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Journal of Nanobiotechnology Nov 2023Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes and the main cause of non-traumatic amputation, with no ideal treatment....
BACKGROUND
Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes and the main cause of non-traumatic amputation, with no ideal treatment. Multiple cell-derived exosomes have been reported to improve the progression of DPN. Blood therapy is thought to have a powerful repairing effect. However, whether it could also improve DPN remains unclear.
RESULTS
In this study, we found that microRNA (miRNA) expression in plasma-derived exosomes of healthy rats (hplasma-exos) was significantly different from that of age-matched DPN rats. By injection of hplasma-exos into DPN rats, the mechanical sensitivity of DPN rats was decreased, the thermal sensitivity and motor ability were increased, and the nerve conduction speed was accelerated. Histological analysis showed myelin regeneration of the sciatic nerve, increased intraepidermal nerve fibers, distal local blood perfusion, and enhanced neuromuscular junction and muscle spindle innervation after hplasma-exos administration. Compared with plasma exosomes in DPN, miR-20b-3p was specifically enriched in exosomes of healthy plasma and was found to be re-upregulated in the sciatic nerve of DPN rats after hplasma-exos treatment. Moreover, miR-20b-3p agomir improved DPN symptoms to a level similar to hplasma-exos, both of which also alleviated autophagy impairment induced by high glucose in Schwann cells. Mechanistic studies found that miR-20b-3p targeted Stat3 and consequently reduced the amount of p-Stat3, which then negatively regulated autophagy processes and contributed to DPN improvement.
CONCLUSIONS
This study demonstrated that miRNA of plasma exosomes was different between DPN and age-matched healthy rats. MiR-20b-3p was enriched in hplasma-exos, and both of them could alleviated DPN symptoms. MiR-20b-3p regulated autophagy of Schwann cells in pathological states by targeting Stat3 and thereby inhibited the progression of DPN.
Topics: Animals; Rats; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Exosomes; MicroRNAs; Peripheral Nervous System Diseases
PubMed: 38001489
DOI: 10.1186/s12951-023-02222-5 -
Journal of Biomechanics Jan 2024Literature reports paradoxical findings regarding effects of low-back pain (LBP) on trunk motor control. Compared to healthy individuals, patients with LBP, especially...
Literature reports paradoxical findings regarding effects of low-back pain (LBP) on trunk motor control. Compared to healthy individuals, patients with LBP, especially those with high pain-related anxiety, showed stronger trunk extensor reflexes and more resistance against perturbations. On the other hand, LBP patients and especially those with high pain-related anxiety showed decreased precision in unperturbed trunk movement and posture. These paradoxical effects might be explained by arousal potentially increasing average and variance of muscle spindle firing rates. Increased average firing rates could increase resistance against perturbations, but increased variance could decrease precision. We performed a simulation study to test this hypothesis. We modeled the trunk as a 2D inverted pendulum, stabilized by two antagonistic Hill-type muscles, based on their open-loop muscle activation dependent intrinsic stiffness and damping and through 25 ms-delayed, noisy contractile element length and velocity feedback. Reference feedback gains and sensory noise levels were tuned based on previously reported experimental data. We assessed the effect of increasing feedback gains on precision of trunk orientation at different perturbation magnitudes and assessed sensitivity of the effects to open-loop muscle stimulation and noise levels. At low perturbation magnitudes, increasing reflex gains consistently caused an increase in the variance of trunk orientation. At larger perturbation magnitudes, increasing reflex gains consistently caused a decrease in the variance of trunk orientation. Our results support the notion that LBP and related anxiety may increase reflex gains, resulting in an increase in the average and variance of spindle afference, which in turn increase resistance against perturbations and decrease movement precision.
Topics: Humans; Muscle, Skeletal; Feedback; Back Pain; Low Back Pain; Movement; Electromyography
PubMed: 37989619
DOI: 10.1016/j.jbiomech.2023.111876 -
World Journal of Clinical Cases Oct 2023Aggressive angiomyolipoma is an extremely rare benign mesenchymal tumor that was originally described as a locally recurrent mucinous spindle cell tumour. Aggressive...
BACKGROUND
Aggressive angiomyolipoma is an extremely rare benign mesenchymal tumor that was originally described as a locally recurrent mucinous spindle cell tumour. Aggressive angiomyolipoma originates from myofibroblasts, vascular smooth muscle cells, or fibroblasts, and displays various phenotypes of myofibroblasts and abnormal muscle arteries. Aggressive angiomyolipoma was first identified in 1983 and fewer than 50 male patients have been reported to date. It is an extremely rare mesenchymal tumour and often confused with other diseases. Patients with epididymal aggressive angiomyolipoma lack typical symptoms, most of which occur incidentally, although some patients may experience mild pain, discomfort, and swelling. Pain may be exacerbated by pressure from the mass.
