Objectives: The Parabens are synthetic compounds used as antibacterial and antifungal preservatives in many products. The nephrotoxicity and diabetogenic development during exposure of rats to propyl paraben and role of of Safawi Date Extract (SDE) supplementation were investigated. Materials and Methods: Male Wistar albino rats were assigned into five groups; (6 rats each). Group I served as the control while groups II-IV were given 100, 200, 300 mg/ kg bw/day propylparaben respectively. Group V; rats received 300 mg propyl paraben and treated with 100 mg SDE for four weeks. Results: Data obtained showed that rats given propyl paraben at 100 mg/kg b.w showed a non significant changes in the levels of glycated Hemoglobin (HbA1c), Malondialdhyde (MDA), creatinine, glucose, insulin, antioxidant enzyme activities and GSH content. However, propyl paraben at 200 or 300 mg/kg b.w after 3 weeks, showed a significant elevated HbA1c, MDA, fasting blood glucose, creatinine levels (p<0.001) while insulin level, were significantly reduced (p<0.001). The antioxidant enzymes activities (GPx, Grase, SOD, Catalase) were reduced in rats given propylparaben versus control. Treatment of rats with SDE ameliorate these abnormal changes. It was concluded that flavonoids (epicatechin, catechin and procyanidin) from SDE showed protective effect against abnormal variability induced by propylparaben by enhancing antioxidants activities, reduces lipid peroxidation and insulin sensitivity. Conclusion: Alarming the consumers for uses, the products contain propyl paraben for its toxic effect and diabetogenic effect. Identifying the mechanism of diabetogensis due to exposure of propylparaben for long time.

Background: Herbal medicine and its bioproducts are rich in bioactive compounds that promising in drug development. These phytochemical constituents may be secondary metabolites that exert high potency. Materials and Methods: This study investigated the phyto-constituents bioactive compounds from the aerial parts of some Saudi medicinal plants using n-hexane fragrantissima) and a mixture of essentials oils in equal ratio (Arnica montana, Chamomile, Salvia officinalis, Oenothera, Walnut leaves and Flaxseed) using GC-MS. Results: The GC-MS analysis of plants and essentials oils revealed the presence of various compounds like terpenoids and vitamins related to its anti-microbial activity, antioxidant and anti-inflammatory activity. Conclusion: It was concluded that, the broad range of terpenoids and vitamins are the main components in the hexane extract. These possess different biological activities. Further studies will be carried out in vivo and in vitro to identify the mechanism of action via signaling pathway.

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.

Chemotherapy resistance is the main reason for treatment failure in acute myeloid leukemia (AML) and the major cause of its mortality. Etoposide is a DNA topoisomerase-II inhibitor that is used either as a single agent or in combination with cytarabine, azacytidine, vinca alkaloids, and anthracyclines for the treatment of relapsed /refractory AML. In this study, we sought to determine and understand the mechanism of etoposide resistance in AML using the HL60 cell line.HL60 cells were treated with incremental doses of etoposide and resistant colonies were isolated by culturing the resistant cells in semi-solid culture media. Three clones were selected for etoposide resistance namely, HL60-EtopR H1A, HL60-EtopR H1B, and HL60-EtopR H1C which demonstrated 4.78, 2.39, and 4.42-fold higher resistance to etoposide compared with the parental cells. To determine molecular differences between the etoposide-resistant HL60-EtopR cells and the parental cells, microarray-based gene expression profiling was performed. We found up regulation of members of the src tyrosine kinase family genes in the etoposide resistant cells. Further studies are required to evaluate the role of Src inhibitors in targeting etoposide resistant cells.

