Search Results (644)

Background/Objectives: Chemotherapy-induced neuropathic pain (CINP) represents a critical challenge in oncology, emerging as a common and debilitating side effect of widely used chemotherapeutic agents, such as paclitaxel (PTX). Current therapeutic interventions and preventive strategies for CINP are largely insufficient, as they fail to address the underlying peripheral nerve damage, highlighting an urgent need for the development of new drugs. This study aimed to investigate the dual-function effects on normal cell protection and tumor suppression of BMX-001, a redox-active manganese metalloporphyrin that has demonstrated antioxidant and anti-inflammatory properties, which offers potential in protecting central nervous system tissues and treating CINP. Methods: This study assessed BMX-001’s different roles in protecting normal cells while acting as a pro-oxidant and pro-inflammatory molecule in cancer cells in vitro. We also evaluated its neuroprotective effect in preclinical PTX-induced CINP models in vivo. Results: Our results showed significant reductions in mechanical and cold allodynia, decreased pro-inflammatory cytokine levels, and restored antioxidant capacity in peripheral nerves and dorsal root ganglia (DRGs) following BMX-001 treatment. Conclusions: Overall, our study highlights the therapeutic potential of BMX-001 to mitigate CINP and enhance anticancer efficiency. Its dual-selective mechanism supports the future clinical investigation of BMX-001 as a novel adjunct to chemotherapeutic regimens. Full article

Melanoma is a highly aggressive skin cancer with limited therapeutic response. Targeting intracellular signaling pathways and promoting tumor cell differentiation are promising therapeutic strategies. Pentoxifylline (PTX) and norcantharidin (NCTD) have demonstrated antitumor properties, but their combined mechanisms of action in melanoma remain poorly understood. The effects of PTX (30 and 60 mg/kg) and NCTD (0.75 and 3 mg/kg), administered alone or in combination, in a DBA/2J murine B16-F1 melanoma model via intraperitoneal and intratumoral (IT) routes were evaluated. Tumor growth was monitored, and molecular analyses included RNA sequencing and immunofluorescence quantification of PI3K, AKT1, mTOR, ERBB2, BRAF, and MITF protein levels, and molecular docking simulations were performed. In the final stage of the experiment, combination therapy significantly reduced tumor volume compared to monotherapies, with the relative tumor volume decreasing from 18.1 ± 1.2 (SD) in the IT Control group to 0.6 ± 0.1 (SD) in the IT combination-treated group (n = 6 per group; p < 0.001). RNA-seq revealed over 3000 differentially expressed genes in intratumoral treatments, with enrichment in pathways related to oxidative stress, immune response, and translation regulation (KEGG and Reactome analyses). Minimal transcript-level changes were observed for BRAF and PI3K/AKT/mTOR genes; however, immunofluorescence showed reduced total and phosphorylated levels of PI3K, AKT1, mTOR, BRAF, and ERBB2. MITF protein levels and pigmentation increased, especially in PTX-treated groups, indicating enhanced melanocytic differentiation. Docking analyses predicted direct binding of both drugs to PI3K, AKT1, mTOR, and BRAF, with affinities ranging from −5.7 to −7.4 kcal/mol. The combination of PTX and NCTD suppresses melanoma progression through dual mechanisms: inhibition of PI3K/AKT/mTOR signaling and promotion of tumor cell differentiation. Full article

