Search Results (347)

Despite significant advances in neurosurgical and critical care, traumatic brain injury (TBI) remains a major cause of morbidity and mortality. Surgical treatment of intracranial hemorrhagic lesions can only target the primary mechanical injuries and their immediate consequences but fails to address the biochemical pathological cascade that unfolds during the second injury. This review synthesizes current knowledge regarding the use of several biomarkers in diagnosis and prognosis assessment. A structured literature search was conducted by querying the PubMed database. Articles evaluating diagnostic and prognostic biomarkers in adult TBI were screened according to Prisma guidelines, and data regarding biomarkers type, cut-off values, and correlations with the outcome were extracted and summarized. Among Central Nervous System (CNS)-Specific markers, S100 calcium-binding protein (S100B) emerged as a remarkably strong negative predictor for Computed Tomography (CT)-visible intracranial lesions (NPV = 97.3–100%), whereas glial fibrillary acidic protein (GFAP) yielded both high NPV and brain specificity. Coagulation parameters such as the international normalized ratio (INR) and fibrinogen were independently correlated with mortality and unfavorable outcomes. Fibrinogen displayed a bidirectional relationship with increased mortality risk at both low (<2 g/L) and high (>4.5 g/L) values. In conclusion, biomarkers quantify the otherwise invisible progression of secondary traumatic brain injury that persists even after successful surgery. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by the viral spike proteins, which are key structural components that mediate host cell binding and entry and alter downstream signaling through multiple interactions with endothelial surface receptors. Endothelial dysfunction is a central consequence of COVID-19, contributing to vascular inflammation, barrier disruption, thrombosis, and multi-organ injury affecting the pulmonary, cardiovascular, cerebral, and renal systems. Emerging evidence demonstrates that spike protein-mediated effects, independent of productive viral infection, disrupt endothelial homeostasis through angiotensin-converting enzyme 2 (ACE2) dysregulation, integrin engagement, altered calcium signaling, junctional protein remodeling, oxidative stress, and pro-inflammatory and pro-apoptotic pathways. This review is intentionally focused on spike (S) protein-driven mechanisms of endothelial dysfunction; pathogenic vascular effects attributed to other SARS-CoV-2 structural proteins, including the nucleocapsid (N) protein, are beyond the scope of this discussion. In this review, we synthesize current experimental and translational data detailing the molecular mechanisms by which the SARS-CoV-2 spike protein drives endothelial dysfunction across multiple organ systems and discuss potential therapeutic strategies aimed at preserving endothelial integrity in acute COVID-19 and its long-term vascular sequela. Full article

An increasing number of stroke survivors are burdened by persistent disabilities, requiring long-term rehabilitation. However, the extent of functional gain is highly variable, severely impairing patients’ quality of life. This variability highlights a critical gap in current prognostic tools, which rely primarily on clinical and neuroimaging data. The aim of this review is to synthesize the current literature on serum biomarkers in stroke survivors and to evaluate their prognostic value for rehabilitation outcomes. Our synthesis indicates that biomarkers reflecting distinct pathophysiological processes are emerging as key prognostic indicators. Markers of inflammation such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6), and Interleukin-1 beta (IL-1β), and neuro-glial injury, including S100 Calcium-Binding Protein B (S100B), Neuron-Specific Enolase (NSE), Glial Fibrillary Acidic Protein (GFAP), and Neurofilament Light Chain (NfL), are consistently associated with poorer functional outcomes. Conversely, markers of neuroplasticity, such as Brain-Derived Neurotrophic Factor (BDNF) and Insulin-like Growth Factor-1 (IGF-1), serve as potential indicators of recovery potential, although their predictive accuracy remains inconsistent across studies. Furthermore, emerging biomarkers of synaptic activity, such as Syntaxin-1a (STX1A) and Synaptosomal-Associated Protein, 25kDa (SNAP-25), and neuromuscular junction integrity, such as C-terminal Agrin Fragment (CAF), offer novel insights into brain–periphery communication, though their clinical utility is still under investigation. While promising, the translation of these biomarkers into clinical practice is hindered by methodological limitations, including assay heterogeneity and lack of large-scale validation. Future standardization of these molecular signatures is a critical step toward implementing precision medicine in stroke rehabilitation. Full article

