Search Results (180)

Background: Diabetic vascular complications are a major cause of poor prognosis in patients with diabetes mellitus (DM). Mitophagy activation is a potential therapeutic target for type 2 diabetes mellitus (T2DM), but the role of low-intensity pulsed ultrasound (LIPUS) in this context remains unclear. Methods: The biological effects of LIPUS on endothelial cells under high glucose conditions were systematically evaluated using high glucose-treated human umbilical vein endothelial cells (HUVECs) and aortic tissues from diabetic rats as models, in combination with bioinformatics analysis and standard molecular and cellular biology techniques. Histological staining was further used to assess the protective role of LIPUS in the aortas of diabetic rats. Results: Bioinformatics analysis predicted that high glucose induces mitochondrial dysfunction, suppresses autophagy in HUVECs, impairs endothelial cell function, and activates fibroblasts. In vitro results were in agreement with these predictions. LIPUS treatment significantly counteracted these effects, restoring migration (p < 0.001) and angiogenesis (p < 0.05), increasing proliferation (p < 0.001), and decreasing apoptosis (p < 0.05). Mechanistically, LIPUS enhanced mitophagy, and its therapeutic effects were markedly diminished upon addition of the autophagy inhibitor 3-Methyladenine (3-MA). In vivo, LIPUS attenuated aortic endothelial damage and reduced collagen deposition in diabetic rats (p < 0.01). Conclusions: LIPUS may ameliorate hyperglycemia-induced endothelial cell dysfunction by activating mitophagy, and it also attenuates pathological damage in the abdominal aorta of diabetic rats, thereby providing experimental evidence for its application in the treatment of diabetic macrovascular complications. Full article

The aorta is the largest vascular conduit in humans, comprising three layers and a multitude of varying cell types collectively maintaining homeostasis and normal aortic wall function. Amongst these layers, the tunica adventitia is the external-most layer, where microvessels, termed vasa vasorum, can be found. These comprise pericytes and endothelial cells (ECs) and provide nourishment to the tunica adventitia and the outer media layers in the thoracic aorta. Adjacent to these microvessels, stem/progenitor group populations can be found, together forming a perivascular niche. Eventually, however, many of these cells and components can become dysregulated and contribute to development of thoracic aortic aneurysm (TAA). The purpose of this narrative review is to evaluate the recent literature related to marker gene expression in tunica adventitia pericytes, as well as the contribution of these populations to the development of aneurysm in the thoracic aorta. Pericytes in TAA generally exhibit phenotypic changes, which could be driven, in part, by loss of fibroblast growth factor (FGF) signaling. These changes eventually lead to vasa vasorum remodeling in the thoracic aorta, in turn contributing to the development of TAA. Full article

Background/Objectives: Nuclear receptor corepressors NCOR1 and NCOR2 are key regulators of transcriptional repression, chromatin remodelling, and immunometabolic signalling. While NCOR1 has already been linked to vascular biology, its relevance in abdominal aortic aneurysm (AAA) remains unclear, particularly for NCOR2. This study aimed to investigate the expression, cellular localisation, and molecular interactions of NCOR1/2 in human AAA tissue. Methods: Human AAA samples (elective and ruptured) (n = 45) and non-aneurysmal control aortas (n = 18) were obtained from our Swiss Vascular Biobank. Transcriptomic profiling was performed using ribosomal RNA-depleted RNA sequencing. Differential expression and correlation analyses were performed using DESeq2/EdgeR and Spearman rank correlation with Benjamini–Hochberg correction. Cellular localisation was assessed through immunohistochemistry (IHC). Results: Bulk transcriptomic analyses showed no significant differences in NCOR1 or NCOR2 expression between AAA and controls. IHC revealed that NCOR1 was found in endothelial cells (ECs), smooth muscle cells (SMCs), and inflammatory infiltrates, while NCOR2 was primarily associated with macrophages. Correlation analyses suggest that NCOR1 interacts with various cellular markers, proteolytic enzymes, inflammatory mediators, and epigenetic regulators, including the lncRNA MALAT1. NCOR2 showed distinct associations with remodelling enzymes, TGFB1 signalling, selective epigenetic modifiers, and lncRNA H19. Conclusions: The lack of transcriptional differences in NCOR1 and NCOR2 between AAA and controls does not exclude cell-type-specific regulation or functional relevance. The specific cellular distributions and molecular associations in human AAA imply that NCOR1 and NCOR2 play non-redundant roles in vascular remodelling, inflammation, and epigenetic regulation. Our findings highlight NCOR pathways as potential modulators of AAA pathophysiology and promising targets for future therapies. Full article

