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The network of any IT system is subject to continuous changes, such as the addition of new nodes, software installations, and the emergence of new vulnerabilities. On the other hand, the importance of nodes within the IT system’s network varies due to various factors, impacting the severity of potential node exploitation. Additionally, the interconnected nature of the nodes means that the security of each node is interdependent on the others nodes. In this context, effective risk assessment methodologies that consider the factors which impact the security of the system are crucial. This paper introduces an innovative methodology that takes into account the aforementioned factors. The proposed approach evaluates vulnerabilities, interconnections, and dynamic changes to deliver a comprehensive and up-to-date security risk assessment. By employing this methodology, administrators gain better control over system security with dynamic evaluations that support well-informed decisions. Furthermore, the methodology facilitates risk assessment for specific nodes and enables the quantification of their security levels. Due to a thorough assessment, the proposed methodology empowers IT administrators to improve the overall security of the system.

Background: Anthracycline drugs play a fundamental role in breast cancer treatment; however, the cardiotoxicity side effects obscure the advantages of treatment. Curcumin has antioxidant and anti-inflammatory effects., Materials and Methods: In this study, we investigated the effect of nanocurcumin supplementation on Doxorubicin induced Cardiotoxicity. In this randomized clinical trial, a week before starting the doxorubicin regimen for breast cancer patients, the control group received placebo and curcumin group received 80 mg daily dosage of nano curcumin capsules for six months. Echocardiography parameter changes before chemotherapy and after six months were evaluated., Results: 46 patients were included. Left ventricle (LV) ejection fraction significantly decreased and LV end diastolic volume significantly increased in control group but no significant changes were observed in the curcumin group (LVEF: 2.62 ± 59.35 to 4.23 ± 56.85, p -value: 0.014 vs 59.55 ± 1.91 to 58.46 ± 3.41, p -value:0.135; LVEDV: 77.09 ± 15.33 to 80.65 ± 14.54, p -value:0.023 vs 72.41 ± 15.34 74.00 ± 14.25, p -value: 0.294). Additionally, LVEF, LV end systolic diameter (LVESD), and end diastolic diameter (LVEDD) insignificantly more decreased in control group versus curcumin group (LVEF: 4.13 ± 2.50- vs 3.36 ± 1.08-, p -value: 0.223; LVESD: 0.27 ± 0.06-vs 0.120.45 ±, p -value:0.110; LVEDD: -0.44 ± 0.33 vs 0.070.33 ±, p -value:0.269). Furthermore, symptomatic cardiomyopathy and ejection fraction ratio less than 53% were not observed. The LVEF reduction >15% was observed was also high in the control group, ( p -value = 0.020)., Conclusion: This study shows the possible effect of nanocurcumin capsules to reduce the cardiotoxicity of anthracycline chemotherapy medications., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, and is due to the degeneration of dopaminergic neurons. It is multifactorial, caused by genetic and environmental factors and currently has no definitive cure. We have investigated the protective effects of parthenolide (PTN), a compound with known anti-inflammatory and antioxidant properties, in an in vitro model of PD, that is induced by 6-OHDA, and that causes neurotoxicity in SH-SY5Y human neuroblastoma cells., Methods and Results: SH-SY5Y cells were pretreated with PTN to assess its protective effects in 6-OHDA-induced cellular damage. Cell viability was measured using Alamar blue. Apoptosis was evaluated using an Annexin V-FITC/PI kit. Reactive oxygen species (ROS) levels were quantified, and expression levels of apoptotic markers (Bax, Bcl-2, p53) and NF-κB were analyzed via Western blotting and Quantitative real-time- (qRT-) PCR. We found that 6-OHDA reduced cell viability, that was inhibited significantly by pre-treatment with PTN (p < 0.05). Flow cytometry revealed that PTN reduced apoptosis induced by 6-OHDA. PTN also reduced the ROS levels raised by 6-OHDA (p < 0.05). Moreover, PTN decreased the expression of Bax, p53, NF-κB, and p-NF-κB that were increased by treatment with 6-OHDA., Conclusion: These findings indicate the potential beneficial