:Background and Objective: Heroin abuse and addiction represent one of the major problems globally. The objective of this study is to evaluate the oxidative stress enzyme markers, apoptosis, sperm quality and testosterone of heroin administered rats via intraperitoneal injection.
The p53 protein is a tumor suppressor encoded by the TP53 gene and consists of 393 amino acids with four main functional domains. This protein responds to various cellular stresses to regulate the expression of target genes, thereby causing DNA repair, cell cycle arrest, apoptosis, metabolic changes, and aging. Mutations in the TP53 gene and the functions of the wild-type p53 protein (wtp53) have been linked to various human cancers. Eight TP53 gene mutations are located in codons, constituting 28% of all p53 mutations. The p53 can be used as a biomarker for tumor progression and an excellent target for designing cancer treatment strategies. In wild-type p53-carrying cancers, abnormal signaling of the p53 pathway usually occurs due to other unusual settings, such as high MDM2 expression. These differences between cancer cell p53 and normal cells have made p53 one of the most important targets for cancer treatment. In this review, we have dealt with various issues, such as the relative contribution of wild-type p53 loss of function, including transactivation-dependent and transactivation-independent activities in oncogenic processes and their role in cancer development. We also discuss the role of p53 in the process of ferroptosis and its targeting in cancer treatment. Finally, we focus on p53-related drug delivery systems and investigate the challenges and solutions.
Different kinds of vitamins can be used as promising candidates to mitigate the structural changes of proteins and associated cytotoxicity stimulated by NPs. Therefore, the structural changes of α-syn molecules and their associated cytotoxicity in the presence of SWCNTs either alone or co-incubated with vitamin K1 were studied by spectroscopic, bioinformatical, and cellular assays. Methods: Intrinsic and ThT fluorescence, CD, and Congo red absorption spectroscopic approaches as well as TEM investigation, molecular docking, and molecular dynamics were used to explore the protective effect of vitamin K1 on the structural changes of α-syn induced by SWCNTs. The cytotoxicity of α-syn/SWCNTs co-incubated with vitamin K1 against SH-SY5Y cells was also carried out by MTT, LDH, and caspase-3 assays. Results: Fluorescence spectroscopy showed that vitamin K1 has a significant effect in reducing SWCNT-induced fluorescence quenching and aggregation of αsyn. CD, Congo red adsorption, and TEM investigations determined that co-incubation of αsyn with vitamin K1 inhibited the propensity of α-syn into the structural changes and amorphous aggregation in the presence of SWCNT. Docking studies determined the occupation of preferred docked site of SWCNT by vitamin K1 on αsyn conformation. A molecular dynamics study also showed that vitamin K1 reduced the structural changes of αsyn induced by SWCNT. Cellular data exhibited that the cytotoxicity of αsyn co-incubated with vitamin K1 in the presence of SWCNTs is less than the outcomes obtained in the absence of the vitamin K1. Conclusion: It may be concluded that vitamin K1 decreases the propensity of αsyn aggregation in the presence of SWCNTs and induction of cytotoxicity.
The present study was designed to investigate the relation between severity of atherosclerosis via angiography and alteration of some important biochemical, hormonal and hematological variables in patients underwent Coronary Artery Bypass Graft (CABG) surgery. Eighty adult patients underwent coronary angiography were included in this study, and a standardized case-control study of acute myocardial infarction was established through taking 20 healthy individuals. Diagnostic coronary angiography was performed by a team of expert cardiologists. The patients were grouped according the number of major epicardial coronary arteries into one vessel disease (1VD), two vessels disease (2VD) or three vessels disease (3VD). The evaluation of biochemical tests were performed. The results of association of measurements with the severity of disease showed the priority of cholesterol and its related indexes (especially LDL) rather than TG indicating the severity of atherosclerosis. While, blood glucose and HbA1c were not apparently related to the degree of atherosclerosis. Significant reduction of T3 hormone and platelets and elevation in MPV were recorded in patients suffering from three vessels occlusion. This finding suggested strong association between severity of atherosclerosis and LDL, MPV and T3 in CABG patients.
Opioids are perhaps the most efficacious analgesic agents influencing a large number of body functions. The objective of this study is to observe changes in hemodynamic, electrolytes, and kidney and thyroid functions of opium treatment in rats. Thirty male rats were randomly distributed into three groups. Group 1 regarded as control, while in group 2 and 3, the animals were daily injected intraperitoneally with opium for seven successive days. Intraperitoneal opium injection caused a dose-deponent increase in serum calcium (Ca +2 )and phosphate (PO4 -) levels, whereas the nitric oxide (NO), triiodothyronine (T3) and thyroxine (T4) levels were significantly decreased in both doses. The significant decrease in serum (NO )level and increase serum (Ca 2+ ) and (PO4 -) levels resulted in significant elevation of systolic blood pressure (SBP) accompanied by elevation of serum bilirubin and urea. Our finding suggests that opium causes hypertension, kidney and thyroid function abnormalities mostly in concentration dependent manner.
In December 2019, a new coronavirus disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared in Wuhan city and quickly became a global health issue. COVID-19 causes various symptoms ranging from no symptoms to potentially deadly pneumonia. The study aimed to understand the effects of SARS-CoV-2 infection on immune response and the differences in inflammatory, coagulation, and cardiac biomarkers between male and female patients. Between June 1st and November 1st, 2020, 95 cases of SARS-CoV-2 infected individuals were studied at Zanko Hospital. SARS-CoV-2 infection was confirmed using the real-time RT-PCR technique. All cases were analyzed for clinical, epidemiological, and laboratory data. On average, the patients were 50.64 (SEM= 2.359) years old, with 61 males and 34 females. The patients had elevated C-reactive protein (CRP), which was 43.96 (SEM= 6.154), while the erythrocyte sedimentation rate (ESR) was 50.50 (SEM= 5.498). The mean of D-Dimer, ferritin and lactate dehydrogenase (LDH) were 1.204 (SEM= 0.164), 534.7 (SEM= 61.48), and 366.6 (SEM= 36.81), respectively. There were no significant differences in the study's data mentioned above between male and female patients. In conclusion, inflammation is the most prominent symptom in COVID-19 patients, and males and females are nearly equally affected.
Triple Negative Breast Cancer (TNBC) is the aggressive and lethal type of breast malignancy that develops resistance to current therapies. Combination therapy has proven to be an effective strategy on TNBC. We aimed to study whether the nano-formulation of polyphenolic curcumin (Gemini-Cur) would affect the cisplatin-induced toxicity in MDA-MB-231 breast cancer cells. MDA-MB-231 cells were treated with Gemini-Cur, cisplatin and combination of Gemini-Cur/Cisplatin in a time- and dose-dependent manner. Cell viability was studied by using MTT, fluorescence microscopy and cell cycle assays. The mode of death was also determined by Hoechst staining and annexin V-FITC. Real-time PCR and western blotting were employed to detect the expression of BAX and BCL-2 genes. Our data demonstrated that Gemini-Cur significantly sensitizes cancer cells to cisplatin (combination index ≤ 1) and decreases IC50 values in comparison with Gemini-cur or cisplatin. Further studies confirmed that Gemini-Cur/Cisplatin suppresses cancer cell growth through induction of apoptosis (p < 0.001). In conclusion, the data confirm the synergistic effect of polyphenolic curcumin on cisplatin toxicity and provide attractive strategy to attain its apoptotic effect on TNBC.
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