Aflatoxin Contamination: An Overview on Health Issues, Detection and Management Strategies.

Aflatoxins (AFs) represent one of the main mycotoxins produced by Aspergillus flavus and Aspergillus parasiticus, with the most prevalent and lethal subtypes being AFB1, AFB2, AFG1, and AFG2. AFs are responsible for causing significant public health issues and economic concerns that affect consumers and farmers globally. Chronic exposure to AFs has been linked to liver cancer, oxidative stress, and fetal growth abnormalities among other health-related risks. Although there are various technologies, such as physical, chemical, and biological controls that have been employed to alleviate the toxic effects of AF, there is still no clearly elucidated universal method available to reduce AF levels in food and feed; the only mitigation is early detection of the toxin in the management of AF contamination. Numerous detection methods, including cultures, molecular techniques, immunochemical, electrochemical immunosensor, chromatographic, and spectroscopic means, are used to determine AF contamination in agricultural products. Recent research has shown that incorporating crops with higher resistance, such as sorghum, into animal feed can reduce the risk of AF contamination in milk and cheese. This review provides a current overview of the health-related risks of chronic dietary AF exposure, recent detection techniques, and management strategies to guide future researchers in developing better detection and management strategies for this toxin.

Microbial Genomics: Innovative Targets and Mechanisms.

Multidrug resistance (MDR) has become an increasing threat to global health because bacteria can develop resistance to antibiotics over time. Scientists worldwide are searching for new approaches that go beyond traditional antibiotic discovery and development pipelines. Advances in genomics, however, opened up an unexplored therapeutic opportunity for the discovery of new antibacterial agents. Genomic approaches have been used to discover several novel antibiotics that target critical processes for bacterial growth and survival, including histidine kinases (HKs), LpxC, FabI, peptide deformylase (PDF), and aminoacyl-tRNA synthetases (AaRS). In this review, we will discuss the use of microbial genomics in the search for innovative and promising drug targets as well as the mechanisms of action for novel antimicrobial agents. We will also discuss future directions on how the utilization of the microbial genomics approach could improve the odds of antibiotic development having a more successful outcome.

Identification of NRAS Diagnostic Biomarkers and Drug Targets for Endometrial Cancer-An Integrated in Silico Approach.

The diagnosis of endometrial cancer involves sequential, invasive tests to assess the thickness of the endometrium by a transvaginal ultrasound scan. In 6−33% of cases, endometrial biopsy results in inadequate tissue for a conclusive pathological diagnosis and 6% of postmenopausal women with non-diagnostic specimens are later discovered to have severe endometrial lesions. Thus, identifying diagnostic biomarkers could offer a non-invasive diagnosis for community or home-based triage of symptomatic or asymptomatic women. Herein, this study identified high-risk pathogenic nsSNPs in the NRAS gene. The nsSNPs of NRAS were retrieved from the NCBI database. PROVEAN, SIFT, PolyPhen-2, SNPs&GO, PhD-SNP and PANTHER were used to predict the pathogenicity of the nsSNPs. Eleven nsSNPs were identified as "damaging", and further stability analysis using I-Mutant 2.0 and MutPred 2 indicated eight nsSNPs to cause decreased stability (DDG scores < −0.5). Post-translational modification and protein−protein interactions (PPI) analysis showed putative phosphorylation sites. The PPI network indicated a GFR-MAPK signalling pathway with higher node degrees that were further evaluated for drug targets. The P34L, G12C and Y64D showed significantly lower binding affinity towards GTP than wild-type. Furthermore, the Kaplan−Meier bioinformatics analyses indicated that the NRAS gene deregulation affected the overall survival rate of patients with endometrial cancer, leading to prognostic significance. Findings from this could be considered novel diagnostic and therapeutic markers.

Biochemical Composition and Biological Activities of Date Palm (Phoenix dactylifera L.) Seeds: A Review.