effects of PTN in an in vitro model of PD via mitigating oxidative stress and inflammation, suggested PTN as a promising agent to be used for PD therapy, warranting further investigation in preclinical and clinical studies., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The Low-Profile Visualized Intraluminal Support (LVIS) device has been frequently used as an intracranial stent for treating intracranial aneurysms. However, the feasibility and efficacy of LVIS devices in Y-stent-assisted coiling (Y-SAC) have remained contentious. This study aimed to evaluate long-term angiographic and clinical outcomes of Y-SAC using LVIS devices., Methods: We retrospectively reviewed the clinical presentation and angiography data of patients treated with Y-SAC using LVIS stents. The vascular angle geometry between the parent and the 2 branch vessels, before and after stent deployment and after coiling, were analyzed. Based on the Raymond-Roy Occlusion Classification (RROC), aneurysm occlusion status was classified. Clinical outcomes were assessed using the modified Rankin Scale., Results: Forty patients with 40 aneurysms were included in this study. Immediate postprocedural angiograms showed complete/near-complete occlusion (RROC 1 and 2) in 31 aneurysms (77.5%). The long-term follow-up angiographic studies were available in 32 patients and showed RROC class 1 and 2 in 93.8% of patients. Y-SAC with LVIS devices significantly decreased the angle between the bifurcation branches from 171.90° ± 48.0° (standard deviation) to 130.21° ± 46.3° (standard deviation) (P < 0.0001). Periprocedural complications occurred in 5 patients (12.5%) including 4 in-stent thromboses (10.5%). Thirty-six patients (90.0%) had favorable clinical outcomes at the final follow-up. Univariate analysis showed that World Federation of Neurological Societies grade 3-5, thickness of subarachnoid hemorrhage on head computed tomography, intraprocedural complications, and in-stent thrombosis were predictors of poor outcome., Conclusions: Y-SAC using the LVIS device for intracranial bifurcation aneurysms is a feasible and relatively safe procedure with favorable long-term angiographic and clinical outcomes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Endovascular treatment (EVT) is the primary approach used to treat indirect carotid-cavernous fistulas (CCFs). In this study, the authors evaluated the immediate and long-term efficacy and safety of different endovascular techniques for indirect CCFs., Methods: The databases of two endovascular centers were retrospectively reviewed to collect the patients with indirect CCFs treated using endovascular techniques between 2013 and 2023. Demographics, clinical presentation, CCF features, EVT characteristics, and clinical and radiological outcomes were evaluated and analyzed. The analysis was performed to compare the clinical and radiological data between different endovascular approaches and different embolic materials., Results: Ninety-eight patients were included in the study. EVT was successful in 95 patients (96.9%). Immediate complete obliteration of the CCF was achieved in 93.9% of patients, with 98% undergoing embolization with liquid embolic agents (LEAs) and 95.6% undergoing coiling alone. Complete CCF obliteration was higher in the transvenous than in the transarterial approach (94.3% vs 75%, p = 0.010). At ≥ 6 months follow-up, complete CCF obliteration was achieved in all patients (100%). The rate of procedure-related complications was higher following LEAs than with coiling alone (32.0% vs 15.6%). New cranial nerve (CN) palsy was diagnosed in 26.0% and 2.2% after embolization with LEAs and coiling alone, respectively (p = 0.001), with complete CN palsy recovery in 78.6%. Procedure-related intracranial hemorrhage occurred in 3 patients (3.1%). Two patients experienced an ischemic stroke following Onyx migration into the internal carotid artery. Ocular symptoms improved in 93% (83/89) of the patients who were followed., Conclusions: In this study, complete obliteration of an indirect CCF was achieved in more than 90% of patients. Despite the occurrence of some new postprocedural ocular CN palsy, ocular symptoms improved in most patients in long-term follow-up. The transvenous approach was the most effective method for treating the indirect CCF. Coiling was safer than LEAs for the embolization of the indirect CCF.

