Search Results (1,030)

Neuronal proteins synthesized locally in axons and dendrites contribute to growth, plasticity, survival, and retrograde signaling underlying these cellular processes. Advances in molecular tools to profile localized mRNAs, along with single-molecule detection approaches for RNAs and proteins, have significantly expanded our understanding of the diverse proteins produced in subcellular compartments. These investigations have also uncovered key molecular mechanisms that regulate mRNA transport, storage, stability, and translation within neurons. The long distances that axons extend render their processes vulnerable, especially when injury necessitates regeneration to restore connectivity. Localized mRNA translation in axons helps initiate and sustain axon regeneration in the peripheral nervous system and promotes axon growth in the central nervous system. Recent and ongoing studies suggest that axonal RNA transport, storage, and stability mechanisms represent promising targets for enhancing regenerative capacity. Here, we summarize critical post-transcriptional regulatory mechanisms, emphasizing translation in the axonal compartment and highlighting potential strategies for the development of new regeneration-promoting therapeutics. Full article

Background: Peripheral endovascular intervention (PEVI) is routinely performed using standard-dose radiation (SDR), which is associated with elevated levels of radiation. No study has evaluated the outcomes of minimal-dose radiation (MDR) in PEVI. Methods: We performed a prospective observational study of 184 patients (65 ± 12 years) at an academic medical center from January 2019 to March 2020 (mean follow-up of 3.9 ± 3.6 months) and compared the outcomes of MDR (n = 24, 13.0%) and SDR (n = 160, 87.0%) in PEVI. Primary endpoints included air kerma, dose area product (DAP), fluoroscopy time, and contrast use. Secondary endpoints included all-cause mortality, cardiac mortality, acute myocardial infarction, acute kidney injury, stroke, repeat revascularization, vessel dissection/perforation, major adverse limb event, access site complications, and composite of complications. Results: For MDR (68 ± 10 years, mean follow-up of 4.3 ± 5.2 months), the primary endpoints were significantly less than SDR (65 ± 12 years, mean follow-up of 3.8 ± 3.2 months; p < 0.001). Regarding the secondary endpoints, one vessel dissection occurred using MDR, while 36 total complications occurred with SDR (p = 0.037). Conclusions: PEVI using MDR was safe and efficacious. MDR showed a significant decrement in radiation parameters and fluoroscopy time. Therefore, MDR can serve as an effective alternative for PEVI in acute or critical limb ischemia. Full article

In recent years, a long list of relevant studies has highlighted the engagement of the nervous system in the fine-tuning of tumor development and progression. Several authors have shown that different types of nerve fibres (sympathetic, parasympathetic/vagal or somatosensory fibres) may contribute to tumor innervation affecting cancer initiation, progression and metastasis. A large presence of nerve fibres is frequently observed in tumors with respect to the corresponding healthy tissues. In this regard, it is worth noting that in some cases a reduced innervation may associate with slow tumor growth in a tissue-specific manner. Current studies have begun to shed light over the role played in this specific process by Schwann cells (SCs), the most abundant glial cells of the peripheral nervous system. SCs observed in cancer tissues share strong similarities with repair SCs that appear after nerve injury. A large body of research indicates that SCs may have a role in shaping the microenvironment of tumors by regulating the immune response and influencing their invasiveness. In this review, we summarize data relevant to the role of peripheral innervation in general, and of SCs in particular, in defining the progression of different tumors: melanoma that originate in the skin with mainly sensory innervation; pancreatic and liver-derived tumors (e.g., pancreatic adenocarcinoma and cholangiocarcinoma) with mainly autonomous innervation. We conclude by summarizing data regarding hepatocarcinoma (with anatomical predominance of small autonomic nerve fibres) in which the potential relationship between innervation and tumor progression has been little explored, and largely remains to be defined. Full article

