Search Results (1,988)

Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation, demyelination, and neurodegeneration within the central nervous system (CNS). While the inflammatory components of MS have been extensively studied, the progressive neurodegenerative aspect remains a critical factor contributing to long-term disability. Therefore, the identification and validation of biomarkers associated with neurodegenerative processes are essential for improved diagnosis, prognosis, and treatment monitoring. This review explores cerebrospinal fluid (CSF) and blood-based biomarkers, including neurofilaments, lipid markers, kynurenines, and other molecular indicators that provide insights into neurodegeneration in MS. Full article

Chronic inflammation is increasingly recognized as a key driver of tumorigenesis, affecting both the tumor microenvironment and host response. In this context, circulating inflammatory proteins may provide valuable insights into cancer activity. This study evaluated the diagnostic performance of the inflammatory protein ratio (IPR), a composite index derived from serum protein electrophoresis, in detecting active cancer among hospitalized patients. We retrospectively analyzed clinical and laboratory data from 312 adult patients admitted to the Internal Medicine and Aging Department at Policlinico Foggia, Italy, between November 2023 and July 2024. Patients were stratified according to the presence of active cancer, defined by NICE criteria. The diagnostic accuracy of the IPR was compared with that of conventional inflammatory markers, including C-reactive protein (CRP) and the neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), monocyte–lymphocyte ratio (MLR), and systemic immune–inflammation index (SII). The IPR showed the highest diagnostic performance, with a sensitivity of 88.1%, a specificity of 75.2%, and an area under the receiver operating characteristic curve (AUC) of 0.868. Its negative predictive value reached 97.6%, underscoring its potential as a rule-out tool for malignancy in hospitalized patients. These findings support the IPR as a promising and cost-effective inflammation-based biomarker for cancer detection, warranting further validation in prospective and molecularly characterized cohorts. Full article

Marker-based, IMU-based (6-axis IMU), and smartphone-based (OpenCap) motion capture methods are commonly used for motion analysis. The accuracy and reliability of these methods are crucial for applications in rehabilitation and sports training. This study compares the accuracy and inter-operator reliability of inverse kinematics (IK) solutions obtained from these methods, aiming to assist researchers in selecting the most appropriate system. For most lower limb inverse kinematics during walking motion, the IMU-based method and OpenCap show comparable accuracy to marker-based methods. The IMU-based method demonstrates higher accuracy in knee angle (5.74 ± 0.80 versus 7.36 ± 3.14 deg, with p = 0.020) and ankle angle (7.47 ± 3.91 versus 8.20 ± 3.00 deg, with p = 0.011), while OpenCap shows higher accuracy than IMU in pelvis tilt (5.49 ± 2.22 versus 4.28 ± 1.47 deg, with p = 0.013), hip adduction (6.10 ± 1.35 versus 4.06 ± 0.78 deg, with p = 0.019) and hip rotation (6.09 ± 1.74 versus 4.82 ± 2.30 deg, with p = 0.009). The inter-operator reliability of the marker-based method and the IMU-based method shows no significant differences in most motions except for hip adduction (evaluated by the intraclass correlation coefficient-ICC, 0.910 versus 0.511, with p = 0.016). In conclusion, for measuring lower-limb kinematics, wearable sensors (6-axis IMUs) achieve comparable accuracy and reliability to the gold standard, marker-based motion capture method, with lower equipment requirements and fewer movement constraints during data acquisition. Full article

