Mohammad A. Alzohairy

Green synthesis of silver nanoparticles and characterization of their inhibitory effects on AGEs formation using biophysical techniques.

Advanced glycation end-products (AGEs) resulting from non-enzymatic glycation are one of the major factors implicated in secondary complications of diabetes. Scientists are focusing on discovering new compounds that may be used as potential AGEs inhibitors without affecting the normal structure and function of biomolecules. A number of natural and synthetic compounds have been proposed as AGE inhibitors. In this study, we investigated the inhibitory effects of AgNPs (silver nanoparticles) in AGEs formation. AgNPs (~30.5 nm) synthesized from Aloe Vera leaf extract were characterized using UV-Vis spectroscopy, energy-dispersive X-ray spectroscopy (EDX), high resolution-transmission electron microscopy, X-ray diffraction and dynamic light scattering (DLS) techniques. The inhibitory effects of AgNPs on AGEs formation were evaluated by investigating the degree of reactivity of free amino groups (lysine and arginine residues), protein-bound carbonyl and carboxymethyl lysine (CML) content, and the effects on protein structure using various physicochemical techniques. The results showed that AgNPs significantly inhibit AGEs formation in a concentration dependent manner and that AgNPs have a positive effect on protein structure. These findings strongly suggest that AgNPs may play a therapeutic role in diabetes-related complications.

Therapeutics Role of Azadirachta indica (Neem) and Their Active Constituents in Diseases Prevention and Treatment

Neem (Azadirachta indica) is a member of the Meliaceae family and its role as health-promoting effect is attributed because it is rich source of antioxidant. It has been widely used in Chinese, Ayurvedic, and Unani medicines worldwide especially in Indian Subcontinent in the treatment and prevention of various diseases. Earlier finding confirmed that neem and its constituents play role in the scavenging of free radical generation and prevention of disease pathogenesis. The studies based on animal model established that neem and its chief constituents play pivotal role in anticancer management through the modulation of various molecular pathways including p53, pTEN, NF-κB, PI3K/Akt, Bcl-2, and VEGF. It is considered as safe medicinal plants and modulates the numerous biological processes without any adverse effect. In this review, I summarize the role of Azadirachta indica in the prevention and treatment of diseases via the regulation of various biological and physiological pathways.

Therapeutic Implications of Black Seed and Its Constituent Thymoquinone in the Prevention of Cancer through Inactivation and Activation of Molecular Pathways

The cancer is probably the most dreaded disease in both men and women and also major health problem worldwide. Despite its high prevalence, the exact molecular mechanisms of the development and progression are not fully understood. The current chemotherapy/radiotherapy regime used to treat cancer shows adverse side effect and may alter gene functions. Natural products are generally safe, effective, and less expensive substitutes of anticancer chemotherapeutics. Based on previous studies of their potential therapeutic uses, Nigella sativa and its constituents may be proved as good therapeutic options in the prevention of cancer. Black seeds are used as staple food in the Middle Eastern Countries for thousands of years and also in the treatment of diseases. Earlier studies have shown that N. sativa and its constituent thymoquinone (TQ) have important roles in the prevention and treatment of cancer by modulating cell signaling pathways. In this review, we summarize the role of N. sativa and its constituents TQ in the prevention of cancer through the activation or inactivation of molecular cell signaling pathways.

Staphylococcus aureus nasal carriage among outpatients attending primary health care centers: a comparative study of two cities in Saudi Arabia and Egypt

Epidemiological and molecular data on community acquired methicillin resistant Staphylococcus aureus (CA-MRSA) are still scarce in both Egypt and Saudi Arabia. There is almost no data regarding methicillin resistant Staphylococcus aureus (MRSA) prevalence in both countries. This study was conducted to investigate the prevalence and molecular epidemiology of S. aureus and MRSA nasal carriage among outpatients attending primary health care centers in two big cities in both countries. A total of 206 nasal swabs were obtained, 103 swabs from each country. S. aureus isolates were characterized by antibiotic susceptibility, presence of mecA and PVL genes, SCCmec-typing and spa typing, the corresponding Multi locus sequence typing clonal complex was assigned for each spa type based on Ridom StaphType database. MRSA was detected in 32% of the Egyptian outpatients while it was found in 25% of the Saudi Arabian outpatients. All MRSA isolates belonged to SCCmec type V and IVa, where some isolates in Saudi Arabia remained nontypeable. Surprisingly PVL(+) isolates were low in frequency: 15% of MRSA Egyptian isolates and 12% of MRSA isolates in Saudi Arabia. Two novel spa types were detected t11839 in Egypt, and t11841 in Saudi Arabia. We found 8 spa types among 20 isolates from Egypt, and 12 spa types out of 15 isolates from Saudi Arabia. Only two spa types t008 and t223 coexisted in both countries. Four clonal complexes (CC5, CC8, CC22, and CC80) were identified in both Egypt and Saudi Arabia. However, the data collected lacked a representation of isolates from different parts of each country as only one health center from each country was included, it still partially illustrates the CA-MRSA situation in both countries. In conclusion a set of control measures is required to prevent further increase in MRSA prevalence.