Feline calicivirus (FCV) is a highly variable RNA virus that infects domestic cats and circulates endemically within feline populations, causing a wide spectrum of clinical manifestations, from asymptomatic infections to severe disease. Genomic analysis of 69 FCV strains revealed a high prevalence of the virus across multiple provinces in China. In vitro infection of CRFK cells with laboratory isolates FCV-BJ616 and FCV-BJDX40 resulted in significant cytotoxic effects. Serum proteomic analysis identified 221 upregulated and 123 downregulated proteins following infection with FCV-BJ616, and 233 upregulated and 165 downregulated proteins following infection with FCV-BJDX40. Among these, 215 proteins exhibited shared differential expression. Functional analyses revealed enriched pathways, including TNF signaling and ferroptosis. Notably, upregulation of Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) was correlated with lung injury, while downregulation of S100 Calcium Binding Protein A2 (S100A2) was associated with poor prognosis in FCV-associated oral disease. The differential expression of ACSL4 and S100A2 was further validated through Western blot analysis. These results suggest that ACSL4 and S100A2 are promising candidate biomarkers for monitoring FCV infection and disease progression, laying a foundation for future diagnostic and prognostic applications. Full article

Hyperphosphorylated collapsin response mediator protein 2 (CRMP2) is elevated in the cerebral cortex of an APP-SAA knock-in mouse model of Alzheimer’s disease and binds the adenine nucleotide translocase (ANT) in a phosphorylation-dependent manner. We propose that, in Alzheimer’s disease (AD) mitochondria, dissociation of hyperphosphorylated CRMP2 from ANT promotes opening of the permeability transition pore (PTP). We showed that purified ANT, when reconstituted into giant liposomes, forms large calcium-dependent channels resembling the PTP, which are effectively blocked by recombinant, unphosphorylated CRMP2. In synaptic mitochondria isolated from the cortices of APP-SAA knock-in mice and control B6J hAbeta mice, we observed an increased susceptibility to permeability transition pore (PTP) induction in AD mitochondria, accompanied by reduced viability of cultured cortical neurons. Pre-treatment of AD mice with the CRMP2-binding small molecule (S)-lacosamide ((S)-LCM), which prevents CRMP2 hyperphosphorylation and restores its interaction with ANT, attenuated PTP induction and improved neuronal viability. Interestingly, direct application of (S)-LCM to isolated mitochondria failed to suppress PTP induction, indicating that its protective effect requires upstream cellular mechanisms. These findings support a phosphorylation-dependent role for CRMP2 in regulating PTP induction in AD mitochondria and highlight (S)-LCM as a promising therapeutic candidate for mitigating mitochondrial dysfunction and enhancing neuronal viability in AD. Full article

Preeclampsia (PE) is the onset of hypertension in pregnancy with systemic involvement; PE poses significant risks of cerebral complications, including eclampsia and long-term cognitive impairment. This review explores the potential of neurological biomarkers—neurofilament light chain (NfL), neuron-specific enolase (NSE), S100 Calcium Binding Protein B (S100B), and tau—as indicators of cerebral injury in PE. A literature search identified studies comparing biomarker levels in preeclamptic and healthy pregnancies. Findings reveal elevated plasma levels of NfL, NSE, S100B, and Tau in PE, with NfL showing the strongest association with blood–brain barrier dysfunction, cognitive symptoms, and disease severity. Variations between plasma and cerebrospinal fluid levels suggest impaired BBB integrity rather than increased central nervous system production. Despite promising correlations, limitations include small sample sizes, lack of standardized thresholds, and limited CSF data. While NfL emerges as a particularly promising marker for risk stratification, further research is needed to validate the clinical utility of these biomarkers in routine PE management. Full article

Background: The apicomplexan parasite Toxoplasma gondii causes serious diseases in animals and humans. The in vitro efficacy of the antimicrobial peptide mixture tyrothricin, composed of tyrocidines and gramicidins, against T. gondii tachyzoites was investigated. Methods: Effects against T. gondii were determined by monitoring inhibition of tachyzoite proliferation and electron microscopy, host cell and splenocyte toxicity was measured by Alamar blue assay, and early embryo toxicity was assessed using zebrafish embryos. Differential affinity chromatography coupled to mass spectrometry and proteomics (DAC-MS-proteomics) was employed to identify potential molecular targets in T. gondii cell-free extracts. Results: Tyrothricin inhibited T. gondii proliferation at IC₅₀s < 100 nM, with tyrocidine A being the active and gramicidin A the inactive component. Tyrothricin also impaired fibroblast, T cell and zebrafish embryo viability at 1 µM. Electron microscopy carried out after 6 h of treatment revealed cytoplasmic vacuolization and structural alterations in the parasite mitochondrion, but these changes appeared only transiently, and tachyzoites recovered after 96 h. Tyrothricin also induced a reduction in the mitochondrial membrane potential. DAC-MS-proteomics identified 521 proteins binding only to tyrocidine A. No specific binding to gramicidin A was noted, and four proteins were common to both peptides. Among the proteins binding specifically to tyrocidine A were several SRS surface antigens and secretory proteins, mitochondrial inner and outer membrane proteins associated with the electron transfer chain and porin, and several calcium-binding proteins putatively involved in signaling. Discussion: These results suggest that tyrocidine A potentially affected multiple pathways important for parasite survival and development. Full article