In the current studies two naproxen derivatives (NPD) were evaluated for analgesic and anti-inflammatory properties. The acetic acid and hot plate animal models were used to screen the compounds for analgesic potential. While the anti-inflammatory potential was evaluated through animal paw edema, induced by several inflammatory mediators (carrageenan, bradykinin, and prostaglandin E2), the xylene-induced ear edema was also used as an inflammatory model. Both NPDs showed significant (p < 0.001) antinociceptive effects in the acetic acid-induced writhing paradigm. In the case of the hot plate, the NPD 1  at the tested dose of 5 mg/kg enhanced the latency time after 60 min of injection, which remained significant (p < 0.001) up to the end of the experiment duration. The maximum percent inhibition of NPD 1 was 87.53. The naloxone injection significantly lowered the latency time of NPD 1 as compared to NPD 2 . Regarding the anti-inflammatory effect, both of the tested NPDs demonstrated a significant reduction in paw edema against various inflammatory mediators, as mentioned above; however, the anti-inflammatory effect of NPD 1 was better. The maximal percent inhibition by NPD 1 and 2 was 43.24 (after 60 min) and 45.93 (after 90 min). A considerable effect also resulted from xylene-induced ere edema. Further, a molecular docking study was carried out to investigate the binding modes of the NPD. The docking analysis revealed that the NPD significantly interacted with the COX2 enzyme. Furthermore, molecular dynamics simulation was carried out for the docked complexes. The MD simulation analysis revealed the high stability of the two naproxen derivatives., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Non-Hodgkin lymphoma of B cell origin is the common type of lymphoma- related malignancy with poor response rate with conventional front-line therapies., Aim: The aim of the present study was to investigate the potential of new anti-inflammatory oxadiazole derivatives of Diclofenac as an anti-lymphoma agent through in vitro and in silico approaches., Methods: Anti-lymphoma potential was evaluated by alamar blue technique. MTT assay employed for cytotoxicity. Gene and protein expression studies was performed by qRT-PCR and ELISA respectively. Docking studies was performed by using MOE program., Results: Among five diclofenac derivatives, (II) showed promising anti-lymphoma effects, where it inhibited the expression of BCL-2, p-38 MAPK and TGF-β in both follicular and Burkitt's lymphoma cells and was non-toxic against normal human fibroblast cells. The in silico studies against BCL-2 revealed that the unsubstituted Sulphur group in (II) is involved in the crucial interactions with the binding site residue., Conclusion: The compound (II) can be a potential therapeutic candidate for B-cell non-Hodgkin lymphoma and deserves further development as a novel anti-lymphoma agent., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: With the evolution of neuroendovascular treatments, there is a great trend to treat acutely ruptured wide-necked aneurysms with stent-assisted coiling (SAC) and flow diverters (FDs), which inevitably requires dual antiplatelet therapy (DAPT). This therapy can increase the rate of hemorrhagic complications following other neurosurgical maneuvers, such as external ventricular drain (EVD) placement or removal. In this study, the authors aimed to evaluate the safety of DAPT in patients with aneurysmal subarachnoid hemorrhage (SAH) treated with SAC or FDs and the therapy's potential benefit in reducing cerebral ischemia and cerebral vasospasm., Methods: In this retrospective study, the authors reviewed the records of patients who had been admitted to their hospital with acute aneurysmal SAH and treated with SAC, FDs, and/or coiling between 2012 and 2022. Patients were classified into two groups: a DAPT group, including patients who had received DAPT for SAC or FDs, and a non-DAPT group, including patients who had not received any antiplatelet regimen and had been treated with coiling. Perioperative hemorrhagic and ischemic complications and clinical outcomes were compared between the two groups., Results: From among 938 cases of acute ruptured aneurysms treated during 10 years of study, 192 patients were included in this analysis, with 96 patients in each treatment group, after propensity score matching. All basic clinical and imaging characteristics were equivalent between the two groups except for the neck size of aneurysms (p < 0.001). EVD-related hemorrhage was significantly higher in the DAPT group than in the non-DAPT group (p = 0.035). In most patients, however, the EVD-related hemorrhage was insignificant. Parent artery or stent-induced thrombosis was higher in the DAPT group than in the non-DAPT group (p = 0.003). The rate of cerebral ischemia was slightly lower in the DAPT group than in the non-DAPT group (11.5% vs 15.6%, p = 0.399). In the multivariate analysis, cerebral ischemia, rebleeding before securing the aneurysm, extracranial hemorrhage, and cerebral vasospasm were the predictive factors of a poor clinical outcome (p < 0.001, p < 0.001, p = 0.038, and p = 0.038, respectively)., Conclusions: The DAPT regimen may be safe in the setting of acute aneurysmal SAH. Although EVD-related hemorrhage is more common in the DAPT group than the non-DAPT group, it is usually insignificant without any neurological deficit.