CASE SUMMARY
A 66-year-old male was admitted to the hospital on January 14, 2022 with chief complaint of swelling in the left scrotum for one year. There was no apparent cause for the swelling. The patient did not consult with any doctor or receive any treatment for the swelling. The enlarged scrotum increased in size gradually until it reached approximately the size of a goose egg, and was accompanied by discomfort and swelling of the left cavity of the scrotum. The patient had no history of any testicular trauma, infection, or urinary tract infection. The patient urinated freely, 1-2 times at night, without urgency, dysuria (painful urination), or haematuria. There was no significant family history of malignancy. The patient underwent excision of the enlarged tumour and the left epididymis under general anaesthesia on January 18, 2022. Twelve months of follow-up revealed no recurrence. The patient was satisfied with the treatment.
CONCLUSION
Aggressive angiomyolipoma is extremely rare clinically and often confused with other diseases. The pathogenesis of aggressive angiomyolipoma is unclear and the clinical presentation is mostly a painless enlarged mass. The diagnosis of aggressive angiomyolipoma requires a combination of medical history, preoperative imaging such as computed tomography and magnetic resonance imaging, cytological examination and preoperative and postoperative pathological biopsy. The preferred treatment is surgery, with the possibility of a new alternative treatment option after hormonal therapy. Aggressive angiomyolipoma should be considered in the differential diagnosis of parametrial tumors of the male genital area that present as clinically significant masses. The high recurrence rate of aggressive angiomyolipoma may be related to incomplete tumor resection, and patients with aggressive angiomyolipoma are advised to undergo annual postoperative follow-up and imaging for recurrence.
PubMed: 37946787
DOI: 10.12998/wjcc.v11.i29.7214 -
Journal of Comparative Pathology Nov 2023This report documents the pathological features of primary cardiac myxoid tumour (MT) in 11 dogs. Macroscopically, all the tumours were located in the tricuspid valve... (Review)
Review
This report documents the pathological features of primary cardiac myxoid tumour (MT) in 11 dogs. Macroscopically, all the tumours were located in the tricuspid valve (TV), its septal leaflet being predominantly affected. Therefore, it appears that the TV is the most common site of occurrence for cardiac MT in dogs. Two gross anatomical types of canine valvular MT were evident. Seven of the 11 tumours were round or oval with a smooth or gently lobulated and glistening surface, while the other four were gelatinous, multilobulated and polypoid, with an irregular surface. Microscopically, in nine cases the tumours had an abundant myxoid matrix within which elongated spindle-shaped cells with no remarkable cytological atypia were sparsely embedded, suggesting a benign character (ie, myxoma). In the other two cases the tumours consisted of variably dense, haphazardly arranged, interlacing streams of anaplastic spindle-shaped or polygonal cells containing many mitotic figures, indicative of a malignant form of myxoma (ie, myxosarcoma). Isolated or clustered collections of myxoma cells (eg, cords, rings, syncytia) characteristic of human atrial myxoma were only rarely evident or lacking in all 11 cases, indicating that rarity or absence of such structural features may be specific to valvular MTs. Immunohistochemical findings were indicative of smooth muscle differentiation of the neoplastic cells. Tumour embolization to the intrapulmonary arteries and/or tumour implantation on the endocardium of the right heart chambers was evident only in the four cases of irregular-surfaced MT.
Topics: Humans; Dogs; Animals; Heart Neoplasms; Myxoma; Endocardium; Myxosarcoma; Dog Diseases
PubMed: 37944473
DOI: 10.1016/j.jcpa.2023.10.004 -
Life Science Alliance Jan 2024The intracellular positioning of the centrosome, a major microtubule-organizing center, is important for cellular functions. One of the features of centrosome...
The intracellular positioning of the centrosome, a major microtubule-organizing center, is important for cellular functions. One of the features of centrosome positioning is the spacing between centrosomes; however, the underlying mechanisms are not fully understood. To characterize the spacing activity in embryos, a genetic setup was developed to produce enucleated embryos. The centrosome was duplicated multiple times in the enucleated embryo, which enabled us to characterize the chromosome-independent spacing activity between sister and non-sister centrosome pairs. We found that the timely spacing depended on cytoplasmic dynein, and we propose a stoichiometric model of cortical and cytoplasmic pulling forces for the spacing between centrosomes. We also observed dynein-independent but non-muscle myosin II-dependent movement of centrosomes in the later cell cycle phase. The spacing mechanisms revealed in this study are expected to function between centrosomes in general, regardless of the presence of a chromosome/nucleus between them, including centrosome separation and spindle elongation.
