Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this condition. Diabetic peripheral neuropathy, a common complication of diabetes, is characterized by nerve damage due to high blood sugar levels that lead to symptoms, such as pain, tingling, and numbness, primarily in the hands and feet. The aim of this systematic review was to evaluate the efficacy of neuromodulatory techniques as potential therapeutic interventions for patients with diabetic peripheral neuropathy, while also examining recent developments in this domain. The investigation encompassed an array of neuromodulation methods, including frequency rhythmic electrical modulated systems, dorsal root ganglion stimulation, and spinal cord stimulation. This systematic review suggests that neuromodulatory techniques may be useful in the treatment of diabetic peripheral neuropathy. Understanding the advantages of these treatments will enable physicians and other healthcare providers to offer additional options for patients with symptoms refractory to standard pharmacologic treatments. Through these efforts, we may improve quality of life and increase functional capacity in patients suffering from complications related to diabetic neuropathy.

Sepsis is a critical condition characterized by an abnormal immune response to infection, resulting in systemic inflammation, organ failure, and high mortality rate. Postoperative sepsis, accounting for nearly one-third of all sepsis cases, predominantly affects the elderly and individuals with pre-existing conditions, with fatality rates between 30 and 50%. Surgical stress induces immune, hormonal, and metabolic disturbances, heightening susceptibility to immune dysregulation and sepsis. Neurocognitive disorders related to postoperative sepsis, which share pathophysiological similarities with sepsis-associated encephalopathy, involve neuroinflammation, blood-brain barrier disruption, and mitochondrial dysfunction. Cognitive impairments, such as delirium, are frequent postoperative complications that vary in severity depending on the surgical complexity. This review examined the underlying mechanisms of these dysfunctions, the influence of different surgical procedures, and predictive and therapeutic strategies, including machine learning models, aimed at improving patient outcomes.

Glufosinate-ammonium (GLA) is a highly water-soluble and broad-spectrum herbicide, which poses a potential risk to aquatic organisms in aquatic ecosystems. In this study, the neurotoxic effects of GLA exposure on juvenile Eriocheir sinensis were evaluated from the perspective of microbiota-intestine-brain axis. The acute toxicity test was conducted by semi-static method. The results showed that GLA exposure induced neurotoxicity in juvenile crabs, mainly manifested by significantly increased neuronal apoptosis rate, DNA damage and neuron-specific enolase activity in serum, and showed a dose-dependent manner. The expression of apoptosis-related genes showed a similar trend. Moreover, GLA exposure significantly affected the depolarization and hyperpolarization signal transduction processes in the nervous system of juvenile crabs. In addition, compared with the control group, GLA exposure resulted in significantly changed of metabolic profile in ganglia, especially amino acid metabolism and glycerophospholipid metabolism. The intestinal microbial diversity changed significantly at the phylum, family and genus levels exposed to GLA. These results revealed the potential role of microbiota-intestine-brain axis in GLA-induced neurotoxicity in juvenile crabs. Taken together, this study suggested that GLA may induce neurotoxicity damage in juvenile crabs by affecting the neurotransmitter system and nerve signal transduction, and the inapplicability of the blood-brain barrier in crustaceans may intense the effect of microbial changes on neurological function. The results of this study provide new insights into the mechanism of GLA-induced neurotoxicity and preliminarily demonstrate the toxic risk of GLA exposure to non-target aquatic species.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by amyloid-beta (Aβ) accumulation and neuroinflammation. A previous multicenter, phase 2, double-blind, placebo-controlled trial randomized 179 participants into placebo or resveratrol over 52 weeks. Sub-analysis of CSF biomarkers of neuronal damage, inflammation, and microglial activity was performed in a subset of patients treated with a placebo (n = 21) versus resveratrol (n = 30). Markers of neuronal damage, including neuron-specific enolase and hyperphosphorylated neurofilaments, were reduced. Microglial activation was measured via a triggering receptor expressed on myeloid cells (TREM)-2 at baseline and after resveratrol treatment. Resveratrol significantly reduced CSF TREM2 levels and decreased inflammation and tissue damage, including matrix metalloprotease (MMP)-9. Cathepsin D, a lysosomal marker of autophagy, was reduced in the resveratrol group compared with placebo, while angiogenin, a marker of vascular angiogenesis, was increased. These data suggest that resveratrol may exert anti-inflammatory and neuroprotective effects in AD by reducing CSF TREM2 and other markers of neuronal damage. Further research is needed to assess the significance of these biomarker changes on clinical outcomes in patients with neurodegenerative diseases.

With the advent of new therapeutic approaches, there is hope that anticancer treatment will eventually be possible without the use of chemotherapy. Efficient immunotherapeutic options have recently emerged in many cancers, offering a less aggressive approach, with overall better tolerance, making them also suitable for frail patients. Response to immunotherapy relies on the availability, functionality, and efficacy of the host's immune effector mechanisms. One of the key factors determining the efficacy of immunotherapy is the tumor microenvironment, which encompasses various immune effectors, including macrophages, which play a crucial role in regulating immune responses through phagocytosis and antigen presentation. Macrophages are prototypically divided, according to their polarization, into either the pro-inflammatory M1 type or the anti-inflammatory M2 type. In the tumor microenvironment, M2-polarized macrophages, known as tumor-associated macrophages (TAMs), are the predominant phenotype and are associated with tumor progression. The M1/M2 paradigm contributes to the understanding of tumor progression. Due to the variable microenvironment, the mechanisms regulating TAMs can vary across different cancers. Variations in TAM polarization may account for the different treatment responses in patients with similar diseases. This paper investigates the connection between TAMs, disease progression, and treatment responses in the most frequent solid hematologic cancer, diffuse large B-cell lymphoma.

The circulating enteroviruses (EVs) serotypes in hand, foot and mouth disease (HFMD) inpatients remained unclear. This study aimed to investigate the serotype-specific associations between clinical characteristics and severity of HFMD inpatients. The study utilised a prospective, hospital-based cohort design and a tiered diagnostic algorithm incorporating real-time RT-PCR and nested RT-PCR for serotyping. Clinical data were prospectively collected throughout hospitalization. Clinical severity was measured using diagnoses of central nervous system (CNS) complications and three other outcomes. A total of 1768 inpatients were enrolled consecutively between February 2017 and February 2018. The proportions of CNS complications varied by serotype (p < 0.001), with the highest for EV-A71 (40%), followed by CV-A4 (17%), CV-A2 (13%), CV-A10 (10%), CV-A6 (7%), and CV-A16 (4%). Children with CV-A2 and CV-A4 were less likely to have rashes on hands, feet, or buttocks and more likely to develop high fever, while those with EV-A71 had fewer mouth lesions. Of 230 lab-confirmed HFMD inpatients with CNS complications, EV-A71 accounted for 45% while CV-A6, CV-A16, CV-A4, CV-A10 and CV-A2 accounted for 35%. The logistic regression analysis revealed that non-CNS-specific symptoms such as cold limbs and vomiting, and clinical testing indicators including blood globulin, platelet, serum chloride and neutrophil counts, were associated with CNS complications. Non-EV-A71 EVs can also cause severe diseases, but those with EV-A71 infection are more likely to suffer CNS complications and other severe manifestations. The study highlighted the emergence of enterovirus serotypes, suggesting the need for future research on virus changes and associated disease burden.