Background/Objectives: Nerve injuries cause functional loss and psychosocial issues due to prolonged rehabilitation. Recently, 3D-modeled nerve conduits have been used to aid in surgical planning. This study investigated the impact of 3D-bioprinted PLA, chitosan, alginate, and collagen conduits on nerve regeneration in a rat sciatic nerve crush injury model. Methods: This study, conducted at Kütahya University of Health Sciences, involves 50 rats were divided into four groups: (1) sham-operated controls, (2) sciatic nerve injury without treatment, (3) injury treated with a PLA conduit, and (4) injury treated with 3D-printed tubes composed of chitosan and alginate. The procedures were performed, blood was collected, and the rats were sacrificed after two months. Weekly checks for infection, scar healing, and motor responses were performed. Results: Rats with nerve conduits showed less macroscopic scarring. Weekly assessments of motor nerve recovery showed no movement restrictions in limbs treated with PLA conduits, graft conduits, or conduits bridging retracted nerve stumps, based on responses to stimulus checks. An infection developed in the sciatic nerve and surrounding muscle tissue of one rat with a bio-graft conduit, prompting histopathological examination to investigate its cause. Conclusions: This proof-of-principle study demonstrates the feasibility of using 3D-printed biocompatible nerve conduits for peripheral nerve repair, providing a basis for future, more comprehensive investigations. Full article

Background: Iatrogenic nerve injuries (NIs) are an under-recognized complication of urological surgery. Though less common than vascular or organ damage, they may cause lasting sensory and motor deficits, significantly affecting patients’ quality of life. With increasing complexity in pelvic procedures, a consolidated understanding of nerve injuries is essential. Purpose: This review aims to synthesize current knowledge regarding peripheral and autonomic NIs in urological surgery, highlighting mechanisms of injury, associated procedures, preventative strategies, and treatment options. Scope: Focused on common urological interventions such as radical prostatectomy, cystectomy, pelvic lymphadenectomy, and reconstructive techniques, the review explores injuries from positional compression, traction, and intraoperative transection to their surgical management. Key Findings: The review categorizes nerve injuries into crush and transection types and details intraoperative signs and repair techniques. Skeletonization of nerves, avoidance of energy devices near neural structures, and prompt end-to-end anastomosis using 7-0 polypropylene are central to management. Adoption of novel sutureless nerve coaptation devices have also been described with promising outcomes. Early repair offers a better prognosis. New intraoperative technologies like NeuroSAFE during robotic-assisted procedures may enhance nerve preservation. Conclusion: Iatrogenic NIs, although rare, are clinically significant and often preventable. Prompt intraoperative recognition and repair are critical. Further research is warranted to develop standardized preventative protocols and enhance intraoperative nerve monitoring. A multidisciplinary approach, extended across surgical specialties, could improve outcomes and guide timely treatment of nerve injuries. Full article

The aim of this study is to assess endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) at the time of type 1 diabetes (T1D) recognition concerning patients’ clinical state, remaining insulin secretion, and further partial remission (PR) occurrence. We recruited 45 children that were admitted to hospital due to newly diagnosed T1D (median age 10.8 yrs), and 20 healthy peers as a control group. EPC and CEC levels were measured at disease onset in PBMC isolated from whole peripheral blood with the use of flow cytometry. Clinical data regarding patients’ condition, C-peptide secretion, and further PR prevalence were analyzed. T1D-diagnosed patients presented higher EPC levels than the control group (p = 0.026), while no statistical differences in CEC levels and EPC/CEC ratio were observed. Considering only T1D patients, those with better clinical conditions presented lower EPCs (p = 0.021) and lower EPC/CEC ratios (p = 0.0002). Patients with C-peptide secretion within a normal range at disease onset presented lower EPC/CEC ratios (p = 0.027). Higher levels of EPCs were observed more frequently in patients with higher glucose, decreased fasting C-peptide, and lower stimulated C-peptide (all p < 0.05). The presence of DKA was related to higher EPC/CEC ratios (p = 0.034). Significantly higher levels of CECs were observed in patients who presented partial remission of the disease at 6 months after diagnosis (p = 0.03) only. In the study group, positive correlations of CECs with age, BMI at onset, and BMI in following years were observed. EPC/CEC ratios correlated positively with glucose levels at hospital admission and negatively with age, BMI, pH, and stimulated C-peptide level. We reveal a new potential for the application of EPCs and CECs as biomarkers, reflecting both endothelial injury and reconstruction processes in children with T1D. There is a need for further research in order to reduce cardiovascular risk in children with T1D. Full article