Background: Septic arthritis is an orthopedic emergency. However, optimal biomarkers and diagnostic criteria remain unclear. The study aimed to evaluate the diagnostic performance of routinely used and novel biomarkers, including serum C-reactive protein (CRP), synovial white blood cells (WBC), pentraxin-3 (PTX3), interleukin-6 (IL-6), and presepsin, in distinguishing septic from non-septic arthritis. Methods: Thirty-one patients undergoing arthrocentesis were included. Patients were categorized into septic and non-septic arthritis groups. Synovial fluid and serum samples were analyzed for five biomarkers. Diagnostic performance was assessed by calculating the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Synovial WBC demonstrated the highest diagnostic performance among single biomarkers (AUC = 0.837, p = 0.012). Among novel biomarkers, PTX3 showed the highest accuracy and sensitivity. The serum CRP and synovial WBC combination yielded an AUC of 0.853, with 100% sensitivity, 68.0% specificity, 42.9% PPV, and 100% NPV. Adding all three novel biomarkers to this combination increased the AUC to 0.887 (p = 0.004), maintaining 100% sensitivity and NPV. When individually added, PTX3 achieved 100% sensitivity and NPV, while presepsin showed the highest specificity (96.0%), PPV (75.0%), and accuracy (87.1%). Conclusions: Serum CRP and synovial WBC remain essential biomarkers for diagnosing septic arthritis; however, combining them with PTX3, IL-6, and presepsin improved diagnostic accuracy. PTX3 is best suited for ruling out septic arthritis due to its high sensitivity and NPV, whereas presepsin is more useful for confirmation, given its specificity and PPV. These results support a tailored biomarker approach aligned with diagnostic intent. Full article

Background/Objectives: Chemically or genetically detoxified pertussis toxin (PTx) is a crucial antigen component of the acellular pertussis vaccine. Chemical detoxification using glutaraldehyde generally causes significant structural changes to the toxin. However, how these structural changes in PTx affect its antigenic properties remains unclear. Additionally, there is limited knowledge regarding how many alterations in antigenic properties impact immunogenicity. Methods: To investigate the impact of structural changes on antigenic properties, we developed a sandwich ELISA to quantify the neutralizing epitopes on PTx. Subsequently, we analyzed different PTx toxoid (PTd) preparations with the assay. Additionally, we assessed the immunogenicity of various acellular pertussis vaccine candidates containing these PTd preparations. Finally, the assay was applied to evaluate the consistency of commercial batches of PTx and PTd intermediates. Results: The assay demonstrated reasonable specificity, accuracy, and precision, and it was sensitive enough to quantify variations in neutralizing epitopes among different PTd samples that shared the same protein concentration. Importantly, we found a positive correlation between the number of neutralizing epitopes in detoxified PTx and its immunogenicity, indicating that the amount of neutralizing epitopes present determines the immunogenicity of glutaraldehyde-inactivated PTx. Moreover, commercial batches of PTx and PTd intermediates exhibited minor variations in neutralizing epitopes. Conclusions: These findings have significant implications for developing acellular pertussis vaccines as they highlight the importance of preserving the neutralizing epitopes of PTx during detoxification to ensure the vaccine’s effectiveness. This assay is also valuable for the quality control of PTd as it more accurately represents the actual antigenic changes of PTx. Full article

Hodgkin lymphoma (HL) is a common neoplasm in adolescents and young adults, primarily treated with doxorubicin (DOX) and bleomycin (BLM), which may cause severe adverse effects. The cure rate decreases to 75% in advanced-stage disease, highlighting the need for improved treatment strategies. Pentoxifylline (PTX), an NF-κB pathway inhibitor, enhances chemotherapy-induced apoptosis in cancer cells, making it a promising candidate for HL therapy. This study assessed the effects of PTX, DOX, and BLM on apoptosis, proliferation, and senescence in Hs-445 HL cells. Cell viability and clonogenicity were measured by spectrophotometry and spectrofluorimetry, while apoptosis, caspase activity, cell cycle, mitochondrial membrane potential (ΔΨm), proliferation, and senescence were analyzed via flow cytometry. Gene expression was assessed by qPCR. PTX significantly induced apoptosis, especially when combined with BLM or BLM+DOX (triple therapy), and modulated gene expression by upregulating proapoptotic and downregulating antiapoptotic markers. PTX increased caspase-3, -8, and -9 activity and disrupted the ΔΨm, particularly with BLM or triple therapy. Furthermore, PTX abolished DOX-induced G2 cell cycle arrest, reduced proliferation, and clonogenicity, and reversed DOX- and BLM-induced senescence. In conclusion, PTX induces apoptosis in HL cells, enhances DOX and BLM cytotoxicity synergistically, and reverses senescence, suggesting its potential as an adjunct therapy for HL. Full article