(1) The link between periodontal disease (PD) and acute coronary syndromes (ACSs) is predominantly attributed to the atherosclerotic process, mediated by systemic inflammation. However, the correlation between the severity of PD, characterized by the presence of periodontal pathogens, and systemic inflammation in patients with ACS remains inadequately clarified. (2) This study aims to assess the association between the severity of PD and systemic inflammatory biomarkers, along with lipid profiles, in patients with ACS. (3) In total, 42 patients with ACS and concomitant PD were divided into two groups based on the presence of periodontal pathogens belonging to the red or red-orange complexes. Group 1–29 patients displayed pathogens from the red complex (RC) and group 2–13 patients displayed pathogens from the red-orange complex (ROC). All participants underwent a comprehensive dental examination, including DNA sampling from the periodontal pockets for pathogen detection. Systemic inflammation was evaluated alongside assessments of lipid profiles. (4) Inflammatory markers were more pronounced in the RC group compared with the ROC group. Moreover, patients in the RC group showed significantly higher monocyte-to-lymphocyte ratios (0.41 ± 0.20 vs. 0.28 ± 0.12; p = 0.002), platelet-to-lymphocyte ratios (139.50 ± 33.85 vs. 100.90 ± 8.84; p = 0.02), serum C-reactive protein levels (9.34 ± 1.08 mg/L vs. 5.46 ± 1.03 mg/L; p = 0.03), and serum uric acid levels (6.9 ± 0.49 mg/dL vs. 5.4 ± 0.26 mg/dL; p = 0.006). Concerning lipid profiles, the RC group exhibited significantly higher low-density lipoprotein cholesterol (LDL) levels (169.60 ± 12.63 mg/dL vs. 106.70 ± 9.34 mg/dL; p = 0.0007) and significantly lower high-density lipoprotein cholesterol (HDL) levels (29.29 ± 3.50 mg/dL vs. 39.56 ± 2.07 mg/dL; p = 0.002). (5) The severity of PD, indicated by the concomitant presence of pathogens from the red and orange complexes, is associated with an unfavorable lipid profile and elevated inflammatory biomarkers. These findings highlight the potential importance of periodontal intervention in the prevention of ACS. Full article

Hepatitis E virus (HEV) is a positive-sense, single-stranded RNA virus that poses a significant public health risk, yet its study is hindered by the complexity of conventional RNA-based reverse genetics systems. These systems require multiple steps, including genome cloning, in vitro transcription, and capping, making them labor-intensive and susceptible to RNA degradation. In this study, we developed a single-step, plasmid-based HEV expression system that enabled direct intracellular transcription of the full-length HEV genome under a cytomegalovirus immediate-early (CMV-IE) promoter. The viral genome was flanked by hammerhead (HH) and hepatitis delta virus (HDV) ribozymes to ensure precise self-cleavage and the generation of authentic 5′ and 3′ termini. This system successfully supported HEV genome replication, viral protein expression, and progeny virion production at levels comparable to those obtained using in vitro-transcribed, capped HEV RNA. Additionally, a genetic marker introduced into the plasmid construct was stably retained in progeny virions, demonstrating the feasibility of targeted genetic modifications. However, plasmid-derived HEV exhibited delayed replication kinetics, likely due to the absence of an immediate 5′ cap. Attempts to enhance capping efficiency through co-expression of the vaccinia virus capping enzyme failed to improve HEV replication, suggesting that alternative strategies, such as optimizing the promoter design for capping, may be required. This plasmid-based HEV reverse genetics system simplifies the study of HEV replication and pathogenesis and provides a versatile platform for the genetic engineering of the HEV genome. Full article

Industrial exoskeletons (a.k.a. wearable robots) have been developed to reduce musculoskeletal fatigue and work injuries. Human joint kinematics and human–robot alignment are important measurements in understanding the effects of industrial exoskeletons. Recently, markerless pose estimation systems based on monocular color (red, green, blue—RGB) and depth cameras are being used to estimate human joint positions. This study analyzes the performance of monocular markerless pose estimation systems on human skeletal joint estimation while wearing exoskeletons. Two pose estimation systems producing RGB and depth images from ten viewpoints are evaluated for one subject in 14 industrial poses. The experiment was repeated for three different types of exoskeletons on the same subject. An optical tracking system (OTS) was used as a reference system. The image acceptance rate was 56% for the RGB, 22% for the depth, and 78% for the OTS pose estimation system. The key sources of pose estimation error were the occlusions from the exoskeletons, industrial poses, and viewpoints. The reference system showed decreased performance when the optical markers were occluded by the exoskeleton or when the markers’ position shifted with the exoskeleton. This study performs a systematic comparison of two types of monocular markerless pose estimation systems and an optical tracking system, as well as a proposed metric, based on a tracking quality ratio, to assess whether a skeletal joint estimation would be acceptable for human kinematics analysis in exoskeleton studies. Full article