Peripheral circulatory failure refers to a condition in which the blood flow through superficial capillaries is markedly reduced or completely occluded. In clinical practice, nurses strictly adhere to regular repositioning protocols to prevent peripheral circulatory failure, during which the skin condition is evaluated visually. In this study, skin colour changes resulting from pressure application were continuously captured using a camera, and supervised machine learning was employed to classify the data into two categories: before and after pressure. The evaluation of practical colour space components revealed that the h component of the JCh colour space demonstrated the highest discriminative performance (Area Under the Curve (AUC) = 0.88), followed by the a* component of the CIELAB colour space (AUC = 0.84) and the H component of the HSV colour space (AUC = 0.83). These findings demonstrate that it is feasible to quantitatively evaluate skin colour changes associated with pressure, suggesting that this approach can serve as a valuable indicator for dimensionality reduction in feature extraction for machine learning and is potentially an effective method for preventing pressure-induced skin injuries. Full article

Background/Objectives: Recent breakthroughs in three-dimensional (3D) printing and high-resolution imaging have opened up new possibilities in personalized medicine, surgical planning, and forensic reconstruction. This study breaks new ground by evaluating the integration of high-resolution peripheral quantitative computed tomography (HR-pQCT) with multimodal imaging and additive manufacturing to assess a chronic, infected gunshot injury in the knee joint of a red deer. This unique approach serves as a translational model for complex skeletal trauma. Methods: Multimodal imaging—including clinical CT, MRI, and HR-pQCT—was used to characterise the extent of osseous and soft tissue damage. Histopathological and molecular analyses were performed to confirm the infectious agent. HR-pQCT datasets were segmented and processed for 3D printing using PolyJet, stereolithography (SLA), and fused deposition modelling (FDM). Printed models were quantitatively benchmarked through 3D surface deviation analysis. Results: Imaging revealed comminuted fractures, cortical and trabecular degradation, and soft tissue involvement, consistent with chronic osteomyelitis. Sphingomonas sp., a bacterium that forms biofilms, was identified as the pathogen. Among the printing methods, PolyJet and SLA demonstrated the highest anatomical accuracy, whereas FDM exhibited greater geometric deviation. Conclusions: HR-pQCT-guided 3D printing provides a powerful tool for the anatomical visualisation and quantitative assessment of complex bone pathology. This approach not only enhances diagnostic precision but also supports applications in surgical rehearsal and forensic analysis. It illustrates the potential of digital imaging and additive manufacturing to advance orthopaedic and trauma care, inspiring future research and applications in the field. Full article

Syndecan-3 (SDC3), a transmembrane heparan sulfate proteoglycan involved in cell signaling and endocytosis, has recently been implicated in the pathogenesis of neurodegenerative disorders. While preclinical studies have demonstrated its role in Alzheimer’s disease (AD), its diagnostic relevance in peripheral blood remains unexplored. In this human cohort study, we measured SDC3 expression in peripheral blood mononuclear cells (PBMCs) from 22 clinically diagnosed AD patients and 20 cognitively unimpaired non-AD controls using a custom ELISA. The findings were compared with plasma p-tau217 levels and a panel of systemic laboratory markers. PBMC-expressed SDC3 was significantly elevated in AD patients and moderately correlated with AD status (r = 0.309, p = 0.0465) independent of age. Notably, SDC3 levels were inversely correlated with systemic inflammatory markers, including C-reactive protein (CRP; r = −0.421, p = 0.0055) and D-dimer (r = −0.343, p = 0.038), suggesting an AD-associated immune phenotype distinct from acute-phase or vascular inflammation. Conversely, plasma p-tau217 levels did not significantly differ between groups but correlated with markers of tissue injury and inflammation (LDH, GOT, and ferritin), potentially reflecting systemic influences in non-AD controls. A multivariable logistic regression model incorporating SDC3, p-tau217, and age demonstrated high diagnostic accuracy (AUC = 0.85). These findings identify PBMC-expressed SDC3 as a promising blood-based biomarker candidate for AD, warranting further validation in larger, biomarker-confirmed cohorts. Full article