Date palm (Phoenix dactylifera L.) is an essential agricultural crop in most Middle Eastern countries, and its fruit, known as dates, is consumed by millions of people. Date seeds, a by-product of the date fruit processing industry, are a waste product used as food for domestic farm animals. Date seeds contain abundant sources of carbohydrates, oil, dietary fiber, and protein; they also contain bioactive phenolic compounds that may possess potential biological properties. In addition, its rich chemical composition makes date seeds suitable for use in food product formulation, cosmetics, and medicinal supplements. This review aims to provide a discourse on the nutritional value of date seeds. The latest data on the cytotoxicity of date seed compounds against cancer cell lines, its ability to combat diabetes, antioxidant potential, antimicrobial effect, and anti-inflammatory activity will be provided, considering its potential to be a nutritional therapeutic agent for chronic diseases. Application of date seeds in the form of powder and oil will also be discussed.

Host-Bacterial Interactions: Outcomes of Antimicrobial Peptide Applications.

The bacterial membrane is part of a secretion system which plays an integral role to secrete proteins responsible for cell viability and pathogenicity; pathogenic bacteria, for example, secrete virulence factors and other membrane-associated proteins to invade the host cells through various types of secretion systems (Type I to Type IX). The bacterial membrane can also mediate microbial communities' communication through quorum sensing (QS), by secreting auto-stimulants to coordinate gene expression. QS plays an important role in regulating various physiological processes, including bacterial biofilm formation while providing increased virulence, subsequently leading to antimicrobial resistance. Multi-drug resistant (MDR) bacteria have emerged as a threat to global health, and various strategies targeting QS and biofilm formation have been explored by researchers worldwide. Since the bacterial secretion systems play such a crucial role in host-bacterial interactions, this review intends to outline current understanding of bacterial membrane systems, which may provide new insights for designing approaches aimed at antimicrobials discovery. Various mechanisms pertaining interaction of the bacterial membrane with host cells and antimicrobial agents will be highlighted, as well as the evolution of bacterial membranes in evasion of antimicrobial agents. Finally, the use of antimicrobial peptides (AMPs) as a cellular device for bacterial secretion systems will be discussed as emerging potential candidates for the treatment of multidrug resistance infections.

Prevalence, Antibiotic-Resistance, and Growth Profile of Vibrio spp. Isolated From Fish and Shellfish in Subtropical-Arid Area.

The study aimed to determine the prevalence of different species of Vibrio spp. in fish and shellfish sold in subtropical-arid countries (United Arab Emirates). It also examined the antimicrobial resistance of the isolated species and their growth behavior upon in vitro environmental changes concerning temperature, pH, and salinity. The prevalence of Vibrio spp. in fish and shellfish samples, was 64.5 and 92%, respectively. However, Vibrio parahemolyticus were detected in a mere 7.5 and 13.0% of the samples, respectively. On the other hand, Vibrio mimicus was detected in 1.5 and 8.5% of the samples, respectively. None of the six antibiotics studied except for Sulfamethoxazole-trimethoprim were effective against fish Vibrio spp. isolates. On a similar note, three antibiotics, namely Penicillin, Daptomycin, and Vancomycin, were ineffective against the shellfish isolates. The growth of the microorganisms did not show any significant trend with changes in pH and salinity. The optimum temperature for Vibrio spp. growth was observed to be 37°C.

The Missing Piece: Recent Approaches Investigating the Antimicrobial Mode of Action of Essential Oils.

Antibiotic resistance is a major global health issue that has seen alarming rates of increase in all parts of the world over the past two decades. The surge in antibiotic resistance has resulted in longer hospital stays, higher medical costs, and elevated mortality rates. Constant attempts have been made to discover newer and more effective antimicrobials to reduce the severity of antibiotic resistance. Plant secondary metabolites, such as essential oils, have been the major focus due to their complexity and bioactive nature. However, the underlying mechanism of their antimicrobial effect remains largely unknown. Understanding the antimicrobial mode of action of essential oils is crucial in developing potential strategies for the use of essential oils in a clinical setting. Recent advances in genomics and proteomics have enhanced our understanding of the antimicrobial mode of action of essential oils. We might well be at the dawn of completing a mystery on how essential oils carry out their antimicrobial activities. Therefore, an overview of essential oils with regard to their antimicrobial activities and mode of action is discussed in this review. Recent approaches used in identifying the antimicrobial mode of action of essential oils, specifically from the perspective of genomics and proteomics, are also synthesized. Based on the information gathered from this review, we offer recommendations for future strategies and prospects for the study of essential oils and their function as antimicrobials.

