosed as benign spindle cell neoplasms, necessitating partial gastrectomy.
CLINICAL DISCUSSION
The differential diagnosis of cutaneous leiomyomas includes various soft tissue tumors, requiring histopathological confirmation. Genetic mutations affecting proteins critical to cellular energy production and tumor suppression underlie these conditions. Treatment options include pharmacological management and surgical excision. The discovery of GISTs in this patient aligns with rare literature reports, emphasizing the need for vigilant evaluation of systemic malignancies in patients with leiomyomatosis.
CONCLUSION
This case highlights the potential of cutaneous leiomyomas to indicate deeper malignancies like GISTs, stressing the importance of interdisciplinary collaboration in diagnosis and treatment. It underscores the interconnectedness of benign dermatological conditions and internal malignancies, advocating for comprehensive evaluation in patients with leiomyomatosis.
METHODS
This case report meticulously follows the SCARE 2023 guidelines: updating consensus Surgical Case Report guidelines (Sohrabi et al., 2023 [1]). These guidelines ensure high-quality reporting in surgical case reports. The report details the evaluation, diagnosis, and a comprehensive review of the literature pertaining to a patient with multiple leiomyoma cutis associated with gastrointestinal stromal tumors. By employing a multidisciplinary approach, this report achieves a thorough and standardized presentation of the case, serving as an additional tool for raising awareness regarding such rare conditions.
PubMed: 38851074
DOI: 10.1016/j.ijscr.2024.109870