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Serum total and free calcium reflect the status of the body health and disease. Smoking is risk factor for many diseases as cardiovascular, lung, and cancers. The goal of this work is to evaluate the correlation between serum lead, cadmium arsenate resulting from passive smoking, and bone status in females. This study was conducted on two hundred women (age 30-50 years) divided into four groups (each 50). Group I, control, included non-smoking healthy women. Group II included heavy smoker (>20 cigarettes/day). Group III, nonsmoker women with osteoporosis, have many fractures. Group IV, smoking women with osteoporosis, included heavy smokers (>20 cigarettes/day) with osteoporotic women and have many fractures. Data obtained showed that T-score of osteoporotic smokers was -3.5 that indicated reduced bone mineral density (BMD) while serum total and ionized calcium were statistically significant decreased in smokers with or without osteoporosis compared with nonsmokers (p < 0.001). A negative correlation between total and free calcium and cadmium levels in smokers was compared with nonsmokers (r =-0.65). The levels of C-terminal pro-peptide of pro-collagen type I (PICP) and N-terminal pro-peptide of procollagen type I (PINP) were higher in smoker osteoporotic women than nonsmokers. It was concluded that cadmium resulting from smoking may compete with absorption of calcium and reduced its level and BMD and increased incidence of osteoporosis. The elevated PICP and PINP indicated decreased rate of proto collagen I turnover in bone tissue and increased incidence of osteoporosis.

Acute rheumatic fever (ARF) triggered by Group A streptococcus bacterium due to post-infectious and non-supportive pharyngeal infection. Depending on certain conditions, such as genetic predisposition to the disease, the prevalence of various cases of rheumatism and socioeconomic status in different regions, ARF can have different clinical manifestations. The disease typically manifested by one or more acute episodes, whereas 30-50% of all repeated ARF status can result in chronic rheumatic heart disease (RHD) with gradual and irreversible heart valve damage and also have been found to be correlated with a raised risk of myocardial infarction (MI), cardiovascular disease (CVD) and dyslipidemia. The RHD is the only long-term consequence of ARF and the most serious. The development to chronic RHD is determined by many factors, most notably the frequent episodes of rheumatic fever (RF). The RHD is known socially and economically as being the most frequent heart disease in vulnerable populations. H.pylori infection has been proposed to be involved RHD greater than that of the normal healthy people. H.pylori can be considered as one of the probable risk factor for RHD.It was concluded that patients with H. Pylori should be advised to follow up in cardiology clinics to avoid any complications.

Amongst the various types of cancer, breast cancer is a highly heterogeneous disease and known as the leading cause of death among women globally. The extensive interdisciplinary investigation in nanotechnology and cancer biomedical research has been evolved over the years for its effective treatment. However, the advent of chemotherapeutic resistance in breast cancer is one of the major confront researchers are facing in achieving successful chemotherapy. Research in the area of cancer nanotechnology over the years have now been revolutionized through the development of smart polymers, lipids, inorganic materials and eventually their surface-engineering with targeting ligands. Moreover, nanotechnology further extended and brings in the notice the new theranostic approach which combining the therapy and imaging simultaneously. Currently, research is being envisaged in the area of novel nano-pharmaceutical design viz. liposome, nanotubes, polymer lipid hybrid system, which focuses to make the chemotherapy curative and long-lasting. In this review, we aimed to discuss the recent advancement of different surface-engineered/targeted nanomedicines that improved the drug efficacy in breast cancer.

Background: Viral hemorrhagic fevers (VHF) refers to a group of febrile illnesses caused by different viruses that result in high mortality in animals and humans. Many risk factors like increased human-animal interactions, climate change, increased mobility of people and limited diagnostic facility have contributed to the rapid spread of VHF. Materials: The history of VHFs in the Saudi Arabian Peninsula has been documented since the 19th century, in which many outbreaks have been reported from the southwestern region of Saudi Arabia. Despite presence of regional network of experts and technical organizations, which expedite support and respond during outbreaks, there are some more challenges that need to be addressed immediately. Gaps in funding, exhaustive and inclusive response plans and improved surveillance systems are some areas of concern in the region which can be dealt productively. This review primarily focusses on the hem- orrhagic fevers that are caused by three most common viruses namely, the Alkhurma hemorrhagic fever virus, Rift valley fever virus, and Dengue fever virus. Conclusion: In summary, effective vector control, health education, possible use of vaccine and concerted synchronized efforts between different government organizations and private research institutions will help in planning effective out- break-prevention and response strategies in future. Keywords: Viral fever; hemorrhagic fever (VHF); Saudi Arabia; challenges; management; future considerations.