Nutraceuticals: Transformation of Conventional Foods into Health Promoters/Disease Preventers and Safety Considerations.

Nutraceuticals are essential food constituents that provide nutritional benefits as well as medicinal effects. The benefits of these foods are due to the presence of active compounds such as carotenoids, collagen hydrolysate, and dietary fibers. Nutraceuticals have been found to positively affect cardiovascular and immune system health and have a role in infection and cancer prevention. Nutraceuticals can be categorized into different classes based on their nature and mode of action. In this review, different classifications of nutraceuticals and their potential therapeutic activity, such as anti-cancer, antioxidant, anti-inflammatory and anti-lipid activity in disease will be reviewed. Moreover, the different mechanisms of action of these products, applications, and safety upon consumers including current trends and future prospect of nutraceuticals will be included.

An Overview of the Potential Therapeutic Applications of Essential Oils.

The emergence of antimicrobial resistance (AMR) has urged researchers to explore therapeutic alternatives, one of which includes the use of natural plant products such as essential oils (EO). In fact, EO obtained from clove, oregano, thymus, cinnamon bark, rosemary, eucalyptus, and lavender have been shown to present significant inhibitory effects on bacteria, fungi, and viruses; many studies have been done to measure EO efficacy against microorganisms. The strategy of combinatory effects via conventional and non-conventional methods revealed that the combined effects of EO-EO or EO-antibiotic exhibit enhanced efficacy. This paper aims to review the antimicrobial effects of EO, modes of EO action (membrane disruption, efflux inhibition, increase membrane permeability, and decrease in intracellular ATP), and their compounds' potential as effective agents against bacteria, fungi, and viruses. It is hoped that the integration of EO applications in this work can be used to consider EO for future clinical applications.

Middle Eastern Plant Extracts: An Alternative to Modern Medicine Problems.

Middle Eastern countries are primarily known for their dry sand deserts; however, they have a wider physiographic range which includes upland plateau and mountain ranges. The Middle East is home to various types of plants, such as Phoenix dactylifera (date palm tree), Scrophularia striata (herbaceous plants), and Opuntia ficus-indica (cactus). These plants have been found to have various types of bioactivities, such as antimicrobial activities against both bacteria and fungi, in addition to exhibiting anti-inflammatory effects and anti-cancer characteristics which can be utilized in the clinical setting for treatment. Due to limited reviews focusing on plant extracts from the Middle East, we aim to provide a discourse on plants from this region which have various bioactivities and to provide information on the compounds that can be identified from these plants. This is to enhance our understanding to improve modern medicine problems such as antimicrobial resistance and to find an alternative cure for cancer. It is hoped that the collation of information from this review will enable an assessment of the direct role of Middle Eastern plants in providing therapeutic options to address the predicaments in the medical field.

Lavender essential oil induces oxidative stress which modifies the bacterial membrane permeability of carbapenemase producing Klebsiella pneumoniae.

