Search Results (4,045)

Cervical cancer (CC) is the fourth most common cancer among women globally, with venous thromboembolism (VTE) representing a life-threatening complication. Cancer-associated thrombosis (CAT) arises from tumor-driven activation of hemostasis, worsening prognosis. Recently, circulating microRNAs (miRNAs) have emerged as potential biomarkers for both CAT and cervical tumorigenesis. Thus, this study aimed to assess the implications of five miRNAs—miR-20a-5p, -23a-3p, -125b-5p, -145-5p, and -616-3p—in CC-related VTE context. These miRNAs were quantified by RT-qPCR in plasma from 69 CC patients before treatment. Briefly, VTE occurred in nine patients, decreasing overall survival (OS) [log-rank test, p = 0.005; hazard ratio (HR) = 4.78; 95% confidence interval (CI), 1.42–16.05]. Lower miR-20a-5p levels predicted VTE (ꭓ² test, p = 0.027) and, in subgroup analyses, they were linked to cervical squamous cell carcinoma (CSCC) and older age (ꭓ² test, p = 0.003 and p = 0.043, respectively). In VTE patients, miR-145-5p downregulation was associated with improved OS (log-rank test, p = 0.018), an effect also observed in the adenocarcinoma (ADC) subgroup (log-rank test, p = 0.039). The remaining miRNAs showed subtype-specific links to clinicopathological features and survival. These findings highlight the potential value of circulating miRNAs in thrombotic risk and prognosis assessment in CC. Full article

This study aims to identify molecular markers with prognostic value for biochemical pregnancy in follicular fluid (FF) samples from women with endometriosis after assisted reproductive technology (ART) intervention. Levels of growth differentiation factor-9 (GDF-9), bone morphogenetic protein-15 (BMP-15), and anti-Mullerian hormone (AMH) proteins were semi-quantified by Western blotting and microRNAs 20a_1, 145_1, 320a_1, 125-b-5p, 212-3p, and 199_a by qPCR in FF samples from women submitted to ART with a previous diagnosis of endometriosis (n = 20) or male factor infertility (controls) (n = 44). An increase in GDF-9 and BMP-15 and a decrease in AMH mature protein were observed, as well as an increase in miR20a_1 (p = 0.04), miR145_1 (p = 0.003), and miR320a_1 (p = 0.006) in FF samples collected from women with endometriosis compared with controls. A reduction was observed in miR125b-5p (p = 0.004) and 212-3p (p = 0.02) in endometriosis. Receiver operating characteristic (ROC) curve analysis indicated that miR125b-5p, miR212-3p, and miR-145_1 are potential predictors of endometriosis, and miR145_1 and miR320a_1 of biochemical pregnancy in controls. Although limited by a small sample size, the current study demonstrated alterations in AMH, BMP-15, GDF-9, and specific miRNA levels in FF samples harvested from women with endometriosis, emphasizing their potential roles in endometriosis-related infertility. These microRNAs, dysregulated in women with endometriosis, unveil their biomarker properties and their predictive value for ART success. Full article

We experimentally investigate the structural, magnetic, transport, and electronic properties of two d⁵ iridate double perovskite materials La₂BIrO₆ (B = Mg, Zn). Notably, despite similar crystallographic structure, the two compounds show distinctly different magnetic behaviors. The M = Mg compound shows an antiferromagnetic-like linear field-dependent isothermal magnetization below its transition temperature, whereas the M = Zn counterpart displays a clear hysteresis loop followed by a noticeable coercive field, indicative of ferromagnetic components arising from a non-collinear Ir spin arrangement. The local structure studies authenticate perceptible M/Ir antisite disorder in both systems, which complicates the magnetic exchange interaction scenario by introducing Ir-O-Ir superexchange pathways in addition to the nominal Ir-O-B-O-Ir super-superexchange interactions expected for an ideally ordered structure. While spin–orbit coupling (SOC) plays a crucial role in establishing insulating behavior for both these compounds, the rotational and tilting distortions of the IrO₆ (and MO₆) octahedral units further lift the ideal cubic symmetry. Finally, by measuring the Ir-L₃ edge resonant inelastic X-ray scattering (RIXS) spectra for both the compounds, giving evidence of spin–orbit-derived low-energy inter-J-state (intra t_2g) transitions (below ~1 eV), the charge transfer (O 2p → Ir 5d), and the crystal field (Ir t_2g → e_g) excitations, we put forward a qualitative argument for the interplay among effective SOC, non-cubic crystal field, and intersite hopping in these two compounds. Full article