As an important class of microorganisms, filamentous fungi have crucial roles in protein secretion, secondary metabolite production and environmental pollution control. However, characteristics such as apical growth, heterokaryon, low homologous recombination (HR) efficiency and the scarcity of genetic markers mean that the application of traditional gene editing technology in filamentous fungi faces great challenges. The introduction of the RNA-mediated CRISPR/Cas (clustered regularly interspaced short palindromic repeat/CRlSPR-associated protein) system in filamentous fungi in recent years has revolutionized gene editing in filamentous fungi. In addition, the continuously expressed CRISPR system has significantly improved the editing efficiency, while the optimized sgRNA design and reduced cas9 concentration have effectively reduced the off-target effect, further enhancing the safety and reliability of the technology. In this review, we systematically analyze the molecular mechanism and regulatory factors of CRISPR/Cas9, focus on the optimization of its expression system and the improvement of the transformation efficiency in filamentous fungi, and reveal the core regulatory roles of HR and non-homologous end-joining (NHEJ) pathways in gene editing. Based on the analysis of various filamentous fungi applications, this review reveals the outstanding advantages of CRISPR/Cas9 in the enhancement of protein secretion, addresses the reconstruction of secondary metabolic pathways and pollutant degradation in the past decade, and provides a theoretical basis and practical guidance for the optimization of the technology and engineering applications. Full article

Background: Photodynamic therapy (PDT) utilizing nano-based photosensitizers (PSs) offers promising cancer treatment potential but requires rigorous safety evaluation. Conjugated polymer nanoparticles (CPNs) doped with porphyrins, such as platinum porphyrin–doped poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT), exhibit enhanced photodynamic efficiency but lack comprehensive preclinical toxicity data. This study aimed to evaluate the biocompatibility, biodistribution, and acute/subacute toxicity of these CPNs to establish their safety profile for clinical translation. Methods: CPNs were synthesized via nanoprecipitation using amphiphilic stabilizers (PSMA or PS-PEG-COOH) and characterized for colloidal stability in parenteral solutions. Hemolysis assays were used to assess blood compatibility. Single-dose (0.3 and 1 mg/kg, intravenous) and repeated-dose (0.1–1 mg/kg, intraperitoneal, every 48 h for 28 days) toxicity studies were conducted in BALB/c mice. Hematological, biochemical, histopathological, and biodistribution analyses (via ICP-MS) were performed to evaluate systemic and organ-specific effects. Results: CPNs demonstrated excellent colloidal stability in 5% dextrose, with minimal aggregation. No hemolytic activity was observed at concentrations up to 50 mg/L. Single and repeated administrations revealed no significant changes in body/organ weights, hematological parameters (except transient fibrinogen elevation), or liver/kidney function markers (ALT, AST, BUN, Cr). Histopathology showed preserved tissue architecture in major organs, with mild hepatocyte vacuolation at 30 days. Biodistribution indicated hepatic/splenic accumulation and rapid blood clearance, suggesting hepatobiliary elimination. Conclusions: Platinum porphyrin–doped F8BT CPNs exhibited minimal acute and subacute toxicity, favorable biocompatibility, and no systemic adverse effects in murine models. These findings support their potential as safe PS candidates for PDT. However, chronic toxicity studies are warranted to address long-term organ accumulation and metabolic impacts. This preclinical evaluation provides a critical foundation for advancing CPNs toward clinical applications in oncology. Full article