Fast-twitch and slow-twitch muscle fibers not only differ in metabolic characteristics and physiological functions but also significantly influence the texture of livestock meat. RNA editing represents an important post-transcriptional regulatory process that can influence both gene expression and the resulting protein function. However, studies on RNA editing events in yak muscle remain limited. This study systematically identified RNA editing events in yak biceps femoris (BF, n = 3) and obliquus externus abdominis (OEA, n = 3) using transcriptomic data, discovering 17,713 unique editing sites, most located in non-coding regions. Within coding regions, 3350 sites were detected, with 1195 resulting in non-synonymous amino acid substitutions. Further analysis revealed that 785 sites potentially affected miRNA binding sites, suggesting RNA editing may participate in miRNA-mediated gene regulation. Tukey’s post hoc test (p < 0.05) identified 242 sites (involving 170 genes) with significantly different editing levels between BF and OEA. KEGG pathway analysis indicated that genes with differential RNA editing were predominantly associated with pathways involved in muscle fiber type transitions, including the MAPK and calcium signaling pathways. Collectively, this study maps the RNA editing landscape in yak muscle tissue and identifies distinct, fiber-type-specific RNA editing patterns between oxidative and glycolytic muscle fibers, including differences in editing levels and site distributions, supporting a potential association between RNA editing and muscle fiber type transformation. Full article

This study evaluated the protective effects of naringin (NG) against intestinal injury in 7-day-old piglets infected with porcine epidemic diarrhea virus (PEDV). Eighteen piglets (Duroc × Landrace × Large, body weight = 2.58 ± 0.05 kg) were divided into three treatment groups based on similar body weights and equal numbers of males and females: the blank control group (CON group), the PEDV infection group (PEDV group), and the NG intervention + PEDV infection group (NG + PEDV group) (n = 6 per group). The experiment lasted for 11 days, comprising a pre-feeding period from days 0 to 3 and a formal experimental period from days 4 to 10. On days 4–10 of the experiment, piglets in the NG + PEDV group were orally administered NG (10 mg/kg). On Day 8 of the experiment, piglets in the PEDV and NG + PEDV groups were inoculated with PEDV (3 mL, 10⁶ 50% tissue culture infective dose (TCID₅₀) per milliliter). On day 11 of the experiment, piglets were euthanized for sample collection. PEDV infection caused significant intestinal damage, including a decreased (p < 0.05) villus height in the duodenum and ileum and an increased (p < 0.05) crypt depth in all intestinal segments. This intestinal damage was accompanied by an impaired absorptive function, as indicated by reduced (p < 0.05) serum D-xylose. Further results showed that PEDV compromised the intestinal antioxidant capacity by decreasing (p < 0.05) glutathione peroxidase and catalase activities, and it stimulated the intestinal inflammatory response by upregulating (p < 0.05) the expression of key inflammatory genes, including regenerating family member 3 gamma (REG3G; duodenum, jejunum, colon), S100 calcium binding protein A9 (S100A9; ileum, colon), interleukin 1 beta (IL-1β; ileum, colon), and S100 calcium binding protein A8 (S100A8; colon). PEDV also suppressed the intestinal lipid metabolism pathway by downregulating (p < 0.05) the ileal expression of Solute Carrier Family 27 Member 4 (SLC27A4), Microsomal Triglyceride Transfer Protein (MTTP), Apolipoprotein A4 (APOA4), Apolipoprotein C3 (APOC3), Diacylglycerol O-Acyltransferase 1 (DGAT1), and Cytochrome P450 Family 2 Subfamily J Member 34 (CYP2J34). Moreover, PEDV suppressed the intestinal antiviral ability by downregulating (p < 0.05) interferon (IFN) signaling pathway genes, including MX dynamin like GTPase 1 (MX1) and ISG15 ubiquitin like modifier (ISG15) in the duodenum; weakened intestinal water and ion transport by downregulating (p < 0.05) aquaporin 10 (AQP10) and potassium inwardly rectifying channel subfamily J member 13 (KCNJ13) in the duodenum, aquaporin 7 (AQP7) and transient receptor potential cation channel subfamily V member 6 (TRPV6) in the ileum, and TRPV6 and transient receptor potential cation channel subfamily M member 6 (TRPM6) in the colon; and inhibited intestinal digestive and absorptive function by downregulating (p < 0.05) phosphoenolpyruvate carboxykinase 1 (PCK1) in the duodenum and sucrase-isomaltase (SI) in the ileum. Notably, NG effectively counteracted these detrimental effects. Moreover, NG activated the IFN signaling pathway in the jejunum and suppressed PEDV replication in the colon. In conclusion, NG alleviates PEDV-induced intestinal injury by enhancing the antioxidant capacity, suppressing inflammation, normalizing the expression of metabolic and transport genes, and improving the antiviral ability. Full article