Atopic dermatitis (AD) is the most common inflammatory skin disease in the pediatric population. In recent years, the role of microRNAs in inflammatory and immunological mechanisms as specific biomarkers of AD has received growing attention. The aim of the present study was a quantitative assessment of serum expression levels of miR-100, miR-224 and miR-155 in children with AD compared with healthy peers, and an analysis of their potential associations with clinical disease phenotype, severity of skin lesions (SCORAD), cytokine profile, immunological parameters and the presence of concomitant allergic diseases. The study included 12 children with AD and 9 healthy children. Selected miRNAs were isolated from serum, followed by reverse transcription using universal primers and quantification by qRT-PCR. Children with AD exhibited significantly higher expression levels of miR-155 compared with controls (p = 0.003). No statistically significant differences were observed for miR-100 and miR-224. miR-100 expression was significantly higher in children with a positive history of inhalant allergy compared with those without such a diagnosis (p = 0.014). A positive correlation was observed between miR-100 levels and the percentage of eosinophils (r = 0.599; p = 0.052) as well as absolute eosinophil count (r = 0.600; p = 0.051). MiR-155 is significantly upregulated in children with AD suggesting it as a candidate biomarker worthy of further investigation in larger cohorts. Although miR-100 did not differentiate the groups, its correlation with eosinophilia and inhalant allergy suggests a role in disease phenotyping. Full article

Background: Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy with poor clinical outcomes. microRNA-7-5p (miR-7-5p) has been described as both a tumour suppressor and an oncomiR depending on the tissue context, but its role in HNSCC remains unclear. This study aimed to clarify the clinical significance and biological function of miR-7-5p in HNSCC by integrating data from multiple sources. Methods: A systematic review of the literature was conducted to identify studies analysing miRNA expression in human head and neck tissues. A meta-analysis of individual patient data from Gene Expression Omnibus (GEO), ArrayExpress, and The Cancer Genome Atlas (TCGA) was performed to assess miR-7-5p expression in tumours and normal tissues, and its associations with clinical parameters and prognostic outcomes. Bioinformatics analyses were used to predict miR-7-5p target genes, classify hub genes, and perform gene ontology enrichment analysis. MicroRNA in situ hybridisation (miRNA ISH) and real-time quantitative PCR (RT-qPCR) were conducted on tissue samples, HNSCC cell lines, and an in vitro model of oral oncogenesis to validate miR-7-5p expression patterns. Results: miR-7-5p was significantly upregulated in tumours compared to normal tissues and associated with larger tumour size, HPV-negative status, poor disease-specific survival, and shorter progression-free intervals. Bioinformatics analysis highlighted miR-7-5p target genes enriched in pathways related to cell growth, survival, and tumourigenesis. Despite evidence supporting the anti-cancer role of exogenous miR-7-5p in preclinical models, the observed endogenous upregulation in tumours suggests that miR-7-5p expression may represent a compensatory or stress-responsive mechanism during tumourigenesis, rather than acting as a primary oncogenic driver. Conclusions: This study provides new insights into the complex role of miR-7-5p in HNSCC, supporting its potential as both a biomarker and a therapeutic target. Understanding the context-specific functions of miR-7-5p is essential for its development as an RNA-based therapeutic in HNSCC. Full article

Heart failure (HF) remains a major cause of mortality despite the advances in pharmacological treatment. Anticoagulation therapies, including Clopidogrel, Aspirin, Warfarin, and novel oral anticoagulants (NOACs) such as Apixaban, Rivaroxaban, Edoxaban, and Dabigatran, are frequently administered to HF patients to prevent thromboembolism and adverse, life-threatening outcomes (e.g., stroke and myocardial infarction). In these settings, drug resistance and variability in responsivity to therapeutic approaches are challenging issues. Recent studies suggest that non-coding RNAs, particularly microRNAs (miRs) may play a modulatory role in HF therapy context, affecting drug efficacy. Specific miRs have been associated with resistance to Clopidogrel (e.g., miR-223 and miR-26a), Aspirin (e.g., miR-19b-1-5p and miR-92a) and Warfarin (e.g., miR-133 and miR-137). Moreover, Digoxin, a cardiac glycoside acting also over bleeding risk, upregulates miR-132, which is involved in HF-associated cardiac alteration and hypertrophy. Evidence linking miR expression to NOAC pharmacodynamics, cardiac remodeling and regulation of the coagulation is growing. These findings highlight the need of deeply harnessing the potential of miRs as predictive biomarkers or therapeutic targets in HF. Improving the knowledge on the relationship between miR and anticoagulant drugs in HF patients will contribute to personalization of the anticoagulant therapies, aimed at enhancing patient responsivity and minimizing adverse effects, ultimately improving patient life quality. Full article