Background: We aimed to evaluate the clinical significance of abnormal rotational thromboelastometry (ROTEM) findings in trauma patients and investigate the relationships between FIBTEM-maximum clot firmness (MCF), fibrinogen concentration and patient outcomes. Methods: A retrospective cohort analysis was conducted on adult trauma patients who underwent on-admission ROTEM testing between January 2020 and January 2021. Univariate analyses compared data based on injury severity, ROTEM findings (normal vs. abnormal), and initial fibrinogen concentration (normal vs. hypofibrinogenemia). ROC curve analysis was performed to determine the diagnostic performance of FIBTEM A10/MCF for its association with hypofibrinogenemia. Results: A total of 1488 patients were included in this study; the mean age was 36.4 ± 14.2 years and 92% were male. In total, 376 (25.3%) patients had ROTEM abnormalities. Severe injuries (ISS ≥ 16) were associated with a higher shock index, positive troponin T levels, standard coagulation abnormalities, hypofibrinogenemia, and abnormal ROTEM parameters (p < 0.05). These patients also had higher rates of massive transfusions and in-hospital mortality (p = 0.001). Coagulation alterations were significantly associated with higher injury severity score (ISS), shock index, head abbreviated injury score (AIS), hypofibrinogenemia, transfusion need, and mortality (p < 0.05). Hypofibrinogenemic patients were younger, sustained severe injuries, had higher shock indices and coagulation marker levels, required more intensive treatments, had longer hospital stays, and had higher mortality (p < 0.05). A significant positive correlation was found between plasma fibrinogen concentration and FIBTEM-MCF (r = 0.294; p = 0.001). Conclusions: Approximately one-fourth of the patients had early traumatic coagulopathy, as assessed by ROTEM. The FIBTEM A10/MCF may serves as a surrogate marker for plasma fibrinogen concentration. While prior studies have established the link between ROTEM and injury severity, our findings reinforce its relevance across varying trauma severity levels. However, prospective studies are warranted to validate its role within diverse trauma systems and evolving resuscitation protocols. Full article

Background/Objectives: Anastomosing hemangioma (AH) is a rare, benign vascular tumor predominantly found in the genitourinary tract and often associated with impaired renal function. Due to its nonspecific radiological features, AH is frequently misinterpreted as a malignant vascular neoplasm, particularly angiosarcoma (AS), leading to potentially unnecessary surgical interventions. This study presents a systematic review of AH cases and describes a rare instance of retroperitoneal AH arising from the left gonadal vein, which was resected due to diagnostic uncertainty. Methods: A 68-year-old man underwent imaging for benign prostatic hyperplasia, incidentally revealing a 15-mm hypervascular retroperitoneal nodule adjacent to the left psoas muscle. Imaging findings, including moderate metabolic uptake on 18FDG-PET/CT, raised suspicion for AS. Given the diagnostic uncertainty and high-risk location, the multidisciplinary team (MDT) recommended surgical resection. Laparoscopic excision was performed, and histopathological analysis confirmed AH. The patient remained asymptomatic at a 22 month follow-up. In addition, a systematic review of 159 cases from 64 studies (2009–2024) was conducted to analyze radiological features, treatment approaches, and outcomes. Results: Among the reviewed cases, 68% were incidentally diagnosed, with AH occurring predominantly in the genitourinary system (70%), especially in the kidney, adrenal gland, and ovary. Chronic kidney disease (CKD) was present in 23.3% of cases, while 19.5% had a history of malignancy. Imaging was inconclusive in differentiating AH from malignancies: CT (71.9%) and MRI (6.1%) were the most used modalities, but none could reliably exclude AS. Management strategies included upfront surgical resection in 85%, while a growing proportion (9%) of cases underwent biopsy-based observation rather than immediate surgery. No cases were followed with imaging alone. Conclusions: AH remains a diagnostic challenge due to its overlap with malignant vascular tumors. While surgical excision is often performed, our review highlights an increasing trend toward conservative management with biopsy-based diagnosis. Improved awareness and the integration of histopathology, molecular markers, and MDT-based decision-making are crucial to prevent overtreatment in cases of suspected AH. Full article