High-altitude pulmonary edema (HAPE) is a severe condition associated with high-altitude environments, and its molecular mechanism has not been fully elucidated. This study systematically analyzed the DNA methylation status of HAPE patients and healthy controls using reduced-representation bisulfite sequencing (RRBS) and 850K DNA methylation chips, identifying key differentially methylated regions (DMRs). Targeted bisulfite sequencing (TBS) revealed significant abnormalities in DMRs of five genes, azurocidin 1 (AZU1), growth factor receptor bound protein 7 (GRB7), mannose receptor C-type 2 (MRC2), RUNX family transcription factor 3 (RUNX3), and septin 9 (SEPT9). The abnormal expression of AZU1 was validated using peripheral blood leukocytes from HAPE patients and normal controls, as well as rat lung tissue, indicating its potential importance in the pathogenesis of HAPE. To further validate the function of AZU1, we conducted experimental studies using a hypobaric hypoxia injury model in Human Umbilical Vein Endothelial Cells (HUVEC). The results showed that AZU1 was significantly upregulated under hypobaric hypoxia. Knocking down AZU1 mitigates the reduction in HUVEC proliferation, angiogenesis, and oxidative stress damage induced by acute hypobaric hypoxia. AZU1 induces cellular oxidative stress via the p38/mitogen-activated protein kinase (p38/MAPK) signaling pathway. This study is the first to elucidate the mechanism of AZU1 in HAPE via the p38/MAPK pathway, offering novel insights into the molecular pathology of HAPE and laying a foundation for future diagnostic and therapeutic strategies. Full article

Background: Prevention and clinical management of musculoskeletal injuries have historically focused on the assessment and training of modifiable physical factors, but perceptual decision-making has only recently been recognized as a potentially important capability. Immersive virtual reality (VR) systems can measure the speed, accuracy, and consistency of body movements corresponding to stimulus–response instructions for the completion of a forced-choice task. Methods: A cohort of 26 female college soccer players (age 19.5 ± 1.3 years) included 10 players who participated in a baseline assessment, 10 perceptual-response training (PRT) sessions, a post-training assessment that preceded the first soccer practice, and a post-season assessment. The remaining 16 players completed an assessment prior to the team’s first pre-season practice session, and a post-season assessment. The assessments and training sessions involved left- or right-directed neck rotation, arm reach, and step-lunge reactions to 40 presentations of different types of horizontally moving visual stimuli. The PRT program included 4 levels of difficulty created by changes in initial stimulus location, addition of distractor stimuli, and increased movement speed, with ≥90% response accuracy used as the criterion for training progression. Perceptual latency (PL) was defined as the time elapsed from stimulus appearance to initiation of neck rotation toward a peripheral virtual target. The speed–accuracy tradeoff was represented by Rate Correct per Second (RCS) of PL, and inconsistency across trials derived from their standard deviation for PL was represented by intra-individual variability (IIV). Perceptual Decision Efficiency (PDE) represented the ratio of RCS to IIV, which provided a single value representing speed, accuracy, and consistency. Statistical procedures included the bivariate correlation between RCS and IIV, dependent t-test comparisons of pre- and post-training metrics, repeated measures analysis of variance for group X session pre- to post-season comparisons, receiver operating characteristic analysis, and Kaplan–Meier time to injury event analysis. Results: Statistically significant (p < 0.05) results were found for pre- to post-training change, and pre-season to post-season group differences, for RCS, IIV, and PDE. An inverse logarithmic relationship was found between RCS and IIV (Spearman’s Rho = −0.795). The best discriminator between injured and non-injured statuses was PDE ≤ 21.6 (93% Sensitivity; 42% Specificity; OR = 9.29). Conclusions: The 10-session PRT program produced significant improvement in perceptual decision-making that appears to provide a transfer benefit, as the PDE metric provided good prospective prediction of musculoskeletal injury. Full article