Background/Objectives: Tacrolimus is the most used immunosuppressive agent in solid organ transplantation due to its efficacy in preventing acute rejection, but it has a narrow therapeutic range, and overexposure often leads to toxicities, including neurological side effects like tremors. Tremor affects up to 54% of renal transplant patients under tacrolimus. Extended-release tacrolimus (LCPT) has demonstrated efficacy in reducing tremor severity, as evidenced by studies employing quality of life (QoL) questionnaires, the Fahn–Tolosa–Marin (FTM) scale, and Accelerometer devices. The objectives of this study were to evaluate the benefits of the conversion to LCPT formulation in kidney transplant recipients experiencing tremors on prolonged-release tacrolimus (PR-TAC) treatment and to validate the DyCare device, a wearable wireless sensor for tremors. Results: The DyCare device measured tremor frequencies of 8.74 ± 0.11 Hz and 1.36 ± 0.08° and 17.38 ± 1.16°, as root mean square (RMSx100 for accelerometer and Gyroscope, respectively) in PR-TAC patients. After switching ten patients to LCPT, tremor severity significantly decreased, as confirmed by DyCare and the QoL in the Essential Tremor Questionnaire (QUEST). Additionally, LCPT allowed a 34% reduction in tacrolimus dosage while maintaining therapeutic trough concentrations. Immunological and pharmacodynamic biomarkers (p-miR-210-3p, p-IL10, p-IL12p70, p-IFNγ uCXCL10, NFAT-regulated gene expression) confirmed stable immunosuppression post-conversion. Conclusions: The conversion to the LCPT formulation significantly reduced tremors in kidney transplant recipients without altering their immunological status, as confirmed through a panel of immunologic and pharmacodynamic biomarkers. The DyCare device enables a precise quantification of tremors in transplant recipients, allowing physicians to optimize treatment strategies. Full article

Lung-protective ventilation and other experimental conditions raise arterial carbon dioxide tension (PaCO₂) and alter pH. Short-term benefits are reported in non-infectious settings, whereas infection and/or prolonged exposure are typically harmful. This scoping review systematically maps immune-mediated effects of hypercapnia on innate immunity and alveolar epithelial repair. Scoping review per Levac et al. and PRISMA Extension for Scoping Reviews (Open Science Framework protocol: 10.17605/OSF.IO/WV85T; post hoc). We searched original preclinical studies (in vivo/in vitro) in PubMed, Web of Science, ScienceDirect, Cochrane Reviews, and SciELO (2008–2023). PaCO₂ (mmHg) was prioritized; %Fraction of inspired Carbon Dioxide (%FiCO₂) was recorded when PaCO₂ was unavailable; pH was classified as buffered/unbuffered. Data were organized by context, PaCO₂, and exposure duration; synthesis used heat maps (0–120 h) and a narrative description for >120 h. Mechanistic axes extracted the following: NF-κB (canonical/non-canonical), Bcl-2/Bcl-xL–Beclin-1/autophagy, AMPK/PKA/CaMKKβ/ERK1/2 and ENaC/Na,K-ATPase trafficking, Wnt/β-catenin in AT2 cells, and miR-183/IDH2/ATP. Thirty-five studies met the inclusion criteria. In non-infectious models, a “protective window” emerged, with moderate PaCO₂ and brief exposure (65–95 mmHg; ≤4–6 h), featuring NF-κB attenuation and preserved epithelial ion transport. In infectious models and/or with prolonged exposure or higher PaCO₂, harmful signals predominated: reduced phagocytosis/autophagy (Bcl-2/Bcl-xL–Beclin-1 axis), AMPK/PKA/ERK1/2-mediated internalization of ENaC/Na,K-ATPase, depressed β-catenin signaling in AT2 cells, impaired alveolar fluid clearance, and increased bacterial burden. Chronic exposures (>120 h) reinforced injury. Hypercapnia is a context-, dose-, time-, and pH-dependent double-edged modulator. The safe window is narrow; standardized, parallel reporting of PaCO₂ and pH—with explicit comparisons of buffered vs. unbuffered hypercapnia—is essential to guide clinical translation. Full article