The brain-derived neurotrophic factor (BDNF) has become one of the cornerstones of neuropathology, influencing synaptic plasticity, cognitive resilience, and neuronal survival. Apart from its molecular biology, BDNF is a powerful target for transformative benefit in precision medicine, leading to innovative therapeutic approaches for neurodegenerative and psychiatric diseases like Alzheimer’s disease (AD), Parkinson’s disease (PD), major depressive disorder (MDD), and post-traumatic stress disorder (PTSD). Nevertheless, clinical applicability is obstructed by hurdles in delivery, patient-specific diversity, and pleiotropic signaling. Here, we summarize findings in BDNF research, including its regulatory pathways and diagnostic/prognostic biomarkers and integrative therapeutic approaches. We describe innovative delivery systems, such as lipid nanoparticle-based mRNA therapies and CRISPR-dCas9-based epigenetic editing that bypass obstacles such as BBB (blood–brain barrier) and enzymatic degradation. The recent implementation of multiplex panels combining BDNF biodynamic indicators with tau and amyloid-β signaling markers showcases novel levels of specificity for both early detection and potential therapeutic monitoring. Humanized preclinical models like iPSC-derived neurons and organoids point to the key role of BDNF in neurodeveloping and neurodegenerative processes, paralleling advances in bridging preclinical observation and clinical environments. Moreover, novel therapeutic tools delivering TrkB activators or the implementation of AI-based dynamic care platforms enable tailored and scalable treatments. This review also aims to extend a framework used in the understanding of BDNF’s relevance to traditional neurodegenerative models by situating more recent work detailing BDNF’s actions in ischemic tissues and the gut–brain axis in the context of systemic health. Finally, we outline a roadmap for the incorporation of BDNF-centered therapies into worldwide healthcare, highlighting ethical issues, equity, and interdisciplinary decomposition. The therapeutic potential of BDNF heralds a new era in neuroscience and medicine, revolutionizing brain health and paving the way for the advancement of precision medicine. Full article

The myogenic differentiation of muscle satellite cells (MuSCs) is an important biological process that plays a key role in the regeneration and repair of skeletal muscles. However, the mechanisms regulating myoblast myogenesis require further investigation. In this study, we found that STEAP3 is involved in myogenic differentiation based on the Yunan black pig MuSCs model in vitro using cell transfection and other methods. Furthermore, the expression of myogenic differentiation marker genes MyoG and MyoD and the number of myotubes formed by the differentiation of cells from the si-STEAP3 treated group were significantly decreased but increased in the STEAP3 overexpression group compared to that in the control group. STEAP3 played a role in iron ion metabolism, affecting myogenic differentiation via the uptake of iron ions and enhancing IRP-IRE homeostasis. STEAP3 also activated the PI3K/AKT pathway, thus promoting myoblast differentiation of Yunan black pig MuSCs. The results of this study showed that STEAP3 overexpression increased intracellular iron ion content and activated the homeostatic IRP-IRE system to regulate intracellular iron ion metabolism. Full article

Background: Choroid plexus is a complex structure in the human brain that is responsible for the secretion of extracellular vesicles (EVs) in cerebrospinal fluid. Few studies to date have generated choroid plexus (ChP) organoids differentiated from human induced pluripotent stem cells (hiPSCs) and analyzed their secreted EVs. The scalable Vertical-Wheel bioreactors (VWBRs) provide low shear stress and a controlled environment. Methods: This study utilized VWBRs for the differentiation of hiPSCs into ChP organoids and generation of the secreted EVs compared to a static culture. Additionally, this study loaded curcumin into ChP organoid-derived EVs, performed EV lyophilization, and determined the ability of the re-hydrated EVs to alleviate neuro-inflammation. Results: The results demonstrated that the VWBR culture exhibited more aerobic metabolism and active glucose and glutamine consumption than the static control. Consequently, the ChP markers and Endosomal Sorting Complexes Required for Transport-dependent and -independent EV biogenesis genes were significantly upregulated (2–3-fold) in the VWBR, producing four-fold-higher EVs per mL media than the static control. The EVs retained similar size and zeta potential after lyophilization and re-hydration. The cells exposed to amyloid beta 42 oligomers and treated with the curcumin-loaded re-hydrated EVs showed high viability and the reduced inflammatory response determined by TNF-α and IL-6 expression. Conclusions: This study demonstrates a scalable bioreactor system to promote ChP organoid differentiation and generation of EV-based cell-free therapeutics to treat neural inflammation in various neurological disorders. Full article