Background/Objectives: Paclitaxel (PTX) is widely used in the treatment of a variety of solid tumours due to its broad-spectrum anti-tumour activity, but its use in brain gliomas is limited by insufficient blood–brain tumour barrier (BBTB) penetration and systemic toxicity. The aim of this study was to develop a Solutol HS-15-based micellar nanoparticle (PSM) to enhance the brain glioma targeting of PTX and reduce toxicity. Methods: PSMs were prepared by solvent injection and characterised for particle size, encapsulation rate, haemolysis rate and in vitro release properties. A C6 in situ glioma mouse model was used to assess the brain targeting and anti-tumour effects of the PSM by in vivo imaging, tissue homogenate fluorescence analysis and bioluminescence monitoring. Meanwhile, its safety was evaluated by weight monitoring, serum biochemical indexes and histopathological analysis. Results: The particle size of PSMs was 13.45 ± 0.70 nm, with an encapsulation rate of 96.39%, and it demonstrated excellent cellular uptake. In tumour-bearing mice, PSMs significantly enhanced brain tumour targeting with a brain drug concentration 5.94 times higher than that of free PTX. Compared with Taxol, PSMs significantly inhibited tumour growth (terminal luminescence intensity <1 × 10⁶ p/s/cm²/Sr) and did not cause significant liver or kidney toxicity or body weight loss. Conclusions: PSMs achieve an efficient accumulation of brain gliomas through passive targeting and EPR effects while significantly reducing the systemic toxicity of PTX. Its simple preparation process and excellent therapeutic efficacy support its use as a potential clinically translational candidate for glioma treatment. Full article

Power-to-X (ptx) technologies are considered a promising solution for enabling the storage and sectoral integration of renewable energy, playing a vital role in the sustainable transition of industrialized energy systems. This study investigates the public acceptance of ptx technologies in Germany using a quantitative, environmental–psychological framework. Key influencing factors such as social and personal norms, environmental awareness, and openness to innovation are analyzed. A particular focus is placed on generational differences, comparing the perceptions of youth (16–25 years) and adults (>25 years) through a representative online survey. The results reveal a general lack of knowledge about ptx technologies yet a positive assessment of their decarbonization potential. Ecological impact—particularly the ability to reduce CO₂ emissions—emerges as the strongest predictor of acceptance. This is closely tied to conditions such as the use of renewable electricity and sustainable sourcing of carbon and water. Notably, acceptance among youth is also influenced by environmental awareness, prior knowledge, and perceived behavioral control. The results show that, in general, there is still a need for improved science communication to address the existing uncertainties in the population. At the same time, age-specific approaches are required, as perceptions and acceptance factors differ significantly between younger and older age groups. Full article

Breast cancer is the most frequently diagnosed cancer among women. In recent years, immunotherapy, a key targeted treatment strategy, has gained prominence in the management of this disease. Immune cells within the tumor microenvironment can significantly affect treatment outcomes. Among immunotherapeutic approaches, or programmed death protein 1(PD-1) and programmed death-ligand 1(PD-L1)-targeted therapies are increasingly recognized for their role in modulating cancer–immune system interactions. This study investigated the impact of PD-1/PD-L1 pathway inhibition on the expression of drug resistance-related proteins in an in vitro breast cancer model incorporating immune cells. MDA-MB-231 and MCF-7 cell lines were used as breast cancer cells, while THP-1 and Jurkat cells represented monocytes and lymphocytes, respectively. The effects of paclitaxel (PTX), doxorubicin (Dox), and PD-1/PD-L1 inhibitors (BMS-1166 and Human PD-L1 Inhibitor IV (PI4)) on cell viability were evaluated using an MTT assay, and the IC₅₀ values were determined. Flow cytometry was used to analyze PD-1/PD-L1 expression and the drug resistance proteins ABCG2 (ATP-binding cassette sub-family G member 2, breast cancer resistance protein), MDR-1 (multidrug resistance protein 1), and MRP-1 (multidrug resistance-associated protein 1) across co-culture models. Based on the results, Dox reduced PD-L1 expression in all groups except for MDA-MB-231:THP-1, while generally lowering drug resistance protein levels, except in MDA-MB-231:Jurkat. BMS-1166 significantly decreased cell viability and enhanced chemotherapy-induced cytotoxicity. Interestingly, in the MDA-MB-231:Jurkat co-culture, both inhibitors reduced PD-L1 but increased drug resistance protein expression. Paclitaxel’s effect on PD-L1 varied depending on the immune context. These findings highlight that PD-1/PD-L1 inhibitors and chemotherapeutic agents differentially affect PD-L1 and drug resistance-related protein expression depending on the immune cell composition within the tumor microenvironment. Full article