To develop and validate a multimodal deep learning (DL) model based on computed tomography (CT) images and clinical knowledge to predict lymph node metastasis (LNM) in early lung adenocarcinoma.

A total of 724 pathologically confirmed early invasive lung adenocarcinoma patients were retrospectively included from two centers. Clinical and CT semantic features of the patients were collected, and 3D radiomics features were extracted from nonenhanced CT images. We proposed a multimodal feature fusion DL network based on the InceptionResNetV2 architecture, which can effectively extract and integrate image and clinical knowledge to predict LNM.

A total of 524 lung adenocarcinoma patients from Center 1 were randomly divided into training (n=418) and internal validation (n=106) sets in a 4:1 ratio, while 200 lung adenocarcinoma patients from Center 2 served as the independent test set. Among the 16 collected clinical and imaging features, 8 were selected: gender, serum carcinoembryonic antigen, cytokeratin 19 fragment antigen 21-1, neuron-specific enolase, tumor size, location, density, and centrality. From the 1595 extracted radiomics features, six key features were identified. The CS-RS-DL fusion model achieved the highest area under the receiver operating characteristic curve in both the internal validation set (0.877) and the independent test set (0.906) compared to other models. The Delong test results for the independent test set indicated that the CS-RS-DL model significantly outperformed the clinical model (0.844), radiomics model (0.850), CS-RS model (0.872), single DL model (0.848), and the CS-DL model (0.875) (all P<0.05). Additionally, the CS-RS-DL model exhibited the highest sensitivity (0.941) and average precision (0.642).

The knowledge derived from clinical, radiomics, and DL is complementary in predicting LNM in lung adenocarcinoma. The integration of clinical and radiomics scores through DL can significantly improve the accuracy of lymph node status assessment.

The rapid identification of stroke is critical to improving stroke patient outcomes. Existing protocols for assessing the risk of stroke are subjective and may be further complicated by nonspecific symptoms, increasing the risk of misdiagnosis. Neuron-specific enolase (NSE) has emerged as a promising stroke biomarker. However, current detection methods such as the electrochemiluminescence immunoassay (ECLIA) are time-consuming and costly. In this research, we developed an electrochemical biosensor for the rapid quantification of NSE in whole blood. Mouse stroke models were established, and blood samples collected were analyzed using both hospital-standard ECLIA as well as the biosensor. The biosensor limit of detection was 1.15 ng/mL. NSE measurements were highly correlated between the two methods and were obtained in 5 min using 20 μL of unprocessed whole blood samples. Notably, the biosensor could accurately quantify elevated blood NSE blood that was associated with more severe stroke. Our results demonstrate the utility of the proposed biosensor in pre-hospital settings. Combined with existing stroke assessment methods, the biosensor may enable emergency personnel to identify stroke risk with greater accuracy to optimize the chances of receiving necessary treatment within the effective window.

Diagnosing traumatic brain injury (TBI) remains challenging due to an incomplete understanding of its neuropathological mechanisms. TBI is recognised as a complex condition involving both primary and secondary injuries. Although oxidative stress is a non-specific molecular phenomenon observed in various neuropathological conditions, it plays a crucial role in brain injury response and recovery. Due to these aspects, we aimed to evaluate the interaction between some known TBI molecular biomarkers and oxidative stress in providing evidence for its possible relevance in clinical diagnosis and outcome prediction. We found that while many of the currently validated molecular biomarkers interact with oxidative pathways, their patterns of variation could assist the diagnosis, prognosis, and outcomes prediction in TBI cases.

The National Institutes of Health Stroke Scale (NIHSS) is a known risk factor for post-stroke depression (PSD). However, more objective indicators are needed. The role of neuron-specific enolase (NSE) in PSD development remains unclear. This study aimed to ascertain the correlation of NIHSS score and NSE with PSD risk, and establish a novel nomogram combining NSE and NIHSS for early PSD prediction.

A total of 172 patients with acute ischemic stroke (AIS) were involved. Baseline clinical data including NSE and NIHSS were collected. At 3-month follow-up, patients were categorized into PSD and non-PSD groups. Logistic models and restricted cubic spline curve were used to investigate the correlation between NIHSS, NSE and PSD. A corresponding nomogram was formulated.

Among 172 patients with AIS, 63 (36.63%) were diagnosed with PSD, while 109 (63.37%) were non-PSD. The baseline NIHSS and NSE were positively correlated with the risk of 3-month PSD (P < 0.05). Multivariate logistic regression revealed that sex (OR= 2.168, 95% CI 1.038 ∼ 4.526), age (OR= 1.035, 95% CI 1.002 ∼ 1.070), NIHSS (OR= 1.164, 95% CI 1.022 ∼ 1.325) and NSE (OR= 1.180, 95% CI 1.037 ∼ 1.343) were independently associated with 3-month PSD (all P < 0.05). The nomogram constructed using sex, age, baseline NIHSS score and NSE showed good discrimination, calibration, and clinical utility.

NSE is a valuable tool for early identification of PSD risk. A combined prediction model incorporating NIHSS and NSE has been established for the personalized prevention and intervention of PSD.

Neuroendocrine neoplasms (NENs) comprise a heterogeneous tumor group arising from neuroendocrine cells, commonly originating in the gastroenteropancreatic tract and bronchopulmonary system. Their incidence has risen significantly, owing to improved diagnostic techniques and increased clinical recognition. While previous reviews have explored the molecular and genetic basis of NENs, limited attention has been given to the role of epigenetic modifications, particularly DNA methylation, in tumorigenesis and disease progression. This review focuses on lung, pancreas, and thyroid well-differentiated neuroendocrine tumors (NETs), highlighting epigenetic mechanisms, particularly DNA methylation, as promising biomarkers for early diagnosis and risk stratification. Aberrant DNA methylation can silence key tumor suppressor genes, including RASSF1A and CDKN2A, thereby promoting tumorigenesis. Integrating DNA methylation profiles with conventional biomarkers such as chromogranin A (CgA) may enhance diagnostic accuracy and inform therapeutic strategies. Emerging epigenetic therapies offer potential avenues for personalized treatment based on molecular profiling. Unlike prior reviews that broadly cover genetic and epigenetic changes in NENs, this review uniquely emphasizes the translational potential of epigenetic biomarkers in clinical practice. By synthesizing recent findings and evaluating their clinical implications, we aim to bridge the gap between molecular research and practical applications in diagnosis, prognosis, and therapy.