Chronic inflammation driven by Cyclooxygenase-2 (COX-2) overexpression plays a key role in lung cancer (LC) progression, making it a critical therapeutic target. This study explores thymoquinone (TQ), a potent bioactive phytochemical derived from Nigella sativa, known for its anti-inflammatory and anti-cancer effects, focusing on its ability to suppress lipopolysaccharide (LPS)-induced COX-2 expression via microRNA hsa-miR-199a-3p modulation in LC cells. Using A549 and SHP-77 LC cells, we tested the effect of TQ under LPS stimulation and miRNA inhibition. Advanced techniques like TaqMan qPCR, luciferase reporter gene constructs, and anti-miRNA transfection confirmed that miR-199a-3p directly silences COX-2. Western blot and ELISA assays revealed that TQ dramatically reduces COX-2 protein and PGE2 levels by boosting miRNA-199a-3p. Importantly, TQ also blocked MAPK (p38, JNK, ERK) and NF-κB activation, even when miR-199a-3p was suppressed, proving its multi-targeted action beyond miRNA regulation. These findings reveal a novel anti-inflammatory mechanism, where TQ curbs COX-2-driven inflammation by enhancing miR-199a-3p, simultaneously shutting down pro-cancer MAPK/NF-κB signaling pathways. Given the strong link between chronic inflammation and LC aggressiveness, this study positions TQ as a promising therapeutic candidate, especially for inflammation-mediated lung cancer progression. Its dual ability to modulate miRNA and key signaling cascades makes it a compelling option for future LC treatment strategies. Full article

Background: Stomach adenocarcinoma is a major contributor to worldwide mortality and significantly impacts life expectancy. The main objective of the current study was to identify a prognostic biomarker for stomach adenocarcinoma to advance translational medicine and improve patient outcomes. Method: various databases (GEPIA, UALCAN, miRNet, StarBase, and Kaplan Meier plotter) bioinformatics tools (cytoscape) and were used in this study. Results: Ten novel unfavorable prognosis-associated genes were identified. In addition, 41 potential miRNAs were predicted. ELAVL3-hsa-mir-29a-3p and CALCR-hsa-mir-29a-3p were identified as the two critical networks in the oncogenesis of stomach adenocarcinoma via bioinformatics analysis. Subsequently, the binding of lncRNAs to hsa-mir-29a-3p was predicted utilizing the starBase and miRNet databases. Following the execution of both expression and survival analyses for the predicted lncRNAs, it was determined that only one lncRNA, KCNQ1OT1, exhibited significant overexpression in stomach adenocarcinoma, and its elevated expression was associated with an unfavorable prognosis. Subsequently, we constructed a triple ceRNA network involving mRNA, miRNA, and lncRNA, which is associated with the prognosis of stomach adenocarcinoma. Conclusions: In summary, the current study provides an extensive ceRNA network that highlights novel prognostic biomarkers for stomach adenocarcinoma. Full article