Background and Objectives: Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening vascular disease with limited effective diagnostic and therapeutic strategies. Although endothelial barrier dysfunction represents an early event in TAAD pathogenesis, the role of endothelial tight junction proteins remains largely undefined. In this study, we systematically explored the function of claudin-5 (CLDN5), an endothelial-specific tight junction sealing protein, in TAAD through integrated bioinformatic, clinical, and experimental approaches. Materials and Methods: In the study, we combined bioinformatic analysis of the CLDN5 gene with clinical and cellular investigations. The clinical cohort included 44 patients with thoracic aortic dissection (TAAD) and 41 healthy controls. Plasma CLDN5 levels were measured by ELISA. Cellular studies involved treating human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-α (TNF-α) and performing CLDN5 knockdown, with barrier function assessed using transendothelial electrical resistance and permeability assays. Results: Plasma CLDN5 was significantly elevated in TAAD patients (14.20 ± 1.394 ng/mL) compared to controls (6.061 ± 0.8208 ng/mL, p < 0.05) and showed strong diagnostic potential with an area under the receiver operating characteristic curve (AUC) of 0.7877 (95% CI: 0.6897–0.8857). In cellular experiments, TNF-α treatment induced the release of CLDN5 fragments into the supernatant and reduced membrane CLDN5. Furthermore, CLDN5 knockdown directly impaired endothelial barrier function. Conclusions: Our findings identify CLDN5 as a promising circulating biomarker for TAAD diagnosis and provide new insights into TAAD pathogenesis, offering potential diagnostic strategies. Full article

Abdominal aortic aneurysm (AAA) is a lethal vascular disease characterized by intramural hemorrhage. This study delineates the signatures of heme and its metabolic imbalance related to progression and inflammation in AAA. Clinical analyses of patients undergoing open AAA surgery show that AAA patients exhibit vascular inflammation, with elevated serum CRP, IL-6, and heme levels correlating with the expression of heme-regulated gene Hmox1/HO-1 (heme oxygenase-1) in the affected aortic wall. Oxidation of hemoglobin to ferri state leading to accumulation of methemoglobin readily releasing heme occurs in human AAA and in angiotensin II (AngII)-induced AAA in apolipoprotein E-deficient mice. Transcriptomic analysis for AngII-induced AAA identifies upregulated genes predominantly enriched in inflammatory signaling, extracellular matrix degradation, oxidative stress pathways, and altered expression of genes related to heme metabolism including Hmox1. Immunohistochemistry for IL1β and TNFα confirms inflammatory activation within AAA tissues. The signatures of heme-responsive gene inductions, enhanced expression of HO-1 and H-ferritin, are detected. Mechanistic studies employing endothelial cells and smooth muscle cells reveal that heme exposure of resident cells markedly enhances the expression of IL1β and ICAM1, as well as the inflammasome component NLRP3, and such inflammatory response is controlled by HO-1. Intervention with Normosang (heme arginate), an HO-1 inducer, attenuates aneurysm progression, whereas HO-1 inhibition by Tin protoporphyrin IX abolishes this protection. Induction of HO-1 accompanied by elevated H-ferritin level also mitigated aortic wall inflammation as reflected by lowering IL1β and TNFα. These findings highlight the heme-HO-1-H-ferritin axis as an element of AAA pathogenesis and a potential therapeutic target. Full article