Traumatic brain injury (TBI) refers to an impact of the brain within the skull resulting in an altered mental state. The study aim is to determine the effect of a high dose of N-acetylcysteine (NAC) on biochemical and inflammatory markers of neuronal damage and clinical outcomes in patients with moderate to severe TBI.

A randomized open label-controlled trial was conducted on 40 patients with moderate to severe TBI patients presented to the emergency unit within < 24 h since the trauma occurred and randomized into NAC and control groups 20 patients each. Serum samples for evaluation of biomarkers: malondialdehyde (MDA), interleukin-6 (IL-6), neuron-specific enolase (NSE), and S100B were withdrawn at baseline and on day 7. The patients were followed for 7 days and evaluated clinically by the Glasgow Coma Scale (GCS).

There was a significant decrease in NSE and MDA levels on day 7 from baseline in NAC group (p < 0.001 and p < 0.001). Also, S100B and IL-6 decreased significantly in NAC group on day 7 from baseline (p = 0.003 and p < 0.001 consequently) compared to control group. Moreover, patients in NAC group showed a significantly shorter length of stay at intensive care unit (ICU) (p = 0.038). There was a significant increase in GCS in NAC group on day 7 from baseline (p = 0.001).

Adjunctive early use of high-dose NAC significantly reduced inflammatory and oxidative markers and had neuroprotective effect which may be a novel treatment option for moderate to severe TBI patients.

Pactr.org identifier: (PACTR202209548995270) on 14 September 2022.

Each year, approximately 84 out of 100 000 individuals in Europe sustain a cardiac arrest; many die or suffer long-term neurological injury. Early prognostication can be of assistance for treatment planning and for the holding of evidencebased discussions with these patients' families to make decisions about treatment.

This narrative review is based on pertinent guidelines and on publications retrieved by a selective search in Medline/ PubMed.

The survival rate of in-hospital cardiac arrest (IHCA) is 15-34%, that of out-of-hospital cardiac arrest (OHCA) approximately 10%. Survivors have an elevated risk of severe neurological injury: 22.9% (IHCA) and 67.7% (OHCA) go on to die in an intensive care unit of severe brain damage. Among those who are still alive one year after cardiac arrest, 83.3% have a good neurological outcome (cerebral performance category [CPC] score, 1-2), although many suffer from post-intensive care syndrome. Early prognostication is generally difficult, and an initial assessment can often only be made 72 hours or more after the event, on the basis of multimodal diagnostic testing. Risk models and biomarkers are available as aids to early prognostication but have not yet come into broad use.

Many successfully resuscitated patients die shortly thereafter. Those who survive for one year generally have good neurological function. Early prognostication is of fundamental importance for decision-making about continuing treatment or whether resuscitation should be attempted again in the case of a second arrest. Physicians communicating with the affected patients and their families should also be mindful of the commonly associated emotional stress.

Biochemical markers can be used in addition to neuroimaging techniques to evaluate the extent of ischemic brain injuries and to enable earlier diagnosis and faster intervention following the ischemic event. Among the potential biomarkers of ischemic brain injuries during surgery, neuron-specific enolase (NSE) and S100B are the most frequently studied and were shown to be the most promising. The aim of this review was to summarize the role of NSE and S100B as biomarkers of ischemic brain injuries that occur during selected surgical procedures, predominantly carotid endarterectomy (CEA). Some other invasive interventions that cause ischemic brain injuries, like extracorporeal membrane oxygenation, were also included. We can conclude that these biomarkers can be useful for the evaluation of ischemic brain injuries that occur during various surgical procedures. They can help to determine the most optimal conditions for performing the surgery and therefore improve the procedures to consequently minimize brain damage caused during surgery. Because of a significant delay between sample collection and obtaining the results, they are not suitable for real-time assessment of brain injuries. Some improvement can be expected with the future development of laboratory methods. The association of the changes in NSE and S100B levels during surgery with potential consequences of ischemic brain injury have been described in numerous studies. However, even in a very homogenous group of surgical procedures like CEA, these findings cannot be summarized into a common final conclusion; therefore, the prognostic value of the two markers is not clearly supported at the present time.

Cardiotoxicity has become a major concern in cancer patients, especially those with lung cancer, as anti-tumor therapies can significantly affect patient survival and quality of life. This study aims to develop and validate a dynamic nomogram based on the Inflammation Burden Index (IBI) to predict the risk of cardiac injury within one year after anti-tumor treatment in lung cancer patients.

This single-center, retrospective study included 1386 lung cancer patients who underwent myocardial enzyme testing between July 2018 and January 2023. The IBI was calculated as: IBI = (CRP (mg/dL) × Neutrophils (/μL)) / Lymphocytes (/μL). Statistical analysis using SPSS 22.0 and R 4.4.1, including machine learning algorithms and multivariate logistic analysis, identified independent predictors of cardiac injury. An online dynamic nomogram was developed and validated using internal validation, ROC curves, and decision curve analysis (DCA).

The average age of the 1386 patients was 61.98 ± 9.22 years. Significant independent predictors included age, BMI, hypertension, immunotherapy, D-dimer, LDH, NSE, CKMB, and IBI. The nomogram showed strong discriminative ability with AUC-ROC values of 0.85 for the training set and 0.86 for the validation set. Calibration curves confirmed good fit, and DCA showed high clinical utility.

An online dynamic nomogram based on clinical and inflammatory markers was developed to predict cardiac injury in lung cancer patients following anti-tumor therapy. The model shows strong discriminative ability and potential clinical value, which can provide vital information for oncologists when designing customized clinical treatments.

Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is one of the severe complications that can occur after acute carbon monoxide poisoning (ACOP). The pathogenesis of DEACMP is complex, featuring a delitescence onset and poor prognosis. As a result, many scholars are concentrating on identifying predictors of DEACMP and evaluating their effects, including clinical characteristics, laboratory indicators, neuroelectrophysiology, imaging examination, and genetic susceptibility. However, current identified predictors lack consensus and their clinical application is limited. Therefore, we need to explore new predictors. Exosomes, the smallest extracellular vesicles (EVs) with nano-size, participate in both the physiological and pathological processes of the brain, and the changes in their content can provide valuable information for clinical diagnosis and evaluation of neurodegenerative diseases, suggesting that they may serve as a potential biomarker. However, the practicability of exosomes as biomarkers of DEACMP remains unclear. In the present review, we first introduced the pathogenesis of DEACMP and the currently identified predictors. Then, we also discussed the possibility of exosomes as the biomarkers of DEACMP, aiming to stimulate more attention and discussion on this topic, thereby providing meaningful insights for future research.

Neuroblastoma is an aggressive pediatric tumor condition derived from neural crest cells that typically affect infants and children under the age of five. It can often originate in the adrenal glands but can also develop in the sympathetic nervous system. G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases have been shown in recent research to have a vital role in the progression of neuroblastoma. GPCR-RTK crosstalk stimulates signaling pathways such as MAP kinase, and the activation of the GPCR-AKT signaling pathway plays a critical role in neuroblastoma progression by promoting cell growth, survival, and resistance to apoptosis through complex interactions with insulin signaling pathways. ALK (Anaplastic lymphoma kinase), a member of the RTK family, and any mutations can lead to oncogenic signaling and resistance to targeted therapy in neuroblastoma. By interfering with cellular signaling via novel therapeutic strategies by selective RET inhibitors, ALK inhibitors, and Trk-specific inhibitors may be able to reduce the prevalence of neuroblastoma. Understanding the complicated signaling relationships between GPCRs, RTKs, and the insulin pathway is critical when developing new cancer treatments. The integration of these signaling networks offers promising avenues for enhancing the effectiveness of existing treatments and improving patient outcomes in neuroblastoma.

Cerebral ischemia-reperfusion injury (CIRI) is a complex pathophysiological process faced by brain tissues after ischemic stroke treatment, which involves mechanisms of inflammatory response, oxidative stress and apoptosis, and severely affects treatment outcome. Lipocalin-2 (LCN2), an acute-phase protein, is significantly up-regulated after CIRI and promotes neural repair by enhancing astrocyte phagocytosis, but its over-activation may also trigger secondary inflammation and demyelination injury. LCN2 also plays a key role in neuroinflammation regulation by regulating the polarization state of astrocytes and the release of inflammatory factors, and may affect the integrity of the blood-brain barrier and a variety of pathologic injury processes. In view of the important role of LCN2 in CIRI, this article reviews the mechanism of LCN2, aiming to provide new ideas and methods for the treatment of ischemic stroke.

Early diagnosis and treatment of endometriosis (EM) remain challenging because of the lack of knowledge about EM development. While oxidative stress (OS) has been associated with EM, the link is unclear. We explored OS-related genes (OSRGs) and their role in EM pathogenesis.

We combined two ectopic endometrium (EC) and eutopic endometrium (EU) datasets (GSE11691 and GSE25628) into a dataset for analysis. Bioinformatic analyses were used to identify differentially expressed genes (DEGs), OS-related genes (OSRGs), enriched pathways, competitive endogenous RNA network, and immune cell infiltration. Finally, real time-quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB) were used to validate the expression of key OSRGs in clinical patient samples.

Bioinformatic analysis identified 459 DEGs between EC and EU samples, including 67 OSRGs. A ceRNA network was established, encompassing 28 DE-OSRGs, 32 miRNAs, and 53 lncRNAs. Four key OSRGs (CYP17A1, NR3C1, ENO2, and NGF) were selected from protein-protein interaction network analysis. The RT-qPCR and WB analysis showed that these genes' abnormal changes in RNA and protein levels were consistent with data in public databases. Weighted gene co-expression network analysis identified three immune-related OSRGs (CYP17A1, NR3C1, and NGF) and 20 lncRNAs that may regulate NR3C1 through 10 miRNAs.

The key OSRGs may function via multilayered networks in EM. We provide insights into EM and underscore the potential significance of OSRGs and the immune environment for diagnostic and prognosis evaluation.

Neuron-specific-enolase is used as a marker of neurological prognosis after cardiopulmonary resuscitation. It is also present in red blood cells and platelets. It is not known whether hemolysis increases the values of neuron-specific-enolase enough to clinically affect its interpretation in critically ill patients who are to be introduced to veno-arterial extracorporeal oxygenation. In this study, we examined the relationships among neuron-specific-enolase and hemolysis indicators such as free hemoglobin and lactate dehydrogenase after the introduction of veno-arterial extracorporeal oxygenation. Of the 91 patients who underwent veno-arterial extracorporeal membrane oxygenation in our hospital from January 1, 2018, to February 24, 2021, 68 patients survived for more than 24 h. Of these, 14 patients who were categorized into the better cerebral performance categories (1-3) and 19 patients who were categorized into the poor neurological prognosis category (4) were included. After the introduction of veno-arterial extracorporeal membrane oxygenation, neuron-specific-enolase was markedly higher in the poor neurological prognosis group than in the good neurological prognosis group (41.6 vs. 92.0, p = 0.04). A significant positive correlation was revealed between neuron-specific-enolase and free hemoglobin in the good neurological prognosis group (rs = 0.643, p = 0.0131). A similar relationship was observed for lactate dehydrogenase and neuron-specific-enolase in both the conscious (rs = 0.737, p = 0.00263) and non-conscious groups (rs = 0.544, p = 0.0176). When neuron-specific-enolase is used as a marker for neuroprognostic evaluation, an abnormally high value is likely to indicate the lack of consciousness, whereas a lower elevation should be interpreted with caution, taking into account the effects of hemolysis.

Background: Severe injuries caused by accidents, such as traumatic brain injury (TBI) or thoracic trauma (TT), continue to be the leading cause of death in younger people with relevant socioeconomic impact. Fast and targeted diagnostics is essential for further therapy decisions and prognosis. The following study investigates neuron-specific enolase (NSE) as a potential biomarker for lung injury after blunt TT. Methods: This is a retrospective analysis of prospectively collected data in a level 1 trauma center from 2014 to 2020. Serum levels of NSE and ILs (IL-6, IL-10) in injured patients (n = 41) with isolated TT (Abbreviated Injury Scale score of the thorax ≥3) compared with isolated TBI (Abbreviated Injury Scale score of the head ≥3) were assessed from days 0 to 5 after trauma. The extent of lung injury was quantified by Hounsfield scale in computed tomography scans. Results : Thirty patients with TT (median Injury Severity Score = 20, age 50 ± 17 years, 83.3% were male) and 11 patients with TBI (median Injury Severity Score = 25, age 54 ± 17 years, 27.3% were male) were included. After TT, NSE concentration increased initially after trauma with a peak value on the day of admission (8.51 ± 3.68 ng/mL) compared with healthy controls (4.51 ± 1.504 ng/mL, P < 0.001). Isolated TT and TBI lead to equally strong NSE release ad the day of admission. There is a significant linear relationship ( r = 0.636, P = 0.035) between serum NSE levels and severity of pulmonary contusion at the time of admission and after 24 h. Conclusion : A significant NSE release after isolated TT peaks on the day of admission. The extent of lung contusion volume (defined as alveolar parenchymal density) correlates with NSE serum concentration. Thus, NSE has predictive value for the extent of pulmonary contusion. However, according to these data, NSE seems to have no diagnostic value as a TBI biomarker in concomitant TT.