The elevated blood sugar slowly attacks reactive amino group of functional proteins and impairs its functions, generates reactive oxygen species (ROS) as byproduct and increases risk of cancer. Bioactive peptides might act as protecting agent via trapping excess sugar. In this study, the bioactivity of peptides from Vicia faba by tryptic digestion was evaluated as antiglycation, antioxidant and antiproliferative assays. Results obtained indicated that V. faba peptides fractions

This study investigated the in vitro antioxidant, proapoptotic and anti-proliferative activity of phycocyanin extracted from Ulva lactuca (Chlorophyta) algae extract loaded on albumin nanoparticle (ULANP). The characterization of ULANP profile was done by using FTIR and its cytotoxicity was investigated by using MTT assay against HepG2 and MCF7 cell lines. The proapoptotic markers caspase 8 & 9 were measured. Analysis of ULANP by FTIR showed the characteristic band (2100 cm−1 ~3700 cm−1) that is indicated primarily by COO, CO and conjugated double bond. These bonds showed the spectral band at peaks of 2985 cm−1 and 2860 cm−1, 2986 cm−1 respectively. The antioxidant potential and radical scavenging property of ULANP was also appreciable as compared to the vitamin C and gallic acid. The antiproliferative assay carried out by WST-1 suggests that ULANP was effective against both HepG2 (93.17%) and MCF7 (91.3%). Caspase-8 and −9 were significantly elevated (p

Background: The metabolic pathways can be affected by dysregulation in thyroid hormone levels which in turn can arise from environmental chemical exposure. This study investigated the association of selected trace elements with thyroid dis- orders in a Saudi population. Methods: Urine samples collected from 100 participants (50 thyroid disorder patients and 50 controls) were analyzed to determine trace elements using inductively coupled plasma-mass spectrometer. Non-parametric Mann-Whitney Test, were used to examine the association between socio-demographic as well as clinical characteristics of thyroid profile levels (T3,T4 and TSH) and urinary trace element concentrations. Results: Urine from patients with thyroid disorders had significantly higher concentrations of Ni, Cu, and Cd (p-values

Nowadays, phthalates widely employed in many products are distributed around us which contributed to the development of many chronic diseases. We investigated the incidence of type 2 diabetes mellitus (T2DM) in Saudi subjects and correlated it with urinary phthalate metabolites' screening study.We selected a total of 100 cases early diagnosed as type 2 diabetes mellitus (FBS ≥ 126 mg/dl, PP 2 h, ≥ 140 mg/dl) and 50 normal subjects (FBS ≤ 90 mg/dl) as control. Overnight fasting blood samples were subjected for assay of FBS, glycated hemoglobin, insulin, C-peptide, HOMA-IR, advanced glycation end products (AGEs), and urinary assay of some phthalate metabolite levels.Data obtained showed a significant elevation of FBS, HA1c, AGEs, insulin, and C-peptide and HOMA-IR in diabetic patients compared with the control (p 0.001). Urinary phthalate metabolites such as mono-ethyl phthalate (mEP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), and mono-n-butyl phthalate (mBP) were detected in significant concentrations in diabetic patients compared with control. A positive correlation was found between mEP and mBP and HOMA-IR and C-peptide.Phthalate toxicity is considered as one of the risk factors that contributed to insulin resistance and development of T2DM via increasing the levels of HOMA-IR and C-peptide.This will result in the risk of phthalate exposure for diabetogensis and its economic cost for treatment lifetime.

Introduction The typical herpes simplex viral encephalitis (HSVE) course is an acute illness, less commonly it may present as a chronic course, mainly in children, and rarely may it be subacute. Subacute HSVE is rarely described in the literature being reported 4 times only. Case report We here report 2 cases of subacute HSV1 encephalitis diagnosed based on cerebrospinal fluid polymerase chain reaction and magnetic resonance imaging findings and review the literature trying to find any specific clinical, laboratory, radiologic diagnostic or prognostic criteria regarding this subacute form of HSVE. Conclusion There is subacute form of HSVE and should be suspected with any subacute febrile illness with nonspecific cognitive impairment even in the absence of focal neurological symptoms and in cases with rapidly progressive dementia. This form has similar radiologic finding and good response to acyclovir but carry even better prognosis than that the acute HSVE.

The rational of this study to find out the impact of auxins in prevention of diabetic complications in rats. Seventy-five rats were randomly grouped into five groups: Group I; control (n = 15). (Groups 2-5, 60 rats) were received a single dose of STZ i.p, at dose of 65 mg/kg for induction diabetes. Group II; diabetic untreated. Group III; Rats were given auxin subcutaneous (2.5 µg/kg b.w). Group IV; rats were given auxin (5 µg/kg b.w). Group V; rats were injected insulin (5 units/kg b.w/day) as positive control. Treatment of diabetic rats with auxin (2.5 or 5 ug/kg b.w) for 8 weeks reversed the oxidant/antioxidant imbalance. The protective effect of auxin due to defence against oxygen free radicals production in retinal tissue. Also, auxin inhibit formation of AGEs and inhibit release of inflammatory mediators. It was concluded that, auxin may be used as promising therapeutic agents against diabetic complications.