The close connections between the intestine and distal systems, known as axes, are a growing focus of scientific research; however, the gut–vascular axis, particularly as a target of microbial metabolites, remains underexplored. In this study, three supernatants derived from probiotic formulations composed of Lactobacillus and Bifidobacterium strains (MIX-1, MIX-2, and MIX-3) were evaluated in counteracting vascular alterations associated with dysbiosis. Human aortic smooth muscle (HASMCs) and endothelial (HAECs) cells were exposed to pro-oxidative (H₂O₂) and pro-inflammatory (TMAO) stimuli. Concentrations up to 5–10% (v/v) were tolerated in both cell lines, with MIX-1 and MIX-3 showing the greatest protective efficacy. These formulations exerted antioxidant effects by reducing H₂O₂-induced ROS production and cell viability loss, and anti-inflammatory effects by limiting TMAO-induced IL-1β release. MIX-1 also attenuated TMAO-induced IL-6 release. Further analyses indicated a partial involvement of the SIRT1-pathway in its vascular antioxidant effects. Chromatographic profiling revealed comparable qualitative metabolites among the probiotic supernatants, while quantitative differences were observed, with higher lactate levels in MIX-1 and MIX-3 compared to MIX-2. Finally, we have determined that Limosilactobacillus reuteri-PBS072 is mainly responsible for the antioxidant effect of MIX-1 and MIX-3. Overall, these findings highlight the potential of probiotic-derived metabolites in modulating the gut–vascular axis and promoting vascular protection. Full article

Vascular endothelial injury is a key pathological characteristic of multiple diseases, such as atherosclerosis, stroke, and mastitis. Aspirin eugenol ester (AEE) has been confirmed to exert a significant protective effect on vascular endothelial injury. However, the universal action patterns and underlying mechanisms of AEE across different pathological scenarios have not been systematically elucidated. This study aimed to investigate the effect and mechanism of AEE in alleviating multiple vascular endothelial injury models. Nine vascular endothelial injury models were established by treating bovine aortic endothelial cells (BAECs), mouse aortic endothelial cells (MAECs), and human umbilical vein endothelial cells (Huvecs) with ethanol (EtOH), hydrogen peroxide (H₂O₂), and copper sulfate (CuSO₄), respectively. The protective effects of AEE were systematically evaluated via morphological observation, detection of inflammatory responses, and oxidative stress markers. Furthermore, metabolomics was employed to identify and analyze differentially expressed metabolites between the nine model groups and AEE groups. AEE exerted protective effects on all nine vascular endothelial injury models, inhibiting inflammation and oxidative stress induced by all inducers. Metabolomic analysis revealed that the differentially expressed metabolites modulated by AEE in most models were primarily enriched in lipid metabolism, amino acid metabolism, coenzyme biosynthesis, and other related pathways. AEE could improve vascular endothelial injury by upregulating antioxidant substance which included eicosapentaenoic acid (EPA), choline, coenzyme A (CoA), glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD), as well as downregulating substances that cause endothelial oxidative damage, including phytosphingosine (PS), palmitic acid (PA), and arachidonic acid (AA). Full article

Dorsomorphin, a pyrazolo[1,5-a]pyrimidine derivative, inhibits the bone morphogenetic protein (BMP) pathway by targeting the type I BMP receptors active in receptor-like kinases. However, the investigation of its—and its derivatives’—antiproliferative activity towards endothelial and cancer cell lines still requires reinforcement with additional studies. In the presented work, several dorsomorphin derivatives have been efficiently synthesized, based on a previously reported synthetic protocol with minor modifications. The endeavor was reinforced by a molecular docking study on the interactions of the designed derivatives with various protein targets, while the inhibitory effects of the synthesized novel molecules on the proliferation of murine leukemia cells (L1210), human T-lymphocyte cells (CEM), human cervix carcinoma cells (HeLa), and endothelial cells (human dermal microvascular, HMEC-1, and bovine aortic endothelial cells, BAECs) were investigated. Among the compounds tested, diphenol 22, emerged as the most promising bioactive lead since it demonstrated half-maximal inhibitory concentration (IC₅₀) values below 9 μM in all tested lines except HeLa cells. In the same context, the carbamate derivative 6 was determined as a potent inhibitor of endothelial cell proliferation in BAECs at a low micromolar range. In conclusion, the presented work not only reveals promising antiproliferative dorsomorphin derivatives but also sets the basis for further exploitation of dorsomorphin’s bioactive portfolio, based on bioactivity results and molecular modeling calculations. Full article