Since the initial report indicating that LPA₁ signaling plays a key role in initiating nerve injury-induced neuropathic pain (NeuP), subsequent studies using knockout mice and LPA_1/3 antagonists have demonstrated that LPA₁ and LPA₃ signaling impact NeuP and fibromyalgia (FM) models. In the present study, we identified hyperalgesia sexual dimorphism involving LPA_1/3 signaling in the intermittent psychological stress induced-related FM-like model called intermittent psychological stress (IPS)-induced generalized pain (IPGP) model where the hyperalgesia in IPGP mice was abolished in LPA₁- and LPA₃-knock-out mice. Pharmacological intervention by intraperitoneal (i.p.) treatments with the LPA_1/3 antagonist Ki16425 consistently prevented hyperalgesia. However, intracerebroventricular treatments with Ki16425 abolished hyperalgesia in male, but not female, mice. Notably, intrathecal treatments of Ki16425 did not prevent hyperalgesia. Further studies revealed that splenocytes derived from female IPGP mice could initiate hyperalgesia via adoptive transfer in naïve mice, and this effect was abolished when donor mice were pre-treated with Ki16425 (i.p.). Thus, these studies identify male-specific LPA_1/3-mediated mechanisms in the brain underlying IPGP, as well as distinct LPA-LPA_1/3-mediated peripheral immune mechanisms. Full article

Background: Numerous experimental studies aim to improve outcomes of peripheral nerve repair following trauma. This study evaluates the efficacy of the human epineural patch (hEP) compared to the human amniotic membrane (hAM) in promoting nerve regeneration following sciatic nerve crush injury. Methods: Thirty-six athymic nude rats were divided into three groups (n = 12 per group) following nerve crush: (1) an unprotected injury site; (2) crush injury wrapped with hEP; and (3) crush injury wrapped with hAM. Animals were assessed over 6 or 12 weeks post-injury. Evaluations included motor recovery (Toe-Spread test), sensory recovery (Pinprick test), muscle denervation atrophy (the gastrocnemius muscle index (GMI)), histomorphometry (myelin thickness, axonal density, fiber diameter, and percentage of myelinated fibers), and immunofluorescence (GFAP, Laminin B, NGF, S-100, VEGF, vWF, HLA-DR, and HLA-I) assessments. Results: The hEP group showed superior motor recovery, axonal density and higher GMI values compared to the hAM and control groups. The increased expression of neurogenic and angiogenic markers highlighted its neuroregenerative potential. Negligible HLA-DR and HLA-I expression confirmed the lack of hEP and hAM immunogenicity. Conclusions: The application of hEP following sciatic nerve crush injury facilitated nerve regeneration, improved functional outcomes, and offered a viable alternative to hAM. Structural stability and the regenerative capacity position hEP as a new, promising off-the-shelf product for nerve regeneration. Full article

We previously showed that selective suppression of CD44 in the corneal epithelium leads to structural abnormalities in the mouse cornea. Our comparative studies of young and aged ocular biopsies revealed that CD44 expression is downregulated in aged corneas, while leucine-rich repeats and immunoglobulin-like domain 1 (Lrig1+) stem cells remain preserved in the peripheral limbus. These findings suggest an age-related shift in the corneal stem cell compartmentalization, characterized by impaired CD44 expression in the central cornea and preservation of Lrig1+ stem cells in the limbus, which become the main stem cells in the senescent cornea. To investigate this further, we performed topical tamoxifen-inducible, diphtheria toxin-mediated ablation of Lrig1+ stem cells in mouse corneas. We then assessed both activated and non-activated beta-catenin expression in wild-type (WT) and CD44 knockout (CD44KO) mice, given that CD44 modulates the Wingless-related integration site (Wnt) pathway. Our results indicate that two distinct stem cell populations operate in the mouse cornea: Lrig1-derived stem cells and Wnt-activity/CD44-dependent stem cells. The Lrig1-derived cells act as a reservoir of quiescent stem cells that regenerate the cornea upon injury, whereas under homeostatic conditions, the Wnt-activity/CD44-dependent stem cells are primarily responsible for corneal renewal. In the aged cornea, the loss of CD44 expression leads to reduced Wnt signaling, making the tissue increasingly dependent on Lrig1+ stem cells for regeneration. In mice, Lrig1+ stem cells are capable of sustaining permanent corneal renewal, even in the absence of CD44. Full article