Topics: Animals; Caenorhabditis elegans; Dyneins; Spindle Apparatus; Microtubules; Centrosome
PubMed: 37931957
DOI: 10.26508/lsa.202302427 -
Cureus Oct 2023Renal oncopathology in adults, as a field of pathology, is dominated by a single entity - clear cell renal cell carcinoma (RCC) with other entries, such as urothelial...
Renal oncopathology in adults, as a field of pathology, is dominated by a single entity - clear cell renal cell carcinoma (RCC) with other entries, such as urothelial carcinoma of the renal pelvis, angiosarcoma, and others being extremely rare. Herein, we report two histopathological cases with differential diagnoses of spindle cell renal neoplasms. The first patient, a 42-year-old male, presented with new-onset right-sided abdominal flank pain, and imaging showed a 12 cm renal tumor. Histopathology showed a spindle cell neoplasm, with significant mitotic activity and giant cell, with immunohistochemistry being positive for caldesmon and vimentin, focally for smooth muscle actin (SMA). No reaction was noted for pan-cytokeratin (CK AE1/AE3), epithelial membrane antigen (EMA), cytokeratin (CK) 7, cluster of differentiation (CD) 117, soluble 100 protein (S100), human melanoma black (HMB) 45, Melan A, CD10, and desmin. Due to peculiar histomorphology and the immunophenotype, the tumor was interpreted as primary renal leiomyosarcoma. Due to continuous outpatient consultations, treatment initiation was delayed, and three months later, the patient had already developed an 87 mm local recurrence and liver metastasis. The second patient, a 53-year-old male, presented to our institution for consultation of an already excised renal tumor, diagnosed as an incidental finding on a prophylactic abdominal ultrasound. The tumor presented for consultation histologically grew as intertwining bundles of spindle cells with polymorphic hyperchromic nuclei with prominent nucleoli and had extensive areas with necrosis. Immunohistochemically, the tumor diffusely expressed CK AE1/AE3 and caldesmon and had a patchy reaction for EMA and CD10. The SMA, desmin, CD117, and CK7 reactions were negative; hence, the tumor was interpreted as a spindle cell variety (sub-type) of clear RCC.
PubMed: 37927619
DOI: 10.7759/cureus.46449 -
Epilepsia Open Feb 2024Identification of EEG waveforms is critical for diagnosing Lennox-Gastaut Syndrome (LGS) but is complicated by the progressive nature of the disease. Here, we assess the...
OBJECTIVE
Identification of EEG waveforms is critical for diagnosing Lennox-Gastaut Syndrome (LGS) but is complicated by the progressive nature of the disease. Here, we assess the interrater reliability (IRR) among pediatric epileptologists for classifying EEG waveforms associated with LGS.
METHODS
A novel automated algorithm was used to objectively identify epochs of EEG with transient high power, which were termed events of interest (EOIs). The algorithm was applied to EEG from 20 LGS subjects and 20 healthy controls during NREM sleep, and 1350 EOIs were identified. Three raters independently reviewed the EOIs within isolated 15-second EEG segments in a randomized, blinded fashion. For each EOI, the raters assigned a waveform label (spike and slow wave, generalized paroxysmal fast activity, seizure, spindle, vertex, muscle, artifact, nothing, or other) and indicated the perceived subject type (LGS or control).
RESULTS
Labeling of subject type had 85% accuracy across all EOIs and an IRR of κ =0.790, suggesting that brief segments of EEG containing high-power waveforms can be reliably classified as pathological or normal. Waveform labels were less consistent, with κ =0.558, and the results were highly variable for different categories of waveforms. Label mismatches typically occurred when one reviewer selected "nothing," suggesting that reviewers had different thresholds for applying named labels.
SIGNIFICANCE
Classification of EEG waveforms associated with LGS has weak IRR, due in part to varying thresholds applied during visual review. Computational methods to objectively define EEG biomarkers of LGS may improve IRR and aid clinical decision-making.
Topics: Humans; Child; Lennox Gastaut Syndrome; Reproducibility of Results; Electroencephalography; Seizures; Head
PubMed: 37920928
DOI: 10.1002/epi4.12858 -
Scientific Reports Oct 2023During atherosclerotic plaque formation, smooth muscle cells (SMCs) switch from a contractile/differentiated to a synthetic/dedifferentiated phenotype. We previously...