Dendritic cells (DCs) are major contributors to generating an effective immune response due to their ability to present antigens to T cells. Recently, nanoparticles have been widely used in different medical applications, such as drug-delivery systems, to enhance the function of impaired immune cells. Objectives: This research aims to develop an effective antitumor DC-based vaccine by adsorption of chitosan-nanoparticles (CH-NPs) onto DCs. Methods: Undifferentiated mouse bone marrow progenitor cells were differentiated into mature DCs using cytokines and lipopolysaccharides. CH-NPs were prepared using the ionic gelation method and subsequently used to coat the stimulated DCs. The MTT assay was employed to assess the cytotoxicity of all formulations. To compare the antitumor effect of CH-NPs, DCs, and DCs-CH-NPs, mice were divided into five groups and injected with the respective vaccine formulations. Following immunization, flow cytometry was used to analyze DC and CD4⁺ T cell activation in blood and spleen tissues. Histological samples from the spleen and lymph nodes were also collected. Results: Our findings show that co-stimulatory molecules CD80/CD86 and the DC maturation marker CD83 were upregulated in the vaccinated DCs, indicating their maturation. Moreover, CD83, CD11c, and MHC-II were upregulated in blood and spleen samples in vivo. The DC-CH-NPs vaccinated group had a higher mean percentage of CD83 expression in blood samples (76.7 ± 17.1) compared to the DCs group (47.7 ± 11.0) and the CH-NPs group (37.7 ± 8.6). DC markers, particularly CD83, were highly expressed in spleen samples. Additionally, the DC-CH-NPs vaccinated group had a significantly higher number of CD4⁺ T cells (MFI = 26.1 ± 2.3) compared to the DCs (18.6 ± 1.6) and CH-NPs (13.3 ± 1.4) groups. Conclusions: The present study concludes that the DC-CH-NPs vaccine formulation can induce a potent in vivo immune response. These data may provide valuable insights for developing effective delivery systems for antitumor vaccines. Full article

Background: The albumin–bilirubin (ALBI) score, initially a hepatic function marker, may also reflect systemic inflammation and oxidative stress, both linked to the no-reflow phenomenon (NRP). This study investigates the ALBI score’s predictive value for the NRP and compares it with conventional risk models. Methods: This retrospective, single-center study included 1563 NSTE-ACS patients who underwent PCI between January 2023 and February 2024. Two predictive models were developed: (i) a fitted model with variables selected based on the XGBoost algorithm and SHapley Additive ExPlanations (SHAP) values, and (ii) an ALBI model including the ALBI score. Machine learning via the XGBoost algorithm was used for modeling, with SHAP applied to assess the significance of predictors. Results: The NRP occurred in 14.8% (231/1563) of patients. The ALBI score emerged as an independent predictor (OR = 12.10, 95% CI: 7.75–18.89, p < 0.001). The ALBI model demonstrated superior predictive power compared to the fitted model (C-index: 0.860 vs. 0.799), with significant improvements in discrimination (11.1%, p < 0.001) and reclassification (14.5%, p = 0.002). SHAP analysis ranked the ALBI score (1.025) as the strongest predictor, followed by hs-TnI (0.814), e-GFR (0.582), and pre-dilatation (0.283). The ALBI model exhibited better specificity (AUC: 0.860 vs. 0.798), calibration (Brier score: 0.088 vs. 0.102), and model fit (AIC: 964.7 vs. 1098.3) compared to the fitted model, indicating superior overall performance. Conclusions: The ALBI score significantly enhances the prediction of the NRP in NSTE-ACS patients undergoing PCI, outperforming traditional risk models. Incorporating the ALBI score into predictive frameworks may improve early risk stratification and guide clinical decision-making. Full article