Obesity is the accumulation of abnormal or excessive fat that may interfere with the maintenance of an optimal state of health. The excess of macronutrients in the adipose tissues stimulates them to ...release inflammatory mediators such as tumor necrosis factor α and interleukin 6, and reduces production of adiponectin, predisposing to a pro-inflammatory state and oxidative stress. The increased level of interleukin 6 stimulates the liver to synthesize and secrete C-reactive protein. As a risk factor, inflammation is an imbedded mechanism of developed cardiovascular diseases including coagulation, atherosclerosis, metabolic syndrome, insulin resistance, and diabetes mellitus. It is also associated with development of non-cardiovascular diseases such as psoriasis, depression, cancer, and renal diseases. On the other hand, a reduced level of adiponectin, a significant predictor of cardiovascular mortality, is associated with impaired fasting glucose, leading to type-2 diabetes development, metabolic abnormalities, coronary artery calcification, and stroke. Finally, managing obesity can help reduce the risks of cardiovascular diseases and poor outcome via inhibiting inflammatory mechanisms.
A new series of benzoxazole derivatives were designed and synthesised to have the main essential pharmacophoric features of VEGFR-2 inhibitors. Cytotoxic activities were evaluated for all derivatives ...against two human cancer cell lines, MCF-7 and HepG2. Also, the effect of the most cytotoxic derivatives on VEGFR-2 protein concentration was assessed by ELISA. Compounds 14o, 14l, and 14b showed the highest activities with VEGFR-2 protein concentrations of 586.3, 636.2, and 705.7 pg/ml, respectively. Additionally, the anti-angiogenic property of compound 14b against human umbilical vascular endothelial cell (HUVEC) was performed using a wound healing migration assay. Compound 14b reduced proliferation and migratory potential of HUVEC cells. Furthermore, compound 14b was subjected to further biological investigations including cell cycle and apoptosis analyses. Compound 14b arrested the HepG2 cell growth at the Pre-G1 phase and induced apoptosis by 16.52%, compared to 0.67% in the control (HepG2) cells. The effect of apoptosis was buttressed by a 4.8-fold increase in caspase-3 level compared to the control cells. Besides, different in silico docking studies were also performed to get better insights into the possible binding mode of the target compounds with VEGFR-2 active sites.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
This study focuses on the preparation of PbI
2
and PbI
2
:Sn thin films using inexpensive chemical bath deposition (CBD) method. The structural, optical, and electrical properties of the PbI
2
film ...before and after doping with Sn dopant were studied. X-ray diffraction (XRD) confirmed that the grown PbI
2
and Sn-doped PbI
2
films are crystalline, exhibiting a hexagonal phase, while peaks corresponding to the SnI
4
phase were detected. The energy-dispersive X-ray (EDX) analysis and elemental mapping results reveal the presence of the Sn dopant. Scanning electron microscopy (SEM) studies confirm that the prepared PbI
2
and Sn-doped PbI
2
films have a hexagonal structure. The energy gap of the deposited PbI
2
film decreases from 2.7 to 2.5 eV after doping with Sn. The room-temperature current–voltage characteristics of PbI
2
/Si and PbI
2
:Sn/Si heterojunction photodetectors were measured under dark and illumination conditions. The spectral responsivity, specific detectivity, and external quantum efficiency of the photodetectors were determined before and after doping. The peak response of the PbI
2
/Si photodetector was found at 550 nm with a responsivity of 0.08 A/W, while the peak response of the PbI
2
:Sn/Si photodetector was located at 500 nm with a responsivity of 0.29 A/W. The external quantum efficiency of PbI
2
/Si and PbI
2
:Sn/Si was 18 and 82%, respectively. The specific detectivity of the photodetector increases from 3.1 × 10
11
to 9.2 × 10
11
after doping. The energy band diagram of PbI
2
:Sn/Si under illumination is presented.
The primary goal of this research is to investigate the dynamics of nanoparticle-mediated blood flow in the presence of bioconvection effects caused by microorganisms. The boundary layer problem of ...unsteady magnetohydrodynamic blood flow in the porous medium of tissues in stretching motion is studied. The Casson fluid model of blood flow is mathematically represented by a system of partial differential equations (PDE). The resulting set of governing equations is numerically solved, and the physical interpretation is given for the outcomes that are presented as graphs and tables. The temperature and concentration distribution of blood, along with the organism density profile in the corresponding boundary layer, are plotted, and the effects of various physical parameters, including magnetic field, radiation, chemical reaction, and permeability of the porous medium, on the results are investigated. Additionally, physical effects on the heat and mass transfer coefficients of the flow are also discussed. It is observed that the rate of heat transfer and the temperature profile are improved by increasing the values of the thermophoresis and Brownian motion parameters. Furthermore, at the lowest value of the permeability parameter and the highest value of the Brownian motion factor, the maximum heat transfer rate is observed. The findings of the study bear the promise of significant application in targeted drug delivery, magnetic therapy, and therapeutic hyperthermia treatments.
