Cytotoxic Effect of YH239-EE and Its Enantiomer on MCF7 Cell Line.

OBJECTIVE: This study aimed to discover the cytotoxic effect of YH239-EE and YH239 alone and their enantiomer potency in cytotoxic effect on the MCF7 cell line. METHODS: We used the cytotoxic study on MDM2 cell lines by detecting the percentage of apoptosis and necrosis by annexin v methods. RESULT: This result shows that YH239-EE causes more apoptosis and necrosis 40% in comparison to YH239 without ethyl ester, about 4.92 %,  and The (+) enantiomer of YH239-EE demonstrated a markedly higher induction of apoptosis and necrosis (84.48%) in MCF7 cells compared to the (-) enantiomer (48.71%). CONCLUSION: The ethyl ester group in YH239-EE might play a crucial role in enhancing the compound's ability to induce cell death, and The high efficacy of the (+) enantiomer of YH239-EE in inducing cell death in MCF7 cells suggests it may be a more promising therapeutic candidate for breast cancer treatment, specifically for subtypes represented by MCF7 cells.

Chemotherapy-induced cardiotoxicity: a new perspective on the role of Digoxin, ATG7 activators, Resveratrol, and herbal drugs.

Cancer is a major public health problem, and chemotherapy plays a significant role in the management of neoplastic diseases. However, chemotherapy-induced cardiotoxicity is a serious side effect secondary to cardiac damage caused by antineoplastic's direct and indirect toxicity. Currently, there are no reliable and approved methods for preventing or treating chemotherapy-induced cardiotoxicity. Understanding the mechanisms of chemotherapy-induced cardiotoxicity may be vital to improving survival. The independent risk factors for developing cardiotoxicity must be considered to prevent myocardial damage without decreasing the therapeutic efficacy of cancer treatment. This systematic review aimed to identify and analyze the evidence on chemotherapy-induced cardiotoxicity, associated risk factors, and methods to decrease or prevent it. We conducted a comprehensive search on PubMed, Google Scholar, and Directory of Open Access Journals (DOAJ) using the following keywords: "doxorubicin cardiotoxicity", "anthracycline cardiotoxicity", "chemotherapy", "digoxin decrease cardiotoxicity", "ATG7 activators", retrieving 59 articles fulfilling the inclusion criteria. Therapeutic schemes can be changed by choosing prolonged infusion application over boluses. In addition, some agents like Dexrazoxane can reduce chemotherapy-induced cardiotoxicity in high-risk groups. Recent research found that Digoxin, ATG7 activators, Resveratrol, and other medical substances or herbal compounds have a comparable effect on Dexrazoxane in anthracycline-induced cardiotoxicity.

Non-alcoholic fatty liver disease: relation to juvenile obesity, lipid profile, and hepatic enzymes.

The prevalence of juvenile obesity is increasing, reaching epidemic proportions, presenting a link not only to NAFLD (non-alcoholic fatty liver disease) but to abnormal lipid profiles and liver enzyme abnormalities. Liver ultrasonography is a sensitive and specific tool for the recognition of NAFLD. This study aims to assess the association between NAFLD and juvenile obesity and to determine the other related changes in a set of indicators, including lipid profile abnormalities and serum transaminases. The sample included 470 obese and 210 non-obese individuals aged 6-16. Anthropometric measures were assessed, with the serum lipid profile and liver transaminases, and abdominal ultrasonography was used to detect NAFLD. Fatty liver was found in 38% of the obese subjects and none of the non-obese subjects. Within obese subjects, mean body mass index (BMI) and waist circumference increased significantly in patients with NAFLD compared to those without fatty liver. Moreover, LDL (low-density lipoprotein), CHOL (cholesterol), and serum liver enzymes were significantly higher in the presence of NAFLD. In conclusion, NAFLD commonly associates with juvenile obesity, relating to obesity and the abnormal lipid profile (including elevated CHOL and LDL) among obese people, reflecting elevated liver transaminases, which increase the risk of cirrhosis.

Efficacy of Aflibercept as initial treatment for neovascular age-related macular degeneration in an Iraqi patient sample.

