Pharmacological characterization of the antidiabetic drug metformin in atherosclerosis inhibition: A comprehensive insight.

BACKGROUND: Atherosclerosis (AS) is a progressive disease that interferes with blood flow, leading to cardiovascular complications such as hypertension, ischemic heart disease, ischemic stroke, and vascular ischemia. The progression of AS is correlated with inflammation, oxidative stress, and endothelial dysfunction. Various signaling pathways, like nuclear erythroid-related factor 2 (Nrf2) and Kruppel-like factor 2 (KLF2), are involved in the pathogenesis of AS. Nrf2 and KLF2 have anti-inflammatory and antioxidant properties. Thus, activation of these pathways may reduce the development of AS. Metformin, an insulin-sensitizing drug used in the management of type 2 diabetes mellitus (T2DM), increases the expression of Nrf2 and KLF2. AS is a common long-term macrovascular complication of T2DM. Thus, metformin, through its pleiotropic anti-inflammatory effect, may attenuate the development and progression of AS. AIMS: Therefore, this review aims to investigate the possible role of metformin in AS concerning its effect on Nrf2 and KLF2 and inhibition of reactive oxygen species (ROS) formation. In addition to its antidiabetic effect, metformin can reduce cardiovascular morbidities and mortalities compared to other antidiabetic agents, even with similar blood glucose control by the Nrf2/KLF2 pathway activation. CONCLUSION: In conclusion, metformin is an effective therapeutic strategy against the development and progression of AS, mainly through activation of the KLF2/Nrf2 axis.

The effects of cholesterol and statins on Parkinson's neuropathology: a narrative review.

Parkinson disease (PD) is chronic and progressive neurodegenerative disease of the brain characterized by motor symptoms including tremors, rigidity, postural instability, and bradykinesia. PD neuropathology is due to the progressive degeneration of dopaminergic neurons in the substantia nigra and accumulation of Lewy bodies in the survival neurons. The brain contains a largest amount of cholesterol which is mainly synthesized from astrocytes and glial cells. Cholesterol is intricate in the pathogenesis of PD and may be beneficial or deleterious. Therefore, there are controversial points concerning the role of cholesterol in PD neuropathology. In addition, cholesterol-lowering agents' statins can affect brain cholesterol. Different studies highlighted that statins, via inhibition of brain HMG-CoA, can affect neuronal integrity through suppression of neuronal cholesterol, which regulates synaptic plasticity and neurotransmitter release. Furthermore, statins affect the development and progression of different neurodegenerative diseases in bidirectional ways that could be beneficial or detrimental. Therefore, the objective of the present review was to clarify the double-sward effects of cholesterol and statins on PD neuropathology.

Variations of blood viscosity in acute typhoid fever: A cross-sectional study.

Typhoid fever (TF) is a systemic infection caused by Salmonella Typhi (Salmonella Enterica) transmitted through contaminated water, food, or contact with infected individuals. In various infectious diseases, blood viscosity (BV) is affected by changes in hemoglobin concentrations and acute phase reactants. Inflammatory responses can lead to elevated plasma protein levels and further affect BV. This study aimed to investigate BV changes in patients with acute TF. A cross-sectional study was performed involving 55 patients with acute TF compared to 38 healthy controls. BV and inflammatory parameters were measured in both groups. TF patients showed reduced blood cells compared to healthy controls (p=0.001). Additionally, plasma total protein (TP) levels significantly increased to 10.79±1.05 g/L in TF patients compared to 7.035±1.44 g/L in healthy controls (p=0.03). Hematocrit (HCT) levels were 11.67±2.89% in TF patients and 12.84±2.02% in healthy controls (p=0.07), suggesting a trend towards increased BV in TF patients. Elevated BV is involved in the pathogenesis of different inflammatory and infectious diseases. The increased BV in TF patients may raise the risk of complications. Therefore, monitoring BV might be a crucial tool in TF patients, mainly in the high-risk group, for early detection of cardiovascular complications.

Ellagic acid-rich Pomegranate extracts synergizes moxifloxacin against methicillin resistance Staphylococcus aureus (MRSA).

OBJECTIVE: To elucidate the anti- Methicillin resistance Staphylococcus aureus (MRSA) effect of pomegranate alone and in combination with moxifloxacin fluoroquinolone. METHODS: A total of five clinical isolates of MRSA (ATCC 43300) were used in the study. Disc diffusion method was used to determine the anti-MRSA effect of pomegranate and/or moxifloxacin by using Mueller-Hinton agar. Minimal inhibitory concentration (MIC), fractional inhibitory concentration (FIC) of moxifloxacin and pomegranate were calculated, the dynamic picture of the bactericidal effect of pomegranate and/or moxifloxacin was determined. SPSS version 20.00 was used for data analysis. RESULTS: Zone of inhibition (ZOI) of moxifloxacin was 19.67±4.84mm which was not significant compared with pomegranate ZOI 14.59±2.73mm, (P=0.07). The combination of moxifloxacin and pomegranate led to more significant ZOI (26.83±4.91mm) compared with moxifloxacin (P=0.04) and pomegranate alone (P=0.0012). MIC of pomegranate was high (31.62±6.95mg/mL) compared with low MIC of moxifloxacin (2.70±0.63 mg/mL), (P<0.0001), while MIC of the combination was low (1.22±0.85mg/mL) compared MIC of moxifloxacin, (P=0.012). FIC of pomegranate was 0.038 and FIC of moxifloxacin was 0.45, therefore sFIC index was 0.488, equal to the synergistic effect. The kill rates of combination were higher than those of pomegranate or moxifloxacin, against MRSA ATCC 43300. CONCLUSIONS: Ellagic acid-rich pomegranate extract alone has significant antibacterial activity and synergizes the bactericidal effect of moxifloxacin against MRSA.

Endothelial dysfunction in acute acquired toxoplasmosis.

BACKGROUND: Acute toxoplasmosis (AT) which is caused by Toxoplasma gondii (T. gondii) leads to induction of pro-inflammatory and/or oxidative stress changes through activation of host immune response. Therefore, the endeavor of the present study was to assess endothelial dysfunction(ED) and oxidative stress in patients with acute toxoplasmosis. METHODS: This study involved 21 patients with AT compared with 20 healthy controls. Serum immunoglobulin levels [IgG], IgM, IgA), Interleukin-6 (IL-6), endothelin-1 (ET-1), and human malondialdehyde (MDA) serum levels were evaluated. RESULTS: IgM, IgG, and IgA levels were high patients with AT as compared with the control (P < 0.01). IL-6, MDA, and ET-1 serum levels were high in patients with AT compared with control (P < 0.01). In patients with AT, IgM serum level was significantly correlated with other immunoglobulin, and with the biomarker of oxidative stress, lipid peroxidation, and ED (P = 0.0001). CONCLUSION: AT is linked with oxidative stress and pro-inflammatory changes which together provoke ED.