Breast cancer invasive 2.3 million women worldly and second prominent factor of cancer-related mortality. Finding a new site-specific and safe small molecule is a current need in this field. With the ...aid of deep learning Algorithms, we analyzed the published big database from cancer CBioportal to find the best target protein. Further, Multi-omics analysis such as enrichment analysis, scores of molecular, RNA biological function at a cellular level, and protein domain were obtained and matched to find the better hit molecules. The gene analysis output shows nucleolar protein 6 plays a significant responsibility in breast carcinoma and 354 natural and synthetic lead molecules are docked inside the active site. Docking result gave the output hit molecule falavan-3-ols with a binding score of −5.325 (Kcal/mol) and interaction analysis illustrates, 13 active amino acids favoring the binding interaction with functional groups of the hit molecule compared to the standard molecule Abemacilib (−2.857 (Kcal/mol)). Best docked complex of flavan-3-ols and NOL6 protein subjected to dynamic simulation 100 ns to study the stability. The results proved that π-π stacked, carbon‑hydrogen and electrostatic interactions are stable throughout the 100 ns simulation. The overall results conclude the hit molecule flavan-3-ol will be a safe and potent lead molecule to generate and treat breast carcinoma patients.
Atherosclerotic cardiovascular disease (CVD) is a collective term comprising of a group of disorders of the heart and blood vessels. These diseases are the largest cause of morbidity and premature ...death worldwide. Coronary heart disease and cerebrovascular disease (stroke) are the most frequently occurring diseases. The two major initiators involved in the development of atherosclerotic CVD are vascular production of reactive oxygen species (ROS) and lipid oxidation. In atherosclerosis development, ROS is associated with rapid loss of anti-inflammatory and anti-atherogenic activities of the endothelium-derived nitric oxide (NO
·
) resulting in endothelial dysfunction. In part involving activation of the transcription factor NF-κB, ROS have been involved in signaling cascades leading to vascular pro-inflammatory and pro-thrombotic gene expression. ROS is also a potent activator of matrix metalloproteinases (MMPs), which indicate plaque destabilization and rupture. The second initiator involved in atherosclerotic CVD is the oxidation of low-density lipoproteins (LDL). Oxidation of LDL in vessel wall leads to an inflammatory cascade that activates atherogenic pathway leading to foam cell formation. The accumulation of foam cells leads to fatty streak formation, which is the earliest visible atherosclerotic lesion. In contrast, the cardiac sarco/endoplasmic reticulum Ca
2+
-ATPase (SERCA2a) and hepatic apolipoprotein E (apoE) expression can improve cardiovascular function. SERCA2a regulates the cardiac contractile function by lowering cytoplasmic calcium levels during relaxation, and affecting NO
·
action in vascular cells, while apoE is a critical ligand in the plasma clearance of triglyceride- and cholesterol-rich lipoproteins.
The medicinal administration of Aloe vera gel has become promising in pharmaceutical and cosmetic applications particularly with the development of the nanotechnology concept. Nowadays, effective H. ...pylori treatment is a global problem; therefore, the development of natural products with nanopolymers such as chitosan nanoparticles (CSNPs) could represent a novel strategy for the treatment of gastric infection of H. pylori. HPLC analysis of A. vera gel indicated the presence of chlorogenic acid as the main constituent (1637.09 µg/mL) with other compounds pyrocatechol (1637.09 µg/mL), catechin (1552.92 µg/mL), naringenin (528.78 µg/mL), rutin (194.39 µg/mL), quercetin (295.25 µg/mL), and cinnamic acid (37.50 µg/mL). CSNPs and A. vera gel incorporated with CSNPs were examined via TEM, indicating mean sizes of 83.46 nm and 36.54 nm, respectively. FTIR spectra showed various and different functional groups in CSNPs, A. vera gel, and A. vera gel incorporated with CSNPs. Two strains of H. pylori were inhibited using A. vera gel with inhibition zones of 16 and 16.5 mm, while A. vera gel incorporated with CSNPs exhibited the highest inhibition zones of 28 and 30 nm with resistant and sensitive strains, respectively. The minimal inhibitory concentration (MIC) was 15.62 and 3.9 µg/mL, while the minimal bactericidal concentration (MBC) was 15.60 and 7.8 µg/mL with MBC/MIC 1 and 2 indexes using A. vera gel and A. vera gel incorporated with CSNPs, respectively, against the resistance strain. DPPH Scavenging (%) of the antioxidant activity exhibited an IC50 of 138.82 μg/mL using A.vera gel extract, and 81.7 μg/mL when A.vera gel was incorporated with CSNPs. A.vera gel incorporated with CSNPs enhanced the hemolysis inhibition (%) compared to using A.vera gel alone. Molecular docking studies through the interaction of chlorogenic acid and pyrocatechol as the main components of A. vera gel and CSNPs with the crystal structure of the H. pylori (4HI0) protein supported the results of anti-H. pylori activity.