Background: Bariatric surgery delivers substantial weight loss for obese patients with comorbidities like diabetes mellitus. We aimed to investigate the impacts of bariatric surgery on diabetic markers after 5 years of follow-up. Methods: This is a retrospective study on patients with diabetes and a history of bariatric surgery between 2016-2017. The diabetic markers before and 5 years following surgery, including a lipid profile, glucose level, and the required antidiabetic medications, were evaluated. Results: 34 consecutive patients were included, 30 (88.2%) women, with a mean age of 52.71±8.53 years. The majority (65%) of surgeries were Roux-en-Y gastric bypass (RYGB), and the remaining were one anastomosis gastric bypass (OAGB) and sleeve gastrectomy (SG). The serum levels of diabetic markers reduced during follow-up ( P =0.001), except for high-density lipoprotein levels and serum total cholesterol, which increased ( P =0.011, P =0.838). Low-density lipoprotein levels reduced, but it was insignificant ( P =0.194). Surgery types had affected the changes of diabetic markers ( P >0.05). Demand for oral medication was reduced significantly, but insulin injection reduction was not significant ( P =0.006 and P =0.099, respectively). Conclusion: Our study showed favorable bariatric surgery results on patients with diabetes in long-term follow-up. However, dyslipidemia is still a concern., Competing Interests: Competing Interests The authors declare no conflict of interest related to this work., (© 2023 Middle East Journal of Digestive Diseases.)

Background: Quinoline and acyl thiourea scaffolds have major chemical significance in medicinal chemistry. Quinoline-based acyl thiourea derivatives may potentially target the urease enzyme. Materials & methods: Quinoline-based acyl thiourea derivatives 1 - 26 were synthesized and tested for urease inhibitory activity. Results: 19 derivatives ( 1 - 19 ) showed enhanced urease enzyme inhibitory potential (IC 50  = 1.19-18.92 μM) compared with standard thiourea (IC 50  = 19.53 ± 0.032 μM), whereas compounds 20 - 26 were inactive. Compounds with OCH 3 , OC 2 H 5 , Br and CH 3 on the aryl ring showed significantly greater inhibitory potential than compounds with hydrocarbon chains of varying length. Molecular docking studies were conducted to investigate ligand interactions with the enzyme's active site. Conclusion: The identified hits can serve as potential leads against the drug target urease in advanced studies.