Human exposure to phthalates is ubiquitous and has received considerable attention due to their association with adverse health outcomes, including type 2 diabetes mellitus (T2DM). Nevertheless, earlier studies that link phthalate exposure to T2DM yielded ambiguous results. Furthermore, studies that associate phthalate exposure with oxidative stress and then with T2DM are scant. In this diabetic case-control study, urine samples collected from 101 individuals aged 28–68 years from Jeddah, Saudi Arabia, were analyzed to determine 20 phthalate metabolites (PhMs) and seven oxidative stress biomarkers (OSBs). Unconditional logistic regression was used to estimate odds ratios for the association between diabetes and urinary PhMs and OSBs in participants, stratified by age, gender, nationality, smoking status, occupation, and urinary creatinine. Twelve PhMs and five OSBs were found at detection rates above 50%, with geometric mean concentrations of 0.61–100 and 0.35–10.7 ng/mL (1.04–171 and 0.61–18.6 μg/g creatinine), respectively. Almost all exposures were significantly higher in diabetic cases than in controls. The 12 PhMs were positively associated with higher urinary concentrations of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-PGF2α). Individuals in the 3rd and/or 4th quartile(s) for urinary concentrations of PhMs and OSBs showed 3.7- and 7.3-fold increase, respectively, in the odds of having diabetes compared with those in the 1st quartile. The rank order of association of PhMs/OSBs with diabetes followed the order of: mEP ≈ mBP > mEHP > mCPP > mECPP ≈ mEOHP ≈ mEHHP ≈ mIBP ≈ mMP > mCMHP ≈ mBzP and 8-OHdG > 8-PGF2α ≈ 15-PGF2α. The relationship between phthalate exposure and risk of developing T2DM was mediated in part by phthalate-induced oxidative stress, especially 8-OHdG. Our study suggests that human exposure to phthalates is associated with increased oxidative stress which mediates the development of T2DM. Keywords: Diabetes, Phthalate metabolites, Oxidative stress, Biomonitoring, Urine

Aim: This study evaluated the effect of Phyocyanin extracted from Chlorophyta Ulva lactuca algae loaded on albumin nano-particles (ULANP) on diabetic rats. Materials and Methods: Fifty albino rats were divided into 5 goups. GPI: control and GPII: rats were injected with alloxan (75 mg /kg) i.p for six consecutive days for induction of diabetes. This group was subdivided into 4 subgroups: GP IIa: (Untreated diabetic): GP IIb: rats were given with ULANP (100 mg/kg).GP IIc: Rats were given ULANP (200 mg/kg) i.p. GP IId: Rats were given insulin (100 unit/ day). Serum NO, interleukin-6 glucose, AGEs and fatty acids profile was determined. Results: Analysis of ULANP by FTIR showed the characteristic band (2100 cm-1~ 3700 cm-1) that is indicated mainly from -COO, – CO and conjugated double bond. These bonds showed spectral bands peak 2985 cm-1 and 2860 cm-1, 2986 cm-1. Administration of ULANP in diabetic rats exerted an anti-inflammatory by lowering NO and IL-6 levels and hypoglycemic effects by decreased glucose and reduced AGEs levels. In addition, ULAPN lowered percent of saturated fatty acids while elevated unsaturated fatty acids percent. Conclusion: It was concluded that, ULAPN is a promising effective anti-inflammatory and hypoglycemic agent compared with other therapeutic agents with lower site effects.

Background: Oxidative stress is defined as imbalance between oxidant and antioxidant ratio, that lead to oxidative damage of biologically active molecules, finally lead to different disease and initiate carcinogenesis. The drug discovery using natural products as medicinal plants or marine organism still an important target for recent research. This study investigated anticancer activity of algae extract obtained from Red sea at Jeddah. Materials and Methods: Aqueousand methanol extracts ofDictyotaciliolata(DC) were tested on HCT-116 and HepG2 cell lines using WST-1. Aqueous extract (AEDC) and methanol extract (MEDC) at doses 0.05, 0.1, 0.5, 1 mg/ml and positive control 0.3% H2O2 at doses 0.5 mg/ml for 24,48 and 72 h (for two cell lines). Results: AEDC showed the mosteffective antitumor activity against HCT116 and HePG2, the IC50 dose for HCT116 cells was 0.05 mg/ml at 72 h, while for the HePG2 it was 0.01 mg/ml at 72 h. These results showed that HePG2cells was more sensitive to the AEDC. However, IC50 for MEDC were 0.01 mg/ml for HCT116 and 0.05 for HepG2 at 48 Hrs. The algae extracts contain sulfated polysaccharides and different pigments as chlorophylls, carotenoids and phycobiliproteins. These pigments were approved as biological active biomolecules that exert different biological activities as antioxidants, antitumor and rich source of micronutrients. In addition, AEDC or MEDC exert apoptotic activity by increase activity of caspase 3 and 9 in HepG2. Conclusıon: The antitumor effect of AEDC or MEDC is promising for development of chemotherapeutic agent as effective with no side effects.

This study investigated the impact of Shikimic Acid (SA) obtained from leaves of Artemisia absinthium on protein glycation in the retina of diabetic rats. The GC/MS analysis of A. absinthium showed that the most abundant bioactive compound was SA (C7H10O5) with a measured retention Index (RI) of 1960 compared to that of the reference sample (1712). Male albino rats were divided into two main groups, Group I (control) and Group II (diabetic); Group II was further divided into four subgroups: Group IIa (diabetic control), Group IIb (diabetic rats were given SA orally [50 mg/kg, body weight (bw)/day], Group IIc diabetic rats were given SA orally [100 mg/kg, bw/day], and Group IId (diabetic rats were given metformin orally [100 mg/kg, bw/day] as positive control). The data obtained suggested that SA reduced glucose and glycated hemoglobin levels. In addition, SA also decreased the formation of glucose-derived advanced glycation end products. Interestingly, SA showed interference with the release of inflammatory mediators in retina and possess antioxidant potential. In conclusion, SA protected the tissues from detrimental effects of hyperglycemia and enhanced antioxidant activity. SA could be a potential lead in the process of drug development in the future to prevent retinopathy in diabetic subjects.