Background/Objectives: Cardiac arrest (CA) continues to be one of the leading causes of mortality and long-term neurological disability worldwide. Accurate early neuroprognostication after return of spontaneous circulation is essential for guiding post-resuscitation care. The calcium-binding astrocytic protein S100B has been identified as a potential biomarker for hypoxic–ischemic brain injury. This systematic review and meta-analysis assessed the prognostic and diagnostic efficacy of serum S100B in forecasting neurological outcomes after CA. Methods: Thorough searches of PubMed, Embase, Scopus, Web of Science, CENTRAL, and CINAHL from their inception to November 2025 uncovered 40 observational studies. Results: Pooled analyses employing random-effects models revealed markedly reduced S100B concentrations in patients with favourable neurological outcomes compared to those with unfavourable outcomes (standardized mean difference −1.78, 95%CI: −2.25 to −1.31; p < 0.001). The diagnostic accuracy was high, with pooled sensitivity and specificity of 0.63 and 0.93, respectively, and an area under the curve of 0.89 (95% CI 0.85–0.92). Subgroup and sensitivity analyses confirmed the robustness of these findings across various study populations and temporal points, with negligible evidence of publication bias. Conclusions: These results indicate that serum S100B is a reliable early biomarker of neurological prognosis after CA. Incorporating S100B into multimodal predictive frameworks may enhance post-resuscitation decision-making. Full article

Traumatic brain injury (TBI) is a major global health concern and a leading cause of mortality and disability. Head computed tomography (CT) remains indispensable for the detection of intracranial hemorrhage; however, its indiscriminate use in mild trauma increases radiation exposure, cumulative oncogenic risk, and healthcare costs. Consequently, there is growing interest in tools capable of improving sensitivity in mild or early-stage TBI. Protein-based biomarkers are promising complements to conventional assessment. Molecules such as glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), S100 calcium-binding protein B (S100B), and neurofilament light chain (NfL) reflect astroglial activation, neuronal injury, and axonal damage, enabling objective evaluation of neurotrauma. Beyond protein biomarkers, metabolomic and lipidomic approaches capture alterations associated with early metabolic distress, oxidative stress, mitochondrial dysfunction, and membrane disruption following TBI. High-resolution mass spectrometry studies have identified reproducible metabolite and lipid signatures correlating with injury severity and functional outcomes. Longitudinal profiling further reveals dynamic metabolic trajectories that distinguish secondary injury progression from stabilization, supporting predictive modeling and risk stratification. Together, these advances pave the way toward precision medicine in neurotrauma. Nevertheless, variability in assay performance and sampling timing continues to limit widespread clinical adoption. Future research should prioritize methodological standardization, analytical validation, and the integration of multi-omic data with machine learning–based predictive models. Full article