Background/Objectives: PEGylated liposomes are widely recognized for their biocompatibility and capacity to extend systemic circulation via “stealth” properties. However, the PEG corona often limits tumor penetration and cellular internalization. Targeting matrix metalloproteinase-2 (MMP-2), frequently upregulated in breast cancer stroma, presents an opportunity to enhance tissue-specific drug delivery. In this study, we engineered MMP-2-responsive GPLGVRG peptide-modified cleavable PEGylated liposomes for targeted paclitaxel (PTX) delivery. Methods: Molecular docking simulations employed the MMP-2 crystal structure (PDB ID: 7XJO) to assess GPLGVRG peptide binding affinity. A cleavable, enzyme-sensitive peptide-PEG conjugate (Chol-PEG_2K-GPLGVRG-PEG_5K) was synthesized via small-molecule liquid-phase synthesis and characterized by ¹H NMR and MALDI-TOF MS. Liposomes incorporating this conjugate (S-Peps-PEG_5K) were formulated to evaluate whether MMP-2-mediated peptide degradation triggers detachment of long-chain PEG moieties, thereby enhancing internalization by 4T1 breast cancer cells. Additionally, the effects of tumor microenvironmental pH (~6.5) and MMP-2 concentration on drug release dynamics were investigated. Results: Molecular docking revealed robust GPLGVRG-MMP-2 interactions, yielding a binding energy of −7.1 kcal/mol. The peptide formed hydrogen bonds with MMP-2 residues Tyr A:23 and Arg A:53 (bond lengths: 2.4–2.5 Å) and engaged in hydrophobic contacts, confirming MMP-2 as the primary recognition site. Formulations containing 5 mol% Chol-PEG_2K-GPLGVRG-PEG_5K combined with 0.15 µg/mL MMP-2 (S-Peps-PEG_5K +MMP) exhibited superior internalization efficiency and significantly reduced clonogenic survival compared to controls. Notably, acidic pH (~6.5) induced MMP-2-mediated cleavage of the GPLGVRG peptide, accelerating S-Peps-PEG_5K dissociation and facilitating drug release. Conclusions: MMP-2-responsive, cleavable PEGylated liposomes markedly improve PTX accumulation and controlled release at tumor sites by dynamically modulating their stealth properties, offering a promising strategy to enhance chemotherapy efficacy in breast cancer. Full article