Long non-coding RNAs (lncRNAs), a type of cellular RNA, play a critical regulatory role in several physiological developments and pathological processes, such as tumorigenesis and tumor progression. Obesity is a risk factor for a number of serious health conditions, including breast cancer (BC). However, the underlying mechanisms behind the association between obesity and increased BC incidence and mortality remain unclear. Several studies have reported changes in lncRNA expression due to obesity and BC, independently encouraging further investigation of the relationship between the two in connection with lncRNAs. The present study was designed to first screen for the expression of 29 selected lncRNAs that showed a link to cancer or obesity in the blood of a selected cohort of 6 obese and 6 non-obese patients with BC. The expression levels of significantly expressed lncRNAs, AP001429.1, PCAT6, P5549, P19461 and P3134, were further investigated in a larger cohort of 69 patients with BC (36 obese and 33 non-obese), using reverse transcription-quantitative polymerase chain reaction. Results showed not only that AP001429.1 remained significantly downregulated in the larger cohort (P=0.002), but also that it was associated with several clinicopathological characteristics, such as negative HER2 status, negative E-cadherin expression, negative vascular invasion, negative margin invasion and LCIS. These findings suggest that obesity may have a role in inhibiting AP001429.1 expression, which may serve as a novel potential biomarker and therapeutic target for BC.

Bioactive peptides produced from natural sources are considered as strategic target for drug discovery. Hyperglycemia caused protein glycation alters the structure of many tissues that impairs their functions and lead complications diseases in human body. This study investigated the bioactive peptides produced from red and brown Lens culinaris that might inhibit protein glycation to prevent diabetic complications. In this study, red and brown Lens culinaris protein hydrolysates were prepared by tryptic digestion, using an enzyme/substrate ratio of 1:20 (g/g), at 37°C, 12 hr then peptide fractions

SARS coronavirus (COVID-19) is a real health challenge of the 21st century for scientists, health workers, politicians, and all humans that has severe cause epidemic worldwide. The virus exerts its pathogenic activity through by mechanism and gains the entry via spike proteins (S) and Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins on host cells. The present work is an effort for a computational target to block the residual binding protein (RBP) on spike proteins (S), Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins by probiotics namely Plantaricin BN, Plantaricin JLA-9, Plantaricin W, Plantaricin D along with RNA-dependent RNA polymerase (RdRp). Docking studies were designed in order to obtain the binding energies for Plantaricin metabolites. The binding energies for Plantaricin W were −14.64, −11.1 and −12.68 for polymerase, RBD and ACE2 respectively comparatively very high with other compounds. Plantaricin W, D, and JLA-9 were able to block the residues (THR556, ALA558) surrounding the deep grove catalytic site (VAL557) of RdRp making them more therapeutically active for COVID-19. Molecular dynamics studies further strengthen stability of the complexes of plantaricin w and SARS-CoV-2 RdRp enzyme, RBD of spike protein, and human ACE2 receptor. The present study present multi-way options either by blocking RBD on S proteins or interaction of S protein with ACE2 receptor proteins or inhibiting RdRp to counter any effect of COVID-19 by Plantaricin molecules paving a way that can be useful in the treatment of COVID-19 until some better option will be available. Communicated by Ramaswamy H. Sarma

Thymoquinone (TQ), a naturally occurring anticancer compound extracted from Nigella sativa oil, has been extensively reported to possess potent anti-cancer properties. Experimental studies showed the anti-proliferative, pro-apoptotic, and anti-metastatic effects of TQ on different cancer cells. One of the possible mechanisms underlying these effects includes alteration in key metabolic pathways that are critical for cancer cell survival. However, an extensive landscape of the metabolites altered by TQ in cancer cells remains elusive. Here, we performed an untargeted metabolomics study using leukemic cancer cell lines during treatment with TQ and found alteration in approximately 335 metabolites. Pathway analysis showed alteration in key metabolic pathways like TCA cycle, amino acid metabolism, sphingolipid metabolism and nucleotide metabolism, which are critical for leukemic cell survival and death. We found a dramatic increase in metabolites like thymine glycol in TQ-treated cancer cells, a metabolite known to induce DNA damage and apoptosis. Similarly, we observed a sharp decline in cellular guanine levels, important for leukemic cancer cell survival. Overall, we provided an extensive metabolic landscape of leukemic cancer cells and identified the key metabolites and pathways altered, which could be critical and responsible for the anti-proliferative function of TQ.

Antimicrobial resistance (AMR) is the major issue posing a serious global health threat. Low- and middle-income countries are likely to be the most affected, both in terms of impact on public health and economic burden. Recent studies highlighted the role of resistance networks on the transmission of AMR organisms, with this network being driven by complex interactions between clinical (e.g., human health, animal husbandry and veterinary medicine) and other components, including environmental factors (e.g., persistence of AMR in wastewater). Many studies have highlighted the role of wastewater as a significant environmental reservoir of AMR as it represents an ideal environment for AMR bacteria (ARB) and antimicrobial resistant genes (ARGs) to persist. Although the treatment process can help in removing or reducing the ARB load, it has limited impact on ARGs. ARGs are not degradable; therefore, they can be spread among microbial communities in the environment through horizontal gene transfer, which is the main resistance mechanism in most Gram-negative bacteria. Here we analysed the recent literature to highlight the contribution of wastewater to the emergence, persistence and transmission of AMR under different settings, particularly those associated with mass gathering events (e.g., Hajj and Kumbh Mela).

