According to recent evidence, some groups of semaphorins (SEMAs) have been associated with cancer progression. These proteins are able to modulate the cellular signaling of particular receptor tyrosine kinases (RTKs) via the stimulation of SEMA-specific coreceptors, namely plexins (plexin-A, -B, -C, -D) and neuropilins (Np1, Np2), which share common domains with RTKs, leading to the coactivation of the latter receptors. MET, ERBB2, VEGFR2, PFGFR, and EGFR, among others, represent acknowledged targets of semaphorins that are often associated with tumor progression or poor prognosis. In particular, higher expression of SEMA6 family proteins in cancer cells and stromal cells of the cancer niche is often associated with enhanced tumor angiogenesis, metastasis, and resistance to anticancer therapy. Notably, high SEMA6 expression in malignant tumor cells such as melanoma, pleural mesothelioma, gastric cancer, lung adenocarcinoma, and glioblastoma may serve as a prognostic biomarker of tumor progression. To date, very few studies have focused on the mechanisms of transmembrane SEMA6-driven tumor progression and its underlying interplay with RTKs within the tumor microenvironment. This review presents the growing evidence in the literature on the complex and shaping role of SEMA6 family proteins in cancer responsiveness to environmental stimuli.

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have become integral in treating both diabetes mellitus and heart failure, independent of left ventricular ejection fraction. Their pleiotropic effect influences multiple mechanisms, enhancing the function of various systems within the body. They exhibit nephroprotective and cardioprotective effects by improving cell metabolism, endothelial function, and slowing the fibrosis of the cardiac muscle, and they also have a beneficial impact on other organs. At the cellular level, they protect against the harmful effects of free radicals both by lowering glucose levels and by supporting the function of the antioxidant system. Moreover, SGLT-2 inhibitors can modify the metabolism of adipocytes by affecting the production of cytokines such as adiponectin—which increases insulin sensitivity, leading to weight loss and improved glycemic control.

Semaphorins (SEMAs), ADAM, and ADAMTS family members are implicated in various cancer progression events within the tumor microenvironment across different cancers. In this study, we aimed to evaluate the expression of SEMA7A, SEMA4D, ADAM8, and ADAMTS10 in colorectal cancer (CRC) in relation to the mutational landscape of KRAS, NRAS, BRAF, PIK3CA, and AKT genes, microsatellite instability (MSI) status, and clinicopathological features. We also examined the associations between the expression of these proteins and selected cytokines, chemokines, and growth factors, assessed using a multiplex assay. Protein concentrations were quantified using ELISA in CRC tumors and tumor-free surgical margin tissue homogenates. Gene mutations were evaluated via RT-PCR, and MSI status was determined using immunohistochemistry (IHC). GSEA and statistical analyses were performed using R Studio. We observed a significantly elevated expression of SEMA7A in BRAF-mutant CRC tumors and an overexpression of ADAM8 in KRAS 12/13-mutant tumors. The expression of ADAMTS10 was decreased in PIK3CA-mutant CRC tumors. No significant differences in the expression of the examined proteins were observed based on MSI status. The SEMA7A and SEMA4D expressions were correlated with the expression of numerous cytokines associated with various immune processes. The potential immunomodulatory functions of these molecules and their suitability as therapeutic targets require further investigation.

Rationale: Tick-borne encephalitis (TBE) can present with neurological symptoms mimicking Guillain-Barré syndrome (GBS), posing a significant diagnostic challenge. Misidentification may lead to delayed or inappropriate treatment, increasing the risk of complications. Patient concerns: A 49-year-old man presented with flu-like symptoms and progressive paralysis of the left upper limb following a tick bite. His condition rapidly deteriorated despite initial therapy, including facial nerve palsy, further paralysis of the left upper limb, and swallowing difficulties. Diagnoses: The initial clinical picture, cerebrospinal fluid analysis showing elevated protein, and electromyography suggested GBS. Interventions: The patient underwent 6 plasmapheresis sessions for suspected GBS, with no neurological improvement. Outcomes: Due to a lack of improvement and further magnetic resonance imaging findings, a repeated lumbar puncture and serological testing revealed the correct diagnosis of TBE, confirmed by the presence of IgM and IgG antibodies against the TBE virus. After stabilization and intensive care unit discharge, the patient was transferred to a neurology ward and later to a rehabilitation unit. Significant neurological improvement was observed, although partial left upper limb paresis and facial nerve palsy persisted. He was eventually discharged with continued outpatient neurology and cardiology follow-up. Lessons: This case highlights the importance of detailed medical history, including tick exposure, and maintaining a broad differential diagnosis in acute flaccid paralysis. Early consideration of infectious etiologies, particularly in endemic regions, is essential to prevent unnecessary interventions and improve patient outcomes.

Cartilage oligomeric matrix protein (COMP) influences extracellular matrix remodeling. We investigated its clinical, prognostic, and immunomodulatory significance in colorectal cancer (CRC). COMP was quantified via ELISA in 107 paired CRC and normal tissues. Expression was correlated with clinicopathological features, mutational profiles, microsatellite instability (MSI), tumor-infiltrating lymphocytes (TILs), immune checkpoints, and multiplex cytokine networks. For transcriptomic validation, the FieldEffectCrc dataset was used for Gene Set Enrichment Analysis (GSEA), and The Cancer Genome Atlas (TCGA) CRC cohort for survival analysis. COMP was significantly upregulated in CRC tissues (p < 0.001) and correlated with advanced T, N, and overall pathological stages (all p < 0.05, tau = 0.18, 0.21, and 0.23, respectively). High COMP expression was linked to restricted immune infiltration (reduced stromal TILs, p < 0.05, tau = −0.23), elevated levels in microsatellite stable (MSS) compared to MSI tumors (p < 0.01), and correlated positively with immune exhaustion markers (T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), galectin-9 (GAL9), sialic acid-binding Ig-like lectin 9 (SIGLEC9)). Transcriptomic data linked high COMP to worse disease-specific and progression-free survival, and enrichment in pro-tumorigenic pathways (epithelial-to-mesenchymal transition, angiogenesis, IL-6 signaling). COMP upregulation defines an immunosuppressive microenvironment in CRC, particularly in MSS tumors. It represents an important prognostic biomarker and potential therapeutic target for overcoming immunotherapy resistance.

(1). Background: Therapeutic plasma exchange (TPE) is a method of extracorporeal plasma filtration designed to remove immunoglobulins and pro-inflammatory factors as pathogenesis of numerous diseases. Procedures are performed in intensive care units (ICUs); however, the complications and treatment outcomes remain unclear. The aim of the study was to evaluate clinical outcomes and identify risk factors of complications associated with TPE. (2). Methods: In this multi-center, retrospective, 5-year cohort study, we analyzed a database of 56 adult ICU patients who had undergone TPE at two academic hospitals and one regional hospital. (3). Results: In our study, the median APACHE II was 7.5 IQR 12.5 (4–16.5) and SOFA score was 2 IQR 4 (1–5). In the multivariate analysis, the APACHE II (p = 0.043) and SOFA score (p = 0.046) were the predictors of prolonged length of stay. The SOFA score was a predictor of hospital-acquired infection (HAI) (p = 0.011). Multivariate logistic regression revealed age (p = 0.011), SOFA (p = 0.011), and APACHE II score (p = 0.032) as independent predictors of the development of shock as a TPE complication. (4). Conclusions: Our results suggest that the SOFA and APACHE II scores are significant predictors of the length of hospitalization and the occurrence of shock. In addition, the SOFA score was a predictor of HAI in patients treated TPE in ICU.