Obesity is well associated as being an interfering factor in metabolic diseases such as hypertension and diabetes by increasing the secretion of proinflammatory markers from adipose tissue. Having ...healthy effects, vitamin C could work as an anti-inflammatory agent through its antioxidant capacity.
FPSK_Mac 1304.
The aim of the study reported here was to identify the effect of vitamin C on reducing the levels of inflammatory markers in hypertensive and/or diabetic obese adults.
Sixty-four obese patients, who were hypertensive and/or diabetic and had high levels of inflammatory markers, from primary health care centers in Gaza City, Palestine, were enrolled into one of two groups in an open-label, parallel, randomized controlled trial. A total of 33 patients were randomized into a control group and 31 patients were randomized into an experimental group. The experimental group was treated with 500 mg vitamin C twice a day.
In the experimental group, vitamin C significantly reduced the levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), fasting blood glucose (FBG), and triglyceride (TG) after 8 weeks of treatment (overall: P<0.001); no changes appeared in total cholesterol (TC). In the control group, there were significant reductions in FBG and TG (P=0.001 and P=0.026, respectively), and no changes in hs-CRP, IL-6, or TC. On comparing the changes in the experimental group with those in the control group at the endpoint, vitamin C was found to have achieved clinical significance in treating effectiveness for reducing hs-CRP, IL-6, and FBG levels (P=0.01, P=0.001, and P<0.001, respectively), but no significant changes in TC or TG were found.
Vitamin C (500 mg twice daily) has potential effects in alleviating inflammatory status by reducing hs-CRP, IL-6, and FBG in hypertensive and/or diabetic obese patients.
The current study was designed to evaluate the potential abatement effect of pantoprazole against cisplatin-induced nephrotoxicity and establishing the possible protective mechanisms. Thirty-two male ...mice were allocated for treatment with saline, single dose of cisplatin (10 mg/kg/i.p), pantoprazole (30 mg/kg/once daily) for 5 days or combination of pantoprazole and cisplatin for 5 days. Urine, blood, and both kidneys were collected for further evaluations. Pantoprazole significantly countermand cisplatin-induced disfigurement of renal histology, kidney weight to body weight ratio, serum levels of creatinine and urea, and microalbuminuria. Furthermore, pantoprazole mostly normalized cisplatin-induced distortion of renal levels of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, interleukin-10) and renal content of apoptosis regulating protein expressions (Bax, Bcl2, and active caspase 3). In addition, pantoprazole significantly subsided cisplatin-induced distortion of renal lipid peroxidation marker (MDA), renal superoxide dismutase, and catalase activities and renal reduced glutathione content. This study provides an evidence for the protective utility of short-term pantoprazole against cisplatin-induced nephrotoxicity in mice. The protective mechanism of pantoprazole could be through diminution of cisplatin-induced inflammation, oxidative stress, and their subsequent apoptotic renal cell death via abatement of apoptosis regulating protein expressions (Bax, Bcl2, and active caspase3).
Abstract Background To find out the differences on biomedical data between obese and non-obese participants, and to identify risk factors associated with systemic inflammation in healthy Palestinian ...adults. Methodology A cross-sectional study involved 105 apparently healthy adults. Interview questionnaire was used to collect personal information. Participants were excluded if they suffered from acute or chronic inflammatory diseases, or continued using medicines, which might affect the biomedical results. Results In association with increased body mass index (BMI), the obese group displayed significant higher markers including: interleukin 6 (IL-6), high sensitivity C reactive protein (hs-CRP), total cholesterol (TC), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Obese group in association with increased waist circumference (WC) was higher significantly in inflammatory markers (IL-6, hs-CRP), lipid profile (TC) and triglyceride (TG), and blood pressure (SBP, DBP). A tertile of a feature of systemic inflammation (hs-CRP) was created, by Ordinal Logistic Regression, after adjusting for the age, gender, smoking habits, physical activity pattern, father and mother's health history; risk factors were the increased BMI OR: 1.24 (95%CI: 1.005–1.548, P = 0.050), IL-6 OR: 3.35 (95%CI: 1.341–8.398, P = 0.010), DBP OR: 1.19 (95%CI: 1.034–1.367, P = 0.015), and reduced Adiponectin OR: 0.59 (95%CI: 0.435–0.820, P = 0.001). Finally, BMI correlated with IL-6 and hs-CRP ( r = 0.326, P = 0.005; r = 0.347, P˂0.001; respectively), hs-CRP correlated with IL-6 ( r = 0.303, P = 0.010), and inversely with Adiponectin ( r = − 0.342, P = 0.001). Conclusion The increased level of IL-6 and reduced Adiponectin, which strongly associated with obesity indicated that having high BMI is a useful marker in association with IL-6 and further developed systemic inflammation.
PDF