A few epidemiologic studies suggest that exposure to bisphenol A (BPA) is associated with type 2 diabetes mellitus (T2DM). However, little is known about association between other phenolic endocrine disrupting chemicals (EDCs) and T2DM. In this case-control study, we measured urinary concentrations of 23 phenolic EDCs in 101 individuals from Jeddah, Saudi Arabia, to examine the association of parabens, antimicrobials, bisphenols, benzophenones and bisphenol A diglycidyl ethers with T2DM. Urine samples were collected from 54 T2DM cases and 47 non-diabetic individuals (controls), aged 28-68 years old, during 2015-2016. Unconditional logistic regression was performed to estimate odd ratios (ORs) for the association between diabetes and EDC exposures after adjusting for confounders including age, gender, nationality, smoking status and occupation. Age from 40 to 59 years (OR 5.56, 95% CI 2.20-14.0) and smoking status (OR 2.92, 95% CI 1.25-6.79) showed significant positive associations with T2DM. After adjusting for potential confounders, we found that T2DM cases had high urinary levels of parabens (i.e., methyl- (MeP), ethyl- (EtP), propyl- (PrP) and 4-hydroxy benzoic acid (4-HB)), bisphenols (i.e., bisphenols A (BPA) and F (BPF)), and benzophenone (i.e., 4-hydroxybenzophenone (4-OH-BP)) relative to the controls. Individuals in the 4th quartile for urinary concentrations of MeP, EtP, PrP, 4-HB and BPF and in the 3rd quartile for BPA and 4-OH-BP showed over a 6-fold increase in the odds of having diabetes compared with those in the first quartile. Overall, our study shows that urinary levels of multiple phenolic EDCs were associated with increased risk for diabetes. Further prospective studies are required to verify these associations.

p21Waf1/Cip1, the cyclin-dependent kinase (CDK) inhibitor belonging to the KIP/CIP family, was initially regarded as a tumor suppressor protein because it was recognized as the chief mediator of p53-dependent cell cycle arrest elicited by DNA damage. Conversely, it has been proposed that p21Waf1/Cip1 may also function as an oncogene because it can inhibit apoptosis. Thus, p21Waf1/Cip1 is regarded as a protein with a dual behavior, as its expression might cause potential benefits or dangerous effects in breast cancer. Consequently, careful planning is required in targeting p21Waf1/Cip1 expression for therapy of breast cancer patients. This review illustrates the discovery and mechanisms of induction of p21Waf1/Cip1. Then, we focus on elucidating the paradoxical effect of p21Waf1/Cip1 expression on human breast carcinogenesis and explaining how the subcellular localization (nuclear or cytoplasmic) of p21Waf1/Cip1 has an impact on both determining its fate as either cell-growth inhibitor or antiapoptotic molecule and, its effect on clinicopathological factors and prognosis of breast cancer patients. Moreover, we explore how the pattern of the p21Waf1/Cip1 could affect the responsiveness of human breast cancer to chemotherapy. Furthermore, the pharmacological approaches to target p21Waf1/Cip1 expression for therapy of breast cancer are clarified.

In this study, we investigated the inhibitory effects of m-coumaric acid on the glycosylation of proteins in the retinas of diabetic rats. Male rats were divided into two main groups, Group I (normal control) and Group II (diabetic); Group II was further divided into four subgroups: Group IIa (diabetic control), Group IIb (diabetic rats were given m-coumaric acid orally [150 mg/kg, body weight (bw)/day]), Group IIc (diabetic rats were given HCA m-coumaric acid orally [300 mg/kg bw/day]), and Group IId (diabetic rats were given insulin [10 units/kg bw/day]) as a positive control). The treatment lasted for six weeks, and the data obtained suggested that m-coumaric acid reduced glucose and glycated hemoglobin levels, which further decreased the formation of glucose-derived advanced glycation end products. Hence, it protected the tissues from the detrimental effects of hyperglycemia and enhanced antioxidant activity. In conclusion, m-coumaric acid could be a potential candidate to prevent the onset and progression of retinopathy in diabetic patients.

Background: The current study evaluated level of serum asymmetric dimethylarginine (ADMA) and its association to cardiac biomarkers in thalassemia patients for early diagnosis of abnormality in myocardial infarction. Subjects and methods: This study was conducted on 80 subjects divided into four groups each with 20 subjects. Group I: Control: healthy subjects. Group II: Myocardial infarction: Patients with elevated serum troponin T. Group III: thalassemia patients. Group IV: thalassemia with myocardial infarction patients: Included 20 thalassemia patients with Myocardial infarction. Serum samples were subjected for assay of creatine kinase (CK:MB), Lactate dehydrogenase, troponin I ,ADMA, Serum MDA level was determined. Results: Data obtained showed that serum CKMB, LDH1, AST, Troponin T and ADMA levels were significant elevated in MI with or without Thalassemia compared with control groups. Serum MDA was statistically significantly elevated in MI with or without Thalassemia compared with control groups. The serum level of troponin T showed an area under curve (AUC) of 0.92 ,(sensitivity 91.0 % and specificity, 88%). Also, the ADMA supported the diagnostic profile, showing an AUC of 0.85 with (sensitivity, 92.0%; specificity, 91,9%). Conclusion: Serum ADMA is sensitive marker for incidence of MI in thalassemia patients. Keywords: CKMB, LDH1, AST, Troponin T, asymmetric dimethylarginie, Thalassemia.