Antimicrobial potential of bacteriocins: in therapy, agriculture and food preservation.

Due to the appearance of antibiotic resistance and the toxicity associated with currently used antibiotics, peptide antibiotics are the need of the hour. Thus, demand for new antimicrobial agents has brought great interest in new technologies to enhance safety. One such antimicrobial molecule is bacteriocin, synthesised by various micro-organisms. Bacteriocins are widely used in agriculture, veterinary medicine as a therapeutic, and as a food preservative agent to control various infectious and food-borne pathogens. In this review, we highlight the potential therapeutic and food preservative applications of bacteriocin.

In Silico Analysis of Green Tea Polyphenols as Inhibitors of AChE and BChE Enzymes in Alzheimer's Disease Treatment.

Alzheimers disease (AD) is the most frequent cause of dementia, especially in the elderly. AD is the most common progressive neurodegenerative disorder, which involves the loss of structure and function of cholinergic neurons. Moreover, if these neuronal changes cannot be compensated, this may ultimately lead to neurodegenerative processes. Therefore, most of the drug therapies are based on the cholinergic hypothesis, which suggests that AD begins as a deficiency in the production of the neurotransmitter acetylcholine. In this context, many inhibitors play an important role in AD treatment among which acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have more potential in the treatment process of AD. In this study, we selected tea polyphenols of green tea which are reported as AChE and BChE inhibitors used in the treatment of AD. The molecular docking results revealed that polyphenols exhibit interactions and inhibit by binding with AChE and BChE. The amount of energy to bind with AChE and BChE needed by Epigallocatechin-3-gallate was lowest at about -14.45 and -13.30 kcal/mol, respectively. All compounds showed binding energy values ranging between -14.45 to -9.75 kcal/mol for both types of enzymes. The present docking study suggests that tea polyphenols inhibit AChE as well as BChE and enhance the cholinergic neurotransmission by prolonging the time. However, AChE molecules remain in the synaptic cleft. In consideration to these findings, cholinesterase inhibitors are suggested as the standard drugs for the treatment of AD.

Antiglycating Potential of Gum Arabic Capped-Silver Nanoparticles

Advanced glycation end products are major contributors to the pathology of diabetes, Alzheimer’s disease, and atherosclerosis; accordingly, identification of antiglycation compounds is attracting considerable interest. In the present study, the inhibitory effect of gum arabic capped-silver nanoparticles on advanced glycation end products formation was monitored by several biophysical techniques. Silver nanoparticles were characterized by ultraviolet–visible, high-resolution transmission electron microscopy, and energy-dispersive X-ray spectroscopy. Bovine serum albumin and methylglyoxal mixtures incubated with increasing concentrations of silver nanoparticles showed significant reductions in advanced glycation end product formation that were confirmed by ultraviolet–visible, fluorescence spectrometry, and high-performance liquid chromatography techniques. High-performance liquid chromatography showed decreased adduct formation of glycated protein in the presence of silver nanoparticles. The structural changes induced by silver nanoparticles were further confirmed by circular dichroism and Fourier transform infrared spectroscopy. Strong inhibition of advanced glycation end product formation was observed in the presence of elevated silver nanoparticles. The results of this study suggest that silver nanoparticles are a potent antiglycating agent.

Inflammatory markers and haptoglobin polymorphism in Saudi with non-insulin-dependent diabetes mellitus.