Age-related macular degeneration (AMD) is a progressive degenerative eye disorder that primarily affects individuals over 50. It causes gradual loss of central vision and can lead to irreversible severe visual loss if left untreated. AMD is a leading cause of blindness in the developed world. This study aimed to investigate the effects of a loading dosage of intravitreal Aflibercept on functional and morphological responses in neovascular AMD, considering demographic characteristics and the link between AMD-related retinal symptoms at presentations. A prospective interventional study was conducted from November 2021 to September 2022 on a sample of Iraqi patients with neovascular AMD who had active choroidal neovascularization (CNV) lesions confirmed by OCT-A and received intravitreal Aflibercept 2mg injection as initial therapy (3 loading doses). Best-corrected visual acuity (BCVA) was used to measure functional responses, and central macular thickness (CMT) and maximum area of the retinal thickness (MART) (by SD-OCT) were used to measure morphological responses. The study included 48 patients (57 eyes) with active neovascular AMD. The mean difference of BCVA in log MAR (0.2 ± 0.7) significantly improved from 1.3±0.7 at baseline to 1.1±0.8 after loading Aflibercept (P=0.034). The mean difference in CMT 113.6 ± 125.9 was statistically significant (P<0.0001). Also, the mean change in MART significantly decreased from 444.2 ± 127.1 µm at baseline to 348.7±74.5 µm (p < 0.0001) after loading Aflibercept. This study demonstrated that Aflibercept is a functionally and anatomically successful treatment for neovascular AMD.

Neutrophil Extracellular Traps (NETs) and Covid-19: A new frontiers for therapeutic modality.

Coronavirus disease 2019 (Covid-19) is a worldwide infectious disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2). In severe SARS-CoV-2 infection, there is severe inflammatory reactions due to neutrophil recruitments and infiltration in the different organs with the formation of neutrophil extracellular traps (NETs), which involved various complications of SARS-CoV-2 infection. Therefore, the objective of the present review was to explore the potential role of NETs in the pathogenesis of SARS-CoV-2 infection and to identify the targeting drugs against NETs in Covid-19 patients. Different enzyme types are involved in the formation of NETs, such as neutrophil elastase (NE), which degrades nuclear protein and release histones, peptidyl arginine deiminase type 4 (PADA4), which releases chromosomal DNA and gasdermin D, which creates pores in the NTs cell membrane that facilitating expulsion of NT contents. Despite of the beneficial effects of NETs in controlling of invading pathogens, sustained formations of NETs during respiratory viral infections are associated with collateral tissue injury. Excessive development of NETs in SARS-CoV-2 infection is linked with the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) due to creation of the NETs-IL-1ß loop. Also, aberrant NTs activation alone or through NETs formation may augment SARS-CoV-2-induced cytokine storm (CS) and macrophage activation syndrome (MAS) in patients with severe Covid-19. Furthermore, NETs formation in SARS-CoV-2 infection is associated with immuno-thrombosis and the development of ALI/ARDS. Therefore, anti-NETs therapy of natural or synthetic sources may mitigate SARS-CoV-2 infection-induced exaggerated immune response, hyperinflammation, immuno-thrombosis, and other complications.

The role of COVID-19 in myopathy: incidence, causes, treatment, and prevention.

Myopathy is a disease characterized by muscle dysfunction in general and may be associated with genetics, medication such as statins, or inflammation. In 2019, an epidemic viral infection (SARS-CoV-2 virus) that invaded most countries worldwide appeared and caused acute respiratory disease. Consequently, patients had to take a group of drugs for a relatively long treatment period. According to several studies, there was an increase in the cases of muscular disorders due to several factors. This study aimed to (1) investigate the relationship between COVID-19 and myopathy and (2) identify the causes and prevention methods. A systematic review was conducted, analyzing several articles from the following databases: ResearchGate, Medline, DOAJ (The Directory of Open-Access Journals), PubMed, and Google Scholar. After performing the search and filtering the results, we included 61 articles. There was a strong relationship between COVID-19 and myopathy, especially in patients admitted to the ICU department, due to medication or neurological dysregulation with multiorgan dysfunctions such as polyneuropathy, peripheral nerve involvement, dysautonomia, Guillain-Barré syndrome, and many others.

Leptin hormone and its effectiveness in reproduction, metabolism, immunity, diabetes, hopes and ambitions.

Leptin is a hormone derived from adipose tissue and the small intestine, mainly in enterocytes; it helps regulate the energy balance by suppressing hunger, resulting in decreased fat mass in adipocytes. Leptin has specific receptors in the ventromedial and arcuate nuclei and other parts of the hypothalamus and the feeding center in the ventral tegmental area. It also plays a role in regulatory aspects other than fat cells, such as obesity, which is linked to a loss of sensitivity of leptin receptors, resulting in an inability to produce satiety and an increase in food intake. Moreover, leptin plays a part in lactation, bone density, the immune system, diabetes treatments, and hypertriglyceridemia. The latest studies in leptin suggest that an analog of leptin may treat DM and hypertriglyceridemia. Further research should be conducted on the effectiveness of leptin on other related diseases.