Hepatocellular carcinoma is one of the most common causes of cancer-related deaths globally. Bioavailable, effective and safe therapeutic agents are urgently needed for cancer treatment. This study evaluated the metabolomics profiling, anti-proliferative and pro-apoptotic effects of strigol/albumin/chitosan nanoparticles (S/A/CNP) on HepG2 cell line. The diameter of S/A/CNP was (5 ± 0.01) nm. The IC50 was 180.4 nM and 47.6 nM for Strigol1 and S/A/CNP, respectively, after incubation for 24 h with HepG2 cells. By increasing the concentration of S/A/CNP, there was chromatin condensation, degranulation in the cytoplasm and shrinking in cell size indicating pro-apoptotic activity. Metabolomics profiling of the exposed cells by LC/MS/MS revealed that S/A/CNP up-regulated epigenetic intermediates (spermine and spermidine) and down-regulated energy production pathway and significantly decreased glutamine (P

During the early stages of atherosclerosis, monocytes bind and migrate into the endothelial layer, promoting inflammation within the aorta. In order to prevent the development of atherosclerosis, it is critical to inhibit such inflammation. The therapeutic effects of ginger have been investigated in several models of cardiovascular disease. However, although a number of previous studies have focused on specific compounds, the mechanisms of action responsible remain unclear. Here, we investigated five major compounds present in ginger, and observed that gingerenone A exhibited the strongest inhibitory effects against tumor necrosis factor (TNF)-α and lipopolysaccharide (LPS) induced monocyte-endothelial adhesion. Furthermore, gingerenone A significantly suppressed the expression of TNF-α and LPS-induced vascular cell adhesion molecule-1 (VCAM-1) and chemokine (C-C motif) ligand 2 (CCL2), key mediators of the interaction between monocytes, and endothelial cells. Transactivation of nuclear factor-κB (NF-κB), which is a key transcription factor of VCAM-1 and CCL2, was induced by TNF-α and LPS, and inhibited by treatment of gingerenone A. Gingerenone A also inhibited the phosphorylation of NF-κB inhibitor (IκB) α and IκB Kinase. Taken together, these results demonstrate that gingerenone A attenuates TNF-α and LPS-induced monocyte adhesion and the expression of adhesion factors in endothelial cells via the suppression of NF-κB signaling. J. Cell. Biochem. 119: 260-268, 2018. © 2017 Wiley Periodicals, Inc.

Background: The present study was conducted to evaluate the protective role of pomegranate juice alone or in combination with propolis extract against isoproterenol (ISO) induced myocardial infarction in rats.Material and Methods: Male Wister albino rats (n=60) weighing 220-280g were divided into six groups each group contain ten rats; group I: negative control fed standard diet. Group (II-VI): Rats were injected subcutaneously with isoproterenol (150 mg/kg) for 3 days. Group III: Rats were given pomegranate juice 1ml /rat / day. Group IV: Rats were given propolis extract (50 mg/kg BW). Group V: Rats were given pomegranate juice + propolis extract. Group VI: Rats were given glyceronitrate (2.6mg/kg.bw/day).Results: The ISO-induced myocardial infarction in untreated rats has indicated by significant (p < 0.001) elevation of cardiac marker enzymes such as aspartate aminotransferase (AST), Lactate dehydrogenase (LDH), creatine kinase (CK), and cardiac troponin I (CnI ) when compared with control group. Rats treated with pomegranate juice and propolis extracts showed highly significant (p

Background: Aspartame (APM), a common artificial sweetener, has been used for diabetic subjects and body weight control for a long time. The goal of the present study was to evaluate the impact of APM consumption on neurotransmitters and oxidative stress in rat’s brain. Materials and Methods: Four groups of male Wistar albino rats was used: Group1, control (Rats fed on normal diet). Group 2: Rats were received aspartame (50 mg/kg b w). Group3: Rats were received aspartame (75 mg/kg b w). Group 4: Rats were received aspartame (125 mg/kg b w). Five rats were decapitated after 10, 20, 30 and 40 days from start of experiment. Blood and brain tissue were collected for biochemical analysis. Biochemical analysis of brain tissue includes neurotransmitters (Acetylcholine, epinephrine, norepinephrine, γ-aminobutyric acid and serotonin). Serum for determination of lipid peroxidation (MDA), reduced glutathione and superoxide dismutase (SOD). Results: the data obtained showed that antioxidant activities (SOD and GSH) were reduced significantly (p

OBJECTIVE We examined the expression status of p21^{Waf1/Cip1} and p57^{Kip2} in breast cancer as well as their relationship with clinicopathological factors. Moreover, the diagnostic value of gene promoter methylation of p21^Waf1/Cip1 and p57^Kip2 was assessed in breast cancer patients. METHODS This study involved 85 patients diagnosed with breast cancer and 36 patients with benign breast lesions. The expression of p21^{Waf1/Cip1} and p57^{Kip2} in cell lysates was analyzed by ELISA and Western blot, respectively. The gene promoter methylation of p21^Waf1/Cip1 and p57^Kip2 was examined in cell lysates by methylation specific PCR. RESULTS p21^{Waf1/Cip1} expression was higher while p57^{Kip2} level was lower in breast cancer patients compared to patients with benign breast lesions. The combined use of p21^{Waf1/Cip1} and p57^{Kip2} provided sensitivity and specificity of 82.35% and 86.11%, respectively. None of the malignant and benign breast tumors were found to be hypermethylated at p21^Waf1/Cip1 gene promoter. However, aberrant methylation of p57^Kip2 gene promoter was detected in 49 of 85 (57.65%) of breast cancer tumors. High p21^{Waf1/Cip1} level was associated with high grade, late stages and lymph node involvement, whereas low p57^{Kip2} level was correlated with high grade and HER2 overexpressing breast cancer. Moreover, hypermethylated p57^Kip2 gene promoter was associated with high grade. CONCLUSION Our findings show that the overexpression of p21^{Waf1/Cip1}, down-expression of p57^{Kip2} and gene promoter methylation of p57^Kip2 could be considered as promising diagnostic markers for breast cancer.