Background/Objectives: Secondary hyperparathyroidism (SHPT) is a prevalent complication in end-stage renal disease, often necessitating surgical intervention when refractory to medical therapy. The optimal surgical strategy—subtotal parathyroidectomy (SPTX) versus total parathyroidectomy with/without autotransplantation (TPTX ± AT)—remains debated, especially considering postoperative complications like persistent HPT and hungry bone syndrome (HBS). This study aimed to compare early surgical outcomes and identify predictors for postoperative complications in patients undergoing SPTX and TPTX + AT. Methods: We conducted a retrospective, single-center observational study involving 93 dialysis patients who underwent PTX for drug-refractory SHPT. Patients were analyzed according to surgical procedure (SPTX vs. TPTX + AT), focusing on postoperative complications such as cervical bleeding, reintervention rates, and the incidence of HBS. Multivariate logistic regression was utilized to identify predictors of these outcomes. Results: TPTX + AT demonstrated superior control of HPT, with significantly lower rates of reintervention compared to SPTX (7.1% vs. 23.5%, p = 0.037). However, TPTX + AT was associated with a higher incidence of HBS (57.1% vs. 35.3%, p = 0.039). Independent predictors of reintervention included absence of concomitant thymectomy, preoperative hypercalcemia, fewer visualized glands preoperatively, and preoperative PTH > 2000 pg/mL. Elevated alkaline phosphatase levels (>300 U/L), severe bone pain, and the TPTX procedure itself were significant predictors of HBS. Conclusions: Surgical strategy for SHPT should be individualized, balancing the lower recurrence risk associated with TPTX + AT against its higher likelihood of postoperative hypocalcemia. Preoperative biochemical markers and clinical features could potentially influence operative decision-making and optimize patient outcomes. Full article

In this paper, a multifunctional polymer BT-PGA-TPE-HNPE was designed and synthesized by modifying γ-polyglutamic acid (γ-PGA) with biotin, the tetraphenylethylene derivative O-TPE-HNPE and an acid-sensitive imine bond. The polymer was used to fabricate paclitaxel (PTX)-loaded micelles. As expected, the BT-PGA-TPE-HNPE micelles demonstrated strong AIE characteristics, fluorescing yellow under normal conditions and blue in acidic settings. Moreover, the drug was specifically released under acidic conditions. In vitro and in vivo tumor suppression experiments showed that the micelles had enhanced antitumor activity with minimal systemic toxicity. The BT-PGA-TPE-HNPE micelles had wide application prospects in the fields of chemotherapy and bioimaging. Full article

Background/Objectives: The aims of this study were to re-evaluate the necessity routine post-biopsy chest X-rays by evaluating the incidence, timing, and clinical relevance of pneumothorax (PTX) following CT-guided lung biopsies, and to determine whether symptom-based monitoring can safely replace routine imaging. Methods: This retrospective, single-center study included 112 patients (mean age: 69.3 years; 55% male) who underwent CT-guided lung biopsy between 9 January 2020 and 16 April 2025. PTX occurrence was assessed both intraprocedurally and during follow-up within 7 days. The primary outcome was the development of PTX; secondary outcomes were chest drainage need and delayed PTX identification. Logistic regression analysis and descriptive statistics were used to identify predictors and associations. Results: Intra-procedural PTX occurred in 43.8%, of whom 10.7% required immediate drainage. Clinically silent PTX that did not require intervention occurred in 25.9%. Routine chest X-rays were obtained 4 h post-biopsy for all patients. Importantly, no asymptomatic patient required any intervention. These results suggest that routine 4 h imaging may be unnecessary in the absence of symptoms. Conclusions: PTX is frequent after CT-guided lung biopsy but is often asymptomatic and self-limiting. The absence of clinically significant findings among asymptomatic patients supports a shift toward symptom-based monitoring. Implementing this strategy may help reduce unnecessary post-biopsy imaging and optimize healthcare resource utilization without compromising patient safety. Full article

Background/Objectives: Primary hyperparathyroidism (PHPT) has been associated with systemic inflammation and metabolic disturbances. This study aimed to evaluate changes in the Systemic Immune-Inflammation Index (SII) and Prognostic Nutritional Index (PNI) following parathyroidectomy (PTX) in PHPT patients, and to assess their return toward healthy control values. Materials and Methods: This retrospective study was conducted between January 2010 and March 2022. It analyzed the demographic characteristics, clinical findings, and laboratory results of patients diagnosed with and operated for PHPT, with comparisons to healthy controls. Postoperative values were recorded at least six months after surgery. Bone mineral density was classified according to World Health Organization criteria, and nephrolithiasis was assessed with imaging. Results: After applying exclusion criteria, 415 PHPT patients and 410 controls were included. PHPT patients were older (p < 0.001) and had a higher proportion of females (p = 0.016). Compared to controls, they had lower phosphorus, albumin, high-density lipoprotein cholesterol, total cholesterol, hemoglobin, and PNI (p < 0.001 for all), while triglycerides, monocytes, platelets, CRP, and SII were higher (p < 0.05). Postoperatively, albumin, platelets, total cholesterol, and triglycerides increased (p < 0.001), while calcium, white blood cell count, neutrophils, lymphocytes, and CRP decreased (p < 0.05), approaching healthy control values. In age- and sex-matched comparisons (propensity score matching, n = 259 in each group), platelets (p = 0.002) and hemoglobin (p = 0.018) were found to be higher postoperatively. Conclusions: Preoperative SII and PNI levels were significantly altered in PHPT patients compared to healthy controls. Following PTX, both of these markers and other parameters showed significant improvements, reflecting positive changes in systemic inflammation and nutritional status. Full article