During atherosclerotic plaque formation, smooth muscle cells (SMCs) switch from a contractile/differentiated to a synthetic/dedifferentiated phenotype. We previously isolated differentiated spindle-shaped (S) and dedifferentiated rhomboid (R) SMCs from porcine coronary artery. R-SMCs express S100A4, a calcium-binding protein. We investigated the role of apelin in this phenotypic conversion, as well as its relationship with S100A4. We found that apelin was highly expressed in R-SMCs compared with S-SMCs. We observed a nuclear expression of apelin in SMCs within experimentally-induced intimal thickening of the porcine coronary artery and rat aorta. Plasmids targeting apelin to the nucleus (N. Ap) and to the secretory vesicles (S. Ap) were transfected into S-SMCs where apelin was barely detectable. Both plasmids induced the SMC transition towards a R-phenotype. Overexpression of N. Ap, and to a lesser degree S. Ap, led to a nuclear localization of S100A4. Stimulation of S-SMCs with platelet-derived growth factor-BB, known to induce the transition toward the R-phenotype, yielded the direct interaction and nuclear expression of both apelin and S100A4. In conclusion, apelin induces a SMC phenotypic transition towards the synthetic phenotype. These results suggest that apelin acts via nuclear re-localization of S100A4, raising the possibility of a new pro-atherogenic relationship between apelin and S100A4.
Topics: Animals; Rats; Apelin; Atherosclerosis; Cell Movement; Cells, Cultured; Myocytes, Smooth Muscle; Phenotype; Swine
PubMed: 37907514
DOI: 10.1038/s41598-023-45470-z -
In Vivo (Athens, Greece) 2023Low-grade fibromyxoid sarcoma (LGFMS) is a rare type of sarcoma which is observed in the soft tissue of proximal extremities, typically in young and middle-aged adults....
BACKGROUND
Low-grade fibromyxoid sarcoma (LGFMS) is a rare type of sarcoma which is observed in the soft tissue of proximal extremities, typically in young and middle-aged adults. It consists of a solid proliferation of bland spindle cells within collagenous and myxoid stroma.
CASE REPORT
Herein, we report a case of LGFMS with massive degeneration and hyalinization. A 30-year-old man presented with a well-circumscribed mass measuring 15 cm in diameter in his left biceps femoris muscle. Marginal tumor resection was performed under the clinical diagnosis of an ancient schwannoma or chronic expanding hematoma (CEH). The resected tissue revealed a well-demarcated tumor mass with massive degeneration and hyalinization with focal calcification. Proliferation of spindle tumor cells with abundant collagenous stroma, which resembled the fibrous capsule of CEH, was observed exclusively in a small area of the periphery of the tumor. No nuclear palisading, myxoid stroma, or collagen rosettes were identified. Immunohistochemical analysis demonstrated that the spindle tumor cells expressed mucin 4 and epithelial membrane antigen. Reverse transcriptase-polymerase chain reaction analysis detected mRNA expression of fused in sarcoma::CAMP-responsive element binding protein 3-like protein 2 (FUS::CREB3L2) fusion gene. Thus, a final diagnosis of LGFMS with massive degeneration and FUS::CREB3L2 fusion was made.
CONCLUSION
The recognition of massive degeneration and hyalinization as unusual features of LGFMS might be helpful to differentiate it from CEH and other benign spindle-cell tumors.
Topics: Adult; Middle Aged; Male; Humans; Biomarkers, Tumor; Fibrosarcoma; Sarcoma; Soft Tissue Neoplasms
PubMed: 37905642
DOI: 10.21873/invivo.13404 -
Frontiers in Pain Research (Lausanne,... 2023Low back pain (LBP) is the leading cause of disability worldwide. Most LBP is non-specific or idiopathic, which is defined as symptoms of unknown origin without a clear...
Low back pain (LBP) is the leading cause of disability worldwide. Most LBP is non-specific or idiopathic, which is defined as symptoms of unknown origin without a clear specific cause or pathology. Current guidelines for clinical evaluation are based on ruling out underlying serious medical conditions, but not on addressing underlying potential contributors to pain. Although efforts have been made to identify subgroups within this population based on response to treatment, a comprehensive framework to guide assessment is still lacking. In this paper, we propose a model for a personalized mechanism-based assessment based on the available evidence that seeks to identify the underlying pathologies that may initiate and perpetuate central sensitization associated with chronic non-specific low back pain (nsLBP). We propose that central sensitization can have downstream effects on the "myofascial unit", defined as an integrated anatomical and functional structure that includes muscle fibers, fascia (including endomysium, perimysium and epimysium) and its associated innervations (free nerve endings, muscle spindles), lymphatics, and blood vessels. The tissue-level abnormalities can be perpetuated through a vicious cycle of neurogenic inflammation, impaired fascial gliding, and interstitial inflammatory stasis that manifest as the clinical findings for nsLBP. We postulate that our proposed model offers biological plausibility for the complex spectrum of clinical findings, including tissue-level abnormalities, biomechanical dysfunction and postural asymmetry, ecological and psychosocial factors, associated with nsLBP. The model suggests a multi-domain evaluation that is personalized, feasible and helps rule out specific causes for back pain guiding clinically relevant management. It may also provide a roadmap for future research to elucidate mechanisms underlying this ubiquitous and complex problem.
PubMed: 37901614
DOI: 10.3389/fpain.2023.1237802