Microproteins are small polypeptides translated from short open reading frames (sORFs) that typically encode < 100 amino acids. Advances in ribosome profiling, mass spectrometry, and computational prediction have revealed a growing number of microproteins that play important roles in cellular metabolism, organelle function, and stress adaptation; however, these were considered non-coding or functionally insignificant. At the mitochondrial level, microproteins, such as MTLN (also known as mitoregulin/MOXI) and BRAWNIN, contribute to lipid oxidation, oxidative phosphorylation efficiency, and respiratory chain assembly. Other microproteins at the endoplasmic reticulum–mitochondria interface, including PIGBOS and several muscle-resident regulators of calcium cycling, show diverse biological contexts in which these microproteins act. A subset of microproteins responds to nutrient availability. For example, SMIM26 modulates mitochondrial complex I translation under serine limitation, and non-coding RNA expressed in mesoderm-inducing cells encoded with peptides facilitates glucose uptake during differentiation, indicating that some microproteins can affect metabolic adaptation through localized translational- or organelle-level mechanisms. Rather than functioning as primary nutrient sensors, these microproteins complement classical nutrient-responsive pathways such as AMP-activated protein kinase-, peroxisome proliferator-activated receptor-, and carbohydrate response element binding protein-mediated signaling. As the catalog of microproteins continues to expand, integrating proteogenomics, nutrient biology, and functional studies will be central to defining their physiological relevance; these integrative approaches will also help reveal their potential applications in metabolic health. Full article

Mitochondrial dysfunction is a pivotal contributor to neurodegeneration. Neurons heavily rely on mitochondrial oxidative metabolism and therefore need highly efficient quality control mechanisms, including proteostasis, mitochondrial biogenesis, fusion–fission dynamics, and mitophagy, to sustain bioenergetics and synaptic function. With aging, deterioration of mitochondrial quality control pathways leads to impaired oxidative phosphorylation, excessive reactive oxygen species generation, calcium imbalance, and defective clearance of damaged organelles, ultimately compromising neuronal viability. Pathological protein aggregates, such as α-synuclein in Parkinson’s disease, β-amyloid and tau in Alzheimer’s disease, and misfolded superoxide dismutase 1 and transactive response DNA-binding protein 43 in amyotrophic lateral sclerosis, further aggravate mitochondrial stress, establishing self-perpetuating cycles of neurotoxicity. Such mitochondrial defects underscore mitochondria as a convergent pathogenic hub and a promising therapeutic target for neuroprotection. Intermediate filaments (IFs), traditionally viewed as passive structural elements, have recently gained attention for their roles in cytoplasmic organization, mitochondrial positioning, and energy regulation. Emerging evidence indicates that IF–mitochondria interactions critically influence organelle morphology and function in neurons. This review highlights the multifaceted involvement of mitochondrial dysfunction and IF dynamics in neurodegeneration, emphasizing their potential as targets for novel therapeutic strategies. Full article

Background/Objectives: Perinatal depression poses significant risks to maternal and fetal health, yet biomarkers for treatment response in the field remain limited. Given the overlap in symptoms with major depressive disorder (MDD) and the comparatively more vast MDD literature, identifying promising MDD biomarkers for treatment response and examining corresponding perinatal depression biomarkers can reveal translational opportunities. Methods: PUBMED searches were conducted for individual biomarkers and MDD and perinatal depression, as well as with treatment response to antidepressant pharmacological treatment and neuromodulation treatments. When available, evidence from meta-analyses and systematic reviews were preferentially summarized. Review: This narrative review presents the current evidence on MDD and perinatal depression treatment response biomarkers, including brain-derived neurotrophic factor (BDNF), S100 calcium-binding protein B (S100B), electroencephalography, event-related potentials, metabolomics, hypothalamic–pituitary–adrenal axis hormones, neuroimaging markers, inflammatory markers, and neuroactive steroids. Conclusions: Biomarker research in MDD yields insights on promising biomarkers for treatment response, including BDNF, S100B, theta band density and cordance, inflammatory markers IL-8, CRP, and TNF- α, and neuroactive steroids. Full article

Excitation–contraction (EC) coupling in skeletal muscle requires a physical interaction between the voltage-gated calcium channel, dihydropyridine receptor (DHPR), and the ryanodine receptor (RyR1) Ca²⁺ release channel. Although the exact mode of communication that links these two membrane proteins remains to be fully resolved, both the α_1s and β_1a subunits of DHPR are two of a select number of critical proteins involved in this process. A detailed in vitro interaction study of these two proteins reveals that their association occurs between the β_1a SH3 domain and the polyproline motifs located in a critical region of the α_1s II-III loop. We demonstrate that subtle changes in the composition of the β_1a SH3 domain influences the ability of β proteins to bind to II-III loop proteins and investigate the effect of these changes on EC skeletal coupling. Furthermore, investigation into the composition of the II-III loop shows that previously identified amino acids demonstrated to be important in EC coupling are implicated in in vitro binding. In summary, we ascribe a role for the DHPR β_1a which involves the engagement of its SH3 domain with the α_1s II-III loop and propose a scenario whereby this interaction may facilitate skeletal muscle EC coupling. Full article