Palmitic acid (PA) is the most common dietary saturated fatty acid, and is abundant in palm and cottonseed oil, butter, and cheese, whereas oleic acid (OA) is a monounsaturated omega-9 fatty acid found in olive oil. The differences in the cytotoxic and pro-inflammatory effects of PA and OA across endothelial cells (ECs) isolated from different vascular beds have not been investigated in detail. Here, we incubated primary human aortic valve (HAVEC), saphenous vein (HSaVEC), internal thoracic artery (HITAEC), and microvascular (HMVEC) ECs with albumin-bound PA or OA for 24 h and found that PA induced a considerable cytotoxic response, accompanied by an elevated expression of the genes encoding cell adhesion molecules (VCAM1, ICAM1, SELE, and SELP) and pro-inflammatory cytokines (MIF, PTX3, CSF2, CSF3, IL1A, IL6, CCL2, CCL5, CCL20, CSF2, CSF3, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, and CXCL10), followed by an increased release of interleukin-6 and interleukin-8. HAVEC and HSaVEC were more susceptible to PA, whereas OA had mild-to-moderate cytotoxic effects on HAVEC and HMVEC but did not induce generalized EC activation. Compared with other EC types, HITAEC was the most resistant to PA and OA treatment. Collectively, these results indicate considerable heterogeneity across the ECs of distinct origin in response to PA. Full article

Citri grandis exocarpium (Citri grandis) has been consumed by human beings for fifteen hundred years. It is commonly consumed as a health drink and dietary supplement in China. However, its nutritional and healthcare functions are still not fully understood. Objective: Our previous study found that oral administration of Citri grandis extract can significantly decrease the blood lipid levels of hyperlipidemic mice fed a high-fat diet. The aim of this study was to confirm the preventative effects of Citri grandis extract against atherosclerosis. Methods: Atherosclerotic lesion models were induced in HUVECs and apoE^−/− C57BL/6J mice. ApoE^−/− mice fed a high-fat diet were orally administered Citri grandis extract (0.4, 0.8, and 1.6 g/kg/d BW) and Simvastatin (1 mg/kg/d BW) on the first day of model establishment. After a 16-week treatment, serum samples and aorta and liver tissues were collected. Observation of pathological changes in aortic and liver tissues was performed using a light microscope with oil red O, H&E, Masson’s trichrome staining, and TEM. Biochemical detection was employed to determine the serum levels of TC, TG, LDL-C, and HDL-C as well as the activities of AST and ALT. In addition, expression studies of TGF-β, PI3K, AKT1, PPAR-γ, LXR-α, and ABCA1 were performed via qPCR and Western blot analysis. Results: Compared with cholesterol-induced HUVECs, Citri grandis extract significantly enhanced cell viability, attenuated the morphological changes in HUVECs, and reduced LDH release. Furthermore, after treatment with Citri grandis extract, the levels of TC, TG, and LDL-C significantly decreased in the atherosclerosis model apoE^−/− mice after 16 weeks, and aortic plaque, lipid deposition, and endothelial injury were obviously ameliorated. The mRNA and protein expression of TGF-β, PPAR-γ, LXR-α, and ABCA1 in aortic and liver of atherosclerosis apoE^−/− mice were upregulated (p < 0.05, p < 0.01), while those of PI3K and Akt1 were suppressed (p < 0.05, p < 0.01). Conclusions: Citri grandis extract can significantly decrease the high circulating lipid levels and the liver lipid deposition of high-fat-diet-fed apoE^−/− mice and reduce aorta lipid accumulation and atherosclerotic plaques by regulating the expression of TGF-β1, PI3K, AKT1, PPAR-γ, LXR-α, and ABCA1. Citri grandis extract can be used as a healthcare dietary supplement for the prevention of abnormal lipid metabolism and atherosclerosis. Full article