Background: Thymol (2-isopropyl-5-methylphenol) is a colorless crystalline derivative of cymene, that possesses pleotropic pharmacological properties, including analgesic, antibacterial, antispasmodic, and anti-inflammatory activities. Thymol has also been recognized for its beneficial effect as an anti-tumor agent, but the precise mechanism for this has not been fully elucidated. We aimed to identifying whether thymol exerts anti-cancer activity in human U-87 malignant glioblastoma (GB) cells (U-87)., Methods and Results: Cell viability and apoptosis was evaluated in U-87 cells treated with thymol at different concentrations. Reactive oxygen species (ROS) production, mRNA expressions of apoptosis-related genes and cell cycle characteristics were assessed. The cytotoxic activity of the co-exposure of thymol and temozolomide (TMZ) was also evaluated. The half-maximal inhibitory concentration (IC50) of thymol in the U-87 cells was 230 μM assessed at 24 h after exposure. Thymol did not exhibit any cytotoxic effects on normal L929 cells at this concentration. Thymol treatment increased the expression of Bax and p53, and also increased apoptotic cell death, and excessive generation of ROS. Moreover, the cytotoxic activity of thymol on the U-87 cells may be related to the arrest of the cell cycle at the G0/G1 interface. Combination therapy showed that the cytotoxic effects of thymol synergized with TMZ, and combined treatment had more cytotoxic potential compared to either of the agents alone., Conclusions: Our data indicate the potential cytotoxic activities of thymol on U-87 cells. Further studies are required to evaluate the spectrum of the antitumor activity of thymol on GB cells., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Novel ibuprofen derivatives 1-19 including ibuprofen hydrazide 1, and substituted thiourea derivatives 2-19 were synthesized and characterized by EI-MS, FAB-MS, HREI-MS, HRFAB-MS, 1 H-, and 13 C-NMR spectroscopic techniques. The synthetic molecules 1-19 were examined for their in vitro urease inhibition and were found to display a diversified degree of inhibitory potential in the range of IC 50  = 2.96-178 μM as compared to the standard thiourea (IC 50  = 21.32 ± 0.22 μM). Out of nineteen, thirteen derivatives 2-4, 6, 7, 9, 11-15, 17, and 18 demonstrated remarkable inhibitory activity with IC 50 values of 2.96 ± 1.11 to 16.1 ± 1.07 μM, compound 5 exhibited moderate inhibition with IC 50 value of 37.3 ± 0.41 μM, whereas, compounds 1, 8, and 10 demonstrated weak inhibition against urease enzyme. Almost all structural features are participating in the activity; however, limited structure-activity relationship was discussed on the basis of different structural features, i.e., different functional groups and their positions at aryl part. In addition, molecular docking study was performed in order to understand the ligands binding interactions with the active site of urease enzyme.

Benzotriazoles (4-6) were synthesized which were further reacted with different substituted benzoic acids and phenacyl bromides to synthesize benzotriazole derivatives (7-40). The synthetic compounds (7-40) were characterized via different spectroscopic techniques including EI-MS, HREI-MS, 1 H-, and 13 C NMR. These molecules were examined for their anti-hyperglycemic potential hence were evaluated for α-glucosidase and α-amylase inhibitory activities. All benzotriazoles displayed moderate to good inhibitory activity in the range of IC 50 values of 2.00-5.6 and 2.04-5.72 μM against α-glucosidase and α-amylase enzymes, respectively. The synthetic compounds were divided into two categories "A" and "B", in order to understand the structure-activity relationship. Compounds 25 (IC 50  = 2.41 ± 1.31 μM), (IC 50  = 2.5 ± 1.21 μM), 36 (IC 50  = 2.12 ± 1.35 μM), (IC 50  = 2.21 ± 1.08 μM), and 37 (IC 50  = 2.00 ± 1.22 μM), (IC 50  = 2.04 ± 1.4 μM) with chloro substitution/s at aryl ring were found to be most active against α-glucosidase and α-amylase enzymes. Molecular docking studies on all compounds were performed which revealed that chloro substitutions are playing a pivotal role in the binding interactions. The enzyme inhibition mode was also studied and the kinetic studies revealed that the synthetic molecules have shown competitive mode of inhibition against α-amylase and non-competitive mode of inhibition against α-glucosidase enzyme., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)