An FDA-approved kinase inhibitor called sorafenib (SOR) is used to treat primary kidney and liver cancer as well as to stop the spread of advanced breast cancer. Side effects from SOR, such as palmar–plantar erythrodysesthesia syndrome, can negatively impact an individual’s quality of life. There are a lot of data supporting the importance of lycopene (LYC) in preventing cancer. The antitumor properties of the combination of sorafenib and lycopene were examined in this study. A viability test against MDA-MB-231 was used to assess the anticancer efficacy of sorafenib, lycopene, and their combination in vitro. Moreover, a cell cycle analysis and Annexin-V/PI double staining were performed by using flow cytometry. In addition, the protein level of JNK-1, ERK-1, Beclin-1, P38, and P53 of the MDA-MB-231 cell line was estimated using ELISA kits. In addition, mice with SEC were divided into four equal groups at random (n = 10) to investigate the possible processes underlying the in vivo antitumor effect. Group IV (SEC-SOR-LYC) received SOR (30 mg/kg/day, p.o.) and LYC (20 mg/kg/day, p.o.); Group I received the SEC control; Group II received SEC-SOR (30 mg/kg/day, p.o.); and Group III received SEC-LYC (20 mg/kg/day, p.o.). The findings demonstrated that the combination of sorafenib and lycopene was superior to sorafenib and lycopene alone in causing early cell cycle arrest, suppressing the viability of cancer cells, and increasing cell apoptosis and autophagy. Likewise, the combination of sorafenib and lycopene demonstrated inhibition of the levels of Bcl-2, Ki-67, VEGF, IL-1β, and TNF-α protein. Otherwise, the quantities of the proteins BAX, P53, and caspase 3 were amplified. Furthermore, the combined treatment led to a substantial increase in TNF-α, caspase 3, and VEGF gene expression compared to the equivalent dosages of monotherapy. The combination of sorafenib and lycopene enhanced apoptosis and reduced inflammation, as seen by the tumor’s decreased weight and volume, hence demonstrating its potential anticancer effect.

Verapamil (VER) and cilostazol (Cilo) are mostly used as cardiovascular drugs; they have beneficial effects on different organs toxicities. we investigated whether the Nuclear factor erythroid 2-related factor 2 (Nrf2), Glycogen synthase kinase-3β (GSK-3β), and Nuclear factor-kappa B (NF-κB) pathway involved in the protective role of these drugs against Thioacetamide (TAA) induced hepatotoxicity. male rats were randomized divided into five groups, each group (n = 10): control, TAA, VER+TAA, Cilo+TAA, and VER+Cilo+TAA groups. Hepatotoxicity induced in rats by TAA injection once on the 7th day of the experiment. TAA-induced hepatotoxicity indicated by a significant elevated in serum markers (Alanine aminotransferases (ALT), Aspartate aminotransferases (AST), and bilirubin), oxidative stress markers (Malondialdehyde (MDA), and Nitric oxide (NO)), and protein levels markers (NF-κB, and S100 calcium-binding protein A4 (S100A4)). Also, TAA decreased Nrf2, and increased GSK-3β genes expression. Histopathological alterations in the liver also appeared as a response to TAA injection. On the other hand VER and/or Cilo significantly prevented TAA-induced hepatotoxicity in rats through significantly decreased in ALT, AST, bilirubin, MDA, NO, NF-κB, and S100A4 protein levels. Also, they increased Nrf2 and decreased GSK-3β genes expression which caused improvement in the histopathological changes of the liver. the addition of verapamil to cilostazol potentiated the hepatoprotective activity, and inhibited the progression of hepatotoxicity caused by TAA through the Nrf2/GSK-3β/NF-κBpathway and their activity on oxidative stress, inflammation, and NF-κB protein expression.

Deferasirox belongs to a new is a bishydroxyphenyltriazoles iron chelator used for treatment of chronic iron overload. The use of Deferasirox is associated with hepatotoxicity. Silymarin is a benzo gamma-pyrones flavonoid which affords hepatoprotection and preserves hepatocyte membranes by its antioxidant effect. Curcumin is a poly-phenol compound naturally concentrated in the herb Curcuma longa. The present study was conducted to evaluate and compare the hepatoprotective effects of both silymarin and curcumin against deferasirox-induced hepatotoxicity in rats and to explore the potential mechanisms account for their hepatoprotective effects. The present study was carried out using 32 male wistar randomly assigned into 4 groups (8 rats each) as follows; Group1: served as normal control group in which rats received distilled water (0.5ml per rat) by oral gavage. Group II (Deferasirox group) in which hepatotoxicity was induced by oral administration of deferasirox in a dose of 100 mg/kg once daily for 4 weeks dissolved in distilled water for a concentration of 35mg/ml. Group III (deferasirox+ curcumin) in which rats received curcumin in a dose of 100 mg/kg daily dose by oral gavage for 4 weeks suspended in distilled water for a concentration of 35 mg/ml one hour before administration of deferasirox. Group IV (deferasirox+ silymarin) in which rats received silymarin in dose of 7.56 mg/kg once daily by oral gavage for 4 weeks suspended in distilled water for a concentration of 2.7mg/ml one hour before administration of deferasirox. At the end of the treatment period, all rats were sacrificed by cervical dislocation, blood samples were collected for measurement of ALT, AST, ALP and total bilirubin. Liver samples were used for measurement of MDA, GSH and IL-6. Histopathological and immunohistochemistry were also done. The present data revealed that rats pretreated with curcumin or silymarin exhibited significant reduction in ALT, AST, ALP, total bilirubin, IL-6 and MDA levels with significant elevation of GSH level compared to deferasirox group. In-between group comparison revealed that there was a more significant reduction in ALT, AST, ALP, total bilirubin, IL-6 and MDA in group IV compared to group III. In conclusion, both curcumin and silymarin represent natural protective agents against Deferasirox-induced hepatotoxicity due to their antioxidant and anti-inflammatory effects.

The journal retracts the article “Potential Antitumor Activity of Combined Lycopene and Sorafenib against Solid Ehrlich Carcinoma via Targeting Autophagy and Apoptosis and Suppressing Proliferation”

PurposeMaintenance of systemic homeostasis and prevention of secondary injury are a cornerstone of treatment in neurocritical care to prevent organ dysfunction and adverse effect on neurological outcome. This is a pilot study on prospective observational research aiming to measure and characterize the incidence of secondary insults occurring during intensive care unit stay in patients with catastrophic brain injury potentially evolving to brain death.MethodsAdult patients admitted to intensive care unit for acute brain damage and with Glasgow coma score ≤ 5 have been enrolled. Arterial blood pressure, heart rate and SpO2 were collected minute by minute from a central station connected to patients’ bedside monitors during ICU stay.ResultsWe report on 25 patients recruited prospectively from the University Hospital of Messina, Italy as a part of a larger ongoing multi-centre study. Patient monitoring data were 8-3000 hours (0.3-125 days). Admission diagnoses were intracerebral haemorrhage (N= 14), TBI (N=4), SAH (N=3) and ischaemic stroke (N=4). Median age was 69 (IQR 47-88) and 56% were female. Nine out of 25 patients (38%) evolved to brain death. The proportion of valid monitoring time spent with secondary insults are presented and discussed. Day 3 and 4 post ICU admission demonstrated the largest number of secondary insults, mainly hypotension. Patients who subsequently underwent brain death testing exhibited a more severe and sustained hypotensive burden compared with non–brain death–tested patients.ConclusionsIn patients with catastrophic brain injury, the incidence of hypotension remains the highest among secondary insults in patients evolved to BD.