Background/Objectives: Endothelial activation by lipopolysaccharides (LPS) contributes to inflammation and the development of cardiovascular disease, making n-3 polyunsaturated fatty acids (PUFAs) potential modulators capable of mitigating endothelial dysfunction. The current study examines the effects of long-chain eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), along with their precursor, α-linolenic acid (ALA), on oxidative stress, adhesion molecule expression, and cytokine milieu in LPS-stimulated human aortic endothelial cells (HAECs). Methods: HAECs (fifth passage) were cultured in control medium under standard conditions: ~37 °C, 5% CO₂, ≥80% humidity. Cells were incubated in control basal cell medium or medium supplemented with ALA, EPA, DHA, and their combination (50 µM; n = 5 per group). After 48 h, cells were treated overnight (~16 h) with LPS from E. coli (0.75 and 1 µg/mL). HAECs and supernatants were collected for flow cytometry, Luminex, and ELISA assays. Significance was assessed using two-way analysis of variance ANOVA, followed by post hoc analyses (p < 0.05). Spearman’s correlation analysis was performed between markers, and p-values were adjusted using the Benjamini–Hochberg (BH) correction. Results: PUFA supplementation, particularly with DHA and ALA, significantly reduced intracellular reactive oxygen species (ROS) production and the expression of adhesion molecules (ICAM-1, E-selectin) in HAECs under both basal and LPS-stimulated inflammatory conditions. All PUFAs reduced pro-inflammatory cytokine levels (IFNγ, TNFα, IL-6), while ALA increased IL-1α and endoglin expression, indicating differential immunomodulatory effects. EPA exhibited antioxidant and anti-inflammatory effects primarily at higher LPS concentrations. Correlation analysis demonstrated strong interdependence between oxidative stress, inflammatory markers, and vascular activation, further confirming PUFA-mediated endothelial protection. Conclusions: PUFA supplementation produced molecule-specific effects on endothelial inflammation. DHA and ALA consistently showed anti-inflammatory and antioxidative effects, while EPA’s beneficial effect was more pronounced under inflammatory conditions, emphasising the importance of PUFA type and context in managing vascular inflammation. Full article

Hemodynamics significantly impact the biology of endothelial cells (ECs) lining the blood vessels. ECs are exposed to various hemodynamic forces, particularly frictional shear stress from flowing blood. While physiological flows are critical for the normal functioning of ECs, abnormal flow dynamics, known as disturbed flows, may trigger endothelial dysfunction leading to atherosclerosis and other vascular conditions. Such flows can occur due to sudden geometrical variations and vascular abnormalities in the cardiovascular system. In the current study, a microfluidic system was used to investigate the impact of different flow conditions (i.e, normal vs. disturbed) on ECs in vitro. We particularly explored the relationship between specific flow patterns and cellular pathways linked to oxidative stress and inflammation related to atherosclerosis. Here, we utilized a 2D cell culture perfusion system featuring an immortalized human vascular endothelial cell line (EA.hy926) connected to a modified peristaltic pump system to generate either steady laminar flows, representing healthy conditions, or disturbed oscillatory flows, representing diseased conditions. EA.hy926 were exposed to an oscillatory flow shear stress of 0.5 dynes/cm² or a laminar flow shear stress of 2 dynes/cm² up to 24 h. Following flow exposure, cells were harvested from the perfusion chamber for quantitative PCR analysis of gene expression. Reactive oxygen species (ROS) generation under various shear stress conditions was also measured using DCFDA/H2DCFDA fluorescent assays. Under oscillatory shear stress flow conditions (0.5 dynes/cm²), EA.hy926 ECs showed a 3.5-fold increase in the transcription factor nuclear factor (NFκ-B) and a remarkable 28.6-fold increase in cyclooxygenase-2 (COX-2) mRNA expression, which are both proinflammatory markers, compared to static culture. Transforming growth factor-beta (TGFβ) mRNA expression was downregulated in oscillatory and laminar flow conditions compared to the static culture. Apoptosis marker transcription factor Jun (C-Jun) mRNA expression increased in both flow conditions. Apoptosis marker C/EBP homologous protein (CHOP) mRNA levels increased significantly in oscillatory flow, with no difference in laminar flow. Endothelial nitric oxide synthase (eNOS) mRNA expression was significantly decreased in cells exposed to oscillatory flow, whereas there was no change in laminar flow. Endothelin-1 (ET-1) mRNA expression levels dropped significantly by 0.5- and 0.8-fold in cells exposed to oscillatory and laminar flow, respectively. ECs subjected to oscillatory flow exhibited a significant increase in ROS at both 4 and 24 h compared to the control and laminar flow. Laminar flow-treated cells exhibited a ROS generation pattern similar to that of static culture, but at a significantly lower level. Overall, by exposing ECs to disturbed and normal flows with varying shear stresses, significant changes in gene expression related to inflammation, endothelial function, and oxidative stress were observed. In this study, we present a practical, optimized system as an in vitro model that can be employed to investigate flow-associated diseases, such as atherosclerosis and aortic aneurysm, thereby supporting the understanding of the underlying molecular mechanisms. Full article