Misuse of antibiotics in the clinical and agricultural sectors has caused the emergence of multidrug-resistant (MDR) Klebsiella pneumoniae which contributes a threat to human health. In this study, we assessed the feasibility of lavender essential oil (LVO) as an antimicrobial agent in combinatory therapy with meropenem in suppressing the growth of carbapenemase-producing K. pneumoniae (KPC-KP). Synergistic interactions between LVO and meropenem were detected, which significantly reduce the inhibitory concentration of both LVO and meropenem by 15 and 4-fold respectively. Comparative proteomic profiling identified a disruption in the bacterial membrane via oxidative stress that was indicated by loss of membrane and cytoplasmic proteins and the upregulation of oxidative regulators. As a proof of concept, zeta potential measurements showed a change in cell surface charge while outer membrane permeability measurement indicated an increase in membrane permeability following exposure to LVO. This was indicative of a disrupted outer membrane. Ethidium bromide influx/efflux assays demonstrated no significant efflux pump inhibition by LVO, and scanning electron microscopy revealed irregularities on the cell surface after exposure to LVO. Oxidative stress was also detected with increased level of ROS and lipid peroxidation in LVO-treated cells. In conclusion, our data suggest that LVO induced oxidative stress in K. pneumoniae which oxidizes the outer membrane, enabling the influx of generated ROS, LVO and meropenem into the bacterial cells, causing damage to the cells and eventually death.

Mechanisms of Antimicrobial Resistance (AMR) and Alternative Approaches to Overcome AMR.

Antimicrobials are useful compounds intended to eradicate or stop the growth of harmful microorganisms. The sustained increase in the rates of antimicrobial resistance (AMR) worldwide is worrying and poses a major public health threat. The development of new antimicrobial agents is one of the critical approaches to overcome AMR. However, in the race towards developing alternative approaches to combat AMR, it appears that the scientific community is falling behind when pitched against the evolutionary capacity of multi-drug resistant (MDR) bacteria. Although the "pioneering strategy" of discovering completely new drugs is a rational approach, the time and effort taken are considerable, the process of drug development could instead be expedited if efforts were concentrated on enhancing the efficacy of existing antimicrobials through: combination therapies; bacteriophage therapy; antimicrobial adjuvants therapy or the application of nanotechnology. This review will briefly detail the causes and mechanisms of AMR as background, and then provide insights into a novel, future emerging or evolving strategies that are currently being evaluated and which may be developed in the future to tackle the progression of AMR.

Terpene Derivatives as a Potential Agent against Antimicrobial Resistance (AMR) Pathogens.

The evolution of antimicrobial resistance (AMR) in pathogens has prompted extensive research to find alternative therapeutics. Plants rich with natural secondary metabolites are one of the go-to reservoirs for discovery of potential resources to alleviate this problem. Terpenes and their derivatives comprising of hydrocarbons, are usually found in essential oils (EOs). They have been reported to have potent antimicrobial activity, exhibiting bacteriostatic and bactericidal effects against tested pathogens. This brief review discusses the activity of terpenes and derivatives against pathogenic bacteria, describing the potential of the activity against AMR followed by the possible mechanism exerted by each terpene class. Finally, ongoing research and possible improvisation to the usage of terpenes and terpenoids in therapeutic practice against AMR are discussed.

Disruption of KPC-producing Klebsiella pneumoniae membrane via induction of oxidative stress by cinnamon bark (Cinnamomum verum J. Presl) essential oil.

Klebsiella pneumoniae (KP) remains the most prevalent nosocomial pathogen and carries the carbapenemase (KPC) gene which confers resistance towards carbapenem. Thus, it is necessary to discover novel antimicrobials to address the issue of antimicrobial resistance in such pathogens. Natural products such as essential oils are a promising source due to their complex composition. Essential oils have been shown to be effective against pathogens, but the overall mechanisms have yet to be fully explained. Understanding the molecular mechanisms of essential oil towards KPC-KP cells would provide a deeper understanding of their potential use in clinical settings. Therefore, we aimed to investigate the mode of action of essential oil against KPC-KP cells from a proteomic perspective by comparing the overall proteome profile of KPC-KP cells treated with cinnamon bark (Cinnamomum verum J. Presl) essential oil (CBO) at their sub-inhibitory concentration of 0.08% (v/v). A total of 384 proteins were successfully identified from the non-treated cells, whereas only 242 proteins were identified from the CBO-treated cells. Proteins were then categorized based on their biological processes, cellular components and molecular function prior to pathway analysis. Pathway analysis showed that CBO induced oxidative stress in the KPC-KP cells as indicated by the abundance of oxidative stress regulator proteins such as glycyl radical cofactor, catalase peroxidase and DNA mismatch repair protein. Oxidative stress is likely to oxidize and disrupt the bacterial membrane as shown by the loss of major membrane proteins. Several genes selected for qRT-PCR analysis validated the proteomic profile and were congruent with the proteomic abundance profiles. In conclusion, KPC-KP cells exposed to CBO undergo oxidative stress that eventually disrupts the bacterial membrane possibly via interaction with the phospholipid bilayer. Interestingly, several pathways involved in the bacterial membrane repair system were also affected by oxidative stress, contributing to the loss of cells viability.