Background: Pneumothorax (PTX) is the most common complication of CT-guided lung biopsies. New technical advances, namely the optimization of needle approach angles within an a priori defined “safe zone,” are intended to reduce this risk. This study evaluates whether PTX incidence and chest tube placement decreased significantly after these technical advances were implemented. Methods: We retrospectively analyzed 118 consecutive patients who had undergone CT-guided lung biopsy between 9 January 2020, and 4 April 2025. The study was divided into three periods of increasingly growing institutional procedural experience: Pre-Knowledge (January 2020–March 2022; n = 45), Partial Knowledge (April–December 2022; n = 18), and Full Knowledge (January 2023–April 2025; n = 55). PTX incidence and chest tube use were compared across periods using chi-square and Fisher’s exact tests, while Kaplan–Meier survival analysis was used to evaluate PTX-free survival over time. Results: Overall PTX incidence significantly declined from 71.1% in the Pre-Knowledge Period to 21.8% in the Full Knowledge Period (p < 0.000001). Rates of chest tube placements also decreased from 17.8% to 9.1%, although this difference was not statistically significant (p = 0.372). Kaplan–Meier analysis showed a statistically significant improvement in PTX-free survival over time (indicating improvement in the timing of complication onset; p = 0.0042). Procedural optimization was also fostered by a large median intrapulmonary needle length and consistent needle angulation within the safe zone. Conclusions: Formal implementation of needle angle optimization and procedural protocol standardization has effectively reduced the frequency and severity of PTX following CT-guided lung biopsies. These results highlight the benefit of continuous education and technique standardization in improving patient safety and clinical outcomes. Full article

Thoracic injuries account for a high percentage of combat casualty mortalities, with 80% of preventable deaths resulting from abdominal or thoracic hemorrhage. An effective method for detecting and triaging thoracic injuries is point-of-care ultrasound (POCUS), as it is a cheap and portable noninvasive imaging method. POCUS image interpretation of pneumothorax (PTX) or hemothorax (HTX) injuries requires a skilled radiologist, which will likely not be available in austere situations where injury detection and triage are most critical. With the recent growth in artificial intelligence (AI) for healthcare, the hypothesis for this study is that deep learning (DL) models for classifying images as showing HTX or PTX injury, or being negative for injury can be developed for lowering the skill threshold for POCUS diagnostics on the future battlefield. Three-class deep learning classification AI models were developed using a motion-mode ultrasound dataset captured in animal study experiments from more than 25 swine subjects. Cluster analysis was used to define the “population” based on brightness, contrast, and kurtosis properties. A MobileNetV3 DL model architecture was tuned across a variety of hyperparameters, with the results ultimately being evaluated using images captured in real-time. Different hyperparameter configurations were blind-tested, resulting in models trained on filtered data having a real-time accuracy from 89 to 96%, as opposed to 78–95% when trained without filtering and optimization. The best model achieved a blind accuracy of 85% when inferencing on data collected in real-time, surpassing previous YOLOv8 models by 17%. AI models can be developed that are suitable for high performance in real-time for thoracic injury determination and are suitable for potentially addressing challenges with responding to emergency casualty situations and reducing the skill threshold for using and interpreting POCUS. Full article