The cerebellum is the largest part of the hindbrain. As an important part of nervous system, it can be affected by oxidative stress. Dietary supplements had been proved that they have antioxidants properties that may protect our bodies against the effects of free radicals. One of these supplements is Aphanizomenon flos-aquae (AFA) that has health-improving effects especially on the nervous system. Cyclophosphamide (CP) is a widely used medication in chemotherapy and can cause oxidative stress. This study was conducted to investigate the role of AFA in preventing cyclophosphamide-induced adverse effects on the cerebellum of treated rats with CP. It is an experimental study carried out in the period from January 2021 to August 2021. It was carried out on 36 rats with body weights of 270-300 g. The animals were divided into three groups. The first is control group, the second one is CP treated group, received one dose of CP at 100 mg/kg-1 BW), and last one is CP +AFA group, received orally extract of AFA after CP injection. The structures of the cerebellum were compared in the different groups histologically. Examined sections showed significant cellular injury in the second group in comparison to the control groups. The third group showed marked improvement in the changes that occurred compared to the second group. These results provide evidence that AFA has a protective effect as they reduced the cellular injuries in the cerebellum induced by cyclophosphamide.

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

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.

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.

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.

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 concen-tration 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 < 0.001). These findings demonstrated that S/A/CNP has anti-proliferative, apoptotic effects and modulate energetic, and epigenetic metabolites in the hepatocellular carcinoma cell line (HepG2).

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 disorders 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 <0.0005). In contrast, urinary Cr and Zn (p-values <0.013 and 0.005) were low in thyroid patients compared to the control. Conclusion First study to report urinary trace element levels showed a possible link between thyroid disorders and trace element exposure which reflect the environmental pollution..

The ultrasonography is able to reveal in-depth anatomical components of brachial plexus and to locate any lesions have been demonstrated. This study aimed to evaluate the normal cross-sectional area (CSA) of the brachial plexus nerves in the interscalene groove. Also, to correlate the anatomical specimen's with image the brachial plexus nerves. Lateral photographs of twenty plastinated sections of head and neck specimen to study the brachial plexus roots in the groove between middle and anterior scalene muscles. On the same time, fifty-five healthy volunteers of different age groups were included in our study. Ultrasound of roots of the cervical nerves was performed on both sides. The average cross-sectional area of the roots was estimated. There was a positive statistical association between the CSA of cervical nerves. These data may be beneficial in future studies designed to assess the brachial plexus injures.

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.

Paclitaxel (PTx) and D-L Sulforaphane (SFN) natural derivatives could inhibit many types of cancerous cells proliferation through apoptosis and autophagy. Toxicity of PTx and SFN to Caco-2 cells was concentration dependent using MTT assay. Sole SFN was significantly toxic than sole PTx. PTx and SFN combination induced a synergetic potential of PTX toxicity than sole form and the recorded IC50 in mu gm / ml was in the order of (862.8,2.,8 and 22.37) for sole PTx, SFN and combined form respectively. PTx and SFN sole and combined form induced Caco-2 cells DNA accumulation at the G2/M phase but not significantly at the Go/G1 and S phases. Apoptosis was proved via a significant up regulation of P53, Cy-c, Bax, casp-3 and down regulation of Bcl-2 with elevated Bax/Bcl-2 ratio. Antioxidant activity supported apoptotic potential showed significantly elevated ROS, MDA and reduced GSH.

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 < 3 kDa trapped extra glucose and fructose, inhibited in vitro glycation up to 49.5%, protected bovine serum albumin from glycation induced fibril formation, neutralized DPPH free radical and exhibited a cytotoxic effect against PC3, MCF-7 and HepG2 cell lines with a significant decrease in cell viability after 48 h of incubation (IC50 0.54 mg/ml to 7.58 mg/ml). Vicia faba peptides promising consumed as nutritional supplements due to its effective biological protection against diabetic complications and anticancer agent. Peptides obtained from Vicia faba were tested as antiglycation, antioxidants and antitumor activity against different cell lines. Different techniques and methods used including separation and identification of peptides from V. faba, peptides reactivity with reducing sugars, measuring peptides, measuring free sugars, antiglycation activity, MTT assay, DPPH radical assay and anti-proliferative effect of obtained peptides. Vicia faba could have the potential use as food ingredients or nutritional supplements due to its encapsulation of bioactive peptides.

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.

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 hemorrhagic 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 outbreak-prevention and response strategies in future.