Background: The goal of this study was identification signaling molecules mediated the formation of AGEs in brain of rats injected with CdCl2 and the role of camel whey proteins and Brassicaceae extract on formation of AGEs in brain.Methods: Ninety male rats were randomly grouped into five groups; Normal control (GpI) and the other rats (groups II-V) were received a single dose of cadmium chloride i.p (5 μg/kg/b.w) for induction of neurodegeneration. Rats in groups III-V were treated daily with whey protein (1g/kg b.w) or Brassicaceae extract (1mg/kg b.w) or combined respectively for 12 weeks.Results: It was found that whey protein combined with Brassicaceae extract prevented the formation of AGEs and enhance the antioxidant activity compared with untreated group (p

Human hepatocellular carcinoma (HCC) is the most common and recurrent type of primary adult liver cancer without any effective therapy. Plant-derived compounds acting as anticancer agents can induce apoptosis by targeting several signaling pathways. Strigolactone (SL) is a novel class of phytohormone, whose analogues have been reported to possess anticancer properties on a panel of human cancer cell lines through inducing cell cycle arrest, destabilizing microtubular integrity, reducing damaged in the DNA repair machinery, and inducing apoptosis. In our previous study, we reported that a novel SL analogue, TIT3, reduces HepG2 cell proliferation, inhibits cell migration, and induces apoptosis. To decipher the mechanisms of TIT3-induced anticancer activity in HepG2, we performed RNA sequencing and the differential expression of genes was analyzed using different tools. RNA-Seq data showed that the genes responsible for microtubule organization such as TUBB, BUB1B, TUBG2, TUBGCP6, TPX2, and MAP7 were significantly downregulated. Several epigenetic modulators such as UHRF1, HDAC7, and DNMT1 were also considerably downregulated, and this effect was associated with significant upregulation of various proapoptotic genes including CASP3, TNF-α, CASP7, and CDKN1A (p21). Likewise, damaged DNA repair genes such as RAD51, RAD52, and DDB2 were also significantly downregulated. This study indicates that TIT3-induced antiproliferative and proapoptotic activities on HCC cells could involve several signaling pathways. Our results suggest that TIT3 might be a promising drug to treat HCC.

Background The role of Notch signaling dysregulation in causing metastatic breast cancer is not yet elucidated, therefore, this study aimed to investigate the expression of DLL4 and JAG1 in metastatic breast cancer. Moreover, we examined the possible association between clinicopathological features and studied parameters. Design and Methods A total of 90 patients with invasive ductal breast carcinomas (52 non-metastatic and 38 metastatic) were enrolled in the current study. Furthermore, there were 42 patients with benign breast diseases. The mRNA and protein expression of DLL4 and JAG1 were analyzed by RT-PCR and ELISA, respectively in breast cell lysates. Results The mRNA and protein expression of DLL4 and JAG1 were obviously higher in patients with breast cancer compared to patients with benign breast diseases and in metastatic versus non-metastatic breast cancer. A significant positive correlation was declared between DLL4 and JAG1 at both mRNA and protein levels in metastatic and localized breast cancer patients. Highly expressed mRNA and protein of DLL4 and JAG1 were associated with late tumor stages; moreover, upregulation of mRNA and protein of JAG1 was correlated with poorly differentiated tumors. Conclusion Our data emphasize that overexpression of DLL4 and JAG1 could predict the development of distant metastasis in breast cancer patients.

Background: The objective of this study was to investigate the fatty acids profiling in diabetic rats induced by sterptozocine (STZ) and their response to administration of lutein and carnitine.Materials and methods: Ninety male albino rats were divided into 6 groups as follows: Normal control. The remaining rats were injected i.p a single dose of STZ (65 mg /kg bw) for induction of diabetes. Diabetic rats were grouped as: GP II: (Untreated): GP III: Rats were given orally with L-lutein (100 mg/kg bw).GP IV: Rats were given carnitine (30 μg/kg) i.p. GP V: Rats were given carnitine and lutein GP VI were given metformin (100mg/kg bw/d) for 6 weeks.Results: Treatment of diabetic rats with lutein, L-carnitine, combined decreased the levels of glucose, HA1C compared with untreated diabetic (p

Background: The present study was undertaken to assess whether boiling water mint extract (BWME) modulates the cytochrome P 450 mixed function oxidase system. Materials and methods: Male albino rats were randomly divided into two groups, comprising 12 animals each. The first group served as control, whereas the second was maintained on BWME (10 % w/v) as its sole drinking liquid for six weeks. Liver microsomal were separated and subjected for phase I and II enzymes (cytochrome P 450 mixed function oxidase) analysis Results: The results obtained showed that, BWME caused a significant elevation in the activity of epoxide hydrolase (p