Objectives: Haptoglobin (Hp) polymorphism associated with clinical evolution of several inflammatory diseases and considered as a predictive factor for development of diabetes complications. We designed the present study to investigate the frequency distribution of Hp phenotypes among Saudi with non-insulin-dependent diabetes mellitus compared to healthy nondiabetic subjects. Moreover, we explored the possibility of relationship between serum levels of inflammatory markers (namely, high-sensitive C-reactive proteins “hs-CRP”, interleukin (IL)-6, and Hp) and Hp phenotypes. Methods: In the present case-control study, we enrolled 60 type 2 diabetic patients as the study group and 60 healthy subjects as the control group. We assayed serum levels of Hp and hs-CRP by immunoturbidimetric method; while IL-6 was measured by ELISA. Native polyacrylamide gel electrophoresis was used for determination of Hp phenotypes. Results: In type 2 diabetics, serum concentrations of IL-6, hs-CRP, and Hp were significantly elevated and correlated to body mass index. Moreover, there was a significant correlation between plasma glucose level and Hp (r = 0.577, p = 0.000), IL-6 (r = 0.448, p = 0.000), and hs-CRP (r = 0.380, p = 0.001). In addition, data demonstrated a positive correlation between HbA1c and Hp (r = 0.521, p = 0.000), IL-6 (r = 0.420, p = 0.001), and hs-CRP (r = 0.353, p = 0.008). Hp 2-1 phenotype predominated among subjects in both study and control groups. No significant association between Hp phenotypes with any of the investigated inflammatory markers was documented. Conclusion: Inflammation may represent the link between type 2 diabetes and obesity. Hp 2-1 was the predominant phenotype among Saudi type 2 diabetics as well as healthy subjects. In addition to Hp; other possible genetic polymorphisms like CRP may have its effect on diabetes through different mechanisms.

Effect of chronic unpredictable stress on short term dietary restriction and its modulation by multivitamin-mineral supplementation

Dietary restriction (DR) lowers steady-state levels of oxidative stress and alters behavioral, physiological and biochemical responses in mammals. However, various factors effect its application in humans like socio-cultural, appetite and the daily life stress. Physiological and psychological stress owing to fast-paced lifestyles, translates into oxidative stress. In this work, the role of chronic unpredictable stress (CUS) on the effects of short term DR in mice in terms of biochemical and oxidative stress parameters was investigated. Further, the modulatory role of multivitamin-mineral supplement (MVM) on CUS and DR induced biochemical changes was studied to delineate the role of micronutrient supplementation. DR treatment increased the antioxidant status in the circulation and liver of mice but in the presence of chronic stressors there was a significant shift towards the pro-oxidant state. A decrease was found in the activities of antioxidant enzymes superoxide dismutase, catalase, and glutathione-S-transferase and glutathione reductase in the rats exposed to CUS with DR (CUS+DR), with an increased malondialdehyde and a decreased glutathione (GSH) levels as compared to the controls. Liver function enzymes-glutamate oxaloacetate transaminase and glutamate pyruvate transaminase were increased and a significant DNA damage was observed. Oral MVM supplement significantly improved this oxidative deterioration. Hence, MVM supplementation appears to potentially offer an effective intervention in the DR regimen to combat daily life physical and mental stress.

Biochemical, histopathological, and transmission electron microscopic ultrastructural changes in mice after exposure to silver nanoparticles

Four‐week‐old mice, weighing about 25–35 g were divided into five groups (8 mice in each group): vehicle control, low‐ (0.5 g/kg), middle‐ (1 g/kg), high‐ (3 g/kg), and exceptionally high‐dose (5 g/kg). After first and second weeks of intraperitoneal exposure to AgNPs, biochemical, histopathological, and electron microscopic ultrastructural changes were investigated. No significant changes were observed in SGOT and ALP levels after first week of exposure, while the level of SGPT significantly increased (p < 0.05) in 2nd week treated mice, indicating that inflammatory of liver might be induced by high‐dose (3 and 5 g/kg) of AgNPs. No obvious changes were observed for UA and BUN in all groups of treated mice. However, significant (p < 0.05) decrease in CR level was noticed in all groups of treated mice only at high‐dose (3 and 5 g/kg). No remarkable changes in lipid profile were observed. Light microscopic histopathological investigation shows that first week treatment had not perceptible effect on the cytoarchitecture on liver, kidney, and spleen; while, second week treatment had only sporadic mild effects on these organs. However, no ultrastructural electron microscopic changes were observed in liver, kidney, and spleen of mice treated with 0.5, 1, and 3 g/kg of AgNPs when sacrificed on first and second week; while, exceptionally high‐dose (5 g/kg) of AgNPs resulted in slight nuclear chromatin condensation and irregularities in nuclear membrane. The results suggested that AgNPs could be well tolerated in mice when given intraperitoneally and no death has been found during the experiment in any groups of treated mice. Interestingly, significant (<0.05) decrease in glucose levels in all experiment group is suggestive of curious hypoglycemic role of AgNPs warranting further study to explore its possible therapeutic potential in hyperglycemic conditions as well as its mechanism of action at molecular level.