Background/Objectives: The relationship between gut microbiota (GM) and microRNAs (miRs) related to lipid metabolism in individuals with metabolic syndrome (MetS) remains unclear. This pilot study examined the relationship between Bacteroidetes and Firmicutes abundance at the phylum level and the plasma levels of miR-122 and miR-370, both of which are associated with lipid metabolism, in Korean individuals with MetS and in healthy controls. We also evaluated the potential of these miRs as biomarkers for MetS. Methods: This study enrolled 7 individuals with MetS and 8 controls. The abundance of GM was analyzed by 16S rRNA amplicon sequencing. To evaluate the relationship between the dominant phyla in the 2 groups, the log ratio of Firmicutes to Bacteroidetes (F/B) was calculated using a centered log-ratio (CLR) transformation. The abundance of the 2 plasma miRs was also quantified by real-time quantitative PCR (RT-qPCR). Pearson’s and Spearman’s correlation analyses were then performed to evaluate the relationship between Bacteroidetes and Firmicutes abundance, the clinical parameters, and plasma levels of the 2 miRs. Additionally, the area under the curve (AUC) value of the receiver operating characteristic (ROC) curve was calculated to evaluate the potential of the 2 miRs as MetS biomarkers. Results: The 2 most abundant phyla were Bacteroidetes and Firmicutes. Bacteroidetes made up an average of 24.7% in the MetS group and 69.7% in the control group. Meanwhile, the average abundance of Firmicutes was 69.8% in the MetS group and 26.5% in the control group. The log F/B ratios in the MetS and control groups were 0.7 ± 0.5 and −0.4 ± 0.1 (p < 0.001), respectively. FDR analysis revealed significant correlations between Bacteroidetes abundance and BMI, DBP, FBG, total chol, insulin and HOMA-IR (FDR-adjusted p < 0.05), as well as between Firmicutes abundance and BMI, FBG, total chol, insulin and HOMA-IR (FDR-adjusted p < 0.05). Plasma levels of the 2 miRs differed significantly between the MetS and control groups: miR-122 (1.43 vs. 0.73; p = 0.0065) and miR-370 (1.39 vs. 0.83; p = 0.0089). The AUC values for miR-122 and miR-370 were 0.946 (p < 0.001) and 0.964 (p < 0.001), respectively. Pearson’s and Spearman’s correlation analyses revealed significant negative correlations between Bacteroidetes abundance and levels of miR-122 (p = 0.0048 and p = 0.0045, respectively) and miR-370 (p = 0.0003 and p < 0.0001, respectively), as well as significant positive correlations between Firmicutes abundance and levels of miR-122 (p = 0.0038 and p = 0.0027, respectively) and miR-370 (p = 0.0004 and p < 0.0001, respectively). However, as our exploratory findings were based on a small sample size, the high correlation results may partly reflect the separation between the MetS and control groups. Conclusions: Our exploratory findings suggest that the GM abundances of individuals with MetS may be significantly associated with plasma levels of miR-122 and miR-370, which are related to lipid metabolism. These miRs may therefore serve as potential MetS biomarkers. Full article

Intracranial aneurysms (IAs) are potentially devastating cerebrovascular lesions, and predicting rupture risk remains a major clinical challenge. Conventional radiological and clinical scores offer only partial risk stratification, highlighting the need for complementary approaches. Liquid biopsy represents a promising non-invasive strategy to identify circulating biomarkers that reflect aneurysm biology and instability. We conducted a systematic review according to PRISMA 2020 guidelines, screening PubMed, Scopus, and Web of Science up to August 2025. Forty-eight eligible studies, encompassing 3515 IA patients, evaluated circulating RNA species, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in serum, plasma, blood, or cerebrospinal fluid. Multiple candidates emerged as consistently dysregulated: upregulation of miR-21, miR-126, and miR-200a-3p, and downregulation of miR-143 and let-7b-5p were recurrently observed across independent cohorts. LncRNAs, such as MALAT1 and MIAT, and circRNAs, including circ_0000690 and circ_0021001, demonstrated diagnostic and prognostic potential, with some correlating with rupture status and clinical severity indices. Despite encouraging findings, heterogeneity in study design, sample handling, and analytic methods limits reproducibility. Large-scale, multicenter validation studies are essential to translate these biomarkers into clinical practice. Full article