Early cellular alterations in abdominal aortic aneurysm (AAA) are scarcely investigated. Aortic remodeling inflammation-related suggested the CXCR2/CXCL1/IL-8 axis as a therapeutic target. This study investigates CXCR1/CXCR2 antagonism in primary human aortic endothelial (HAOEC) and smooth muscle cells (HAOSMC) conditioned with IL-8 or serum from patients with AAA (sPT). Ladarixin (10 μM Lad or 25 μM) served as an inhibitor. Readouts included RT-qPCR for CXCL1, CXCL8, CXCR2, MMP9, NFKB1, and VEGF-A; zymography for MMP9 activity confocal microscopy for F-actin and mitochondria; NADPH/NADH diaphorase histochemistry for redox activity; and ATP assay. In HAOEC, IL-8 downregulated CXCR2, increased MMP9 activity, and induced cytoskeletal and mitochondria disorganization without altering NADH/NADPH diaphorases but increasing ATP release. At concentration of 10 μM Lad rescued cell organization and gene expression. sPT upregulated CXCL8, CXCR2, and MMP9, decreased NADH/NADPH diaphorases, and altered cytoskeleton and mitochondria organization in HAOEC. At concentration of 10 μM Lad (partially) and 25 μM Lad reverted gene upregulation and mitochondria distribution; both doses increased diaphorase and released ATP. HAOSMC were scantily susceptible to IL-8 and weakly responsive to sPT, slightly upregulating CXCR2 and VEGF-A but increasing proMMP9 gelatinolysis. Ladarixin recovered proMMP9 activity and modulated CXCL1. AAA-like vascular cell alterations involve multiple inflammatory factors and are modulable by inhibition of IL-8 receptors. The results underline careful dose calibration. Full article

Nicotinamide adenine-dinucleotide (NAD⁺) supplementation is a promising strategy to delay cellular aging in different areas, including cosmetic dermatology. However, low bioavailability and stability of NAD⁺ formulations are the main factors limiting its effectiveness as an anti-aging treatment. In light of the above, a liposomal formulation of NAD⁺ (LF-NAD⁺) was tested in this study and compared to NAD⁺ alone in primary human aortic endothelial cells (HAECs) and primary human epidermal keratinocytes (HEKas). Intracellular NAD⁺ was measured using a colorimetric assay. Cell survival was derived from lactate dehydrogenase release in supernatants. Cell senescence was measured by senescence-associated β-galactosidase staining. Molecular mechanisms underlying the reported effects were analyzed by Western blot. Skin penetration of NAD⁺ was measured ex vivo in skin explants, using infrared spectroscopy. Compared to control NAD⁺ alone, the LF-NAD⁺ formulation increased the intracellular NAD⁺ content and cell survival in HAECs, but not in HEKas. Instead, a significant reduction in the number of senescent cells was observed in both HAECs and HEKas. LF-NAD⁺ treatment was associated with a reduced expression of p16 in both HAECs and HEKas, and to a significant reduction in p21 in HEKas alone. Finally, LF-NAD⁺ increases the skin penetration of the active substance NAD⁺ by 30% compared to the application of NAD⁺ alone. LF-NAD⁺, enhances the anti-aging effects of NAD⁺ on vascular and skin cells. Such in vitro findings might indicate a potential anti-aging role in the microcirculation and in the epidermidis. Full article

Antihypertensive drugs are widely used for the treatment of hypertension, and the choice of drug and dosage is based on trial and error. The variability in drug response and adverse reactions leads to the poor adherence to treatment. Epigenetic modulation is one of the major mechanisms that may contribute to the variability in drug responses, and microRNAs (miRNAs) can serve as crucial epigenetic regulators and have also been reported to be associated with hypertension pathogenesis. The objective of this study is to investigate the regulatory effects of commonly used antihypertensive drugs on the endothelial miRNome in human aortic endothelial cells. We aim to integrate miRNA expression data with proteomic analyses to elucidate drug-induced molecular mechanisms relevant to hypertension treatment. Whole genome small RNA sequencing was performed, followed by whole proteome analysis using LC-MS/MS comparing between control and treated samples. The treatments induced significant differential regulation of several miRNAs and proteins; among these, a few reflected reverse relationships with miRNA regulation and protein expression. Certain miRNAs and their corresponding target proteins seem to distinguish between good therapeutic outcomes and potential side effects. This study unravels the potential role of drug-induced miRNAs in inducing post-transcriptional modifications to cause the differential expression of certain proteins that may induce not only therapeutic effects or drug side effects but can also indicate the potential for drug-repurposing in other diseases. Full article