Encephalopathy following sepsis is defined as life-threatening organ failure due to the irregular response of the host to infection and has high mortality and morbidity rates. The present study aimed to investigate the effects of inflammation and the gamma-aminobutyric acid-A (GABAA) receptor antagonist, bicuculline, on brain tissue in rats with sepsis. Sepsis was experimentally generated using lipopolysaccharide (LPS). The rats were divided into four groups: control, LPS (10 mg/kg i.p.), bicuculline (1.5 mg/kg s.c.), and LPS+Bic. Electrophysiologic recordings and body temperature measurements were completed at the 24th hour, and samples were taken. TNF-α, IL-10, GABA, and MDA levels were measured. Tissue imaging was performed using S100-ß, NEUN, and synaptophysin antibodies. One-way ANOVA followed by the Tukey test was performed for statistical analysis. Inflammatory parameters significantly increased in brain tissue in the LPS group compared with the other groups (TNF-α, [F (3.14) = 6.015, p = 0.042]; IL-10, [F (3.15) = 9.013, p = 0.02]). Tissue imaging results were as follows: S100-ß involvement increased, and NeuN and synaptophysin involvement decreased in the LPS group [F (3.21) = 18.016, p = 0.006, for S100-ß; F (3.21) = 19.071, p = 0.003, for NeuN; F (3.21) = 18.098, p = 0.005, for synaptophysin]. In electrophysiologic recordings, we observed activity consistent with acute non-focal seizures in the LPS group. Contrarily, the control and other comparison groups exhibited normal resting neural activity. Bicuculline may be used as a therapeutic agent in sepsis to maintain the neurotransmitter and pro- and anti-inflammatory cytokine balance and reduce lipid peroxidation with its effects of acetylcholine esterase inhibition and GABAA receptor antagonism.

The purpose of this study was to examine the protective and therapeutic effects of okra (Abelmoschus esculentus [AE]) seed extract, with its known antioxidant, immunomodulatory, and anti-inflammatory properties, in an acetaminophen (paracetamol, N-acetyl- para-aminophenol)-induced model of hepatotoxicity and subsequent acute non-traumatic brain damage.

Forty male Wistar rats were randomly divided into five equal groups, control, paracetamol (P), okra seed extract (AE), okra seed extract + paracetamol (P + AE), and okra seed extract + paracetamol + N-acetyl cysteine (NAC) (P + AE + N). AE was administered by oral gavage through a gastric tube at 600 mg/kg/day for seven days. On the eighth day of the procedure, a single 1 g/kg dose of paracetamol and 300 mg/kg NAC were injected via the intraperitoneal route 1.5 h after AE administration. Rat tissue specimens were subsequently subjected to biochemical and histopathological analyses. Levels of markers such as S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), and matrix membrane metalloproteinase-9 (MMP-9) were investigated from rat serum specimens. Malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured to determine oxidant-antioxidant status.

S100B, NSE, MMP-9, MDA levels, and SOD enzyme activities were examined using biochemical methods. MDA levels were significantly lower in the P + AE group and MMP-9 levels in the AE, P + AE, and P + AE + N groups compared to the P group. Histopathological examination results supported the biochemical findings.

Okra seed extract exhibits a protective and therapeutic effect against non-traumatic brain damage resulting from acute paracetamol intoxication. We think that this benefit of AE derives from its antioxidant property.

Background/Objectives: Malignant pleural effusions (MPEs) pose a significant challenge in clinical practice and exert a considerable socio-economic burden on the healthcare system, affecting approximately 1 million individuals annually. These effusions are a leading cause of debilitating dyspnea and a diminished quality of life among cancer patients, with distant metastasis to the pleural layers occurring in about 20% of cases during treatment. Methods: A cross-sectional, observational case-control study was conducted on 151 Bulgarian patients with a hydrothorax. The control group included 72 patients with benign diseases, confirmed via biopsy, with 38 having inflammatory and 34 non-inflammatory pleural effusions. The other 79 patients had malignant pleural involvement. These groups are representative of the main types of pleural pathology. Results: The study found that all of the tumor markers, except for PIVKA-II (Protein induced by vitamin K absence-II), showed statistically significant differences between the malignant and non-malignant patient groups, with CAE (carcinoembryonic antigen) and CA19-9 showing the most notable differences. The Receiver Operating Characteristic (ROC) analysis revealed that CA72-4 had the best ability to distinguish between the two groups, while PIVKA was the weakest, with optimal cut-off values for all of the relevant tumor markers being derived using the Youden index. Conclusions: In conclusion, our study highlights the transformative potential of pleural fluid tumor markers as precise and minimally invasive resources for distinguishing malignant from non-malignant pleural effusions. These findings pave the way for improved diagnostic accuracy and personalized clinical management, addressing a critical gap in the care of patients with pleural pathologies.

The study of blood and cerebrospinal fluid biomarkers is a promising and rapidly advancing field in the research of disorders of consciousness (DoC). The use of advanced biochemical and analytic techniques in biomarker research has improved our ability to identify new biomarkers that can aid in the diagnosis, prognosis, and treatment of patients with brain injury. However, the use of biomarkers in clinical practice is limited by several challenges, including the lack of standardization in test and research methodologies. Despite this, identifying the most promising biomarkers and supporting their findings with strong evidence can improve their clinical utility. This chapter discusses the most promising biomarkers for DoC, which fall into four categories: neuronal, glial, inflammatory, and metabolic biomarkers. Understanding the role of each category in DoC can provide valuable insights into the mechanisms of brain injury and inform the development of more effective diagnostic and treatment strategies. By integrating biomarker research with clinical practice, we can improve our understanding of DoC and provide better care for these patients.