Background/Objectives: To investigate microRNA (miRNA) expression profiles in the anterior lens capsules of patients with glucocorticoid-induced cataracts (GIC) and to identify miRNAs potentially associated with glucocorticoid (GC) exposure and posterior subcapsular cataract (PSC) formation. Methods: A total of 33 participants were divided into four groups based on their GC usage history and cataract type: GIC (n = 10), age-related PSC (n = 6), GC-treated age-related cataract (ARC) (n = 7), and normal control (n = 10). Anterior lens capsule samples were obtained during cataract surgery and total RNA was extracted for quantitative real-time polymerase chain reaction (qRT-PCR). The expression levels of 12 selected miRNAs were quantified using a customized miScript miRNA PCR array. Results: Among the twelve miRNAs analyzed, seven (let-7a-5p, let-7d-5p, miR-15a-5p, miR-16-5p, miR-23b-3p, miR-26a-5p, and miR-125a-5p) were significantly differentially expressed among the groups (p < 0.05). In the GIC group, let-7a-5p, miR-23b-3p, miR-26a-5p, and miR-125a-5p were significantly upregulated, whereas let-7d-5p, miR-15a-5p and miR-16-5p were significantly downregulated compared to that in the normal control group. No significant differences in miRNA expression were observed between the GIC and age-related PSC groups or between the GIC and GC-treated ARC groups. Conclusions: This study demonstrates distinct miRNA expression patterns in the anterior lens capsules of patients with GIC. Altered expression of specific miRNAs may be linked to the pathogenesis of GC-induced PSC formation. These findings provide a molecular basis for further investigation into the regulatory roles of miRNAs in GC-associated cataracts. Full article

Objectives: miR-21-5p, miR-145-5p and miR-382-5p have been associated with angiogenesis, which plays a central role in tumor growth and metastasis formation. The aim of the study was to determine whether expression of these three potentially angiogenic miRNAs is related to the lymphatic spread capability of gastric adenocarcinoma and patient survival. Methods: Pathoclinical data of 123 patients who underwent elective gastric resection for adenocarcinoma between 1 August 2006 and 31 December 2013 were retrospectively retrieved. The major concerns were the total number of lymph nodes retrieved, the number of positive nodes, depth of the tumor invasion to the stomach wall, pTNM stage of the disease, Lauren histological tumor type, presence of a mucinous component in the cancer tissue, tumor location in the stomach and survival outcome. The cancer tissues of patients were examined for the expression levels of miR-21-5p, miR-145-5p and miR-382-5p. Results: Elevated hsa-miR-21-5p expression levels and downregulated hsa-miR-145-5p levels were observed in patients with a higher pT stage, lymph node metastasis and advanced pTNM stage. Additionally, hsa-miR-145-5p expression was lower in patients with cardia involvement and a Lauren intestinal-type carcinoma. hsa-miR-382-5p levels were higher in patients with non-mucinous gastric carcinoma. Both hsa-miR-145-5p and hsa-miR-21-5p were predictors of the presence of node metastasis, even when adjusted for pT status. hsa-miR-145-5p was significantly associated with improved survival. hsa-miR-145-5p was significantly associated with an increased probability of surviving 3 years, while increased hsa-miR-21 expression was significantly associated with reduced 3-year survival. All these associations were confirmed in multivariate models, which also included pT and M staging. Conclusions: The upregulation of miR-21-5p and downregulation of miR-145-5p are independent prognostic factors for lymph node metastasis and could serve as specific biomarkers of the lymphatic spread of gastric adenocarcinoma. miR-145-5p downregulation is an independent prognostic factor for overall survival. Full article

Dipeptidyl-peptidase IV (DPP4) inhibitors have shown potential anti-tumor properties. This study investigates the therapeutic potential of evogliptin, a DPP4 inhibitor, both as a single agent and in combination with temozolomide (TMZ), in glioma models. In vitro studies were performed using U87 and U373 glioma cell lines exposed to different concentrations of TMZ (250, 500 μM) and evogliptin (250, 500 ng/mL), either alone or together, for 24, 48, and 72 h. Cell viability was determined with the MTT assay. In vivo effectiveness was tested in a xenograft mouse model treated with intraperitoneal injections of evogliptin (60 mg/k g/day), TMZ (15 mg/kg/day), or their combination over 3 weeks. The combination of TMZ and evogliptin markedly reduced cell viability compared to single-agent treatments. DPP4 mRNA levels decreased more substantially with combination therapy. miRNA expression profiling with Affymetrix arrays indicated that certain miRNAs, such as miR-4440 and miR-6780b-5p, were upregulated after treatment with evogliptin or the combination regimen, whereas others were downregulated. These miRNAs could play a role in limiting glioma growth through DPP4 regulation. In the animal model, evogliptin alone did not provide a survival advantage. Analysis of TCGA data showed that glioma patients with decreased DPP4 expression had improved survival rates. The co-administration of evogliptin and temozolomide resulted in distinct miRNA profile changes. Nevertheless, both in vitro and in vivo, the added cytotoxicity from the combination was minimal. Full article