Degradation of myofibrillar, sarcoplasmic and connective tissue proteins by plant proteolytic enzymes and their impact on camel meat tenderness.

Inside round muscles (Adductor) from camels treated with bromelain or ficin or papain at 50 or 100 ppm were subsequently stored at 4 °C for 4 days to study the impact on quality attributes, protein degradation and textural changes. Results revealed that papain (100 ppm) treated camel meat showed higher drip loss and lower water holding capacity compared to other treatments. Total protein, sarcoplasmic protein solubility, trichloroacetic acid (TCA)-soluble peptides and soluble collagen were higher in papain and bromelain treated samples at 100 ppm compared to other treatments. Electrophoretic profile of whole camel meat, isolated sarcoplasmic and myofibrillar proteins depicted a noticeable degradation of various proteins in enzyme treated samples, with papain and bromelain (100 ppm) displaying pronounced effect. Meat treated with papain at 100 ppm displayed lower hardness and shear force (P < 0.05). Thus, enzymes treatment at 100 ppm displayed good potential to tenderize camel meat with the papain being more effective among all.

In vitro investigation of anticancer, antihypertensive, antidiabetic, and antioxidant activities of camel milk fermented with camel milk probiotic: A comparative study with fermented bovine milk.

This study aimed to investigate in vitro anticancer activity by antiproliferative activity, antihypertensive activity by angiotensin-converting enzyme inhibition, antidiabetic activity by α-amylase and α-glucosidase inhibitions, and antioxidant activities of camel milk fermented with camel milk probiotic compared with fermented bovine milk. The camel milk probiotic strain Lactococcus lactis KX881782 (Lc.K782) and control Lactobacillus acidophilus DSM9126 (La.DSM) were used to prepare fermented camel and bovine milks separately. The proteolytic activities of water-soluble extract (WSE) in all fermented camel milk were higher than those in fermented bovine milk. The α-glucosidase inhibitions in both milk types fermented by Lc.K782 ranged from 30 to 40%. Camel milk fermented by Lc.K782 had the highest antioxidant activity by 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulphonic acid). The highest angiotensin-converting enzyme inhibition of WSE in camel milk fermented by Lc.K782 was >80%. The proliferations of Caco-2, MCF-7, and HELA cells were more inhibited when treated with WSE of fermented camel milk extracts.

Health-promoting benefits of low-fat akawi cheese made by exopolysaccharide-producing probiotic Lactobacillus plantarum isolated from camel milk.