Sunitinib is an orally administered, multi-target tyrosine kinase inhibitor that has been approved by the FDA for the treatment of renal cell carcinoma and imatinib resistant gastro-intestinal tumors. Anti-leukemic activity of sunitinib has been examined in early clinical trials with limited success. However, recent trials on acute myeloid leukemia (AML) patients carrying FLT3 mutations have shown promising results. Effects of sunitinib on leukemic clonogenic cells and potential leukemic stem cells have not been examined so far. We analyzed the anti-proliferative and apoptotic properties of sunitinib on AML-derived cell lines. We also tested the effect of sunitinib on AML patient derived clonogenic cells (AML-CFC), as well as flow-sorted potential leukemic progenitors. Peripheral blood or bone marrow samples were obtained from newly diagnosed AML patients and flow sorted for CD34+ CD133+ or ALDH+ cells. Umbilical cord blood derived CD34+ cells were used as normal controls. Sunitinib induced growth arrest and apoptosis in AML derived cell lines. In addition, 7 μM sunitinib induced 75% reduction of AML-CFC as compared to DMSO treated control (±6.79%; n = 4). In contrast, 7 μM sunitinib treatment of umbilical cord blood derived normal CD34+ cells showed 29% reduction in AML-CFC (±6.77%; n = 5). Treatment of ALDH+ cells sorted from 2 AML cases and CD34+ CD133+ cells from one patient showed reduction of AML-CFC on treatment with sunitinib. Our study highlighted a potent anti-proliferative and proapoptotic effect of sunitinib on AML cell lines, AML patient derived clonogenic cells and potential leukemic stem cells.

Information regarding transcriptome and metabolome has significantly contributed to the identification of potential therapeutic targets for the management of a variety of cancers. Obesity has been shown to have profound effects on both cancer cell transcriptome and metabolome and to affect the outcome of cancer therapy. The information regarding the potential effects of obesity on breast cancer (BC) transcriptome, metabolome, and its integration to identify novel pathways related to disease progression are still elusive. We assessed the whole blood transcriptome and serum metabolome as circulating metabolites, of obese BC patients and compared them with non-obese BC patients. In these patients, 186 differentially expressed genes (DEGs) were observed, with 156 upregulated and 30 downregulated, significantly. The DEGs were enriched in different cellular pathways: cell cycle, one carbon pathway, homologous recombination cellular senescence, and notch signaling pathway. Our results confirmed the altered expression of several DEGs by quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, 96 deregulated metabolites were identified when untargeted metabolomics was performed in obese BC patients when compared to non-obese BC patients, these were enriched in 71 pathways, most of them involved in ATP generation and cell proliferation. Finally, to provide a more comprehensive understanding of the association between obesity and BC, integration analysis between transcriptome and metabolomics data at the pathway level, revealed seven enriched pathways in obese BC vs. non-obese BC patients, that includes glutathione metabolism, glycine and serine metabolism, valine, leucine, and isoleucine degradation, purine metabolism, pyrimidine metabolism, thyroid hormone synthesis, and vitamin B6 metabolism; which may provide resistance for BC cell to dodge the circulating immune cells in whole blood. In conclusion, this study provides information on the unique pathways alteration at transcriptome and metabolome levels in obese BC patients, which may become an important tool for researchers and contribute to a rise in the knowledge on the molecular interaction between obesity and BC. Further studies are needed to confirm this and to elucidate the exact underlying mechanism for the effects of obesity on the BC initiation or/and progression. Citation Format: Mohammed Abdullah Hassan, Kaltoom Al-Sakkaf, Mohammed Razeeth Shait Mohammed, Ashraf Dallol, Jaudah Al-Maghrabi, Alia Aldahlawi, Sawsan Ashoor, Mabrouka Maamra, Jiannis Ragoussis, Wei Wu, Mohammad Imran Khan, Abdulrahman Al-Malki, Hani Choudhry. Integration of transcriptome and metabolome provides unique insights to pathways associated with obese breast cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 243.

Natural polyamines such as putrescine, spermidine, and spermine are crucial in the cell proliferation and maintenance in all the eukaryotes. However, the requirement of polyamines in tumor cells is stepped up to maintain tumorigenicity. Many synthetic polyamine analogues have been designed recently to target the polyamine metabolism in tumors to induce apoptosis. N4-Erucoyl spermidine (designed as N4-Eru), a novel acylspermidine derivative, has been shown to exert selective inhibitory effects on both hematological and solid tumors, but its mechanisms of action are unknown. In this study, RNA sequencing was performed to investigate the anticancer mechanisms of N4-Eru-treated T-cell acute lymphoblastic leukemia (ALL) cell line (Jurkat cells), and gene expression was examined through different tools. We could show that many key oncogenes including NDRG1, CACNA1G, TGFBR2, NOTCH1,2,3, UHRF1, DNMT1,3, HDAC1,3, KDM3A, KDM4B, KDM4C, FOS, and SATB1 were downregulated, whereas several tumor suppressor genes such as CDKN2AIPNL, KISS1, DDIT3, TP53I13, PPARG, FOXP1 were upregulated. Data obtained through RNA-Seq further showed that N4-Eru inhibited the NOTCH/Wnt/JAK-STAT axis. This study also indicated that N4-Eru-induced apoptosis could involve several key signaling pathways in cancer. Altogether, our results suggest that N4-Eru is a promising drug to treat ALL.