The field of psychoneuroimmunology has significantly expanded in the last few decades and so has our understanding of the bidirectional communications between the immune and central nervous systems (CNS). There is a preponderance of evidence supporting the fact that immunological pathways and neuroinflammation are involved in the pathophysiology of multiple neurological and mental health conditions. In this chapter, we have explored various neuroimmunological biomarkers involved in these pathways, responsible for developing and perpetuating different neuropsychiatric disorders. This chapter will examine inflammatory biomarkers and those associated with intestinal homeostasis, blood-brain barrier (BBB) permeability, glial cells, and neuronal injury. A range of tests has been developed to evaluate these markers, and we will also explore the existing methods currently employed for these techniques. Further studies of these inflammatory and neurological markers are needed to support their utility as biomarkers for diagnosis and prognosis and to inform treatment strategies for various neuropsychiatric disorders.

Neuron-specific enolase (NSE) is one of the most common biomarkers of small cell lung cancer (SCLC) and is widely used in lung cancer screening. But its specificity is affected by many factors. Using residual correction and machine learning, corrected NSE and its reference range were constructed based on metabolic factors and smoking history affecting NSE in the training set of 48,009 healthy individuals recruited from the First Affiliated Hospital of Nanjing Medical University. External validation including additional 64,553 healthy subjects and 105 SCLC patients were enrolled to evaluate the efficacy of NSEcorrected for SCLC screening. The reference range of NSEcorrected could significantly improve the specificity of NSE for SCLC and reduce false positives. In the external validation set, NSEcorrected increased the specificity from 85.71 % to 97.09 %(P < 0.0001), and reduced the false positive rate from 14.26 % to 2.91 %(P < 0.0001). ROC curve, calibration curve and decision analysis curve also showed that NSEcorrected had better screening performance. The calculation of NSEcorrected was converted into an online R-based app for more convenient use. NSEcorrected can improve the screening effect of SCLC, reduce the false positive rate, and is more suitable for large population screening and optimize the allocation of lung cancer resources.

Neuron-specific enolase (NSE) is currently the most reliable biomarker for small cell lung cancer (SCLC), which is important for disease monitoring, clinical evaluation and diagnosis. However, traditional methods suffer from various disadvantages, including instability, complexity, time-consuming operations, and the necessity for standards. In this study, we developed a calibration-free concentration analysis (CFCA) method based on surface plasmon resonance (SPR) technology, to accurately quantify the active concentration of NSE without relying on any standards. Based on the principle of CFCA, the active concentration of NSE can be calculated by observing binding rate variations at two flow rates under partial mass transport limitation and combining it with the known diffusion coefficient of the NSE. Using the method of CFCA, the active concentration of NSE was determined was only 0.48 mg/mL with an intra-day repeatability of 4.75%. The method has the advantages of simplicity, rapidity, realistic analysis and ease of implementation of high-throughput automated detection. Therefore, the method is expected to become the main measurement method for protein active concentration, which will be beneficial for the development of active protein standards.

The nervous system regulates perception, cognition and behavioral responses by serving as the body's primary communication system for receiving, regulating and transmitting information. Neurons are the fundamental structures and units of the nervous system. Their differentiation and maturation processes rely on the expression of specific biomarkers. Neuron-specific intracellular markers can be used to determine the degree of neuronal maturation. Neuronal cytoskeletal proteins dictate the shape and structure of neurons, while synaptic plasticity and signaling processes are intricately associated with neuronal synaptic markers. Furthermore, abnormal expression levels of biomarkers can serve as diagnostic indicators for nervous system diseases. This article reviews the markers of mature neuronal differentiation and their relationship with nervous system diseases.

Background: Incomptine A (IA) has been reported to have cytotoxic activity in non-Hodgkin lymphoma cancer cell lines and have effects on U-937 cells, including the induction of apoptosis, the production of reactive oxygen species, and the inhibition of glycolytic enzymes. Also, IA has cytotoxic activity in the triple-negative subtypes, HER2+, and luminal A of breast cancer cells, with its properties being associated with an effect on the antiapoptotic function of Hexokinase II (HKII). Objectives: In this research, we reviewed the altered levels of proteins present in the lymph nodes of male Balb/c mice inoculated with U-937 cells and treated with IA or methotrexate, as well as mice only inoculated with cancer cells. Methods: Five approaches, including Tandem Mass Tag (TMT), Gene ontology (GO), Reactome, KEGG pathway analysis, and molecular docking, were used. Results: TMT showed that 74 proteins were differentially expressed, out of which 12 presented overexpression (FC ≥ 1.5) and 62 were under expressed (FC ≤ 0.67). In general, the TMT approach showed that IA had a better effect on proteins than methotrexate. Gene ontology, Reactome, and KEGG pathway analysis showed that proteins with altered levels may be implicated in several processes, including gene silencing by RNA, oxidative phosphorylation, glycolysis/gluconeogenesis, cytoskeleton organization, and ATP metabolic and energetic processes. The molecular docking analysis, which used 23 altered proteins as targets, revealed that IA interacted with all the proteins used. Conclusions: The results obtained using the five bioinformatic approaches provide information and show that IA could be used to treat non-Hodgkin lymphoma induced with the U-937 cell line. Also, it could provide a basis for future research and the development of clinical trials.

Background: SGLT-2 inhibitors (SGLT-2i) and GLP-1 receptor agonists (GLP-1RA) have demonstrated nephro- and cardioprotective effects, but their neuroprotective properties, especially concerning stroke severity, and mechanisms are not unambiguous. We aimed to study the influence of SGLT-2i with different selectivity and GLP-1RA on brain damage volume and neurological status in non-diabetic and diabetic rats and to investigate the underlying mechanisms. Methods: Non-diabetic Wistar rats were divided into five groups (n = 10 each) and received empagliflozin, canagliflozin, or dulaglutide as study drugs and metformin as comparison drug. Control animals were administered 0.9% NaCl for 7 days before stroke. At 48 h after stroke, we assessed neurological deficit, neuronal and astroglial damage markers, and brain damage volume. We also modeled type 2 DM in Wistar rats using the high-fat diet+nicotinamide/streptozotocin method and established similar treatment groups. After 8 weeks, rats were subjected to stroke with further neurological deficit, neuroglial damage markers, and brain necrosis volume measurement. Results: In non-diabetic rats, all the drugs showed an infarct-limiting effect; SGLT-2i and dulaglutide were more effective than metformin. DULA improved neurological status compared with MET and SGLT-2i treatment. All the drugs decreased neurofilament light chains (NLCs) level and neuronal damage markers, but none of them decreased the glial damage marker S100BB. In DM, similarly, all the drugs had infarct-limiting effects. Neurological deficit was most pronounced in the untreated diabetic rats and was reduced by all study drugs. All the drugs reduced NLC level; dulaglutide and empagliflozin, but not canagliflozin, also decreased S100BB. None of the drugs affected neuron-specific enolase. Conclusions: SGLT-2i and GLP-1RA are neuroprotective in experimental stroke. GLP-1RA might be more effective than SGLT-2i as in non-diabetic conditions it influences both brain damage volume and neurological status. All study drugs decrease neuronal damage, while GLP-1RA and highly selective SGLT-2i EMPA, but not low-selective CANA, also have an impact on neuroglia in diabetic conditions.