Lactic acid bacteria isolated from camel milk exhibit remarkable probiotic and exopolysaccharide (EPS)-producing characteristics. The health-promoting benefits of exopolysaccharide-producing probiotic Lactobacillus plantarum isolated from camel milk used for making low-fat akawi cheese were investigated. Three low-fat akawi cheeses were made using traditional culture (non-EPS-producing, EPS-), commercial EPS-producing (MEPS+), and camel milk EPS-producing (CEPS+) cultures. α-Amylase and α-glucosidase inhibitory activities, antioxidant activities, angiotensin-converting enzyme (ACE) inhibition, and antiproliferative activity were determined. Cheese made with CEPS+ culture exhibited comparable α-amylase inhibition to that of cheeses made with MEPS+. Scavenging rates of cheese made with EPS+ cultures were higher than those of cheese made with EPS- cultures. The percentage of α-glucosidase inhibition ranged from >45% at 0 d to ∼55% at 21 d of storage. After 7 d of storage, the scavenging rate in CEPS+ cheese increased >60% by ABTS assay [2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid)] and >20% by DPPH assay (1,1-diphenyl-2-picrylhydrazyl). Throughout storage, cheese made with EPS+ cultures showed higher ACE-inhibition activity compared with EPS- cultures. Cheese made with CEPS+ showed ACE inhibition >70% after 7 d of storage. Antiproliferation activity of CEPS+ cheese increased from 38 to 48% during 7 d of storage and was maintained above 45% with prolonged storage. Low-fat akawi cheese produced with these cultures exhibited similar or greater health-promoting benefits compared with cheese made using commercial starter cultures. Therefore, incorporation of these cultures in food is promising for commercial uses.

Retardation of quality changes in camel meat sausages by phenolic compounds and phenolic extracts.

Impact of tannic acid (TA), date seed extract (DSE), catechin (CT) and green tea extract (GTE) on lipid oxidation, microbial load and textural properties of camel meat sausages during 12 days of refrigerated storage was investigated. TA and CT showed higher activities in all antioxidative assays compared to DSE and GTE. Lipid oxidation and microbial growth was higher for control sausages when compared to other samples. TA and CT at a level of 200 mg/kg were more effective in retarding lipid oxidation and lowering microbial count (P < 0.05). Sausages treated with TA and DSE were found to have higher hardness, gumminess and chewiness values compared to other treatments (P < 0.05). Addition of different phenolic compounds or extract did not influence the sensory color of sausages. Furthermore, sensory quality was also found to be superior in TA and CT treated sausages. Therefore, pure phenolic compounds (TA and CT) proved to be more effective in retaining microbial and sensorial qualities of camel meat sausages compared to phenolic extracts (GTE and DSE) over 12 days of storage at 4°C.

Behavior of Escherichia coli O157:H7 and Listeria monocytogenes during fermentation and storage of camel yogurt.

In addition to its nutritional and therapeutic properties, camel milk has the ability to suppress the growth of a wide range of foodborne pathogens, but there is a lack of information regarding the behavior of these pathogens in products such as yogurt produced from camel milk. The objective of the current study was to investigate the behavior of Listeria monocytogenes and Escherichia coli O157:H7 during manufacture and storage of camel yogurt. Camel milk inoculated with L. monocytogenes and E. coli O157:H7 was fermented at 43° C for 5h using freeze-dried lactic acid bacteria (LAB) starter cultures (Streptococcus thermophilus and Lactobacillus bulgaricus) and stored at 4 or 10 °C for 14 d. Camel milk inoculated with L. monocytogenes and E. coli O157:H7 without starter culture was also prepared. During fermentation, the numbers of L. monocytogenes and E. coli O157:H7 increased 0.3 and 1.6 log cfu/mL, respectively, in the presence of LAB, and by 0.3 and 2.7 log cfu/mL in the absence of LAB. During storage at 4 or 10 °C, L. monocytogenes increased 0.8 to 1.2 log cfu/mL by 14 d in camel milk without LAB, but in the presence of LAB, the numbers of L. monocytogenes were reduced by 1.2 to 1.7 log cfu/mL by 14 d. Further, E. coli O157:H7 numbers in camel milk were reduced by 3.4 to 3.5 log cfu/mL in the absence of LAB, but E. coli O157:H7 was not detected (6.3 log cfu/mL reduction) by 7d in camel yogurt made with LAB and stored at either temperature. Although camel milk contains high concentrations of natural antimicrobials, L. monocytogenes was able to tolerate these compounds in camel yogurt stored at refrigerator temperatures. Therefore, appropriate care should be taken during production of yogurt from camel milk to minimize the potential for postprocess contamination by this and other foodborne pathogens.