This study aims to evaluate the correlation between miRNAs and known nerve injury markers neuron-specific enolase (NSE) and S100β in ischemic stroke (IS) patients, exploring its efficacy.

We retrospectively analyzed 86 IS patients and 32 healthy controls. Clinical and neurological examinations were performed in the admitted patients and the severity of neurological deficits was assessed by National Institutes of Health Stroke Scale (NIHSS). Plasma extraction and serum isolation were performed on all subjects before and 2 weeks after admission. miR-142-5p in serum, and NSE and S100β contents were measured by RT-qPCR and ELISA.

Ischemic lesions were more severe in IS patients, and NSE and S100β were abnormally elevated. miR-142-5p in the serum of IS patients was 2.85 times higher. After 2 weeks of treatment, serum miR-142-5, NSE, and S100β decreased. Patients' serum levels of miR-142-5p were 57.5% lower. Serum miR-142-5, NSE, and S100β were lower in patients with disease improvement than in patients with poor recovery. Additionally, miR-142-5 was positively correlated with NSE (P < 0.0001) and S100β (P = 0.0147), and also with the NIHSS score (P = 0.0004).

miR-142-5p, NSE, and S100β in peripheral blood (PB) of IS patients are elevated, and miR-142-5p is positively correlated with NSE and S100β.

Previous studies revealed that the elevation of serum tumor markers (TMs) can serve as a prognostic indicator for diseases other than cancer, but little is known about its association with acute ischemic stroke (AIS). Based on a series of molecular markers and gene pathways shared in both stroke and cancer, we aimed to investigate whether the elevation of TMs could predict clinical outcomes after AIS.

Patients diagnosed with AIS were enrolled and classified into the elevated TMs group and the non-elevated TMs group according to whether any TMs were elevated or not. Then they were followed up 6 months to assess clinical outcomes. Poor functional outcomes were defined as modified Rankin Scale (mRS) > 2 points.

289 AIS patients were finally enrolled, of which 197 (68.2%) were classified as the elevated TMs group. Patients in the elevated TMs group were more likely (OR = 2.384; p = 0.005) to have poor functional outcomes at follow-up than those in the non-elevated TMs group. However, no specific TM was significantly more elevated than the other TMs in the patients with poor functional outcome. The combination of TMs was more sensitive than individual TM in terms of prognosis prediction. Furthermore, rather than the number of elevated items, whether any TM was elevated or not was the most appropriate discriminator for functional outcomes after AIS.

Elevation of TMs may indicate poor functional outcomes after AIS. Consequently, AIS patients with elevated TMs required close clinical monitoring and intensified treatment.

Neuron-specific enolase (NSE) is a biomarker indicative of neuronal cell damage. The aim of this study is to assess the NSE levels in patients diagnosed with post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). Blood samples were collected from 43 individuals with PTSD (age range 11-17), 43 individuals with MDD (age range 10-17), and 40 age- and gender-matched healthy controls. The NSE levels were analyzed, and participants completed the Post-traumatic Stress Reaction Index, the Children's Depression Inventory, and the Screen for Child Anxiety Related Disorders. Additionally, the Clinical Global Impressions Scale was filled out by the researcher. Results indicated that the NSE levels in the PTSD group were significantly higher than those in both the MDD group and the healthy control group. No significant difference in NSE levels was observed between the MDD group and the healthy control group.

The findings suggest that elevated NSE levels in PTSD may be indicative of stress-related neuronal damage, distinguishing PTSD from MDD and healthy controls. These results underline the need for further research to explore the potential of NSE as a biomarker for PTSD and its implications for diagnosis and intervention strategies.

• Neuron-specific enolase (NSE) is a biomarker indicative of neuronal cell damage. • Elevated NSE levels have been observed in certain neuropsychiatric and neurological conditions, reflecting neuronal damage or stress.

• NSE levels in adolescents with PTSD are significantly higher than those in both MDD patients and healthy controls, suggesting a specific association with trauma-related neuronal damage. • No significant difference in NSE levels was observed between MDD patients and healthy controls, highlighting the distinct neurobiological impact of trauma compared to depressive disorders.

Despite numerous studies conducted by various research teams, predicting long-term outcomes (known as Post-COVID-19 Syndrome, PCS) that may result from Coronavirus Disease 2019 (COVID-19) remains challenging. PCS affects over a million people, primarily those with comorbid conditions. Therefore, it is crucial to undertake research aimed at developing a predictive model for early diagnosis of PCS, which in turn would enable faster preventive actions. The aim of this study was to assess the value of measuring and attempt a quantitative evaluation using Enzyme-Linked Immunosorbent Assay (ELISA) tests of three non-serum proteins, whose presence in the blood during COVID-19 was associated with severe disease progression: neutrophil elastase (NE), calcium-binding protein S100B, and neuron-specific enolase (NSE). The concentrations of these proteins were measured in blood serum samples collected before the COVID-19 pandemic from (1) patients with type 2 diabetes (T2DM); (2) advanced stage diabetic nephropathy (NfT2DM); (3) a healthy group; and in blood serum samples collected two years after recovering from COVID-19 from patients with (4) T2DM and (5) NfT2DM. It was found that elevated levels of NE and NSE were significantly more common (p < 0.05) in patients with NfT2DM after recovering from COVID-19 compared to the other groups, while elevated levels of S100B were significantly more frequently observed in patients with T2DM after recovering from COVID-19 (p < 0.05). Demonstrating differences in the prevalence of NE, NSE, and S100B in individuals who recovered from COVID-19 with T2DM and NfT2DM makes these proteins important components of the developing predictive model for early detection of PCS. To our knowledge, this is the first study showing the significance of NE, NSE, and S100B in PCS in the context of T2DM and NfT2DM.

Traumatic brain injury is a highly irreversible process that consists of primary as well as secondary injury which develops and progresses over months to years, leading to cognitive dysfunctions. Vitamin B12 received considerable interest due to its potential therapeutic properties. The pathways of vitamin B12 are closely related to neuronal survival but its effects on the pathophysiology of injury with respect to cognition is a relatively unexplored area of research. In this study, we investigated, the effect of vitamin B12 and its involvement in neuroprotection on TBI-induced pathophysiology in male Swiss albino mice. Our findings suggested that vitamin B12 supplementation improves TBI-mediated neurological impairments, spatial and recognition memory, and anxiety-like behavior. Furthermore, the oxidative stress was reduced by declined homocysteine level with vitamin B12 supplementation validating declined expression of astrocytes and TBI biomarkers. The studies on neuronal morphology revealed that vitamin B12 supplementation increases the dendritic arborization and density of mushroom and filopodia-shaped spines and further increases the expression of synaptic plasticity-related genes and proteins. Taken together, our findings reveal that, supplementation of vitamin B12 restored the TBI-induced downregulation of dendritic arborization, and spine density which ultimately increases synaptic plasticity, cell survival, and recovery of cognitive dysfunctions.

The aim of the study is to investigate the relationship between serum neuron-specific enolase (NSE) and welders' pneumoconiosis, through chest x-ray and serum NSE.

The exposed group included 37 welders. The nonexposed group included 38 administrative workers. Both groups underwent history taking, clinical examination, chest x-ray, serum chromium, and serum neuron-specific enolase. Air sampling was done for total suspended particles, respirable particles, and welding fumes.

All the air samples were within the national threshold limit values. Chest x-ray abnormalities were found in eight welders (21.6%), and included reticular opacities, scattered nodules or ground-glass opacities. Serum chromium and NSE were significantly higher among welders. Serum NSE correlated positively with the duration of exposure and serum chromium level among welders.

Serum NSE can be used as a biomarker for early detection of welders' pneumoconiosis.

Over the past decade, liquid biopsy (LB) has become a routine diagnostic test essential for the treatment of malignant tumors of various localizations. Its capabilities include early diagnosis, molecular genotyping, prognosis, prediction, and monitoring of tumor response. Typically, liquid biopsy involves the extraction of a single type of tumor-derived molecules or cellular elements from blood and subsequent molecular analysis. These elements may include circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), circulating tumor RNA (ctRNA), or contents of extracellular vesicles (exosomes). Despite the technical sophistication of molecular analysis methods for circulating biomarkers, this diagnostic approach has limited relevance. In a significant proportion of cancer patients (ranging from 10 to 50%, depending on the tumor type), none of these analytes can be detected and analyzed, even in the presence of large, progressing neoplastic foci in the body. It seems reasonable to suggest that heterogeneous fractions of the circulating tumor-specific biomarkers complement each other, thus simultaneous analysis of several fractions will not only increase sensitivity of the method but also more accurately characterize and predict the clinical situation. This review examines the possibilities and advantages of applying a combined multiparametric approach to liquid biopsy, which involves testing multiple circulating analytes in a single blood sample.

Infantile epileptic spasms syndrome (IESS) with epileptic spasms as the main seizure type, is treated with adrenocorticotropic hormone (ACTH). This study, for the first time, examines the effects of epileptic spasms and ACTH on blood-brain barrier (BBB) permeability in patients with IESS of unknown etiology.

We prospectively evaluated the changes in BBB permeability in patients with IESS of unknown etiology at the Saitama Children's Medical Center between February 2012 and February 2024. We compared the levels of serum-albumin, cerebrospinal fluid (CSF)-albumin, Q-albumin, and CSF-neuron-specific enolase (NSE) before and after ACTH therapy. We also assessed the correlation between the frequency of epileptic spasms and these markers.

Overall, 16 patients with IESS (8 males) were included in the study. The median age at IESS onset was 5 (range, 2-9) months. The median duration between the epileptic spasms onset and the serum and CSF sample examination before ACTH therapy was 26 (range, 1-154) days. After ACTH therapy, CSF-albumin and Q-albumin levels significantly decreased (CSF-albumin: 13.5 (9.0-32.0) mg/dL vs 11.0 (7.0-19.0) mg/dL, p = 0.001. Q-albumin: 3.7× 10-3 (2.2 × 10-3-7.3 × 10-3) vs 2.8× 10-3 (1.9 × 10-3-4.5 × 10-3), p = 0.003). No correlation was observed between the epileptic spasms frequency and levels of serum-albumin, CSF-albumin, Q-albumin, and CSF-NSE (Spearman's coefficient: r = 0.291, r = 0.141, r = 0.094, and r = -0.471, respectively).

ACTH therapy is one of the factors that play a role in restoring BBB permeability in patients with IESS of unknown etiology. Our findings may be useful in elucidating the mechanism of ACTH action and IESS pathophysiology.

The cerebral biomarkers, neurofilament light chain (NfL), amyloid-β, tau, and neuron specific enolase (NSE) reflect a wide spectrum of neurological damage in the brain and spinal cord. With this study, we aimed to assess whether these biomarkers hold any potential diagnostic value for the three most common canine neurological diseases. Canines suffering from meningoencephalitis of unknown origin (MUO), brain tumors, and selected non-infectious myelopathies were included. For each diagnosis, we analyzed these biomarkers in the cerebrospinal fluid collected via cranial puncture from the cisterna magna. Elevated levels of CSF tau, NfL, and NSE were observed in MUO, with all three biomarkers being intercorrelated. Tau and NSE were increased while amyloid-β was decreased in dogs suffering from tumors. In contrast, no biomarker changes were observed in dogs with myelopathies. Covariates such as age, sex, or castration had minimal impact. CSF biomarkers may reflect molecular changes related to MUO and tumors, but not to non-infectious myelopathies. The combination of NfL, tau, and NSE may represent useful biomarkers for MUO as they reflect the same pathology and are not influenced by age.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. The heterogeneous nature of ALS at the clinical, genetic, and pathological levels makes it challenging to develop diagnostic and prognostic tools that fit all disease phenotypes. Limitations associated with the functional scales and the qualitative nature of mainstay electrophysiological testing prompt the investigation of more objective quantitative assessment. Biofluid biomarkers have the potential to fill that gap by providing evidence of a disease process potentially early in the disease, its progression, and its response to therapy. In contrast to other neurodegenerative diseases, no biomarker has yet been validated in clinical use for ALS. Several fluid biomarkers have been investigated in clinical studies in ALS. Biofluid biomarkers reflect the different pathophysiological processes, from protein aggregation to muscle denervation. This review takes a pathophysiologic approach to summarizing the findings of clinical studies utilizing quantitative biofluid biomarkers in ALS, discusses the utility and shortcomings of each biomarker, and highlights the superiority of neurofilaments as biomarkers of neurodegeneration over other candidate biomarkers.